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Fang D, Zhang X, Li J, Zhang L, Zhang Y. Full consideration of the pollen exposure effect in clinical trial design for pollen-induced allergic rhinitis. Expert Rev Clin Immunol 2025:1-13. [PMID: 40347108 DOI: 10.1080/1744666x.2025.2504987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 04/21/2025] [Accepted: 05/08/2025] [Indexed: 05/12/2025]
Abstract
INTRODUCTION Allergic rhinitis (AR) is global health concern with an increasing prevalence. Among them, pollen-induced AR (PIAR) exhibits more severe and intense symptoms, decreased quality of life, prominent local inflammation, and is thus more challenging to control. Due to the difficulties in disease control, in recent years, an increasing number of treatment methods, including pharmacotherapy, allergen-specific immunotherapy, and newly developed biologics, have focused on PIAR. It has been shown that the pollen exposure has a significant impact on the symptoms of PIAR and the efficacy of intervention. From this perspective, clinical trials for PIAR need to take full account of pollen exposure, especially when assessing efficacy. AREAS COVERED This review summarized the effect of pollen exposure on PIAR, including immune responses, symptoms and clinic visits. Current definitions for the pollen season (PS) and the peak pollen season (PPS) are discussed. Based on the previous PIAR-related clinical studies and the available recommendations for clinical trial design, a detailed account of trial protocols which fully considered pollen exposure is provided. EXPERT OPINION Pollen exposure has a significant impact on PIAR. With fully considering the pollen exposure in the clinical trial design for PIAR, future protocols for PIAR-related studies may be more objective and better harmonized and, therefore, comparable.
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Affiliation(s)
- Dandan Fang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Xu Zhang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Laboratory for Environmental Health and Allergic Nasal Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
| | - Jingyun Li
- Beijing Laboratory of Allergic Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Luo Zhang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Yuan Zhang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Laboratory for Environmental Health and Allergic Nasal Diseases, Laboratory for Clinical Medicine, Capital Medical University, Beijing, China
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Cheng X, Zhou Y, Hao Y, Long Z, Hu Q, Huo B, Xie T, Chen S, Zhou L, Zhou T, Li L, Cheng Q, Chen J. Recent Studies and Prospects of Biologics in Allergic Rhinitis Treatment. Int J Mol Sci 2025; 26:4509. [PMID: 40429652 DOI: 10.3390/ijms26104509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/09/2025] [Accepted: 04/27/2025] [Indexed: 05/29/2025] Open
Abstract
Allergic rhinitis (AR) is a common and increasingly prevalent chronic inflammatory disorder of the nasal mucosa that severely impacts patients' quality of life, causing symptoms like nasal congestion, sneezing, and itching. AR is primarily mediated by immunoglobulin E (IgE) when allergens are present, making it challenging to manage despite available therapies like pharmacotherapy, immunotherapy, and surgery. Recently, research has focused on biologics as an emerging therapeutic option for AR. Biologics target specific immune pathways in type 2 inflammation, which underlies many allergic diseases including AR. Biologics offer a targeted and potentially more effective alternative to traditional therapies, addressing the underlying immune mechanisms rather than simply alleviating symptoms. Based on key clinical trial evidence, this paper tentatively proposes a multidimensional strategy for selecting biologics in AR, integrating serum IgE levels, disease phenotypes (seasonal/persistent), and comorbid characteristics to guide individualized treatment. However, the long-term cost-effectiveness, optimal dosing regimens, and patient adherence to biologics require further validation through real-world data. Despite these challenges, recent advancements in biologics represent a promising step forward in AR management. With ongoing research and clinical trials, biologics may soon provide more effective and lasting relief for patients suffering from allergic rhinitis.
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Affiliation(s)
- Xiangning Cheng
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yue Zhou
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Yuzhe Hao
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Ziyi Long
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Qianxue Hu
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Bingyue Huo
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Tianjian Xie
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Shan Chen
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Liuqing Zhou
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Tao Zhou
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Liyue Li
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Qing Cheng
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
| | - Jianjun Chen
- Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
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Zhang Y, Li J, Wang M, Li X, Yan B, Liu J, Shi L, Cao Z, Feng Y, Liu W, Xu Z, Ma R, Gao X, Liu W, Xue J, Ren X, Li X, Song X, Yang Y, Wang Y, Xing Z, Quan F, Pan J, Sun Y, Shi F, Chen X, Yan H, Zhao G, Chen B, Wang C, Zhang L. Stapokibart for moderate-to-severe seasonal allergic rhinitis: a randomized phase 3 trial. Nat Med 2025:10.1038/s41591-025-03651-5. [PMID: 40186079 DOI: 10.1038/s41591-025-03651-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 03/10/2025] [Indexed: 04/07/2025]
Abstract
Seasonal allergic rhinitis (SAR) places a significant socioeconomic burden, particularly on individuals with poorly managed recurrent and severe symptoms despite standard-of-care treatment. Stapokibart, a humanized monoclonal antibody that targets the interleukin (IL)-4 receptor subunit alpha, inhibits its interaction with both IL-4 and IL-13 in type 2 inflammation. Here we aim to assess the efficacy and safety of stapokibart as an add-on therapy in adults with moderate-to-severe SAR. The study was a phase 3 multicenter, randomized, double-blind, placebo-controlled clinical trial with 108 patients diagnosed with moderate-to-severe SAR and having baseline blood eosinophil counts ≥300 cells μl-1. Participants were randomized (1:1) to receive 600 mg (loading dose) to 300 mg stapokibart subcutaneously or a placebo every 2 weeks for 4 weeks. The primary endpoint was mean change from baseline in daily reflective total nasal symptom score (rTNSS) over the first 2 weeks. Multiplicity-tested secondary endpoints included changes in rTNSS over 4 weeks, reflective total ocular symptom score and Rhinoconjunctivitis Quality of Life Questionnaire score over 2 weeks and 4 weeks. Compared with the placebo, stapokibart led to a significant improvement in the mean change from baseline in daily rTNSS during the 2-week (least-squares mean difference, -1.3; 95% confidence interval, -2.0 to -0.6; P = 0.0008) and 4-week (least-squares mean difference, -1.7; 95% confidence interval, -2.5 to -0.8; P = 0.0002) treatments. Stapokibart significantly improved the multiplicity-tested secondary endpoints. Treatment-emergent adverse events were comparable between the groups. Pharmacodynamics and exploratory analyses indicated that the observed improvements in outcomes during pollen season may be attributed to the reduction of type 2 inflammation in response to stapokibart treatment. The results of this trial show that pollen seasonal administration of stapokibart improved both nasal and ocular symptoms and quality of life in patients with moderate-to-severe SAR. ClinicalTrials.gov registration: NCT05908032 .
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Affiliation(s)
- Yuan Zhang
- The Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- The Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China
- National Engineering Research Center of Innovative Drugs for Allergic Diseases, Beijing, China
- Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Allergic Diseases, Ministry of Education; Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Jingyun Li
- The Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China
- National Engineering Research Center of Innovative Drugs for Allergic Diseases, Beijing, China
- Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Allergic Diseases, Ministry of Education; Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Menglin Wang
- The Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China
- National Engineering Research Center of Innovative Drugs for Allergic Diseases, Beijing, China
- Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Allergic Diseases, Ministry of Education; Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Xian Li
- The Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- The Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China
- National Engineering Research Center of Innovative Drugs for Allergic Diseases, Beijing, China
- Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Allergic Diseases, Ministry of Education; Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Bing Yan
- The Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China
- National Engineering Research Center of Innovative Drugs for Allergic Diseases, Beijing, China
- Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Allergic Diseases, Ministry of Education; Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China
| | - Jixiang Liu
- The Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin Union Medical Center, Tianjin, China
| | - Li Shi
- The Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China
- Shandong Provincial Key Medical and Health Discipline of Allergy, Shandong Second Provincial General Hospital, Jinan, China
| | - Zhiwei Cao
- The Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yan Feng
- The Department of Otorhinolaryngology Head and Neck Surgery, The First Hospital of Shanxi Medical University, Taiyuan, China
| | - Weiwei Liu
- The Department of Otolaryngology, Cangzhou Central Hospital, Cangzhou, China
| | - Zhendong Xu
- E.N.T. Department, Baotou Central Hospital in Inner Mongolia Autonomous Region, Baotou, China
| | - Ruixia Ma
- The Department of Otorhinolaryngology Head and Neck Surgery, The First People's Hospital of Yinchuan, Yinchuan, China
| | - Xiaoping Gao
- The Department of Otolaryngology Head and Neck Surgery, General Hospital of Ningxia Medical University, Yinchuan, China
| | - Wen Liu
- The Department of Otorhinolaryngology, Zibo Central Hospital, Zibo, China
| | - Jinmei Xue
- The Department of Otorhinolaryngology, Head and Neck Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaoyong Ren
- The Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xuezhong Li
- The Department of Otorhinolaryngology, Qilu Hospital of Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Jinan, China
| | - Xicheng Song
- The Department of Otorhinolaryngology Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Yi Yang
- Otolaryngology Department, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Yusheng Wang
- The Department of Otolaryngology Head and Neck Surgery, First Hospital of Jilin University, Changchun, China
| | - Zhimin Xing
- The Department of Otorhinolaryngology-Head and Neck Surgery, Peking University People's Hospital, Beijing, China
| | - Fang Quan
- The Department of Otolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jing Pan
- The Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin Union Medical Center, Tianjin, China
| | - Yue Sun
- The Department of Otorhinolaryngology, Head and Neck Surgery, Tianjin Union Medical Center, Tianjin, China
| | - Fengpo Shi
- The Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, China
- Shandong Provincial Key Medical and Health Discipline of Allergy, Shandong Second Provincial General Hospital, Jinan, China
| | - Xiaoqiu Chen
- The Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hongyue Yan
- Keymed Biosciences (Chengdu) Co., Ltd., Chengdu, China
| | - Guoqing Zhao
- Keymed Biosciences (Chengdu) Co., Ltd., Chengdu, China
| | - Bo Chen
- Keymed Biosciences (Chengdu) Co., Ltd., Chengdu, China
| | - Chengshuo Wang
- The Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China.
- National Engineering Research Center of Innovative Drugs for Allergic Diseases, Beijing, China.
- Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Allergic Diseases, Ministry of Education; Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China.
| | - Luo Zhang
- The Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
- The Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal Disease, Beijing, China.
- National Engineering Research Center of Innovative Drugs for Allergic Diseases, Beijing, China.
- Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Allergic Diseases, Ministry of Education; Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing, China.
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Wang M, Zhang Y, Li J, Wang C, Zhang L. Stapokibart (CM310) in patients with uncontrolled seasonal allergic rhinitis (PHECDA): Rationale and design of a multicentre, randomized, double-blind, placebo-controlled study. Asia Pac Allergy 2025; 15:15-20. [PMID: 40051426 PMCID: PMC11882218 DOI: 10.5415/apallergy.0000000000000174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 11/17/2024] [Indexed: 03/09/2025] Open
Abstract
Background Seasonal allergic rhinitis (SAR) is a global health issue, and the current standard of care (SoC) has limited effectiveness in controlling the disease. There is a need for innovative treatments to better manage uncontrolled SAR and advance beyond the uniform SoC, and biologics targeting type 2 inflammation driving allergic rhinitis is promising. Objective To evaluate the efficacy and safety of Stapokibart, a humanized monoclonal antibody targeting interleukin-4 receptor subunit alpha, as an add-on therapy in patients with uncontrolled SAR. Methods The PHECDA is a multicenter, randomized, double-blind, placebo-controlled, phase 3 clinical study designed to evaluate the efficacy and safety of Stapokibart in treating uncontrolled SAR in adults. Conducted across 18 centers in China during the pollen season, the study plans to recruit 108 adult patients with moderate to severe nasal symptoms despite receiving SoC during the previous seasonal pollen period, along with a 1-week run-in period and a baseline blood eosinophil count of at least 300 cells·μL-1. The study consists of a screening/run-in period (1 week), treatment period (4 weeks), and follow-up period (8 weeks). In addition to SoC, which includes mometasone furoate nasal spray and loratadine, participants are randomly assigned using a centralized interactive-web-response-system to receive either subcutaneous Stapokibart 600 (loading dose)-300 mg or a placebo every 2 weeks for 4 weeks. The primary endpoint of the study is the mean change from baseline in the daily reflective total nasal symptom score over the first 2 weeks of treatment. Subjects who have been administered at least 1 dose of the investigational drug will be included in the assessments of both efficacy and safety. Results This article outlines the methodology utilized in a multicenter trial studying Stapokibar for seasonal allergic rhinitis, with expectations to discuss its significant effects in subsequent analyses based on trial outcomes. Conclusion The PHECDA study is for the first time to provide insight into the efficacy and safety of a seasonal add-on Stapokibart for patients with uncontrolled SAR during pollen exposure. Trial registration NCT05908032.
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Affiliation(s)
- Menglin Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education of China, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuan Zhang
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education of China, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China
| | - Jingyun Li
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education of China, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Chengshuo Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education of China, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education of China, Beijing, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing, China
- Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, China
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Ogulur I, Mitamura Y, Yazici D, Pat Y, Ardicli S, Li M, D'Avino P, Beha C, Babayev H, Zhao B, Zeyneloglu C, Giannelli Viscardi O, Ardicli O, Kiykim A, Garcia-Sanchez A, Lopez JF, Shi LL, Yang M, Schneider SR, Skolnick S, Dhir R, Radzikowska U, Kulkarni AJ, Imam MB, Veen WVD, Sokolowska M, Martin-Fontecha M, Palomares O, Nadeau KC, Akdis M, Akdis CA. Type 2 immunity in allergic diseases. Cell Mol Immunol 2025; 22:211-242. [PMID: 39962262 PMCID: PMC11868591 DOI: 10.1038/s41423-025-01261-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 01/09/2025] [Indexed: 03/01/2025] Open
Abstract
Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.
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Affiliation(s)
- Ismail Ogulur
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yasutaka Mitamura
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Duygu Yazici
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Yagiz Pat
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Sena Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Genetics, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey
| | - Manru Li
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Paolo D'Avino
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Carina Beha
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Huseyn Babayev
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Bingjie Zhao
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Can Zeyneloglu
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | | | - Ozge Ardicli
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Division of Food Processing, Milk and Dairy Products Technology Program, Karacabey Vocational School, Bursa Uludag University, Bursa, Turkey
| | - Ayca Kiykim
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Pediatrics, Division of Pediatric Allergy and Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Asuncion Garcia-Sanchez
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Biomedical and Diagnostic Science, School of Medicine, University of Salamanca, Salamanca, Spain
| | - Juan-Felipe Lopez
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Li-Li Shi
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China
| | - Minglin Yang
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Stephan R Schneider
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Stephen Skolnick
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Seed Health Inc., Los Angeles, CA, USA
| | - Raja Dhir
- Seed Health Inc., Los Angeles, CA, USA
| | - Urszula Radzikowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Abhijeet J Kulkarni
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Manal Bel Imam
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Willem van de Veen
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Mar Martin-Fontecha
- Departamento de Quimica Organica, Facultad de Optica y Optometria, Complutense University of Madrid, Madrid, Spain
| | - Oscar Palomares
- Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain
| | - Kari C Nadeau
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mubeccel Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
| | - Cezmi A Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
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Ramonell RP, Gauthier MC, Ray A, Wenzel SE. Biologic Medications for Severe Asthma: Implications for Understanding Pathogenic Heterogeneity and Endotypes. Annu Rev Med 2025; 76:339-355. [PMID: 39586024 DOI: 10.1146/annurev-med-070323-103158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Asthma is a chronic inflammatory disease of the airways long known for phenotypic heterogeneity. Phenotyping studies in asthma have led to a better characterization of disease pathogenesis, yet further work is needed to pair available treatments with disease endotypes. In this review, the biology of targeted pathways is discussed along with the efficacy of biologic therapies targeting those pathways. Results of asthma clinical trials are included, as well as results of trials in related diseases. This review then analyzes how biologics help to inform the complex immunobiology of asthma and further guide their use while identifying areas for future research.
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Affiliation(s)
- Richard P Ramonell
- Asthma and Environmental Lung Health Institute at UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
| | - Marc C Gauthier
- Asthma and Environmental Lung Health Institute at UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
| | - Anuradha Ray
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
| | - Sally E Wenzel
- Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Asthma and Environmental Lung Health Institute at UPMC, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;
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7
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Jung CG, Buchheit KM, Bochenek G, Dzoba E, Cho SH. Upper airway comorbidities of asthma. J Allergy Clin Immunol 2024; 154:1343-1354. [PMID: 39426424 DOI: 10.1016/j.jaci.2024.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 10/03/2024] [Accepted: 10/10/2024] [Indexed: 10/21/2024]
Abstract
Asthma, characterized as a chronic heterogeneous airway disease, often presents with common comorbid conditions. The concept of "one airway, one disease" was coined more than 20 years ago, emphasizing the connection between asthma and upper airway comorbidities (UACs) such as allergic or nonallergic rhinitis, chronic rhinosinusitis with or without nasal polyps, and aspirin/nonsteroidal anti-inflammatory drug-exacerbated respiratory disease. Since then, numerous studies have demonstrated that UACs are closely related and affect asthma phenotypes. Recognizing these UACs and managing them are crucial aspects of comprehensive asthma care. Addressing these conditions as part of asthma treatment can lead to better control of symptoms, improved lung function, and better quality of life. Moreover, it is important to explore the field of respiratory biologics, which represents the latest advancements in medical treatment options for patients with asthma and UACs.
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Affiliation(s)
- Chang-Gyu Jung
- Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida Morsani College of Medicine, Tampa, Fla; Department of Allergy and Clinical Immunology, Keimyung University School of Medicine, Daegu, Korea
| | - Kathleen M Buchheit
- Department of Medicine, Harvard Medical School, the Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Grazyna Bochenek
- Department of Internal Medicine, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
| | - Emily Dzoba
- Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida Morsani College of Medicine, Tampa, Fla
| | - Seong Ho Cho
- Division of Allergy-Immunology, Department of Internal Medicine, Morsani College of Medicine, University of South Florida Morsani College of Medicine, Tampa, Fla.
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8
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Yamani I, Bu Saeed K, Alsulami A, Sait S, Althumali AH. Efficacy of Biologic Therapies in the Management of Allergic Rhinitis: A Systematic Review. Cureus 2024; 16:e71408. [PMID: 39539920 PMCID: PMC11558228 DOI: 10.7759/cureus.71408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2024] [Indexed: 11/16/2024] Open
Abstract
Allergic rhinitis (AR) is a common chronic condition characterized by nasal congestion, sneezing, and itching, which significantly impacts quality of life. Traditional treatments, including antihistamines and intranasal corticosteroids, often fall short in managing moderate-to-severe cases. Recently, biologic therapies such as omalizumab and dupilumab have emerged as potential alternatives. This systematic review aims to evaluate the efficacy and safety of these biologic therapies in the management of AR. A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, and Web of Science to identify studies published between 2000 and 2024. Studies included were randomized controlled trials, cohort studies, and post-hoc analyses that assessed the impact of biologics on AR symptoms. Data on study characteristics, population demographics, intervention details, and outcomes were extracted and analyzed. The review included nine studies evaluating omalizumab and dupilumab. Omalizumab demonstrated significant improvements in nasal symptoms and quality of life, with notable efficacy in reducing symptoms and improving asthma control in patients with moderate-to-severe AR. Dupilumab also showed positive outcomes, particularly in patients with comorbid asthma and perennial AR, by reducing severe exacerbations and improving symptom scores. Biologic therapies, including omalizumab and dupilumab, offer promising alternatives for the management of AR, especially in cases that are severe or refractory to conventional treatments. The evidence supports their efficacy in improving symptoms and quality of life. Nevertheless, further research is required to address the limitations identified, including the need for long-term data and clarification of the mechanisms of action. These findings underscore the potential of biologics in advancing the treatment of AR and highlight the importance of ongoing research to optimize patient outcomes.
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Affiliation(s)
- Ibtihal Yamani
- Otolaryngology - Head and Neck Surgery, King Abdullah Medical City, Makkah, SAU
| | - Khulud Bu Saeed
- Otolaryngology - Head and Neck Surgery, Alhada Armed Forces Hospital, Taif, SAU
| | - Amjaad Alsulami
- Otolaryngology - Head and Neck Surgery, King Abdullah Medical City, Makkah, SAU
| | - Salam Sait
- Otolaryngology - Head and Neck Surgery, King Abdullah Medical City, Makkah, SAU
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9
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Goto T, Miwa T, Hashimoto K, Amesara K, Unno Y, Sakamoto H. Evaluating the Efficacy of Omalizumab in Severe Cedar Seasonal Allergic Rhinitis in Japan. Cureus 2024; 16:e63714. [PMID: 39100005 PMCID: PMC11294711 DOI: 10.7759/cureus.63714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/02/2024] [Indexed: 08/06/2024] Open
Abstract
BACKGROUND Traditional treatments for cedar seasonal allergic rhinitis include second-generation antihistamines, nasal corticosteroids, and sublingual immunotherapy (SLIT). Omalizumab (Xolair®), an anti-immunoglobulin E (IgE) monoclonal antibody, is an additional option for severe cases unresponsive to existing therapies. Numerous studies have demonstrated the therapeutic effectiveness of omalizumab for cedar seasonal allergic rhinitis; however, most reported results after only up to four weeks of follow-up. Therefore, this study evaluates the clinical efficacy of omalizumab throughout one whole cedar pollen season. Subjects and methods: This study included patients from our department and the Otorhinolaryngology Department of Minami Osaka Hospital between 2021 and 2023 who were ≥ 12 years old and had serum total IgE levels of 30-1,500 IU/mL, a baseline weight of 30-150 kg, and persistent severe nasal symptoms despite conventional treatments. Patients taking oral steroids at the time of enrollment or had fewer than two omalizumab doses were excluded. Forty-six patients (26 males, 20 females; mean age, 19.1 ± 11.2 years) met these criteria and received subcutaneous omalizumab every 2 or 4 weeks based on their IgE levels and weight. Symptoms were assessed at baseline and 4, 8, and 12 weeks post-administration using the Total Nasal Symptom Score (TNSS) and the Japanese Standard Quality of Life Questionnaire (JRQLQ No. 1) for allergic rhinitis. Results: Thirty-six patients were followed up for 8 weeks and 13 for 12 weeks. TNSS significantly improved from 6.6 to 4.5 at 4 weeks, 4.2 at 8 weeks, and 4.1 at 12 weeks (p<0.05). Nasal discharge, sneezing, nasal obstruction, itchy eyes, and tearfulness showed significant improvements (p<0.05). Quality of life scores improved in daily activities, sleep, and physical health from week 4 to week 12. Discussion: Consistent with previous findings, omalizumab significantly improved nasal and ocular symptoms and quality of life in patients with severe cedar seasonal allergic rhinitis. Despite many patients discontinuing the drug after eight weeks due to high costs, the drug's effectiveness in preventing symptom recurrence suggests potential long-term benefits. Combining omalizumab with SLIT showed no significant differences in outcomes; however, further pharmacoeconomic studies are warranted to evaluate cost-effectiveness. Conclusion: Omalizumab proved to be an effective treatment for severe cedar seasonal allergic rhinitis, providing significant symptom relief and quality of life improvements. Further studies should investigate its long-term efficacy and safety, including potential adverse effects and the development of anti-omalizumab antibodies.
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Affiliation(s)
| | - Toru Miwa
- Otolaryngology, Osaka Metropolitan University, Osaka, JPN
- Otolaryngology, Kytoto University, Kyoto, JPN
| | | | | | - Yuko Unno
- Otolaryngology, ISEIKAI International General Hospital, Osaka, JPN
| | - Hirokazu Sakamoto
- Otolaryngology, Osaka Metropolitan University, Osaka, JPN
- Otolaryngology, Osaka Metropolitan University, Osaka, JPN
- Otolaryngology, ISEIKAI International General Hospital, Osaka, JPN
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10
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Wang K, Zhang Y, Wan L, Li J, Wang C, Zhang L. Comparison of clinical traits for seasonal and perennial allergic rhinitis during allergen exposure. Allergy Asthma Proc 2024; 45:173-179. [PMID: 38755782 DOI: 10.2500/aap.2024.45.240009] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/18/2024]
Abstract
Background: Allergic rhinitis (AR) is traditionally subdivided into seasonal AR (SAR) and perennial AR (PAR) according to the type of allergen and the occurrence of symptoms during the year. There are currently no reports on the comparison of trait profiles for SAR and PAR during the allergen exposure. Purpose: The purpose of this study was to analyze the clinical characteristics of SAR and PAR during respective allergen exposure periods to provide valuable information for the development of treatment strategies. Methods: This study was performed between August 1, 2021, and January 31, 2022, in the Department of Allergy, Beijing Tongren Hospital. We continuously included diagnosed SAR and PAR outpatients who volunteered to participate in the survey. A questionnaire with regard to medical history, severity of symptoms, and diagnosis and treatment status was collected. Results: A total of 296 patients with SAR and 448 with PAR were finally recruited. Patients with SAR had more severe rhinorrhea compared with patients with PAR (p < 0.001), whereas there was no statistically significant difference in the severity of itching, sneezing, and congestion between the two entities (p ≥ 0.05). Both the gritty and watery eyes of patients with SAR were noticeably more severe than those of patients with PAR (PTotal Ocular Symptom Score [PTOSS] < 0.001). AR symptom severity is mainly associated with the comorbid allergic conjunctivitis (odds ratio 1.94 [95% confidence interval, 1.21-3.09]). SAR patients and PAR patients show no statistically significant differences in terms of their frequency of visits, annual expenditure, and choice of medication treatment for AR (p > 0.05). The overall control under standard medication of both patients with PAR and those with SAR is not ideal, especially in SAR. Conclusion: The current cross-sectional study demonstrated that the patients with SAR exhibited more severe overall clinical symptoms than those with PAR, especially nasal rhinorrhea and gritty and watery eyes. Both of the two disease entities have poor control under standardized medication treatment, especially in SAR. Further multicenter longitudinal studies that involve larger and more diverse populations should be conducted to provide a more accurate and comprehensive understanding of the condition.
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Affiliation(s)
- Kunpeng Wang
- From the Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yuan Zhang
- From the Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Lianqi Wan
- From the Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Jingyun Li
- Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China, and
| | - Chengshuo Wang
- From the Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Luo Zhang
- From the Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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11
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Zhang Y, Yan B, Zhu Z, Wang X, Song X, Zhu D, Ma T, Zhang Y, Meng C, Wang G, Wang C, Zhang L. Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial. EClinicalMedicine 2024; 69:102467. [PMID: 38356731 PMCID: PMC10864214 DOI: 10.1016/j.eclinm.2024.102467] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/18/2024] [Accepted: 01/19/2024] [Indexed: 02/16/2024] Open
Abstract
Background There is no trial to assess the benefits of periodically using biologics during the pollen season in patients with uncontrolled seasonal allergic rhinitis (SAR), who have moderate-to-severe symptoms even after standard-of-care. This trial aimed to evaluate the efficacy and safety of the add-on administration of stapokibart, a humanised monoclonal antibody that targets interleukin-4 receptor alpha, in patients with uncontrolled SAR. Methods In this investigator-initiated, randomised, double-blind, placebo-controlled trial, eligible patients received either stapokibart 600-300 mg weekly (QW), every 2 weeks (Q2W), or placebo QW for 4 weeks. All patients were given mometasone furoate nasal spray and loratadine throughout the trial. The primary endpoint was the mean change from baseline in daily reflective total nasal symptom score (rTNSS) during 2-week treatment. Secondary efficacy outcomes included: the mean change from baseline in daily rTNSS during 4-week treatment; the mean changes and the mean percentage changes from baseline during 2-week and 4-week treatment in 1) daily rTNSS and reflective total ocular symptom score (rTOSS), 2) morning (AM)/evening (PM) rTNSS and rTOSS, 3) AM instantaneous total nasal symptom score (iTNSS) and instantaneous total ocular symptom score (iTOSS), 4) individual nasal and ocular symptoms; the change from baseline in Rhinoconjunctivitis Quality of-Life Questionnaire score during 4-week treatment. Exploratory endpoints included the change of prespecified markers related to type 2 inflammation pre- and post-treatment. Safety, immunogenicity, and pharmacokinetics were also evaluated. This study is registered with www.clinicaltrials.gov (NCT05470647). Findings Between August 17, 2022, and December 28, 2022, 92 patients with uncontrolled SAR were enrolled from 4 centres in China and randomly assigned to receive stapokibart 600-300 mg QW (n = 31), stapokibart 600-300 mg Q2W (n = 30), or placebo QW (n = 31), of whom 86 (93%) completed the study. Both stapokibart Q2W and QW did not significantly improve mean change from baseline in daily rTNSS compared with placebo in 2 weeks. The least-squares (LS) mean differences (97.5% confidence interval [CI]) compared with placebo were -1.0 (-2.3, 0.2) in stapokibart Q2W group (p = 0.065) and -0.2 (-1.5, 1.0) in stapokibart QW group (p = 0.67). For the secondary outcomes, compared with placebo, stapokibart Q2W presented significant improvements in the mean percentage change from baseline in daily rTNSS in 2 weeks (LS mean difference -12.9%, 95% CI -25.3%, -0.4%, p = 0.043), as well as AM iTNSS over 2 weeks (LS mean difference -17.4%, 95% CI -31.0%, -3.8%, p = 0.013) and 4 weeks (LS mean difference -15.4%, 95% CI -29.0%, -1.9%, p = 0.026). Additionally, the nasal congestion score was significantly lower in stapokibart Q2W than placebo during 2-week (LS mean difference -0.4, 95% CI -0.7, -0.1, p = 0.014) and 4-week (LS mean difference -0.4, 95% CI -0.7, -0.04, p = 0.028) treatment. Treatment-emergent adverse events (TEAEs) occurred in 48% (15/31), 33% (10/30), and 61% (19/31) of patients receiving stapokibart QW, Q2W, and placebo, respectively. Most reported TEAEs were sinus bradycardia, hyperlipidaemia, and blood uric acid increased. Interpretation In this phase 2 trial, both stapokibart regimens had an acceptable safety and tolerability profile but did not significantly improve daily rTNSS in patients with uncontrolled SAR. The efficacy of stapokibart in patients with uncontrolled SAR is being further investigated in ongoing phase 3 trials (clinicaltrials.gov, NCT05908032). Funding Ministry of Science and Technology of the People's Republic of China; Ministry of Education of the People's Republic of China; National Natural Science Foundation of China; Chinese Academy of Medical Sciences.
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Affiliation(s)
- Yuan Zhang
- Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing 100005, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing 100005, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Bing Yan
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing 100005, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Zehua Zhu
- Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing 100005, China
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing 100005, China
| | - Xueyan Wang
- Allergy Centre, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Xicheng Song
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, China
- Shandong Provincial Clinical Research Centre for Otorhinolaryngologic Diseases, Yantai, Shandong 264000, China
| | - Dongdong Zhu
- Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
- Jilin Provincial Key Laboratory of Precise Diagnosis and Treatment of Upper Airway Allergic Diseases, Changchun, Jilin 130033, China
| | - Tingting Ma
- Allergy Centre, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Yu Zhang
- Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, China
- Shandong Provincial Clinical Research Centre for Otorhinolaryngologic Diseases, Yantai, Shandong 264000, China
| | - Cuida Meng
- Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
- Jilin Provincial Key Laboratory of Precise Diagnosis and Treatment of Upper Airway Allergic Diseases, Changchun, Jilin 130033, China
| | - Guangke Wang
- Department of Otolaryngology, Head and Neck Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, China
| | - Chengshuo Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing 100005, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100005, China
| | - Luo Zhang
- Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing 100005, China
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China
- Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of Nasal Diseases, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing 100005, China
- Research Unit of Diagnosis and Treatment of Chronic Nasal Diseases, Chinese Academy of Medical Sciences, Beijing 100005, China
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12
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Zhang Y, Zhang L. Current challenges with adherence to pharmacotherapy in allergic rhinitis. Expert Opin Pharmacother 2024; 25:335-338. [PMID: 38602452 DOI: 10.1080/14656566.2024.2336082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 03/25/2024] [Indexed: 04/12/2024]
Affiliation(s)
- Yuan Zhang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
| | - Luo Zhang
- Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing, China
- Beijing Laboratory of Allergic Diseases and Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, China
- Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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13
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Fan T, Jiang K, Wang Z, Chang Y, Tian H, Huang J. Crocetin inhibits mast cell-dependent immediate-type allergic reactions through Ca 2+/PLC/IP3 and TNF pathway. Int Immunopharmacol 2024; 128:111583. [PMID: 38286072 DOI: 10.1016/j.intimp.2024.111583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Revised: 01/21/2024] [Accepted: 01/22/2024] [Indexed: 01/31/2024]
Abstract
Crocetin is a kind of glycocone naturally occurring in Crocus sativus L.. It is an active metabolite produced by biohydrolysis of Crocus sativus L.. Crocetin has anti-cardiovascular diseases and antioxidant effects, but its anti-allergic effect has not been reported. In this study, the inhibitory effect of crocetin on immunoglobulin E (IgE) - mediated allergic reaction and the mechanism of action were investigated. The passive cutaneous anaphylaxis (PCA) was used to elucidate the anti-allergic effects of crocetin in vivo. Degranulation assay, calcium imaging, and cytokine release assay were to evaluate the anti-allergic effect of crocetin in vitro. We found that crocetin IgE-mediated RBL-2H3 cell degranulation and allergy both in vitro and in vivo. The TNF pathway was inhibited by crocetin in our RNA-seq sequences, Furthermore, crocetin inhibits IgE-mediated calcium influx, and PLC / IP3 phosphorylation in RBL-2H3 cells. Our findings suggested that crocetin revealed prominent anti-allergy activity through TNF and Ca2+/PLC/IP3 pathway.
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Affiliation(s)
- Ting Fan
- Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Kai Jiang
- Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Zixiao Wang
- Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Yu Chang
- Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Hua Tian
- Department of Respiratory and geriatrics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
| | - Jing Huang
- Department of Clinical Pharmacy, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
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14
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Iwasaki Y, Okada Y, Imai T. A case of cow's milk allergy treated with rush oral immunotherapy with omalizumab. Pediatr Int 2024; 66:e15802. [PMID: 39076029 DOI: 10.1111/ped.15802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 05/01/2024] [Accepted: 05/27/2024] [Indexed: 07/31/2024]
Affiliation(s)
- Yasushi Iwasaki
- Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
| | - Yuki Okada
- Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
| | - Tananori Imai
- Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan
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15
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Lin Y, Wang W, Zhu Z, Aodeng S, Wang L, Liu Y, Li J, Zha Y, Wang X, Lv W. Adverse Events for Monoclonal Antibodies in Patients with Allergic Rhinitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J Clin Med 2023; 12:2848. [PMID: 37109185 PMCID: PMC10144224 DOI: 10.3390/jcm12082848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/02/2023] [Accepted: 03/06/2023] [Indexed: 04/29/2023] Open
Abstract
(1) Background: Allergic rhinitis (AR) is a common disease in otolaryngology and novel biological therapies are required for clinical needs. To assess the tolerability of monoclonal antibodies, justifying their clinical applications, we presented a comprehensive safety profile of biologics in AR; (2) Methods: A systematic literature search was conducted following PRISMA guidelines for randomized clinical trials comparing monoclonal antibodies and placebo in AR. PubMed, Web of Science, Medline, and Cochrane were searched up until 9 January 2023. Among 3590 records in total, 12 studies with more than 2600 patients were included. Quality was assessed for all studies using Cochrane risk-of-bias tool for randomized trials, and subgrouped meta-analysis was performed; (3) Results: We accomplished an up-to-date literature overview and analysis on adverse events of monoclonal antibodies in AR. Total, common, severe, discontinuation-causing, and serious adverse events failed to reach statistical significance. Country was an essential factor for heterogeneity, and urticaria was the adverse event at highest risk (RR 2.81, 95% CI 0.79-9.95); (4) Conclusions: Monoclonal antibodies are considered well tolerated and relatively safe in patients with AR. The regions of patients and hypersensitive adverse reactions such as urticaria require a special caution in biological treatments in AR.
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Affiliation(s)
- Yuxi Lin
- 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100006, China
| | - Weiqing Wang
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Zhenzhen Zhu
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Surita Aodeng
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Lei Wang
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Yuzhuo Liu
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Jingjing Li
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Yang Zha
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Xiaowei Wang
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
| | - Wei Lv
- Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100006, China
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Wise SK, Damask C, Roland LT, Ebert C, Levy JM, Lin S, Luong A, Rodriguez K, Sedaghat AR, Toskala E, Villwock J, Abdullah B, Akdis C, Alt JA, Ansotegui IJ, Azar A, Baroody F, Benninger MS, Bernstein J, Brook C, Campbell R, Casale T, Chaaban MR, Chew FT, Chambliss J, Cianferoni A, Custovic A, Davis EM, DelGaudio JM, Ellis AK, Flanagan C, Fokkens WJ, Franzese C, Greenhawt M, Gill A, Halderman A, Hohlfeld JM, Incorvaia C, Joe SA, Joshi S, Kuruvilla ME, Kim J, Klein AM, Krouse HJ, Kuan EC, Lang D, Larenas-Linnemann D, Laury AM, Lechner M, Lee SE, Lee VS, Loftus P, Marcus S, Marzouk H, Mattos J, McCoul E, Melen E, Mims JW, Mullol J, Nayak JV, Oppenheimer J, Orlandi RR, Phillips K, Platt M, Ramanathan M, Raymond M, Rhee CS, Reitsma S, Ryan M, Sastre J, Schlosser RJ, Schuman TA, Shaker MS, Sheikh A, Smith KA, Soyka MB, Takashima M, Tang M, Tantilipikorn P, Taw MB, Tversky J, Tyler MA, Veling MC, Wallace D, Wang DY, White A, Zhang L. International consensus statement on allergy and rhinology: Allergic rhinitis - 2023. Int Forum Allergy Rhinol 2023; 13:293-859. [PMID: 36878860 DOI: 10.1002/alr.23090] [Citation(s) in RCA: 160] [Impact Index Per Article: 80.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 11/11/2022] [Accepted: 09/13/2022] [Indexed: 03/08/2023]
Abstract
BACKGROUND In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR-Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR-Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence-based findings and recommendation from the full document. METHODS ICAR-Allergic Rhinitis 2023 employed established evidence-based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. RESULTS ICAR-Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. CONCLUSION The ICAR-Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.
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Affiliation(s)
- Sarah K Wise
- Otolaryngology-HNS, Emory University, Atlanta, Georgia, USA
| | - Cecelia Damask
- Otolaryngology-HNS, Private Practice, University of Central Florida, Lake Mary, Florida, USA
| | - Lauren T Roland
- Otolaryngology-HNS, Washington University, St. Louis, Missouri, USA
| | - Charles Ebert
- Otolaryngology-HNS, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Joshua M Levy
- Otolaryngology-HNS, Emory University, Atlanta, Georgia, USA
| | - Sandra Lin
- Otolaryngology-HNS, University of Wisconsin, Madison, Wisconsin, USA
| | - Amber Luong
- Otolaryngology-HNS, McGovern Medical School of the University of Texas, Houston, Texas, USA
| | - Kenneth Rodriguez
- Otolaryngology-HNS, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Ahmad R Sedaghat
- Otolaryngology-HNS, University of Cincinnati, Cincinnati, Ohio, USA
| | - Elina Toskala
- Otolaryngology-HNS, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | | | - Baharudin Abdullah
- Otolaryngology-HNS, Universiti Sains Malaysia, Kubang, Kerian, Kelantan, Malaysia
| | - Cezmi Akdis
- Immunology, Infectious Diseases, Swiss Institute of Allergy and Asthma Research, Davos, Switzerland
| | - Jeremiah A Alt
- Otolaryngology-HNS, University of Utah, Salt Lake City, Utah, USA
| | | | - Antoine Azar
- Allergy/Immunology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Fuad Baroody
- Otolaryngology-HNS, University of Chicago, Chicago, Illinois, USA
| | | | | | - Christopher Brook
- Otolaryngology-HNS, Harvard University, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Raewyn Campbell
- Otolaryngology-HNS, Macquarie University, Sydney, NSW, Australia
| | - Thomas Casale
- Allergy/Immunology, University of South Florida College of Medicine, Tampa, Florida, USA
| | - Mohamad R Chaaban
- Otolaryngology-HNS, Cleveland Clinic, Case Western Reserve University, Cleveland, Ohio, USA
| | - Fook Tim Chew
- Allergy/Immunology, Genetics, National University of Singapore, Singapore, Singapore
| | - Jeffrey Chambliss
- Allergy/Immunology, University of Texas Southwestern, Dallas, Texas, USA
| | - Antonella Cianferoni
- Allergy/Immunology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | | | | | | | - Anne K Ellis
- Allergy/Immunology, Queens University, Kingston, ON, Canada
| | | | - Wytske J Fokkens
- Otorhinolaryngology, Amsterdam University Medical Centres, Amsterdam, Netherlands
| | | | - Matthew Greenhawt
- Allergy/Immunology, Pediatrics, University of Colorado, Children's Hospital Colorado, Aurora, Colorado, USA
| | - Amarbir Gill
- Otolaryngology-HNS, University of Michigan, Ann Arbor, Michigan, USA
| | - Ashleigh Halderman
- Otolaryngology-HNS, University of Texas Southwestern, Dallas, Texas, USA
| | - Jens M Hohlfeld
- Respiratory Medicine, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover Medical School, German Center for Lung Research, Hannover, Germany
| | | | - Stephanie A Joe
- Otolaryngology-HNS, University of Illinois Chicago, Chicago, Illinois, USA
| | - Shyam Joshi
- Allergy/Immunology, Oregon Health and Science University, Portland, Oregon, USA
| | | | - Jean Kim
- Otolaryngology-HNS, Johns Hopkins University, Baltimore, Maryland, USA
| | - Adam M Klein
- Otolaryngology-HNS, Emory University, Atlanta, Georgia, USA
| | - Helene J Krouse
- Otorhinolaryngology Nursing, University of Texas Rio Grande Valley, Edinburg, Texas, USA
| | - Edward C Kuan
- Otolaryngology-HNS, University of California Irvine, Orange, California, USA
| | - David Lang
- Allergy/Immunology, Cleveland Clinic, Cleveland, Ohio, USA
| | | | | | - Matt Lechner
- Otolaryngology-HNS, University College London, Barts Health NHS Trust, London, UK
| | - Stella E Lee
- Otolaryngology-HNS, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Victoria S Lee
- Otolaryngology-HNS, University of Illinois Chicago, Chicago, Illinois, USA
| | - Patricia Loftus
- Otolaryngology-HNS, University of California San Francisco, San Francisco, California, USA
| | - Sonya Marcus
- Otolaryngology-HNS, Stony Brook University, Stony Brook, New York, USA
| | - Haidy Marzouk
- Otolaryngology-HNS, State University of New York Upstate, Syracuse, New York, USA
| | - Jose Mattos
- Otolaryngology-HNS, University of Virginia, Charlottesville, Virginia, USA
| | - Edward McCoul
- Otolaryngology-HNS, Ochsner Clinic, New Orleans, Louisiana, USA
| | - Erik Melen
- Pediatric Allergy, Karolinska Institutet, Stockholm, Sweden
| | - James W Mims
- Otolaryngology-HNS, Wake Forest University, Winston Salem, North Carolina, USA
| | - Joaquim Mullol
- Otorhinolaryngology, Hospital Clinic Barcelona, Barcelona, Spain
| | - Jayakar V Nayak
- Otolaryngology-HNS, Stanford University, Palo Alto, California, USA
| | - John Oppenheimer
- Allergy/Immunology, Rutgers, State University of New Jersey, Newark, New Jersey, USA
| | | | - Katie Phillips
- Otolaryngology-HNS, University of Cincinnati, Cincinnati, Ohio, USA
| | - Michael Platt
- Otolaryngology-HNS, Boston University, Boston, Massachusetts, USA
| | | | | | - Chae-Seo Rhee
- Rhinology/Allergy, Seoul National University Hospital and College of Medicine, Seoul, Korea
| | - Sietze Reitsma
- Otolaryngology-HNS, University of Amsterdam, Amsterdam, Netherlands
| | - Matthew Ryan
- Otolaryngology-HNS, University of Texas Southwestern, Dallas, Texas, USA
| | - Joaquin Sastre
- Allergy, Fundacion Jiminez Diaz, University Autonoma de Madrid, Madrid, Spain
| | - Rodney J Schlosser
- Otolaryngology-HNS, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Theodore A Schuman
- Otolaryngology-HNS, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Marcus S Shaker
- Allergy/Immunology, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
| | - Aziz Sheikh
- Primary Care, University of Edinburgh, Edinburgh, Scotland
| | - Kristine A Smith
- Otolaryngology-HNS, University of Utah, Salt Lake City, Utah, USA
| | - Michael B Soyka
- Otolaryngology-HNS, University of Zurich, University Hospital of Zurich, Zurich, Switzerland
| | - Masayoshi Takashima
- Otolaryngology-HNS, Houston Methodist Academic Institute, Houston, Texas, USA
| | - Monica Tang
- Allergy/Immunology, University of California San Francisco, San Francisco, California, USA
| | | | - Malcolm B Taw
- Integrative East-West Medicine, University of California Los Angeles, Westlake Village, California, USA
| | - Jody Tversky
- Allergy/Immunology, Johns Hopkins University, Baltimore, Maryland, USA
| | - Matthew A Tyler
- Otolaryngology-HNS, University of Minnesota, Minneapolis, Minnesota, USA
| | - Maria C Veling
- Otolaryngology-HNS, University of Texas Southwestern, Dallas, Texas, USA
| | - Dana Wallace
- Allergy/Immunology, Nova Southeastern University, Ft. Lauderdale, Florida, USA
| | - De Yun Wang
- Otolaryngology-HNS, National University of Singapore, Singapore, Singapore
| | - Andrew White
- Allergy/Immunology, Scripps Clinic, San Diego, California, USA
| | - Luo Zhang
- Otolaryngology-HNS, Beijing Tongren Hospital, Beijing, China
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Grimm D, Hwang PH, Lin YT. The link between allergic rhinitis and chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg 2023; 31:3-10. [PMID: 36729858 DOI: 10.1097/moo.0000000000000865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE OF REVIEW Allergic rhinitis and chronic rhinosinusitis (CRS) are common disorders affecting millions of people worldwide. Although allergic rhinitis and CRS are distinct clinical entities, certain CRS endotypes share similar pathological mechanisms as those seen in patients with allergic rhinitis. This review assesses the literature behind the similarities and differences seen in patients with CRS and allergic rhinitis, and the role atopy might play in the pathophysiology of CRS. RECENT FINDINGS In examining the associations between allergic rhinitis and CRS, most studies have focused primarily on CRS with nasal polyps and type 2 inflammation in CRS. Recent studies have demonstrated the similarities and differences in pathologic mechanisms behind allergic rhinitis and CRS, with an emphasis on patient endotypes, genetics, and the nasoepithelial immunologic barrier. Related immunopathology shared by allergic rhinitis and type 2 inflammation in CRS has allowed for therapeutic overlap with biologic treatments. SUMMARY Allergic rhinitis and CRS often present as comorbid conditions, and understanding the relationship between allergic rhinitis and CRS is important when considering treatment options. Advances in understanding the genetics and immunology, as well as biologic and immunotherapeutic treatments have improved outcomes in patients with CRS, especially in the setting of atopy.
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Affiliation(s)
| | - Peter H Hwang
- Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Yi-Tsen Lin
- Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan
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Atanasio A, Orengo JM, Sleeman MA, Stahl N. Biologics as novel therapeutics for the treatment of allergy: Challenges and opportunities. FRONTIERS IN ALLERGY 2022; 3:1019255. [DOI: 10.3389/falgy.2022.1019255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 09/29/2022] [Indexed: 11/06/2022] Open
Abstract
Over the last 4 decades there has been a significant global increase in the incidence and prevalence of IgE-mediated allergy. Although much progress has been made in the management of allergy via patient education, pharmacotherapy and immunomodulatory treatment regimens, significant unmet need remains. Advancements in our knowledge base surrounding the type 2 immune response, production of IgE and maintenance of immunological memory has led the field to explore targeted intervention of allergic pathways using monoclonal antibodies (mAbs). Intervention at various stages of the allergic cascade offers the opportunity to prevent initiation and/or maintenance of the type 2 immune response and effectively provide therapeutic benefit to patients. Furthermore, a better understanding of the protective mechanisms involved in allergen specific immunotherapy (AIT) has led us to appreciate the interplay of immunoglobulins in the allergic response, specifically the benefit in shifting the IgG:IgE ratio in favor of functionally relevant blocking IgG. Thus, treatments that lower IgE or boost IgG with the ability to outcompete IgE binding to allergen also present a favorable approach in the treatment of allergy. In this short review we discuss and highlight recent advances in the use of biologics to treat severe allergy, highlighting the key challenges but also the significant opportunities and advances to date.
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Tang R, Lei S, Zhu L, Lv Y, Li H. Prevention of omalizumab for seasonal allergic rhinoconjunctivitis: a retrospective cohort study. Front Immunol 2022; 13:913424. [PMID: 35967427 PMCID: PMC9366907 DOI: 10.3389/fimmu.2022.913424] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 05/30/2022] [Indexed: 12/04/2022] Open
Abstract
Background Allergic rhinoconjunctivitis (ARC) is an allergic disease that is characterized by conjunctival and nasal symptoms such as edema and congestion of conjunctiva, rhinorrhea, sneezing, and blocked nose. Seasonal ARC (SARC) is usually induced by seasonal allergens and often occurs at specific times during the year. Traditional treatments of SARC include nasal corticosteroids, antihistamines, and mast cell membrane stabilizers. Biological agents such as omalizumab have also been proved effective in the treatment of SARC. Objectives We aim to certify the preventative efficacy of omalizumab for SARC and explore its influence factors. Methods Medical records of 64 SARC patients were retrospectively analyzed, and generalized linear models were used to analyze influence factors of efficacy of omalizumab. Results Compared with forepassed pollen season without omalizumab treatment, the combined symptom and medication score (CSMS) of ARC with pre-seasonal omalizumab was significantly lower (with omalizumab: 0.67[0.00,1.83], without omalizumab: 4.00[2.83,4.96], p<0.001, max score=6). Subgroup analysis was conducted to explore the influence factor of preventative efficacy of omalizumab. The CSMS with omalizumab treatment were not significantly different among different age, gender, dosage, number of injections, and injection date subgroups (p>0.05). Conclusion Pre-seasonal omalizumab treatment could significantly relieve SARC related symptoms and reduce medication use. This preventative efficacy would not be influenced by the dosage and number of injections of omalizumab. A single dose of 150mg omalizumab could achieve a satisfactory outcome.
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Affiliation(s)
- Rui Tang
- Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Disease, National Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID), Beijing, China
| | - Shubin Lei
- Eight-year program of Clinical Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Liping Zhu
- Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yuzhen Lv
- Pneumology Department, Yangquan Coal Industry (Group) General Hospital, Shanxi, China
| | - Hong Li
- Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Disease, National Clinical Research Center for Dermatologic and Immunologic Diseases(NCRC-DID), Beijing, China
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20
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Kawakami T, Kasakura K, Kawakami Y, Ando T. Immunoglobulin E-Dependent Activation of Immune Cells in Rhinovirus-Induced Asthma Exacerbation. FRONTIERS IN ALLERGY 2022; 3:835748. [PMID: 35386658 PMCID: PMC8974681 DOI: 10.3389/falgy.2022.835748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 01/24/2022] [Indexed: 11/26/2022] Open
Abstract
Acute exacerbation is the major cause of asthma morbidity, mortality, and health-care costs. Respiratory viral infections, particularly rhinovirus (RV) infections, are associated with the majority of asthma exacerbations. The risk for bronchoconstriction with RV is associated with allergic sensitization and type 2 airway inflammation. The efficacy of the humanized anti-IgE monoclonal antibody omalizumab in treating asthma and reducing the frequency and severity of RV-induced asthma exacerbation is well-known. Despite these clinical data, mechanistic details of omalizumab's effects on RV-induced asthma exacerbation have not been well-defined for years due to the lack of appropriate animal models. In this Perspective, we discuss potential IgE-dependent roles of mast cells and dendritic cells in asthma exacerbations.
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Affiliation(s)
- Toshiaki Kawakami
- Laboratory of Allergic Diseases, Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, United States
- Department of Dermatology, School of Medicine, University of California, San Diego, La Jolla, CA, United States
- *Correspondence: Toshiaki Kawakami
| | - Kazumi Kasakura
- Laboratory of Allergic Diseases, Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, United States
| | - Yu Kawakami
- Laboratory of Allergic Diseases, Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA, United States
| | - Tomoaki Ando
- Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan
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21
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Zhang Y, Xi L, Gao Y, Huang Y, Cao F, Xiong W, Wang C, Zhang L. Omalizumab is effective in the preseasonal treatment of seasonal allergic rhinitis. Clin Transl Allergy 2022; 12:e12094. [PMID: 35024137 PMCID: PMC8727318 DOI: 10.1002/clt2.12094] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 11/26/2021] [Accepted: 12/12/2021] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND To date no study has evaluated the efficacy of preseasonal omalizumab therapy with cost effective dose and at appropriate time point compared with standard medication in seasonal allergic rhinitis (SAR) patients. METHODS This was a prospective randomized controlled open-label single-centre trial. 32 SAR patients were randomized to receive a single injection of omalizumab 300-mg approximately two weeks before start of the pollen period (PP) or medication therapy. All patients completed daily questionnaires; recording symptoms, medication use and quality of life (QoL) throughout the observation period. The primary efficacy parameter was the mean daily Combined Symptom and Medication Score (CSMS). RESULTS Preseasonal omalizumab significantly reduced the changes of mean daily CSMS of nose during the PP (p < 0.001), peak pollen period (PPP) and PP after PPP (PPP-PP) (p = 0.002) and Post-PP (p = 0.009) compared to standard medication. The proportion of allergy symptoms-relieving medication-free days during PPP-PP was also significantly higher in preseasonal omalizumab-treated group (76.2(16.7-98.8))% than in medication-treated group (19.0(0-71.4))% (p = 0.030). Omalizumab could achieve the same nasal symptom control during the entire pollen season and better eye symptoms relieving results in PP (p = 0.046) and PPP-PP (p = 0.004) than medication treatment. Significantly greater improvement in QoL was also obtained with omalizumab-pretreatment during the PP (p = 0.037) and PPP-PP (p = 0.004). CONCLUSIONS Administration of a single injection of 300 mg omalizumab two weeks before start of the pollen season achieves better overall control of symptoms and QoL, with significantly reduced allergy symptoms-relieving medication usage, compared with standard pharmacotherapy in SAR patients.
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Affiliation(s)
- Yuan Zhang
- Department of AllergyBeijing TongRen HospitalCapital Medical UniversityBeijingChina
- Beijing Key Laboratory of Nasal DiseasesBeijing Institute of OtolaryngologyBeijingChina
- Research Unit of Diagnosis and Treatment of Chronic Nasal DiseasesChinese Academy of Medical SciencesBeijingChina
| | - Lin Xi
- Department of AllergyBeijing TongRen HospitalCapital Medical UniversityBeijingChina
- Beijing Key Laboratory of Nasal DiseasesBeijing Institute of OtolaryngologyBeijingChina
- Research Unit of Diagnosis and Treatment of Chronic Nasal DiseasesChinese Academy of Medical SciencesBeijingChina
| | - Yunbo Gao
- Department of Otolaryngology Head and Neck SurgeryBeijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Yanran Huang
- Department of Otolaryngology Head and Neck SurgeryBeijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Feifei Cao
- Department of AllergyBeijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Wei Xiong
- Department of AllergyBeijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Chengshuo Wang
- Department of AllergyBeijing TongRen HospitalCapital Medical UniversityBeijingChina
- Beijing Key Laboratory of Nasal DiseasesBeijing Institute of OtolaryngologyBeijingChina
- Research Unit of Diagnosis and Treatment of Chronic Nasal DiseasesChinese Academy of Medical SciencesBeijingChina
- Department of Otolaryngology Head and Neck SurgeryBeijing TongRen HospitalCapital Medical UniversityBeijingChina
| | - Luo Zhang
- Department of AllergyBeijing TongRen HospitalCapital Medical UniversityBeijingChina
- Beijing Key Laboratory of Nasal DiseasesBeijing Institute of OtolaryngologyBeijingChina
- Research Unit of Diagnosis and Treatment of Chronic Nasal DiseasesChinese Academy of Medical SciencesBeijingChina
- Department of Otolaryngology Head and Neck SurgeryBeijing TongRen HospitalCapital Medical UniversityBeijingChina
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Layhadi JA, Palmer E, Sharif H, Shamji MH. Current Drug Treatments for Allergy. ENCYCLOPEDIA OF RESPIRATORY MEDICINE 2022:477-490. [DOI: 10.1016/b978-0-08-102723-3.00236-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Tsabouri S, Ntritsos G, Koskeridis F, Evangelou E, Olsson P, Kostikas K. Omalizumab for the treatment of allergic rhinitis: a systematic review and meta-analysis. Rhinology 2021; 59:501-510. [PMID: 34714895 DOI: 10.4193/rhin21.159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND Allergic rhinitis (AR), an IgE mediated inflammatory disease, significantly impacts quality of life of a considerable proportion of the general population. Omalizumab, a humanized monoclonal antibody against IgE, has been evaluated for both seasonal and perennial AR. We aimed to assess the efficacy and safety of omalizumab in randomized controlled trials (RCTs) in inadequately controlled AR. METHODS We conducted a systematic literature search of RCTs evaluating the safety and efficacy of omalizumab in AR. We synthesized evidence for clinical improvement of AR symptoms, quality of life, reduction of the use of rescue medication, and adverse events. RESULTS The systematic search returned 289 articles, of which 12 RCTs were eligible for data extraction and meta-analysis. Omalizumab reduced the Daily Nasal Symptom Severity Score (DNSSS) by a summary standardized mean difference of -0.41 points with large heterogeneity; omalizumab significantly reduced the DNSSS both in the 3 cedar pollen-induced AR trials by -0.97 points and to a lower extent in the remaining five non-cedar trials by -0.19 points. Omalizumab also improved the Daily Ocular Symptom Severity Score (DOSSS) by a summary standardized mean difference of -0.30 points with large heterogeneity; the Rhino-conjunctivitis Quality of Life Questionnaire by a summary standardized mean difference of -0.45 points with no heterogeneity and the mean daily consumption of rescue antihistamines by a summary standardized mean difference of -0.21 with large heterogeneity. No statistically significant difference in the occurrence of adverse events was observed between omalizumab and placebo. CONCLUSION Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with a conventional treatment.
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Affiliation(s)
- S Tsabouri
- University of Ioannina, Medical School, Ioannina, Greece
| | - G Ntritsos
- University of Ioannina, Medical School, Ioannina, Greece
| | - F Koskeridis
- University of Ioannina, Medical School, Ioannina, Greece
| | - E Evangelou
- University of Ioannina, Medical School, Ioannina, Greece
| | | | - K Kostikas
- University of Ioannina, Medical School, Ioannina, Greece
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Igarashi A, Kaur H, Choubey A, Popli A, Muthukumar M, Yoshisue H, Funakubo M, Ohta K. Cost-Effectiveness Analysis of Omalizumab for Severe Allergic Asthma in Japan Using Real-World Evidence. Value Health Reg Issues 2021; 27:41-48. [PMID: 34784547 DOI: 10.1016/j.vhri.2021.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 06/09/2021] [Accepted: 07/13/2021] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Omalizumab is a recommended add-on therapy for patients with severe allergic asthma who remain uncontrolled despite treatment with standard of care (SoC). This study evaluated the cost-effectiveness of omalizumab compared with SoC applying real-world clinical outcomes in adult patients with severe allergic asthma in Japan. METHODS A validated Markov model was adapted for Japan and compared the cost-effectiveness of omalizumab as an add-on therapy to SoC versus SoC alone using the most recently updated price of omalizumab. A Japanese real-world postmarketing surveillance and a pivotal randomized clinical trial were used as inputs for clinical effectiveness. Japanese life tables and literature were accessed for mortality data and unit costs were extracted from a Japanese insurance claims database. Quality of life data were retrieved from the clinical trial. RESULTS In the base case, the incremental cost-effectiveness ratio for omalizumab add-on therapy was ¥2.85 million per quality-adjusted life-year gained (approximately €21 000; 1€ = ¥133.26) compared with SoC alone. The model appeared to be most sensitive to changes in clinically significant severe exacerbation fatality, day-to-day asthma symptom utilities for SoC, discount rates for benefits, day-to-day asthma symptom utilities for omalizumab responders, time horizon, and the annual cost of omalizumab. The results of the probabilistic sensitivity analysis showed that the probability of omalizumab being cost-effective was 93% to 98% at a threshold of ¥5 to ¥6 million (willingness-to-pay for 1 quality-adjusted life-year). CONCLUSIONS Omalizumab add-on therapy is cost-effective compared with SoC alone in Japan in severe allergic asthma population who are uncontrolled with high-dose inhaled corticosteroid and other controllers.
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Affiliation(s)
- Ataru Igarashi
- Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
| | - Harneet Kaur
- Value & Access, CONEXTS, Novartis Healthcare Pvt. Ltd., Hyderabad, India
| | - Abhay Choubey
- Value & Access, CONEXTS, Novartis Healthcare Pvt. Ltd., Hyderabad, India
| | - Akshay Popli
- Value & Access, CONEXTS, Novartis Healthcare Pvt. Ltd., Hyderabad, India
| | | | | | - Minako Funakubo
- Health Economic & Outcomes Research, Novartis Pharma KK, Tokyo, Japan
| | - Ken Ohta
- Department of Respiratory Medicine and Allergology, Japan Anti-Tuberculosis Association (JATA), Fukujuji Hospital, Tokyo, Japan
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Efficacy predictors of omalizumab in Chinese patients with moderate-to-severe allergic asthma: Findings from a post-hoc analysis of a randomised phase III study. World Allergy Organ J 2021; 13:100469. [PMID: 34611470 PMCID: PMC8461112 DOI: 10.1016/j.waojou.2020.100469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 08/19/2020] [Accepted: 09/09/2020] [Indexed: 02/05/2023] Open
Abstract
Background Omalizumab has demonstrated efficacy as an add-on therapy in Chinese patients with moderate-to-severe allergic asthma. This post-hoc analysis assessed the potential predictors for the efficacy of omalizumab in these patients. Methods A post-hoc analysis was performed on a Phase III, randomised, controlled study conducted in Chinese patients with moderate-to-severe persistent allergic asthma (NCT01202903). We evaluated if levels of pre-treatment serum total immunoglobulin-E (IgE) and blood eosinophil (EOS), asthma severity, allergen profile, history of perennial allergic rhinitis (PAR), and free IgE level during omalizumab treatment were predictive of omalizumab's efficacy. Results This analysis included 608 patients (omalizumab, N = 306; placebo, N = 302). Improvements in forced expiratory volume in 1 s (FEV1), standardized Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE) scores with omalizumab treatment compared with placebo were observed in patients with baseline IgE levels ≥76 IU/mL (irrespective of the EOS count). Relatively greater improvements with omalizumab treatment was also noted in patients with both moderate or severe allergic asthma (regardless of asthma severity), and patients sensitised to >3 allergens and with a history of PAR. All patients who were treated with omalizumab achieved free IgE levels below 50 ng/mL by Week 1. Similar clinical outcomes were observed in the subset of patients who achieved free IgE levels of <25 and ≥ 25 ng/mL. Conclusions In Chinese patients with moderate-to-severe allergic asthma, baseline IgE and allergen profile (number/PAR history) are potential predictors of treatment response to omalizumab. Trial registration NCT01202903 (www.clinicaltrials.gov).
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Key Words
- ACQ, Asthma Control Questionnaire
- ANCOVA, Analysis of covariance
- AQLQ, Asthma Quality of Life Questionnaire
- Allergic
- Asthma
- CMH, Cochran-Mantel-Haenszel
- China
- EOS, Eosinophil
- Eosinophils
- FAS, Full analysis set
- FCεR1, High affinity IgE binding receptor 1
- FEV1, Forced expiratory volume in 1 s
- GETE, Global Evaluation of Treatment Effectiveness
- ICS, Inhaled corticosteroid
- IL-5, Interleukin-5
- IgE, Immunoglobulin-E
- Immunoglobulin E
- LABA, Long-acting β agonist
- LSM, Least squares mean
- LSM-TD, Least squares mean treatment differences
- OMA, Omalizumab
- Omalizumab
- PAR, Perennial allergic rhinitis
- PBO, Placebo
- PD, Pharmacodynamics
- PEF, Peak expiratory flow
- PK, Pharmacokinetic
- QoL, Quality of life
- RAST, Radio-allergosorbent test
- RMU, Rescue medication use
- SAR, Seasonal allergic rhinitis
- ULOQ, Upper limit of quantification
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The Role of IgE in Upper and Lower Airway Disease: More Than Just Allergy! Clin Rev Allergy Immunol 2021; 62:200-215. [PMID: 34536215 PMCID: PMC8818003 DOI: 10.1007/s12016-021-08901-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/03/2021] [Indexed: 12/25/2022]
Abstract
Immunoglobulin E (IgE) is a well-known key factor in allergic airway disease; however, its central role in non-allergic airway inflammation is often underestimated. In some airway diseases, IgE is produced as a result of allergic sensitization. However, in others, IgE production occurs despite the lack of a specific allergen. Although multiple pathways contribute to the production of IgE in airway disease, it is its activity in mediating the inflammatory response that is associated with disease. Therefore, an understanding of IgE as the unifying component of upper and lower airway diseases has important implications for both diagnosis and treatment. Understanding the role of IgE in each upper and lower airway disease highlights its potential utility as a diagnostic marker and therapeutic target. Further classification of these diseases by whether they are IgE mediated or non–IgE mediated, rather than by the existence of an underlying allergic component, accounts for both systemic and localized IgE activity. Improvements in diagnostic methodologies and standardization of clinical practices with this classification in mind can help identify patients with IgE-mediated diseases. In doing so, this group of patients can receive optimal care through targeted anti-IgE therapeutics, which have already demonstrated efficacy across numerous IgE-mediated upper and lower airway diseases.
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Doherty S, Mulholland M, Shields M, McCrossan P. Can omalizumab be used effectively to treat severe conjunctivitis in children with asthma? A case example and review of the literature. World J Clin Pediatr 2021; 10:48-52. [PMID: 34316438 PMCID: PMC8290994 DOI: 10.5409/wjcp.v10.i4.48] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 02/12/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
A 14-year-old girl with poorly controlled asthma attended the difficult-to-treat asthma clinic for review. Although she has eosinophilia and significantly raised immunoglobulin E levels, she is not currently a candidate for omalizumab (Xolair). She also suffers from chronic urticaria, eosinophilic eosophagitis and severe conjunctivitis. You wonder if omalizumab would be effective in treating her multiple atopic conditions, in particular her troublesome conjunctivitis. PubMed was searched using the following search terms: (Omalizumab) or (Xolair) and (conjunctivitis). Searches were conducted in November 2020. Abstracts were selected for full text review if the study population identified asthma as a comorbidity. Non-paediatric studies and those that were not written in English were excluded. The use of omalizumab has the potential to be effective in the treatment of conjunctivitis associated with asthma and other atopic conditions. However, research is needed to address the question, in the form of multicenter, double-blind randomized control trials.
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Affiliation(s)
- Stephen Doherty
- Department of Paediatrics, Royal Belfast Hospital for Sick Children, Belfast BT12 6BA, United Kingdom
| | - Melissa Mulholland
- Department of Paediatric Education and Simulation, Royal Belfast Hospital for Sick Children, Belfast BT12 6BA, United Kingdom
| | - Michael Shields
- Department of Child Health, Queens University Belfast, Belfast BT12 6BJ, United Kingdom
| | - Patrick McCrossan
- Centre of Medical Education, Queens University Belfast, School of Medicine, Belfast BT9 7BL, United Kingdom
- Department of Paediatric Respiratory, Royal Belfast Hospital for Sick Children, Belfast BT12 6BA, United Kingdom
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Abstract
Biologics have been widely adopted in multiple subspecialties of otolaryngology. This article provides an overview of past, present, and future uses of biologics in otolaryngology with emphasis on allergic rhinitis, chronic rhinosinusitis with polyposis, head and neck squamous cell carcinoma, salivary and skull base tumors, hearing loss, and other otologic disorders.
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Ranford D, Hopkins C. Safety review of current systemic treatments for severe chronic rhinosinusitis with nasal polyps and future directions. Expert Opin Drug Saf 2021; 20:1177-1189. [PMID: 33957840 DOI: 10.1080/14740338.2021.1926981] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Introduction: Chronic rhinosinusitis is a common condition characterized by inflammation of the nasal and sinus linings, rhinorrhea, nasal blockage, facial pain, and loss of sense of smell for longer than 12 weeks. CRS can occur with or without nasal polyps.Areas covered: First-line treatment in chronic rhinosinusitis with nasal polyps is long-term intranasal corticosteroids, which have few adverse events associated with their use, as second-generation intranasal corticosteroids having a bioavailability of <0.5%. Systemic corticosteroids are used when intranasal steroids fail to achieve symptom control. However, the repeated use of oral corticosteroids is associated with numerous adverse events and the benefit from a course of oral corticosteroids is lost within three to six months.Expert opinion: Antibiotics are commonly prescribed in nasal polyposis although there is also very little evidence for their use outside of acute infection. Macrolide antibiotics are also associated with a transient increase in the risk of arrhythmias. Biologics offer a steroid-sparing alternative to the treatment of severe nasal polyposis. They have shown to be relatively well tolerated in studies to date; however, studies suggest that there is no disease modifying effect and that any benefit is lost within weeks of finishing treatment.
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Affiliation(s)
- David Ranford
- ENT Department, Guy's and St Thomas NHS Foundation Trust, London, UK
| | - Claire Hopkins
- ENT Department, Guy's and St Thomas NHS Foundation Trust, London, UK
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Singh RB, Liu L, Yung A, Anchouche S, Mittal SK, Blanco T, Dohlman TH, Yin J, Dana R. Ocular redness - II: Progress in development of therapeutics for the management of conjunctival hyperemia. Ocul Surf 2021; 21:66-77. [PMID: 34000363 DOI: 10.1016/j.jtos.2021.05.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 05/11/2021] [Accepted: 05/12/2021] [Indexed: 11/30/2022]
Abstract
Conjunctival hyperemia is one of the most common causes for visits to primary care physicians, optometrists, ophthalmologists, and emergency rooms. Despite its high incidence, the treatment options for patients with conjunctival hyperemia are restricted to over-the-counter drugs that provide symptomatic relief due to short duration of action, tachyphylaxis and rebound redness. As our understanding of the immunopathological pathways causing conjunctival hyperemia expands, newer therapeutic targets are being discovered. These insights have also contributed to the development of animal models for mimicking the pathogenic changes in microvasculature causing hyperemia. Furthermore, this progress has catalyzed the development of novel therapeutics that provide efficacious, long-term relief from conjunctival hyperemia with minimal adverse effects.
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Affiliation(s)
- Rohan Bir Singh
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Lingjia Liu
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Ann Yung
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Sonia Anchouche
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; Faculty of Medicine, McGill University, Montreal, Quebec, Canada
| | - Sharad K Mittal
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Tomas Blanco
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Thomas H Dohlman
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Jia Yin
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA
| | - Reza Dana
- Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
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31
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Bachert C, Maurer M, Palomares O, Busse WW. What is the contribution of IgE to nasal polyposis? J Allergy Clin Immunol 2021; 147:1997-2008. [PMID: 33757720 DOI: 10.1016/j.jaci.2021.03.016] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/10/2021] [Accepted: 03/17/2021] [Indexed: 02/07/2023]
Abstract
Taking a novel approach, this narrative review collates knowledge about nasal polyposis and the biological functions of IgE in several diseases (allergic rhinitis, allergic asthma, nonsteroidal anti-inflammatory drugs-exacerbated respiratory disease, and chronic spontaneous urticaria) to consider which IgE-mediated mechanisms are relevant to nasal polyposis pathology. A type 2 eosinophil-dominated inflammatory signature is typical in nasal polyp tissue of European patients with nasal polyposis, with a shift toward this endotype observed in Asian populations in recent years. Elevated polyclonal IgE is present in the nasal tissue of patients with and without allergy. It is derived from many different B-cell clones and, importantly, is functional (proinflammatory). Staphylococcus aureus enterotoxins are thought to act as superantigens, inducing production of polyclonal IgE via B-cell and T-cell activation, and triggering release of inflammatory mediators. In some patients, exposure to antigens/triggers leads to production of high levels of antigen-specific IgE, which mediates cross-linking of the high-affinity IgE receptor on various cells, causing release of inflammatory mediators. The efficacy of omalizumab confirms IgE as an important inflammatory mediator in nasal polyposis. By blocking IgE, omalizumab targets the T2 inflammation in nasal polyposis, reduces nasal polyp score and improves symptoms.
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Affiliation(s)
- Claus Bachert
- Upper Airways Research Laboratory, Ghent University, Ghent, Belgium; Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden.
| | - Marcus Maurer
- Dermatological Allergology, Allergie-Centrum-Charité, Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Oscar Palomares
- Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain
| | - William W Busse
- Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis
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MacGlashan D, Saini S, Schroeder JT. Response of peripheral blood basophils in subjects with chronic spontaneous urticaria during treatment with omalizumab. J Allergy Clin Immunol 2021; 147:2295-2304.e12. [PMID: 33716077 DOI: 10.1016/j.jaci.2021.02.039] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 01/11/2021] [Accepted: 02/08/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Treatment of patients with asthma or food allergy with omalizumab results in several consistent changes in circulating basophils. The multiple basophil phenotypes observed in patients with chronic spontaneous urticaria (CSU) present some unique attributes that may not respond in a similar fashion to patients with asthma or food allergy. As part of a clinical study on the therapeutic outcomes of omalizumab treatment in CSU, the basophil compartment was examined for changes in characteristics predicted by prior studies. OBJECTIVE This study sought to examine the changes in basophil function and its relationship to auto-antibodies in serum during treatment with omalizumab. METHODS At multiple time points before and during omalizumab treatment of patients with CSU, basophil surface IgE and FcεRI expression, cellular spleen tyrosine kinase (SYK) expression, IgE-mediated histamine release (HR), and the presence of auto-antibodies in serum were determined. RESULTS Three basophil phenotypes were enumerated in the clinical study and used to group results in this basophil study: subjects with (1) basopenia, (2) normal basophil numbers with normal IgE-mediated HR, and (3) normal basophil numbers with poor HR. Basopenia was highly associated with the presence of auto-antibodies to unoccupied FcεRI and basophil numbers did not change during treatment. Likewise, subjects who are basopenic showed no changes in SYK expression or HR during treatment. In basophils of subjects who are nonbasopenic, increases in SYK expression and HR showed the expected inverse relationship to starting SYK and HR levels. Treatment with omalizumab resulted in similar kinetics for decreases in surface FcεRI and IgE in all 3 groups. CONCLUSIONS A unifying interpretation of the results revolves around the presence of auto-antibodies to FcεRI in CSU. If present, basopenia and an absence of changes in basophils during omalizumab treatment are observed. If auto-antibodies are absent, the changes in the basophil compartment are consistent with prior studies of asthma and food allergy. These group differences also are related to efficacy of the treatment for clinical outcomes, as found in the parent clinical study.
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Affiliation(s)
| | - Sarbjit Saini
- Asthma and Allergy Center, Johns Hopkins University, Baltimore, Md
| | - John T Schroeder
- Asthma and Allergy Center, Johns Hopkins University, Baltimore, Md
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Anti-IgE: A treatment option in allergic rhinitis? Allergol Select 2021; 5:119-127. [PMID: 33644635 PMCID: PMC7905705 DOI: 10.5414/alx02205e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 02/10/2021] [Indexed: 11/21/2022] Open
Abstract
Background: Allergic rhinitis (AR) is the most common IgE-mediated allergic disease. Multiple clinical trials have demonstrated promising results on the AR treatment with biologics, in particular with the use of omalizumab – an anti-IgE antibody. Omalizumab has also been established in the routine management of allergic asthma and chronic idiopathic urticaria. However, currently there is no approved license for the use of biologics in AR in Germany. Materials and methods: A systematic literature review has been completed including randomized controlled trials, meta-analyses, and reviews on the treatment of AR with omalizumab. Results: The systematic review demonstrates strong evidence supporting the use of omalizumab in the treatment of AR with regard to symptom control, safety profile, and management of comorbidities. Conclusion: Omalizumab is a good and safe option in the treatment of AR in terms of symptom control and the management of pre-existing comorbidities. Further clinical trials with other biologics in the management of AR are needed and are expected to follow soon.
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34
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Ma T, Wang H, Wang X. Effectiveness and Response Predictors of Omalizumab in Treating Patients with Seasonal Allergic Rhinitis: A Real-World Study. J Asthma Allergy 2021; 14:59-66. [PMID: 33519214 PMCID: PMC7837594 DOI: 10.2147/jaa.s288952] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 01/07/2021] [Indexed: 11/23/2022] Open
Abstract
Background Omalizumab has been proven effective and safety in treating seasonal allergic rhinitis (SAR) by several randomized clinical trials in many countries. However, there is lack of clinical reports of Chinese patients with SAR treated by omalizumab. Objective In the present real-world-designed study, we aimed to investigate the effectiveness of omalizumab in treating patients with SAR. Methods SAR patients administered omalizumab in various dosages were recruited, and follow-up was done. Their quality of life (QOL) and symptoms were assessed by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Total Nasal Symptoms Score (TNSS), Asthma Control Test (ACT), and clinical outcomes were compared between post- and pre-treatment conditions. Results Sixty SAR patients received omalizumab therapy in the study (mean age 35.47±17.02 years, 35 females). Omalizumab treatment significantly improved the quality of life (change in RQLQ overall score: -2.08±1.01, paired t-test p<0.001) and nasal symptoms (change in TNSS: -7.33±2.50, paired t-test p<0.001) of SAR patients. In 21 patients with co-existing asthma, the ACT score significantly increased from 16.10 to 22.57 on average (paired t-test p<0.001), indicating better-controlled asthma. Using a threshold of ≥1 point improvement in RQLQ overall score, 83.3% of patients responded to omalizumab. The responder group had a higher baseline RQLQ score and TNSS (p<0.05), but both responders and non-responders had comparable scores after treatment. Multiple linear regression analysis identified the baseline RQLQ overall score as a predictor of change in the RQLQ score in omalizumab-treated SAR. Conclusion Omalizumab is effective and safe in SAR treatment in a real-world setting.
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Affiliation(s)
- Tingting Ma
- Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, People's Republic of China
| | - Hongtian Wang
- Department of Otolaryngology Head and Neck Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People's Republic of China
| | - Xueyan Wang
- Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Rational Drug Use, Beijing 100038, People's Republic of China
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35
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Rowe RK, Pyle DM, Farrar JD, Gill MA. IgE-mediated regulation of IL-10 and type I IFN enhances rhinovirus-induced Th2 differentiation by primary human monocytes. Eur J Immunol 2020; 50:1550-1559. [PMID: 32383224 DOI: 10.1002/eji.201948396] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Revised: 03/18/2020] [Accepted: 05/04/2020] [Indexed: 11/08/2022]
Abstract
Rhinovirus (RV) infections are linked to the development and exacerbation of allergic diseases including allergic asthma. IgE, another contributor to atopic disease pathogenesis, has been shown to regulate DC antiviral functions and influence T cell priming by monocytes. We previously demonstrated that IgE-mediated stimulation of monocytes alters multiple cellular functions including cytokine secretion, phagocytosis, and influenza-induced Th1 development. In this study, we investigate the effects of IgE-mediated stimulation on monocyte-driven, RV-induced T cell development utilizing primary human monocyte-T cell co-cultures. We demonstrate that IgE crosslinking of RV-exposed monocytes enhances monocyte-driven Th2 differentiation. This increase in RV-induced Th2 development was regulated by IgE-mediated inhibition of virus-induced type I IFN and induction of IL-10. These findings suggest an additional mechanism by which two clinically significant risk factors for allergic disease exacerbations-IgE-mediated stimulation and rhinovirus infection-may synergistically promote Th2 differentiation and allergic inflammation.
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Affiliation(s)
- Regina K Rowe
- Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
- Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
- Departments of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas
- Department of Pediatrics, University of Rochester Medical Center, Rochester, New York
| | - David M Pyle
- Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
- Departments of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - J David Farrar
- Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Michelle A Gill
- Departments of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
- Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
- Departments of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas
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36
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Yao Y, Wang N, Chen C, Pan L, Wang Z, Yunis J, Chen Z, Zhang Y, Hu S, Xu X, Zhu R, Yu D, Liu Z. CD23 expression on switched memory B cells bridges T-B cell interaction in allergic rhinitis. Allergy 2020; 75:2599-2612. [PMID: 32198890 DOI: 10.1111/all.14288] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2019] [Revised: 02/10/2020] [Accepted: 02/29/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND The contribution of B-cell subsets and T-B cell interaction to the pathogenesis of allergic rhinitis (AR) and mechanisms of allergen immunotherapy (AIT) remain poorly understood. This study aimed to outline circulating B-cell signature, the underlying mechanism, and its association with clinical response to AIT in patients with AR. METHODS IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies and phenotypes of B cells. Correlations between B cells, T cells, antigen-specific IgE, and disease severity in AR patients were investigated. Switched memory B cells were co-cultured with type 2 follicular helper T (Tfh2) cells and follicular regulatory T (Tfr) cells. Associations between B-cell subsets and clinical benefits of AIT were analyzed. RESULTS Frequencies and absolute numbers of circulating memory B cells were increased in AR patients. CD23 expression on CD19+ CD20+ CD27+ IgD- switched memory B cells was significantly enhanced and positively correlated with antigen-specific IgE levels, symptom scores, and Tfh2/Tfr cell ratio in AR patients. Compared with those from healthy controls, Tfh2 cells from AR patients had a greater capacity to induce CD23 expression on switched memory B cells via IL-4, which was unable to be sufficiently suppressed by AR-associated Tfr cells with defective IL-10 expression. CD23 expression on switched memory B cells was downregulated after 12-month AIT, which positively associated with disease remission in AR patients. CONCLUSION T-B cell interaction, bridged by CD23 expression particularly on switched memory B cells, may be involved in the disease pathogenesis and mechanism of AIT in patients with AR.
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Affiliation(s)
- Yin Yao
- Department of Otolaryngology‐Head and Neck Surgery Tongji Medical College Tongji Hospital Huazhong University of Science and Technology Wuhan China
| | - Nan Wang
- Department of Otolaryngology‐Head and Neck Surgery Tongji Medical College Tongji Hospital Huazhong University of Science and Technology Wuhan China
| | - Cai‐Ling Chen
- Department of Otolaryngology‐Head and Neck Surgery Tongji Medical College Tongji Hospital Huazhong University of Science and Technology Wuhan China
| | - Li Pan
- Department of Otolaryngology‐Head and Neck Surgery Tongji Medical College Tongji Hospital Huazhong University of Science and Technology Wuhan China
| | - Zhi‐Chao Wang
- Department of Otolaryngology‐Head and Neck Surgery Tongji Medical College Tongji Hospital Huazhong University of Science and Technology Wuhan China
| | - Joseph Yunis
- Faculty of Medicine The University of Queensland Diamantina Institute The University of Queensland Brisbane QLD Australia
| | - Zhi‐An Chen
- Department of Immunology and Infectious Disease John Curtin School of Medical Research Australian National University Canberra ACT Australia
| | - Yu Zhang
- Laboratory of Immunology for Environment and Health Shandong Analysis and Test Center Qilu University of Technology (Shandong Academy of Sciences) Jinan China
| | - Si‐Tao Hu
- Department of Otolaryngology‐Head and Neck Surgery Tongji Medical College Tongji Hospital Huazhong University of Science and Technology Wuhan China
| | - Xiao‐Yan Xu
- Department of Otolaryngology‐Head and Neck Surgery China Resources & Wisco General Hospital Wuhan China
| | - Rong‐Fei Zhu
- Department of Allergy Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China
| | - Di Yu
- Department of Immunology and Infectious Disease John Curtin School of Medical Research Australian National University Canberra ACT Australia
- Laboratory of Immunology for Environment and Health Shandong Analysis and Test Center Qilu University of Technology (Shandong Academy of Sciences) Jinan China
| | - Zheng Liu
- Department of Otolaryngology‐Head and Neck Surgery Tongji Medical College Tongji Hospital Huazhong University of Science and Technology Wuhan China
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Walter S, Ho J, Alvarado R, Rimmer J, Campbell R, Kalish L, Sacks R, Harvey RJ. Effect of monoclonal antibody drug therapy on mucosal biomarkers in airway disease: A systematic review. Clin Exp Allergy 2020; 50:1212-1222. [PMID: 32808380 DOI: 10.1111/cea.13721] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 08/14/2020] [Accepted: 08/14/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Monoclonal antibody therapies have a growing role in treating refractory airway disease. OBJECTIVE The review aimed to summarize the response of respiratory mucosa to monoclonal antibody treatments in inflammatory airway conditions. DESIGN We conducted a systematic review including risk of bias assessment. DATA SOURCES MEDLINE, EMBASE and PubMed from 1 January 2000 to 16 November 2019 were searched. ELIGIBILITY CRITERIA Eligible studies assessed the immunological and histological response of airway mucosa to monoclonal antibody therapy compared with baseline or a comparison group in patients with respiratory diseases (asthma, chronic rhinosinusitis and allergic rhinitis). Any prospective interventional studies, including randomized controlled trials (RCTs) and single-arm trials, were eligible. RESULTS There were 4195 articles screened, and full-text analysis produced n = 11 studies with extractable data. Nine were RCTs, and two were single-arm trials. These studies focused on asthma (n = 9 articles), chronic rhinosinusitis (n = 1) and allergic rhinitis (n = 1). Five monoclonal antibody drugs were assessed (omalizumab, mepolizumab, dupilumab, benralizumab and tralokinumab). Risk of bias was low (n = 6) or unclear (n = 3) in the RCTs and moderate in the single-arm trials. Omalizumab reduced the mucosal concentration of its target, IgE. Dupilumab reduced the concentration of one of its targets, IL-13, but not IL-4. Omalizumab, mepolizumab and benralizumab reduced tissue eosinophil cell density. Dupilumab decreased mucosal eosinophil granule proteins. Tralokinumab did not affect airway mucosa. CONCLUSIONS Knowledge of the expected biological response of monoclonal antibody therapy on biomarkers in disease tissue provides an important supplement to data about clinical outcomes. An understanding of the biological effect is essential to identify likely responders, reasons for treatment failure and necessary adjustments to monoclonal antibody treatment. Further investigation into the effect of monoclonal antibody therapy on disease mucosa and more precise endotyping are required to move closer to achieving personalized medicine.
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Affiliation(s)
- Sophie Walter
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia
| | - Jacqueline Ho
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia
| | - Raquel Alvarado
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia
| | - Janet Rimmer
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia.,Woolcock Institute, University of Sydney, Sydney, New South Wales, Australia.,Faculty of Medicine, Notre Dame University, Sydney, New South Wales, Australia
| | - Raewyn Campbell
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia.,Department of Otolaryngology Head and Neck Surgery, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Larry Kalish
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia.,Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Raymond Sacks
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.,Department of Otolaryngology, Head and Neck Surgery, Concord General Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Richard J Harvey
- Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, New South Wales, Australia.,Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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Okubo K, Okano M, Sato N, Tamaki Y, Suzuki H, Uddin A, Fogel R. Add-On Omalizumab for Inadequately Controlled Severe Pollinosis Despite Standard-of-Care: A Randomized Study. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 8:3130-3140.e2. [PMID: 32422373 DOI: 10.1016/j.jaip.2020.04.068] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 04/29/2020] [Accepted: 04/29/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Cedar pollinosis (CP), a common form of seasonal allergic rhinitis (AR), is a substantial medical problem in Japan due to its high prevalence and severe symptoms. Omalizumab (anti-IgE therapy) has previously proven to be effective in CP/AR, but no studies for inadequately controlled severe CP/AR despite standard-of-care (SoC) have been conducted. OBJECTIVE To determine the efficacy of omalizumab added to SoC in patients with inadequately controlled severe CP in a randomized, double-blinded, placebo-controlled, phase III study. METHODS Adult/adolescent patients with severe CP whose symptoms were inadequately controlled despite nasal corticosteroids plus 1 or more oral medications in the previous 2 seasons were randomized to receive omalizumab (n = 162) or placebo (n = 175). All patients received concomitant antihistamines and nasal corticosteroids as SoC. The primary endpoint was the mean nasal symptom score during the severe symptom period. Secondary endpoints included mean ocular symptom score, quality of life (QoL), and safety. RESULTS The SoC + omalizumab treatment had statistically significantly and clinically important lower nasal (least squares mean difference, -1.03, P < .001) and ocular (-0.87, P < .001) symptom scores compared with SoC + placebo, respectively. Differences in scores for individual components of nasal and ocular symptoms were also statistically and clinically significant. SoC + omalizumab also improved QoL scores as overall and in all domains. No unexpected safety signals were observed. CONCLUSIONS In patients with severe CP, omalizumab added to SoC demonstrated consistent efficacy in improving symptoms and QoL, and was well tolerated. These results indicate that omalizumab could be a promising therapeutic option for severe CP/AR.
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Affiliation(s)
- Kimihiro Okubo
- Department of Otolaryngology, Nippon Medical School, Tokyo, Japan.
| | - Mitsuhiro Okano
- Department of Otorhinolaryngology, International University of Health and Welfare School of Medicine, Narita, Japan
| | | | | | | | - Alkaz Uddin
- Novartis Pharmaceuticals Corporation, East Hanover, NJ
| | - Robert Fogel
- Novartis Pharmaceuticals Corporation, East Hanover, NJ
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Dupuis P, Prokopich CL, Hynes A, Kim H. A contemporary look at allergic conjunctivitis. Allergy Asthma Clin Immunol 2020; 16:5. [PMID: 31993069 PMCID: PMC6975089 DOI: 10.1186/s13223-020-0403-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 01/09/2020] [Indexed: 01/16/2023] Open
Abstract
Allergic eye disease is common, yet often overlooked in North America. In the U.S., up to 40% of the population is deemed to be affected and this number is growing. Symptoms and signs of ocular allergy can lead to decreased productivity and negatively impact quality of life (QoL). Various treatment options exist to achieve symptom control. For allergic conjunctivitis, ophthalmic agents include antihistamines, mast cell stabilizers, dual-activity agents, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and some off-label treatments. Immunotherapy is recommended as a therapeutic option. This review provides a summary of the forms of ocular allergies, with a focus on symptoms and signs, impact on QoL, physical examination, diagnosis and therapeutic options of allergic conjunctivitis. Through multidisciplinary collaborations, a simplified algorithm for the treatment of allergic conjunctivitis is proposed for Canadian clinical practice.
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Affiliation(s)
- Pascale Dupuis
- 1Division of Clinical Immunology and Allergy, Department of Medicine, St. Joseph's Hospital, Western University, Room B3-102, 268 Grosvenor Street, London, ON N6A 4V2 Canada
| | - C Lisa Prokopich
- 2School of Optometry & Vision Science, University of Waterloo, 200 Columbia St W., Waterloo, ON N2L 3G1 Canada
| | | | - Harold Kim
- 1Division of Clinical Immunology and Allergy, Department of Medicine, St. Joseph's Hospital, Western University, Room B3-102, 268 Grosvenor Street, London, ON N6A 4V2 Canada.,4Division of Clinical Immunology and Allergy, Department of Medicine, McMaster University Health Sciences Centre, 1280 Main St. W., Hamilton, ON L8S 4K1 Canada
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Bayar Muluk N, Bafaqeeh SA, Cingi C. Anti-IgE treatment in allergic rhinitis. Int J Pediatr Otorhinolaryngol 2019; 127:109674. [PMID: 31526939 DOI: 10.1016/j.ijporl.2019.109674] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 08/08/2019] [Accepted: 09/05/2019] [Indexed: 10/26/2022]
Abstract
OBJECTIVES To review the efficacy of anti-IgE therapy in allergic rhinitis (AR). METHODS Literature search was performed using the PubMed and Proquest Central databases at Kırıkkale University Library. RESULTS Although the skin prick testing in patients suffering from AR is positive (indicating that antigen-specific Immunoglobulin E has been produced), there is no association with overall circulating IgE levels. Correlation was lacking between circulating IgE level and either skin prick tests or laboratory testing for specific IgE. Omalizumab binds to uncomplexed IgE in man more avidly than does Fc-epsilon. The effect of omalizumab is to lower the level of IgE and downgrade production of FceRI receptors (which bind IgE) in mast cells and basophils, causing less mast cell recruitment and responsivity and thus diminishing eosinophilic infiltration and activation. Anti-IgE therapy through omalizumab may shorten the lifetime of mast cells and causes dendritic cells to downgrade their production of FcεRI. There are reports indicating benefit from omalizumab in managing food allergies, nasal polyp formation, essential anaphylaxis, AR, venom allergy and eczema. Omalizumab acts to lessen circulating IgE levels, whilst reducing production of FceRI by mast cells and basophils. The fact that omalizumab influences how eosinophils respond may be down to disruption of the antigen-IgE-mast cell interactions, with mast cells being recruited at lower levels and thus chemotactic eosinophilic recruitment via cytokines being greatly reduced. Omalizumab has the effect in cases of perennial AR of blocking the increased eosinophilic recruitment and tissue infiltration initiated by seasonal antigens. Likewise, in omalizumab-treated cases, circulating unbound IgE levels showed significant decreases. For patients with perennial AR, the average daily nasal severity score was significantly reduced where omalizumab was administered, compared to placebo. CONCLUSION Omalizumab has efficacy in ameliorating symptoms and reduces the necessity for additional medication in both seasonal and perennial allergic rhinitis.
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Affiliation(s)
- Nuray Bayar Muluk
- Kirikkale University, Medical Faculty, Department of Otorhinolaryngology, Kirikkale, Turkey.
| | - Sameer Ali Bafaqeeh
- King Saud University, Faculty of Medicine, Department of Otorhinolaryngology, Riyadh, Saudi Arabia.
| | - Cemal Cingi
- Eskisehir Osmangazi University, Medical Faculty, Department of Otorhinolaryngology, Eskisehir, Turkey.
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Yu C, Wang K, Cui X, Lu L, Dong J, Wang M, Gao X. Clinical Efficacy and Safety of Omalizumab in the Treatment of Allergic Rhinitis: A Systematic Review and Meta-analysis of Randomized Clinical Trials. Am J Rhinol Allergy 2019; 34:196-208. [PMID: 31672020 DOI: 10.1177/1945892419884774] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background Patients with moderate to severe allergic rhinitis (AR) who are treated according to the current rhinitis management guidelines may be inadequately controlled. These patients are at risk of serious comorbidities, such as asthma and chronic sinusitis. These symptoms, sneezing and an itchy, runny, stuffy nose, may have a negative impact on patients’ daily functioning. Omalizumab is being developed as a new choice for the treatment of AR. We therefore undertook a meta-analysis to assess the efficacy and safety of omalizumab in the treatment of AR. Methods We systematically searched PubMed, Cochrane Library, and MEDLINE databases for randomized controlled studies on the treatment of AR with omalizumab. Our evaluation outcomes were symptom scores, medication efficacy, combined symptom and medication scores, and adverse events. We descriptively summarized and quantitatively synthesized original data to evaluate the efficacy and safety of omalizumab in the treatment of AR by using Stata12.0 software for meta-analyses. Results The results of our meta-analysis showed that there were statistically significant differences between the omalizumab group and the control group in the following aspects: daily nasal symptom score (standardized mean difference [SMD] = –0.443, 95% confidence interval [CI]: –0.538 to –0.347, P < .001); daily ocular symptom score (SMD = –0.385, 95% CI: –0.5 to –0.269, P < .001); daily nasal medication symptom scores (SMD = –0.421, 95% CI: –0.591 to –0.251, P < .001); proportion of days of emergency drug use (risk ratio [RR] = 0.488, 95% CI: 0.307 to 0.788, P < .005); rhinoconjunctivitis-specific quality of life questionnaire (SMD = –0.286, 95% CI: –0.418 to –0.154, P < .001); and overall evaluation (RR = 1.435, 95% CI: 1.303–1.582, P < .001). There was no statistically significant difference in safety indicator: adverse events (RR = 1.026, 95% CI: 0.916–1.150, P = .655). Conclusion Omalizumab is effective and relatively safe in patients with AR; omalizumab used in conjunction with special immunotherapy has shown promising results, especially in reducing adverse events.
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Affiliation(s)
- Chenjie Yu
- Department of Otorhinolaryngology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, The People’s Republic of China
- Department of Otorhinolaryngology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, The People’s Republic of China
- Research Institute of Otorhinolaryngology, Drum Tower Hospital, Nanjing, The People’s Republic of China
| | - Kaijian Wang
- Department of Otorhinolaryngology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, The People’s Republic of China
| | - Xinyan Cui
- Department of Otorhinolaryngology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, The People’s Republic of China
| | - Ling Lu
- Department of Otorhinolaryngology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, The People’s Republic of China
- Department of Otorhinolaryngology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, The People’s Republic of China
- Research Institute of Otorhinolaryngology, Drum Tower Hospital, Nanjing, The People’s Republic of China
| | - Jianfei Dong
- Department of Otorhinolaryngology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, The People’s Republic of China
- Department of Otorhinolaryngology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, The People’s Republic of China
- Research Institute of Otorhinolaryngology, Drum Tower Hospital, Nanjing, The People’s Republic of China
| | - Maohua Wang
- Department of Otorhinolaryngology, Second Xiangya Hospital, Central South University, Changsha, The People’s Republic of China
| | - Xia Gao
- Department of Otorhinolaryngology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline, Nanjing, The People’s Republic of China
- Department of Otorhinolaryngology, Drum Tower Clinical Medical College, Nanjing Medical University, Nanjing, The People’s Republic of China
- Research Institute of Otorhinolaryngology, Drum Tower Hospital, Nanjing, The People’s Republic of China
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Shinee T, Sutikno B, Abdullah B. The use of biologics in children with allergic rhinitis and chronic rhinosinusitis: Current updates. Pediatr Investig 2019; 3:165-172. [PMID: 32851312 PMCID: PMC7331348 DOI: 10.1002/ped4.12146] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Accepted: 07/23/2019] [Indexed: 01/25/2023] Open
Abstract
The therapeutic goals of the treatment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are symptom relief, avoiding complications, and improving quality of life. In the treatment of AR and CRS, several limitations of currently prescribed medicines have been identified. Antihistamine administration (both oral and topical) together with intranasal corticosteroids bring relief to the majority of patients, but their dependency on the medications and a necessity to maintain strict compliance with regular medication regimes pose a challenge. Immunotherapeutic agents are an option in some patients, but polysensitized patients, the risk of anaphylaxis, and the need for daily administration for years are limiting it from becoming the main therapy modality. Immunotherapy in any form requires commitment by the patient, which renders adherence and compliance issues particularly relevant. The procedure involved are generally time-consuming and entail an associated risk of severe adverse reactions. The use of biologics could overcome the limitations of other therapeutic modalities. They could be used as a monotherapy or combined with pre-existing medications. The benefits of targeted therapy include less adverse effects and optimal efficacy. The aim of the present review was to investigate the collective literature to date pertaining to the role of biologics in managing children with AR and CRS.
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Affiliation(s)
- Tan Shinee
- Department of Otorhinolaryngology Head & Neck SurgeryHospital TawauSabahMalaysia
| | - Budi Sutikno
- Department of Otorhinolaryngology Head and Neck SurgeryAirlangga UniversitySchool of Medicine/Dr Soetomo General HospitalSurabayaIndonesia
| | - Baharudin Abdullah
- Department of Otorhinolaryngology Head & Neck SurgerySchool of Medical Sciences, Universiti Sains Malaysia Health Campus16150Kubang KerianKelantanMalaysia
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Giallongo A, Parisi GF, Licari A, Pulvirenti G, Cuppari C, Salpietro C, Marseglia GL, Leonardi S. Novel therapeutic targets for allergic airway disease in children. Drugs Context 2019; 8:212590. [PMID: 31391855 PMCID: PMC6668505 DOI: 10.7573/dic.212590] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 05/30/2019] [Accepted: 06/03/2019] [Indexed: 12/22/2022] Open
Abstract
The aim of precision medicine is setting up targeted therapies for selected patients that would ideally have high effectiveness and few side effects. This is made possible by targeted therapy drugs that selectively act on a specific pathway. Precision medicine is spreading to many medical specialties, and there is increasing interest in the context of allergic airway diseases, such as allergic rhinitis, chronic rhinosinusitis, and asthma. This review is an update of new targets in the treatment of childhood allergic upper airway diseases and asthma, including the most recent biologic drugs that have already been licensed or are in the pipeline to be tested with children.
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Affiliation(s)
- Alessandro Giallongo
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Giuseppe Fabio Parisi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Amelia Licari
- Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Giulio Pulvirenti
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Caterina Cuppari
- Department of Human Pathology of the Adult and Developmental Age ‘Gaetano Barresi,’ Unit of Pediatric Emergency, University of Messina, Messina, Italy
| | - Carmelo Salpietro
- Department of Human Pathology of the Adult and Developmental Age ‘Gaetano Barresi,’ Unit of Pediatric Emergency, University of Messina, Messina, Italy
| | - Gian Luigi Marseglia
- Department of Pediatrics, Foundation IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
| | - Salvatore Leonardi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
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Biomarkers and asthma management: analysis and potential applications. Curr Opin Allergy Clin Immunol 2019; 18:96-108. [PMID: 29389730 DOI: 10.1097/aci.0000000000000426] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Asthma features a high degree of heterogeneity in both pathophysiology and therapeutic response, resulting in many asthma patients being treated inadequately. Biomarkers indicative of underlying pathological processes could be used to identify disease subtypes, determine prognosis and to predict or monitor treatment response. However, the newly identified as well as more established biomarkers have different applications and limitations. RECENT FINDINGS Conventional markers for type 2-high asthma, such as blood eosinophils, fraction of exhaled nitric oxide, serum IgE and periostin, feature limited sensitivity and specificity despite their significant correlations. More distinctive models have been developed by combining biomarkers and/or using omics techniques. Recently, a model with a positive predictive value of 100% for identification of type 2-high asthma based on a combination of minimally invasive biomarkers was developed. SUMMARY Individualisation of asthma treatment regimens on the basis of biomarkers is necessary to improve asthma control. However, the suboptimal properties of currently available conventional biomarkers limit its clinical utility. Newly identified biomarkers and models based on combinations and/or omics analysis must be validated and standardised before they can be routinely applied in clinical practice. The development of robust biomarkers will allow development of more efficacious precision medicine-based treatment approaches for asthma.
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Humbert M, Bousquet J, Bachert C, Palomares O, Pfister P, Kottakis I, Jaumont X, Thomsen SF, Papadopoulos NG. IgE-Mediated Multimorbidities in Allergic Asthma and the Potential for Omalizumab Therapy. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2019; 7:1418-1429. [PMID: 30928481 DOI: 10.1016/j.jaip.2019.02.030] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 02/27/2019] [Accepted: 02/28/2019] [Indexed: 12/15/2022]
Abstract
Allergic asthma often coexists with different pathological conditions, called multimorbidities, that are mostly of allergic nature and share a common underlying inflammatory pathophysiological mechanism. Multimorbidities of allergic asthma may influence asthma control, its severity, and patients' response to treatment, and contribute to the overall socioeconomic burden of the disease. Immunoglobulin E (IgE) is known to play a central role in the pathogenesis of various allergic diseases, including asthma. Thus, IgE-mediated immunologic pathways present an attractive target for intervention in asthma and multimorbidities. In this review, we discuss the most frequently reported IgE-mediated multimorbidities in allergic asthma, including allergic rhinitis, rhinoconjunctivitis, atopic dermatitis, vernal keratoconjunctivitis, chronic rhinosinusitis with nasal polyps, food allergies, and allergic bronchopulmonary aspergillosis. Omalizumab is a recombinant humanized monoclonal antibody against IgE and has been in use to treat allergic asthma for more than a decade. We comprehensively review the clinical evidence for omalizumab in the treatment of the aforementioned multimorbidities in allergic asthma.
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Affiliation(s)
- Marc Humbert
- Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
| | - Jean Bousquet
- MACVIA-France, Contre les Maladies Chroniques pour un Vieillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier, France
| | - Claus Bachert
- Upper Airways Research Laboratory and Department of Oto-Rhino-Laryngology, Ghent University and Ghent University Hospital, Ghent, Belgium
| | - Oscar Palomares
- Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain
| | | | | | | | - Simon Francis Thomsen
- Department of Dermatology, Bispebjerg University Hospital, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nikolaos G Papadopoulos
- Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, United Kingdom; Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece
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Cardet JC, Casale TB. New insights into the utility of omalizumab. J Allergy Clin Immunol 2019; 143:923-926.e1. [PMID: 30690050 DOI: 10.1016/j.jaci.2019.01.016] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 12/27/2018] [Accepted: 01/17/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Juan Carlos Cardet
- Department of Internal Medicine, Division of Allergy and Immunology, Morsani College of Medicine, University of South Florida, Tampa, Fla
| | - Thomas B Casale
- Department of Internal Medicine, Division of Allergy and Immunology, Morsani College of Medicine, University of South Florida, Tampa, Fla.
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Nishima S, Kozawa M, Milligan KL, Papadopoulos NG. Omalizumab and unmet needs in severe asthma and allergic comorbidities in Japanese children. Asia Pac Allergy 2019; 9:e7. [PMID: 30740355 PMCID: PMC6365659 DOI: 10.5415/apallergy.2019.9.e7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Accepted: 01/17/2019] [Indexed: 01/20/2023] Open
Abstract
Childhood asthma is one condition within a family of allergic diseases, which includes allergic rhinitis, atopic dermatitis, and food allergy, among others. Omalizumab is an anti-IgE antibody therapy that was approved in Japan for children with asthma and added to the Japanese pediatric asthma guidelines in 2017. This review highlights the Japanese clinical perspectives in pediatric allergic asthma, and consideration for allergic comorbidities, and reflects on omalizumab clinical trials in progress to present comprehensive future opportunities.
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Affiliation(s)
- Sankei Nishima
- National Hospital Organization, Fukuoka National Hospital, Fukuoka, Japan
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Beswick DM, Gray ST, Smith TL. Pharmacological Management of Chronic Rhinosinusitis: Current and Evolving Treatments. Drugs 2018; 77:1713-1721. [PMID: 28853058 DOI: 10.1007/s40265-017-0803-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Chronic rhinosinusitis (CRS) is an inflammatory sinonasal condition with multiple etiologic factors that is associated with a vast economic cost. Treatment is most frequently pharmacologic and has centered on agents that ameliorate inflammation, decrease bacterial or pathogen load, and facilitate egress of mucus or purulence from the sinonasal cavity. Nasal saline irrigations, topical nasal steroids, certain antibiotics, and systemic steroids have shown some efficacy in the management of CRS. Recently, biologic therapeutics that target specific inflammatory pathways associated with subsets of CRS have been developed and evaluated. Early data evaluating these biologic treatments suggest a potential role in treating a subset of CRS with refractory, poorly controlled disease. Additional studies are necessary to identify which patients would benefit most from biologic therapies and to assess the cost of these therapies compared with the benefit they provide. This review describes the pathophysiology of CRS and summarizes both established and novel biologic pharmacologic treatments.
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Affiliation(s)
- Daniel M Beswick
- Department of Otolaryngology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA
| | - Stacey T Gray
- Department of Otolaryngology, Harvard Medical School, Boston, MA, USA.,Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
| | - Timothy L Smith
- Department of Otolaryngology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
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50
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Orengo JM, Radin AR, Kamat V, Badithe A, Ben LH, Bennett BL, Zhong S, Birchard D, Limnander A, Rafique A, Bautista J, Kostic A, Newell D, Duan X, Franklin MC, Olson W, Huang T, Gandhi NA, Lipsich L, Stahl N, Papadopoulos NJ, Murphy AJ, Yancopoulos GD. Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement. Nat Commun 2018. [PMID: 29650949 DOI: 10.1038/s41467-018-03636-8.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.
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Affiliation(s)
- J M Orengo
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA.
| | - A R Radin
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - V Kamat
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - A Badithe
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - L H Ben
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - B L Bennett
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - S Zhong
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - D Birchard
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - A Limnander
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - A Rafique
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - J Bautista
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - A Kostic
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - D Newell
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - X Duan
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - M C Franklin
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - W Olson
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - T Huang
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - N A Gandhi
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - L Lipsich
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - N Stahl
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - N J Papadopoulos
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - A J Murphy
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
| | - G D Yancopoulos
- Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY, 10591, USA
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