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Cheng L, Zhang Y, Xu Q, Li Z, Liu Z, Dai F. Hyaluronic acid/silk fibroin nanoparticles loaded with methotrexate for topical treatment of psoriasis. Int J Pharm X 2025; 9:100312. [PMID: 39802890 PMCID: PMC11722578 DOI: 10.1016/j.ijpx.2024.100312] [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: 09/19/2024] [Revised: 11/11/2024] [Accepted: 12/12/2024] [Indexed: 01/16/2025] Open
Abstract
Systemic administration of methotrexate (MTX), widely regarded as one of the most effective treatments for psoriasis, poses significant challenges due to its high toxicity, limited solubility, and potential for adverse effects. Consequently, developing a topical form of MTX may offer a safer and more effective strategy for psoriasis management. Silk fibroin (SF), a protein-based biomacromolecule, has shown considerable promise as a nanocarrier for sustained and targeted drug delivery, owing to its exceptional physicochemical and biological properties. This study aimed to develop and characterize a novel drug delivery nanocarrier for MTX using SF nanoparticles modified with hyaluronic acid (HA) and to assess their potential for skin-targeted drug delivery with reduced transdermal permeation. The nanoparticles were thoroughly characterized, demonstrating a uniform particle size, high drug-loading capacity, pH sensitivity, and excellent slow-release properties. In vitro and in vivo experiments further indicated that these nanoparticles effectively reduced psoriasis-induced inflammatory responses, including erythema and scaling, by inhibiting keratinocyte proliferation and decreasing levels of pro-inflammatory cytokines. The inclusion of HA improved nanoparticle targeting, particularly through interactions with overexpressed CD44 proteins in psoriatic skin, resulting in enhanced methotrexate accumulation at the sites of inflammation and improved therapeutic efficacy. Our findings suggest that HA/SF nanoparticles loaded with MTX represent a promising, safe transdermal delivery system for the localized treatment of psoriasis.
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Affiliation(s)
- Lan Cheng
- State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China
| | - Yanhua Zhang
- State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China
- Luoyang Central Hospital, No. 288 Zhongzhou middle road, Xigong district, Luoyang, Henan province, 471000, China
| | - Qian Xu
- State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China
| | - Zheng Li
- State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China
| | - Zulan Liu
- State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China
| | - Fangyin Dai
- State Key Laboratory of Resource Insects, Key Laboratory for Sericulture Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Yibin Academy, Southwest University, Chongqing 400715, China
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Mao M, Yuan Y, Li R, Kuang Y, Lu Y, Zhu W, Chen W. Modulation of gut propionate and intestinal mucosal protection by Bifidobacterium longum: Mitigating methotrexate side effects without compromising the efficacy of psoriasis therapy. Int Immunopharmacol 2025; 149:114196. [PMID: 39904035 DOI: 10.1016/j.intimp.2025.114196] [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: 11/18/2024] [Revised: 01/26/2025] [Accepted: 01/27/2025] [Indexed: 02/06/2025]
Abstract
Methotrexate (MTX) is a widely used medication that can also be employed in the treatment of psoriasis. Previous studies have emphasized that MTX can induce dysbiosis of the gut microbiota, leading to intestinal damage. In this study, the serum levels of calprotectin and zonulin were elevated in patients treated with MTX, while no significant increase in patients treated with MTX combined with probiotics. Furthermore, we established an imiquimod (IMQ) induced psoriasis-like dermatitis mouse model and treated it with MTX (50 µL, 0.3 mg/mL) and B. longum (200 µL, 1 × 1011 CFU/mL). The results showed that B. longum treatment reduced FITC-dextran intestinal permeability and lowered serum levels of calprotectin and zonulin. It also decreased the expression and secretion levels of inflammatory factors in intestinal tissues, such as IL-6, TNF-α, and IL-23A, while increasing the expression and secretion of the protective factor IL-10. Moreover, B. longum treatment maintained barrier integrity by increasing the abundance of propionate in the gut, thereby regulating the balance of Th17/Treg cells. In conclusion, this study suggests that incorporating B. longum into the traditional MTX regimen may enhance its effectiveness in treating psoriasis while preserving the integrity of the intestinal mucosa.
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Affiliation(s)
- Manyun Mao
- Chinese Academy of Medical Sciences Institute of Dermatology, Nanjing, Jiangsu, China
| | - Yan Yuan
- Chinese Academy of Medical Sciences Institute of Dermatology, Nanjing, Jiangsu, China
| | - Rao Li
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Yehong Kuang
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Yan Lu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Wu Zhu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China.
| | - Wangqing Chen
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China; Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China.
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Zhang P, Tang J, Cheng L, Xue Y, Yang J, Sun Z, Liu J. Hyaluronic acid modified liposomes with enhanced transdermal delivery of methotrexate for psoriasis treatment. Colloids Surf B Biointerfaces 2025; 247:114457. [PMID: 39689591 DOI: 10.1016/j.colsurfb.2024.114457] [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: 10/09/2024] [Revised: 12/08/2024] [Accepted: 12/12/2024] [Indexed: 12/19/2024]
Abstract
Psoriasis is a chronic inflammatory skin disorder characterized by immune dysregulation and cutaneous symptoms. Methotrexate (MTX), efficacious in psoriasis, suffers from limited transdermal permeability due to its hydrophilic nature. Liposomal nanomedicine, which offers increased bioavailability and targeted delivery with minimized systemic effects, is a promising approach. The application of hyaluronic acid (HA) as a penetration enhancer and modifier leverages its binding to the upregulated CD44 receptor in psoriasis, enhancing the efficacy of liposomes. In this study, we synthesized HA-modified liposomes by conjugating HA with distearoyl phosphatidyl ethanolamine-poly (ethylene glycol) (DSPE-PEG) and encapsulated methotrexate for targeted treatment of psoriasis. The research entailed the meticulous preparation and physicochemical characterization of these HA-modified liposomes, followed by in vitro transdermal delivery assays, cellular uptake studies, and the development of a psoriasis animal model to rigorously assess therapeutic efficacy. Our findings underscore the significant improvement in methotrexate's transdermal penetration and retention within psoriatic lesions afforded by the HA-modified liposomes, indicating a novel and efficacious therapeutic approach for the management of dermatological disorders.
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Affiliation(s)
- Penglei Zhang
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong 518107, China
| | - Junjie Tang
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong 518107, China
| | - Lili Cheng
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong 518107, China
| | - Yifan Xue
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong 518107, China
| | - Jiahuan Yang
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong 518107, China
| | - Zhongsheng Sun
- Guangdong Second Provincial General Hospital, Guangzhou, Guangdong 510317, China.
| | - Jie Liu
- School of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong 518107, China.
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Greiling T, Young M, Seal MS, Higham RC, Armstrong A. Patient Perspectives on the Prevalence and Burden of Intertriginous Psoriasis: Results from a National Survey of Adults with Psoriasis in the United States. Dermatol Ther (Heidelb) 2024; 14:1839-1847. [PMID: 38874893 PMCID: PMC11265023 DOI: 10.1007/s13555-024-01190-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Accepted: 05/20/2024] [Indexed: 06/15/2024] Open
Abstract
INTRODUCTION A survey was conducted by The Harris Poll on behalf of Arcutis Biotherapeutics in the USA to understand perspectives and burden of patients with psoriasis using prescription topical treatments for their disease. This manuscript presents results from the subset of patients with intertriginous psoriasis. METHODS The survey was conducted online October 21-November 24, 2021, among 507 US adults aged 18+ years with psoriasis diagnosed by a healthcare provider and currently using prescription topical treatment. Participants with intertriginous psoriasis were patients with plaque psoriasis reporting symptoms in the armpit, groin, under breast, stomach fold, or between the buttocks. RESULTS Of the 507 respondents, 320 (64%) reported symptoms in intertriginous areas at some point, typically between the buttocks (31%). Most patients with intertriginous psoriasis reported it made them feel embarrassed (80%), anxious (79%), or depressed (69%). In addition, 45% of these patients reported intertriginous psoriasis caused a negative impact on sexual anxiety or distress. Quality of life impact was reported as "very strong negative impact" in 16% of patients with groin involvement vs. 6% in patients with no groin involvement and 15% in women vs. 6% in men. Patients with intertriginous psoriasis reported that itch (61%), scaling (53%), redness (49%), and skin cracking (46%) related to intertriginous psoriasis had the greatest negative impact on quality of life. Most (86%) of these patients said they would be more adherent if a single treatment option could be used to treat all affected areas of their body. CONCLUSION Psoriasis involvement in intertriginous areas over the course of disease is common and has a negative impact on these patients' quality of life, particularly emotional well-being and sexual health.
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Affiliation(s)
- Teri Greiling
- Department of Dermatology, Oregon Health & Science University, Portland, OR, USA
| | - Melodie Young
- Mindful Dermatology, Modern Research Associates, Dallas, TX, USA
| | - Melissa S Seal
- Arcutis Biotherapeutics, Inc., Westlake Village, CA, USA.
| | | | - April Armstrong
- Department of Dermatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
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Chen Y, Zhu C, Tai Z, Lian T, Zhu Q, Chen Z. Cordycepin Ameliorates Psoriasis-Like Skin Lesion by Regulating p53/MDM2 Feedback Loop. Mol Biotechnol 2024:10.1007/s12033-024-01211-9. [PMID: 38914920 DOI: 10.1007/s12033-024-01211-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 06/04/2024] [Indexed: 06/26/2024]
Abstract
Apoptosis is a natural physiological process of programmed cell death. It is essential for maintaining the homeostasis of the body and the immune system. The dysfunction of apoptosis can lead to the development of autoimmune diseases. In psoriasis, the dysfunction of keratinocyte proliferation manifests as an impairment of apoptosis. Cordycepin is the major active component in cordyceps militaris and has pharmacological effects, including regulation of apoptosis. The pharmacological mechanism of Cordycepin in psoriasis remains unclear. In this study, bioinformatics analysis revealed that the mechanism may be associated with the p53 apoptotic pathway. Further, we confirmed in the experiments that cordycepin inhibited the interleukin (IL)-17A-induced proliferation of HaCaT cells and down-regulated the expression of proliferating cell nuclear antigen (PCNA) and Ki-67. Regulating the expression of apoptotic proteins BAX, Bcl-2, and p53 promote apoptosis. Further investigation of the upstream pathway of apoptosis revealed that cordycepin could normalize the abnormal p53-mouse double minute 2 (MDM2) feedback loop. In vivo results showed that the cordycepin gel could effectively improve imiquimod (IMQ)-induced psoriasis-like skin lesions in mice, and the p53-MDM2 pathway was verified at the protein level. In conclusion, the anti-psoriasis effect of Cordycepin and its potential mechanism have not been discussed in detail. However, our work supports the idea that Cordycepin can be further developed as an Active Pharmaceutical Ingredient (API) for the treatment of psoriasis.
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Affiliation(s)
- Ya Chen
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, China
- Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China
| | - Congcong Zhu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, China
- Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China
| | - Zongguang Tai
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, China
- Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China
| | - Tianyan Lian
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, China
- Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China
| | - Quangang Zhu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, China.
- Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China.
| | - Zhongjian Chen
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai, 200443, China.
- Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai, China.
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Gao X, Lin X, Wang Q, Chen J. Artemisinins: Promising drug candidates for the treatment of autoimmune diseases. Med Res Rev 2024; 44:867-891. [PMID: 38054758 DOI: 10.1002/med.22001] [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: 09/21/2023] [Revised: 11/02/2023] [Accepted: 11/22/2023] [Indexed: 12/07/2023]
Abstract
Autoimmune diseases are characterized by the immune system's attack on one's own tissues which are highly diverse and diseases differ in severity, causing damage in virtually all human systems including connective tissue (e.g., rheumatoid arthritis), neurological system (e.g., multiple sclerosis) and digestive system (e.g., inflammatory bowel disease). Historically, treatments normally include pain-killing medication, anti-inflammatory drugs, corticosteroids, and immunosuppressant drugs. However, given the above characteristics, treatment of autoimmune diseases has always been a challenge. Artemisinin is a natural sesquiterpene lactone initially extracted and separated from Chinese medicine Artemisia annua L., which has a long history of curing malaria. Artemisinin's derivatives such as artesunate, dihydroartemisinin, artemether, artemisitene, and so forth, are a family of artemisinins with antimalarial activity. Over the past decades, accumulating evidence have indicated the promising therapeutic potential of artemisinins in autoimmune diseases. Herein, we systematically summarized the research regarding the immunoregulatory properties of artemisinins including artemisinin and its derivatives, discussing their potential therapeutic viability toward major autoimmune diseases and the underlying mechanisms. This review will provide new directions for basic research and clinical translational medicine of artemisinins.
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Affiliation(s)
- Xu Gao
- Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, China
- Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
- Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen, China
| | - Xian Lin
- Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, China
- Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
- Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen, China
| | - Qingwen Wang
- Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, China
- Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
- Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen, China
| | - Jian Chen
- Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, China
- Institute of Immunology and Inflammatory Diseases, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
- Shenzhen Key Laboratory of Inflammatory and Immunology Diseases, Shenzhen, China
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Zhao P, Li Z, Ling Z, Zheng Y, Chang H. Efficient Loading and Sustained Delivery of Methotrexate Using a Tip-Swellable Microneedle Array Patch for Psoriasis Treatment. ACS Biomater Sci Eng 2024; 10:921-931. [PMID: 38288701 DOI: 10.1021/acsbiomaterials.3c01810] [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: 02/13/2024]
Abstract
Methotrexate (MTX), a primary treatment for moderate to severe psoriasis, is limited in clinical use due to suboptimal results and severe side effects from subcutaneous (SC) injection and oral administration. Microneedles offer a promising alternative for direct MTX delivery to targeted skin lesions, but issues such as drug wastage, dosage inaccuracy, and limited drug residence time in the lesions remain. This study introduces a tip-swellable microneedle array patch (TSMAP) using photo-cross-linked methacrylated hyaluronic acid (MeHA) and biocompatible resin for effective MTX loading and sustained delivery. A two-cast micromolding with vacuum drying is employed to concentrate cross-linked MeHA in about 30% of the needle's height at the tip, thereby ensuring that only the TSMAP tip swells. Efficient MTX loading into TSMAP tips is achieved through a 30 s drug solution immersion and 10 min drying, potentially minimizing drug waste from incomplete skin insertion due to skin elasticity. The MTX-loaded TSMAP effectively penetrates both porcine and psoriasis-like mouse skin with its tips detaching from the resin substrate and embedding deeply into the skin tissue, thereby functioning as a drug release reservoir. TSMAP significantly prolongs drug retention in skin compared with SC injection and dissolvable microneedles. The in vivo study demonstrates that TSMAP-mediated MTX delivery substantially enhances therapeutic outcomes in alleviating psoriasis symptoms and downregulating psoriasis-associated cytokines, outperforming oral administration, SC injection, and dissolvable microneedles. Thus, TSMAP could offer an efficient and user-friendly alternative for drug administration in the treatment of various skin diseases.
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Affiliation(s)
- Puxuan Zhao
- College of Materials Science and Engineering, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, China
- Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang, Hangzhou 310022, China
| | - Zhiming Li
- Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang, Hangzhou 310022, China
| | - Zhixin Ling
- Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang, Hangzhou 310022, China
| | - Yanting Zheng
- Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang, Hangzhou 310022, China
- College of Pharmaceutical Sciences, Zhejiang University of Technology, Zhejiang, Hangzhou 310014, China
| | - Hao Chang
- Hangzhou Institute of Medicine, Chinese Academy of Sciences, Zhejiang, Hangzhou 310022, China
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Salgaonkar SP, Purewal JS, Doshi GM, Fernandes T, Gharat S, Sawarkar SP. New Insights in Psoriasis Management using Herbal Drug Nanocarriers. Curr Pharm Des 2024; 30:2550-2561. [PMID: 39051579 DOI: 10.2174/0113816128330298240708110336] [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: 05/13/2024] [Accepted: 06/19/2024] [Indexed: 07/27/2024]
Abstract
Psoriasis (Pso) is an autoimmune inflammatory skin disease characterized by red plaques covered in silver scales. The existing treatments provide limited benefits and are associated with certain drawbacks which limit their use. Thus, there is a need to explore more options that are highly target-specific and associated with minimal side effects. Researchers have thoroughly investigated the use of herbal drugs for their therapeutic potential. Preclinical studies demonstrate that phytochemicals such as curcumin, psoralen, and dithranol have antipsoriatic effects. These phytoconstituents inhibit the signalling pathways, such as the interleukin (IL) 23/Th17 axis and IL-36 inflammatory loop involved in the pathogenesis of Pso. These phytoconstituents down-regulate the pro-inflammatory cytokines like IL-17 and tumor necrosis factor (TNF)-α. However, their application in clinical settings is limited due to poor bioavailability and access to target sites. Combining phytoconstituents with modern delivery platforms like nanocarriers can address these shortcomings and improve therapeutic efficacy. This review explores the potential of herbal remedies as a substitute for conventional therapies, emphasizing the clinical trials conducted with these herbal medicines. The paper is supported by the discussion on nanocarriers like liposomes, niosomes, emulsomes, ethosomes, nanostructured lipid carriers, nanoemulsions, and dendrimers that are used to deliver herbal medicines.
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Affiliation(s)
- Shreyas P Salgaonkar
- Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India
| | - Japneet Singh Purewal
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India
| | - Gaurav Mahesh Doshi
- Department of Pharmacology, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India
| | - Trinette Fernandes
- Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India
| | - Sankalp Gharat
- Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India
| | - Sujata P Sawarkar
- Department of Pharmaceutics, SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, India
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Bellamy CO, Burt AD. Liver in Systemic Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:1039-1095. [DOI: 10.1016/b978-0-7020-8228-3.00015-6] [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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Hosseini E, Shahbazi F. Methotrexate-induced Severe Pancytopenia in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature. Curr Drug Saf 2024; 19:224-235. [PMID: 37194235 DOI: 10.2174/1574886318666230516115737] [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: 12/24/2022] [Revised: 03/15/2023] [Accepted: 04/03/2023] [Indexed: 05/18/2023]
Abstract
Toxicity associated with low doses of methotrexate (MTX) is low, but it may be fatal. Bone marrow suppression and mucositis are among the common side effects of low dose MTX toxicity. Different risk factors have been reported for toxicities associated with low doses of MTX, including accidental use of higher doses, renal dysfunction, hypoalbuminemia, and polypharmacy. In this paper, we present a female patient who had mistakenly used 7.5 mg of MTX daily instead of the same dose of MTX on Thursday and Friday. She was presented with mucositis and diarrhea to the emergency department. Moreover, we searched the databases Scopus and PubMed for available studies and case reports on toxicities associated with MTX dosing errors. The most frequently observed toxicities included gastrointestinal lesions, nausea, vomiting, skin lesions, and bone marrow suppression. Leucovorin, hydration, and urine alkalinization were among the most frequently used treatments. Finally, we summarize the data on the toxicities of low doses of MTX in different diseases.
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Affiliation(s)
- Elham Hosseini
- Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Foroud Shahbazi
- Department of Clinical Pharmacy, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Asnani D, Singh S, Gupta A. Addressing Diagnostic and Therapeutic Challenges in a Case of Concurrent Tinea and Plaque Psoriasis. Case Rep Dermatol 2024; 16:254-258. [PMID: 39981007 PMCID: PMC11650875 DOI: 10.1159/000542483] [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: 05/27/2024] [Accepted: 11/02/2024] [Indexed: 02/22/2025] Open
Abstract
Introduction The annular lesions of dermatophytosis can closely resemble the plaques of psoriasis, posing significant diagnostic and treatment challenges. Methotrexate, a common treatment for psoriasis, can exacerbate the former due to its immunosuppressive effects. Case Report A middle-aged man with chronic plaque psoriasis was on tablet methotrexate (7.5 mg once weekly) and topical steroids for 1 year. Despite some improvement, new annular lesions emerged whenever topical steroids were tapered. Frustrated with the lack of disease control, the patient finally visited a tertiary care center, where tinea corporis was diagnosed alongside psoriasis via dermoscopy, mycological tests, and histopathology. Methotrexate and steroids were discontinued, and the patient was started on antifungals. Once the dermatophytosis was brought under control, methotrexate was resumed alongside targeted application of steroid and antifungal creams. Conclusion The coexistence of tinea corporis and psoriasis can be challenging to diagnose and treat, necessitating thorough clinical evaluation and mycological testing. Proactive monitoring and timely intervention are crucial to prevent complications and ensure optimal management outcomes in immunosuppressed individuals with dermatophyte infections.
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Affiliation(s)
- Divya Asnani
- Department of Dermatology, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri-Pune, India
| | - Shrishti Singh
- Department of Dermatology, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri-Pune, India
| | - Aayush Gupta
- Department of Dermatology, Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri-Pune, India
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Chen TC, Wang TC, Yiu ZZN, Lee MS, Chen LC, Chan KA, Griffiths CEM, Ashcroft DM. Risk of serious infection and infection mortality in patients with psoriasis: A nationwide cohort study using the Taiwan National Health Insurance claims database. J Eur Acad Dermatol Venereol 2024; 38:136-144. [PMID: 37611288 DOI: 10.1111/jdv.19466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 08/11/2023] [Indexed: 08/25/2023]
Abstract
BACKGROUND The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. OBJECTIVES We examined the incidence of serious infection and infection mortality in patients with psoriasis. METHODS This population-based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate-to-severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). RESULTS Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19-1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate-to-severe psoriasis (aHR: 1.30, 95% CI: 1.27-1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09-1.13), skin/soft-tissue infections (aHR: 1.57, 95% CI: 1.52-1.62), sepsis (aHR: 1.23, 95% CI: 1.19-1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08-1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06-1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32-1.69). Furthermore, psoriasis patients were associated with a higher risk of infection-related mortality (aHR: 1.15, 95% CI: 1.11-1.18) compared to matched comparators. CONCLUSION Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate-to-severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment.
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Affiliation(s)
- Teng-Chou Chen
- Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- Department of Pharmacy, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ting-Chun Wang
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Zenas Z N Yiu
- Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Meng-Sui Lee
- Department of Dermatology, Taipei City Hospital, Taipei, Taiwan
- Department of Dermatology, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Li-Chia Chen
- Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - K Arnold Chan
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Christopher E M Griffiths
- Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
- NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
| | - Darren M Ashcroft
- Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
- NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
- NIHR Greater Manchester Patient Safety Translational Research Centre, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK
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13
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Zhao W, Zheng L, Yang J, Ma Z, Tao X, Wang Q. Dissolving microneedle patch-assisted transdermal delivery of methotrexate improve the therapeutic efficacy of rheumatoid arthritis. Drug Deliv 2023; 30:121-132. [PMID: 36533887 PMCID: PMC9769132 DOI: 10.1080/10717544.2022.2157518] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Methotrexate (MTX) is a first-line treatment for rheumatoid arthritis (RA), but its clinical use is greatly limited by the adverse effects and poor patient compliance caused by traditional oral administration or injection. In recent years, some transdermal drug delivery systems have received considerable attention due to overcoming these shortcomings. In this study, we developed dissolving microneedle patch (DMNP) for transdermal delivery of MTX to treat RA safely and effectively. The morphology, mechanical strength, skin insertion, drug content, in vitro transdermal delivery, and other properties of DMNP were characterized. Meanwhile, the adjuvant-induced arthritis model of rats was established to investigate the therapeutic effect of MTX-loaded DMNP in vivo. The results showed that the microneedles had excellent morphology with neat array and complete needles, good puncture performance and mechanical strength, and rapid intradermal dissolution rate. In vitro transdermal delivery results indicated that microneedles could significantly increase drug transdermal permeation compared with the cream group. The pharmacological study showed that MTX-loaded DMNP significantly alleviated paw swelling, inhibit inflammatory response via downregulating the levels of TNF-α and IL-1β, relieved synovium destruction with less cartilage erosion, and slowed the progression of RA in AIA rats. Besides, DMNP presented better therapeutic performance than cream or intragastric administration at the same dosage of MTX. In conclusion, the MTX-loaded dissolving microneedle patch has advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment of rheumatoid arthritis.
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Affiliation(s)
- Weiman Zhao
- School of Pharmacy, Bengbu Medical College, Bengbu, China
| | - Lijie Zheng
- School of Pharmacy, Bengbu Medical College, Bengbu, China
| | - Jianhui Yang
- School of Pharmacy, Anhui Medical University, Hefei, China
| | - Zihui Ma
- School of Pharmacy, Bengbu Medical College, Bengbu, China
| | - Xinyi Tao
- School of Pharmacy, Bengbu Medical College, Bengbu, China
| | - Qingqing Wang
- School of Pharmacy, Bengbu Medical College, Bengbu, China,Engineering Research Center for Biochemical Pharmaceuticals of Anhui Province, Bengbu Medical College, Bengbu, China,CONTACT Qingqing Wang School of Pharmacy, Bengbu Medical College, Bengbu 233030, China
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14
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Guo J, Zhang H, Lin W, Lu L, Su J, Chen X. Signaling pathways and targeted therapies for psoriasis. Signal Transduct Target Ther 2023; 8:437. [PMID: 38008779 PMCID: PMC10679229 DOI: 10.1038/s41392-023-01655-6] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 09/10/2023] [Accepted: 09/14/2023] [Indexed: 11/28/2023] Open
Abstract
Psoriasis is a common, chronic, and inflammatory skin disease with a high burden on individuals, health systems, and society worldwide. With the immunological pathologies and pathogenesis of psoriasis becoming gradually revealed, the therapeutic approaches for this disease have gained revolutionary progress. Nevertheless, the mechanisms of less common forms of psoriasis remain elusive. Furthermore, severe adverse effects and the recurrence of disease upon treatment cessation should be noted and addressed during the treatment, which, however, has been rarely explored with the integration of preliminary findings. Therefore, it is crucial to have a comprehensive understanding of the mechanisms behind psoriasis pathogenesis, which might offer new insights for research and lead to more substantive progress in therapeutic approaches and expand clinical options for psoriasis treatment. In this review, we looked to briefly introduce the epidemiology, clinical subtypes, pathophysiology, and comorbidities of psoriasis and systematically discuss the signaling pathways involving extracellular cytokines and intracellular transmission, as well as the cross-talk between them. In the discussion, we also paid more attention to the potential metabolic and epigenetic mechanisms of psoriasis and the molecular mechanistic cascades related to its comorbidities. This review also outlined current treatment for psoriasis, especially targeted therapies and novel therapeutic strategies, as well as the potential mechanism of disease recurrence.
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Affiliation(s)
- Jia Guo
- Department of Dermatology, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, Hunan, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, Hunan, China
| | - Hanyi Zhang
- Department of Dermatology, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, Hunan, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, Hunan, China
| | - Wenrui Lin
- Department of Dermatology, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, Hunan, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, Hunan, China
| | - Lixia Lu
- Department of Dermatology, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, Hunan, China
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, 410008, Hunan, China
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, Hunan, China
- Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, Hunan, China
| | - Juan Su
- Department of Dermatology, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, Hunan, China.
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, 410008, Hunan, China.
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, Hunan, China.
- Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, Hunan, China.
| | - Xiang Chen
- Department of Dermatology, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, Hunan, China.
- National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, 410008, Hunan, China.
- Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, Hunan, China.
- Hunan Engineering Research Center of Skin Health and Disease, Changsha, 410008, Hunan, China.
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15
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Orfali RL, Lorenzini D, Bressan A, Tanaka AA, Cerqueira AMMD, Hirayama ADS, Ramos AMC, Proença CC, Silva CMDR, Laczynski CMM, Carneiro FR, Duarte G, Hans Filho G, Gonçalves HDS, Melo LPD, Azulay-Abulafia L, Weber MB, Rivitti-Machado MC, Zaniboni MC, Ogawa M, Pires MC, Ianhez M, Felix PAO, Bonamigo R, Takaoka R, Lazzarini R, Cestari S, Mayor SAS, Cestari T, Oliveira ZNPD, Spuls PI, Gerbens LAA, Aoki V. Consensus on the therapeutic management of atopic dermatitis ‒ Brazilian Society of Dermatology: an update on phototherapy and systemic therapy using e-Delphi technique. An Bras Dermatol 2023; 98:814-836. [PMID: 37302894 PMCID: PMC10589461 DOI: 10.1016/j.abd.2023.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 04/04/2023] [Accepted: 04/09/2023] [Indexed: 06/13/2023] Open
Abstract
This publication is an update of the "Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology" published in 2019, considering the novel, targeted-oriented systemic therapies for atopic dermatitis. The initial recommendations of the current consensus for systemic treatment of patients with atopic dermatitis were based on a recent review of scientific published data and a consensus was reached after voting. The Brazilian Society of Dermatology invited 31 experts from all regions of Brazil and 2 international experts on atopic dermatitis who fully contributed to the process. The methods included an e-Delphi study to avoid bias, a literature search and a final consensus meeting. The authors added novel approved drugs in Brazil and the indication for phototherapy and systemic therapy for AD. The therapeutical response to systemic treatment is hereby reported in a suitable form for clinical practice and is also part of this updated manuscript.
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Affiliation(s)
- Raquel Leao Orfali
- Department of Dermatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
| | - Daniel Lorenzini
- Department of Dermatology, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brazil
| | - Aline Bressan
- Department of Dermatology, Hospital Universitário Pedro Ernesto, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Anber Ancel Tanaka
- Department of Dermatology, Hospital Universitário Evangélico Mackenzie, Curitiba, PR, Brazil
| | | | - André da Silva Hirayama
- Department of Dermatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Andréa Machado Coelho Ramos
- Department of Dermatology, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Carolina Contin Proença
- Dermatology Clinic, Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil
| | | | | | | | - Gleison Duarte
- Department of Dermatology, Instituto Bahiano de Imunoterapia, Salvador, BH, Brazil
| | - Gunter Hans Filho
- Department of Dermatology, Hospital Universitário Maria Aparecida Pedrossian, Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
| | - Heitor de Sá Gonçalves
- Department of Health, National Reference Center in Sanitary Dermatology Dona Libânia, Fortaleza, CE, Brazil
| | - Ligia Pessoa de Melo
- Department of Dermatology, Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE, Brazil; Health Department, Hospital Otávio de Freitas, Recife, PE, Brazil
| | - Luna Azulay-Abulafia
- Department of Dermatology, Hospital Universitário Pedro Ernesto, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Professor Rubem David Azulay Institute of Dermatology, Santa Casa de Misericórdia do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | | | - Maria Cecília Rivitti-Machado
- Department of Dermatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil; Department of Dermatology, Universidade Metropolitana de Santos, Santos, SP, Brazil
| | - Mariana Colombini Zaniboni
- Department of Dermatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Marília Ogawa
- Department of Dermatology, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Mario Cezar Pires
- Department of Dermatology, Complexo Hospitalar Padre Bento, Guarulhos, SP, Brazil; Department of Dermatology, State Public Servant Hospital, São Paulo, SP, Brazil
| | - Mayra Ianhez
- Department of Dermatology, Hospital for Tropical Diseases, Goiânia, GO, Brazil; Department of Dermatology, Universidade Federal de Goiás, Goiânia, GO, Brazil
| | | | - Renan Bonamigo
- Department of Dermatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Roberto Takaoka
- Department of Dermatology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
| | - Rosana Lazzarini
- Dermatology Clinic, Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, SP, Brazil
| | - Silmara Cestari
- Department of Dermatology, Teaching and Research Institute of Hospital Sírio-Libanês, São Paulo, SP, Brazil
| | | | - Tania Cestari
- Department of Dermatology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | | | - Phyllis I Spuls
- Department of Dermatology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, The Netherlands
| | - Louise A A Gerbens
- Department of Dermatology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, The Netherlands
| | - Valeria Aoki
- Department of Dermatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
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16
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Siegfried EC, Arkin LM, Chiu YE, Hebert AA, Callen JP, Castelo-Soccio L, Co DO, Cordoro KM, Curran ML, Dalrymple AM, Flohr C, Gordon KB, Hanna D, Irvine AD, Kim S, Kirkorian AY, Lara-Corrales I, Lindstrom J, Paller AS, Reyes M, Begolka WS, Tom WL, Van Voorhees AS, Vleugels RA, Lee LW, Davies OMT, Brandling-Bennett HA. Methotrexate for inflammatory skin disease in pediatric patients: Consensus treatment guidelines. Pediatr Dermatol 2023; 40:789-808. [PMID: 37316462 DOI: 10.1111/pde.15327] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 03/26/2023] [Indexed: 06/16/2023]
Abstract
Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.
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Affiliation(s)
- Elaine C Siegfried
- SSM Cardinal Glennon Children's Hospital, St. Louis, Missouri, USA
- Saint Louis University School of Medicine, St. Louis, Missouri, USA
| | - Lisa M Arkin
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | - Yvonne E Chiu
- Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Adelaide A Hebert
- UTHealth McGovern Medical School at Houston, Houston, Texas, United States
| | - Jeffrey P Callen
- University of Louisville School of Medicine, Louisville, Kentucky, USA
| | - Leslie Castelo-Soccio
- The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
- University of Pennsylvania Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Dominic O Co
- University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
| | | | - Megan L Curran
- Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Austin M Dalrymple
- SSM Cardinal Glennon Children's Hospital, St. Louis, Missouri, USA
- Saint Louis University School of Medicine, St. Louis, Missouri, USA
| | - Carsten Flohr
- Department of Paediatric Dermatology, St John's Institute of Dermatology, Guy's & St Thomas' NHS Foundation Trust, London, UK
| | - Ken B Gordon
- Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | | | | | - Susan Kim
- University of California, San Francisco, California, USA
| | - A Yasmine Kirkorian
- George Washington University School of Medicine & Health Sciences, Washington, DC, USA
- Children's National Hospital, Washington, DC, USA
| | | | - Jill Lindstrom
- Walter Reed National Military Medical Center, Bethesda, Maryland, USA
| | - Amy S Paller
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Melissa Reyes
- US Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA
| | | | - Wynnis L Tom
- University of California, San Diego School of Medicine, San Diego, California, USA
- Rady Children's Hospital-San Diego, San Diego, California, USA
| | | | - Ruth Ann Vleugels
- Boston Children's Hospital and Brigham and Women's Hospital, Boston, Massachusetts, USA
- Harvard Medical School, Boston, Massachusetts, USA
| | - Lara Wine Lee
- Medical University of South Carolina, Charleston, South Carolina, USA
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17
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Predicting Hepatotoxicity Associated with Low-Dose Methotrexate Using Machine Learning. J Clin Med 2023; 12:jcm12041599. [PMID: 36836131 PMCID: PMC9967588 DOI: 10.3390/jcm12041599] [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] [Received: 01/11/2023] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 02/19/2023] Open
Abstract
An accurate prediction of the hepatotoxicity associated with low-dose methotrexate can provide evidence for a reasonable treatment choice. This study aimed to develop a machine learning-based prediction model to predict hepatotoxicity associated with low-dose methotrexate and explore the associated risk factors. Eligible patients with immune system disorders, who received low-dose methotrexate at West China Hospital between 1 January 2018, and 31 December 2019, were enrolled. A retrospective review of the included patients was conducted. Risk factors were selected from multiple patient characteristics, including demographics, admissions, and treatments. Eight algorithms, including eXtreme Gradient Boosting (XGBoost), AdaBoost, CatBoost, Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LightGBM), Tree-based Pipeline Optimization Tool (TPOT), Random Forest (RF), and Artificial Neural Network (ANN), were used to establish the prediction model. A total of 782 patients were included, and hepatotoxicity was detected in 35.68% (279/782) of the patients. The Random Forest model with the best predictive capacity was chosen to establish the prediction model (receiver operating characteristic curve 0.97, accuracy 64.33%, precision 50.00%, recall 32.14%, and F1 39.13%). Among the 15 risk factors, the highest score was a body mass index of 0.237, followed by age (0.198), the number of drugs (0.151), and the number of comorbidities (0.144). These factors demonstrated their importance in predicting hepatotoxicity associated with low-dose methotrexate. Using machine learning, this novel study established a predictive model for low-dose methotrexate-related hepatotoxicity. The model can improve medication safety in patients taking methotrexate in clinical practice.
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18
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Polesie S, Gillstedt M, Schmidt SAJ, Egeberg A, Pottegård A, Kristensen K. Use of methotrexate and risk of skin cancer: a nationwide case-control study. Br J Cancer 2023; 128:1311-1319. [PMID: 36739322 PMCID: PMC10050200 DOI: 10.1038/s41416-023-02172-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM). METHODS In a nationwide Danish case-control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use. RESULTS Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20-1.38), 1.61 (1.37-1.89) and 1.35 (1.13-1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23-1.67), 1.18 (0.80-1.74) and 1.15 (0.77-1.72), respectively. CONCLUSIONS We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose-response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis.
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Affiliation(s)
- Sam Polesie
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. .,Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden.
| | - Martin Gillstedt
- Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Region Västra Götaland, Sahlgrenska University Hospital, Department of Dermatology and Venereology, Gothenburg, Sweden
| | - Sigrún Alba Jóhannesdóttir Schmidt
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.,Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
| | - Alexander Egeberg
- Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Anton Pottegård
- Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark
| | - Kasper Kristensen
- Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark
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19
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Miyata M, Ishiwata S, Kuroda M, Tasaki K, Migita K, Ohira H. Hepatic failure in a patient with rheumatoid arthritis treated with methotrexate: A case report. Medicine (Baltimore) 2023; 102:e32711. [PMID: 36705384 PMCID: PMC9875947 DOI: 10.1097/md.0000000000032711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
INTRODUCTION Chronic liver damage from methotrexate (MTX) is not uncommon, and fatal outcome is rare. We experienced a case of hepatic failure leading to death. We considered the cause of death through this case and proposed a method to prevent the progression of this liver injury. PATIENT CONCERNS We report the case of a patient with rheumatoid arthritis treated with MTX for 15 years. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES A liver biopsy revealed histological changes similar to those of advanced nonalcoholic steatohepatitis (NASH), most likely induced by MTX. MTX was discontinued after 4 years. Two years after the discontinuation, the patient died of irreversible hepatic failure. Her obesity, complicated by type 2 diabetes mellitus, might have aggravated MTX-induced NASH-like liver injury. CONCLUSION Early diagnosis and immediate MTX discontinuation following NASH diagnosis and strict type 2 diabetes mellitus control might have prevented the irreversible progression of liver injury.
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Affiliation(s)
- Masayuki Miyata
- Center for Rheumatology and Collagen Diseases, Fukushima Red Cross Hospital, Fukushima, Japan
- * Correspondence: Masayuki Miyata, Center of Internal Medicine for Rheumatology and Collagen Disease, Fukushima Red Cross Hospital, 7-7 Yashimacho, Fukushima City, Fukushima 960-8530, Japan (e-mail: )
| | - Sho Ishiwata
- Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Masahito Kuroda
- Department of Gastroenterology, Fukushima Red Cross Hospital, Fukushima, Japan
| | - Kazuhiro Tasaki
- Department of Pathology, Fukushima Red Cross Hospital, Fukushima, Japan
| | - Kiyoshi Migita
- Department of Rheumatology and Collagen Diseases, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Hiromasa Ohira
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
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20
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Little R, Kamath BM, Ricciuto A. Liver Disease in Pediatric Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:129-149. [DOI: 10.1007/978-3-031-14744-9_11] [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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21
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Yongpisarn T, Namasondhi A, Iamsumang W, Rattanakaemakorn P, Suchonwanit P. Liver fibrosis prevalence and risk factors in patients with psoriasis: A systematic review and meta-analysis. Front Med (Lausanne) 2022; 9:1068157. [PMID: 36590962 PMCID: PMC9797863 DOI: 10.3389/fmed.2022.1068157] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Accepted: 12/02/2022] [Indexed: 12/23/2022] Open
Abstract
Background Patients with psoriasis are more likely than matched controls in the general population to have advanced liver fibrosis; however, our understanding of these patients is limited. There is currently no systematic evaluation of the prevalence and risk factors of liver fibrosis in psoriasis patients. Objective To evaluate the prevalence of psoriasis patients who are at high or low risk for advanced liver fibrosis and determine the risk factors for developing liver fibrosis. Methods Electronic searches were conducted using the PubMed, Embase, Scopus, and Cochrane Library databases from the dates of their inception till May 2022, using the PubMed, Embase, Scopus, and Cochrane Library databases. Any observational study describing the prevalence and/or risk factors for liver fibrosis in patients with psoriasis was included. Results Patients with psoriasis at high risk for advanced liver fibrosis had a pooled prevalence of 9.66% [95% confidence interval (CI): 6.92-12.75%, I 2 = 76.34%], whereas patients at low risk for advanced liver fibrosis had a pooled prevalence of 77.79% (95% CI: 73.23-82.05%, I 2 = 85.72%). Studies that recruited methotrexate (MTX)-naïve patients found a lower prevalence of advanced liver fibrosis (4.44, 95% CI: 1.17-9.22%, I 2 = 59.34%) than those that recruited MTX-user cohorts (12.25, 95% CI: 6.02-20.08%, I 2 = 82.34%). Age, sex, BMI, PASI score, psoriasis duration, MTX cumulative dose, and the prevalence of obesity, MTX users, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome were not identified as sources of heterogeneity by meta-regression analysis. The pooled odds ratios for age >50 years, BMI > 30, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome were 2.20 (95% CI: 1.42-3.40, I 2 = 0%), 3.67 (95% CI: 2.37-5.68, I 2 = 48.8%), 6.23 (95% CI: 4.39-8.84, I 2 = 42.4%), 2.82 (95% CI: 1.68-4.74, I 2 = 0%), 3.08 (95% CI: 1.90-4.98, I 2 = 0%), and 5.98 (95% CI: 3.63-9.83, I 2 = 17%), respectively. Conclusion Approximately 10% of the population with psoriasis is at high risk for advanced liver fibrosis, while 78% are at low risk. Patients over the age of 50 with obesity, diabetes, hypertension, dyslipidemia, and/or metabolic syndrome have an increased risk of developing liver fibrosis, necessitating monitoring. Systematic review registration [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022303886], identifier [CRD42022303886].
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22
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Mao M, Kuang Y, Chen M, Yan K, Lv C, Liu P, Lu Y, Chen X, Zhu W, Chen W. The HLA-Cw*06 allele may predict the response to methotrexate (MTX) treatment in Chinese arthritis-free psoriasis patients. Arch Dermatol Res 2022; 315:1241-1247. [PMID: 36513862 DOI: 10.1007/s00403-022-02498-x] [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: 10/31/2022] [Revised: 10/31/2022] [Accepted: 11/28/2022] [Indexed: 12/15/2022]
Abstract
MTX in genetically distinctive Chinese psoriatic patients remains less explored. The present study aimed to determine the impact of HLA-Cw*06 on MTX response in a Chinese psoriasis patient population. A total of 204 patients with psoriasis were enrolled in this study. Clinical data and DNA samples from all patients were collected. The allele of HLA-Cw*06 genotyping was detected using direct Sanger sequencing. This study enrolled 204 patients with psoriasis, including 47 (23.04%) psoriatic arthritis patients, 157 (76.96%) patients free of psoriatic arthritis. Overall, 110 (53.92%) of all patients carried the HLA-Cw*06 allele. This frequency in patients with arthritis-free psoriasis was higher than that in those with psoriatic arthritis (58.59 vs. 38.30%, P = 0.014). After 8 weeks of MTX treatment, the arthritis-free psoriasis patients, who tested positive for the HLA-Cw*06 allele, showed significant improvement compared to those who tested negative (For PASI50, 78.57 vs. 55.22%, P = 0.02, and for PASI75, 51.11 vs. 34.33%, P = 0.036). The psoriatic arthritis-free patients who carried the HLA-Cw*06 allele in combination with the ABCB1 rs1045642 CC genotype showed the highest improvement. A regression model containing HLA-Cw*06, rs1045642T > C, and initial PASI scores was used to construct the efficacy prediction model of MTX, which yielded AUC values of 73.2 and 75.6% for PASI50 and PASI75 to MTX, respectively, in arthritis-free psoriasis patients. The HLA-Cw*06 allele is associated with optimal response to MTX treatment in arthritis-free Chinese psoriasis patients. When combined with clinical indicators, the polymorphism explained more than 75% of the individual efficacy differences.
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Affiliation(s)
- Manyun Mao
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Yehong Kuang
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Menglin Chen
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Kexiang Yan
- Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China
| | - Chenzhi Lv
- Department of Dermatology, Dalian Dermatosis Hospital, Dalian, Liaoning, China
| | - Panpan Liu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Yan Lu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Xiang Chen
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China.,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China.,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China
| | - Wu Zhu
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China. .,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China. .,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China.
| | - Wangqing Chen
- The Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China. .,Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Changsha, Hunan, China. .,Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Changsha, Hunan, China.
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23
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Vu A, Ulschmid C, Gordon KB. Anti-IL 23 biologics for the treatment of plaque psoriasis. Expert Opin Biol Ther 2022; 22:1489-1502. [PMID: 36243011 DOI: 10.1080/14712598.2022.2132143] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Psoriasis is a chronic inflammatory disease that can drastically affect a patient's quality-of-life and is associated with multiple comorbid conditions. The most common form of psoriasis is plaque psoriasis, commonly presenting as sharply demarcated, erythematous plaques with overlying silvery scale on the trunk, extensor surfaces, limbs, and scalp. Although initially limited to oral therapies, the choices in systemic therapies for moderate-to-severe plaque psoriasis have evolved with biologic immunotherapies being the main focus. AREAS COVERED In this review, we describe the IL-23/Th17 axis and IL-23 inhibitors as targets for a growing family of biologics. This family includes the FDA-approved medications ustekinumab, guselkumab, tildrakizumab, and risankizumab. We will review the safety and efficacy of these medications throughout various Phase 1,2, and 3, trials for moderate-to-severe psoriasis. A literature search of PubMed was utilized for the following terms: 'psoriasis and IL-23,' 'ustekinumab,' 'guselkumab,' 'tildrakizumab,' and 'risankizumab.' We also searched for clinical trials involving IL-23 inhibitors registered at ClinicalTrials.gov. EXPERT OPINION Anti-IL 23 therapy, especially anti-p19 monoclonal antibodies, should be considered first-line therapy for moderate-to-severe plaque psoriasis due to their efficacy and relative safety. More research is required to expand the scope of anti-p19 therapy to pediatric populations and additional indications such as psoriatic arthritis.
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Affiliation(s)
- Alan Vu
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Caden Ulschmid
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Kenneth B Gordon
- Department of Dermatology, Medical College of Wisconsin, Milwaukee, WI, USA
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24
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Ouellette S, Shah R, Razi S, Ashforth G, Wassef C. Fatal low-dose methotrexate toxicity: A case report and literature review. Dermatol Ther 2022; 35:e15945. [PMID: 36259229 DOI: 10.1111/dth.15945] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 10/12/2022] [Accepted: 10/17/2022] [Indexed: 12/01/2022]
Abstract
Methotrexate (MTX) is a chemotherapeutic agent that acts primarily by inhibiting the folic acid cycle. In addition to its application for treating malignancies, MTX is also used to treat chronic inflammatory diseases including psoriasis. Adverse effects have been reported even at low doses (up to 25 mg/week), and there is risk of toxicity in the form of myelosuppression, hepatotoxicity, or pulmonary fibrosis. Here, we report a case of a 67-year-old male with a past medical history of end stage renal disease on peritoneal dialysis and moderate-to-severe psoriasis with psoriatic arthritis presented with abdominal pain, diarrhea, rash, mucositis, and mucocutaneous ulcers and erosions. The patient was taking methotrexate 10 mg weekly without folic acid supplementation and was found to be pancytopenic. Despite treatment, the patient developed multiorgan failure and passed away after 16 days of hospitalization. Myelosuppression is considered the most serious side effect with the highest risk of mortality. Risk factors for toxicity include renal insufficiency, advanced age, lack of folate supplementation, drug interactions, and medication errors. Importantly, serum levels of MTX do not correlate with toxicity; therefore, folinic acid rescue therapy should be started as soon as MTX toxicity is suspected. MTX toxicity is rare with low dose, proper dose scheduling, and adherence to the recommended guidelines. It is imperative that physicians considering therapy with low dose MTX for dermatologic indications take into consideration a patient's risk factors for toxicity and monitor appropriately.
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Affiliation(s)
- Samantha Ouellette
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
| | - Rohan Shah
- Division of Dermatology, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | | | - Gina Ashforth
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
| | - Cindy Wassef
- Department of Dermatology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
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25
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Vu A, Maloney V, Gordon KB. Deucravacitinib in moderate-to-severe psoriasis. Immunotherapy 2022; 14:1279-1290. [DOI: 10.2217/imt-2022-0109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Psoriasis is a chronic inflammatory disease that affects up to 1 in 20 people worldwide. A patient's quality of life and health can be drastically affected by psoriasis. The number of therapies for patients with moderate to severe psoriasis has steadily grown over the past two decades, with biologic immunotherapies being the primary agents developed. However, new small-molecule oral therapies have lagged in development. Deucravacitinib is an oral small molecule that inhibits the activity of TYK2, a member of the JAK family. Deucravacitinib works by allosterically inhibiting TYK2, increasing the specificity of this agent for TYK2 rather than other members of this kinase family. Deucravacitinib has demonstrated safety and efficacy in moderate to severe plaque psoriasis in clinical trial development, with >50% of patients on deucravacitinib 6 mg daily achieving ≥75% reduction in Psoriasis Area and Severity Index score from baseline at 16 weeks versus 9–13% on placebo and 35–41% on apremilast 30 mg twice daily in phase III clinical trials.
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Affiliation(s)
- Alan Vu
- Department of Dermatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Victoria Maloney
- Department of Dermatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
| | - Kenneth B Gordon
- Department of Dermatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
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26
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Hamed KM, Dighriri IM, Baomar AF, Alharthy BT, Alenazi FE, Alali GH, Alenazy RH, Alhumaidi NT, Alhulayfi DH, Alotaibi YB, Alhumaidan SS, Alhaddad ZA, Humadi AA, Alzahrani SA, Alobaid RH. Overview of Methotrexate Toxicity: A Comprehensive Literature Review. Cureus 2022; 14:e29518. [PMID: 36312688 PMCID: PMC9595261 DOI: 10.7759/cureus.29518] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/23/2022] [Indexed: 02/05/2023] Open
Abstract
Methotrexate (MTX) is significantly more effective than and has a considerable advantage over placebo in patients with severe and persistent rheumatoid arthritis (RA). The drug is used to treat a variety of malignant disorders (leukemia and cancer of the lung, breast, and uterus) and ectopic pregnancy. As its side effects are outweighed by its effectiveness, MTX is a first-line antirheumatic drug in many countries. MTX is found in extracellular compartments, such as the synovium, as well as other organs, such as the kidney and liver. To improve treatment, increase adherence, and decrease mortality in MTX therapy, it is essential to reduce its toxicity and understand its side effects. Therefore, this comprehensive review was conducted to assist physicians and researchers in better understanding the toxicity of MTX and how to deal with this toxicity. MTX is eliminated via the kidneys, which are capable of excretion and reabsorption within the renal tubules. Although higher doses of MTX (known as high-dose MTX (HD-MTX), defined as doses of 500 mg/m2 or greater) are often more beneficial, they can produce toxicity and side effects such as bone marrow suppression, pulmonary toxicity, nephrotoxicity, hematologic toxicity, and an increased risk of infections. Treatment of severe MTX toxicity has three main goals: clearance of MTX from the bloodstream, folinic acid therapy, and organ treatment. Leucovorin is highly beneficial in preventing myelosuppression, gastric toxicity, and neurotoxic effects after HD-MTX therapy. The preferred antidote for MTX poisoning is folinic acid. Glucarpidase has been licensed for the treatment of high plasma MTX levels of >1 μmol/L in patients with compromised renal function who have delayed MTX elimination. In patients with renal deficiency, a lower initial dose is considered with an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/minute. These patients need to be monitored, and a more gradual dosage increase and a lower weekly maximum should be considered regarding their general health situation. MTX is contraindicated in patients with RA if the eGFR is <30 mL/minute.
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Affiliation(s)
| | | | | | - Baidaa T Alharthy
- Pharmaceutical Care, General Network for Healthcare Providers Hospital, Jeddah, SAU
| | | | | | - Rawan H Alenazy
- General Medicine and Surgery, Northern Border University, Arar, SAU
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27
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van Huizen AM, Sikkel R, Caron AGM, Menting SP, Spuls PI. Methotrexate Dosing Regimen for Plaque-type Psoriasis: An Update of a Systematic Review. J DERMATOL TREAT 2022; 33:3104-3118. [PMID: 36043844 DOI: 10.1080/09546634.2022.2117539] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Background Methotrexate (MTX) is a systemic treatment for plaque-type psoriasis. At the time of approval, no dose-ranging studies were performed. Nowadays, a uniform dosing regimen is lacking. This might contribute to suboptimal treatment with the drug.Objective To summarize the literature involving the MTX dosing regimens in psoriasis patients.Methods In this SR, RCTs and documents with aggregated evidence (AgEv) on the MTX dosing regimen in psoriasis were summarized. All randomized controlled trials (RCTs) in which oral, subcutaneous or intramuscular MTX was used in patients with psoriasis and AgEv, were included. The MEDLINE, EMBASE and CENTRAL databases were searched up to June 20, 2022. This SR was registered in PROSPERO.Results Thirty-nine RCTs had a high risk of bias. Test dosages were given in only 3 RCTs. In the RCTs, MTX was usually prescribed in a start dose of 7.5 mg/week (n = 13). MTX was mostly given in a start dose of 15 mg/week, in the AgEv (n = 5). One guideline recommended a test dose, in other aggregated evidence a test dose was not mentioned or even discouraged.Conclusions There is a lack of high-quality evidence and available data for dosing MTX in psoriasis is heterogeneous.
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Affiliation(s)
- Astrid M van Huizen
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
| | - Rosie Sikkel
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
| | - Anouk G M Caron
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
| | - Stef P Menting
- OLVG hospital, Department of Dermatology, Amsterdam, the Netherlands
| | - Phyllis I Spuls
- Amsterdam UMC, location University of Amsterdam, Department of Dermatology, Amsterdam Public Health, Infection and Immunity, Meibergdreef 9, Amsterdam, the Netherlands
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28
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Wang Q, Luo N, Lei M, Chen X, Li C, Hao P. Bullous Grover's Disease in a Chinese Tibetan Adolescent: A Case Report. Clin Cosmet Investig Dermatol 2022; 15:1371-1376. [PMID: 35874457 PMCID: PMC9304631 DOI: 10.2147/ccid.s373228] [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: 05/03/2022] [Accepted: 07/06/2022] [Indexed: 11/23/2022]
Abstract
Grover’s disease (GD), also known as Transient acantholytic dermatosis, has no typical clinical rash features. It usually occurs in elderly white men but very rarely in China. This is a disease of acantholysis and dyskeratosis, which is usually considered to be spontaneous remission. The skin lesions of the disease are diverse, and the main symptom is severe itching. We have reported a case of GD in a 14-year-old Chinese Tibetan male whose clinical manifestations were pruritic red papule, generalized red papules, papulo vesicles and blisters ranging from millet rice to soybean size. Skin lesions change rapidly and variously. In order to confirm the diagnosis, we have done skin biopsies, immunofluorescence, dermoscopy, microscopy and other examinations. Pathological skin biopsy showed acantholysis. Intraepidermal blisters and the presence of blisters on the basal cells as well as under the stratum corneum can be observed on the same pathological section. Type IV collagen immunohistochemistry showed blisters in the epidermis. The diagnosis of GD depended on the exclusion of other diseases. After we performed whole exon sequencing (WES) on DNA from the patient’s blood, pathogenic gene mutations were not found. Pustular psoriasis, Subcorneal pustular dermatosis, Herpesvirus infections, Dermatitis herpetiformis, Pemphigus vulgaris, Norwegian scabies, Darier’s disease, and Hailey-Hailey disease were all excluded. We successfully treated adolescent GD with minocycline combined with methotrexate. The patient was followed up for 19 months without recurrence.
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Affiliation(s)
- Qiuyue Wang
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.,Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Nana Luo
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.,Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Min Lei
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.,Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Xian Chen
- Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Chunxiao Li
- Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
| | - Pingsheng Hao
- Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China
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29
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van Huizen AM, Menting SP, Gyulai R, Iversen L, van der Kraaij GE, Middelkamp-Hup MA, Warren RB, Spuls PI, Schejtman AA, Egeberg A, Firooz A, Kumar AS, Oakley A, Foulkes A, Ramos AMC, Fougerousse AC, Carija A, Akman-Karakas A, Horváth B, Fábos B, Matlock BH, Claréus BW, Castro C, Ferrándiz C, Correa CC, Marchesi C, Goujon C, Gonzalez C, Maldonado-García C, Hong CH, Griffiths CEM, Vestergaard C, Echeverría CM, de la Cruz C, Conrad C, Törocsik D, Drvar DL, Balak D, Jullien D, Appelen D, Kim DH, de Jong EMGJ, El Gamal E, Laffitte E, Mahé E, Sonkoly E, Colombo EP, Vilarrasa E, Willaert F, Novoa FD, Handjani F, Valenzuela F, Vílchez-Márquez F, Gonzalez GO, Krisztián G, Damiani G, Krnjevic-Pezic G, Pellerano G, Carretero G, Hunter HJA, Riad H, Oon HH, Boonen HPJ, Moussa IO, García-Doval I, Csányi I, Brajac I, Turchin I, Grozdev I, Weinberg JM, Nicolopoulos J, Wells J, Lambert JLW, Ingram JR, Prinz JC, de Souza Sittart JA, Sanchez JL, Hsiao JPF, Castro-Ayarza JR, Maul JT, van den Reek JMPA, Trcko K, Barber K, Reich K, Gebauer KA, Khobzei K, Maul LV, Massari LP, Fardet L, le Cleach L, Misery L, Chandrashekar L, Muresanu LI, Lecluse L, Skov L, Frez ML, Babic LT, Puig L, Gomez LC, Ramam M, Dutil M, El-Sayed MH, Olszewska M, Schram ME, Franco MD, Llamas-Velasco M, Gonçalo M, Velásquez-Lopera MM, Abad ME, de Oliveira MDFSP, Seyger MMB, Kaštelan M, Rademaker M, Sikora M, Lebwohl M, Wiseman MC, Ferran M, van Doorn M, Danespazhooh M, Bylaite-Bucinskiene M, Gooderham MJ, Polic MV, de Rie MA, Zheng M, Gómez-Flores M, Salleras I Redonnet M, Silverberg NB, Doss N, Yawalkar N, Chosidow O, Zargari O, de la Cueva P, Fernandez-Peñas P, Cárdenas Rojas PJ, Gisondi P, Grewal P, Sator P, Luna PC, Félix PAO, Varela P, Holló P, Cetkovska P, Calzavara-Pinton P, Ghislain PD, Araujo RR, Romiti R, Kui R, Ceovic R, Vender R, Lafuente-Urrez RF, Del-Río R, Gulin SJ, Handa S, Mahil SK, Kolalapudi SA, Marrón SE, Azimi SZ, Janmohamed SR, da Cruz Costa SA, Choon SE, Urbancek S, Ayanlowo O, Margasin SM, Wong TW, Mälkönen T, Hurtová T, Reciné TR, Huldt-Nystrøm T, Torres T, Liu TY, Leonidze T, Sharma VK, Weightman W, Gulliver W, Veldkamp W. International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis. JAMA Dermatol 2022; 158:561-572. [PMID: 35353175 DOI: 10.1001/jamadermatol.2022.0434] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Importance A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.
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Affiliation(s)
- Astrid M van Huizen
- Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands
| | - Stef P Menting
- Department of Dermatology, OLVG, Amsterdam, the Netherlands
| | - Rolland Gyulai
- Department of Dermatology, University of Pécs, Medical School, Venerology and Oncodermatology, Pécs, Hungary
| | - Lars Iversen
- Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark
| | - Gayle E van der Kraaij
- Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands
| | - Maritza A Middelkamp-Hup
- Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands
| | - Richard B Warren
- The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom
| | - Phyllis I Spuls
- Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands
| | | | | | - Alireza Firooz
- Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Amanda Oakley
- Waikato District Health Board, University of Auckland, Auckland, New Zealand
| | - Amy Foulkes
- The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom
| | | | | | - Antoanela Carija
- School of Medicine, University of Split, University Hospital Centre Split, Croatia
| | - Ayse Akman-Karakas
- Department of Dermatology and Venerology, Akdeniz University School of Medicine, Antalya, Turkey
| | - Barbara Horváth
- Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Béata Fábos
- Department of Dermatology, Teaching Hospital Kaposvar, Kaposvar, Hungary
| | - Benjamin Hidalgo Matlock
- University of Costa Rica/Hospital Nacional de Niños, San Pedro Montes de Oca, San Jose Province, Costa Rica
| | | | - Carla Castro
- Dermatologist Hospital Universitario Austral, Buenos Aires, Argentina
| | - Carlos Ferrándiz
- Department of Dermatology, Hospital universitario Germans Trias i Pujol, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - Carolina Cortés Correa
- Dermatology Service of La Samaritana University Hospital, Bogotá, Colombia
- Pontificia Universidad Javeriana/National University of Colombia, Bogotá, Colombia
| | | | - Catherine Goujon
- Department of Immunology and Clinical Allergology, Lyon sud Hospital, Saint-Genis-Laval, France
| | | | | | - Chih-Ho Hong
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
| | - Christopher E M Griffiths
- The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom
| | | | | | | | - Curdin Conrad
- Department of Dermatology, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - Dániel Törocsik
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Daniela Ledic Drvar
- Department of Dermatology and Venereology, University Hospital Centre Zagreb, School of Medicine University of Zagreb, Croatia
| | - Deepak Balak
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - Denis Jullien
- Hospices Civils de Lyon, Hôpital E. Herriot, Service de Dermatologie, Lyon, France
| | | | - Dong Hyun Kim
- Department of Dermatology, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam, Republic of Korea
| | | | - Emad El Gamal
- Damietta Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Emmanuel Laffitte
- Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland
| | - Emmanuel Mahé
- Service de Dermatologie, Hôpital Victor Dupouy, Argenteuil, France
| | - Enikö Sonkoly
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Eva Vilarrasa
- Dermatology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | | | - Farhad Handjani
- Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fernando Valenzuela
- Department of Dermatology University of Chile and Centro Internacional de Estudios Clinicos, Probity Medical Research, Santiago, Chile
| | | | | | - Gáspár Krisztián
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - Giovanni Damiani
- Department of Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | | | | | - Gregorio Carretero
- Servicio de Dermatología, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
| | - Hamish J A Hunter
- The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom
| | | | | | | | | | - Ignacio García-Doval
- Dermatology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Ildíko Csányi
- Department of Dermatology and Allergology, Albert Szent-Györgyi Health Center, Department of Dermatology and Allergology, Szeged, Hungary
| | - Ines Brajac
- Department of Dermatovenerology, University Hospital Clinic Rijeka, Croatia
| | - Irina Turchin
- Brunswick Dermatology Center, Fredericton, New Brunswick, Canada
- Dalhousie University, Halifax, Nova Scotia, Canada
- Probity Medical Research, Waterloo, Ontario, Canada
| | - Ivan Grozdev
- Department of Dermatology, Brugmann University Hospital, Brussels, Belgium
| | | | - Jenny Nicolopoulos
- Department of Dermatology, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Jillian Wells
- University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia
| | - Jo L W Lambert
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - John R Ingram
- Department of Dermatology, Division of Infection & Immunity, Cardiff University, Cardiff, Wales
| | - Jörg Christoph Prinz
- Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany
| | | | - Jose Luis Sanchez
- Department of Dermatology, General Hospital Valencia, Valencia, Spain
| | | | | | - Julia-Tatjana Maul
- Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland
| | | | - Katarina Trcko
- Department of Dermatology and Venereal Diseases, University Medical Centre Maribor, Maribor, Slovenia
| | - Kirk Barber
- University of Calgary, Calgary, Alberta, Canada
| | - Kristian Reich
- Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Germany
| | | | - Kuzma Khobzei
- Kyiv Medical University, Medical Centre Khobzei Clinic, Kyiv, Ukraine
| | - Lara V Maul
- Department of Dermatology, University Hospital of Basel, Basel, Switzerland
| | - Larisa Prpic Massari
- Department of Dermatovenerology, Clinical Hospital Center Rijeka, Medical Faculty University of Rijeka, Rijeka, Croatia
| | - Laurence Fardet
- Department of dermatology, Hôpital Henri Mondor, Creteil, France
| | - Laurence le Cleach
- University Paris Est Créteil, Créteil, France
- Department of Dermatology, Hôpitaux universitaires Henri Mondor, UPEC, Créteil, France
| | - Laurent Misery
- Department of Dermatology, University Hospital of Brest, Department of Dermatology, Brest, France
| | | | | | | | - Lone Skov
- Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Ma Lorna Frez
- University of the Philippines College of Medicine, Philippine General Hospital, Manila, Philippines
| | | | - Lluís Puig
- Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona School of Medicine, Barcelona, Spain
| | - Luis Castro Gomez
- Hospital Militar Central Universidad Militar Nueva Granada, Bogota, Colombia
| | - M Ramam
- All India Institute of Medical Sciences, New Delhi, India
| | - Maha Dutil
- University of Toronto, Toronto, Ontario, Canada
| | | | | | | | | | - Mar Llamas-Velasco
- Dermatology Department, Hospital Universitario de la Princesa, Madrid, Spain
| | - Margarida Gonçalo
- Department of Dermatology, Coimbra University Hospital and Faculty of Medicine, University of Coimbra, Coimbra, Portugal
| | | | | | | | - Marieke M B Seyger
- Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands
| | - Marija Kaštelan
- Department of Dermatovenergology, Referral Center for Psoriasis, CHC Rijeka, University of Rijeka, Rijeka, Croatia
| | - Marius Rademaker
- Waikato Clinical School, School of Medicine, University of Auckland, Auckland, New Zealand
| | - Mariusz Sikora
- National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
| | - Mark Lebwohl
- Icahn School of Medicine at Mount Sinai, New York, New York
| | - Marni C Wiseman
- Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Marta Ferran
- Department of Dermatology, Hospital del Mar, Barcelona, Spain
| | - Martijn van Doorn
- Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands
| | - Maryam Danespazhooh
- Department of Dermatology, Tehran University of Medical Sciences, Tehran, Iran
| | - Matilda Bylaite-Bucinskiene
- Clinic of Infectious Diseases and Dermatovenereology, Centre of Dermatovenereology, Vilnius University, Vilnius, Lithuania
| | - Melinda J Gooderham
- SKiN Centre for Dermatology and Probity Medical Research, Queen's University, Peterborough, Ontario, Canada
| | | | - Menno A de Rie
- Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands
| | - Min Zheng
- School of Medicine, the Second Affiliated Hospital of Zhejiang University, Hangzhou, China
| | | | | | | | - Nejib Doss
- Golden Towers Médical Centre, Tunis, Tunisia
| | - Nikhil Yawalkar
- Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | | | - Pablo de la Cueva
- Dermatology Department, Hospital Unuversitario Infanta Leonor, Madrid, Spain
| | - Pablo Fernandez-Peñas
- Department of Dermatology, University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia
| | | | - Paolo Gisondi
- Section of Dermatology and Venereology, University of Verona, Verona, Italy
| | | | - Paul Sator
- Department of Dermatology, Clinic Hietzing, Vienna, Austria
| | | | | | - Paulo Varela
- Dermatology Department, Centro Hospitalar VN Gaia, Portugal
| | - Péter Holló
- Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary
| | - Petra Cetkovska
- Department of Dermatovenereology, Faculty of Medicine, Charles University, Prague, Czech Republic
| | | | | | - Raquel Ruiz Araujo
- University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia
| | - Ricardo Romiti
- Department of Dermatology, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil
| | - Róbert Kui
- Department of Dermatology and AllergologyAlbert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
| | - Romana Ceovic
- Department of Dermatology and Venereology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia
| | | | | | - Rubén Del-Río
- Hospital L´Esperit Sant, Santa Coloma de Gramenet, Spain
| | - Sandra J Gulin
- Department of Dermatology, Ryhov County Hospital, Jonkoping, Sweden
| | - Sanjeev Handa
- Department of Dermatology, Venereology & Leprology, Chandigarh, India
| | - Satveer K Mahil
- St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, England
| | | | - Servando E Marrón
- Dermatology Department, University Hospital Miguel Servet, Zaragoza, Spain
- Aragon Psychodermatology Research Group, Zaragoza, Spain
| | | | - Sherief R Janmohamed
- Department of Dermatology, Unit Pediatric Dermatology, SKIN Research Group, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | | | - Siew Eng Choon
- Clinical School Johor Bahru, Monash University Malaysia, Subang Jaya, Malaysia
| | - Slavomir Urbancek
- Department of Dermatology, F.D. Roosevelt Hospital, Banska Bystrica, Slovakia
| | - Olusola Ayanlowo
- Dermatology Unit, Department of Medicine, Faculty of Clinical Sciences, University of Lagos, Lagos, Nigeria
| | - Susana M Margasin
- Consultorios Integrados Rosio, Hospital I Carrasco Rosario, Argentina
| | - Tak-Wah Wong
- Departments of Dermatology, Biochemistry & Molecular Biology, Center of Applied Nanomedicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Tarja Mälkönen
- Helsinki University Hospital, Skin and Allergy Hospital, Helsinki, Finland
| | - Tatiana Hurtová
- Jessenius Faculty of Medicine, Martin, Comenius University, Bratislava, Slovakia
| | | | | | - Tiago Torres
- Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Tong-Yun Liu
- First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Tsira Leonidze
- Akad.N.Kipshidze Central University Clinic, Tbilisi, Georgia
| | - Vinod Kumar Sharma
- School of Medical Sciences and Research, Sharda University, Uttar Pradesh, India
| | | | - Wayne Gulliver
- Faculty of Medicine, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland and Labrador, Canada
| | - Wendelien Veldkamp
- Department of Dermatology, Radboudumc Nijmegen, Nijmegen, the Netherlands
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Wang Y, Fu S, Lu Y, Lai R, Liu Z, Luo W, Xu Y. Chitosan/hyaluronan nanogels co-delivering methotrexate and 5-aminolevulinic acid: A combined chemo-photodynamic therapy for psoriasis. Carbohydr Polym 2022; 277:118819. [PMID: 34893236 DOI: 10.1016/j.carbpol.2021.118819] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/24/2021] [Accepted: 10/25/2021] [Indexed: 12/19/2022]
Abstract
Psoriasis does not respond adequately to the monotherapy, tailoring combined strategies for synergistical treatment remains challenging. We fabricated chitosan/hyaluronan nanogels to co-load methotrexate (MTX) and 5-aminoleavulinic acid (ALA), i.e., MTX-ALA NGs, for a combined chemo-photodynamic therapy for psoriasis. Compared with MTX-ALA suspension, the NGs enhanced the penetration and retention of MTX and ALA through and into the skin in vitro and in vivo (p < 0.001). NGs enhanced the cellular uptake (p < 0.001), protoporphyrin IX conversion (p < 0.001), and reactive oxygen species generation (3.93-fold), subsequently exerted the synergistical anti-proliferation and apoptosis on lipopolysaccharide-irritated HaCaT cells with the apoptosis rate of 78.6%. MTX-ALA NGs efficiently ameliorated the skin manifestations and down-regulated the proinflammatory cytokines of TNF-α and IL-17A in imiquimod-induced psoriatic mice (p < 0.001). Importantly, MTX-ALA NGs reduced the toxicities of oral MTX to the liver and kidney. The results support that MTX-ALA NG is a convenient, effective, and safe combined chemo-photodynamic strategy for psoriasis treatment.
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Affiliation(s)
- Yixuan Wang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
| | - Shijia Fu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
| | - Yi Lu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
| | - Rongrong Lai
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
| | - Ziyi Liu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
| | - Weixuan Luo
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
| | - Yuehong Xu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
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Kunkel J, Schott E. Rheumatologie und Hepatologie
interdisziplinär. AKTUEL RHEUMATOL 2021. [DOI: 10.1055/a-1626-8710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
ZusammenfassungRheumatologische und hepatologische Erkrankungen haben einige
Überschneidungen, die für Behandler aus beiden Disziplinen
relevant sind. In dieser Übersicht wird ein Schlaglicht auf 2
Erkrankungen geworfen, die sich an der Schnittstelle befinden: Arthropathie bei
Hämochromatose und Systemische Sklerose bei Primär
Biliärer Cholangitis. Daneben werden hepatologische Fragestellungen bei
rheumatologischer Therapie beleuchtet.
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Affiliation(s)
- Jan Kunkel
- Klinik für Innere Medizin II, HELIOS Klinikum Emil von Behring
Berlin-Zehlendorf, Berlin, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II, HELIOS Klinikum Emil von Behring
Berlin-Zehlendorf, Berlin, Deutschland
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Mehta H, Narang T, Dogra S, Kumar B. Methotrexate in erythema nodosum leprosum: Pitfalls to avoid. Trop Doct 2021; 52:226-227. [PMID: 34787533 DOI: 10.1177/00494755211056170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We read with interest the short report by Rani et al. entitled "An uncommon variant of erythema nodosum leprosum responding well to methotrexate: Report of two cases." The article describes two cases of erythema nodosum leprosum (ENL) with 'atypical features' and good response to low dose methotrexate. The authors address a few concerns regarding methotrexate in ENL, emphasizing the rational usage of this agent.
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Affiliation(s)
- Hitaishi Mehta
- Department of Dermatology, Venereology and Leprology; 29751Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Tarun Narang
- Department of Dermatology, Venereology and Leprology; 29751Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sunil Dogra
- Department of Dermatology, Venereology and Leprology; 29751Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Bhushan Kumar
- Department of Dermatology, Shalby Hospital, SAS Nagar, Punjab, India
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Kivitz AJ, FitzGerald O, Nash P, Pang S, Azevedo VF, Wang C, Takiya L. Efficacy and safety of tofacitinib by background methotrexate dose in psoriatic arthritis: post hoc exploratory analysis from two phase III trials. Clin Rheumatol 2021; 41:499-511. [PMID: 34510295 PMCID: PMC8782818 DOI: 10.1007/s10067-021-05894-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 11/05/2022]
Abstract
Objective Analyze tofacitinib efficacy and safety by background methotrexate (MTX) dose in patients with psoriatic arthritis (PsA). Methods This post hoc analysis pooled data from two phase III, double-blind trials (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) including patients receiving tofacitinib 5 or 10 mg twice daily (BID), or placebo, with stable MTX. Efficacy outcomes at month 3 stratified by MTX dose (≤ 15 month 3 stratified by MTX dose vs > 15 mg/week) were American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI); Psoriasis Area and Severity Index (PASI)50/75; change from baseline in HAQ-DI; physician’s global assessment of PsA (PGA-PsA-visual analog scale [VAS]); patient’s global joint and skin assessment (PGJS-VAS), Leeds Enthesitis Index (LEI); and Dactylitis Severity Score (DSS). Safety assessments included adverse events and laboratory parameters. Results Five hundred fifty-six patients received tofacitinib 5 mg BID (n = 186), 10 mg BID (n = 178), or placebo (n = 192), plus MTX (≤ 15 mg/week, n = 371; > 15 mg/week, n = 185). At month 3, tofacitinib efficacy was generally greater than placebo. Patients receiving tofacitinib 5 mg BID demonstrated greater numerical improvements in efficacy outcomes at month 3 with MTX > 15 mg/week vs MTX ≤ 15 mg/week; patients receiving tofacitinib 10 mg BID displayed the opposite. The safety profile was generally consistent between groups; headache was associated with MTX > 15 mg/week; decreased hemoglobin levels were observed in patients receiving tofacitinib 10 mg BID and MTX ≤ 15 mg/week. Conclusion Efficacy of tofacitinib was generally numerically greater than placebo, regardless of MTX dose. Tofacitinib 5 mg BID was generally more efficacious with MTX > 15 mg/week vs ≤ 15 mg/week; the opposite was observed for tofacitinib 10 mg BID. Headache was more frequent with MTX > 15 mg/week. Trial registration ClinicalTrials.gov. Identifier: NCT01877668 (registration: June 14, 2013) and NCT01882439 (registration: June 20, 2013). Key Points • Methotrexate is widely used in the treatment of psoriatic arthritis; however, there are limited data on the impact of varying background methotrexate doses on the efficacy and safety of Janus kinase inhibitors in patients with psoriatic arthritis. • This post hoc analysis assessed the impact of background methotrexate dose (≤ 15 or > 15 mg/week) on tofacitinib efficacy and safety in patients with psoriatic arthritis. • Results indicated that tofacitinib efficacy was generally numerically greater than placebo, regardless of methotrexate dose. Tofacitinib 5 mg twice daily, in combination with a higher dose of background methotrexate, was more efficacious compared with a lower dose of background methotrexate; the opposite was observed for tofacitinib 10 mg twice daily. • Headache was more frequent with the higher methotrexate dose. Data should be interpreted with caution due to the small sample sizes. |
Supplementary Information The online version contains supplementary material available at 10.1007/s10067-021-05894-2.
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Affiliation(s)
- Alan J Kivitz
- Department of Rheumatology, Altoona Center for Clinical Research, Duncansville, PA, USA
| | - Oliver FitzGerald
- Department of Rheumatology, Conway Institute for Biomolecular Research, University College, Dublin, Ireland
| | - Peter Nash
- School of Medicine, Griffith University, Brisbane, Australia
| | - Shirley Pang
- St. Joseph Heritage Healthcare, Fullerton, CA, USA
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Psoriasis and Cardiovascular Disease: Novel Mechanisms and Evolving Therapeutics. Curr Atheroscler Rep 2021; 23:67. [PMID: 34468875 PMCID: PMC9744099 DOI: 10.1007/s11883-021-00963-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/26/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW Psoriasis is a chronic inflammatory skin condition that is associated with increased cardiovascular risk compared to those without psoriasis. This review will cover emerging mechanisms of cardiovascular risk, key pathways targeted with biologic therapies, and the current evidence on therapies to modulate this risk in patients with psoriasis. RECENT FINDINGS Recent scientific work has highlighted mechanisms that contribute to this enhanced risk, including the role of vascular endothelial dysfunction, platelet activation, dyslipidemia, and increased cardiometabolic comorbidities. Newer biologic and targeted synthetic therapies have transformed psoriasis treatment with high rates of clinical remission and durable skin disease control now possible. Epidemiological evidence suggests that many of these therapies may lower cardiovascular risk in psoriasis, although prospective interventional data is lacking (or mixed). Recently, caution has also been raised that some treatments may negatively affect cardiovascular risk. Overall, the current data suggests a positive or neutral ability to reduce cardiovascular risk for TNF, IL-17A, and IL-12/23p40 inhibitors, but current evidence remains conflicting for anti-IL-23/p19 and JAK inhibitors. More studies that include prospective cohorts, larger number of patients, treatment duration, and validated surrogate outcomes are needed to better evaluate the role of biologic therapies on cardiovascular risk in psoriasis.
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Tsai MH, C Chan T, Lee MS, Lai MS. Cardiovascular Risk Associated with Methotrexate versus Retinoids in Patients with Psoriasis: A Nationwide Taiwanese Cohort Study. Clin Epidemiol 2021; 13:693-705. [PMID: 34408498 PMCID: PMC8364829 DOI: 10.2147/clep.s305126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 07/22/2021] [Indexed: 01/22/2023] Open
Abstract
Purpose Psoriasis is an inflammatory disease associated with cardiovascular disease. Methotrexate (MTX) is a first-line systemic anti-psoriatic agent that may also protect against cardiovascular disease. We examined the cardiovascular risks among patients with psoriasis who were receiving MTX or the comparator, retinoids. Patients and Methods We analysed data from the Taiwanese National Health Insurance database. The primary outcome was a composite of hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality (composite cardiovascular outcome). Propensity score-weighted analyses were used to evaluate patients who were followed from therapy initiation to the earliest instance of outcome occurrence, insurance disenrollment, death or study termination. Results We identified 13,777 patients who received MTX and 6020 patients who received retinoids from 2000 to 2012. Compared to retinoids, MTX was associated with lower crude incidences of cardiovascular outcomes, hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality. In intention-to-treat analyses, MTX was associated with lower risks of composite cardiovascular outcomes (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76–0.94), ischaemic heart disease (HR: 0.87, 95% CI: 0.71–1.06), ischaemic stroke (HR: 1.06, 95% CI: 0.89–1.27) and all-cause mortality (HR: 0.75, 95% CI: 0.66–0.85). Similar results were found in as-treated analyses. Conclusion In this nationwide cohort of patients with psoriasis, compared to retinoids, MTX was associated with a modestly lower risk of cardiovascular events.
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Affiliation(s)
- Ming-Hsueh Tsai
- Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan
| | - Tom C Chan
- Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Meng-Sui Lee
- Department of Dermatology, Taipei City Hospital, Taipei, Taiwan.,Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Mei-Shu Lai
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
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Contemporary treatment patterns in plaque psoriasis and psoriatic arthritis. Postepy Dermatol Alergol 2021; 38:80-84. [PMID: 34408571 PMCID: PMC8362784 DOI: 10.5114/ada.2019.91502] [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: 03/05/2019] [Accepted: 07/15/2019] [Indexed: 11/22/2022] Open
Abstract
Introduction Psoriasis is a chronic inflammatory skin disease affecting about 2% of the general population. Although there are many treatment options, and new medications have been introduced, the disease is considered not curable, and it may seriously affect patients’ quality of life. Aim The authors present contemporary treatment patterns used by dermatologists in Poland to manage plaque psoriasis and psoriatic arthritis, particularly regarding systemic treatment. The authors also aimed to analyse how these treatment patterns are influenced by the guidelines of the Polish Dermatological Society. Material and methods The author’s questionnaire, consisting of 13 questions was used. It included demographic and professional characteristics of questioned dermatologists, as well as the assessment of the attitudes towards management of plaque psoriasis and psoriatic arthritis. Results A total of 132 dermatologists completed the questionnaire. Most of the specialists worked in out-patient clinics and private practices. The most commonly used topicals for psoriasis included: glucocorticosteroids, a combination of glucocorticosteroid and vitamin D analogue and salicylic acid. Regarding the treatment of psoriatic arthritis, most of the specialists declared using systemic therapy and a combination of systemic therapy and phototherapy. The majority of the respondents were particularly concerned with possible side effects or difficulties in qualifying and monitoring the patients, and less frequently on the cost of the therapy. Conclusions Observations suggest that 60% of physicians have some reservation to initiate systemic treatment in outpatient clinics, and they admit that they lack additional training. On the other hand, it seems also that the organization of systemic treatment in psoriasis may generate these difficulties and thus necessitate additional effort. Another factor could be the budget – not only regarding healthcare professionals, but also the patient, sometimes financing various investigations from private resources.
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Methotrexate-Loaded Gelatin and Polyvinyl Alcohol (Gel/PVA) Hydrogel as a pH-Sensitive Matrix. Polymers (Basel) 2021; 13:polym13142300. [PMID: 34301057 PMCID: PMC8309343 DOI: 10.3390/polym13142300] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 06/20/2021] [Accepted: 06/22/2021] [Indexed: 12/17/2022] Open
Abstract
The aim was to formulate and evaluate Gel/PVA hydrogels as a pH-sensitive matrix to deliver methotrexate (MTX) to colon. The primed Gel/PVA hydrogels were subjected to evaluation for swelling behavior, diffusion coefficient, sol-gel characteristic and porosity using an acidic (pH 1.2) and phosphate buffer (PBS) (pH 6.8 & pH 7.4) media. Fourier transform infrared spectroscopy (FTIR) and thermal gravimetric analysis (TGA) were performed to evaluate the chemical compatibility of the Gel/PVA hydrogel. The shape alteration and release of Gel/PVA hydrogel was conducted at pH 1.2, pH 6.8 and pH 7.4. The drug release kinetic mechanism was determined using various kinetic equations. The physicochemical evaluation tests and drug release profile results were found to be significant (p < 0.01). However, it was dependent on the polymers' concentration, the pH of the release media and the amount of the cross-linking agent. Hydrogels containing the maximum amount of gel showed a dynamic equilibrium of 10.09 ± 0.18 and drug release of 93.75 ± 0.13% at pH 1.2. The kinetic models showed the release of MTX from the Gel/PVA hydrogel was non-Fickian. The results confirmed that the newly formed Gel/PVA hydrogels are potential drug delivery systems for a controlled delivery of MTX to the colon.
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Yang X, Tang Y, Wang M, Wang Y, Wang W, Pang M, Xu Y. Co-delivery of methotrexate and nicotinamide by cerosomes for topical psoriasis treatment with enhanced efficacy. Int J Pharm 2021; 605:120826. [PMID: 34171426 DOI: 10.1016/j.ijpharm.2021.120826] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/30/2021] [Accepted: 06/20/2021] [Indexed: 12/23/2022]
Abstract
Psoriasis is an immune-mediated skin disorder that affects populations worldwide. Methotrexate (MTX) is a cytotoxic drug with powerful anti-proliferative and anti-inflammatory effects that has gained prominence in treating inflammatory diseases including psoriasis. However, low solubility and side effects through oral administration hinder its systemic application. In this study, we developed a novel niosomes based on ceramide (cerosomes) to co-deliver MTX and nicotinamide (NIC), i.e., MTX/NIC cerosomes, for topically treating psoriasis with the aim to enhancing the efficacy and reducing the toxicity. NIC significantly solublized MTX by forming hydrogen bonds with MTX. In vitro and in vivo permeation studies showed that the cerosomes significantly promoted drug permeation through and retention in the skin, and the enhancing mechanism was clarified by Fourier transform infraredand Raman spectroscopy. MTX/NIC cerosomes exhibited strong anti-proliferation effect on lipopolysaccharide- irritated HaCaT cells by arresting the cell cycle at S phase and inducing apoptosis. Importantly, compared to MTX oral administration, topical application of MTX/NIC cerosomes on imiquimod (IMQ)-induced psoriatic mouse model exhibited a superior performance in ameliorating skin lesions, reducing spleen index and epidermal thickness, and downregulating the mRNA expression levels of proinflammatory cytokines including TNFα, IL-23, IL-17A, IL-6, IL-1β, and IL-22. Taken together, MTX/NIC cerosomes is a promising approach for psoriasis topical treatment.
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Affiliation(s)
- Xiaoyuan Yang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Yujia Tang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Meng Wang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Yixuan Wang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Wenxiu Wang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Meilu Pang
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
| | - Yuehong Xu
- School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
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Noninvasive assessment of liver fibrosis in Crohn's disease patients exposed to methotrexate. Eur J Gastroenterol Hepatol 2021; 33:794-798. [PMID: 32804842 DOI: 10.1097/meg.0000000000001799] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Methotrexate is widely used to treat some inflammatory chronic disorders, though it is hampered by the risk of liver fibrosis. Many recommendations have been made to assess methotrexate-related hepatotoxicity, including liver biopsy. However, other noninvasive methods to assess liver fibrosis have been developed and could be implemented for patients treated with methotrexate. AIM The aim of the study was to compare the prevalence of liver fibrosis by means of noninvasive methods [aspartate transaminase-to-platelet ratio index (APRI) Forns index, and transient elastography] in patients with Crohn's disease exposed or not to methotrexate, and to identify risk factors for liver fibrosis. METHODS Prospective, cross-sectional study. All patients with Crohn's disease exposed to methotrexate were included and compared to an unselected cohort of outpatients with Crohn's disease never exposed to methotrexate. RESULTS A total of 84 patients with Crohn's disease, 56 exposed to methotrexate, and 28 controls, were included. Significant liver fibrosis was found in 7% of methotrexate-exposed patients with Crohn's disease and 10% of controls as measured by transient elastography, and in 7% of controls as measured by the Forns index. No cases of liver fibrosis were detected by APRI. Only alcohol consumption, diabetes mellitus, and age were associated with significant liver fibrosis. CONCLUSIONS Significant liver fibrosis is uncommon among patients with Crohn's disease, even among those exposed to methotrexate. The risk of liver fibrosis in Crohn's disease seems to depend on common risk factors for liver disease.
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Rattanakaemakorn P, Pinyowiwat P, Iamsumang W, Chanprapaph K, Suchonwanit P. Incidence and Risk Factors of Hepatic Fibrosis in Psoriatic Patients Receiving Methotrexate with Concomitant Acitretin Therapy and Methotrexate Monotherapy. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:2299-2307. [PMID: 34093007 PMCID: PMC8170124 DOI: 10.2147/dddt.s304168] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 05/12/2021] [Indexed: 12/24/2022]
Abstract
Background The use of methotrexate-acitretin (MTX-ACI) combination therapy in treating psoriasis has been limited due to concerns related to hepatic fibrosis. However, in vitro evidence revealed a protective effect of acitretin in methotrexate (MTX)-induced liver fibrosis. Objective This study aimed to compare the real-life incidence of hepatic fibrosis in patients with psoriasis receiving MTX-ACI and MTX monotherapy and to investigate factors associated with hepatic fibrosis in MTX-exposed patients. Methods A retrospective cohort study was conducted based on a real-life registry containing data on patients with psoriasis who were administered MTX-ACI or MTX between 2008 and 2019 and underwent transient elastography according to cumulative MTX dose of 1.0–1.5 g and/or 3.5–4.0 g. Time-to-event analysis was performed to determine the cumulative incidence, incidence rate, and factors potentially affecting the occurrence of hepatic fibrosis. Results Of the 160 patients, 32 (20%) were treated with MTX-ACI, and 128 (80%) with MTX alone. Four patients (12.5%) in MTX-ACI group and 21 (16.4%) in MTX group developed hepatic fibrosis (p = 0.59). There was no statistically significant difference in cumulative incidence (16% in MTX-ACI vs 17% in MTX, p = 0.89) and incidence rate (37 cases per 1000 person-year in MTX-ACI vs 23 cases per 1000 person-year in MTX; hazard ratio [HR] = 1.07; p = 0.90) of hepatic fibrosis between the two groups. Diabetes and obesity were identified as significant factors associated with hepatic fibrosis (adjusted HR = 2.40, 95% confidence interval [CI]: 1.05–5.51; p = 0.04 and adjusted HR = 3.28, 95% CI: 1.18–9.16; p = 0.02, respectively) regardless of the cumulative MTX dose. Conclusion The incidence of hepatic fibrosis in a real-life clinical situation, determined by transient elastography in patients with psoriasis receiving MTX-ACI, was not increased compared to those receiving MTX monotherapy. Type 2 diabetes mellitus and obesity were identified as risk factors of hepatic fibrosis; hence, patients with these factors receiving long-term MTX therapy should be regularly monitored for this particular event.
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Affiliation(s)
- Ploysyne Rattanakaemakorn
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Prinpat Pinyowiwat
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Wimolsiri Iamsumang
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Kumutnart Chanprapaph
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Poonkiat Suchonwanit
- Division of Dermatology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury. Am J Gastroenterol 2021; 116:878-898. [PMID: 33929376 DOI: 10.14309/ajg.0000000000001259] [Citation(s) in RCA: 142] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 01/25/2021] [Indexed: 12/11/2022]
Abstract
Idiosyncratic drug-induced liver injury (DILI) is common in gastroenterology and hepatology practices, and it can have multiple presentations, ranging from asymptomatic elevations in liver biochemistries to hepatocellular or cholestatic jaundice, liver failure, or chronic hepatitis. Antimicrobials, herbal and dietary supplements, and anticancer therapeutics (e.g., tyrosine kinase inhibitors or immune-checkpoint inhibitors) are the most common classes of agents to cause DILI in the Western world. DILI is a diagnosis of exclusion, and thus, careful assessment for other etiologies of liver disease should be undertaken before establishing a diagnosis of DILI. Model for end-stage liver disease score and comorbidity burden are important determinants of mortality in patients presenting with suspected DILI. DILI carries a mortality rate up to 10% when hepatocellular jaundice is present. Patients with DILI who develop progressive jaundice with or without coagulopathy should be referred to a tertiary care center for specialized care, including consideration for potential liver transplantation. The role of systemic corticosteroids is controversial, but they may be administered when a liver injury event cannot be distinguished between autoimmune hepatitis or DILI or when a DILI event presents with prominent autoimmune hepatitis features.
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Munera-Campos M, Vilar-Alejo J, Rivera R, Carrascosa JM, Daudén E, Herrera-Acosta E, Sahuquillo-Torralba A, Gómez-García FJ, Baniandrés-Rodríguez O, de la Cueva P, López-Estebaranz JL, Belinchón I, Ferran M, Riera-Monroig J, Rodriguez L, Carretero G, García-Donoso C, Ballescá F, Llamas-Velasco M, Herrera-Ceballos E, Pujol-Marco C, Nieto-Benito LM, Ruiz-Genao DP, Alsina M, Descalzo MA, García-Doval I. The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry. J DERMATOL TREAT 2021; 33:2110-2117. [PMID: 33913796 DOI: 10.1080/09546634.2021.1922572] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% CI 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = 0.0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.
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Affiliation(s)
- M Munera-Campos
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - J Vilar-Alejo
- Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - R Rivera
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - J M Carrascosa
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - E Daudén
- Department of Dermatology. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Madrid, Spain
| | - E Herrera-Acosta
- Department of Dermatology, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - A Sahuquillo-Torralba
- Department of Dermatology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - F J Gómez-García
- Department of Dermatology, Hospital Universitario Reina Sofía, Cordoba, Spain
| | - O Baniandrés-Rodríguez
- Department of Dermatology, CEIMI Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - P de la Cueva
- Department of Dermatology, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - J L López-Estebaranz
- Department of Dermatology, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - I Belinchón
- Department of Dermatology, Hospital General Universitario de Alicante-ISABIAL, Alicante, Spain
| | - M Ferran
- Department of Dermatology, Hospital del Mar, Parc de Salut Mar, Barcelona, Spain
| | - J Riera-Monroig
- Department of Dermatology, Hospital Clínic de Barcelona, UB, Barcelona, Spain
| | - L Rodriguez
- Department of Dermatology, Hospital Virgen del Rocío, Sevilla, Spain
| | - G Carretero
- Department of Dermatology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain
| | - C García-Donoso
- Department of Dermatology, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - F Ballescá
- Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, Universidad Autónoma de Barcelona, Barcelona, Spain
| | - M Llamas-Velasco
- Department of Dermatology. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Madrid, Spain
| | - E Herrera-Ceballos
- Department of Dermatology, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - C Pujol-Marco
- Department of Dermatology, Hospital Universitario y Politécnico La Fe, Valencia, Spain
| | - L M Nieto-Benito
- Department of Dermatology, CEIMI Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - D P Ruiz-Genao
- Department of Dermatology, Hospital Universitario Fundación Alcorcón, Madrid, Spain
| | - M Alsina
- Department of Dermatology, Hospital Clínic de Barcelona, UB, Barcelona, Spain
| | - M A Descalzo
- Research Unit. Fundación Piel Sana AEDV, Madrid, Spain
| | - I García-Doval
- Research Unit. Fundación Piel Sana AEDV, Madrid, Spain.,Department of Dermatology, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
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Cao RH, Grimm MC. Pregnancy and medications in inflammatory bowel disease. Obstet Med 2021; 14:4-11. [PMID: 33995565 PMCID: PMC8107959 DOI: 10.1177/1753495x20919214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 01/20/2020] [Accepted: 02/21/2020] [Indexed: 12/27/2022] Open
Abstract
Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians.
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Affiliation(s)
- Rena H Cao
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
| | - Michael C Grimm
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
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Gelfand JM, Wan J, Zhang H, Shin DB, Ogdie A, Syed MN, Egeberg A. Risk of liver disease in patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis receiving methotrexate: A population-based study. J Am Acad Dermatol 2021; 84:1636-1643. [PMID: 33607181 DOI: 10.1016/j.jaad.2021.02.019] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 01/26/2021] [Accepted: 02/08/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Patients with psoriatic disease may be more susceptible to methotrexate hepatotoxicity than those with rheumatoid arthritis (RA); however, direct evidence supporting this notion is lacking. OBJECTIVE To compare liver disease risk among patients with psoriasis (PsO), psoriatic arthritis (PsA), or RA receiving methotrexate. METHODS In a population-based cohort study, Danish individuals with PsO, PsA, or RA receiving methotrexate between 1997 and 2015 were compared according to 4 disease outcomes: mild liver disease, moderate-to-severe liver disease, cirrhosis, and cirrhosis-related hospitalization. RESULTS Among 5687, 6520, and 28,030 patients with PsO, PsA, and RA, respectively, the incidence rate of any liver disease was greatest for PsO, followed by PsA, and lowest for RA. Compared with patients with RA, patients with PsO were 1.6-3.4 times more likely to develop at least one of the liver disease outcomes, whereas those with PsA were 1.3-1.6 times more likely to develop mild liver disease and cirrhosis after adjusting for demographics, smoking, alcohol use, comorbidities, and methotrexate dose. LIMITATIONS Confounding due to unmeasured variables, misclassification, and surveillance bias. CONCLUSION PsO, PsA, and RA differentially influence liver disease risk in the setting of methotrexate use independent of other major risk factors. More conservative monitoring should be considered in patients receiving methotrexate for psoriatic disease, particularly in PsO patients.
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Affiliation(s)
- Joel M Gelfand
- Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
| | - Joy Wan
- Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - He Zhang
- Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Daniel B Shin
- Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Alexis Ogdie
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania; Division of Rheumatology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Maha N Syed
- Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Alexander Egeberg
- Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
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Yu WJ, Huang DX, Liu S, Sha YL, Gao FH, Liu H. Polymeric Nanoscale Drug Carriers Mediate the Delivery of Methotrexate for Developing Therapeutic Interventions Against Cancer and Rheumatoid Arthritis. Front Oncol 2020; 10:1734. [PMID: 33042817 PMCID: PMC7526065 DOI: 10.3389/fonc.2020.01734] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 08/03/2020] [Indexed: 01/21/2023] Open
Abstract
Methotrexate (MTX) is widely used as an anticancer and anti-inflammtory drug for treating various types of cancer and autoimmune diseases. The optimal dose of MTX is known to inhibit the dihydrofolatereductase that hinders the replication of purines. The nanobiomedicine has been extensively explored in the past decade to develop myriad functional nanostructures to facilitate the delivery of therapeutic agents for various medical applications. This review is focused on understanding the design and development of MTX-loaded nanoparticles alongside the inclusion of recent findings for the treatment of cancers. In this paper, we have made a coordinated effort to show the potential of novel drug delivery systems by achieving effective and target-specific delivery of methotrexate.
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Affiliation(s)
- Wen-Jun Yu
- The Eastern Division, Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Dong-Xu Huang
- The Eastern Division, Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Shuang Liu
- The Eastern Division, Department of Nursing Management, The First Hospital of Jilin University, Changchun, China
| | - Ying-Li Sha
- The Eastern Division, Department of Pediatrics, The First Hospital of Jilin University, Changchun, China
| | - Feng-Hui Gao
- The Eastern Division, Department of Orthopaedics, The First Hospital of Jilin University, Changchun, China
| | - Hong Liu
- The Eastern Division, Department of Otolaryngology, The First Hospital of Jilin University, Changchun, China
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García DS, Saturansky EI, Poncino D, Martínez-Artola Y, Rosenberg S, Abritta G, Ascimani-Peña C, Cravero A. "Hepatic toxicity by methotrexate with weekly single doses associated with folic acid in rheumatoid and psoriatic arthritis. What is its real frequency?". Ann Hepatol 2020; 18:765-769. [PMID: 31105018 DOI: 10.1016/j.aohep.2019.01.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Revised: 01/31/2019] [Accepted: 01/31/2019] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Liver injury caused by methotrexate (MTX) has mostly been investigated without applying criteria for the assessment of causality of drug induced liver injury (DILI). Hence, the existence of DILI by MTX in many cases is debatable. This study aimed to describe the frequency and characteristics of liver injury caused by MTX, applying DILI diagnostic criteria. MATERIAL AND METHODS Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients who were treated with MTX in association with folic acid were included. Serial determinations of alanine amino transferase (ALT) and aspartate amino transferase (AST) were performed. The Roussel Uclaf Causality Assessment Method (RUCAM) was applied in cases of increases of ALT/AST over 1.5 upper limit of normal. Liver biopsy was considered when the total cumulative dosage (TCD) of MTX was ≥3.5g. RESULTS A total of 43 patients were analyzed (median follow up 32 (range: 1-48) months; 3.33 ALT/AST determinations per year). Five subjects presented an increase of ALT/AST. All presented a RUCAM score for MTX≤2 (improbable). Three had a RUCAM score for non-steroidal anti-inflammatory drugs ≥7 (probable) and two patients presented non-alcoholic fatty liver disease. Five patients with no other cause for liver disease consented to liver biopsy (TCD MTX: median 5.1; range: 3.5-7.4g). No significant fibrosis or steatosis was evident on histology. CONCLUSIONS No biochemical or significant histological liver toxicity for MTX was demonstrated when applying causality criteria for DILI. More studies with this methodology are necessary in order to improve the assessment of its frequency.
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Affiliation(s)
- Daniel S García
- Department of Hepatology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina.
| | - Etel I Saturansky
- Department of Rheumatology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina
| | - Daniel Poncino
- Department of Hepatology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina
| | - Yamila Martínez-Artola
- Department of Hepatology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina
| | - Silvia Rosenberg
- Department of Rheumatology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina
| | - Gloria Abritta
- Department of Rheumatology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina
| | - Carlos Ascimani-Peña
- Department of Rheumatology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina
| | - Amerys Cravero
- Department of Pathology, Sanatorio "Dr. Julio Méndez", Ciudad Autónoma de Buenos Aires, Argentina
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Balak DMW, Gerdes S, Parodi A, Salgado-Boquete L. Long-term Safety of Oral Systemic Therapies for Psoriasis: A Comprehensive Review of the Literature. Dermatol Ther (Heidelb) 2020; 10:589-613. [PMID: 32529393 PMCID: PMC7367959 DOI: 10.1007/s13555-020-00409-4] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Indexed: 01/10/2023] Open
Abstract
Oral systemic therapies are important treatment options for patients with moderate-to-severe psoriasis, either as monotherapy or in therapy-recalcitrant cases as combination therapy with phototherapy, other oral systemics or biologics. Long-term treatment is needed to maintain sufficient disease control in psoriasis, but continuous use of systemic treatments is limited by adverse events (AEs) and cumulative toxicity risks. The primary aim of this comprehensive literature review was to examine the long-term safety profiles of oral agents commonly used in the treatment of adults with psoriasis. Searches were conducted in EMBASE and PubMed up to November 2018, and 157 relevant publications were included. Long-term treatment with acitretin could be associated with skeletal toxicity and hepatotoxicity, although evidence for skeletal toxicity is mixed and hepatotoxicity is rare, particularly at low doses. Other safety issues include hyperlipidaemia and potential for teratogenicity up to 2-3 years after discontinuation of treatment. There is a paucity of data on long-term treatment with apremilast. Continued exposure to apremilast does not seem to increase the incidence of common AEs, such as gastrointestinal (GI) AEs, upper respiratory tract infections and headache, while the long-term risks for depression, suicidal thoughts and weight loss are unknown. Long-term ciclosporin treatment is associated with renal toxicity, hypertension, non-melanoma skin cancer, neurological AEs and GI AEs. Long-term methotrexate treatment is associated with hepatotoxicity, GI AEs, haematological toxicity, renal toxicity and alopecia. Finally, long-term treatment with fumaric acid esters (FAE) is associated with GI AEs, flushing, lymphocytopenia, proteinuria and elevated liver enzymes. Median drug survival estimates varied considerably: ~ 2.9-9.7 months for apremilast; ~ 5.4 months for ciclosporin; ~ 8.6 months for acitretin; ~ 12.1-21.6 months for methotrexate; and ~ 54.8 months for FAE. These long-term safety profiles may help to guide clinicians to select the optimal oral systemic treatment for the long-term treatment of psoriasis in adults.
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Affiliation(s)
- Deepak M W Balak
- Department of Dermatology, LangeLand Ziekenhuis, Zoetermeer, the Netherlands.
| | - Sascha Gerdes
- Department of Dermatology, Psoriasis-Center, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Aurora Parodi
- DiSSal Section of Dermatology, University of Genoa-Ospedale-Policlinico San Martino IRCCS, Genoa, Italy
| | - Laura Salgado-Boquete
- Department of Dermatology, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
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Klujszo EH, Parcheta P, Witkowska AB, Krecisz B. Non-alcoholic fatty liver disease in patients with psoriasis: therapeutic implications. Postepy Dermatol Alergol 2020; 37:468-474. [PMID: 32994765 PMCID: PMC7507165 DOI: 10.5114/ada.2019.83983] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Accepted: 10/25/2018] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common liver pathology in the western countries. Psoriatic patients are at higher risk of having NAFLD, and at higher risk of experiencing a more severe form of the disease with poorer outcomes. The components of the metabolic syndrome - obesity, lipid abnormalities, hypertension, and type 2 diabetes - significantly correlate with NAFLD progression. The inflammatory state present in psoriasis plays a significant role in development of NAFLD and the metabolic syndrome. All patients with psoriasis and insulin resistance and risk factors for metabolic syndrome should also been screened for NAFLD, and planning of the treatment options should always take into consideration the possible risks related to the liver, especially in patients with NAFLD.
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Affiliation(s)
| | - Piotr Parcheta
- Department of Dermatology, Regional Hospital, Kielce, Poland
| | | | - Beata Krecisz
- Faculty of Medicine and Health Science, Jan Kochanowski University, Kielce, Poland
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Abstract
Therapeutic management of pustular psoriasis remains a challenge despite the rapid advance in psoriasis research and the development of drugs, especially biologics. Treatment guidelines have been established for pustular psoriasis, but no controlled studies are present for juvenile pustular psoriasis (JPP). Search of the literature reveals that current evidence of JPP treatment is limited to case reports and case series. Among the conventional drugs for JPP, oral retinoid is the most commonly used, yet concerns for growth disturbance exist. Cyclosporine and methotrexate have also been administered as first-line treatment. Etanercept is the first biological agent approved for juvenile plaque psoriasis, followed by adalimumab. However, infliximab is usually recommended for JPP because of the rapidity of onset, despite not being approved for use in pediatric psoriasis patients. More recently, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab have been approved for adult pustular psoriasis in selected countries. Controlled studies are needed to prove the efficacy and long-term safety of the therapeutic treatments currently used for JPP.
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Affiliation(s)
- Yi-Wei Huang
- Department of Education, National Taiwan University Hospital, Taipei, Taiwan
| | - Tsen-Fang Tsai
- Department of Dermatology, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, Taiwan.
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