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Animalu C, Singh N, Guice KC, Maner K. Febrile Pancytopenia and Hemophagocytosis From Disseminated Histoplasmosis in HIV/AIDS Patients: Two Cases and a Review of Combined Antifungal and Steroid Therapy. Case Rep Infect Dis 2025; 2025:2623694. [PMID: 40276474 PMCID: PMC12021483 DOI: 10.1155/crdi/2623694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 01/16/2025] [Accepted: 02/21/2025] [Indexed: 04/26/2025] Open
Abstract
Hemophagocytosis is a clinical condition characterized by the engulfment of bone marrow cellular elements, including erythrocytes, leukocytes, platelets, and their precursors, by activated macrophages. It has been associated with several infectious organisms, including the Epstein-Barr virus (EBV) and histoplasmosis. Human immunodeficiency virus (HIV) has been known to trigger hemophagocytosis in the presence or absence of other infections. Disseminated histoplasmosis is a common opportunistic infection in advanced patients with acquired immunodeficiency syndrome (AIDS) in endemic areas; however, the best treatment for histoplasmosis associated with hemophagocytosis is uncertain. This article presents two cases of patients with AIDS secondary to uncontrolled HIV who were admitted with fever, malaise, low CD4 + counts, and a history of noncompliance with antiretroviral therapy (ART). Both patients had pancytopenia, markedly elevated serum ferritin, and elevated liver transaminases. The diagnosis of histoplasmosis was confirmed by positive fungal blood cultures, buffy coat smears showing intracellular fungal organisms, and positive urine Histoplasma antigen. Bone marrow biopsies revealed Histoplasma capsulatum (H. capsulatum) in Grocott methenamine silver (GMS) stains and fungal cultures, histiocytes with intracellular red blood cells, and precursors of granulocytes, consistent with hemophagocytosis. Both patients received amphotericin B but remained febrile and pancytopenic, eventually requiring corticosteroid therapy. We present our experience with these patients and discuss the management of hemophagocytosis in patients with AIDS with disseminated histoplasmosis. We also completed a literature review and created a list of all known cases of disseminated histoplasmosis complicated by HIV/AIDS and hemophagocytosis and listed previous treatments.
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Affiliation(s)
- Chinelo Animalu
- Division of Infectious Diseases, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Nupur Singh
- College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
| | - Kenneth Cory Guice
- Department of Pulmonology, University of Alabama, Birmingham, Alabama, USA
| | - Kase Maner
- College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
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Montoro RA, Moran M, Overmyer KA, Periaccante A, Coon JJ, Lanjewar S, Knoll LJ, Striker R. Fatal toxoplasmic encephalitis triggered by anti-TNF therapy. Heliyon 2025; 11:e41965. [PMID: 39959486 PMCID: PMC11830312 DOI: 10.1016/j.heliyon.2025.e41965] [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: 07/11/2024] [Revised: 01/13/2025] [Accepted: 01/13/2025] [Indexed: 02/18/2025] Open
Abstract
Reactivation of a latent infection by the protozoan parasite Toxoplasma gondii can result in severe neurologic outcomes and even death. T. gondii reactivation cases have been strongly associated with acquired immunodeficiency syndrome, but other immunosuppressive situations are also associated. Anti-TNF-α therapy reliably triggers the reactivation of T. gondii latent cysts in mice models. Reactivation of T. gondii by TNF-a blockade is rare in humans though despite widespread use of TNF-a blockers. Serologic evidence of a possible latent T. gondii infection in humans is common worldwide, so why anti-TNF-α reactivation isn't more common is unknown. Here we present a 74-year-old woman who developed fatal cerebral toxoplasmosis after anti-tumor necrosis factor-α (TNF-α). After presenting to a local urgent care with confusion, a worsening cognitive status led to an emergency room visit. Computed tomography resulted in suspicion of metastatic disease leading to treatment with steroids. Lumbar puncture ruled out bacterial or viral meningitis. With continued cognitive decline, magnetic resonance imaging of the head revealed an increased number of lesions with T. gondii-associated ring-enhancing lesions. A brain biopsy confirmed the presence of T. gondii parasites. Despite standard treatment for toxoplasmosis, the patient expired. At least two possible factors may have contributed to this unfortunate outcome. First, in addition to her rheumatoid arthritis pathology, there is evidence of loss of immune resilience and abnormal T cell subsets. Second, some strains of T. gondii are more virulent than others. Post-mortem mass spectrometry and proteomic analysis of her cerebrospinal fluid show several T. gondii peptides. A literature review suggests that risks associated with anti-TNF-α therapy for patients who are seropositive for T. gondii have not been adequately recognized. We advise T. gondii seropositivity testing be considered before and after initiation of anti-TNF-α therapy as is done for other infections such as tuberculosis.
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Affiliation(s)
- Rodrigo A. Montoro
- Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI, 53706, United States
| | - Michael Moran
- Department of Medicine, University of Wisconsin-Madison, United States
| | | | - Andrew Periaccante
- Department of Biochemistry, University of Wisconsin-Madison, United States
| | - Joshua J. Coon
- Department of Biochemistry, University of Wisconsin-Madison, United States
| | - Swapnil Lanjewar
- Department of Medicine, University of Wisconsin-Madison, United States
| | - Laura J. Knoll
- Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI, 53706, United States
| | - Rob Striker
- Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI, 53706, United States
- Department of Medicine, University of Wisconsin-Madison, United States
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Bienvenu AL, Leray V, Guichon C, Bourget S, Chapuis C, Duréault A, Pavese P, Roux S, Kahale E, Chaabane W, Subtil F, Maucort-Boulch D, Talbot F, Dode X, Ghesquières H, Leboucher G. ANTIFON-CLIC®, a new clinical decision support system for the treatment of invasive aspergillosis: is it clinically relevant? ANNALES PHARMACEUTIQUES FRANÇAISES 2024; 82:514-521. [PMID: 38000506 DOI: 10.1016/j.pharma.2023.11.002] [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: 10/31/2023] [Revised: 11/17/2023] [Accepted: 11/20/2023] [Indexed: 11/26/2023]
Abstract
BACKGROUND Invasive aspergillosis (IA) is increasing especially in new groups of patients. Despite advances in management, morbidity and mortality related to IA remain high. Thus, Clinical Decision Support System (CDSS) dedicated to IA are needed to promote the optimal antifungal for each group of patients. PATIENTS AND METHODS This was a retrospective multicenter cohort study involving intensive care units and medical units. Adult patients who received caspofungin, isavuconazole, itraconazole, liposomal amphotericin B, posaconazole, or voriconazole, for the treatment of IA were eligible for enrollment. The primary objective was the concordance between the clinician's prescription and the prescription recommended by the CDSS. The secondary objective was the concordance according to different hospitals, departments, and indications. RESULTS Eighty-eight patients (n=88) from three medical hospitals were included. The overall concordance was 97% (85/88) including 100% (41/41) for center A, 92% (23/25) for center B, and 95% (21/22) for center C. There was no significant difference in concordance among the hospitals (P=0.973), the departments (P=1.000), and the indications (P=0.799). The concordance was 70% (7/10) for isavuconazole due to its use as an empirical treatment and 100% (78/78) for the other antifungals. DISCUSSION The concordance rate was high whatever the hospital, the department, and the indication. The only discrepancy was attributed to the use of isavuconazole as an empirical treatment which is a therapeutic option not included in the CDSS. CONCLUSIONS This new CDSS dedicated to IA is meeting the clinical practice. Its implementation in routine will help to support antifungal stewardship.
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Affiliation(s)
- A-L Bienvenu
- Service pharmacie, groupement hospitalier nord, hospices civils de Lyon, Lyon, France; Univ Lyon, Malaria Research Unit, SMITh, ICBMS UMR 5246, Lyon, France.
| | - V Leray
- Service d'anesthésie-réanimation, groupement hospitalier centre, hospices civils de Lyon, Lyon, France
| | - C Guichon
- Service d'anesthésie-réanimation, groupement hospitalier nord, Hospices civils de Lyon, Lyon, France
| | - S Bourget
- Service pharmacie, CH de Valence, Valence, France
| | - C Chapuis
- Service de pharmacie, CHU de Grenoble, Grenoble-Alpes, France
| | - A Duréault
- Service des maladies infectieuses, centre hospitalier de Valence, Valence, France
| | - P Pavese
- Service des maladies infectieuses, CHU de Grenoble, Grenoble-Alpes, France
| | - S Roux
- Service des maladies infectieuses et tropicales, hospices civils de Lyon, Lyon, France
| | - E Kahale
- Direction de l'innovation, hospices civils de Lyon, Lyon, France
| | - W Chaabane
- Direction des services numériques, hospices civils de Lyon, Lyon, France
| | - F Subtil
- Service de biostatistique-bioinformatique, hospices civils de Lyon, Lyon, France
| | - D Maucort-Boulch
- Service de biostatistique-bioinformatique, hospices civils de Lyon, Lyon, France
| | - F Talbot
- Direction des services numériques, hospices civils de Lyon, Lyon, France
| | - X Dode
- Service pharmacie, groupement hospitalier est, hospices civils de Lyon, Lyon, France
| | - H Ghesquières
- Service d'hématologie, groupement hospitalier sud, hospices civils de Lyon, Lyon, France
| | - G Leboucher
- Service pharmacie, groupement hospitalier nord, hospices civils de Lyon, Lyon, France
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Romiti R, Hirayama ALDS, Porro AM, Gonçalves HDS, Miot LDB, Durães SMB, Marques SA. Infections in the era of immunobiologicals. An Bras Dermatol 2024; 99:167-180. [PMID: 38238209 PMCID: PMC10943328 DOI: 10.1016/j.abd.2023.08.004] [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: 04/05/2023] [Revised: 08/15/2023] [Accepted: 08/27/2023] [Indexed: 03/11/2024] Open
Abstract
Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.
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Affiliation(s)
- Ricardo Romiti
- Department of Dermatology, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil
| | | | - Adriana Maria Porro
- Department of Dermatology, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Heitor de Sá Gonçalves
- State Health Secretariat of Ceará, Centro de Dermatologia Dona Libânia, Fortaleza, CE, Brazil
| | - Luciane Donida Bartoli Miot
- Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
| | - Sandra Maria Barbosa Durães
- Department of Internal Medicine, Dermatology Unit, Faculty of Medicine, Universidade Federal Fluminense, Niterói, RJ, Brazil
| | - Silvio Alencar Marques
- Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Faculty of Medicine, Universidade Estadual Paulista, Botucatu, SP, Brazil
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Gazitt T, Hayat N, Stein N, Haddad A, Feldhamer I, Cohen AD, Saliba W, Zisman D. The Risk of Herpes Zoster Events in Patients with Spondyloarthritis and the Effect of BNT162b2 mRNA COVID-19 Vaccine. Vaccines (Basel) 2024; 12:85. [PMID: 38250898 PMCID: PMC10821079 DOI: 10.3390/vaccines12010085] [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: 11/23/2023] [Revised: 01/07/2024] [Accepted: 01/10/2024] [Indexed: 01/23/2024] Open
Abstract
The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case-control studies, identifying all new HZ cases diagnosed from 1 January-31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19-2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15-12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68-3.14).
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Affiliation(s)
- Tal Gazitt
- Rheumatology Unit, Carmel Medical Center, Haifa 3436212, Israel; (A.H.); (D.Z.)
- Division of Rheumatology, University of Washington Medical Center, Seattle, WA 98195-6428, USA
| | - Noa Hayat
- Department of Internal Medicine, Carmel Medical Center, Haifa 3436212, Israel;
| | - Nili Stein
- Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 3436212, Israel (W.S.)
| | - Amir Haddad
- Rheumatology Unit, Carmel Medical Center, Haifa 3436212, Israel; (A.H.); (D.Z.)
| | - Ilan Feldhamer
- Chief Physician’s Office, Central Headquarters, Clalit Health Services, Tel Aviv 67754, Israel
| | - Arnon Dov Cohen
- Chief Physician’s Office, Central Headquarters, Clalit Health Services, Tel Aviv 67754, Israel
- Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
| | - Walid Saliba
- Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 3436212, Israel (W.S.)
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
| | - Devy Zisman
- Rheumatology Unit, Carmel Medical Center, Haifa 3436212, Israel; (A.H.); (D.Z.)
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel
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Morel J. Infection prevention and vaccination in the rheumatic diseases. Joint Bone Spine 2023; 90:105568. [PMID: 36990142 DOI: 10.1016/j.jbspin.2023.105568] [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] [Accepted: 07/05/2022] [Indexed: 03/29/2023]
Abstract
Patients with chronic inflammatory rheumatisms (CIR) have a higher risk of infections compared to healthy subjects. Viral and bacterial pneumonia are the most frequent infections observed in CIR with targeted disease modifying anti-rheumatic drugs (DMARDs). Moreover, drugs used to treat CIR (especially biologic and synthetic targeted DMARDs) increase the risk of infection and expose CIR patients to opportunistic infections such as tuberculosis reactivation. To limit the risk of infection, the risk-benefit ratio should be evaluated for each patient based on their characteristics and comorbidities. To prevent infections, an initial pre-treatment work-up must be performed, especially before the initiation of conventional synthetic DMARDs or biological and synthetic targeted DMARDs. This pre-treatment assessment includes the case history, laboratory and radiology findings as well. The physician must make sure a patient's vaccinations are up-to-date. The vaccines recommended for patients with CIR being treated with conventional synthetic DMARDs, bDMARDs, tsDMARDs and/or steroids should be given. Patient education is also very important. During workshops, they learn how to manage their drug treatments in at-risk situations and learn which symptoms require treatment discontinuation.
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Affiliation(s)
- Jacques Morel
- Rheumatology Department, CHU and University of Montpellier, PhyMedExp, Inserm, CNRS, Montpellier, France.
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Cannon L, Pan A, Kovalick L, Sarkissian A, Wu EY. Secondary immunodeficiencies and infectious considerations of biologic immunomodulatory therapies. Ann Allergy Asthma Immunol 2023; 130:718-726. [PMID: 36801438 PMCID: PMC10247415 DOI: 10.1016/j.anai.2023.02.010] [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: 12/22/2022] [Revised: 02/02/2023] [Accepted: 02/13/2023] [Indexed: 02/19/2023]
Abstract
Biologic immunomodulatory medications have rapidly expanded in the previous decades, providing new treatment options for individuals with a spectrum of oncologic, allergic, rheumatologic, and neurologic conditions. Biologic therapies alter immune function and can impair key host defense mechanisms, resulting in secondary immunodeficiency and increased infectious risks. Biologic medications can increase general risk for upper respiratory tract infections but can also be associated with unique infectious risks owing to distinct mechanisms of action. With the widespread use of these medications, providers in every area of medicine will likely care for individuals receiving biologic therapies and understanding their potential infectious complications can help mitigate these risks. This practical review discusses the infectious implications of biologics by class of medication and provides recommendations regarding the examination and screening both before therapy initiation and while the patient is receiving the medication. With this knowledge and background, providers can reduce risk whereas patients receive the treatment benefits of these biologic medications.
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Affiliation(s)
- Laura Cannon
- Division of Pediatric Rheumatology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Alice Pan
- Division of Pediatric Rheumatology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Pharmacy, UNC Health, Chapel Hill, North Carolina
| | - Leonard Kovalick
- Division of Pediatric Rheumatology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Aliese Sarkissian
- Division of Pediatric Rheumatology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Eveline Y Wu
- Division of Pediatric Rheumatology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Division of Pediatric Allergy/Immunology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
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Ledoux MP, Herbrecht R. Invasive Pulmonary Aspergillosis. J Fungi (Basel) 2023; 9:jof9020131. [PMID: 36836246 PMCID: PMC9962768 DOI: 10.3390/jof9020131] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/12/2023] [Accepted: 01/15/2023] [Indexed: 01/19/2023] Open
Abstract
Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific in these populations and the diagnostic work-up has considerably expanded. Computed tomography is key to assess the pulmonary lesions of aspergillosis, whose various features must be acknowledged. Positron-emission tomography can bring additional information for diagnosis and follow-up. The mycological argument for diagnosis is rarely fully conclusive, as biopsy from a sterile site is challenging in most clinical contexts. In patients with a risk and suggestive radiological findings, probable invasive aspergillosis is diagnosed through blood and bronchoalveolar lavage fluid samples by detecting galactomannan or DNA, or by direct microscopy and culture for the latter. Diagnosis is considered possible with mold infection in lack of mycological criterion. Nevertheless, the therapeutic decision should not be hindered by these research-oriented categories, that have been completed by better adapted ones in specific settings. Survival has been improved over the past decades with the development of relevant antifungals, including lipid formulations of amphotericin B and new azoles. New antifungals, including first-in-class molecules, are awaited.
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Koltsova EN, Lukina GV, Schmidt EI, Lytkina KA, Zhilyaev EV. Predictors of biologic disease modifying antirheumatic drugs withdrawal due to the development of adverse events in patients with rheumatoid arthritis. MODERN RHEUMATOLOGY JOURNAL 2022. [DOI: 10.14412/1996-7012-2022-6-26-31] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Currently, a large number of highly effective biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are used for the treatment of rheumatoid arthritis (RA). However, in addition to effectiveness, it is necessary to evaluate the risk of adverse events (AEs) when using them.Objective: to determine the predictors of bDMARDs and tsDMARDs discontinuation due to AEs in patients with RA.Patients and methods. The study included 661 patients with RA who took bDMARDs and tsDMARDs. The search for predictors of targeted therapy discontinuation due to AEs was carried out in two stages. At the first stage, using the Kaplan-Meier method, we selected indicators that showed the greatest significant single-factor relationship with the duration of retention on therapy. At the second stage, significant independent indicators were obtained by iterative selection of variables within the multivariate proportional risk model according to Cox.Results and discussion. The presence of rheumatoid nodules (p<0.001), high doses of glucocorticoids (GC; p<0.001), low doses of methotrexate (MT; p=0.009) are significant independent factors for increasing the risk of drugs discontinuation due to the development of AEs. The type of bDMARDs/tsDMARD used also significantly correlated with the risk of discontinuation of therapy due to AEs. A relatively high risk of treatment discontinuation was observed with infliximab (IFN) and certolizumab pegol (CZP). Cancellation of IFN was associated with the occurrence of infusion reactions and infectious complications, and CZP was associated with infectious complications.Conclusion. An increase in the dose of MT and decrease in the use of GCs can help prevent the development of AEs leading to the abolition of biologics and tsDMARDs. Significant differences were found between bDMARDs in terms of the risk of their cancellation due to AEs.
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Affiliation(s)
| | - G. V. Lukina
- A.S. Loginov Moscow Clinical Scientific Center; V.A. Nasonova Research Institute of Rheumatology
| | | | | | - E. V. Zhilyaev
- European Medical Center; Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia; Pirogov Russian National Research Medical University
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Yu J, Zhao Q, Wang X, Zhou H, Hu J, Gu L, Hu Y, Zeng F, Zhao F, Yue C, Zhou P, Li G, Li Y, Wu W, Zhou Y, Li J. Pathogenesis, multi-omics research, and clinical treatment of psoriasis. J Autoimmun 2022; 133:102916. [PMID: 36209691 DOI: 10.1016/j.jaut.2022.102916] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 09/08/2022] [Accepted: 09/12/2022] [Indexed: 11/07/2022]
Abstract
Psoriasis is a common inflammatory skin disease involving interactions between keratinocytes and immune cells that significantly affects the quality of life. It is characterized by hyperproliferation and abnormal differentiation of keratinocytes and excessive infiltration of immune cells in the dermis and epidermis. The immune mechanism underlying this disease has been elucidated in the past few years. Research shows that psoriasis is regulated by the complex interactions among immune cells, such as keratinocytes, dendritic cells, T lymphocytes, neutrophils, macrophages, natural killer cells, mast cells, and other immune cells. An increasing number of signaling pathways have been found to be involved in the pathogenesis of psoriasis, which has prompted the search for new treatment targets. In the past decades, studies on the pathogenesis of psoriasis have focused on the development of targeted and highly effective therapies. In this review, we have discussed the relationship between various types of immune cells and psoriasis and summarized the major signaling pathways involved in the pathogenesis of psoriasis, including the PI3K/AKT/mTOR, JAK-STAT, JNK, and WNT pathways. In addition, we have discussed the results of the latest omics research on psoriasis and the epigenetics of the disease, which provide insights regarding its pathogenesis and therapeutic prospects; we have also summarized its treatment strategies and observations of clinical trials. In this paper, the various aspects of psoriasis are described in detail, and the limitations of the current treatment methods are emphasized. It is necessary to improve and innovate treatment methods from the molecular level of pathogenesis, and further provide new ideas for the treatment and research of psoriasis.
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Affiliation(s)
- Jiadong Yu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Qixiang Zhao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Xiaoyan Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Hong Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Jing Hu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Linna Gu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Yawen Hu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Fanlian Zeng
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Fulei Zhao
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Chengcheng Yue
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Pei Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Guolin Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Ya Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Wenling Wu
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Yifan Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China
| | - Jiong Li
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, 1 Keyuan 4th Road, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan, 610041, China.
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11
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Ong DSY, Chong GLM, Chemaly RF, Cremer OL. Comparative clinical manifestations and immune effects of cytomegalovirus infections following distinct types of immunosuppression. Clin Microbiol Infect 2022; 28:1335-1344. [PMID: 35709902 DOI: 10.1016/j.cmi.2022.05.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/23/2022] [Accepted: 05/30/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is a well-recognized complication of solid organ and hematopoietic cell transplantation. However, CMV infection also occurs in patients with human immunodeficiency virus (HIV) infection, previously immunocompetent intensive care unit (ICU) patients, and individuals on immunosuppressive medications for various underlying diseases. OBJECTIVES This review describes the comparative effects of CMV infection in distinct types of acquired immunosuppression. SOURCES Selected peer-reviewed publications on CMV infections published until December 2021. CONTENT CMV infection affects various organ systems through direct cytolytic mechanisms, but may also exert indirect effects by promoting pro-inflammatory and immunosuppressive responses. This has been well studied in transplant recipients, for whom antiviral prophylaxis and pre-emptive therapy have now become standard practice. These strategies not only prevent direct CMV disease manifestations, but also mitigate various immunopathological processes to reduce graft-versus-host disease, graft rejection, and the occurrence of secondary bacterial and fungal infections. The efficacy of neither prophylactic nor pre-emptive treatment of CMV infection has been demonstrated for patients with critical illness- or medication-induced immunosuppression. Many observational studies have shown an independent association between CMV reactivation and a prolonged duration of mechanical ventilation or increased mortality in the ICU. Furthermore, data suggest that CMV reactivation may increase pulmonary inflammation and prolong the duration of mechanical ventilation. IMPLICATIONS A large number of observational and experimental studies suggest attributable morbidity and mortality related to CMV infection, not only in transplant recipients and patients with HIV infection but also in patients with critically illness- or medication-induced immunosuppression. Adequately powered randomized controlled trials investigating the efficacy of prophylaxis or pre-emptive treatment of CMV infection in these patients are lacking, with a notable exception for transplant recipients.
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Affiliation(s)
- David S Y Ong
- Department of Medical Microbiology and Infection Control, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
| | - Ga-Lai M Chong
- Erasmus University Medical Center, Department of Medical Microbiology & Infectious Diseases, Rotterdam, the Netherlands
| | - Roy F Chemaly
- Department of Infectious Diseases, Infection Control, & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Olaf L Cremer
- Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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12
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Saltović E, Mijandrušić-Sinčić B, Braut A, Škrobonja I, Sever E, Glažar I, Pezelj-Ribarić S, Muhvić-Urek M. Absence of Oral Opportunistic Infections in Patients with Inflammatory Bowel Disease Receiving Anti-TNF-α and Anti-Integrin-α 4β 7 Therapy. Dent J (Basel) 2022; 10:dj10030032. [PMID: 35323234 PMCID: PMC8947472 DOI: 10.3390/dj10030032] [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: 12/30/2021] [Revised: 02/16/2022] [Accepted: 02/21/2022] [Indexed: 02/04/2023] Open
Abstract
Biological therapy of inflammatory bowel disease (IBD) carries an increased risk for the development of opportunistic infections due to immunomodulation. The aim of this study was to determine the prevalence and types of oral infections in IBD patients treated with biological (anti-TNF-α and anti-integrin-α4β7) and conventional medication protocols. The study included 20 IBD patients receiving anti-TNF-α therapy, 20 IBD patients receiving anti-integrin-α4β7 therapy and 20 IBD patients without immunomodulatory therapy. Participants completed questionnaires on medical information, oral lesions and symptoms. For each patient, clinical examination and a salivary flow rate test were performed, followed by a swab of the oral mucosa. The swab samples were cultured to identify Candida spp. and oral bacteria. No bacterial opportunistic infections were detected. Candidiasis was detected in four participants, with no significant difference between groups (p = 0.765). Hyposalivation was most common in the anti-TNF-α group, with a significant difference between groups (p = 0.036). There were no significant differences between groups in self-reported oral mucosal lesions and symptoms (p > 0.05), or in the distribution of oral mucosal lesions (p > 0.05). This study suggests that IBD patients receiving biological therapy are at no greater risk of developing oral opportunistic infections than IBD patients not receiving immunomodulatory therapy.
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Affiliation(s)
- Ema Saltović
- Clinic of Dental Medicine, Clinical Hospital Center Rijeka, Krešimirova 40, 51000 Rijeka, Croatia; (E.S.); (A.B.); (I.G.); (S.P.-R.)
| | - Brankica Mijandrušić-Sinčić
- Clinic of Internal Medicine, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia;
- Department of Internal Medicine, Faculty of Medicine, University of Rijeka, Braće Branchetta 20/1, 51000 Rijeka, Croatia
| | - Alen Braut
- Clinic of Dental Medicine, Clinical Hospital Center Rijeka, Krešimirova 40, 51000 Rijeka, Croatia; (E.S.); (A.B.); (I.G.); (S.P.-R.)
- Department of Restorative Dentistry and Endodontics, Faculty of Dental Medicine, University of Rijeka, Krešimirova 40, 51000 Rijeka, Croatia
| | - Ivana Škrobonja
- Clinical Department for Clinical Microbiology, Clinical Hospital Center Rijeka, Krešimirova 42, 51000 Rijeka, Croatia;
| | - Ella Sever
- Department of Oral Medicine and Periodontology, Faculty of Dental Medicine, University of Rijeka, Krešimirova 40, 51000 Rijeka, Croatia;
| | - Irena Glažar
- Clinic of Dental Medicine, Clinical Hospital Center Rijeka, Krešimirova 40, 51000 Rijeka, Croatia; (E.S.); (A.B.); (I.G.); (S.P.-R.)
- Department of Oral Medicine and Periodontology, Faculty of Dental Medicine, University of Rijeka, Krešimirova 40, 51000 Rijeka, Croatia;
| | - Sonja Pezelj-Ribarić
- Clinic of Dental Medicine, Clinical Hospital Center Rijeka, Krešimirova 40, 51000 Rijeka, Croatia; (E.S.); (A.B.); (I.G.); (S.P.-R.)
- Department of Oral Medicine and Periodontology, Faculty of Dental Medicine, University of Rijeka, Krešimirova 40, 51000 Rijeka, Croatia;
- Department of Dental Medicine, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31000 Osijek, Croatia
| | - Miranda Muhvić-Urek
- Clinic of Dental Medicine, Clinical Hospital Center Rijeka, Krešimirova 40, 51000 Rijeka, Croatia; (E.S.); (A.B.); (I.G.); (S.P.-R.)
- Department of Oral Medicine and Periodontology, Faculty of Dental Medicine, University of Rijeka, Krešimirova 40, 51000 Rijeka, Croatia;
- Correspondence:
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13
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Abrantes FF, Moraes MPMD, Albuquerque Filho JMVD, Alencar JMD, Lopes AB, Pinto WBVDR, Souza PVSD, Oliveira EMLD, Oliveira ADSBD, Pedroso JL, Barsottini OGP. Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy. ARQUIVOS DE NEURO-PSIQUIATRIA 2021; 79:1012-1025. [PMID: 34816994 DOI: 10.1590/0004-282x-anp-2020-0593] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 03/12/2021] [Indexed: 11/22/2022]
Abstract
For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.
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Affiliation(s)
- Fabiano Ferreira Abrantes
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | | | | | - Jéssica Monique Dias Alencar
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | - Alexandre Bussinger Lopes
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | | | - Paulo Victor Sgobbi de Souza
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | | | | | - José Luiz Pedroso
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
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14
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Aissaoui N, Hamane S, Gits-Muselli M, Petit A, Benderdouche M, Denis B, Alanio A, Dellière S, Bagot M, Bretagne S. Imported leishmaniasis in travelers: a 7-year retrospective from a Parisian hospital in France. BMC Infect Dis 2021; 21:953. [PMID: 34525963 PMCID: PMC8442464 DOI: 10.1186/s12879-021-06631-5] [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: 05/10/2021] [Accepted: 08/19/2021] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Leishmaniases are regularly seen in non-endemic areas due to the increase of international travels. They include cutaneous leishmaniases (CL) and mucocutaneous (MC) caused by different Leishmania species, and visceral leishmaniases (VL) which present with non-specific symptoms. METHODS We reviewed all consecutive leishmaniasis cases seen between September 2012 and May 2020. The diagnostic strategy included microscopy after May-Grünwald-Giemsa staining, a diagnostic quantitative PCR (qPCR) assay, and species identification based on sequencing of the cytochrome b gene. RESULTS Eighty-nine patients had a definitive leishmaniasis diagnosis. Nine patients had VL with Leishmania infantum. Eighty patients had CL. Twelve patients acquired CL after trips in Latin America (7 Leishmania guyanensis, 2 Leishmania braziliensis, 2 Leishmania mexicana, and 1 Leishmania panamensis). Species could be identified in 63 of the 68 CLs mainly after travel in North Africa (59%) with Leishmania major (65%), Leishmania tropica/killicki (24%), and L. infantum (11%), or in West Sub-Saharan Africa (32%), all due to L. major. The median day between appearance of the lesions and diagnosis was 90 [range 60-127]. CONCLUSIONS Our diagnostic strategy allows both positive diagnoses and species identifications. Travelers in West Sub-Saharan Africa and North Africa should be better aware of the risk of contracting leishmananiasis.
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Affiliation(s)
- Nesrine Aissaoui
- Laboratoire de Parasitologie et de Mycologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75475, Paris, France
| | - Samia Hamane
- Laboratoire de Parasitologie et de Mycologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75475, Paris, France
| | - Maud Gits-Muselli
- Laboratoire de Parasitologie et de Mycologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75475, Paris, France.,Université de Paris, Paris, France
| | - Antoine Petit
- Service de Dermatologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Mazouz Benderdouche
- Laboratoire de Parasitologie et de Mycologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75475, Paris, France
| | - Blandine Denis
- Département de Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
| | - Alexandre Alanio
- Laboratoire de Parasitologie et de Mycologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75475, Paris, France.,Université de Paris, Paris, France
| | - Sarah Dellière
- Laboratoire de Parasitologie et de Mycologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75475, Paris, France.,Université de Paris, Paris, France
| | - Martine Bagot
- Service de Dermatologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.,INSERM U976, Paris, France
| | - Stéphane Bretagne
- Laboratoire de Parasitologie et de Mycologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), 1 Avenue Claude Vellefaux, 75475, Paris, France. .,Université de Paris, Paris, France.
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15
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Wang Y, Lin Q, Lin J, Du G, Matucci-Cerinic M. Infliximab Precipitated Urachal Remnant Infection. J Clin Rheumatol 2021; 27:e219-e221. [PMID: 30585998 DOI: 10.1097/rhu.0000000000000946] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
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16
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Sellam J, Morel J, Tournadre A, Bouhnik Y, Cornec D, Devauchelle-Pensec V, Dieudé P, Goupille P, Jullien D, Kluger N, Lazaro E, Le Goff B, de Lédinghen V, Lequerré T, Nocturne G, Seror R, Truchetet ME, Verhoeven F, Pham T, Richez C. PRACTICAL MANAGEMENT of patients on anti-TNF therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI). Joint Bone Spine 2021; 88:105174. [PMID: 33992225 DOI: 10.1016/j.jbspin.2021.105174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Jérémie Sellam
- Service de Rhumatologie, CHU Saint-Antoine, Paris, France
| | - Jacques Morel
- Service de Rhumatologie, CHU Montpellier, Montpellier, France
| | - Anne Tournadre
- Service de Rhumatologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Yoram Bouhnik
- Service de Gastro-entérologie, CHU Hôpital Beaujon, Clichy, France
| | - Divi Cornec
- Service de Rhumatologie, CHRU La Cavale Blanche, Brest, France
| | | | - Philippe Dieudé
- Service de Rhumatologie, CHU Bichat-Claude Bernard, Paris, France
| | | | | | - Nicolas Kluger
- Dpt Dermatology, Helsinki, Finland; Service de Dermatologie, CHU Bichat-Claude Bernard, Paris, France
| | - Estibaliz Lazaro
- Service de Médecine interne, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France
| | | | - Victor de Lédinghen
- Unité d'Hépatologie et transplantation hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France
| | | | | | - Raphaèle Seror
- Service de Rhumatologie, Bicêtre, Le Kremlin-Bicêtre, France
| | | | | | - Thao Pham
- Service de Rhumatologie, CHU Sainte-Marguerite, Marseille, France
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17
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Nocturne G, Ly B, Paoletti A, Pascaud J, Seror R, Nicco C, Mackay F, Vincent FB, Lazure T, Ferlicot S, Stimmer L, Pascal Q, Roulland S, Krzysiek R, Hacein-Bey S, Batteux F, Mariette X. Long-term exposure to monoclonal anti-TNF is associated with an increased risk of lymphoma in BAFF-transgenic mice. Clin Exp Immunol 2021; 205:169-181. [PMID: 33864242 DOI: 10.1111/cei.13602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 03/13/2021] [Accepted: 03/22/2021] [Indexed: 11/28/2022] Open
Abstract
The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of tumor necrosis factor inhibitor (TNFi), comparing monoclonal anti-TNF antibodies to the soluble TNF receptor. We used B cell activating factor belonging to the TNF family (BAFF)-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month-old BAFF-Tg mice were treated with TNFi for 12 months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at euthanasia. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF antibodies compared to both controls and mice treated with the soluble TNF receptor, even at a high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF antibodies. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF antibodies increase the risk of lymphoma in B cell-driven autoimmunity. These data suggest a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF antibodies.
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Affiliation(s)
- Gaetane Nocturne
- Department of Rheumatology, FHU CARE, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,INSERM, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Bineta Ly
- INSERM, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Audrey Paoletti
- INSERM, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Juliette Pascaud
- INSERM, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Raphaele Seror
- Department of Rheumatology, FHU CARE, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,INSERM, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Saclay, Le Kremlin-Bicêtre, France
| | - Carole Nicco
- Cochin Institute, INSERM, University Paris Descartes, Paris, France
| | - Fabienne Mackay
- QIMR Berghofer Medical Research Institute in Brisbane QLD, Herston, QLD, Australia
| | - F B Vincent
- Rheumatology Research Group, Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia
| | - Thierry Lazure
- Department of Pathology, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Sophie Ferlicot
- Department of Pathology, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Lev Stimmer
- US27 Platform for Experimental Pathology, Molecular Imaging Research Center, INSERM-CEA, Fontenay-aux-Roses, France
| | - Quentin Pascal
- US27 Platform for Experimental Pathology, Molecular Imaging Research Center, INSERM-CEA, Fontenay-aux-Roses, France
| | - Sandrine Roulland
- Aix Marseille University, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France
| | - Roman Krzysiek
- Department of Immunology, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Salima Hacein-Bey
- Department of Immunology, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Frederic Batteux
- Cochin Institute, INSERM, University Paris Descartes, Paris, France
| | - Xavier Mariette
- Department of Rheumatology, FHU CARE, AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.,INSERM, Center for Immunology of Viral Infections and Autoimmune Diseases, Université Paris-Saclay, Le Kremlin-Bicêtre, France
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18
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D'Arienzo D, Rumjahn Gryte K, Noya F, Morinville VD. Disseminated and Central Nervous System Vaccine-Strain Herpes Zoster Infection in a Teenager With Crohn's Disease on Maintenance Adalimumab Therapy. JPGN REPORTS 2021; 2:e072. [PMID: 37207068 PMCID: PMC10191570 DOI: 10.1097/pg9.0000000000000072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 03/14/2021] [Indexed: 05/21/2023]
Abstract
Patients on immunosuppression, including inflammatory bowel disease patients on anti-tumor necrosis factor therapies, are at increased risk of severe varicella and herpes zoster infections. Although varicella vaccine-related herpes zoster reactivation is a rare complication, physicians must remain vigilant about this diagnosis, particularly in those on immunosuppressive medications. Here, we report a case of a patient with Crohn disease, on only adalimumab immunosuppression, who developed varicella vaccine-related disseminated herpes zoster with meningitis, over 15 years after immunization.
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Affiliation(s)
- David D'Arienzo
- From the Department of Pediatrics, Montreal Children's Hospital, McGill University
| | | | - Francisco Noya
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Montreal Children's Hospital
| | - Veronique D Morinville
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada
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19
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Menegatti S, Guillemot V, Latis E, Yahia-Cherbal H, Mittermüller D, Rouilly V, Mascia E, Rosine N, Koturan S, Millot GA, Leloup C, Duffy D, Gleizes A, Hacein-Bey-Abina S, Sellam J, Berenbaum F, Miceli-Richard C, Dougados M, Bianchi E, Rogge L. Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo. Ann Rheum Dis 2021; 80:475-486. [PMID: 33268443 PMCID: PMC7958106 DOI: 10.1136/annrheumdis-2020-218304] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 10/30/2020] [Accepted: 10/30/2020] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Antitumour necrosis factor (TNF) therapy has revolutionised treatment of several chronic inflammatory diseases, including spondyloarthritis (SpA). However, TNF inhibitors (TNFi) are not effective in all patients and the biological basis for treatment failure remains unknown. We have analysed induced immune responses to define the mechanism of action of TNF blockers in SpA and to identify immunological correlates of responsiveness to TNFi. METHODS Immune responses to microbial and pathway-specific stimuli were analysed in peripheral blood samples from 80 patients with axial SpA before and after TNFi treatment, using highly standardised whole-blood stimulation assays. Cytokines and chemokines were measured in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, and gene expression was monitored using nCounter assays. RESULTS Anti-TNF therapy induced profound changes in patients' innate immune responses. TNFi action was selective, and had only minor effects on Th1/Th17 immunity. Modular transcriptional repertoire analysis identified prostaglandin E2 synthesis and signalling, leucocyte recirculation, macrophage polarisation, dectin and interleukin (IL)-1 signalling, as well as the nuclear factor kappa B (NF-kB) transcription factor family as key pathways targeted by TNF blockers in vivo. Analysis of induced immune responses before treatment initiation revealed that expression of molecules associated with leucocyte adhesion and invasion, chemotaxis and IL-1 signalling are correlated with therapeutic responses to anti-TNF. CONCLUSIONS We show that TNFi target multiple immune cell pathways that cooperate to resolve inflammation. We propose that immune response profiling provides new insight into the biology of TNF-blocker action in patients and can identify signalling pathways associated with therapeutic responses to biological therapies.
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Affiliation(s)
- Silvia Menegatti
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- INSERM U932, Institut Curie, PSL Research University, Paris, France
| | - Vincent Guillemot
- Bioinformatics and Biostatistics Hub-Département de Biologie Computationelle, Institut Pasteur, USR 3756 IP CNRS, Paris, France
| | - Eleonora Latis
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Hanane Yahia-Cherbal
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Daniela Mittermüller
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
| | | | - Elena Mascia
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
| | - Nicolas Rosine
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Surya Koturan
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Gael A Millot
- Bioinformatics and Biostatistics Hub-Département de Biologie Computationelle, Institut Pasteur, USR 3756 IP CNRS, Paris, France
| | - Claire Leloup
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
| | - Darragh Duffy
- Institut Pasteur, Translational Immunology Laboratory, Department of Immunology, Paris, France
| | - Aude Gleizes
- Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin-Bicêtre, AP-HP, Le-Kremlin-Bicêtre, France
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France
| | - Salima Hacein-Bey-Abina
- Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris-Sud, Hôpital Kremlin-Bicêtre, AP-HP, Le-Kremlin-Bicêtre, France
- UTCBS CNRS UMR 8258, INSERM U1267, Faculté de Pharmacie de Paris, Université de Paris, Paris, France
| | - Jérémie Sellam
- Sorbonne Université, Service de Rhumatologie, Hôpital Saint-Antoine, AP-HP, Paris, France
- Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Paris, France
| | - Francis Berenbaum
- Sorbonne Université, Service de Rhumatologie, Hôpital Saint-Antoine, AP-HP, Paris, France
- Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Paris, France
| | - Corinne Miceli-Richard
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, Paris, France
- Unité Mixte AP-HP/Institut Pasteur, Institut Pasteur, Paris, France
| | - Maxime Dougados
- Paris Descartes University, Rheumatology Department, Cochin Hospital, AP-HP, Paris, France
- Unité Mixte AP-HP/Institut Pasteur, Institut Pasteur, Paris, France
- INSERM U1153 Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
| | - Elisabetta Bianchi
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Unité Mixte AP-HP/Institut Pasteur, Institut Pasteur, Paris, France
| | - Lars Rogge
- Immunoregulation Unit, Department of Immunology, Institut Pasteur, Paris, France
- Unité Mixte AP-HP/Institut Pasteur, Institut Pasteur, Paris, France
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20
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Simon TA, Dong L, Winthrop KL. Risk of opportunistic infections in patients with rheumatoid arthritis initiating abatacept: cumulative clinical trial data. Arthritis Res Ther 2021; 23:17. [PMID: 33430948 PMCID: PMC7798209 DOI: 10.1186/s13075-020-02399-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 12/13/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND To evaluate incidence of opportunistic infections (OIs) in patients with rheumatoid arthritis (RA) treated with abatacept in clinical trials. METHODS This pooled analysis of 16 randomized, double-blind/open-label trials, with ≥ 1 abatacept (intravenous or subcutaneous) arm, and with/without placebo control covered cumulative (controlled short-term and open-label long-term) abatacept exposure periods. OIs were analyzed separately in controlled (abatacept and placebo individually) and cumulative periods. OIs were identified using a prespecified list; events were independently adjudicated. Unadjusted incidence rates (IRs; per 100 patient-years) with 95% confidence intervals (CIs) were calculated. RESULTS In cumulative periods, 7044 patients received abatacept, with a mean (standard deviation) duration of exposure of 36.9 (26.2) months (21,274 patient-years of exposure). IRs (95% CIs) of OIs were 0.17 (0.05-0.43) for abatacept and 0.56 (0.22-1.15) for placebo during the controlled periods and 0.21 (0.15-0.28) for abatacept during the cumulative periods. There was 1 case of tuberculosis in both the abatacept (IR [95% CI] 0.04 [0.00-0.24]) and placebo (IR [95% CI] 0.08 [0.00-0.44]) groups during the controlled periods; 13 verified tuberculosis cases (IR [95% CI] 0.06 [0.03-0.10]) were reported in the cumulative period. Herpes zoster was reported numerically more often with abatacept (IR 1.9 [1.4-2.5]), versus placebo (1.7 [1.1-2.6]) in the controlled periods; within the cumulative period, herpes zoster IR (95% CI) was 1.53 (1.36-1.71) for abatacept-treated patients. CONCLUSION In controlled periods of the clinical trials, abatacept-treated patients had similarly low rates of OIs compared with placebo-treated patients. Overall, OI rates were similar among abatacept-treated patients in the controlled and cumulative periods and consistent with the ranges reported in the literature.
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Affiliation(s)
- Teresa A Simon
- Bristol Myers Squibb, Princeton, NJ, 08543, USA. .,Current affiliation: Physicians Research Center, LLC, Toms River, NJ, 08753, USA.
| | - Lixian Dong
- Bristol Myers Squibb, Princeton, NJ, 08543, USA
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21
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Arantes TE, Lima LH, Bressanin GL, Marques CD, Duarte ÂB, Muccioli C. PRESUMED TUBERCULOUS MULTIFOCAL RETINITIS IN PATIENTS UNDER TREATMENT WITH BIOLOGIC AGENTS. Retin Cases Brief Rep 2021; 15:56-61. [PMID: 29746443 DOI: 10.1097/icb.0000000000000747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
PURPOSE To report unique retinal fundus lesions and treatment outcomes of intraocular tuberculosis in patients under anti-tumor necrosis factor treatment. METHODS Retrospective review of two patients with laboratorial evidence of tuberculosis who had bilateral ocular signs and symptoms not attributable to other diseases. Multimodal imaging was analyzed at the time of presentation and after the treatment initiation. The study patients underwent standard treatment for tuberculosis. RESULTS Clinical and laboratory findings were consistent with the diagnosis of presumed tuberculosis. Color fundus photograph revealed the presence of multifocal yellowish retinal spots in the study eyes. On fluorescein angiography, the retinal lesions seen on color fundus photograph showed early hypofluorescence with progressive staining of its edges. Occlusive vasculitis with peripheral nonperfusion was also observed in both cases. Spectral domain optical coherence tomography demonstrated increased reflectivity and thickness on the topography of retinitis lesions. After specific antibiotic treatment for tuberculosis, there was complete disappearance of the retinal lesions in all study eyes. CONCLUSION We report two unique cases of bilateral presumed intraocular tuberculosis presenting as multifocal retinitis in patients under biologic agent treatment. Anti-tumor necrosis factor agents may be related to unusual fundus manifestations of tuberculosis.
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Affiliation(s)
- Tiago E Arantes
- Department of Ophthalmology, Fundação Altino Ventura, Recife, Brazil
- Department of Ophthalmology, Hospital de Olhos Sadalla Amin Ghanem, Joinville, Brazil
| | - Luiz H Lima
- Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
| | - Gláucio L Bressanin
- Department of Ophthalmology, Hospital da Visão de Toledo, Toledo, Brazil; and
| | - Cláudia D Marques
- Department of Rheumatology, Federal University of Pernambuco, Recife, Brazil
| | - Ângela B Duarte
- Department of Rheumatology, Federal University of Pernambuco, Recife, Brazil
| | - Cristina Muccioli
- Department of Ophthalmology, Federal University of São Paulo (UNIFESP), São Paulo, Brazil
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22
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Lortholary O, Fernandez-Ruiz M, Baddley JW, Manuel O, Mariette X, Winthrop KL. Infectious complications of rheumatoid arthritis and psoriatic arthritis during targeted and biological therapies: a viewpoint in 2020. Ann Rheum Dis 2020; 79:1532-1543. [PMID: 32963049 DOI: 10.1136/annrheumdis-2020-217092] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 05/28/2020] [Accepted: 06/16/2020] [Indexed: 12/13/2022]
Abstract
Biological therapies have improved the outcomes of several major inflammatory, autoimmune and also neoplastic disorders. Those directed towards cytokines or other soluble mediators, cell-surface molecules or receptors or various components of intracellular signalling pathways may be associated with the occurrence of infections whose diversity depends on the particular immune target. In this context and following a keynote lecture given by one of us at the European League Against Rheumatism meeting on June 2018, a multidisciplinary group of experts deeply involved in the use of targeted and biological therapies in rheumatoid and psoriatic arthritis decided to summarise their recent vision of the immunological basis and epidemiology of infections occurring during targeted and biological therapies, and provide useful indications for their management and prevention.
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Affiliation(s)
- Olivier Lortholary
- Paris University, Necker Pasteur Center for Infectious Diseases and Tropical Medicine, IHU Imagine, Necker Enfants malades University Hospital, APHP, Paris, France
- Institut Pasteur, National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, CNRS UMR 2000, Paris, France
| | - Mario Fernandez-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), School of Medicine, Universidad Complutense, Madrid, Spain
- Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain
| | - John W Baddley
- University of Maryland School of Medicine, Division of Infectious Diseases, Baltimore, Maryland, USA
| | - Oriol Manuel
- Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Xavier Mariette
- Rheumatology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux universitaires Paris-Sud - Hôpital Bicêtre, Le Kremlin Bicêtre, France
- Université Paris-Sud, Center for Immunology of Viral Infections and Auto-immune Diseases (IMVA), Institut pour la Santé et la Recherche Médicale (INSERM) UMR 1184, Université Paris-Saclay, Le Kremlin Bicêtre, France
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23
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Kang EH, Jin Y, Tong AY, Desai RJ, Kim SC. Risk of Serious Infection Among Initiators of Tumor Necrosis Factor Inhibitors Plus Methotrexate Versus Triple Therapy for Rheumatoid Arthritis: A Cohort Study. Arthritis Care Res (Hoboken) 2020; 72:1383-1391. [PMID: 31376333 DOI: 10.1002/acr.24038] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 07/30/2019] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To compare the risk of serious infections between the use of tumor necrosis factor inhibitors (TNFi) plus methotrexate (MTX) versus triple therapy among rheumatoid arthritis (RA) patients in a real-world setting. METHODS Using claims data from Truven MarketScan (2003-2014), we conducted a cohort study to compare RA patients receiving MTX who added a TNFi (TNFi plus MTX group) versus MTX plus hydroxychloroquine and sulfasalazine (triple therapy group). The primary outcome was any serious infection (i.e., a composite end point of hospitalized bacterial and opportunistic infections or herpes zoster). Secondary outcomes were individual components of the composite end point. To adjust for baseline confounding, we used propensity score (PS)-based fine stratification and weighting. A weighted Cox proportional hazards model estimated the hazard ratio (HR) and 95% confidence interval (95% CI) of the outcomes. RESULTS After PS stratification (PSS) and weighting, we included a total of 45,208 TNFi plus MTX initiators and 1,387 triple therapy initiators. Mean age was 53 years and 70% were female. The incidence rate of any serious infection per 100 person-years was 2.46 in the TNFi plus MTX group and 2.03 in the triple therapy group. The PSS-weighted HR for any serious infection comparing TNFi plus MTX versus triple therapy was 1.23 (95% CI 0.87-1.74). For the secondary outcomes, the PSS-weighted HR was 1.41 (95% CI 0.85-2.34) for bacterial infection and 0.80 (95% CI 0.55-1.18) for herpes zoster. CONCLUSION In this real-world cohort of RA patients, we noted no substantially different risk of any serious infection, bacterial infection, or herpes zoster after initiating TNFi plus MTX versus triple therapy, although CIs were wide.
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Affiliation(s)
- Eun Ha Kang
- Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Yinzhu Jin
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Angela Y Tong
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Rishi J Desai
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Seoyoung C Kim
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
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Martínez-Barricarte R. Isolated Nocardiosis, an Unrecognized Primary Immunodeficiency? Front Immunol 2020; 11:590239. [PMID: 33193422 PMCID: PMC7606290 DOI: 10.3389/fimmu.2020.590239] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 08/31/2020] [Indexed: 01/19/2023] Open
Abstract
Nocardiosis is an infectious disease caused by the gram-positive bacterium Nocardia spp. Although it is commonly accepted that exposure to Nocardia is almost universal, only a small fraction of exposed individuals develop the disease, while the vast majority remain healthy. Nocardiosis has been described as an "opportunistic" disease of immunocompromised patients, suggesting that exposure to the pathogen is necessary, but a host predisposition is also required. Interestingly, increasing numbers of nocardiosis cases in individuals without any detected risk factors, i.e., without overt immunodeficiency, are being reported. Furthermore, a growing body of evidence have shown that selective susceptibility to a specific pathogen can be caused by a primary immunodeficiency (PID). This raises the question of whether an undiagnosed PID may cause nocardiosis affecting otherwise healthy individuals. This review summarizes the specific clinical and microbiological characteristics of patients with isolated nocardiosis published during the past 30 years. Furthermore, it gives an overview of the known human immune mechanisms to fend off Nocardia spp. obtained from the study of PIDs and patients under immunomodulatory therapies.
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Affiliation(s)
- Rubén Martínez-Barricarte
- Division of Genetic Medicine, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, United States
- Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN, United States
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25
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Singh SRK, Thanikachalam K, Donthireddy V. Desperate times, desperate measures: successful use of chemotherapy in treatment of haemophagocytic lymphohistiocytosis (HLH) due to disseminated histoplasmosis. BMJ Case Rep 2020; 13:13/9/e235144. [PMID: 32878853 DOI: 10.1136/bcr-2020-235144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
We describe a case of haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis, which was treated with chemotherapy in addition to standard antifungal therapy. While HLH in the setting of infections is very well described, its treatment in this setting is controversial, with some physicians treating only the underlying infection, whereas others using immune suppression in addition to antimicrobials. To the best of our knowledge, this is the first report documenting the successful treatment of an adult patient with HLH due to disseminated histoplasmosis using etoposide chemotherapy after initial antifungal therapy failed to show improvement.
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26
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Davis JS, Ferreira D, Paige E, Gedye C, Boyle M. Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies. Clin Microbiol Rev 2020; 33:e00035-19. [PMID: 32522746 PMCID: PMC7289788 DOI: 10.1128/cmr.00035-19] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.
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Affiliation(s)
- Joshua S Davis
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
| | - David Ferreira
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Emma Paige
- Department of Infectious Diseases, Alfred Hospital, Melbourne, VIC, Australia
| | - Craig Gedye
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
- Department of Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia
| | - Michael Boyle
- Department of Infectious Diseases and Immunology, John Hunter Hospital, Newcastle, NSW, Australia
- School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
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27
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28
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Kurizky PS, Marianelli FF, Cesetti MV, Damiani G, Sampaio RNR, Gonçalves LMT, de Sousa CAF, Martins SS, Vernal S, da Mota LMH, Gomes CM. A comprehensive systematic review of leishmaniasis in patients undergoing drug-induced immunosuppression for the treatment of dermatological, rheumatological and gastroenterological diseases. Rev Inst Med Trop Sao Paulo 2020; 62:e28. [PMID: 32401957 PMCID: PMC7232954 DOI: 10.1590/s1678-9946202062028] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 04/17/2020] [Indexed: 04/06/2023] Open
Abstract
Immunosuppression is an important risk factor for leishmaniasis. We assessed the clinical profile, geographic distribution and prevalence of leishmaniasis in patients undergoing immunosuppressive therapy for dermatological, rheumatological or gastroenterological autoimmune diseases. We identified relevant studies in PubMed, EMBASE, Scopus, Web of Science and LILACS on July 3rd, 2018. We included articles that reported at least one case of leishmaniasis in patients undergoing immunosuppressive treatment for dermatological, rheumatological or gastroenterological diseases. Our protocol was registered in PROSPERO (CRD42018103050). We assessed the quality of the included studies with the Joanna Briggs Institute Critical Appraisal Tool. After the removal of duplicates, 5,431 articles were collected and screened. We included 138 articles; the prevalence of leishmaniasis in six methodologically similar studies varied from three to 1,282 cases per 100,000 patients using anti-TNFα drugs, but the results were significantly heterogeneous . Leishmaniasis in patients treated with immunosuppressive drugs is a health problem mostly reported in European countries bordering the Mediterranean Sea; sporadic activities, such as travelling, seem not to be associated with a significant risk of leishmaniasis, although effective control measures must always be observed.
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Affiliation(s)
- Patrícia Shu Kurizky
- Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, Brazil
- Hospital Universitário de Brasília, Brasília, Brazil
- Universidade de Brasília, Faculdade de Medicina, Grupo de Diagnóstico Dermatológico, Brasília, Brazil
- Universidade de Brasília, Faculdade de Medicina, Laboratório de Dermatomicologia, Brasília, Brazil
| | | | - Mariana Vicente Cesetti
- Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, Brazil
| | - Giovanni Damiani
- Case Western Reserve University, Department of Dermatology, Cleveland, Ohio, USA
- IRCCS Istituto Ortopedico Galeazzi, Dermatologia Clinica, Milan, Italy
- Università degli Studi di Milano, Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Milan, Italy
| | - Raimunda Nonata Ribeiro Sampaio
- Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, Brazil
- Universidade de Brasília, Faculdade de Medicina, Grupo de Diagnóstico Dermatológico, Brasília, Brazil
- Universidade de Brasília, Faculdade de Medicina, Laboratório de Dermatomicologia, Brasília, Brazil
- Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, Brasília, Brazil
| | | | | | - Sofia Sales Martins
- Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, Brasília, Brazil
| | - Sebastian Vernal
- Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Clínica Médica, Programa de Pós-Graduação em Clínica Médica, Ribeirão Preto, São Paulo, Brazil
| | - Licia Maria Henrique da Mota
- Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, Brazil
- Hospital Universitário de Brasília, Brasília, Brazil
| | - Ciro Martins Gomes
- Universidade de Brasília, Faculdade de Medicina, Programa de Pós-Graduação em Ciências Médicas, Brasília, Brazil
- Hospital Universitário de Brasília, Brasília, Brazil
- Universidade de Brasília, Faculdade de Medicina, Grupo de Diagnóstico Dermatológico, Brasília, Brazil
- Universidade de Brasília, Faculdade de Medicina, Laboratório de Dermatomicologia, Brasília, Brazil
- Universidade de Brasília, Faculdade de Medicina, Núcleo de Medicina Tropical, Programa de Pós-Graduação em Medicina Tropical, Brasília, Brazil
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29
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Heinemann M, Omansen TF, Hennigs A, Völker K, Menz A, Addo MM, Schmiedel S. Relapsing cutaneous leishmaniasis in a patient requiring TNF-α-inhibitor Infliximab for Takayasu-arteritis: Case report and review of the literature. Travel Med Infect Dis 2020; 37:101700. [PMID: 32339673 DOI: 10.1016/j.tmaid.2020.101700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 04/23/2020] [Indexed: 12/14/2022]
Abstract
Leishmaniasis is a protozoan parasitic infection that can manifest as visceral or cutaneous disease. Immunosuppression, mainly through TNF-α) inhibition, is a risk factor for complicated leishmaniasis that is becoming increasingly known. Here, we present a case of cutaneous leishmaniasis (CL) in a patient who suffers from advanced Takayasu-Arteritis, requiring TNF-α inhibition with infliximab. The primary CL lesions in this 47-year-old, female patient were caused by Leishmaniapanamensis and occurred after a touristic trip to Panama on her right foot. The lesions first resolved under treatment with liposomal amphotericin B. However, ten months later, the patient returned with relapsing lesions requiring further treatment. We discuss the challenges and risks of leishmaniasis in patients with TNF-α inhibition and the rare phenomenon of relapsing CL and the management hereof. We review published cases of CL associated with TNF-α inhibition. A growing body of evidence now suggests that especially CL (and visceral leishmaniasis (VL)) can be associated with TNF-α inhibition. The host response to leishmaniasis is of the Th1-type and TNF-α and interferon-gamma expression are crucial for disease control. Inversely, TNF-α inhibition can lead to complicated and relapsing progression of leishmanial infection. Therefore, we propose that CL and VL should be considered in at-risk patients receiving immunosuppressants.
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Affiliation(s)
- Melina Heinemann
- I. Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till F Omansen
- Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
| | - Annette Hennigs
- I. Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Katrin Völker
- Department of Tropical Medicine at the Bernhard Nocht Institute, German Armed Forces Hospital of Hamburg, Hamburg, Germany
| | - Anne Menz
- Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Marylyn M Addo
- I. Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Schmiedel
- I. Department of Medicine, Division of Infectious Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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30
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Kim BS, Maverakis E, Alexanian C, Wang JZ, Raychaudhuri SP. Incidence, Clinical Features, Management, and Prevention of Herpes Zoster in Patients Receiving Antitumor Necrosis Factor Therapy: A Clinical Review. J Cutan Med Surg 2020; 24:278-284. [PMID: 32238066 PMCID: PMC7238506 DOI: 10.1177/1203475420914622] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Tumor necrosis factor (TNF) inhibitors have been used as an excellent therapeutic option in a variety of chronic inflammatory conditions. However, a recognized significant adverse effect of TNF inhibitor therapy is the increased risk of infections. The influence of TNF inhibitors on the course of coexisting or newly developed viral infections has not been extensively investigated. Therefore, we reviewed the recent publications to highlight the incidence, clinical features, management, and prevention of herpes zoster in patients who are receiving TNF inhibitors.
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Affiliation(s)
- Byung-Soo Kim
- 34996 Department of Dermatology, Pusan National University College of Medicine, Busan, Korea.,Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Emanual Maverakis
- 481070 Department of Dermatology, University of California School of Medicine, Davis, CA, USA
| | - Clarie Alexanian
- 481070 Department of Dermatology, University of California School of Medicine, Davis, CA, USA.,Georgetown University School of Medicine, Washington, DC, USA
| | - Jenny Z Wang
- 481070 Department of Dermatology, University of California School of Medicine, Davis, CA, USA
| | - Siba P Raychaudhuri
- 156053 VA Medical Center Sacramento, Division of Rheumatology & Immunology, Mather, CA, USA.,12218 Division of Rheumatology, Allergy & Clinical immunology, University of California School of Medicine, Davis, CA, USA
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Safety results of ixekizumab with 1822.2 patient-years of exposure: an integrated analysis of 3 clinical trials in adult patients with psoriatic arthritis. Arthritis Res Ther 2020; 22:14. [PMID: 31964419 PMCID: PMC6975022 DOI: 10.1186/s13075-020-2099-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 01/09/2020] [Indexed: 02/08/2023] Open
Abstract
Background The long-term safety was assessed in patients with psoriatic arthritis who were treated with ixekizumab in three clinical trials (SPIRIT-P1/-P2/-P3). Methods Integrated safety data from three trials (controlled and uncontrolled), including two pivotal phase 3, randomized, double-blind clinical trials: SPIRIT-P1 and SPIRIT-P2, were assessed. Safety data were integrated from the all ixekizumab exposure safety population (defined as all patients receiving ≥ 1 dose of ixekizumab). We report exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) at 1-year intervals up to 3 years for adverse events. Results Total exposure to IXE reached 1822.2 PY (1118 patients). The IRs/100 PY for the following treatment discontinuations were as follows: adverse events (5.3); serious infections (1.3); injection-site reactions (12.7); infections (34.2); and deaths (0.3). The IRs for treatment-emergent adverse events decreased or remained stable over time, the most common being upper respiratory tract infection, nasopharyngitis, and injection-site reactions. The IRs for serious adverse events and serious infections remained stable over time, whereas for injection-site reactions and general infections, IRs decreased with longer ixekizumab exposure. Opportunistic infections were limited to oral and esophageal candida and localized herpes zoster. No suicide or self-injury-related behaviors were reported. The IRs/100 PY for safety topics of special interest included inflammatory bowel disease (adjudicated; 0.1), depression (1.6), malignancies (0.7), and major adverse cardiovascular events (0.6). Conclusions The findings of this integrated safety analysis in patients with psoriatic arthritis are consistent with the known safety profile of ixekizumab. No unexpected safety signals were observed with ixekizumab treatment in patients with psoriatic arthritis. Trial registration SPIRIT-P1 (NCT01695239; Registered August 08, 2012), SPIRIT-P2 (NCT02349295; September 23, 2014), and SPIRIT-P3 (NCT02584855; August 04, 2015).
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Burmester GR, Gordon KB, Rosenbaum JT, Arikan D, Lau WL, Li P, Faccin F, Panaccione R. Long-Term Safety of Adalimumab in 29,967 Adult Patients From Global Clinical Trials Across Multiple Indications: An Updated Analysis. Adv Ther 2020; 37:364-380. [PMID: 31748904 PMCID: PMC6979455 DOI: 10.1007/s12325-019-01145-8] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Indexed: 12/17/2022]
Abstract
INTRODUCTION The safety profile of adalimumab was previously reported in 23,458 patients across multiple indications. Here we report the long-term safety of adalimumab in adults with plaque psoriasis (Ps), hidradenitis suppurativa (HS), rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, non-radiographic axial spondyloarthritis, peripheral spondyloarthritis, Crohn's disease (CD), ulcerative colitis (UC), and non-infectious uveitis (UV). METHODS Safety data from 77 clinical trials were pooled. Safety assessments included adverse events (AEs) and serious AEs (SAEs) that occurred after the first study dose and within 70 days (5 half-lives) after the last study dose. RESULTS A total of 29,967 patients were included, representing 56,916 patient-years (PY) of exposure. The most frequently reported SAE of interest was infection (3.7/100 PY) with highest incidences in CD, RA, UV, and UC (3.5/100 PY-6.9/100 PY); serious infections in Ps (1.8/100 PY) and HS (2.8/100 PY) were lower. The observed number of deaths was below what would be expected in an age- and sex-adjusted population for most adalimumab-treated patients (including Ps). Lack of real-life data and limited long-term data (> 5 years) for most patients are limitations of this analysis. CONCLUSION The safety profile of adalimumab was consistent with previous findings and no new safety signals were observed.
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Affiliation(s)
| | | | - James T Rosenbaum
- Oregon Health and Science University and Legacy Devers Eye Institute, Portland, OR, USA
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Leon L, Peñuelas M, Candel FJ, Freites D, Rodriguez-Rodriguez L, Fernandez-Gutierrez B, Jover JA, Abasolo L. Indicator opportunistic infections after biological treatment in rheumatoid arthritis, 10 years follow-up in a real-world setting. Ther Adv Musculoskelet Dis 2019; 11:1759720X19878004. [PMID: 31636721 PMCID: PMC6783660 DOI: 10.1177/1759720x19878004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 08/30/2019] [Indexed: 12/26/2022] Open
Abstract
Background: This research describes the incidence and factors associated with
opportunistic infections in rheumatoid arthritis (RA) patients treated with
biological disease-modifying antirheumatic drugs (bDMARDs). Methods: A retrospective longitudinal study was carried out from 2007 to 2018. We
included RA patients treated with a tumor necrosis factor (TNF)-targeted
bDMARD or non-TNF-targeted bDMARD from the start of bDMARDs. An independent
variable was the development of an indicator of opportunistic infection
after biological (IOIb) treatment. Secondary variables included
sociodemographic, clinical, and treatments. We used survival techniques to
estimate the incidence of IOIb, per 1000 patient-years (95% CI). We
performed a Cox multivariate regression analysis model to compare the risk
of IOIb. Results were expressed as a hazard ratio (HR). Results: A total of 441 RA patients were included, that started 761 different courses
of bDMARDs. A total of 81% were women with a mean age at first bDMARD of
57.3 ± 14 years. A total of 71.3% of the courses were TNF-targeted bDMARDs
and 28.7% were non-TNF-targeted bDMARDs. There were 37 IOIb (25 viral, 6
fungal, 5 bacterial, 1 parasitic). Nine of these required hospitalization
and one died. The global incidence of IOIb was 23.2 (16.8–32). TNF-targeted
bDMARDs had 25 IOIb, incidence 20.5 (13.9–30.4), and non-TNF-targeted
bDMARDs had 12 IOIb, incidence 31.7 (18–55.9). In the multivariate analysis,
glucocorticosteroids (HR 2.17, p = 0.004) and lower
lymphocyte count increased the risk for IOIb (HR 0.99,
p = 0.005). Conclusions: The incidence of IOIb due to bDMARDs was 23 cases per 1000 patient-years.
Close monitoring should be taken in the RA patients treated with bDMARDs and
glucocorticosteroids, mainly in elderly patients and those with a low total
lymphocyte count at the beginning of bDMARD treatment.
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Affiliation(s)
- Leticia Leon
- Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IDISSC), Hospital Clínico San Carlos, Calle Martín Lagos, s/n, Madrid, 28040, Spain
| | - Marina Peñuelas
- Clinical Microbiology and Infectious Diseases Department and IDISSC, Hospital Clínico San Carlos, Madrid, Spain
| | - Francisco Javier Candel
- Clinical Microbiology and Infectious Diseases Department and IDISSC, Hospital Clínico San Carlos, Madrid, Spain
| | - Dalifer Freites
- Rheumatology Department and IDISSC, Hospital Clínico San Carlos, Madrid, Spain
| | | | | | - Juan Angel Jover
- Rheumatology Department and IDISSC, Hospital Clínico San Carlos, Madrid, Spain
| | - Lydia Abasolo
- Rheumatology Department and IDISSC, Hospital Clínico San Carlos, Madrid, Spain
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Bilal J, Berlinberg A, Riaz IB, Faridi W, Bhattacharjee S, Ortega G, Murad MH, Wang Z, Prokop LJ, Alhifany AA, Kwoh CK. Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors: A Systematic Review and Meta-analysis. JAMA Netw Open 2019; 2:e1913102. [PMID: 31626313 PMCID: PMC6813598 DOI: 10.1001/jamanetworkopen.2019.13102] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
IMPORTANCE The safety profile of interleukin (IL) inhibitors is not well established. OBJECTIVE To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors. DATA SOURCES Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus were searched (inception to November 30, 2018). STUDY SELECTION Randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic diseases and reported safety data were included in the analyses. DATA EXTRACTION AND SYNTHESIS This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two investigators independently extracted study data and assessed risk of bias and certainty in the evidence. Fixed-effects meta-analysis was conducted to pool odds ratios (ORs) for serious infections, opportunistic infections, and cancers for IL inhibitors vs placebo. MAIN OUTCOMES AND MEASURES The outcomes of interest were the number of serious infections, opportunistic infections, and cancers in individuals receiving IL inhibitor therapies compared with placebo. RESULTS In this meta-analysis, 74 studies comprising 29 214 patients (24 236 patients for serious infections, 9998 for opportunistic infections, and 21 065 for cancer [number of patients overlaps for each outcome]) were included. Patients receiving IL inhibitors had a higher risk of serious infections (OR, 1.97; 95% CI, 1.58-2.44; P < .001, I2 = 0%; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P = .03, I2 = 0%; moderate certainty), and cancer (OR, 1.52; 95% CI, 1.05-2.19; P = .03, I2 = 11%; moderate certainty). CONCLUSIONS AND RELEVANCE The risk of serious infections, opportunistic infections, and cancer appears to be increased in patients with rheumatologic diseases who are treated with IL inhibitors compared with placebo.
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Affiliation(s)
- Jawad Bilal
- Division of Rheumatology, Department of Medicine, University of Arizona, Tucson
| | - Adam Berlinberg
- Division of Rheumatology, Department of Medicine, University of Colorado, Denver
| | - Irbaz Bin Riaz
- Division of Hematology/Oncology, Department of Medicine, Mayo Clinic Rochester, Rochester, Minnesota
| | - Warda Faridi
- Division of Hematology/Oncology, Department of Medicine, University of Arizona, Tucson
| | - Sandipan Bhattacharjee
- College of Pharmacy, Department of Pharmacy Practice and Science, University of Arizona, Tucson
| | | | - Mohammad H. Murad
- Evidence-Based Practice Center, Mayo Clinic Rochester, Rochester, Minnesota
| | - Zhen Wang
- Evidence-Based Practice Center, Mayo Clinic Rochester, Rochester, Minnesota
| | - Larry J. Prokop
- Mayo Clinic Libraries, Mayo Clinic Rochester, Rochester, Minnesota
| | - Abdullah A. Alhifany
- College of Pharmacy, Department of Clinical Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - C. Kent Kwoh
- Division of Rheumatology, Department of Medicine, University of Arizona, Tucson
- University of Arizona Arthritis Center, University of Arizona, Tucson
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Watanabe N, Saito K, Kiritani A, Fujimoto S, Yamanaka Y, Fujisaki I, Hosoda C, Miyagawa H, Seki Y, Kinoshita A, Takeda H, Endo Y, Kuwano K. A case of invasive pulmonary aspergillosis diagnosed by transbronchial lung biopsy during treatment for diabetic ketoacidosis in a type 1 diabetic patient. J Infect Chemother 2019; 26:274-278. [PMID: 31542205 DOI: 10.1016/j.jiac.2019.08.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 07/26/2019] [Accepted: 08/16/2019] [Indexed: 10/26/2022]
Abstract
Invasive pulmonary aspergillosis (IPA) patients with non-hematological malignancy are far less than with hematological malignancy patients. We encountered a very rare case of IPA in which type 1 diabetes was the only conceivable risk factor. Further, according to the diagnostic categories of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria for IPA, the frequency of proven diagnosis is very low. Here we report a proven IPA, which rapidly developed when the patient with type 1 diabetes was being treated for diabetic ketoacidosis, which was successfully treated with the combination therapy of voriconazole (VRCZ) and micafungin (MCFG), based on early diagnosis using bronchoscopy.
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Affiliation(s)
- Naoaki Watanabe
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan.
| | - Keisuke Saito
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Ayu Kiritani
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Shota Fujimoto
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Yumie Yamanaka
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Ikumi Fujisaki
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Chiaki Hosoda
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Hanae Miyagawa
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Yoshitaka Seki
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Akira Kinoshita
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Hiroshi Takeda
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Yasuhiko Endo
- Department of Pathology, The Jikei University Daisan Hospital, Tokyo, Japan
| | - Kazuyoshi Kuwano
- Division of Respiratory Medicine, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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Infectious adverse events in children with Juvenile Idiopathic Arthritis treated with Biological Agents in a real-life setting: Data from the JIRcohorte. Joint Bone Spine 2019; 87:49-55. [PMID: 31369865 DOI: 10.1016/j.jbspin.2019.07.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 07/17/2019] [Indexed: 12/29/2022]
Abstract
OBJECTIVES The main objective of our study is to assess the infectious adverse events occurring in juvenile idiopathic arthritis (JIA) children treated with biological agents. METHODS Patients were selected from the retrospective module of the JIRcohorte, data concerning the period between January 2001 and August 2015. All infectious adverse events (IAE) were retrieved. For every infectious side effect, the date, the severity, the need for a hospitalization, the type of pathogen and the affected organ were noted. Incidence rates were expressed in number of events per 100 person-years (100p-y), and OR were calculated. RESULTS Six hundred seventy-seven patients with JIA were included in the study. A total of 3075.4 person-years of exposure were analyzed. One hundred eighty-four infectious events were described (6.0 events/100 p-y): 15.5/100 p-y with tocilizumab (TCZ), 9.6/100 p-y with Canakinumab (CAN), 7.4/100 p-y with abatacept (ABA), 6.9/100 p-y with Golimumab (GOL), 6.7/100 p-y with Anakinra (ANA), 6.3/100 p-y with Infliximab, 4.8/100 p-y with Etanercept, and 3.7/100 p-y with Adalimumab. Risk of developing an infection was significantly higher with IL-6 antagonists or IL-1 antagonists than with TNF-inhibitor. Forty point eight percent of the infectious adverse events (IAE) affected the upper respiratory tract or the Ear, nose and throat (ENT) system. Twelve infectious adverse events were described as severe or very severe (0.4/100p-y). No case of tuberculosis or death was reported. CONCLUSION Infectious complications with biologics occurring in children treated for JIA are rare, and in most of the cases have a mild or moderate severity, affecting mainly the upper respiratory tract or the ENT.
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Kim H, Cho S, Lee J, Bae S, Sung Y. Increased risk of opportunistic infection in early rheumatoid arthritis. Int J Rheum Dis 2019; 22:1239-1246. [DOI: 10.1111/1756-185x.13585] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 02/13/2019] [Accepted: 03/18/2019] [Indexed: 01/05/2023]
Affiliation(s)
- Hyoungyoung Kim
- Department of Rheumatology Hanyang University Hospital for Rheumatic Diseases Seoul Korea
| | - Soo‐Kyung Cho
- Department of Rheumatology Hanyang University Hospital for Rheumatic Diseases Seoul Korea
- Clinical Research Center for Rheumatoid Arthritis (CRCRA) Hanyang University Seoul Korea
| | - Jiyoung Lee
- Clinical Research Center for Rheumatoid Arthritis (CRCRA) Hanyang University Seoul Korea
| | - Sang‐Cheol Bae
- Department of Rheumatology Hanyang University Hospital for Rheumatic Diseases Seoul Korea
- Clinical Research Center for Rheumatoid Arthritis (CRCRA) Hanyang University Seoul Korea
| | - Yoon‐Kyoung Sung
- Department of Rheumatology Hanyang University Hospital for Rheumatic Diseases Seoul Korea
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Wu XN, Lightman S, Tomkins‐Netzer O. Viral retinitis: diagnosis and management in the era of biologic immunosuppression: A review. Clin Exp Ophthalmol 2019; 47:381-395. [DOI: 10.1111/ceo.13500] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 02/08/2019] [Accepted: 02/18/2019] [Indexed: 12/19/2022]
Affiliation(s)
- Xia Ni Wu
- Ophthalmology, Moorfields Eye Hospital London UK
- Faculty of Brain Sciences, Institute of Ophthalmology London UK
| | - Sue Lightman
- Ophthalmology, Moorfields Eye Hospital London UK
- Faculty of Brain Sciences, Institute of Ophthalmology London UK
| | - Oren Tomkins‐Netzer
- Ophthalmology, Moorfields Eye Hospital London UK
- Faculty of Brain Sciences, Institute of Ophthalmology London UK
- Department of OphthalmologyBnai Zion Medical Centre Haifa Israel
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Danion F, Rouzaud C, Duréault A, Poirée S, Bougnoux ME, Alanio A, Lanternier F, Lortholary O. Why are so many cases of invasive aspergillosis missed? Med Mycol 2019; 57:S94-S103. [PMID: 30816963 DOI: 10.1093/mmy/myy081] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 08/10/2018] [Indexed: 12/20/2022] Open
Abstract
Invasive aspergillosis (IA) incidence is increasing in several countries like France, and numerous cases are indeed missed and still only diagnosed at autopsy as evidenced by recently published data. Such missed diagnoses are obviously encountered when appropriate diagnostic tools are not available especially in low resource areas or when biologists have not been trained enough in medical mycology (i.e., microscopic examination and culture in most of those areas). Besides logistical issues, which are indeed critical, IA may not be recognized because clinicians failed to consider that risk factors are evolving with the IA burden now observed among patients with chronic lymphoid malignancies or receiving new biotherapies, with diabetes mellitus or liver cirrhosis and/or acute alcoholic hepatitis, with patients from the intensive care unit (ICU) and among patients with some predisposing primary immune deficiencies now reaching the adult's age. This is also the case for human immunodeficiency virus (HIV)-infected patients who failed to meet the classical definitions of IA. From the radiology perspective, new entities of IA have also emerged which absolutely need to be recognized especially bronchial-based-IA among allogeneic stem cell transplant recipients. Finally, from the laboratory side, contribution and limits of indirect blood biomarkers should be integrated to the clinical life in order not to miss IA cases. To conclude, several diagnostic tools should be combined and a constant dialog between laboratory and clinics is crucial to appropriately diagnose IA.
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Affiliation(s)
- François Danion
- Department of Infectious Diseases and Tropical Medicine, Necker-Pasteur Infectious Diseases Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut Imagine, Paris Descartes University, Paris, France.,Aspergillus Unit, Institut Pasteur, Paris, France
| | - Claire Rouzaud
- Department of Infectious Diseases and Tropical Medicine, Necker-Pasteur Infectious Diseases Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut Imagine, Paris Descartes University, Paris, France
| | - Amélie Duréault
- Department of Infectious Diseases and Tropical Medicine, Necker-Pasteur Infectious Diseases Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut Imagine, Paris Descartes University, Paris, France
| | - Sylvain Poirée
- Department of Radiology, Necker-Enfants Malades University Hospital, AP-HP, Paris Descartes University, Paris, France
| | - Marie-Elisabeth Bougnoux
- Department of Mycology, Necker-Enfants Malades University Hospital, AP-HP, Paris Descartes University, Paris, France
| | - Alexandre Alanio
- National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, Institut Pasteur, Paris, France.,Department of Mycology, Saint-Louis Hospital, AP-HP, Paris, France
| | - Fanny Lanternier
- Department of Infectious Diseases and Tropical Medicine, Necker-Pasteur Infectious Diseases Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut Imagine, Paris Descartes University, Paris, France.,National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, Institut Pasteur, Paris, France
| | - Olivier Lortholary
- Department of Infectious Diseases and Tropical Medicine, Necker-Pasteur Infectious Diseases Center, Necker-Enfants Malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut Imagine, Paris Descartes University, Paris, France.,National Reference Center for Invasive Mycoses and Antifungals, Molecular Mycology Unit, Institut Pasteur, Paris, France
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Diagnostic Dilemma of Disseminated Histoplasmosis Mimicking Hemophagocytosis Lymphohistiocytosis in Patient with Rheumatoid Arthritis on Anti-TNF Therapy: Case Report and Review of the Literature. Case Rep Rheumatol 2019; 2019:4169052. [PMID: 30891325 PMCID: PMC6390234 DOI: 10.1155/2019/4169052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 01/31/2019] [Indexed: 11/30/2022] Open
Abstract
Tumor necrosis factor inhibitors (TNFi) have become the cornerstone for the treatment of rheumatoid arthritis and other systemic autoimmune conditions. However, these biologic DMARDs can lead to various opportunistic infections such as viral infection, tuberculosis, and histoplasmosis. Furthermore, these biologics can also cause severe systemic inflammatory reactions known as hemophagocytosis lymphohistiocytosis (HLH) that can lead to multiorgan failure and high mortality. Due to overlapping clinical features and time-intensive microbiological culture methods, distinguishing between HLH and opportunistic infections can be challenging early in the disease course. We present a similar situation with our patient where the patient met the diagnostic criteria for HLH however was found to have disseminated histoplasmosis. This case uniquely evaluates the utility of the HLH diagnostic criteria and hemophagocytosis for accurate diagnosis of HLH.
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Beaugerie L, Kirchgesner J. Balancing Benefit vs Risk of Immunosuppressive Therapy for Individual Patients With Inflammatory Bowel Diseases. Clin Gastroenterol Hepatol 2019; 17:370-379. [PMID: 30031174 DOI: 10.1016/j.cgh.2018.07.013] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2018] [Revised: 06/28/2018] [Accepted: 07/04/2018] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel diseases (IBD) and their treatments, particularly immunosuppressive drugs, increase risk of infections and cancers. However, by promoting mucosal healing, these agents should reduce risks of infections related to intestinal lesions, malnutrition, intravenous devices, and IBD surgeries and reduce risk of cancers associated with chronic mucosal inflammation-although there are few data to support this concept. Corticosteroids increase the risk of vascular thromboembolic events, yet other immunosuppressive drugs that induce deep remission from IBD could decrease the incidence of cardiovascular events attributable to systemic inflammation and IBD-related hospitalizations and/or surgeries. The nature and magnitude of the risks of infections and cancers vary with immunosuppressive drug class and patient sex and age. For example, thiopurines increase risk of viral infections that might be fatal in young patients, whereas tumor necrosis factor antagonists increase risk of bacterial and intracellular infections that can be fatal in patients of any age, but particularly in older patients. The ability of drugs to prevent IBD-associated colorectal cancer varies with IBD location and duration. Models to assess the benefit:risk ratio of long-term use of immunosuppressive drugs for patients with IBD should be adapted based on patients' age, sex, and IBD phenotype, to properly guide patient management. The decision-making process should begin with a clear explanation of treatment risks and then integrate the patient's emotional perception of risks.
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Affiliation(s)
- Laurent Beaugerie
- Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine F-75012 and GRC-UPMC 03, Sorbonne Université, Paris, France.
| | - Julien Kirchgesner
- Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine F-75012 and GRC-UPMC 03, Sorbonne Université, Paris, France
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Saddler K, Castro-Lainez MT, Deliz-Aguirre R, Muñoz J, Aguilar Espinal JA, Sierra-Hoffman M, Chandna H, Howel A, Midturi J, Winn R. Nontyphoidal Salmonella purulent pericarditis presenting with pericardial tamponade in a patient on infliximab therapy. IDCases 2019; 15:e00500. [PMID: 30788216 PMCID: PMC6370545 DOI: 10.1016/j.idcr.2019.e00500] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 01/28/2019] [Accepted: 01/28/2019] [Indexed: 12/15/2022] Open
Abstract
Infection with nontyphoidal Salmonella is traditionally characterized by intestinal manifestations. However, extra-intestinal infections are known to occur, with purulent pericarditis associated with cardiac tamponade being rare. This case report is of a 57-year-old male with Crohn's disease initiated on infliximab therapy two months prior to presentation. He presented with recurrent chest pain and a single occurrence of fever. A Computed Tomography (CT) scan of the chest revealed a pericardial effusion. An echocardiogram confirmed the presence of the fluid with tamponade physiology, requiring immediate surgical decompression. The pericardial fluid culture grew Salmonella enterica, despite the patient having only a single episode of fever, disproportionate to the severity of the infection. Conceivably, the lack of systemic symptoms may be attributed to recent infliximab therapy. Upon conducting a literature review, immunosuppressive factors seem to play a significant role in nontyphoid Salmonella enterica pericardial effusion presenting with cardiac tamponade.
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Affiliation(s)
- Kimberly Saddler
- DeTar Healthcare System, 506 E San Antonio St, Victoria, TX, 77901, United States
| | - Miriams T Castro-Lainez
- Universidad Nacional Autónoma de Honduras, Facultad de Ciencias Médicas, Hospital Escuela Universitario, Boulevard Suyapa, Tegucigalpa, Honduras
| | - Rafael Deliz-Aguirre
- Department of Biology & Chemistry, Texas A&M International University, 5201 University Blvd, Laredo, TX, 78045, United States
| | - Julieta Muñoz
- Loyola Medicine MacNeal Hospital, 3249 S Oak Park Ave Berwyn, IL, 60402, United States
| | | | - Miguel Sierra-Hoffman
- Department of Infectious Disease, Citizens Medical Center, 2701 Hospital Dr, Victoria, TX 77901, United States
| | - Harish Chandna
- Department of Cardiology, DeTar Healthcare System, 506 E. San Antonio, Victoria, TX, 77901, United States
| | - Alan Howel
- Baylor Scott & White Health- Temple, 2401 South 31 Street, Temple, TX, 76508, United States
| | - John Midturi
- Baylor Scott & White Health- Temple, 2401 South 31 Street, Temple, TX, 76508, United States
| | - Richard Winn
- Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, United States
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43
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Duquenne L, Gul H, Emery P. Safety evaluation of adalimumab in immune-mediated inflammatory disorders: a rheumatological point of view. Expert Opin Drug Saf 2018; 18:11-19. [PMID: 30444672 DOI: 10.1080/14740338.2018.1549541] [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: 10/27/2022]
Abstract
INTRODUCTION Immune-mediated inflammatory disorders (IMIDs) are systemic conditions which arise secondary to complex immune mechanism defects and can affect many organs. While previous therapies based on steroids and immunosuppressive agents had a poor risk/benefit balance, TNFα-specific inhibitors such as adalimumab have revolutionized the course of many diseases and patient outcomes. However, concerns were raised regarding the increased risk of infectious diseases and neoplasia due to potential prospective loss of immune control. This is especially true when considering that IMIDs concerns elderly/frail populations, with multiple co-morbidities, organ damage and often long-term steroid therapy. Areas covered: Now prescribed for more than 15 years for a diverse range of indications, long-term data highlighting the efficacy and safety are available and led to recommendations for the daily practice that will be discussed. Expert opinion: The efficacy of adalimumab changed the therapeutic paradigm of many diseases. Its tolerance is good and it is the most widely prescribed therapy in IMIDs. It is now the standard of care arm in head to head trials. In the long term, adalimumab dominant role might be weakened by more targeted therapies but its varied indications among IMIDs should secure its position as an important tool in our future practice.
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Affiliation(s)
- Laurence Duquenne
- a Leeds Institute of Rheumatic & Musculoskeletal Medicine , University of Leeds , Leeds , UK.,b NIHR Leeds Biomedical Research Centre , The Leeds Teaching Hospitals Trust , Leeds , UK
| | - Hanna Gul
- a Leeds Institute of Rheumatic & Musculoskeletal Medicine , University of Leeds , Leeds , UK.,b NIHR Leeds Biomedical Research Centre , The Leeds Teaching Hospitals Trust , Leeds , UK
| | - Paul Emery
- a Leeds Institute of Rheumatic & Musculoskeletal Medicine , University of Leeds , Leeds , UK.,b NIHR Leeds Biomedical Research Centre , The Leeds Teaching Hospitals Trust , Leeds , UK
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Rotjanapan P, Chen YC, Chakrabarti A, Li RY, Rudramurthy SM, Yu J, Kung HC, Watcharananan S, Tan AL, Saffari SE, Tan BH. Epidemiology and clinical characteristics of invasive mould infections: A multicenter, retrospective analysis in five Asian countries. Med Mycol 2018; 56:186-196. [PMID: 28525619 DOI: 10.1093/mmy/myx029] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Accepted: 04/03/2017] [Indexed: 12/12/2022] Open
Abstract
Formal, large-scale, multicenter studies of invasive mould infection (IMI) in Asia are rare. This 1-year, retrospective study was designed to assess the incidence and clinical determinants of IMI in centers in five countries (Thailand, Taiwan, Singapore, China, India). Patients treated in a single year (2012) were identified through discharge diagnoses, microbiology, and histopathology logs, and entered based on published definitions of IMI. A total of 155 cases were included (median age 54 years; 47.7% male). Of these, 47.7% had proven disease; the remainder had probable IMI. The most frequent host factors were prolonged steroid use (39.4%) and recent neutropenia (38.7%). Common underlying conditions included diabetes mellitus (DM; 30.9%), acute myeloid leukemia (19.4%), and rheumatologic conditions (11.6%). DM was more common in patients with no recent history of neutropenia or prolonged steroid use (P = .006). The lung was the most frequently involved site (78.7%), demonstrating a range of features on computed tomography (CT). Aspergillus was the most common mould cultured (71.6%), primarily A. fumigatus and A. flavus, although proportions varied in different centers. The most often used antifungal for empiric therapy was conventional amphotericin. Ninety-day mortality was 32.9%. This is the first multicenter Asian study of IMI not limited to specific patient groups or diagnostic methods. It suggests that DM and rheumatologic conditions be considered as risk factors for IMI and demonstrates that IMI should not be ruled out in patients whose chest features on CT do not fit the conventional criteria.
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Affiliation(s)
- P Rotjanapan
- Division of Infectious Diseases, Ramathibodi Hospital, Bangkok, Thailand
| | - Y C Chen
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - A Chakrabarti
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - R Y Li
- Department of Dermatology, Peking University First Hospital, Beijing, China
| | - S M Rudramurthy
- Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - J Yu
- Department of Dermatology, Peking University First Hospital, Beijing, China
| | - H C Kung
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - S Watcharananan
- Division of Infectious Diseases, Ramathibodi Hospital, Bangkok, Thailand
| | - A L Tan
- Department of Pathology, Singapore General Hospital, Singapore, Singapore
| | - S E Saffari
- Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore
| | - B H Tan
- Department of Infectious Disease, Singapore General Hospital, Singapore, Singapore
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Wroński J, Fiedor P. The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought? J Clin Pharmacol 2018; 59:445-462. [PMID: 30476367 DOI: 10.1002/jcph.1348] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 10/27/2018] [Indexed: 12/12/2022]
Abstract
Tumor necrosis factor (TNF) inhibitors significantly improved the treatment options for patients with ankylosing spondylitis. Unfortunately, currently, there is no strategy for sustaining remission of the disease with TNF inhibitors; after discontinuation, a high percentage of patients experience flares in a short time. Therefore, up-to-date, long-term use of TNF inhibitors in patients with ankylosing spondylitis remains necessary. For this reason, the issue of the long-term safety of TNF inhibitors in patients with ankylosing spondylitis raises concerns. Although TNF inhibitors are well established in ankylosing spondylitis treatment, the majority of studies on TNF inhibitors' safety have been performed in patients with rheumatoid arthritis. Until recently, there were very few studies of TNF inhibitors' safety in ankylosing spondylitis. Meanwhile, TNF inhibitors appear to have different safety profiles in ankylosing spondylitis and rheumatoid arthritis. In this review, we describe available data on the occurrence of adverse events associated with TNF inhibitor treatment in ankylosing spondylitis, including serious adverse events, infections, serious infections, tuberculosis, opportunistic infections, hepatitis B reactivation, malignancies, laboratory test abnormalities, autoimmune diseases, paradoxical adverse events, and heart failure.
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Affiliation(s)
- Jakub Wroński
- Department of Rheumatology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.,Department of Disaster Medicine, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Fiedor
- Department of General and Transplantation Surgery, Medical University of Warsaw, Warsaw, Poland
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Fernández-Ruiz M, Aguado JM. Risk of infection associated with anti-TNF-α therapy. Expert Rev Anti Infect Ther 2018; 16:939-956. [PMID: 30388900 DOI: 10.1080/14787210.2018.1544490] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
INTRODUCTION The advent, more than two decades ago, of monoclonal antibodies and soluble receptors targeting tumor necrosis factor (TNF)-α has revolutionized the therapeutic approach to otherwise difficult-to-treat autoimmune and inflammatory diseases. However, due to the pleiotropic functions played by this pro-inflammatory cytokine (with particular relevance in granuloma maintenance), TNF-α blockade may increase the incidence of serious infections. Areas covered: The present review summarizes the biological rationale supporting the impact of anti-TNF-α therapy on the host's susceptibility to infection. The structure, mode of action, and indications of available agents are reviewed, as well as the clinical evidence coming from clinical trials and observational registries. We discuss the impact of patient- and disease-related factors influencing the occurrence of infection. Finally, strategies for risk minimization are also covered, with particular attention to recommendations for screening of latent tuberculosis infection and management of chronic hepatitis B infection. Expert commentary: Methodological limitations (confounding by indication bias, patient dropout, or switching therapies) should be considered when interpreting observational data. Clinicians must individualize the infection risk assessment not only on the basis of the specific anti-TNF-α agent used or the expected duration of therapy, but also by taking into account the baseline susceptibility of a given patient.
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Affiliation(s)
- Mario Fernández-Ruiz
- a Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine , Universidad Complutense , Madrid , Spain.,b Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0002) , Instituto de Salud Carlos III , Madrid , Spain
| | - José María Aguado
- a Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), School of Medicine , Universidad Complutense , Madrid , Spain.,b Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0002) , Instituto de Salud Carlos III , Madrid , Spain
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Noreña I, Fernández-Ruiz M, Aguado JM. Viral infections in the biologic therapy era. Expert Rev Anti Infect Ther 2018; 16:781-791. [PMID: 30198355 DOI: 10.1080/14787210.2018.1521270] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The development of biologic therapies for treating patients with rheumatic, hematologic, or oncological diseases has increased in the last few years, spreading their use in clinical practice. Areas covered: Clinical experience has evidenced substantial risks for some viral infections and/or reactivations such as viral hepatitis, herpetic infections, and other viruses, as a consequence of specific immune pathway blockages. Biological therapies produce a variable risk of reactivation of viral infections, which is particularly uncertain in the case of the most recently introduced agents. Here we make an extensive review of the viral infections associated with the use of biological drugs and provide a series of recommendations for its prevention and management. Expert commentary: To prevent these infections/reactivations, the practitioner must be aware of the infection-risk profile, performing accurate screening during and after the use of any biologic agent. In some instances, expert recommendations are made for some therapies, while in other scenarios recommendations have not yet been defined making experimental and clinical research an essential approach to elucidate multiple issues yet not resolved in this field.
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Affiliation(s)
- Ivan Noreña
- a Infectious Diseases Unit , Fundación Cardioinfantil-Instituto de Cardiología , Bogotá , Colombia.,b Infectious Diseases Unit , Clínica los Nogales , Bogotá , Colombia
| | - Mario Fernández-Ruiz
- c Infectious Diseases Unit , Hospital Universitario 12 de Octubre , Madrid , Spain.,d Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine , Universidad Complutense , Madrid , Spain
| | - José María Aguado
- c Infectious Diseases Unit , Hospital Universitario 12 de Octubre , Madrid , Spain.,d Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine , Universidad Complutense , Madrid , Spain
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ACUTE RETINAL NECROSIS AFTER ADMINISTRATION OF ADALIMUMAB, A SYSTEMIC ANTITUMOR NECROSIS FACTOR ANTIBODY. Retin Cases Brief Rep 2018; 12:307-309. [PMID: 27997458 DOI: 10.1097/icb.0000000000000499] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To report a case of acute retinal necrosis in a patient on anti-tumor necrosis factor α immunosuppressive therapy. METHODS Case report. RESULTS A 47-year-old man with psoriasis presented with blurred vision and floaters in the left eye 4 days after receiving his fourth dose of adalimumab, a tumor necrosis factor α antagonist. He was diagnosed with acute retinal necrosis and was treated with intravenous acyclovir as well as prophylactic laser barricade. Seven years later, he is 20/20 with no history of a retinal detachment. CONCLUSION Physicians prescribing tumor necrosis factor α antagonist immunosuppressive therapy should be aware of the potential of developing acute retinal necrosis.
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Quinn CS, Jorgenson MR, Descourouez JL, Muth BL, Astor BC, Mandelbrot DA. Management of Tumor Necrosis Factor α Inhibitor Therapy After Renal Transplantation: A Comparative Analysis and Associated Outcomes. Ann Pharmacother 2018; 53:268-275. [PMID: 30234366 DOI: 10.1177/1060028018802814] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Biologic agents inhibiting the tumor necrosis factor α pathway (TNFα-Is) are used to treat systemic inflammatory diseases. The best management of these agents after renal transplantation is unknown. OBJECTIVE Evaluate peritransplant use of TNFα-Is and associated outcomes. METHODS Retrospective, single-center study of adult renal-transplant-recipients (RTRs) transplanted between 1/1/1998-12/31/2017, who received TNFα-Is for inflammatory disease prior to transplant. Qualifying patients were divided into 2 cohorts: patients who resumed TNFα-Is after transplant and those who did not. Outcomes were evaluated. RESULTS A total of 5256 renal transplants occurred in the study window; 14 patients met inclusion criteria. Primary indication for TNFα-I was Crohn's-disease (CD; 57.1%). Infliximab was utilized most frequently (50%). Seven RTRs resumed TNFα-I posttransplant; mean time to resumption of 10.6±4.35 months (median=6 months), 85.7% for CD. Immunosuppression was modified in 2 patients (28.6%) in response to restarting TNFα-I therapy. Seven RTRs did not resume TNFα-Is following transplant; the majority of these had rheumatic diseases. There was no significant difference in time to first bacterial or fungal infection, rejection, or patient survival between the 2 groups. Last measured estimated glomerular-filtration-rate was similar between groups (TNFα-I: 41 ± 14.2 vs 48.6 ± 8.6, P = 0.25). No patient had cytomegalovirus infection; however, 42.8% of each cohort had documented BK virus infection. Malignancy occurred more frequently in the cohort that resumed TNFα-Is (42.8% vs 14.3%, P = 0.24); however, this was not statistically significant. Conclusion and Relevance: TNFα-I therapy prior to renal-transplant is relatively uncommon. The decision to continue therapy after transplant must balance risks of infection and malignancy against inflammatory disease recurrence. A multidisciplinary treatment approach is necessary as use of TNFα-I affects immunosuppressive management and appears to affect transplant outcomes. Future studies are needed to further clarify the role of TNFα-I therapy use in RTRs with inflammatory disorders focusing on its correlation with both BK and malignancy.
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Affiliation(s)
| | | | | | - Brenda L Muth
- 2 University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Brad C Astor
- 2 University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Didier A Mandelbrot
- 2 University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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50
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López-Estebaranz J, de la Cueva-Dobao P, de la Torre Fraga C, Galán Gutiérrez M, González Guerra E, Mollet Sánchez J, Belinchón Romero I. Manejo de la psoriasis moderada-grave en condiciones de práctica habitual en el ámbito hospitalario español. ACTAS DERMO-SIFILIOGRAFICAS 2018; 109:631-642. [DOI: 10.1016/j.ad.2018.02.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 02/12/2018] [Accepted: 02/26/2018] [Indexed: 10/14/2022] Open
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