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      Effectiveness and Safety of Anti-Tumor Necrosis Factor-Alpha Agents Treatment in Behcets’ Disease-Associated Uveitis: A Systematic Review and Meta-Analysis

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          Abstract

          Purpose

          We conducted a systematic review and meta-analysis to determine the effectiveness and safety of anti-tumor necrosis factor-alpha (TNF-α) agents in the treatment of Behcets’ disease (BD)-associated uveitis.

          Method

          Three electronic databases, Embase, MEDLINE, and the Cochrane Library, were searched for eligible papers focusing on the anti-TNF-α agents treatment in BD-associated uveitis with at least 6 months follow-up time. A systematic review and meta-analysis was conducted on selected papers with appropriate clinical and methodological homogeneity. The effectiveness outcomes included inflammation remission, visual acuity (VA) improvement, central macular thickness (CMT) decrease, corticosteroid (CS)-sparing effects, and the safety outcomes included minor and severe drug-related adverse events (AEs).

          Result

          From Jan 2010 to Dec 2019, there were 504 records produced in total, in which 18 clinical trials were selected for meta-analysis (15 trials were retrospective studies, and 3 were prospective studies). The number of patients in each study ranged from 11 to 163 and the mean follow-up time from 0.9 to 6.44 years. During the follow-up, the pooled inflammation remission rate was 68% with a 95% confidence interval (CI) of 0.59–0.79, VA improvement rate was 60% (95% CI 0.47–0.77), CMT decrease was 112.70 μm (95% CI 72.8–153.0 μm). The proportions of patients who had CS-suspended and CS-tapered reached 38% (95% CI 0.23–0.65) and 34% (95% CI 0.16–0.70), respectively. The severe AEs were reported but not common, which included severe infusion reactions, pneumonia, bacteremia, tuberculosis, melanoma, and lymphoma.

          Conclusion

          Anti-TNF-α agents treatment has high effectiveness including efficient inflammation remission, satisfactory VA improvement, obvious CMT reduction, and significant CS-sparing effects. Although some drug-related AEs were reported, the incidence of severe AEs was acceptable. Anti-TNF-α agents treatment is a promising option for controlling BD-associated uveitis.

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          Most cited references47

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          2018 update of the EULAR recommendations for the management of Behçet’s syndrome

          Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.
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            Adalimumab in Patients with Active Noninfectious Uveitis

            Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis.
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              Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial

              Non-infectious uveitis is a potentially sight-threatening ocular disorder caused by chronic inflammation and its complications. Therapeutic success is limited by systemic adverse effects associated with long-term corticosteroid and immunomodulator use if topical medication is not sufficient to control the inflammation. We aimed to assess the efficacy and safety of adalimumab in patients with inactive, non-infectious uveitis controlled by systemic corticosteroids.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                24 June 2020
                2020
                : 11
                : 941
                Affiliations
                [1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou, China
                Author notes

                Edited by: Brian Godman, Karolinska Institutet (KI), Sweden

                Reviewed by: Janet Sultana, University of Messina, Italy; Luis Laranjeira, Eli Lilly, Portugal

                *Correspondence: Wenru Su, suwr3@ 123456mail.sysu.edu.cn ; Dan Liang, liangdan@ 123456gzzoc.com

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2020.00941
                7327708
                32670062
                59f2d44e-7f09-40ef-a811-ac9a5c94f4bf
                Copyright © 2020 Hu, Huang, Yang, Chen, Su and Liang

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 March 2020
                : 09 June 2020
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 52, Pages: 10, Words: 5454
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: U1601226, 81870649, 81670897
                Categories
                Pharmacology
                Systematic Review

                Pharmacology & Pharmaceutical medicine
                anti-tnf-α,behcets’ disease-associated uveitis,inflammation remission rate,visual acuity improvement,central macular thickness decrease,corticosteroid-sparing effect,adverse events,meta-analysis

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