• Malihe Rezaee, Moein Zangiabadian, Amirali Soheili, Tess Moore Calcagno, Maryam Rahmannia, Roshan Dinparastisaleh, Mohammad J Nasiri, and Mehdi Mirsaeidi.
• Medical Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
• Eur. J. Intern. Med. 2023 Mar 1; 109: 424942-49.

ImportanceAnti-tumor necrosis factor-alpha agent (anti-TNF-α) is considered an effective third-line therapy for refractory sarcoidosis,studies observing the efficacy of anti-TNF-α agents show conflicting results.ObjectiveWe performed an up-to-date systemic meta-analysis to determine effectiveness and further elucidate the role of anti-TNF-α in the treatment of sarcoidosis.Data SourcesA systematic search was carried out in PubMed/Medline, EMBASE, and Cochrane Library for studies reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis, published up to April 10, 2022. The study was registered in the international prospective register of systematic reviews (PROSPERO) under ID: CRD42022364614.Study SelectionClinical trials written reporting the therapeutic effects of anti-TNF drugs on patients with pulmonary and extra-pulmonary sarcoidosis were included.Data Extraction And SynthesisStatistical analyses were performed with Comprehensive Meta-Analysis software, and the random-effects model was used. The combined overall treatment success was determined for patients with pulmonary and extrapulmonary sarcoidosis.Main Outcomes And MeasuresOverall treatment success rate wasdefined as no disease progression or improvement in symptoms.ResultsEight clinical trial articles were included in the meta-analysis; four used Infliximab, two Etanercept, one Adalimumab, and one Ustekinumab and Golimumab. The mean age of participants was 48.5 years. The duration of drug therapy ranged from 14 to 45 weeks. We found a combined overall treatment success rate, defined as no disease progression or improvement in symptoms, of 69.9% (95% CI 35.0-90.9, I2: 70%) in the pulmonary sarcoidosis group and 74.5% (95% CI 36.3-93.7, I2: 90%) in the extrapulmonary sarcoidosis group. There was no evidence of publication bias in either group.Conclusion And RelevanceTreatment of refractory sarcoidosis with anti-TNF-α agents was effective in both pulmonary and extrapulmonary sarcoidosis, with a slightly higher efficacy seen in extrapulmonary sarcoidosis. Further randomized controlled trials should be conducted to determine the effects of anti-TNF-α agents as a part of the management strategy of sarcoidosis. Patients with pulmonary sarcoidosis should be studied separately from patients with extrapulmonary sarcoidosis to adjust for confounding results.Copyright © 2022. Published by Elsevier B.V.

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