Anti-tumor necrosis factor agents in sarcoidosis: A systematic review of efficacy and safety

Though anti-tumor necrosis factor agents (anti-TNFs) have been recommended as third-line therapy for sarcoidosis, an up-to-date systematic synthesis of their efficacy and safety is lacking. To systematically review the literature to characterize the efficacy and safety of anti-TNFs in sarcoidosis. All countries and treatment settings were included. We searched MEDLINE, EMBASE, CINAHL, Web of Science, ClinicalTrials.gov, Cochrane Library, and Google Scholar from inception to November 27, 2017. Studies of five or more cases of sarcoidosis treated with anti-TNFs were included. Descriptive statistics were performed. Sixty-five studies (including five randomized controlled trials [RCTs]) were identified, comprising 1525 patients. For pulmonary sarcoidosis, one RCT found infliximab (IFX) significantly improved vital capacity vs. placebo; a second detected no difference. In non-randomized studies, IFX improved pulmonary function in 79% of patients. For cutaneous sarcoidosis, compared to placebo, adalimumab (ADA) showed greater Physician Global Assessment response and significantly reduced target lesion area, and IFX significantly decreased Sarcoidosis Area and Severity Index induration and erythema scores. In non-randomized studies of cutaneous, ocular, neurologic, and multisystem sarcoidosis, IFX improved 89%, 69%, 77%, and 71% of cases, respectively. ADA improved 77% of ocular sarcoidosis cases. IFX displayed a steroid-sparing effect. Half of patients relapsed after discontinuation of IFX, ADA, etanercept, or certolizumab pegol. In RCTs, compared to placebo, anti-TNFs had comparable overall and serious adverse events and slightly more serious infections. Available evidence suggests the efficacy and safety of IFX in pulmonary, cutaneous, ocular, neurologic, and multisystem sarcoidosis, and ADA in cutaneous and ocular sarcoidosis.