Systematic Review of Tumor Necrosis Factor Antagonists in Extraintestinal Manifestations in Inflammatory Bowel Disease

BACKGROUND & AIMS: This systematic review investigated the efficacy and the effectiveness of biologic drugs in extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD). METHODS: Literature search was conducted in PubMed, Embase, and Cochrane until October 2015. Main inclusion criteria were adults with IBD, use of a biologic drug, evolution of EIMs, interventional study, or non-interventional study. RESULTS: Nine interventional studies (2 randomized controlled trials [N = 797], 7 open label trials [N = 1143], and 13 non-interventional studies [N = 914]) were included. Tumor necrosis factor (TNF) antagonists achieved complete response for pyoderma gangrenosum in 21%-25% of patients in interventional studies and in 92%-100% patients in non-interventional studies, with similar results for other cutaneous manifestations such as erythema nodosum or stomatitis. Adalimumab significantly reduced the prevalence of anemia vs placebo after 56 weeks in 1 randomized controlled trial. In 2 non-interventional studies, anti-TNF therapy improved anemia in the short-term (67%) and in the long-term (34%). Complete response after anti-TNF treatment was reported in interventional studies, including arthralgia (reduction in prevalence from 47.1% to 26.8% in the mid-term in 1 open label trial) and arthritis (reduction in prevalence from 8.7% to 2.1% and from 58% to 12.5% in 2 open label trials). Anti-TNFs were beneficial for a majority of patients with ocular manifestations. Infliximab was associated with improved outcomes in bone formation and bone mineral density. CONCLUSIONS: Anti-TNFs appear to be effective alternatives for certain EIMs associated with IBD including musculoskeletal, cutaneous, and ocular manifestations, and some beneficial effect may be obtained in metabolic bone disease and on hematologic or vascular EIMs.