Efficacy of adalimumab for the treatment of extraintestinal manifestations of Crohn's disease

Abstract

Background and aims:Crohn's disease (CD) is commonly associated with inflammatory processes located in organs and systems others than the gut, which are known as extraintestinal manifestations (EIM) of the disease. The aim of this study was to assess the effectiveness of adalimumab (ADA) for the treatment of EIM in patients with CD.Methods: forty two consecutive CD patients with at least one EIM were prospectively included in a open-label study. Patients received ADA (160 mg at week zero, 80 mg at week two and 40 mg every other week) over six months and the effectiveness and safety of ADA for EIMs were assessed. The influence of gender, age, smoking habits, family history of inflammatory bowel disease, phenotype and previous anti-TNF treatment on EIM resolution was also investigated.Results: at month six, 76.2% of the patients showed remission or response in CD (33.3% remission and 42.9% any response). EIM showed a parallel course with CD in most cases, and showed remission or response in 66.7% of patients (38.1% remission and 28.5% any response). Patients with any response of their EIM condition were younger than those with no response (p = 0.04). No relationship was found between sex, tobacco, family history of IBD, phenotype and previous treatment with anti-TNF, and EIM resolution.Conclusions: adalimumab is effective in reducing EIM of CD. Age but not tobacco, CD phenotype and anti-TNF-naïve status appears to influence the response.

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

“…The efficacy of biologic treatment on multiple EIMs was assessed in 4 studies (2 on adalimumab, 2 on infliximab). 23,26,29,30 Favorable results at the end of follow-up period were obtained in all 4 studies, which showed clinical improvement and/or resolution of EIM symptoms in a substantial number of patients.…”

“…In general terms, the studies included in our review showed large heterogeneity in designs, including randomized 22,24 and open label clinical trials, 23,[26][27][28][29][30][31] prospective 32,[35][36][37][38]43,44 and retrospective 33,34,39,40,42 cohort studies, and large case series. 41 Variability in the number of EIMs assessed was also observed, with some studies assessing the clinical benefit of biologic drugs on several different EIMs 23,26,29,30,44 and others evaluating the efficacy or effectiveness on specific EIMs such as musculoskeletal, 27,28 metabolic bone disease, 31-37 mucocutaneous, 22,40,41 hematologic alterations such as anemia 38,39 or hemostasis, and coagulation alterations. 42,43 In addition, outcomes measures used to evaluate efficacy and effectiveness of biologic drugs on EIMs varied from study to study.…”

“…In some cases, variation in the prevalence of specific EIMs from baseline to a certain time point is used, 24,28,29,33,38 and in other cases clinical improvement or clinical resolution, often considering different definitions for the same EIMs, is reported. 22,23,26,27,30,40,41,44 Finally, another set of studies use surrogate measures to assess evolution of EIMs. 31,32,[34][35][36][37]39,42,43 Because of these significant variations, the possibility of meta-analyzing the data was not considered.…”

“…24 Open label trials. The 7 interventional open label trials identified in our search assessed the efficacy of infliximab (n ¼ 4) 23,[26][27][28] and adalimumab (n ¼ 3) [29][30][31] in EIMs. The studies varied considerably in terms of types of EIMs assessed (several vs specific EIMs), sample size, and study duration.…”

“…29 Similar results were reported in the 3 remaining smaller single-center open label studies where treatment efficacy in multiple EIMs was investigated. Barreiro-de-Acosta et al 30 assessed the efficacy of adalimumab in 42 CD patients with at least 1 EIM during a period of 6 months. The most common EIMs at baseline were peripheral arthritis (31 patients) and ankylosing spondylitis (7 patients).…”