Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

Abstract

Background/AimsTo evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy.MethodsElectronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis.ResultsThis meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61).ConclusionsADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.

Short and long-term efficacy of adalimumab in ulcerative colitis: a real-life study

“…The impact or need for combination therapy with adalimumab and immunomodulators has been debated and the results are diverging. Zhang et al presented a metaanalysis including three randomized clinical trials indicating combination therapy to be superior to adalimumab monotherapy [27]. However, exploratory post hoc analyses of the ULTRA 1 and ULTRA 2 studies by Colombel et al did not show any advantage with combination therapy [28].…”

Efficacy and safety of biologic agents and tofacitinib in moderate‐to‐severe ulcerative colitis: A systematic overview of meta‐analyses

“…Several MAs 9,13,14,16,[18][19][20]24,25,27,29,[31][32][33][35][36][37][38][39] provided heterogeneity assessment. Most comparisons versus placebo did not show substantial heterogeneity 16,24,32,36 (Table 1A-D). In many cases, MAs included only one study or fewer than 10 studies, thus tests for small-study effects were not applicable.…”

Safety and effectiveness of adalimumab in the treatment of ulcerative colitis: results from a large-scale, prospective, multicenter, observational study

“…3,8,12,[15][16][17][18][19] Adalimumab, a fully human monoclonal antibody that targets TNF-α, was proven to be effective and safe in clinical trials of up to 4 years in patients in Western countries with moderate to severe UC who were unresponsive to traditional treatments or discontinued therapy because of safety concerns. 8,12,16,17,[19][20][21][22] In addition, results from a 52-week, phase 2/3, randomized, double-blind study demonstrated the safety and efficacy of adalimumab (an initial subcutaneous injection of 160 mg, followed by 80 mg at 2 weeks, then 40 mg every other week from week 4 through 52 [160/80-mg schedule]) in anti-TNF-naive Japanese patients with moderate to severe UC who were refractory to corticosteroids, immunomodulators, or both. 18 Furthermore, an open-label extension of this study in 190 patients reported that the efficacy of adalimumab was maintained for up to 4 years, with no new safety signals identified.…”