DOP62 Efficacy of biologic drugs in short-duration versus long-duration Inflammatory Bowel Disease: A systematic review and an individual-patient data meta-analysis of randomized controlled trials. (21st January 2022)

• Record Type: Journal Article
• Authors: Ben-Horin, S; Novack, L; Mao, R; Guo, J; Zhao, Y; Sergienko, R; Zhang, J; Kobayashi, K; Hibi, T; Chowers, Y; Peyrin-Biroulet, L; Colombel, J F C; Kaplan, G G K; Chen, M H
• Is Part Of: Journal of Crohn's and colitis. Volume 16(2022)Supplement 1
• Page Start: i107
• Page End: i108
• Publication Date: 2022-01-21
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjab232.101
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may associate with higher efficacy, especially in Crohn's disease (CD). Methods: A systematic review and individual-patient-data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (Oct 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction-of-remission in patients with short-duration (≤18months) versus long-duration disease (>18months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome. Study PROSPERO registration: CRD42018041961. Results: We obtained data from five biologics drug manufacturers and included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab or vedolizumab (6, 168 CD, 3, 227 UC patients). In CD, induction-of-remission rates were higher in pooled placebo and active arms' patients with short-disease duration≤18 months (41.4%, 244/589) compared with disease-duration>18months (29.8%, 852/2857, meta-analytically estimated OR=1.33, 95%CI:1.09–1.64). The primary outcome, proportional biologic/placebo treatment effect on induction-of-remission, was not different in short-duration disease ≤18 months (n= 589, OR 1.47, 95%CI:1.01–2.15) compared with longer disease-duration (n=2857, OR 1.43, 95%CI:1.19–1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cut-offs and when modelled for individual-patients' co-variates, including prior anti-TNFs exposure. In exploratory post-hoc analysis comparing patients with colonic-CD (L2) versus small-bowel L1 CD (and excluding ileo-colonic L3 disease) the OR for induction-of-remission in long-duration disease>18months compared with short-duration disease was 0.62 for small-bowel CD (95%CI: 0.42; 0.91) but was not significant in pooled colonic CD population (OR=0.94, 95%CI: 0.66; 1.34) Conclusion: This Individual patient level meta-analysis of clinical trials of multiple biologics found there are higher rates of induction-of-remission in early CD for both biologics and placebo, resulting in a treatment-to-placebo effect ratio which is similar across different disease durations. No such relationships between disease-duration and outcomes is found in UC