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
Ben-Horin, S.(1,2);Novack, L.(3);Mao, R.(2);Guo, J.(2);Zhao, Y.(2);Sergienko, R.(3);Zhang, J.(2);Kobayashi, K.(4);Hibi, T.(4);Chowers, Y.(5);Peyrin-Biroulet, L.(6);Colombel, J.F.C.(7);Kaplan, G.G.K.(8);Chen, M.H.(2);
(1)Tel-HaShomer Sheba Medical Center, Department of Gastroenterology, Ramat Gan, Israel;(2)First affiliated Hospital of the Sun Yatsen University, Gastroenterology, Guangzhou, China;(3)Soroka University Medical Center3- Faculty of Health Sciences- Ben-Gurion University of the Negev-, Clinical research Center, Beer-Sheva, Israel;(4)Kitasato University- Kitasato Institute Hospital, Center for Advanced IBD Research and Treatment, Tokyo, Japan;(5)Rambam Health Care Campus- Bruce & Ruth Rappaport Faculty of Medicine- Technion Institute of Technology, Gastroenterology, Haifa, Israel;(6)Inserm U594- Nancy University Hospital, Gastroenterology, Nancy, France;(7)Icahn School of Medicine- Mount Sinai Hospital, Helmsley Inflammatory Bowel Disease Center, New-York, United States;(8)University of Calgary, Department of Medicine and Community Health Sciences, Calgary, Canada;
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