P457 Biological interventions for induction and maintenance of mucosal healing in ulcerative colitis: A Cochrane systematic review

• Published in: Journal of Crohn's and colitis 2018-01, Vol.12 (supplement_1), p.S335-S336
• Main Authors: Ricciuto, A, Al-Darmaki, A, Stewart, M J, Ding, N S, Shim, H H, Storr, M, Panaccione, R, Seow, C
• Format: Article
• Language: English
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjx180.584

Abstract Background The number of biologics for ulcerative colitis (UC) is rapidly expanding and mucosal healing (MH) is a salient endpoint against which to gauge their efficacy. In this Cochrane review, we synthesised the randomised controlled trial (RCT) data on biologics for inducing and maintaining MH in UC. Methods We searched MEDLINE, EMBASE, Cochrane Library and the Cochrane IBD Group Specialised Trials Register to October 2017 for RCTs investigating biologics for inducing and/or maintaining MH in UC at 4–26 and >26 weeks, respectively. Secondary outcomes were endoscopic response (ER), safety and quality of life (QOL). Pooled risk ratios (RR) were determined using a random-effects model. The quality of the evidence was rated with GRADE. Results The search yielded 13 induction trials (eight low, four unclear, one high-risk of bias). Infliximab (IFX), adalimumab (ADA), golimumab (GOL) and vedolizumab (VDZ) were superior to placebo (PBO) for inducing MH at 6–8 weeks (RR 1.8, 95% CI 1.5–2.1, n = 979, high quality for IFX; RR 1.3, 95% CI 1.1–1.5, n = 940, moderate quality for ADA; RR 1.5, 95% CI 1.2–1.8, n = 1194, high quality for GOL; RR 1.7, 95% CI 1.3–2.3, n = 555, moderate quality for VDZ). IFX plus azathioprine (AZA) was superior to AZA (RR 1.7, 95% CI 1.2–2.4, n = 154, low quality). No difference was seen between IFX and ADA in a single trial (RR 1.0, 95% CI 0.51–2.0, n = 50, very low quality). Seven maintenance trials were identified (all low risk of bias). The ability of a biologic to maintain MH achieved during induction was examined in one ADA trial; no difference was observed between ADA and PBO (RR 1.3, 95% CI 0.90–1.9, n = 180, low quality). Analyses including all randomised patients (regardless of MH status at induction completion) demonstrated higher MH rates at 1 year with IFX, ADA, GOL and VDZ vs. PBO (RR 2.5, 95% CI 1.7–3.8, n = 364 for IFX; RR 1.7, 95% CI 1.2–2.2, n = 767 for ADA; RR 1.6, 95% CI 1.2–2.1, n = 332 for GOL; RR 2.7, 95% CI 1.9–3.9, n = 373 for VDZ; moderate quality for all). ADA and VDZ were effective amongst anti-TNF-naive patients for induction only. The same was true of ADA for maintenance, while VDZ’s maintenance benefit was observed in bio-naive and bio-exposed patients. The IFX and GOL data pertain to anti-TNF-naive patients only. Adverse event rates were similar between groups. All 4 biologics were associated with QOL improvements. Conclusions Moderate-to-high quality evidence supports the efficacy of IFX, ADA, GOL