P081 HISTOLOGIC HEALING RATES OF MEDICAL THERAPIES FOR ULCERATIVE COLITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Abstract

Histologic remission is a potentially valuable means of assessing disease activity and treatment response in ulcerative colitis (UC). However, the efficacy of existing therapies to achieve this outcome is unclear. We performed a systematic review and meta-analysis of histologic outcomes in UC randomized controlled trials (RCTs) and examined the relationship between histologic and endoscopic outcomes. MEDLINE, EMBASE, CENTRAL, and the Cochrane IBD Register were searched for RCTs of aminosalicylates, corticosteroids, immunosuppresives, biologics and small molecules. Histologic and endoscopic remission and response data were independently extracted and pooled using binomial-normal random or fixed-effects models. Pooled efficacy estimates were calculated as risk ratios (RRs) using the Mantel-Haenszel method. Univariable and multivariable random-effect meta-regression models examined factors associated with histologic remission. Seventy-four studies (68 induction, 7 maintenance) were identified. Topical aminosalicylate enemas (37.2%, 95%CI 29.0-46.3%) and suppositories (44.9%, 95%CI 28.9- 62.3%) had the highest induction of histologic remission rates. Aminosalicylate enemas (RR=4.14, 95%CI 2.35-7.31), aminosalicylate suppositories (RR=3.94, 95%CI 1.26-12.32) and budesonide MMX (RR=1.47, 95%CI 1.08-1.99) had higher histologic remission rates than placebo. Studies of other medications either provided continuous histologic data in distinction to rates of response and remission (approved tumor necrosis factor (TNF) antagonists, antiintegrin therapies, non-conventional biologics) or had insufficient studies for meta-analysis (azathioprine, biologics not approved for UC therapy, small molecules). The pooled histologic remission rate for placebo in induction studies was 10.4% (95%CI 7.1-15.2%). Histologic and endoscopic remission correlated strongly (r=0.66 95%CI 0.50-0.78). In multivariate analysis of placebo-arm data, less severe clinical disease activity (OR=1.85, 95% CI 1.14-2.99, p=0.012) and corticosteroid use (OR=1.28, 95% CI 1.02-1.62, p=0.036) were associated with higher histologic remission rates. Similarly, mild clinical disease activity was associated with higher histologic remission rates (OR=1.19, 95% CI 1.07-1.33, p=0.0020) when active-arm data were analyzed. Histologic remission rates for current UC treatments ranged from 15.0% to 44.9% according to drug class and patient population with the highest rates observed for topical aminosalicylates. Placebo remission rates were low with relatively narrow confidence intervals. These data provide benchmarks to inform future trial design. Histologic remission is a potential treatment target in clinical practice.