Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease.

Abstract

Risankizumab (RZB) and ustekinumab (UST), interleukin (IL)-23 and IL-12/23 inhibitors, respectively, are approved treatments for moderately to severely active Crohn's disease (CD); direct comparison between the two is ongoing. We indirectly compared efficacy of RZB versus UST using data from phase3 trials (RZB: NCT03104413; NCT03105128; NCT03105102; UST: NCT01369329; NCT01369342; NCT01369355). Matching-adjusted indirect comparison was conducted using individual patient-level data from RZB trials and published aggregated data from UST trials. During induction, patients received RZB 600mg intravenous (IV) at weeks0, 4, and 8 or a single dose of UST 6mg/kg IV at week0. During maintenance, patients received RZB 180 or 360mg subcutaneous (SC) or UST 90mg SC every 8 or 12weeks to 52weeks. Outcomes included proportion of patients achieving Crohn's Disease Activity Index (CDAI) response (decrease of ≥ 100 points or total score < 150) or remission (CDAI ≤ 150) and endoscopic improvement (measured by the Simple Endoscopic Score in CD [SES-CD]; response, ≥ 50% reduction from baseline; remission, SES-CD ≤ 2) following induction/baseline. Higher proportions of patients achieved clinical and endoscopic outcomes with RZB vs. UST induction treatment, resulting in significantly (p ≤ 0.05) greater percent differences (95% confidence intervals) between groups for CDAI remission (15% [5%, 25%]) and endoscopic response (26% [13%, 40%]) and remission (9% [0%, 19%]). Following maintenance, rates of CDAI remission were similar (range -0.3% to -5.0%) for RZB vs. UST. Differences for endoscopic response and remission ranged from 9.3% to 27.7% and 11.6% to 12.5%, respectively; differences were significant (p < 0.05) for endoscopic response for both doses of RZB compared to UST 12-week dosing. This indirect comparison demonstrated higher rates of clinical and endoscopic outcomes during induction for RZB compared to UST; CDAI remission following maintenance was comparable. Direct comparisons of RZB and UST are warranted to validate these findings.