Extended Risankizumab Benefits Initial Nonresponders in Ulcerative Colitis

BACKGROUND & AIMS: The efficacy and safety of extended induction treatment with risankizumab, an interleukin-23 p19 inhibitor, in patients with moderately to severely active ulcerative colitis (UC) who, per site evaluation, did not achieve clinical response to 12 weeks of risankizumab induction was evaluated. METHODS: In the phase 3 INSPIRE induction study, 209 initial nonresponders to 12 weeks of 1200 mg intravenous (IV) risankizumab induction were rerandomized to receive 12 weeks of additional 1200 mg risankizumab (weeks 12, 16, and 20) or 180 mg or 360 mg subcutaneous [SC] risankizumab (weeks 12 and 20) in a double-blind fashion. Patients from both phase 2b and 3 with week 24 clinical response to SC risankizumab (delayed responders) continued to receive blinded risankizumab at their assigned dose in the phase 3 COMMAND maintenance study. Efficacy and safety were evaluated at week 24 of induction and week 52 of maintenance. RESULTS: Initial nonresponders (1200 mg IV [n = 68], 180 mg SC [n = 71], or 360 mg SC [n = 70]) had week 24 clinical response rates of 50%, 56.3%, and 57.1%, respectively; patients also achieved clinical remission, histologic endoscopic mucosal improvement (8.8%, 12.7%, and 15.7% for both endpoints), endoscopic improvement (17.6%, 18.3%, and 24.3%), and endoscopic remission (1.5%, 8.5%, and 5.7%). Efficacy rates were generally highest with 360 mg. In maintenance, delayed responders demonstrated sustained rates of clinical remission and increased rates of endoscopic outcomes and histologic endoscopic mucosal improvement at week 52. The safety with extended risankizumab treatment was consistent with the known risankizumab safety profile. CONCLUSIONS: Over 50% of initial nonresponders achieved clinical response with extended risankizumab treatment. Additional clinical and endoscopic outcomes were also achieved, with sustained or improved efficacy observed following maintenance. Extended treatment was well tolerated with no new safety risks identified. ClincialTrials.gov, Numbers. NCT03398148 (INSPIRE), NCT03398135 (COMMAND).