Extended Risankizumab Treatment in Patients With Crohn's Disease Who Did Not Achieve Clinical Response to Induction Treatment.

Abstract

Background and aims: The efficacy and safety of extended treatment with risankizumab (RZB), an anti-interleukin-23 p19 monoclonal antibody, were evaluated in patients with moderate to severe Crohn's disease (CD) who did not achieve clinical response to 12 weeks (W) RZB induction treatment ('initial nonresponders').

Methods: Initial nonresponders to intravenous (IV) RZB induction (600mg or 1200mg at W0, W4, and W8) were rerandomized 1:1:1 to receive extended blinded RZB treatment (1200mg IV at W12, W16, and W20, or subcutaneous [SC] 180mg or 360mg at W12 and W20). Patients with clinical response to SC RZB at W24 ('delayed responders') continued their dose in FORTIFY. Clinical, endoscopic, and safety outcomes were evaluated.

Results: Most initial nonresponders achieved SF/APS clinical response by W24 (76.2% [180mg SC], 63.7% [360mg SC], 62.3% [1200mg IV]), while a subset also achieved W24 SF/APS clinical remission (43.0%, 45.1%, 22.1%), endoscopic response (32.4%, 32.5%, 40.5%), and endoscopic remission (25.1%, 18.0%, 23.5%). Most delayed responders to SC RZB continued to demonstrate clinical response at FORTIFY W52 (56.7% [180mg SC], 69.7% [360mg SC]), along with SF/APS clinical remission (43.3%, 54.5%), endoscopic response (36.7%, 45.5%), and endoscopic remission (40.0%, 42.4%). Numerically greater efficacy was generally observed with 360mg SC vs 180mg SC. The safety profile of extended treatment was consistent with previously reported trials.

Conclusion: Most initial nonresponders to IV RZB induction who received 12W of extended RZB treatment demonstrated improved clinical and endoscopic outcomes at W24. Improvements in patients who received SC RZB extended treatment were maintained during FORTIFY. Extended treatment was well tolerated with no new safety risks identified.