Background: Risankizumab (RZB), an anti-interleukin 23p19 monoclonal antibody, demonstrated efficacy for moderately to severely active ulcerative colitis (UC) in the 12-week phase 3 INSPIRE induction study (NCT03398148). Some patients without a clinical response at week 12 may benefit from extended RZB treatment. We describe the efficacy and safety of extended RZB for an additional 12 weeks in patients without an initial clinical response.

Methods: Patients with moderately to severely active UC were randomized 2:1 to receive RZB 1200 mg or placebo intravenously (IV) at weeks 0, 4, and 8 in INSPIRE. Patients without clinical response per Adapted Mayo Score (AMS) to RZB at week 12 were randomized 1:1:1 to extended treatment with RZB (180 mg or 360 mg) subcutaneously (SC) at weeks 12 and 20 or RZB 1200 mg IV at weeks 12, 16, and 20. Patients with clinical response at week 24 on extended RZB SC treatment continued the same RZB SC dose every 8 weeks in the phase 3 COMMAND maintenance study (NCT03398135) for 52 weeks. Clinical response per AMS, clinical remission per AMS, endoscopic improvement, endoscopic remission, histologic-endoscopic mucosal improvement (HEMI), and safety were evaluated after extended induction at week 24 and at maintenance week 52.

Results: Among 650 patients receiving RZB induction for 12 weeks, 209 patients without clinical response per site endoscopy reading received an additional 12 weeks of RZB. At week 24, 56.3%, 57.1%, and 50.0% of patients achieved clinical response and 12.7%, 15.7%, and 8.8% of patients achieved clinical remission on RZB 180 mg SC, RZB 360 mg SC, and RZB 1200 mg IV, respectively (Fig 1). Rates of endoscopic improvement, endoscopic remission, and HEMI were similar across groups. Among the 56 and 44 patients treated with RZB 180 mg SC and RZB 360 mg SC who achieved clinical response at week 24 and continued RZB in COMMAND, 46.4% and 45.3% achieved clinical response, and 17.9% and 22.8% achieved clinical remission at maintenance week 52 (Fig 2). Rates of treatment-emergent adverse events were similar across groups at weeks 24 and 52. No new safety risks were identified.

Conclusion: In patients without clinical response after 12 weeks of RZB IV induction, an additional 12 weeks of RZB SC treatment at maintenance doses may induce clinical response and remission. Patients who respond to extended induction may continue to observe benefits at week 52. There was no observed benefit at week 24 of additional RZB IV treatment over initiation of RZB SC treatment, suggesting that the duration of RZB exposure rather than the dose may be an important factor for the induction of some patients with refractory UC.

David Drobne

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