Efficacy of Risankizumab Maintenance Therapy by Clinical Remission and Endoscopic Improvement Status in Patients With Moderately to Severely Active Ulcerative Colitis: Post Hoc Analysis of the COMMAND Phase 3 Study

Risankizumab is a p19-targeting anti-IL-23 monoclonal antibody that received FDA approval in 2024 for use in adults with moderately to severely active UC. The approval was based on results from the 12-week INSPIRE induction study and the 52-week COMMAND maintenance study, in which risankizumab demonstrated superior CR rates over placebo.^1,2

In the INSPIRE induction study, patients with moderately to severely active UC were randomly assigned 2:1 to receive IV risankizumab 1200 mg or placebo; patients with a clinical response to IV risankizumab induction were enrolled in the COMMAND study and randomly assigned 1:1:1 to receive SC risankizumab 180 mg, SC risankizumab 360 mg, or placebo (risankizumab withdrawal).

In a post hoc analysis, Panaccione and colleagues evaluated outcomes in the COMMAND phase 3 study based on CR and endoscopic improvement (EI) status upon entering the maintenance study.³ Demographic and disease characteristics were generally balanced at baseline of the induction period. At baseline of the maintenance period, the mean disease duration was longer in patients who had not achieved CR or EI (7.1-7.9 years) than in those who had (5.0-6.8 years).

The population of overall responders included all randomized patients who received at least 1 dose of maintenance treatment after receiving IV risankizumab 600 mg, 1200 mg, or 1800 mg in the induction study.

At week 52 in the COMMAND maintenance study, clinical, endoscopic, and histologic outcomes were generally better with risankizumab vs placebo, regardless of CR or EI status at week 0 of maintenance therapy. Week 52 CR rates with risankizumab 180 mg, risankizumab 360 mg, and placebo were 70.2%, 50.0%, and 39.6%, respectively, in patients with CR at week 0, compared with 29.9%, 34.5%, and 19.5%, respectively, in patients without CR at week 0 (Figure 5). Endoscopic remission rates were 53.5%, 27.5%, and 22.6%, respectively, in patients with CR at week 0, compared with 13.4%, 23.6%, and 11.7%, respectively, in patients without CR at week 0.

Figure 5.

Clinical and endoscopic outcomes at week 52 in the COMMAND maintenance study according to clinical remission or endoscopic improvement status at week 0 of maintenance therapy with risankizumab for the overall responders population. SC, subcutaneous.

^aClinical remission: stool frequency score <1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore <1.

^bEndoscopic improvement: Mayo endoscopic subscore <1 without evidence of friability.

Adapted from Panaccione R, et al. Abstract P4377. Presented at: American College of Gastroenterology 2024 Annual Scientific Meeting; October 25-30, 2024; Philadelphia, Pennsylvania.³

Similarly, week 52 CR rates with risankizumab 180 mg, risankizumab 360 mg, and placebo were 58.9%, 41.2%, and 41.0%, respectively, in patients with endoscopic improvement at week 0 compared with 30.2% 35.9%, and 13.7%, respectively, in patients without endoscopic improvement at week 0. Week 52 endoscopic remission rates were 46.7%, 31.3%, and 23.1%, respectively, in patients with endoscopic improvement at week 0, compared with 11.2%, 20.5%, and 8.8%, respectively, in patients without endoscopic improvement at week 0.

Among patients in the maintenance study who attained a clinical response to induction risankizumab but had not achieved CR or endoscopic improvement, SC risankizumab 360 mg was associated with greater rates of improvement over SC risankizumab 180 mg in all outcomes at maintenance week 52.

A benefit with risankizumab compared with placebo was observed in patients with an inadequate response to prior nonadvanced therapy (29.7% vs 8.4%) and in patients with an inadequate response to prior advanced therapy (11.4% vs 4.3%). In this study, there were several important findings: (1) the proportion of patients who had prior failure to advanced therapy was numerically higher for patients who did not achieve CR or EI at maintenance week 0 than for those who achieved it; (2) the rates of each clinical, endoscopic, and histologic outcome were generally numerically higher with risankizumab vs placebo regardless of CR or EI status at maintenance week 52; and (3) among patients with clinical response to the induction treatment who did not achieve CR or EI, risankizumab 360 mg SC demonstrated numerically higher rates of improvement in all presented outcomes over risankizumab 180 mg SC at maintenance week 52. This study highlights that exposure to risankizumab was associated with improved outcome regardless of week 12 (early) outcomes.

—Gary R. Lichtenstein, MD