Two phase III randomized clinical trials found that risankizumab may have improved clinical remission rates compared with placebo when used as both induction and maintenance therapy in patients with moderately to severely active ulcerative colitis.

Risankizumab is a monoclonal antibody targeting the p19 subunit of interleukin-23.

In the induction trial, published in JAMA, researchers enrolled 975 patients aged 18 to 80 years with moderately to severely active ulcerative colitis (adapted Mayo score 5 to 9) and an inadequate response to conventional or advanced therapies. The patients were randomized 2:1 to receive 1,200 mg of intravenous risankizumab or placebo at weeks 0, 4, and 8. 

The researchers reported that 20.3% of patients receiving 1,200 mg of intravenous risankizumab achieved clinical remission at 12 weeks compared with 6.2% of those receiving placebo (adjusted between-group difference = 14.0%, 95% confidence interval [CI] = 10.0%–18.0%, P < .001).

In the maintenance trial, the researchers recruited 548 patients who had an adequate clinical response to risankizumab at 12 weeks during induction. These patients were randomized 1:1:1 to receive 180 mg of subcutaneous risankizumab, 360 mg of subcutaneous risankizumab, or placebo every 8 weeks for 52 weeks. 

The researchers found that clinical remission rates at 52 weeks were 40.2% for 180 mg of subcutaneous risankizumab, 37.6% for 360 mg of risankizumab, and 25.1% for placebo (adjusted between-group difference = 16.3%, 97.5% CI = 6.1%–26.6%, P < .001 for 180 mg vs placebo; 14.2%, 97.5% CI = 4.0%–24.5%, P = .002 for 360 mg vs placebo).

The primary endpoint for both trials was clinical remission, defined as a stool frequency score ≤ 1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤ 1 without friability.

Secondary endpoints included clinical response, endoscopic improvement, endoscopic remission, histological improvement, and patient-reported outcomes. The trials also assessed inflammatory biomarkers and safety outcomes.

In the induction trial, risankizumab significantly improved multiple secondary endpoints compared with placebo, including:

• Clinical response (64.3% vs 35.7%, P < .001)
• Endoscopic improvement (36.5% vs 12.1%, P < .001)
• Endoscopic remission (10.6% vs 3.4%, P < .001)
• Histological, endoscopic, and mucosal improvement (24.5% vs 7.7%, P < .001)
• Absence of bowel urgency (44.1% vs 27.7%, P < .001)
• Absence of nocturnal bowel movements (67.3% vs 43.1%, P < .001).

Risankizumab also significantly improved fatigue scores (change in FACIT-F score = 7.9 vs 3.3, P < .001) and quality of life scores (change in IBDQ score = 42.6 vs 24.3, P < .001) compared with placebo.

In the maintenance trial, both doses of risankizumab showed significant improvements over placebo in multiple secondary endpoints, including:

• Clinical response (68.2% for 180 mg and 62.3% for 360 mg vs 51.9% for placebo, P < .001 and P = .02, respectively)
• Endoscopic improvement (50.8% for 180 mg and 48.3% for 360 mg vs 31.7% for placebo, P < .001 for both)
• Histological, endoscopic, and mucosal improvement (42.8% for 180 mg and 42.2% for 360 mg vs 23.5% for placebo, P < .001 for both).

Both trials showed greater efficacy in patients without prior inadequate response to advanced therapies compared with those with a history of poor treatment response.

In the induction trial, the researchers noted that serious adverse events occurred in 2.3% of the patients treated with risankizumab vs 10.2% of the patients treated with placebo. In the maintenance trial, serious adverse events were reported in 5.2% of the patients in the 180 mg group, 5.1% of those in the 360 mg group, and 8.2% of those in the placebo group.

The most common adverse events in the induction trial were COVID-19 (4.8%) and anemia (3.4%) for risankizumab as well as colitis ulcerative (10.2%) and anemia (6.5%) for placebo. In the maintenance trial, the most common adverse events across all groups were colitis ulcerative (13.0% to 14.8%) and COVID-19 (8.8% to 13.3%).

One treatment-emergent death occurred in the induction trial in the risankizumab group as a result of COVID-19 pneumonia. One nontreatment-emergent death occurred in the maintenance trial in the 360 mg risankizumab group because of preexisting colorectal adenocarcinoma.

These trials demonstrated the safety and efficacy of risankizumab as both induction and maintenance therapy for moderately to severely active ulcerative colitis. However, longer-term studies are needed to assess the benefits beyond 52 weeks and in patients with prior exposure to other emerging therapies.

Full ethics declarations can be found within the study.