Subcutaneous Risankizumab Induction Improves Outcomes in Crohn's Disease Patients

Clinical and Endoscopic Outcomes at 12 Weeks

Endoscopic response was observed in 44% of the active treatment group versus 14.3% in the control group, with both differences being statistically significant (P<0.0001). These findings were presented by Millie D. Long, MD, MPH, from the University of North Carolina at Chapel Hill. The co-primary endpoint rates were also superior in patients who had not previously been exposed to advanced therapies, as well as in those with intolerance or inadequate response to such treatments.

Patient Population and Treatment History

I want to emphasize that we were dealing with a treatment-refractory population, Long stated during a session at the American College of Gastroenterology annual meeting in Nashville, Tennessee. From the perspective of prior failure of advanced therapies, approximately one-third were anti-TNF naive, two-thirds had been exposed to anti-TNF, and there was a proportion that had failed ustekinumab [Stelara], as well as a proportion that had failed JAK inhibitors.

Regulatory Submission and Trial Design

So, this was a clinically refractory population. Clinical Practice Intentions and Drug Mechanism Responding to a question from the session moderator, Long said she was reassured by the difference in response between the risankizumab and placebo groups, especially among those not previously exposed to advanced therapies, adding that in my clinical practice, I intend — once it becomes available — to largely switch to subcutaneous risankizumab. As an interleukin-23 inhibitor, risankizumab was approved by the FDA in 2022 as an intravenous induction therapy, followed by subcutaneous maintenance.

Baseline Characteristics

Based on the 12-week results from the AFFIRM study, AbbVie submitted an application to the FDA for approval of subcutaneous risankizumab as an induction treatment — an option that, Long emphasized, „would offer increased flexibility for our patients.”The double-blind AFFIRM trial included 289 adults with a Crohn's disease diagnosis of at least three months. Participants had to have moderate to severe disease, defined by CDAI, a simple endoscopic score for Crohn's disease (SES-CD) of at least 6 (or at least 4 for those with isolated ileal disease), as well as prior intolerance or inadequate response to conventional and/or advanced therapies.

Additional Efficacy Endpoints at 12 Weeks

The mean age was 38-40 years, 43% were female, 61-65% had a baseline mean CDAI above 300, and 7% had a baseline mean SES-CD of 13. Patients were randomized in a 2:1 ratio to either risankizumab 720 mg or placebo.

Analyzing other efficacy endpoints, endoscopic remission rates at 12 weeks were 27.7% in the risankizumab group versus 10.2% with placebo (P<0.0001), while ulcer-free endoscopy rates were 26.2% and 10.2%, respectively (P=0.0001).

Maintenance Phase Results at 24 Weeks

Long also reported results from a 24-week maintenance phase, in which patients who responded to risankizumab induction received subcutaneous risankizumab 360 mg at weeks 12 and 20, while those in the placebo group continued with subcutaneous placebo. Of the 134 patients who responded to risankizumab induction and continued with risankizumab maintenance therapy, 67.2% achieved clinical remission as defined by CDAI, compared to 29.6% of those who responded to placebo induction up to week 24.

Maintenance Endoscopic Outcomes

Endoscopic response rates were 57.5% with risankizumab versus 11.4% with placebo, endoscopic remission rates were 35.8% and 9.1%, respectively, and ulcer-free endoscopy rates were 36.6% and 9.1%, respectively. Similar to the 12-week results, maintenance phase rates were numerically higher in the population not previously exposed to advanced therapies.

Safety Profile

The rate of adverse events occurring during treatment was lower in the risankizumab group, while the rate of serious adverse events was low in both groups. The only treatment discontinuation due to an adverse event occurred in the placebo group.