Subcutaneous Risankizumab Induction Improved Outcomes in Crohn’s Disease

Subcutaneous risankizumab (Skyrizi) induction therapy significantly improved clinical remission and endoscopic response rates in patients with moderately to severely active Crohn’s disease, results from the phase III AFFIRM trial showed.

At 12 weeks, 55% of patients receiving subcutaneous risankizumab achieved Crohn’s Disease Activity Index (CDAI)-defined clinical remission compared with 29.6% of those receiving placebo, while 44% versus 14.3%, respectively, achieved endoscopic response (P<0.0001 for both comparisons), reported Millie D. Long, MD, MPH, of the University of North Carolina at Chapel Hill.

Rates for the co-primary endpoints were also higher in risankizumab patients who were naive to advanced therapy and those who were intolerant to or had inadequate response to advanced therapy.

“I’d like to highlight this was a treatment-refractory population,” Long said during a session at the American College of Gastroenterology annual meeting in Nashville, Tennessee. “In terms of prior failure to advanced therapies, approximately a third were anti-TNF [tumor necrosis factor] naive, two-thirds were anti-TNF exposed, and … there were a proportion that had failed ustekinumab [Stelara], and a proportion that had failed JAK inhibitors. So this was a medically refractory population.”

Responding to a question from a session moderator, Long said she was reassured by the difference in response between the risankizumab and placebo groups, particularly among those who were advanced therapy-naive, adding that “in my clinical practice I do plan — once this is available — to move predominantly to subcutaneous risankizumab.”

An interleukin-23 inhibitor, risankizumab was approved by the FDA in 2022 as intravenous induction therapy followed by subcutaneous maintenance in patients with moderately to severely active Crohn’s disease.

Based on the 12-week results from AFFIRM, AbbVie submitted an application to the FDA seeking approval for subcutaneous risankizumab as induction therapy — an option which would “provide increased flexibility to our patients,” Long pointed out.

The double-blind AFFIRM trial enrolled 289 adults with a Crohn’s disease diagnosis for at least 3 months. Participants had to have moderate to severe Crohn’s disease as defined by CDAI, a Simple Endoscopic Subscore for Crohn’s Disease (SES-CD) of at least 6 (or at least 4 for those with isolated ileal disease), and prior intolerance or inadequate response to either conventional and/or advanced therapies.

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

Looking at 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).

Long also reported results from a 24-week maintenance phase in which risankizumab induction responders received subcutaneous risankizumab 360 mg at weeks 12 and 20, while placebo responders continued subcutaneous placebo.

Among the 134 risankizumab induction responders who continued with risankizumab maintenance therapy, 67.2% achieved CDAI-defined clinical remission versus 29.6% of placebo induction responders through week 24. 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.

As with 12-week results, the rates in the 24-week maintenance phase were numerically higher in the advanced therapy-naive population and those who were intolerant to or had inadequate response to advanced therapy.

Rates of treatment-emergent adverse events were lower in the risankizumab group, while rates of serious adverse events were low in both groups. The one treatment discontinuation due to an adverse event occurred in the placebo group.