Risankizumab Relieves Crohn's Disease Symptoms in PROs

Risankizumab induction relieved Crohn's disease symptoms and maintenance doses were effective in resolving abdominal pain, with other mixed findings for other patient-reported outcomes in the maintenance phase.

Induction and maintenance treatment with risankizumab (Skyrizi) decreased abdominal pain score (APS) and stool frequency (SF) significantly more than placebo or withdrawal for patients with moderate to severe Crohn’s disease (CD), according to findings from electronically collected patient-reported outcomes (PROs) from the phase 3 ADVANCE, MOTIVATE, and FORTIFY studies presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.

At the end of the 12-week induction period, there was an 18-percentage point difference in APS and a 27.4-point difference in SF with risankizumab versus placebo (P <.001). In the maintenance phase, improvements were seen in APS and SF compared with withdrawal and placebo; however, these primarily only reached statistical significance with the higher dose of risankizumab.

"CD-related symptomatic PROs improved with risankizumab induction therapy,” lead author Ryan Ungaro, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY, said during a presentation of the results. "Both maintenance doses were effective in resolving abdominal pain; however, only the 360 mg subcutaneous risankizumab maintenance dose was significantly different than withdrawal (placebo SC) for improving daily SF and the combined endpoint of complete resolution of AP and SF of 1 or less."

The monoclonal antibody risankizumab inhibits IL-23, a cytokine involved in the pathogenesis of both CD and ulcerative colitis. The treatment was first approved in the United States in 2019 and has since gained indications for moderate-to-severe CD and plaque psoriasis. The indication for CD was the agent's third and was granted in June 2022, based on an assessment of the ADVANCE, MOTIVATE, and FORTIFY studies, which showed significant improvements in endoscopic response with risankizumab versus placebo.

Patient reported outcomes from the induction phase were collected from the ADVANCE and MOTIVATE trials, which randomized patients to placebo (n = 362) or intravenous risankizumab at 600 mg on weeks 0, 4, and 8 (n = 527). The maintenance portion was from the FORTIFY trial and included a matched placebo (n = 164) or subcutaneous risankizumab at either 180 mg (n = 157) or 360 mg (n = 141) ever 8 weeks. An APS of 1 or less and a SF of 2.8 or less was considered symptom remission.

At baseline prior to induction therapy, APS and SF were similar between the placebo and risankizumab arms. Most patients had a moderate APS of 2 (57.5% in placebo group versus 58.1% in the risankizumab arm) and a third of patients had a severe APS of 3. A minority of patients had an APS of 0 (0.8% and 0.6%, for placebo and risankizumab, respectively) or a mild APS of 1 (8.0% and 8.9%, respectively). The mean daily SF was 6.3 in the placebo arm and 5.9 in the risankizumab group.

The number of patients who started the trial with an APS of 1 or more and transitioned to an APS of 0 gradually increased throughout the course of induction therapy. At week 4, there was a 2.7 percentage point difference between the placebo and risankizumab arm, which increased to a statistically significant 8.2 percentage point difference favoring risankizumab by week 8 (P <.001). By week 12, there was an 11.3 percentage point difference between the two groups (P <.001).

The number of patients who started the trial with a mean SF of 2.8 or more at baseline but transitioned to a SF of 1 or less also increased throughout induction therapy. At week 4, there was a 5-percentage point difference between groups, favoring risankizumab (P = .004). By week 8, this had risen to an 11.7-point difference (P <.001) and by week 12 there was a 14.1-percentage point difference between placebo and risankizumab (P <.001).

In the maintenance period, both doses of risankizumab performed similarly for symptom relief and both were superior to placebo for symptom remission for both an APS of 1 or less (P ≤.05) and for SF of 2.8 or less (P ≤.01). The percentage point differences compared with placebo for those experiencing an APS of 0 was 12 for risankizumab 180 mg (P =.009) and 8.9% for the 360 mg dose (P = .05). Additionally, for SF of 1 or less, there was 13.5 percentage point difference favoring risankizumab 360 mg over placebo (P = .006). There was a 9.7 percentage point difference for patients having both APS of 0 and SF of 1 or less at week 52 between 360-mg risankizumab and placebo (P = .021).

At week 52, per tetrachoric correlation, there was a moderate relationship between achieving an SF of 2.8 or less and ulcer-free endoscopy (r, 0.475) and endoscopic remission (r, 0.590). For APS of 1 or less there was also a moderate relationship with under-free endoscopy (r, 0.497) and endoscopic remission (r, 0.554). This correlation was less pronounced at week 12, after induction.

"Symptom improvements and endoscopic outcomes were weakly correlated after induction and moderately correlated during maintenance, underscoring the importance of an objective measure to assess disease activity," said Ungaro.

The oral abstract, “Induction and Maintenance Treatment with Risankizumab Leads to Symptomatic Relief in Patients with Moderate to Severe Crohn’s Disease,” was presented at ACG 2022.