Safety and Efficacy of Risankizumab in Crohn’s Disease: Prospective Real-World Experience and Systematic Literature Review

Risankizumab is a selective inhibitor of interleukin-23 (IL-23) that is approved for the treatment of adults with moderately to severely active CD.^1,2 A prospective study evaluated real-world outcomes in 145 patients with CD who were followed for 12 weeks after the initiation of treatment with risankizumab.³ Of these patients, 81 were treated for active luminal disease and were included in the efficacy analysis, 45 of whom (56%) had received prior treatment with ustekinumab. In the efficacy cohort of 81 patients, the median age was 44 years (interquartile range [IQR], 35-58 years), and the median duration of disease was 15 years (IQR, 9-27 years). More than half of the patients had ileocolonic disease (53%). The most common disease phenotype was stricturing (44%), followed by perianal (31%) and penetrating (20%). In the efficacy cohort, 48% of the patients had received 3 or more prior advanced therapies, and 60% had a history that included bowel resection. By week 12, 70% of patients achieved clinical remission, with 63% achieving corticosteroid-free clinical remission. Most of the patients who achieved clinical remission did so by week 4. Among the patients who were ustekinumab-naive vs those who were ustekinumab-experienced at baseline, the rates of clinical remission were 78% vs 64% (P=.222), and the rates of corticosteroid-free clinical remission were 75% vs 52% (P=.041) (Figure 3); however, in multivariate analysis, prior therapy with ustekinumab was not associated with a lower rate of corticosteroid-free clinical remission at week 12.

Figure 3.

CR and corticosteroid-free CR rates at wk 12 of risankizumab induction therapy in patients with and without prior ustekinumab from the effectiveness cohort and in a subgroup of patients with HBI ≥5 at BL.

BL, baseline; CR, clinical remission; HBI, Harvey-Bradshaw Index; UST, ustekinumab.

Adapted from Zinger et al. Abstract P3532. Presented at: ACG 2023; October 20-25, 2023; Vancouver, British Columbia, Canada.³

A systematic review of literature was conducted to evaluate dosing practices and outcomes in patients who had CD treated with risankizumab.⁴ The study included 5 papers: 1 cohort study, 1 phase 2 randomized controlled clinical trial, 1 phase 2 open-label extension trial, and 2 phase 3 randomized controlled clinical trials. Risankizumab was administered intravenously at doses of 200, 600, and 1200 mg and was administered subcutaneously at a dose of 180 mg. The rate of clinical remission, based on a CDAI of less than 150, was 37% (15/41 patients) with 200 mg of risankizumab in the phase 2 open-label trial; the rates of clinical remission were higher in the 2 phase 3 trials, in which risankizumab was administered at either 600 or 1200 mg (42% vs 40% and 45% vs 42%, respectively). Rates of endoscopic remission in the phase 2 and phase 3 trials ranged from 19% to 24% with 600 mg of risankizumab and from 20% to 24% with 1200 mg of risankizumab. In the phase 3 trials, rates of AEs ranged from 51% to 59% with 1200 mg of risankizumab and from 48% to 56% with 600 mg of risankizumab; in the phase 2 open-label trial, 600 mg of risankizumab was associated with a higher rate of AEs (76%). In the real-world GETAID cohort study, 600 mg of risankizumab was associated with a 20% rate of AEs and a 7% rate of serious AEs.