Risankizumab is effective following ustekinumab failure in Crohn’s disease: A real-world study from a tertiary center

Abstract

BACKGROUND

Crohn’s disease (CD) is a chronic immune-mediated inflammatory condition with significant morbidity. Several advanced therapies are now licenced for its treatment; however, data on superiority and optimal sequencing remain limited. The SEQUENCE trial demonstrated the superiority of risankizumab, a selective interleukin (IL)-23p19 inhibitor, over ustekinumab, an IL-12/23 inhibitor widely used in CD. Prior ustekinumab use may reduce risankizumab efficacy, and it remains unclear whether switching is effective in real-world practice, especially in refractory CD.

AIM

To assess if in those with uncontrolled disease on ustekinumab, switching to risankizumab is effective.

METHODS

A retrospective review of electronic health records was conducted for adult CD patients at a tertiary center who switched directly from ustekinumab to risankizumab between December 2023 and September 2024. Disease activity was assessed using clinical [Harvey-Bradshaw Index (HBI)], biochemical [C-reactive protein (CRP), albumin, faecal calprotectin], and endoscopic parameters at baseline, 3, 6, and 9 months.

RESULTS

Fifty-one patients with a mean disease duration of 12.7 years were included. HBI decreased significantly at all timepoints (P < 0.001), with clinical remission rates increasing from 37.1% at baseline to 94.4% at 9 months. Albumin increased significantly, while CRP and calprotectin showed numerical improvements without statistical significance. Superior responses were seen in patients with secondary loss of response (SLOR) to ustekinumab compared to primary non-response. No serious adverse events occurred.

CONCLUSION

Switching from ustekinumab to risankizumab in active CD led to significant clinical and biochemical improvements and high remission rates, particularly in patients with SLOR. These findings support risankizumab as an effective option following ustekinumab failure in refractory CD.

Keywords: Crohn's disease; Risankizumab; Ustekinumab; Advanced therapy

Core Tip: Despite evidence of superiority of risankizumab over ustekinumab when managing Crohn’s disease, it is unknown if switching from ustekinumab to risankizumab is effective. This retrospective study evaluated outcomes in 51 adults who switched from ustekinumab to risankizumab. Significant reductions in Harvey-Bradshaw Index scores were observed at all timepoints, with remission rates rising from 37.1% to 94.4% over 9 months. Albumin, C-reactive protein and calprotectin also improved. Patients with secondary loss of response to ustekinumab responded better than primary non-responders. No serious adverse events occurred. These findings support risankizumab as a safe, effective option after ustekinumab failure in refractory Crohn’s.