Switching from risankizumab to guselkumab improved clinical and biochemical outcomes in 80% of Crohn's disease patients.
Background
For patients with moderate-to-severe Crohn's disease (CD), interleukin (IL)-23 inhibitors like risankizumab are effective, but a significant proportion experience primary non-response or secondary loss of response. When this occurs, clinicians face a challenge, as switching to another agent within the same IL-23 inhibitor class, especially one with more frequent dosing like guselkumab, lacks supporting evidence. This gap in real-world data leaves an unmet need for salvage strategies in patients failing initial IL-23 blockade.
Study Design
This real-world case series included five CD patients at a Canadian tertiary care center who had either primary non-response or secondary loss of response to risankizumab. Patients were switched to guselkumab, with data collected at baseline, during risankizumab therapy (mean 17.4 months), and after switching. The primary endpoints included changes in CD-PRO2 scores for clinical response and remission, and fecal calprotectin (FCal) for biochemical response and remission. Active disease on baseline endoscopy was noted for four patients.
Results
Among five CD patients with inadequate response to risankizumab, one patient (20%) had primary non-response, and four (80%) experienced secondary loss of response. After switching to guselkumab, with a mean follow-up of 3.8 ± 1.9 months, significant improvements were observed. Mean CD-PRO2 scores dramatically improved from 22.7 to 5.2 post-switching. > Clinical response, defined as a ≥50% reduction in CD-PRO2, was achieved in 4/5 patients (80%), and clinical remission (CD-PRO2 < 8) was similarly achieved in 4/5 patients (80%). Among the four patients with available biochemical data, biochemical response (≥50% reduction in FCal) and remission (normalization of FCal) each occurred in 75% of patients, with a mean FCal reduction of 618 µg/g. Only one patient showed biochemical worsening despite clinical improvement. No safety concerns were reported during the follow-up period.
Key Findings
- Mean
CD-PRO2scores improved from 22.7 to 5.2 after switching to guselkumab. - Clinical response (≥50%
CD-PRO2reduction) was achieved in 4/5 patients (80%). - Clinical remission (
CD-PRO2< 8) was achieved in 4/5 patients (80%). - Biochemical response (≥50%
FCalreduction) occurred in 75% of patients with data. - No safety concerns were reported during the mean 3.8-month follow-up.
Why It Matters
This case series provides initial real-world evidence suggesting that switching from one IL-23 inhibitor (risankizumab) to another (guselkumab) may be a viable salvage strategy for Crohn's disease patients experiencing loss of response. For clinicians and patients, this opens a potential pathway to maintain disease control without resorting to entirely different drug classes, which might have distinct side effect profiles or mechanisms. While not a definitive protocol, the observed clinical and biochemical improvements in 80% of patients indicate that this within-class switch could extend the utility of IL-23 inhibition. Further research is needed to establish optimal timing and patient selection criteria for this approach.
crohn's-disease
risankizumab
guselkumab
il-23-inhibitor
case-series
gastroenterology