Introduction

Perianal Crohn’s disease (pCD) represents a challenging phenotype of Crohn's disease (CD). While risankizumab (RZB) has demonstrated efficacy in luminal CD, its role in pCD remains unknown. We aimed to evaluate the effectiveness of RZB in pCD and compare the outcomes with other biologics including anti-TNF, ustekinumab (UST), and vedolizumab (VDZ).

Aims & Methods

This retrospective multicenter study performed at nine international centers included adult patients with pCD who initiated RZB as advanced-line (second or more) therapy between 2020 and 2024. Historical controls included pairwise propensity-scored matched pCD patients treated with anti-TNF, UST, or VDZ as second- or third-line therapies. The primary outcome was clinical remission in patients with active pCD, defined as complete resolution of perianal symptoms. Secondary outcomes included clinical response (any symptomatic improvement) in active perianal disease, and relapse rates among patients with inactive pCD at baseline, defined as new or recurrent signs or symptoms of perianal disease.

Results

A total of 214 patients with active pCD were included: 59 (27.6%) received RZB, 62 (29.0%) anti-TNF, 57 (26.6%) UST, and 36 (16.8%) VDZ. Clinical remission was achieved in 58% of patients treated with RZB, compared to 32.9% of those receiving non-RZB therapies (p = 0.01), including 27% for anti-TNF, 44% for UST, and 25% for VDZ. Clinical pCD response rates were 81% for RZB, compared to 71% for anti-TNF, 88% for UST, and 44% for VDZ; p < 0.001. In propensity score–matched comparisons, remission rates with RZB were numerically higher than anti-TNF (56% vs. 31%, p = 0.056) and VDZ (58% vs. 29%, p = 0.08), and comparable to UST (53% vs. 43%, p = 0.5). The median time to clinical response with RZB was three months [IQR: 2–3.5], comparable to anti-TNF (3 [IQR: 2–4], p = 0.4), but significantly shorter than UST (5 [IQR: 4–6], p < 0.001) and VDZ (6.5 [IQR: 4–8], p < 0.001).
Among 160 patients with inactive pCD at baseline, matched analysis showed significantly lower relapse rates with RZB compared to anti-TNF (2% vs. 22%, p = 0.004) and VDZ (0% vs. 28%, p = 0.004), with no significant difference compared to UST (3% vs. 15%, p = 0.2).

Conclusion

Risankizumab demonstrates favorable clinical response, faster time to response, and higher remission rates in active pCD, along with the lowest relapse rates in inactive disease. These results support RZB as an effective therapeutic option for pCD, warranting prospective validation.

Disclosure

No conflicts of interest were declared in relation to this study.