Introduction

There is limited real-world evidence regarding the effectiveness and safety of risankizumab in patients with Crohn’s disease. This multicenter observational study aimed to evaluate the clinical outcomes of risankizumab in Crohn’s disease across several hospitals in Andalusia.

Aims & Methods

Clinical and biochemical data were ambvispectively collected from 160 patients who started risankizumab therapy at ten centers participating in the AIRIS-Crohn registry. Clinical remission (CR) was defined as a Harvey-Bradshaw Index (HBI) score below 5. Combined clinical and biochemical remission (CBR) required HBI <5, C-reactive protein (CRP) <5 mg/L, and fecal calprotectin <250 μg/g. Steroid-free remission (SFR) was defined as HBI <5 with no corticosteroid use from week 12 onward. Outcomes were assessed at weeks 12 and 24.

Results

A total of 160 patients were included, with a mean age of 50 years (range 19–84), and 48% were male. Ileal involvement was present in 49%, and upper gastrointestinal involvement in 6%. Extraintestinal manifestations were observed in 38%, and perianal disease in 56%. The average disease duration was 15 years, and 40% had a history of surgery. Patients had previously failed an average of 2.5 advanced therapies. At initiation, 3% were on immunomodulators and 30% on corticosteroids. At week 24, 89% remained on 360 mg every 8 weeks, 6% required dose intensification to every 6 weeks, and 5% to every 4 weeks.
At week 12, among 129 patients, 49% achieved CR (p<0.001) and 8% achieved CBR (p=0.041). At week 24, among 81 patients, 37% achieved CR (p<0.001), 3% achieved CBR (p=0.480), and 34% achieved SFR (p=0.007). The mean baseline HBI was 8, decreasing to 5.4 at week 12 and 6.1 at week 24 (p<0.001). Mean baseline fecal calprotectin was 1761 μg/g, decreasing to 1151 μg/g at week 12 and 1091 μg/g at week 24 (p<0.001). CRP levels also declined, though not significantly (from 12.9 mg/L at baseline to 8.4 mg/L at week 12 and 7.4 mg/L at week 24; p=0.407) (Table 1).
Patients with ≥2 prior advanced treatment failures showed significantly lower 6-month clinical remission (32.9% vs 64.3% in 1-failure group, p=0.029) and steroid-free remission rates (28.9% vs 64.3%, p=0.014).
Treatment discontinuation occurred in 12.5% of patients, primarily due to lack of response. Adverse events were reported in 5.6%, mainly cutaneous reactions, leading to discontinuation in five cases.

Table 1: Effectiveness Outcomes

Conclusion

Risankizumab demonstrated favorable effectiveness and safety in a cohort of highly refractory Crohn’s disease patients, with 88% maintaining therapy through follow-up. Composite remission rates remained low across all groups (<9%), highlighting the challenge of achieving combined clinical and biochemical targets in multirefractory CD. These results align with real-world evidence showing risankizumab maintains effectiveness in patients with multiple biologic failures, though response rates diminish with increasing treatment refractoriness.