Effectiveness and Safety of Risankizumab Induction Therapy in Crohn's Disease: Prospective Real-World Experience in a Large Tertiary Center

Introduction: Risankizumab was approved by the FDA in June 2022 for the treatment of moderately to severely active Crohn’s disease. We report the real-world experience with risankizumab in Crohn’s disease in a large tertiary inflammatory bowel disease (IBD) center. Methods: This is a prospective analysis of clinical outcomes of patients with Crohn’s disease treated with risankizumab. Clinical evaluations occurred at weeks 0, 2, 4, 8 and 12 using the Harvey-Bradshaw Index (HBI), fecal calprotectin (FCP) and C-reactive protein (CRP). Efficacy analysis was performed for patients with active luminal disease at baseline, defined as HBI≥5 and/or FCP≥250µg/g, and/or documentation of ulcers in ileocolonoscopy, and/or evidence of active disease per imaging. Clinical remission was defined as HBI< 5. Clinical response was defined as ≥3-point decrease in HBI and/or HBI< 5. Adverse events were documented. Results: 94 patients were followed for 12 weeks. Patients with ileostomy and patients that started treatment for indications other than active luminal disease were excluded from the effectiveness analysis. 54 patients met criteria to be assessed for treatment efficacy. Baseline characteristics are described in Table 1. Median HBI was noted to decrease by week 2 and plateaued by week 8 (Figure 1A). At week 12, 78% of patients achieved clinical response and 70% achieved clinical remission. This did not differ significantly between ustekinumab-naïve and ustekinumab-experienced patients (80% vs 76% P=0.72, 76% vs 65% P=0.11, respectively). Steroid-free clinical remission was higher in ustekinumab-naïve compared to ustekinumab-experienced patients (72% vs. 55%, P=0.003) (Figure 1B). 67% of patients (22/33) had CRP in the normal range at baseline, compared to 71% at week 12 (15/21). Median FCP decreased from 395 (IQR 329-940, n=9) at baseline, to 114 (IQR 0-163, n=25) at week 12. Minor adverse events were documented in 12% of patients, including fatigue, pruritus, nausea, joint pain, paresthesia, and upper-respiratory tract infection. One patient had a suspected allergic reaction to the infusion and treatment was stopped after one dose. No serious adverse events were observed. Conclusion: We demonstrate the clinical effectiveness and safety of risankizumab in a real-world tertiary population of patients with Crohn’s disease. The benefit was similar even in patients previously treated with ustekinumab. Table 1. - Baseline characteristics of Crohn’s disease patients included in the effectiveness analysis Characteristic n=54 Age, y, median (IQR) 45.5 (36-57) Disease duration y, median (IQR) 19.5 (9-27) Sex n (%) Female 30 (56) Male 24 (44) Smoking history n (%) never 29 (57) former 18 (35) current 4 (8) Disease location and phenotype n (%) Ileal 16 (30) Colonic 7 (13) Ileocolonic 30 (57) Fifrostenotic 15 (28) Penetrating 22 (42) Perianal 24 (44) Baseline HBI, median (IQR) 6 (5-9) Advanced therapy exposed, n (%) Infliximab 29 (53) Adalimumab 35 (65) Vedolizumab 23 (43) Ustekinumab 29 (53) Biologic naïve, n (%) 4 (7) 2 or more prior advanced therapies, n (%) 32 (59) History of bowel resection n (%) 32 (59) Steroid treatment at baseline n (%) 19 (35) Figure 1.: (A) HBI at weeks 0, 2, 4, 8, and 12. (B) Rates of clinical response, clinical remission, and steroid-free clinical remission at week 12 for ustekinumab naïve vs ustekinumab-experienced patients.