Introduction
Risankizumab is a selective IL23 inhibitor that was approved by the FDA for the treatment of moderately to severely active Crohn’s disease (CD) in June 2022. The effectiveness of risankizumab in ustekinumab-experienced patients is of particular interest due to a similar mechanism of action. Here, we present our one-year experience of risankizumab treatment in CD patients, with a focus on the comparison between ustekinumab-naïve and ustekinumab-experienced patients.
Aims & Methods
We prospectively followed patients with CD treated with risankizumab in our center and documented their clinical disease activity using Harvey-Bradshaw Index (HBI) score at baseline and at weeks 12, 26, and 52 after treatment initiation. We included patients who were treated for active luminal disease, defined as HBI≥5, fecal calprotectin (FCP) ≥250, steroid dependance or who had evidence of active disease per ileocolonoscopy or imaging in the effectiveness analysis. We excluded from the effectiveness cohort patients with ileostomy, J-pouch or surgery within the 6 months prior to risankizumab commencement. We recorded adverse events in all patients. Patients who stopped treatment due to ineffectiveness or intolerance were counted as non-responders for the purpose of remission-rate calculations at each time point.
Results
253 patients were treated with risankizumab and had at least 12 weeks of follow up. 153 patients were included in the effectiveness cohort. Demographics and patient characteristics are detailed in Table 1. At week 12, 71.3% (92/129) achieved clinical remission (CR), and 63.6% (82/129) achieved steroid-free clinical remission (SFCR). At week 26, 64.5% (60/93) and 62.4% (58/93) achieved CR and SFCR respectively. At 1 year, CR rate was 53.3% (40/75), and SFCR rate was 48% (36/75). Median FCP was 385.5µg/g (IQR 168.25-905, n=33) at baseline, 102.5µg/g (IQR 39-354, n=20) at week 12, 118µg/g (IQR 40-183, n=24) at week 26, and 63µg/g (IQR 19-122, n=16) at 1 year. 79.6% (74/93) remained on risankizumab 6 months after treatment initiation, and 64.3% (52/75) of patients remained on treatment at one year. In the effectiveness cohort, 47.7% (73/153) of patients were ustekinumab-naïve, and 53.3% (80/153) were ustekinumab-experienced. SFCR rates in ustekinumab-naïve and ustekinumab-experienced patients were 73.8% (45/61) vs. 54.4% (37/68) at week 12 (p=0.0282), 67.4% (31/46) vs. 57.4% (27/47) at week 26 (p=0.3936), and 54.1 (20/37) vs. 42.1% (16/38) at one year (p=0.3588), respectively.
Minor adverse events were documented in 12.6% (32/253) of patients, including fatigue, pruritus, nausea, joint pain, and upper-respiratory tract infection. One patient had a suspected allergic reaction to the first infusion and treatment was not continued. In 1.9% (5/253) of patients, treatment was discontinued d/t adverse events. No serious adverse events were observed.
Characteristic
| All patients (n=253)
| Patients in the effectiveness cohort (n=153)
|
Age, y, median (IQR)
| 42 (30-54) | 41.5 (30.25-54) |
Disease duration y, median (IQR)
| 14 (9-22) | 12 (8-22.75) |
Female sex, n (%)
| 151 (60.9) | 89 (58.2) |
White race
| 198 (80.2) | 116 (75.8) |
Smoking history, n (%)
current
former
| 13 (5.3)
56 (23) | 10 (6,6)
38 (25) |
Baseline HBI, median (IQR)
| 5 (2-8) | 5.5 (3-9) |
Advanced therapy naïve n (%)
| 28 (11) | 14 (9.1) |
History of bowel resection, n (%)
| 158 (65) | 89 (59.3) |
Steroid treatment at baseline, n (%)
| 61 (29) | 48 (33.6) |
Conclusion
In this large real-world experience in patients with CD, we found that risankizumab has excellent efficacy and safety, with notable effectiveness in ustekinumab-experienced patients.
