RISANKIZUMAB EFFECTIVENESS IN USTEKINUMAB-NAIVE AND USTEKINUMAB EXPERIENCED PATIENTS WITH CHROHN'S DISEASE: REAL WORLD DATA FROM A LARGE TERTIARY CENTER

<div style="direction: ltr;">Background and aims: Risankizumab and ustekinumab are both IL23 inhibitors approved the treatment of moderate to severe Crohn’s disease (CD). They are distinguished by the fact that ustekinumab targets p40, the shared subunit of both IL23 and IL12, while risankizumab targets the p19 subunit and thus selectively inhibits IL23. The effectiveness of risankizumab in ustekinumab-experienced patients is of particular interest due to similar mechanisms of action. We present a large long-term real-world experience with risankizumab in ustekinumab-naïve and ustekinumab-experienced patients with CD.
Methods: We prospectively followed patients with CD treated with risankizumab in our center and documented their disease activity score at weeks 0, 2, 4, 8, 12, 26, and 52. Patient who were treated for active luminal disease, defined as HBI≥5, fecal calprotectin≥250, or evidence of active disease per ileocolonoscopy or imaging were included in the effectiveness analysis. Steroid treatment was recorded. Patients who stopped treatment due to ineffectiveness or intolerance were counted as non-responders for the purpose of remission-rate calculation at each time point.
Results: 102 patients with CD who had active luminal disease were treated with risankizumab and had at least 12 weeks of follow-up. Of them 46 (45%) were ustekinumab-naïve, and 56 (55%) were ustekinumab-experienced. The ustekinumab-experienced patients had longer disease duration and higher rates of prior bowel resection and exposure to multiple advanced therapies (Table 1). Baseline median HBI was higher in the ustekinumab-experienced group. Both groups had a continuous downward trend throughout the follow-up period (Figure 1A). At week 12, 74% (34/46) of the ustekinumab-naïve and 55% (31/56) of the ustekinumab-experienced patients achieved steroid-free clinical remission (SFCR) (P=0.06). At week 26, SFCR rates were 76% (25/33) and 60% (21/35) in ustekinumab naïve and experienced patients respectively (P=0.2). In a subgroup of patients with follow-up of one year, 71% (5/7) and 40% (6/15) were in SFCR at week 52 (P=0.36). Of the patients who achieved SFCR at week 12, 85% of patients in both groups maintained SFCR at week 26 (23/27 and 17/20 in ustekinumab-naïve and ustekinumab-experienced cohorts respectively).
Conclusions: In this large real-world experience with long-term follow-up, we found that patients with CD treated with risankizumab were statistically similarly likely to achieve and sustain SFCR regardless of prior ustekinumab experience. Non-statistical differences noted may reflect the longer disease duration and prior treatment exposure of the ustekinumab-experienced group. These findings support the consideration of risankizumab as a treatment option for patients with CD regardless of their prior exposure to ustekinumab.</div><div style="direction: ltr;"> </div>