P0722 Efficacy and Safety of Risankizumab in Patients With Moderate to Severe Crohn’s Disease: Results From the One-Year SEQUENCE Open-Label Long-Term Extension
Authors: Peyrin-Biroulet L , Atreya R , Danese S , Lindsay J O , Chapman J C , Anschutz T , Huang X , Zambrano J , Platt A , Joshi N , Cross R K 
Published: January 2025

Abstract

Background
Part 2 of the ongoing SEQUENCE study examines the long-term efficacy and safety of risankizumab (RZB), an interleukin-23 p19 inhibitor, in patients (pts) with moderate to severe Crohn’s disease (CD). Here, we report the 1-year results from part 2 of the SEQUENCE study.

Methods
In part 2 of SEQUENCE (NCT04524611), pts randomized to the RZB arm who completed the week (wk) 48 visit could continue to receive open-label 360mg subcutaneous (SC) RZB maintenance dose every 8 wks (Q8w).1 Pts with inadequate response (increased symptoms plus objective marker of inflammation) during part 2 could receive rescue therapy (1 x 600 mg intravenous RZB, then 360 mg RZB SC Q8w). Clinical remission (per CD activity index [CDAI] and per stool frequency [SF]/abdominal pain score [APS]), steroid-free clinical remission, Inflammatory Bowel Disease Questionnaire [IBDQ] response, and IBDQ remission (endpoints defined in Figure footnote) were assessed at wks 56 (baseline of OLE), 80, and 104. Data were assessed for all intent-to-treat pts using as observed (AO) regardless of rescue therapy. Data were also assessed per nonresponder imputation (NRI), where patients were categorised as nonresponders for visits with missing assessments, visits after premature discontinuation of study, and visits after initiation of rescue therapy (if applicable). Treatment-emergent adverse events (TEAEs) reported on or after the first dose in part 2 were analysed (cutoff date: July 11, 2024).

Results
A total of 224 pts entered part 2 of SEQUENCE. Among the intent-to-treat pts, clinical remission rates (per AO data) remained stable from wk56 to wk104 (CDAI: 75.3% [168/223] to 84.4% [141/167]; SF/APS: 71.2% [158/222] to 74.7% [124/166]) (Figure). Most pts who achieved clinical remission were not receiving steroids at the corresponding visits (Figure). Pts also demonstrated sustained and clinically meaningful improvements in IBDQ response (86.7% [157/181]; AO data) and IBDQ remission (65.3% [126/193]; AO data) at wk104 (Figure). Similar results to AO data were observed per NRI data (Figure). Sixteen (7.1%) pts received rescue therapy during part 2, of which 77.8% (7/9) achieved wk104 clinical remission (CDAI and SF/APS) (AO data). The profiles of TEAEs and TEAEs of safety interest were consistent with the known safety profile of RZB, and adjudicated major cardiovascular adverse events, malignancies, serious infections and hepatic events remained stable with no new safety risks identified (Table).2,3 No deaths occurred during the OLE.

Conclusion
Pts who received 104 wks of continuous RZB therapy in SEQUENCE demonstrated durable clinical efficacy and quality of life benefits. The safety profile is consistent with the known safety profile of RZB and supports long-term RZB treatment.

References
1.Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease. N Engl J Med. 2024 Jul 18;391(3):213–23.
2.Papp KA, de Vente S, Zeng J, Flack M, Padilla B, Tyring SK. Long-Term Safety and Efficacy of Risankizumab in Patients with Moderate-to-Severe Chronic Plaque Psoriasis: Results from a Phase 2 Open-Label Extension Trial. Dermatol Ther (Heidelb). 2021 Apr;11(2):487–97.
3.Ferrante M, Panaccione R, Colombel JF, Dubinsky M, Hisamatsu T, Lindsay JO, et al. DOP53 Long-term Efficacy and Safety of Risankizumab in Patients With Moderate to Severe Crohn’s Disease up to 3 Years of Treatment: Results From the FORTIFY Open-Label Long-term Extension. Journal of Crohn’s and Colitis. 2024 Jan 24;18(Supplement_1):i168–70.