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

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

Methods: In part 2 of SEQUENCE, pts randomized to the RZB arm who completed the week (wk) 48 visit could continue on open-label 360mg subcutaneous (SC) RZB maintenance dose every 8 wks (Q8w). [1] Pts with inadequate response during part 2 could receive rescue therapy (1x 600mg intravenous RZB, then 360mg RZB SC Q8w). Clinical remission (per CDAI and per stool frequency [SF]/abdominal pain score [APS]), steroid-free clinical remission, Inflammatory Bowel Disease Questionnaire [IBDQ] response, and IBDQ remission were assessed at wks 52 (baseline of OLE), 76, and 100. Data were assessed for all intent-to-treat (ITT) pts using as observed (AO) regardless of rescue therapy as well as 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. Treatment-emergent adverse events (TEAEs) reported on or after the first dose in part 2 were analysed

Results: 224 pts entered part 2 of SEQUENCE. Among the ITT pts, clinical remission rates (AO) remained stable from wk52 to wk100 (CDAI: 75.3% [168/223] to 84.4% [141/167]; SF/APS: 71.2% [158/222] to 74.7% [124/166]) ([Fig. 1]). Most pts who achieved clinical remission were not receiving steroids at the corresponding visits ([Fig. 2]). Pts also demonstrated sustained and clinically meaningful improvements in IBDQ response (86.7% [157/181]; AO) and IBDQ remission (65.3% [126/193]; AO) at wk100 ([Fig. 1]). Similar results to AO were observed per NRI ([Fig. 2]). 16 (7.1%) pts received rescue therapy during part 2, of which 77.8% (7/9) achieved wk100 clinical remission (AO). TEAEs and TEAEs of safety interest were consistent with the known safety profile of RZB. Adjudicated major cardiovascular adverse events, malignancies, serious infections and hepatic events remained stable with no new safety risks identified ([Table 1]). [2] [3] No deaths occurred during the OLE.

Fig. 1  

Fig. 2  

Table 1 

Treatment-Emergent Adverse Events (TEAEs)	600 mg IV/360 mg SC RZB (N=262) n (%)
Overall TEAE
Any TEAE	243 (92.7)
TEAE related to study drug according to the investigator	87 (33.2)
Severe TEAE	65 (24.8)
Serious TEAE	47 (17.9)
TEAE leading to discontinuation study drug	15 (5.7)
Death	0
TEAE of safety interest
Adjudicated MACE events	0
Serious infections	17 (2.9)
Opportunistic infections excluding tuberculosis and herpes zoster	2 (0.3)
Malignant tumours	4 (0.7)
Herpes zoster	3 (0.5)
Non-melanoma skin cancer (NMSC)	2 (0.3)
Hypersensitivity	52 (8.8)
Hepatic events	36 (6.1)
Injection site reactions	13 (2.2)

E, events; CTE, continuous trial extension; MACE, major adverse cardiovascular event; NMSC, non-melanoma skin cancer; OLE, open-label extension; PY, patient-years; RZB, risankizumab; TEAE, treatment-emergent adverse event. E/100PYs=Events per 100 patient-years. Safety summary includes all patients who received at least one dose of study drug during OLE. TEAEs during OLE were defined as events that begin either on or after the first dose of the study drug and within 140 days after the last dose of study drug in OLE for patients who do not participate in CTE or until first dose of CTE if the patient is enrolled into CTE.

Conclusion: Pts who received 100 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 Peyrin-Biroulet L, Chapman JC, Colombel JF, Caprioli F, D’Haens G, Ferrante M. et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease. N Engl J Med 2024; 391: 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; 11: 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; 18: i168-70