DOP016 Efficacy and Safety of Risankizumab in Patients With Moderate to Severe Crohn's Disease With 3 Years of Treatment: Results From the FORTIFY Open-Label Long-Term Extension

Background

The FORTIFY maintenance open-label extension (OLE) is an ongoing phase 3 substudy evaluating the long-term efficacy and safety of risankizumab (RZB), a p19 interleukin-23 inhibitor, in patients (pts) with moderate to severe Crohn’s disease (CD). Previously, we presented the 2-year (Y) results from the OLE assessed through MAR2023, at which time most pts had yet to complete the week (W) 152 visit. Here, we report the full 2Y results with all pts having completed the W152 study visit.

Methods

Pts completing 52W of RZB maintenance were eligible to enroll in the FORTIFY (NCT03105102) OLE1,2, during which pts received 180mg subcutaneous (SC) RZB every 8W (Q8W), starting at W56, except pts who previously received rescue therapy (details in Figure footnote) as they continued 360mg SC Q8W in the OLE. Pts with inadequate response (increased symptoms + objective marker of inflammation) during the OLE received rescue therapy and remained on 360mg SC through the end of the study. Efficacy (endpoint definitions in Figure footnote) was assessed through W152 of RZB treatment (2Y in the OLE) using as observed (AO) and nonresponder imputation (NRI) methods. Data before receiving rescue therapy and upon/after receiving rescue therapy in the OLE are presented separately. All enrolled pts were included in the safety analysis. Treatment-emergent adverse events (TEAEs) reported on/after the first dose in the OLE were summarized (cutoff date: 01MAR2024).

Results

In the OLE, 1148 pts received ≥1 dose of RZB. Prior to receiving rescue therapy (pt numbers in Figure footnote), efficacy rates (per AO data) remained stable from W56 to W152 (both doses) for stool frequency/abdominal pain score (SF/APS) clinical remission (180mg, 69.8% to 74.8%; 360mg, 46.6% to 61.8% (84/136) and per CD Activity Index (CDAI) clinical remission (180mg, 72.9% to 81.1%; 360mg, 54.5% to 72.0%, endoscopic response (180mg: 57.5% to 75.7%; 360mg: 40.7% to 66.0%), and endoscopic remission (180mg: 41.6% to 62.4%; 360mg: 24.7% to 43.8%) (Figure). Similar results were observed per NRI data. Pts who received rescue therapy in the OLE (180mg, n=147; 360mg, n=76) also demonstrated clinical and endoscopic improvements by W152, irrespective of RZB dose received prior to rescue. The profiles of TEAEs and AEs of special interest were consistent with RZB’s known safety profile (Table).3,4

Conclusion

Durable clinical and endoscopic efficacy was observed with long-term RZB maintenance therapy in the FORTIFY OLE. Pts who received rescue therapy in the OLE also showed clinical and endoscopic improvements by W152. No new safety risks for RZB were identified, supporting its long-term use in treating CD.

References

1. Ferrante M, Feagan BG, Panés J, Baert F, Louis E, Dewit O, et al. Long-Term Safety and Efficacy of Risankizumab Treatment in Patients with Crohn’s Disease: Results from the Phase 2 Open-Label Extension Study. Journal of Crohn’s and Colitis. 2021 Jun 2;jjab093.

2. Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. The Lancet. 2022 May;399(10340):2031–46.

3. Papp KA, Blauvelt A, Puig L, Ohtsuki M, Beissert S, Gooderham M, et al. Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis: Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up. Journal of the American Academy of Dermatology. 2023 Dec;89(6):1149–58.

4. 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.