DOP046 Effectiveness and Safety of Mirikizumab after switching from Ustekinumab in patients with moderate to severe Crohn’s disease: results from a long-term extension study
Authors: D'Haens G , Laharie D , Dulai P S , Seibold F , Siegmund B , Abraham B , Malter L , Protic M , Morris N , Hozak R R , Moses R E , Ugolini Lopes M , Durand F , Yu G , Vermeire S 
Published: January 2025

Abstract

Background
Mirikizumab (Miri), an interleukin-23p19 inhibitor, has shown strong efficacy and was well-tolerated in patients with moderately-to-severely active Crohn’s disease (CD) in the Phase 3 study VIVID-1 (NCT03926130) (1). We report one-year efficacy and safety of Miri in patients treated with ustekinumab (Ust) in VIVID-1 who enrolled in the open label extension study VIVID-2 (NCT04232553).

Methods
Patients who completed VIVID-1, on Ust 6mg/kg intravenous (IV) at week (W) 0, then 90mg subcutaneous (SC) every 8 weeks, and enrolled in VIVID-2 received Miri. Dose assignment in VIVID-2 was dependent on achievement of endoscopic response (≥50% reduction from baseline in Simple Endoscopic Score for Crohn’s Disease [SES-CD]) at W52 of VIVID-1. Endoscopic responders to Ust were switched to Miri SC 300mg every 4 weeks (Q4W); endoscopic non-responders received Miri IV 900mg at W0, W4, and W8, followed by Miri SC 300mg Q4W (Miri IV-SC). Outcomes analysed up to W52 in VIVID-2 included endoscopic response, endoscopic remission (SES-CD ≤4 and ≥2-point reduction from baseline, with no subscore &gt;1 in any individual variable) and clinical remission (Crohn’s Disease Activity Index (CDAI) &lt;150). Safety was assessed from the first Miri dose in VIVID-2 to the cutoff date (02Aug2024); patients who entered VIVID-2 after 01Aug2023 were not included in this interim analysis. Discontinuations or missing data were handled using modified non-responder imputation (mNRI) and observed case (OC) approaches.

Results
Among the 92 endoscopic non-responders to Ust who received Miri IV-SC in VIVID-2, 41.4%(mNRI)/46.2%(OC) achieved endoscopic response, 22.0%/24.4% achieved endoscopic remission and 75.0%/84.8% achieved CDAI remission 52 weeks later (Figure 1A). Among the 122 endoscopic responders to Ust, efficacy was maintained across clinical and endoscopic endpoints following switch to Miri SC (Figure 1B). Of the Ust endoscopic responders who were not in remission, after switching to Miri SC 57.2%/60.0% and 26.5%/28.3% gained CDAI and endoscopic remission respectively, 52 weeks later. Treatment-emergent adverse events (AE) were reported in 64.7% and 62.5% of Miri IV-SC and Miri SC patients, respectively. Serious AEs were reported in 6.9% and 7.0%, and discontinuations due to AE were reported in 1% and 2.3% of patients (Table 1).

Conclusion
The results from VIVID-2 showed clinical and endoscopic efficacy of Miri up to 1 year in patients with moderately-to-severely active CD previously exposed to Ust. Over 40% of Ust endoscopic non-responders in VIVID-1 achieved endoscopic response at W52 of Miri treatment. Safety data were consistent with the known Miri safety profile.

References
1Ferrante, M., S. Danese, M. Chen, G. D'Haens, S. Ghosh, T. Hisamatsu, V. Jairath et al. "OP05 Primary efficacy and safety of mirikizumab in moderate to severe Crohn’s disease: results of the treat-through VIVID 1 study." European Crohn's and Colitis Organisation 2024, Stockholm, Sweden.