Efficacy of Mirikizumab in Comparison to Ustekinumab in Patients With Moderate-to-Severe Crohn’s Disease: Results From the Phase 3 VIVID-1 Study

Keywords:  Crohn’s Disease; Mirikizumab; VIVID 1 Study

Objective:  Here we compared mirikizumab (miri), a p19-directed anti-IL-23 antibody, to ustekinumab (uste), a p40 directed anti-IL-12/IL-23 inhibitor, from the Phase 3, randomised, double-blind, double-dummy, active- and PBO-controlled, treat-through (TT) study, VIVID-1 (NCT03926130).

Methods:  Adult pts (N=1065) were randomised 6:3:2 to miri (N=579) 900mg intravenously (IV) every 4 weeks (Q4W) to W12, then 300mg subcutaneously (SC) Q4W to W52, uste (N=287) one ~6 mg/kg IV dose, then 90mg SC Q8W to W52 or PBO (N=199).

Results:  Pts treated with miri achieved all key major secondary endpoints (p<.000001) compared to PBO. Miri achieved non-inferiority to uste for clinical remission by Crohn’s Disease Activity Index (CDAI) (p=0.113117). Although superiority to uste in endoscopic response was not achieved (p=0.51), in biologic failed pts miri demonstrated a numerical trend towards greater response rates compared to uste for endoscopic response and clinical remission by CDAI. The overall safety profile was consistent with the known safety profile of miri. The proportion of treatment-emergent adverse events (TEAE) were similar for miri (78.6%) and uste (77.3%); most common TEAEs were COVID-19, anaemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis and injection-site reaction. Instances of serious adverse events were comparable for miri (10.3%) and uste (10.7%).

Conclusion:  Miri achieved non-inferiority to uste for clinical remission by CDAI. In biologic-failed pts, miri had a numerical trend towards greater response compared to uste in clinical and endoscopic endpoints, with an acceptable safety profile.