DOP059 Lack of significance of treatment-emergent anti-drug antibodies on efficacy of mirikizumab in patients with moderately-to-severely active Crohn’s Disease: Results from the VIVID-1 study
Authors: Jairath V , Ananthakrishnan A , Ben-Horin S , D’Haens G , Hisamatsu T , Sands B , Fisher D A , Protic M , Moses R , Yu G , Chan-Diehl F , Vermeire S 
Published: January 2025

Background

Results from the phase 3 VIVID-1 study, NCT03926130, showed efficacy of mirikizumab (miri), a p19-directed antibody against IL-23, in patients with moderately-to-severely active Crohn’s disease (CD). VIVID-1 co-primary and gated endpoints, including comparison with ustekinumab (uste), are already reported1, 2. Immunogenicity is recognised as a leading contributor of loss of response to biologic therapies for approved treatments in inflammatory bowel disease3. Patients treated with miri were tested for anti-drug antibodies (ADA) in VIVID-1. We present results showing the immunogenicity effect on miri-treated patients.

Methods

Patients were randomised 6:3:2 to miri (N=579), uste (N=287), or placebo (N=199) in VIVID-1. Miri was administered intravenously at week (W) 0, W4 and W8 (induction), then subcutaneously every 4 weeks from W12 to W52 (maintenance). A validated acid-dissociation drug resistant assay was developed for the measurement of ADA in multiple patient samples throughout the study.

Patients in the primary analysis set who were randomised to miri at baseline and had a non-missing baseline ADA result and at least 1 non-missing postbaseline ADA result were used in the analyses. The potential impact of ADA and ADA titer on efficacy outcomes was assessed using the co-primary efficacy endpoints of VIVID-12. These endpoints were assessed according to the presence or absence of treatment emergent (TE) ADA and by titer groupings. Results were analysed separately for low- and high-titer TE ADA based on a cutoff of 1:160, considering high-titer TE ADA may be more associated with clinical outcomes4.

Results

Of 571 participants in the analysis population, 12.6% (n=72) were TE ADA-positive. The majority (66.7%, n=48) of TE ADA-positive patients had ADA titers of &lt;1:160. Figure shows that similar proportions of TE ADA-positive and TE ADA-negative patients achieved composite clinical remission and endoscopic improvement after 52 weeks of continuous treatment. Similarly, the subgroup of patients with high-titer TE ADA ≥1:160 achieved comparable rates of composite clinical remission and endoscopic improvement as TE ADA-negative patients. No overall clinically meaningful differences were observed based on TE ADA positivity.

Conclusion

The results from this study show that the overall immunogenicity of miri is low. TE ADA did not adversely impact the clinical efficacy of miri for patients with moderately-to-severely active CD. This was also true in the subgroup of patients with high-titer TE ADA.

References

1.Jairath V, Sands BE, Bossuyt P, et al. OP35 Efficacy of mirikizumab in comparison to ustekinumab in patients with moderate to severe Crohn’s disease: Results from the phase 3 VIVID 1 study. J Crohns Colitis 2024;18Supplement_1:i62–i64.

2.Ferrante M, Danese S, Chen M, et al. OP05 Primary efficacy and safety of mirikizumab in moderate to severe Crohn’s Disease: results of the treat-through VIVID 1 study. J Crohns Colitis 2024;18Supplement_1:i7-i9.

3.Vermeire S, Gils A, Accossato P, et al. Immunogenicity of biologics in inflammatory bowel disease. Ther Adv Gastroenterol. 2018;11:1–13.

4.Tan EM, Feltkamp TE, Smolen JS, et al. Range of antinuclear antibodies in "healthy" individuals. Arthritis Rheum. 1997;40(9):1601-11.