Mirikizumab Improved the Quality of Life in Patients with Crohn's Disease Regardless of Their Previous Biologic Failure Status: Results from the Phase 3 VIVID-1 Study
Background:
The phase 3, active-controlled, VIVID-1 study (NCT03926130) showed the efficacy of mirikizumab, an anti-IL-23p19 antibody, versus placebo (PBO) and ustekinumab in adults with moderately-to-severely active Crohn’s disease (CD). Co-primary and gated-secondary outcomes, including comparisons with ustekinumab, are presented elsewhere. Here, we present the effect of mirikizumab versus PBO on health-related quality of life (HRQoL) by prior biologic failure in VIVID-1.
Methods:
This analysis used data for adult patients randomized to mirikizumab (N=579) or PBO (N=199), with (bio-failed) and without (not bio-failed) prior biologic failure, defined as an inadequate response, loss of response, or intolerance to ≥1 biologic therapy approved for CD. Mirikizumab was administered intravenously at week (W) 0, W4, and W8, then subcutaneously every 4 weeks from W12 to W52. At W12, PBO responders continued PBO to W52 while PBO non-responders received mirikizumab as described above. HRQoL endpoints assessed at W12 and W52 included change from baseline in the Inflammatory Bowel Disease Questionnaire (IBDQ) total score and the Work Productivity and Activity Impairment Questionnaire (WPAI): CD scores. IBDQ response and IBDQ remission rates were evaluated at W12, W52, and using composite endpoints with W12 clinical response by Patient Reported Outcome (≥30% decrease in stool frequency and/or abdominal pain score and neither score worse than baseline) in consideration of the fact that PBO non-responders were switched to mirikizumab after W12. Missing data and data from PBO non-responders were imputed using modified baseline observation carried forward (continuous endpoints) and non-responder imputation (binary endpoints). All <italic>P-</italic>values reported in this analysis are nominal.
Results:
At W12 and W52, greater changes from baseline in IBDQ total score were observed with mirikizumab in the bio-failed (least squares mean [LSM] difference: W12=19.4; W52=30.4; both <italic>P<</italic> 0.001) and not bio-failed (W12=19.4; W52=25.9; both <italic>P<</italic> 0.001) subgroups. IBDQ response rates were higher for mirikizumab in the bio-failed (difference: W12=26.4; W52=49.4; composite=36.2; all <italic>P<</italic> 0.001) and not bio-failed (W12=21.5; W52=37.1; composite=19.4; all <italic>P<</italic> 0.001) subgroups. Similarly, higher IBDQ remission rates were noted with mirikizumab in the bio-failed (difference: W12=26.8; W52=42.5; composite=31.5; all <italic>P<</italic> 0.001) and not bio-failed (W12=22.7; W52=35.6; composite=23.5; all <italic>P<</italic> 0.001) subgroups. Greater changes from baseline were observed with mirikizumab for all WPAI: CD scores in the bio-failed subgroup at W12 (LSM difference: -7.9 to -11.1; all <italic>P<</italic> 0.05) and W52 (LSM difference: -8.8 to -21.6; all <italic>P<</italic> 0.001). At W12, significant improvements versus placebo were observed with mirikizumab in the not bio-failed subgroup for absenteeism and activity impairment (LSM difference: respectively, -6.9 and -7.9; both <italic>P<</italic> 0.05); significance was not achieved for presenteeism (LSM difference: -4.9) and work impairment (LSM difference: -5.5). At W52, significant improvements with mirikizumab versus placebo were noted for presenteeism, work impairment, and activity impairment in the not bio-failed subgroup (LSM difference: -9.1 to -10.5; all <italic>P<</italic> 0.05) but not for absenteeism (LSM difference: -2.9).
Conclusions:
Mirikizumab improved HRQoL in patients with and without prior biologic failure in the phase 3 VIVID-1 study. The effect of mirikizumab on HRQoL was generally consistent across subgroups, making it a valuable treatment option for patients with moderately-to-severely active CD.
