S749 Mirikizumab Improves Work Productivity and Activity Impairment Questionnaire Scores in Moderately-to-Severely Active UC: The LUCENT-1 and LUCENT-2 Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies

Abstract

Introduction: This analysis compares mirikizumab (miri) to placebo (PBO) for improvement in the Work Productivity and Activity Impairment Questionnaire Ulcerative Colitis (WPAI:UC) in participants of LUCENT-1 and LUCENT-2, phase 3 clinical trials who had moderately-to-severely active UC and had failed prior conventional or biologic therapies. Methods: 1162 patients (pts) in LUCENT-1 12-week induction study were randomized 3:1 to receive 300mg miri or PBO intravenously once every 4 weeks (Q4W). 544 pts who completed induction and achieved Modified Mayo Score (MMS) Clinical Response with miri were rerandomized 2:1 in LUCENT-2 to a 40W maintenance treatment of miri 200mg or PBO subcutaneously Q4W for a total of 52W treatment. Randomization was stratified by previous biologic therapy failure, baseline (BL) corticosteroid use, and region. Stratification for LUCENT-1 included BL disease activity, and LUCENT-2 included LUCENT-1 clinical remission status. WPAI:UC scores between 0%-100% were calculated from pts-reported measurements, with a higher score indicating greater impairment. Evaluations of the WPAI:UC domain of overall activity impairment included all respondents, while domains of absenteeism, presenteeism, and work productivity loss required employment at the time of the analyses. Changes from W0 BL at W12 (induction) and W40 (maintenance; 52W treatment) were evaluated by analysis of covariance. Stratification factors and BL scores were used as covariates. Results were reported as least squares mean differences (LSM diff) of miri vs PBO. Results: At BL, 60.67% (N=705) of pts reported employment. At W12 of induction, activity impairment, absenteeism, presenteeism, and work productivity loss were significantly reduced from BL in miri treated pts vs PBO (Table). Of the pts who achieved W12 MMS Clinical Response, those who continued receiving miri had sustained improvements in the WPAI:UC change from BL at W40 of maintenance vs those who received PBO, including activity impairment, presenteeism, and work productivity loss. Absenteeism was not significantly different between treatment groups at W40 (52W treatment). Conclusion: Compared to PBO, miri treatment provided statistically significant improvements in work productivity and activity impairment as measured by the WPAI:UC. Improvements were observed during induction and maintenance therapy in pts with moderately-to-severely active UC who had failed prior conventional or biologic therapies. Table 1. - Changes from Baseline in Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis Scores at Week 12 and Week 40 (52 Weeks of Continuous Treatment) Activity Impairment of All Participants Absenteeism from Work of Employed Participants Presenteeism at Work of Employed Participants Overall Work Impairment of Employed Participants LSM Change from BL (SE) LSM Diff 1 (SE) LSM Change from BL (SE) LSM Diff 1 (SE) LSM Change from BL (SE) LSM Diff 1 (SE) LSM Change from BL (SE) LSM Diff 1 (SE) Induction Period Change from Baseline (Week 12) PBO IV Q4W (N=294) −12.90 (1.41) −3.45 (1.75) −13.94 (1.75) −14.91 (1.99) Miri 300 mg IV Q4W (N=868) −20.90 (0.87) −8.01 (1.57)*** −7.88 (1.03) −4.43 (1.95)* −19.25 (1.03) −5.31 (1.95)** −20.65 (1.16) −5.74 (2.20)** Maintenance Period Change from Induction Baseline of Miri Induction Responders (Week 40; 52 Weeks of Continuous Therapy) PBO SC Q4W (N=179) −22.91 (1.77) −10.78 (1.68) −19.82 (1.98) −22.59 (2.26) Miri 200 mg SC Q4W (N=365) −32.46 (1.35) −9.55 (1.98)*** −12.85 (1.28) −2.07 (1.93) −29.42 (1.51) −9.60 (2.28)*** −31.72 (1.73) −9.13 (2.61)*** Abbreviats: BL=Baseline; IV=intravenous; LSM=least squares mean; LSM Diff=least squares mean difference; Miri=mirikizumab; N=number of participants in the analysis population; PBO=placebo; Q4W=every 4 weeks; SC=subcutaneous; SD=standard deviation; SE=standard error.1The LSM Diff is the least squares mean change from baseline in WPAI:UC scores of participants receiving mirikizumab minus the LSM change from baseline in WPAI:UC scores of participants receiving placebo. *p< 0.05, **p< 0.01, ***p< 0.001.