S747 Mirikizumab Improves Mental and Physical Health Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies
Bibliographic record
Abstract
Introduction: Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy vs. placebo (PBO) in adult patients (pts) with moderately to severely active ulcerative colitis (UC) in phase 3, randomized, double-blind, PBO-controlled 12-week (W) induction (LUCENT-1/NCT03518086) and 40-W maintenance (LUCENT-2/NCT03524092) studies.1,2 Here we evaluated the effect of miri vs. PBO on Medical Outcomes Study 36-Item Short Form Health Survey (SF-36; version 2) scores. Methods: In the induction study, 1162 pts who had an inadequate response/loss of response/intolerance to conventional/biologic therapy were randomized (3:1) to receive miri 300 mg IV (N=868) or PBO (N=294) every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 in the induction study (miri clinical responders; N=544) were re-randomized (2:1) to miri 200 mg subcutaneous (N=365) or PBO (N=179) Q4W through W40 (i.e., W52 of continuous therapy) in the maintenance study. Least squares mean (LSM) change from baseline in physical (PCS) and mental (MCS) component scores, and 8 domain scores (physical functioning, role-physical, role-emotional, bodily pain, vitality, social functioning, mental and general health) of the SF-36 survey were evaluated at W12 and W40. Treatment comparisons were made using analysis of covariance. Results: During the induction period, significant improvements in PCS (LSM difference vs. PBO [95% CI]: 2.07 [1.21, 2.93]; p< 0.001) and MCS (1.60 [0.56, 2.63]; p=0.002), and all domain scores (p< 0.05) of SF-36 were achieved with miri vs. PBO at W12. These improvements in SF-36 scores were sustained throughout the maintenance period with significant improvements seen with miri vs. PBO group in PCS (2.30 [1.12, 3.49]; p< 0.001) and MCS (1.48 [0.13, 2.82]; p=0.031), and 6/8 domain scores (p< 0.05) at W40 (Table). Conclusion: Miri significantly improves SF-36 mental and physical component scores in patients with moderately to severely active UC during induction (W12) and maintenance (W40). Table 1. - Change From Baseline (ANCOVA with mBOCF*) in SF-36 Physical and Mental Component Scores and Domain Scores at W12 and W40 (Modified Intent-to-treat Population) Induction (W12 analysis) Maintenance (W40 analysis)Miri clinical responder LSM (SE) change from baseline † LSM Diff (95% CI) vs. PBO p-value LSM (SE) change from baseline † LSM Diff (95% CI) vs. PBO p-value PBO IV (N=294) Miri 300 mg IV (N=868) PBO SC (N=179) Miri 200 mg SC (N=365) PCS 3.90 (0.393) 5.97 (0.242) 2.07 (1.21, 2.93) < 0.001 6.66 (0.541) 8.97 (0.412) 2.30 (1.12, 3.49) < 0.001 MCS 3.42 (0.472) 5.02 (0.291) 1.60 (0.56, 2.63) 0.002 5.54 (0.611) 7.02 (0.465) 1.48 (0.13, 2.82) 0.031 Domain scores Physical Functioning 6.57 (0.950) 10.16 (0.585) 3.59 (1.51, 5.67) < 0.001 10.82 (1.221) 13.97 (0.928) 3.16 (0.48, 5.84) 0.021 Role-Physical 10.50 (1.304) 17.21 (0.803) 6.71 (3.86, 9.57) < 0.001 18.51 (1.667) 26.14 (1.266) 7.63 (3.97, 11.28) < 0.001 Role-Emotional 5.25 (1.135) 9.06 (0.701) 3.81 (1.33, 6.30) 0.003 10.35 (1.338) 12.95 (1.019) 2.60 (−0.34, 5.54) 0.083 Bodily Pain 13.40 (1.218) 18.43 (0.751) 5.03 (2.37, 7.70) < 0.001 20.93 (1.663) 26.12 (1.263) 5.19 (1.54, 8.84) 0.005 Vitality 10.38 (1.059) 14.72 (0.652) 4.34 (2.02, 6.65) < 0.001 16.85 (1.493) 21.54 (1.133) 4.70 (1.42, 7.97) 0.005 Social Functioning 11.69 (1.254) 16.74 (0.772) 5.05 (2.30, 7.79) < 0.001 17.25 (1.487) 23.95 (1.129) 6.70 (3.44, 9.96) < 0.001 Mental Health 6.55 (0.887) 9.56 (0.548) 3.00 (1.06, 4.94) 0.002 10.25 (1.233) 12.93 (0.940) 2.67 (−0.04, 5.38) 0.053 General Health 7.03 (0.959) 12.30 (0.592) 5.27 (3.17, 7.37) < 0.001 14.23 (1.362) 19.83 (1.035) 5.59 (2.61, 8.58) < 0.001 *Patients with missing values had their last value carried forward, with the exception that patients who discontinued due to an adverse event had their baseline value carried forward.†Baseline for both Induction and Maintenance is defined as the last non-missing assessment recorded on or prior to the date of the first study drug administration at Visit 1 of Induction.ANCOVA, analysis of covariance; CI, confidence interval; Diff, difference; IV, intravenous; LSM, least squares mean; MCS, mental component score; mBOCF, modified baseline observation carried forward; miri, mirikizumab; PBO, placebo; PCS, physical component score; SC, subcutaneous; SE, standard error; SF-36, medical outcomes study 36-Item short-form health survey; W, week.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".