S1452 Early Symptomatic Improvement With Mirikizumab Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From the Phase 3 VIVID-1 Study
Bibliographic record
Abstract
Introduction: Mirikizumab (miri), an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical, endoscopic, and inflammatory biomarker endpoints, and an acceptable safety profile for patients (pts) with Crohn’s disease (CD) in the Phase 3 VIVID-1 study. We investigated the onset of symptomatic improvement and safety of miri as induction therapy through Week 12 (W12) for pts with CD. Methods: In VIVID-1, 1065 pts had moderately to severely active CD (unweighted daily average stool frequency (SF) ≥4 [loose and watery stools defined as Bristol Stool Scale Category 6 or 7] AND/OR unweighted daily average abdominal pain (AP) ≥2 at baseline) and prior failure to biologic and/or conventional therapy. Pts were randomized in a 6:3:2 ratio to receive miri (single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300mg at W12 and then every 4 weeks), ustekinumab (uste) (6mg/kg IV at W0 and 90mg SC dose at W8 and then every 8 weeks), or placebo (PBO). This analysis compared clinical response by Patient Reported Outcome (PRO) (30% decrease in SF and/or AP with neither score worse than W0), clinical remission by PRO (SF≤3 and not worse than W0 and AP ≤1 and no worse than W0), change from baseline (CFB) in SF, and in AP up to W12 in miri/PBO randomized patients. Results: Baseline characteristics were balanced across the miri (N=579) and PBO (n=199) treatment groups. A greater proportion of the pts on miri achieved clinical response by PRO at W4, W6, W8, and W12, and clinical remission by PRO at W6, W8, and W12 vs PBO. Miri resulted in significant improvements in SF at W6, W8, and W12, and in AP at W4, W6, W8, and W12 vs PBO (Table 1). The overall safety was consistent with the known safety profile of miri. Most common treatment-emergent adverse events (TEAEs) during induction period in miri-treated pts: COVID-19, anemia, and headache. There were lower frequencies of SAEs (miri: 5.9%, PBO: 9.0%) and discontinuations due to adverse events (miri: 2.4%, PBO:4.7%) in miri-treated pts vs PBO. There were no malignancies, no major adverse cardiovascular events (MACEs), no Hy’s law cases or deaths in the miri arm up to W12. One death was reported in the induction period in the PBO group. Conclusion: In pts with moderately to severely active CD, miri induction was associated with higher rates of clinical response, clinical remission and greater improvement in AP as early as W4, SF as early as W6 vs PBO. Increasing treatment effect was observed through W12. Table 1. - Outcome of mirikizumab induction on clinical response, clinical remission, stool frequency and abdominal pain Clinical response by PROa n (%) Clinical remission by PROa n (%) Stool Frequency (CFB)b LSM (SE) Abdominal Pain (CFB)b LSM (SE) MiriN=579 PBON=199 MiriN=579 PBON=199 MiriN=579 PBON=199 MiriN=579 PBON=199 Week 2 224 (38.7) 75 (37.7) 41 (7.1) 10 (5.0) -1.24 (0.076) -1.24 (0.129) -0.38 (0.022) -0.31 (0.036) Week 4 308 (53.2)* 87 (43.7) 90 (15.5) 27 (13.6) -1.74 (0.087) -1.42 (0.146) -0.55 (0.026)* -0.43 (0.043) Week 6 376 (64.9)*** 100 (50.3) 150 (25.9)* 36 (18.1) -2.20 (0.091)* -1.81 (0.153) -0.72 (0.028)*** -0.52 (0.047) Week 8 404 (69.8)**** 101 (50.8) 175 (30.2)** 37 (18.6) -2.43 (0.096)** -1.85 (0.162) -0.80 (0.029)**** -0.56 (0.049) Week 12 409 (70.6)**** 103 (51.8) 216 (37.3)**** 44 (22.1) -2.65 (0.101)**** -1.86 (0.171) -0.90 (0.031)**** -0.61 (0.052) Footnotes: aNonresponder imputation was used. bModified baseline observation carried forward was used.*refers to P < 0.05 significance; ** refers to P < 0.01 significance; *** refers to P < 0.001 significance; **** refers to P < 0.0001 significance.Abbreviations: AP =abdominal pain; CDAI= Crohn’s Disease Activity Index; CFB=change from baseline; PRO=Patient Reported Outcome (2 of the patient-reported items of the CDAI, AP and SF); LSM=least square mean; SE=standard error; SF=stool frequency; miri=mirikizumab; PBO=placebo.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".