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S753 Mirikizumab Significantly Improves Abdominal Pain in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies

2022· article· en· W4316077772 on OpenAlexaff
Edward V. Loftus, Alison Potts Bleakman, Xingyuan Li, Nathan Morris, Emily Hon, Vipul Jairath

Bibliographic record

VenueThe American Journal of Gastroenterology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsWestern University
Fundersnot available
KeywordsMedicineUlcerative colitisAbdominal painPlaceboRandomized controlled trialInternal medicineGastroenterologyAdverse effectPhases of clinical researchClinical endpointClinical trialDiseasePathology

Abstract

fetched live from OpenAlex

Introduction: Abdominal pain (AP) is a frequent and burdensome symptom in patients (pts) with ulcerative colitis (UC).1 Mirikizumab (miri; IL-23p19 inhibitor) demonstrated efficacy vs placebo (PBO) in adult pts with moderately-to-severely active UC in randomized, double-blind, phase 3 LUCENT-1 (induction/NCT03518086) and LUCENT-2 (maintenance/NCT03524092) studies.2.3 Here, we report the effect of miri vs PBO on AP. Methods: In the induction study, pts (N=1162) were randomized 3:1 to receive intravenous (IV) miri 300 mg or PBO every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 (N=544) of induction were re-randomized 2:1 to subcutaneous (SC) miri 200 mg or PBO Q4W through W40 in the maintenance study. Pts recorded “worst AP in the past 24 hours” each day using an 11-point AP Numeric Rating Scale (NRS; 0 = no pain; 10 = worst possible pain) on an electronic diary. AP improvement (AP NRS score ≥30% improvement from baseline [BL] in pts with BL AP NRS ≥3) was evaluated. The Cochran-Mantel-Haenszel test was used to compare the proportion of pts achieving AP improvement with missing data imputed as nonresponse. Results: As early as W4 (miri 43.0% vs PBO 33.7%; risk difference [95% CI]: 9.7 [2.8–16.6], p=0.007) of the induction study, a significant reduction from BL of at least 30% in AP NRS score was observed in the miri-treated pts vs PBO through W12 (66.4% vs 49.2%; 17.4 [10.3–24.6], p< 0.001). In the maintenance study, a greater percentage of miri-treated pts maintained AP NRS improvement compared to PBO. The separation started at W16 (79.2% vs 69.2%; 9.0 [0.5–17.5], p=0.034) and sustained through W40 (76.2% vs 47.2%; 27.4 [18.3–36.4], p< 0.001; Figure). Conclusion: Miri provided early (W4) and sustained improvement (through W40) of AP compared with PBO in pts with moderately-to-severely active UC.Figure 1.: The proportion of patients with AP NRS ≥30% improvement at A. induction and B. maintenance in patients with Abdominal Pain NRS score ≥3 at induction baseline. *p<0.05; **p<0.001 vs. placebo Weekly measures were calculated by averaging data from daily diary entries of AP NRS for a 7-day period. Baseline value for both induction and maintenance was calculated from daily diary entries the week prior to W0 of induction. Abbreviations: AP NRS, Abdominal Pain Numeric Rating Scale; IV, intravenous; miri, mirikizumab; PBO, placebo; SC, subcutaneous

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

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.

Opus teacher head0.008
GPT teacher head0.240
Teacher spread0.232 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

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