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S765 Association of Ulcerative Colitis Bowel Urgency Improvement with Clinical Response and Remission

2022· article· en· W4316081733 on OpenAlexaff
David B. Clemow, Christophe Sapin, Toshifumi Hibi∥, Marla C. Dubinsky, Séverine Vermeire, Stefan Schreiber, Laurent Peyrin‐Biroulet, Mamoru Watanabe, Remo Panaccione

Bibliographic record

VenueThe American Journal of Gastroenterology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsMedicineUlcerative colitisInternal medicineClinical endpointClinical trialGastroenterologyPlaceboRandomized controlled trialMaintenance therapySpontaneous remissionSurgeryChemotherapyDiseasePathology

Abstract

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Introduction: Early bowel movement urgency (BU) improvement association with later clinical endpoint improvements was examined in moderately-to-severely active ulcerative colitis (UC) patients (pts) treated with mirikizumab (miri). Methods: BU was evaluated in Phase 3 randomized placebo (PBO)-controlled 12-week induction (LUCENT-1, NCT03518086) and 40-week maintenance (LUCENT-2, NCT03524092) trials with miri. Pts received IV miri 300mg or PBO during induction. Week (W)12 miri responders were rerandomized at LUCENT-2 baseline (BL) to subcutaneous miri 200mg or PBO. BU was measured with 11-point Urgency Numeric Rating Scale (UNRS) from 0 (no urgency) to 10 (worst possible). Pts’ UNRS scores were an average from 7 consecutive days prior to visit. Association of pts with BU Clinically Meaningful Improvement (CMI) or BU remission between BL and W4 with the proportion of pts achieving clinical response, and clinical, endoscopic, or symptomatic remission at end of W12 was assessed. For pts who achieved clinical response at W12, the analyses were repeated for the end of maintenance based on W12 BU status. Logistic regression models with treatment, urgency (BU CMI or BU Remission), treatment-by-urgency group interaction, and stratification factors were fitted to examine the association between early urgency improvement and later clinical endpoints. Results: Treatment-by-urgency group interactions were not statistically significant across clinical outcomes for induction and maintenance. For induction, treatment and urgency status were statistically significant. Pts experiencing BU CMI or BU remission at W4 were consistently more likely to achieve clinical response, and clinical, endoscopic, or symptomatic remission at W12 for both treatment groups. For remission, only treatment main effect was statistically significant. Among miri induction clinical responders (an enriched population), BU CMI or BU Remission at end of induction (W12) was not associated with later maintenance efficacy outcomes (W52). Miri-treated pts achieved higher rates of clinical response, and clinical, endoscopic, or symptomatic remission at W52 than with PBO regardless of BU CMI or BU Remission at W12 (Table). Conclusion: Early BU Improvement, CMI or Remission, was associated with better clinical outcomes during induction for miri and PBO pts, showing BU is a sensitive predictor of early clinical outcomes. Among miri induction responders, miri consistently provided better maintenance of response and remission rates than PBO. Table 1. - Bowel urgency associations with Clinical Response and Clinical Remission for patients with moderate-to-severely active ulcerative colitis LUCENT-1 Induction Urgency CMI Urgency Remission Endpoint PBO IV (N=276) Miri 300mg IV (N=811) p-value a Endpoint PBO (N=276) Miri 300mg IV (N=811) p-value a Urgency CMI W4 = Yes Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=6168.927.936.149.2 n=23078.737.449.163.5 0.1260.1790.0830.055 Urgency remission W4 = Yes Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=1376.946.246.269.2 n=6581.547.752.370.8 NA b NA b NA b NA b Urgency CMI W4 = No Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=21534.98.816.721.4 n=58157.518.429.638.7 < 0.001< 0.001< 0.001< 0.001 Urgency remission W4 = No Clin. Response W12, (%) Clin. Remission W12, (%) Endo. Remission W12, (%) Sympt. Remission W12, (%) n=26340.711.419.825.5 n=74661.921.733.643.6 < 0.001< 0.001< 0.001< 0.001 LUCENT-2 Maintenance Urgency CMI Urgency Remission Endpoint PBO SC (N=172) Miri 200mg SC (N=336) p-value a Endpoint PBO SC (N=172) Miri 200mg SC (N=336) p-value a Urgency CMI W12 = Yes Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=11252.729.531.343.8 n=21282.553.360.474.1 < 0.001< 0.001< 0.001< 0.001 Urgency remission W12 = Yes Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=5347.234.035.845.3 n=10582.955.261.079.0 < 0.0010.0120.004< 0.001 Urgency CMI W12 = No Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=6045.018.326.735.0 n=12479.047.657.369.4 < 0.001< 0.001< 0.001< 0.001 Urgency remission W12 = No Clin. Response W52 (%) Clin. Remission W52 (%) Endo. Remission W52 (%) Sympt. Remission W52 (%) n=11951.321.826.938.7 n=23180.549.458.469.3 < 0.001< 0.001< 0.001< 0.001 ap-value = within-group treatment comparison from Fisher’s exact tests.bSubgroup N was too small for p-value generation.Urgency CMI: UNRS=≥3 point decrease; Urgency remission: UNRS=0 or 1.Note: Using the Cochran-Mantel-Haenszel (CMH) test, treatment-by-subgroup interactions were not statistically significant.Note: W52 refers to W40 of LUCENT-2, representing 52 weeks of continuous treatment; W12 refers to baseline for LUCENT-2. Abbreviations: CMI=clinically meaningful improvement; PBO=placebo; miri=mirikizumab; IV=intravenous; n=number of patients in the specified category; SC=subcutaneous; W=week.

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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)0.003
metaresearch head score (Gemma)0.007
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.039

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.007
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0120.001

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 head0.005
GPT teacher head0.256
Teacher spread0.251 · 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 designObservational
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".

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Citations1
Published2022
Admission routes1
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