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S907 Guselkumab Improves Abdominal Pain and Bowel Urgency Symptoms in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 QUASAR Induction Study

2023· article· en· W4387750964 on OpenAlexaff
David T. Rubin, Julián Panés, Brian G. Feagan, Shadi Yarandi, Kuan‐Hsiang Gary Huang, Matthew Germinaro, Chenglong Han, Ye Miao, Hongyan Zhang, Yun Qiu, Maria Kłopocka, George Duvall, Gary R. Lichtenstein, Tadakazu Hisamatsu, Brian Bressler, Laurent Peyrin‐Biroulet

Bibliographic record

VenueThe American Journal of Gastroenterology · 2023
Typearticle
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicPharmacological Effects of Natural Compounds
Canadian institutionsSt. Paul's HospitalWestern University
Fundersnot available
KeywordsMedicineUlcerative colitisAbdominal painAbdomenInternal medicineInflammatory bowel diseasePlaceboGastroenterologyRandomized controlled trialSurgeryPhysical therapyDisease

Abstract

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Introduction: Abdominal pain and bowel urgency are prevalent, burdensome symptoms experienced by patients (pts) with ulcerative colitis (UC) that impact daily life, including social activities. In this study, we use data from the QUASAR Phase 3 Induction Study to assess efficacy of guselkumab (GUS) on abdominal pain, bowel urgency, and the impact of bowel urgency on pts’ lives. Methods: Pts were randomized 3:2 to receive IV GUS 200mg or placebo (PBO) at Weeks (Wks) 0, 4, and 8. Abdominal pain and bowel urgency were evaluated at baseline and Wk12 using items from the Inflammatory Bowel Disease Questionnaire, where pts rated trouble with abdominal pain, symptoms of bowel urgency, and the impact of bowel urgency over the past 2 wks using 7-point scales (1=all of the time to 7=none of the time). A ≥2 point increase from baseline was considered clinically meaningful improvement. All analyses were prespecified but not multiplicity controlled; all P values are nominal. Results: At baseline, percentages of pts with abdominal pain (GUS 77.7% and PBO 77.9%), symptoms of bowel urgency (GUS 86.0% and PBO 83.2%), and impact of bowel urgency (GUS 70.8% and PBO 70.4%) at least a little of the time (score ≤5) were similar between groups. GUS-treated pts showed greater improvements at Wk12 in these outcomes compared with PBO (Table 1). For abdominal pain, 52.0% of GUS-treated pts had clinically meaningful improvements from baseline at Wk12 vs 33.0% in the PBO group (P< 0.001), and 21.1% vs 12.3%, respectively, of those with abdominal pain at baseline had resolution at Wk12 (P=0.004; Figure 1A). For symptoms of bowel urgency, 58.6% vs 33.0%, respectively, had clinically meaningful improvements (P< 0.001; Figure 1B), and 24.0% vs 9.8%, respectively, of those with symptoms of bowel urgency at baseline had resolution at Wk12 (P< 0.001). Similarly, 57.7% vs 33.0%, respectively, had clinically meaningful improvements in the impact of bowel urgency (P< 0.001; Figure 1B), and 32.4% vs 13.1%, respectively, of those impacted at baseline had resolution at Wk12 (P< 0.001). Symptoms and impact of bowel urgency were combined into a bowel urgency score; of pts with symptoms or impact scores ≤6 at baseline, 19.7% vs 8.2%, respectively, had resolution of both at Wk12 (P< 0.001; Figure 1B). Conclusion: Pts receiving GUS showed clinically meaningful improvements in health-related quality of life measures related to abdominal pain and bowel urgency, including both the symptoms of bowel urgency and impact on pts’ lives.Figure 1.: Percentages of patients with clinically meaningful improvement (≥2 point change) from baseline to Wk12 among those with symptoms at baseline at least a little bit of the time (score ≤5) and resolution of symptoms at Wk12 among those with symptoms at baseline hardly any of the time (score ≤6) for symptoms of (A) abdominal pain and (B) bowel urgency. All P-values presented are nominal. Table 1. - Changes from baseline to Wk12 in abdominal pain, symptoms of bowel urgency, and impact of bowel urgency Outcome Change from baseline Placebo IV (N=261) Guselkumab 200 mg IV (N=405) P-value Abdominal pain Improved 123 (47.1%) 267 (65.9%) < 0.001 No change 102 (39.1%) 103 (25.4%) Worsened 36 (13.8%) 35 (8.6%) Symptoms of bowel urgency Improved 125 (47.9%) 288 (71.1%) < 0.001 No change 93 (35.6%) 89 (22.0%) Worsened 43 (16.5%) 28 (6.9%) Impact of bowel urgency Improved 110 (42.1%) 246 (60.7%) < 0.001 No change 101 (38.7%) 115 (28.4%) Worsened 50 (19.2%) 44 (10.9%) All P-values are nominal. P-values were based on the Cochran-Mantel-Haenszel (CMH) chi-square Row Mean Score test, stratified by ADT-failure status (Yes/No) and concomitant use of corticosteroids at baseline (Yes/No).

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How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.883
Threshold uncertainty score0.701

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.002
Insufficient payload (model declined to judge)0.0000.000

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 head0.039
GPT teacher head0.375
Teacher spread0.336 · 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 teacher head, 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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Citations0
Published2023
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