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S908 PRA023 Improved Health-Related Quality of Life as Measured by IBDQ-32 in a Phase 2 Trial in Patients with Moderately to Severely Active Ulcerative Colitis

2023· article· en· W4387750786 on OpenAlexaff
David T. Rubin, Bruce E. Sands, Laurent Peyrin‐Biroulet, Silvio Danese, Deanna D. Nguyen, Quinn Dinh, Bin Dong, Christopher Ma, Timothy E. Ritter, Remo Panaccione

Bibliographic record

VenueThe American Journal of Gastroenterology · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicInflammatory Bowel Disease
Canadian institutionsUniversity of Calgary
Fundersnot available
KeywordsMedicineUlcerative colitisInflammatory bowel diseasePlaceboInternal medicineQuality of life (healthcare)Crohn's diseaseAdverse effectRandomized controlled trialClinical trialGastroenterologyPhysical therapyDisease

Abstract

fetched live from OpenAlex

Introduction: PRA023 is a humanized monoclonal antibody against tumor necrosis factor–like cytokine 1A (TL1A) in development for inflammatory bowel diseases. In ARTEMIS-UC, a phase 2, double-blind, placebo-controlled study of PRA023 in adults with moderately to severely active ulcerative colitis (UC), a significantly greater proportion of patients receiving PRA023 achieved clinical remission. This post hoc analysis assessed the impact of PRA023 on health-related quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ-32). Methods: Adults with a modified Mayo score of 4 to 9, centrally read endoscopy subscore of ≥2, rectal bleeding subscore of ≥1, and history of insufficient response, loss of response, and/or intolerance to conventional and/or advanced therapies were stratified by prior biologic exposure and genetic-based diagnostic status and randomized 1:1 to placebo or intravenous PRA023 (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10). IBDQ outcomes measures include IBDQ response (score of ≥16 points from baseline), IBDQ remission (total score ≥170), and mean change from baseline in total and domain scores after 12 weeks of induction therapy. Score changes from baseline were compared between treatment groups, and the impact of prior advanced therapy exposure on IBDQ remission was assessed. Results: Of 135 patients enrolled, 60/67 (89.6%) in the placebo arm and 68/68 (100%) in the PRA023 arm completed the 12-week induction period. Baseline characteristics were similar between the treatment groups. Significantly greater proportions of patients in the PRA023 group achieved IBDQ response (82.4% PRA023 vs 49.3% placebo, ∆33.1%, P< 0.0001) and IBDQ remission (51.5% PRA023 vs 19.4% placebo, ∆32.1%, P=0.0001) at week 12. Prior advanced therapy use did not affect the placebo-adjusted proportion of patients experiencing IBDQ remission in those who received PRA023 (Δ34.4% vs Δ30.0%, respectively, for prior and no prior advanced therapy). The total IBDQ score and all IBDQ domain subscores (bowel symptoms, systemic symptoms, emotional function, and social function) were significantly improved after 12 weeks of PRA023 induction treatment compared to placebo (Table 1). Conclusion: PRA023 significantly improved quality-of-life measures in patients with moderately to severely active UC, regardless of prior advanced therapy use. The greatest benefits were reported in the bowel symptoms and emotional function domains. Table 1. - IBDQ Outcomes with PRA023 Induction Therapy IBDQ outcomes Placebo PRA023 % Difference vs placebo (95% CI) P value IBDQ response (%, n/N)†‡ 49.3 (33/67) 82.4 (56/68) 33.1 (17.2–46.8) < 0.0001 IBDQ remission (%, n/N)‡ 19.4 (13/67) 51.5 (35/68) 32.1 (16.0–45.9) 0.0001 Prior advanced therapy 18.8 (6/32) 53.1 (17/32) 34.4 (10.9–53.1) - No prior advanced therapy 20.0 (7/35) 50.0 (18/36) 30.0 (7.8–48.4) - Change in IBDQ scores from BL, mean±SD Total score 20.8±37.59 48.6±34.85 26.8 (14.6–38.9) < 0.0001 Bowel symptoms subscore 7.1±12.27 17.2±11.79 9.4 (5.3–13.4) < 0.0001 Systemic symptoms subscore 3.0±5.97 7.0±6.56 4.0 (2.0–6.0) 0.0002 Emotional function subscore 6.6±14.59 16.1±13.25 8.9 (4.3–13.5) 0.0002 Social function subscore 4.1±7.74 8.2±7.38 4.4 (2.0–6.8) 0.0004 †Prespecified secondary endpoint.‡Nonresponder imputation was applied to response and remission endpoints.Abbreviations: BL, baseline; IBDQ, Inflammatory Bowel Disease Questionnaire. P values are nominal except IBDQ response.

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 score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0060.001

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 head0.014
GPT teacher head0.290
Teacher spread0.276 · 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".

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Citations0
Published2023
Admission routes1
Has abstractyes

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