The efficacy and safety of guselkumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: Results from the Phase 3 QUASAR Maintenance Study
Bibliographic record
Abstract
Introduction: The Phase 3 QUASAR maintenance (MT) study (NCT04033445) is a randomized-withdrawal, double-blind, placebo (PBO)-controlled, study that evaluated the efficacy and safety of MT treatment with subcutaneous (SC) guselkumab (GUS), a dual-acting IL-23p19 subunit antagonist, in patients (pts) with moderately to severely active ulcerative colitis (UC) who had prior inadequate response or intolerance (failure) to conventional or advanced therapy (ADT) and demonstrated a clinical response to intravenous (IV) GUS induction ([ Fig. 1 ]). Fig. 1 Methodology: At MT baseline (BL), GUS IV induction Week (W) 12 responders and placebo (PBO)→GUS IV induction W24 responders were randomized 1:1:1 to SC GUS 200mg q4w, GUS 100mg q8w, or PBO (GUS withdrawal). Primary endpoint: clinical remission (CR) at W44. Major secondary endpoints: corticosteroid (CS)-free CR, MT of CR, clinical response, symptomatic remission, endoscopic improvement, histo-endoscopic mucosal improvement, endoscopic normalization, IBDQ remission, and fatigue response at W44. Results: The primary analysis included 568 pts (mean age, 40.7yr; mean UC duration, 7.8yr; mean modified Mayo score, 6.9 [63.9% with severe disease]; Mayo endoscopy subscore=3, 66.4%; BL oral CS use, 40.0%). About 42% pts had failed ADT (TNF antagonists/vedolizumab/tofacitinib), of which 48.3% had failed ≥2 ADT. A significantly higher proportion of pts achieved the primary and all major secondary endpoints at W44 in both GUS SC groups vs PBO ([ Fig. 2 ]). The proportion of pts with ≥1 adverse events (AEs) were GUS 200mg q4w, 70.0%; GUS 100mg q8w, 64.5%, and PBO, 68.2%. The most common AEs (combined GUS vs PBO) were COVID-19 (11.2%/14.1%), UC (11.2%/29.7%), and arthralgia (6.1%/6.8%). No deaths, active tuberculosis, opportunistic infections, anaphylaxis, serum sickness, Hy’s Law, or serious hepatic AEs were reported. Two malignancies (clear cell renal carcinoma, rectal adenocarcinoma) and 1 major cardiovascular event (hemorrhagic stroke) were reported in GUS-treated pts. Fig. 2 Conclusion: Among pts with moderately to severely active UC who responded to GUS IV induction, MT therapy with both GUS SC regimens was safe and efficacious. The primary endpoint of CR and all 9 major secondary endpoints across clinical, symptomatic, endoscopic, histologic, and pt-reported outcomes were met with statistical significance by both GUS SC MT regimens. Safety results through MT W44 were consistent with the GUS safety profile in approved indications. Publication History Article published online: 26 September 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
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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 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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".