Tofacitinib for Induction Therapy in Patients with Active Ulcerative Colitis in Two Phase 3 Clinical Trials: Results by Local and Central Endoscopic Assessments
Bibliographic record
Abstract
Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for ulcerative colitis (UC). Two Phase 3 randomized placebo-controlled studies (OCTAVE Induction 1 and 2: NCT01465763, NCT01458951) demonstrated efficacy of tofacitinib 10 mg twice daily (BID) vs placebo as induction therapy for patients (pts) with moderately to severely active UC.1 Here, we describe clinical efficacy endpoints assessed by local endoscopy readings along with the previously reported results assessed by central readings. Methods: Pts in both studies were randomized (4:1) to receive tofacitinib 10 mg BID or placebo for up to 9 weeks (wks). Pts were ≥18 years old with moderately to severely active UC (baseline Mayo score ≥6, rectal bleeding subscore ≥1 and endoscopic subscore ≥2). Pt eligibility was assessed based on central endoscopic reading. Pts had previous failure or intolerance to treatment with ≥1 of corticosteroids, thiopurines, or tumor necrosis factor inhibitors. The following efficacy endpoints were assessed at Wk 8: remission (primary endpoint; Mayo score ≤2, no subscore >1 and rectal bleeding subscore of 0), mucosal healing (Mayo endoscopic subscore ≤1) and clinical response (decrease from baseline Mayo score of ≥3 points and ≥30%, plus decrease in rectal bleeding subscore ≥1 or absolute subscore ≤1). Clinical outcomes were measured using both local (ie site) and central endoscopic readings at baseline and Wk 8.Table 1: Summary of efficacy endpoints at Wk 8 determined by local and central readingResults: At Wk 8, significantly more pts receiving tofacitinib 10 mg BID achieved remission in both studies vs placebo as demonstrated by both central and local endoscopic readings (Table). Similar results were observed with mucosal healing and clinical response at Wk 8. The observed rates as well as the magnitude of treatment differences based on local endoscopic reading were generally higher than those assessed by central reading. There was good agreement between locally and centrally read endoscopic subscores (kappa = 0.63 (95% CI 0.58, 0.67) and 0.62 (95% CI 0.57, 0.67) in OCTAVE Induction 1 and 2, respectively). Conclusion: In pts with moderately to severely active UC, who were qualified for both studies on central reading, treatment effects observed with local endoscopic readings were similar or slightly higher, and consistent with central readings. Both methods demonstrated the significant effect of tofacitinib vs placebo for induction therapy. Funded by Pfizer Inc. 1. Sandborn WJ et al. J Crohns Colitis 2016;10(S1):S15.
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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 | 0.011 | 0.007 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.004 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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.
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".