Symptomatic Improvement Within 3 Days With Tofacitinib Induction Therapy in Patients With Ulcerative Colitis: Results From OCTAVE Induction 1 and 2
Bibliographic record
Abstract
Introduction: Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated for ulcerative colitis (UC). Two Phase (P) 3 UC induction trials demonstrated the efficacy of tofacitinib 10 mg twice daily (BID) at Week 2 in partial Mayo score (PMS).1 We evaluated the onset of symptomatic improvement in a post-hoc analysis of diary data. Methods: OCTAVE Induction 1 (NCT01465763) & 2 (NCT01458951) were identical, randomized, placebo-controlled P3 trials in adult patients (pts) with moderately to severely active UC who had failed or were intolerant to steroids, immunomodulators, or tumor necrosis factor inhibitors. Pts received placebo (N=234) or tofacitinib 10 mg BID (N=905) for 8 weeks. Pooled data for OCTAVE Induction 1 & 2 are presented. At screening, pts electronically recorded their normal number of stools per day. During the study, pts continued a daily diary recording their number of bowel movements per day and the presence and description of any blood in the stools. Daily Mayo stool frequency (SF) and rectal bleeding (RB) subscores were calculated for each pt (subscore range of 0-3) based on that day's diary data for the first 15 days of therapy. Least squares mean (LSM) changes from baseline in SF and RB subscores were compared using a linear mixed-effects model. Binary endpoints were compared using stratified Cochran-Mantel-Haenszel chi-square test based on observed data. Results: At baseline for both the placebo and tofacitinib groups, mean SF Mayo subscore was 2.5 and mean RB Mayo subscore was 1.6. Significant improvements from baseline were observed with tofacitinib vs placebo at Day 3 for SF and RB subscores, and were maintained through to Day 15 (Figure). At Day 15, LSM changes from baseline for SF and RB subscores with tofacitinib were -0.74 and -0.76, respectively, vs -0.35 and -0.44, respectively, with placebo (P < 0.0001). At Day 15, 14.6% of tofacitinib-treated pts had an SF score of 0 vs 8.0% with placebo (P < 0.01), and 41.2% of tofacitinib-treated pts had an RB subscore of 0 vs 21.1% with placebo (P < 0.0001).FigureConclusion: In these two P3 induction studies of tofacitinib for pts with moderately to severely active UC, significant symptomatic improvements were observed with tofacitinib vs placebo as early as Day 3. These results support rapid onset of tofacitinib efficacy previously reported based on improvement in PMS.1 Funded by Pfizer Inc.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".