OP032 Efficacy and safety of oral tofacitinib as maintenance therapy in patients with moderate to severe ulcerative colitis: results from a phase 3 randomised controlled trial
Bibliographic record
Abstract
Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Efficacy and safety of tofacitinib 10 mg twice daily (BID) were reported in OCTAVE Induction 1 & 2 [1]. Methods: OCTAVE Sustain (NCT01458574) was a Phase 3, randomised, double-blind, placebo (PBO) -controlled study that enrolled PBO or tofacitinib patients (pts) who completed OCTAVE Induction 1 or 2 with at least clinical response (≥3 points and ≥30% decrease from baseline (BL) Mayo score plus a decrease in rectal bleeding subscore of ≥1 or absolute rectal bleeding subscore ≤1). Pts were re-randomised (1:1:1) to maintenance treatment with PBO (N=198), tofacitinib 5 (N=198) or 10 mg BID (N=197) for 52 weeks (wks). The primary endpoint was remission (total Mayo score ≤2, no subscore >1, rectal bleeding subscore of 0) at Wk 52. Key secondary endpoints were mucosal healing (Mayo endoscopic subscore ≤1) at Wk 52, and sustained steroid-free remission (remission at Wks 24 and 52; no steroid use ≥4 wks prior to each visit) among pts in remission at BL. Results: At Wk 52, tofacitinib 5 and 10 mg BID had significantly greater effect vs PBO for the primary endpoint of remission, and secondary endpoints of mucosal healing, clinical response as well as sustained remission, sustained mucosal healing and sustained clinical response (Table; p<0.001 all comparisons). Among pts in remission at BL, both tofacitinib groups had significantly higher proportions of pts with sustained steroid-free remission vs PBO (p<0.001 all comparisons). Adverse event (AE), serious AE and serious infection rates were similar among all groups. Despite more frequent infections with tofacitinib vs PBO, discontinuations due to AEs were numerically lower for tofacitinib vs PBO. A dose dependent increase in herpes zoster (HZ) rate was observed. There were no deaths, malignancies (excluding non-melanoma skin cancer) or intestinal perforation AEs in either tofacitinib group. Changes in lipid and creatine kinase levels were consistent with results from tofacitinib studies in other populations. Conclusions: Tofacitinib 5 and 10 mg BID were significantly more effective vs PBO as maintenance therapy over 52 wks in pts with moderately to severely active UC. Despite a dose-dependent increase in HZ, overall, AE rates were similar among both tofacitinib groups. No new safety findings emerged from those previously reported in studies of rheumatoid arthritis. References: [1] Sandborn WJ et al, (2016), Efficacy and safety of oral tofacitinib as induction therapy in patients with moderate-to-severe ulcerative colitis: results from 2 phase 3 randomised controlled trials, J Crohns Colitis, 10: 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 | 0.002 | 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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".