S0703 Tofacitinib for the Treatment of Ulcerative Colitis: Up to 6.8 Years of Safety Data From Global Clinical Trials
Bibliographic record
Abstract
INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Efficacy and safety of tofacitinib were evaluated in randomized, placebo-controlled Phase (P)2 (NCT00787202) and P3 (NCT01465763; NCT01458951; NCT01458574) studies, and in an ongoing, open-label, long-term extension (OLE) study (NCT01470612) (1–3). We report updated tofacitinib safety analyses from the tofacitinib UC clinical program, with exposure up to 6.8 years. METHODS: Two cohorts were analyzed: P3 Maintenance (N = 592; patients [pts] receiving placebo, tofacitinib 5 or 10 mg twice daily [BID]) and Overall (N = 1,157; pts receiving tofacitinib 5 or 10 mg BID in P2/P3/OLE studies; data as of May 2019, database not locked). Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure) were evaluated for adverse events (AEs) of special interest. Opportunistic infections (OIs), malignancies, major adverse cardiovascular events (MACE), and gastrointestinal (GI) perforations were reviewed by independent adjudication committees. RESULTS: Demographics, clinical characteristics, and safety data are shown in the table. In the Overall Cohort, 1,157 pts received ≥ 1 dose of tofacitinib 5 or 10 mg BID; most pts (N = 959, 83%) received an average dose of 10 mg BID. Median treatment duration was 623 (range 1–2,494) days (2,581.3 PY of exposure). IRs (95% confidence interval) for AEs of special interest were: deaths, 0.19 (0.06, 0.44); serious infections, 1.70 (1.24, 2.27); herpes zoster (non-serious and serious), 3.48 (2.79, 4.30); OIs, 1.07 (0.71, 1.55); malignancies (excl. non-melanoma skin cancer [NMSC]), 0.75 (0.46, 1.16); NMSC, 0.73 (0.44, 1.13); MACE, 0.26 (0.11, 0.54); deep vein thrombosis, 0.04 (0.00, 0.21); pulmonary embolism, 0.15 (0.04, 0.38); GI perforations, 0.11 (0.02, 0.33). Results in the Overall Cohort as per the previous Nov 2017 data cut are presented for context (4). CONCLUSION: The safety profile of tofacitinib in pts with UC was manageable and consistent with that of other UC therapies incl. biologics. Overall, IRs for AEs of interest have generally remained stable in the tofacitinib UC clinical program over an extended period of time (up to 6.8 years).Table 1
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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 | 0.041 | 0.024 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".