A202 TOFACITINIB FOR THE TREATMENT OF ULCERATIVE COLITIS: UP TO 5.4 YEARS OF SAFETY DATA FROM GLOBAL CLINICAL TRIALS
Bibliographic record
Abstract
Tofacitinib is an oral, small molecule JAK inhibitor approved in several countries for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib as UC induction and maintenance therapy were evaluated in Phase (P)21 and P32 randomized, placebo-controlled studies, and an ongoing, open-label extension (OLE) study.3 To report updated tofacitinib safety analyses from the UC program, with exposure up to 5.4 years. Patients (pts) who received placebo, tofacitinib 5 or 10 mg twice daily (BID) were analyzed as 2 cohorts: Maintenance (P3 maintenance, N=592) and Overall (pts receiving tofacitinib 5 or 10 mg BID in P2, P3, or the OLE study, N=1157; 2051 pt-years’ exposure; data at Nov 2017). Proportions and incidence rates (IRs; pts with events per 100 pt-years) were evaluated for adverse events (AEs) of special interest. Opportunistic infections, malignancies, major adverse cardiovascular events (MACE), and gastrointestinal perforations were reviewed by independent adjudication committees. Results in the Overall Cohort based on the previous Dec 2016 data cut are presented for context. 1157 pts received ≥1 dose of tofacitinib 5 or 10 mg BID. Demographics and disease characteristics were generally similar among treatment groups across cohorts. For the Overall Cohort, most pts (N=956, 83%) received an average tofacitinib dose of 10 mg BID. IRs for AEs of special interest were: death, 0.2; serious infection, 1.9; opportunistic infection, 1.2; herpes zoster, 3.8; malignancy (excluding non-melanoma skin cancer [NMSC]), 0.6; NMSC, 0.8; MACE, 0.3; and gastrointestinal perforations, 0.1. The safety profile of tofacitinib in pts with UC was manageable and similar to the tofacitinib rheumatoid arthritis program, and that of other UC therapies including biologics. IRs for AEs of special interest did not increase with longer exposure relative to previously reported analyses from the OCTAVE program. A dose-dependent risk of herpes zoster was observed. 1. Sandborn WJ et al. N Engl J Med 2012;367:616–24. 2. Sandborn WJ et al. N Engl J Med 2017;376:1723–36. 3. Lichtenstein GR et al. Am J Gastroenterol 2017;112(S1):Abstract 714. NonePfizer Inc
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.031 | 0.018 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.003 |
| 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) | 0.006 | 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".