S0644 Tofacitinib for the Treatment of Ulcerative Colitis: An Updated Analysis of Infection Rates in the Tofacitinib Ulcerative Colitis Clinical Program
Bibliographic record
Abstract
INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. We present updated infections data from the tofacitinib UC clinical program (1), as of May 2019. METHODS: Infection events were evaluated in a Phase (P)2 induction study (NCT00787202), 2 P3 induction studies (NCT01465763; NCT01458951), a P3 maintenance study (NCT01458574), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612) as 3 cohorts: Induction (P2 and P3; placebo [PBO] or tofacitinib 10 mg twice daily [BID]), Maintenance (P3; PBO, tofacitinib 5 or 10 mg BID), and Overall (all patients [pts] receiving tofacitinib 5 or 10 mg BID in P2/P3/OLE studies; by predominant dose [5 or 10 mg BID based on average daily dose < 15 mg or ≥ 15 mg, respectively]; as of May 2019, database not locked). Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure; censored at time of event) were evaluated for infections, serious infections (SIs), opportunistic infections (OIs; independently adjudicated, incl. non-herpes zoster [HZ] OIs), and HZ. RESULTS: 1,157 pts received ≥ 1 dose of tofacitinib 5 or 10 mg BID (83% predominantly 10 mg BID), with 2,581.3 PY of exposure (up to 6.8 years). Nasopharyngitis was the most frequent infection in the Overall Cohort (251 pts; 21.7%). In induction, SIs and OIs were numerically higher with tofacitinib vs PBO (Table 1). The Overall Cohort SI IR was 1.70, which was generally similar to Maintenance Cohort IRs for tofacitinib 5 and 10 mg BID and PBO, and the Overall Cohort IR (1.75) in the previous report. No SIs resulted in death. OIs were infrequent (28 pts; IR 1.07), and most OIs were HZ (24 pts; IR 0.92; mostly cutaneous). Overall, 87 pts had HZ (non-serious and serious; IR 3.48 [95% CI 2.79, 4.30]); 7 serious. Maintenance Cohort HZ IR was numerically higher for tofacitinib 10 vs 5 mg BID, but with overlapping 95% CIs; Overall Cohort HZ IRs were similar between doses. CONCLUSION: Overall, SIs were generally infrequent, and similar (indirectly) to other UC therapies, incl. biologics (2). In induction, SIs and OIs were more frequent with tofacitinib vs PBO. In the Maintenance Cohort, HZ IR was numerically higher with tofacitinib 10 vs 5 mg BID. Over time in the Overall Cohort, IRs were similar between doses and remained stable vs the previous data cut (1). Non-HZ OIs and viral infections were rare.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 | 0.007 | 0.012 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.003 | 0.006 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".