S0665 Clostridium difficile Infection in Patients With Ulcerative Colitis Treated With Tofacitinib in the Ulcerative Colitis Program: An Update as of May 2019
Bibliographic record
Abstract
INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Patients (pts) with UC are susceptible to C. difficile infection (CDI) (1). In the tofacitinib UC clinical program, previous analyses showed CDI rates among tofacitinib-treated pts to be similar or numerically lower than placebo (PBO)-treated pts and pts treated with immunomodulators and TNFi in a generally comparable claims-based observational cohort (2). Here, we present an updated analysis of CDI in the tofacitinib UC clinical program. METHODS: CDI events were evaluated from 4 randomized, PBO-controlled studies (Phase [P]2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951]; 1 maintenance P3 study [NCT01458574]) and an ongoing, open-label, long-term extension (OLE) study (NCT01470612). 3 cohorts were analyzed: Induction (P2/P3 induction studies), Maintenance (P3 maintenance study) and Overall (pts receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3 or OLE studies; analyzed by pts receiving ≥ 1 dose of tofacitinib and predominant dose [PD; 5 or 10 mg BID based on average daily dose <15 mg or ≥ 15 mg, respectively]; data as of May 2019, database not locked). Proportions and incidence rates (unique pts with events per 100 pt-yrs [PY] of exposure) of CDI were evaluated. All pts underwent CDI screening; a positive test excluded pts from program entry. RESULTS: The Overall Cohort comprised 1,157 pts who received ≥ 1 dose of tofacitinib 5 or 10 mg BID, representing 2,581 PY of tofacitinib exposure and up to 6.8 yrs of treatment. CDI occurred in 3 pts in the Induction Cohort (PBO, n = 1; tofacitinib 10 mg BID, n = 2), 3 pts in the Maintenance Cohort (PBO, n = 3; CDI occurred 68, 81 and 98 days following initiation of PBO) and 9 pts in the Overall Cohort (PD tofacitinib 10 mg BID, n = 9; Table 1). Overall Cohort pts with CDI were mild (n = 4) or moderate (n = 5) in severity; 6 pts continued study treatment without interruption, 1 temporarily discontinued and 2 permanently discontinued. CDI resolved with treatment in 8 pts and CDI was still present in 1 pt at the time of study discontinuation. Two events were reported as serious AEs due to hospitalization. CONCLUSION: In the tofacitinib UC program, CDI rates among pts receiving tofacitinib have remained stable since the previous data cut (2) and are comparable to those reported for other advanced therapies (3).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 | 0.003 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.005 | 0.007 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".