Characterization of Creatine Kinase Levels in the Tofacitinib Ulcerative Colitis Development Program
Bibliographic record
Abstract
Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) elevations have been observed with JAK inhibitors tofacitinib [1-4] and baricitinib [5], and other UC therapies ie infliximab [6]. We evaluated CK levels in tofacitinib-treated patients (pts) with UC. Methods: We analyzed 3 cohorts: Induction, 1 Phase (P)2 and 2 P3 8-week (wk) induction studies (N=1220); Maintenance, 1 P3 52-wk maintenance study (N=592); Overall, all tofacitinib-treated pts in P2, P3, and ongoing open-label extension studies (N=1157 at Nov 2017). Data for tofacitinib-treated pts with rheumatoid arthritis (RA; N=7061; ongoing; data at Mar 2017), psoriasis (N=3663; complete; Aug 2016), and psoriatic arthritis (N=783; ongoing; Jan 2017) are also presented. Results: After 8 wks' induction therapy, there were larger mean increases from baseline in CK with tofacitinib 10 mg twice daily (BID; 91 U/L) vs placebo (19 U/L; Fig). Of pts completing induction with 10 mg BID and rerandomized to 52 wks' maintenance therapy, mean CK decreased for pts switched to placebo, was stable with 5 mg BID, and slightly increased for pts continuing on 10 mg BID. CK elevations meeting protocol-specified discontinuation criteria (2 sequential elevations >10×upper limit of normal) were infrequent (Overall Cohort 0.8%). In the Overall Cohort, the incidence rate of CK elevation adverse events (AEs) was 6.6 pts with events/100 pt-years vs 2.2 and 6.5 for tofacitinib-treated pts with RA and psoriasis, respectively (Table). Most CK elevation AEs were mild/moderate; none were serious. No myopathy AEs were reported in the UC program. 1 pt on placebo during the maintenance study developed rhabdomyolysis 7.4 months after the last dose of 10 mg BID induction therapy. Results for UC were generally consistent with those in other tofacitinib-treated populations (Table). Conclusion: Tofacitinib treatment in pts with UC resulted in reversible elevations in CK levels, the timing of which appeared idiosyncratic and did not lead to clinically significant AEs; as such, there is currently no clear role for routine CK monitoring in tofacitinib-treated pts.620_A Figure 1 No Caption available.620_B Figure 2 No Caption available.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".