Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials

Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20.

Abstract

Background: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated.

Methods: Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization.

Results: Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1-134.1) versus 19.2 U/L (8.5-29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1-63.7), 90.3 (51.9-128.7), and 115.6 U/L (91.6-139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies.

Conclusions: In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases.

Trial registration: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.

Keywords: Creatine kinase; Inflammatory bowel disease; Safety; Tofacitinib; Ulcerative colitis.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Psoriatic / drug therapy
  • Arthritis, Rheumatoid / drug therapy
  • Cohort Studies
  • Colitis, Ulcerative / drug therapy*
  • Creatine Kinase / blood*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperidines / administration & dosage
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use*
  • Psoriasis / drug therapy
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use*
  • Risk Factors

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • tofacitinib
  • Creatine Kinase

Associated data

  • ClinicalTrials.gov/NCT01241591
  • ClinicalTrials.gov/NCT01458574
  • ClinicalTrials.gov/NCT02187055
  • ClinicalTrials.gov/NCT01186744
  • ClinicalTrials.gov/NCT00847613
  • ClinicalTrials.gov/NCT00678210
  • ClinicalTrials.gov/NCT01470612
  • ClinicalTrials.gov/NCT01976364
  • ClinicalTrials.gov/NCT00856544
  • ClinicalTrials.gov/NCT00603512
  • ClinicalTrials.gov/NCT01276639
  • ClinicalTrials.gov/NCT00853385
  • ClinicalTrials.gov/NCT01882439
  • ClinicalTrials.gov/NCT00976599
  • ClinicalTrials.gov/NCT00960440
  • ClinicalTrials.gov/NCT01262118
  • ClinicalTrials.gov/NCT00814307
  • ClinicalTrials.gov/NCT01309737
  • ClinicalTrials.gov/NCT01710046
  • ClinicalTrials.gov/NCT00787202
  • ClinicalTrials.gov/NCT00413660
  • ClinicalTrials.gov/NCT01465763
  • ClinicalTrials.gov/NCT01164579
  • ClinicalTrials.gov/NCT01877668
  • ClinicalTrials.gov/NCT00687193
  • ClinicalTrials.gov/NCT01163253
  • ClinicalTrials.gov/NCT01458951
  • ClinicalTrials.gov/NCT01039688
  • ClinicalTrials.gov/NCT00147498
  • ClinicalTrials.gov/NCT00661661
  • ClinicalTrials.gov/NCT01359150
  • ClinicalTrials.gov/NCT01484561
  • ClinicalTrials.gov/NCT00413699
  • ClinicalTrials.gov/NCT00550446
  • ClinicalTrials.gov/NCT02147587
  • ClinicalTrials.gov/NCT01059864