PMID- 32816215 OWN - NLM STAT- MEDLINE DCOM- 20210922 LR - 20211106 IS - 1573-2568 (Electronic) IS - 0163-2116 (Print) IS - 0163-2116 (Linking) VI - 66 IP - 8 DP - 2021 Aug TI - Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. PG - 2732-2743 LID - 10.1007/s10620-020-06560-4 [doi] AB - 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. CI - (c) 2020. The Author(s). FAU - Panaccione, Remo AU - Panaccione R AUID- ORCID: 0000-0002-5247-940X AD - Department of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada. rpanacci@ucalgary.ca. FAU - Isaacs, John D AU - Isaacs JD AD - Translational and Clinical Research Institute, Newcastle University and Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. FAU - Chen, Lea Ann AU - Chen LA AD - New York University School of Medicine, New York, NY, USA. FAU - Wang, Wenjin AU - Wang W AD - Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA. FAU - Marren, Amy AU - Marren A AD - Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA. FAU - Kwok, Kenneth AU - Kwok K AD - Inflammation and Immunology, Pfizer Inc, New York, NY, USA. FAU - Wang, Lisy AU - Wang L AD - Inflammation and Immunology, Pfizer Inc, Groton, CT, USA. FAU - Chan, Gary AU - Chan G AD - Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA. FAU - Su, Chinyu AU - Su C AD - Inflammation and Immunology, Pfizer Inc, Collegeville, PA, USA. LA - eng SI - ClinicalTrials.gov/NCT01241591 SI - ClinicalTrials.gov/NCT01458574 SI - ClinicalTrials.gov/NCT02187055 SI - ClinicalTrials.gov/NCT01186744 SI - ClinicalTrials.gov/NCT00847613 SI - ClinicalTrials.gov/NCT00678210 SI - ClinicalTrials.gov/NCT01470612 SI - ClinicalTrials.gov/NCT01976364 SI - ClinicalTrials.gov/NCT00856544 SI - ClinicalTrials.gov/NCT00603512 SI - ClinicalTrials.gov/NCT01276639 SI - ClinicalTrials.gov/NCT00853385 SI - ClinicalTrials.gov/NCT01882439 SI - ClinicalTrials.gov/NCT00976599 SI - ClinicalTrials.gov/NCT00960440 SI - ClinicalTrials.gov/NCT01262118 SI - ClinicalTrials.gov/NCT00814307 SI - ClinicalTrials.gov/NCT01309737 SI - ClinicalTrials.gov/NCT01710046 SI - ClinicalTrials.gov/NCT00787202 SI - ClinicalTrials.gov/NCT00413660 SI - ClinicalTrials.gov/NCT01465763 SI - ClinicalTrials.gov/NCT01164579 SI - ClinicalTrials.gov/NCT01877668 SI - ClinicalTrials.gov/NCT00687193 SI - ClinicalTrials.gov/NCT01163253 SI - ClinicalTrials.gov/NCT01458951 SI - ClinicalTrials.gov/NCT01039688 SI - ClinicalTrials.gov/NCT00147498 SI - ClinicalTrials.gov/NCT00661661 SI - ClinicalTrials.gov/NCT01359150 SI - ClinicalTrials.gov/NCT01484561 SI - ClinicalTrials.gov/NCT00413699 SI - ClinicalTrials.gov/NCT00550446 SI - ClinicalTrials.gov/NCT02147587 SI - ClinicalTrials.gov/NCT01059864 GR - K23 DK119544/DK/NIDDK NIH HHS/United States GR - DH_/Department of Health/United Kingdom PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200820 PL - United States TA - Dig Dis Sci JT - Digestive diseases and sciences JID - 7902782 RN - 0 (Piperidines) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrimidines) RN - 87LA6FU830 (tofacitinib) RN - EC 2.7.3.2 (Creatine Kinase) SB - IM EIN - Dig Dis Sci. 2020 Oct 10;:. PMID: 33037970 MH - Adult MH - Arthritis, Psoriatic/drug therapy MH - Arthritis, Rheumatoid/drug therapy MH - Cohort Studies MH - Colitis, Ulcerative/*drug therapy MH - Creatine Kinase/*blood MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Male MH - Middle Aged MH - Piperidines/administration & dosage/*therapeutic use MH - Protein Kinase Inhibitors/administration & dosage/*therapeutic use MH - Psoriasis/drug therapy MH - Pyrimidines/administration & dosage/*therapeutic use MH - Risk Factors PMC - PMC8298233 OTO - NOTNLM OT - Creatine kinase OT - Inflammatory bowel disease OT - Safety OT - Tofacitinib OT - Ulcerative colitis COIS- RP has received consulting fees from AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Biogen, Bristol-Myers Squibb, Celgene, Centocor, Cubist, Eisai, Elan, Ferring, Gilead, GlaxoSmithKline, Janssen, Merck, Pfizer Inc, Robarts Clinical Trials, Salix, Samsung Bioepis, Shire, Takeda, and UCB; has received research Grants from AbbVie, Ferring, Janssen, and Takeda; has received lectures and/or speaker bureau fees from AbbVie, Aptalis, AstraZeneca, Ferring, Janssen, Merck, Prometheus, Shire, and Takeda; and has received advisory board fees from Abbott, AbbVie, Amgen, Aptalis, AstraZeneca, Baxter, Bristol-Myers Squibb, Celgene, Centocor, Cubist, Eisai, Elan, Ferring, Genentech, GlaxoSmithKline, Janssen, Merck, Pfizer Inc, Salix, Schering-Plough, Shire, Takeda, and UCB. JDI has been a consultant for, and/or has received research Grants or speaker fees from, AbbVie, Amgen, Eli Lilly, Gilead, Merck, Pfizer Inc, Roche, and UCB. LAC has served as a consultant for Pfizer Inc; has received research Grants from BioRad, Pfizer Inc, and PredictImmune; and has received advisory board fees from Gilead and Janssen. WW, AM, KK, LW, GC, and CS are employees and stockholders of Pfizer Inc. EDAT- 2020/08/21 06:00 MHDA- 2021/09/23 06:00 PMCR- 2020/08/20 CRDT- 2020/08/21 06:00 PHST- 2020/05/04 00:00 [received] PHST- 2020/08/11 00:00 [accepted] PHST- 2020/08/21 06:00 [pubmed] PHST- 2021/09/23 06:00 [medline] PHST- 2020/08/21 06:00 [entrez] PHST- 2020/08/20 00:00 [pmc-release] AID - 10.1007/s10620-020-06560-4 [pii] AID - 6560 [pii] AID - 10.1007/s10620-020-06560-4 [doi] PST - ppublish SO - Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20.