Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinica
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ORIGINAL ARTICLE
Characterization of Creatine Kinase Levels in Tofacitinib‑Treated Patients with Ulcerative Colitis: Results from Clinical Trials Remo Panaccione1 · John D. Isaacs2 · Lea Ann Chen3 · Wenjin Wang4 · Amy Marren4 · Kenneth Kwok5 · Lisy Wang6 · Gary Chan4 · Chinyu Su4 Received: 4 May 2020 / Accepted: 11 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 openlabel, 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 Ulcerative colitis · Inflammatory bowel disease · Tofacitinib · Creatine kinase · Safety Abbreviations AE Adverse event b.d. Twice daily BMI Body mass index CI Confidence interval CK Creatine kinase Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10620-020-06560-4) contains supplementary material, which is available to authorized users. * Remo Panaccione [email protected]
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