Characterization of Creatine Kinase Levels in the Tofacitinib Ulcerative Colitis Development Program 620

• Published in: The American journal of gastroenterology Vol. 113; no. Supplement; pp. S352 - S353
• Main Authors: Panaccione, Remo, Isaacs, John D., Chen, Lea Ann, Wang, Wenjin, Marren, Amy, Kwok, Kenneth, Wang, Lisy, Chan, Gary, Su, Chinyu
• Format: Journal Article
• Language: English
• Published: New York Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins 01.10.2018
• Subjects: Arthritis; Gastroenterology; Inflammatory bowel disease; Psoriasis
• ISSN: 0002-9270; 1572-0241
• DOI: 10.14309/00000434-201810001-00620

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 >10xupper 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.