Inflamm Bowel Dis. 2023 May 2;29(5):744-751.doi: 10.1093/ibd/izac139.

Edward V Loftus ¹, Daniel C Baumgart ², Krisztina Gecse ³, Jami A Kinnucan ⁴, Susan B Connelly ⁵, Leonardo Salese ⁵, Chinyu Su ⁵, Kenneth K Kwok ⁶, John C Woolcott ⁵, Alessandro Armuzzi ^7 8

Author information

¹Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

²Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada.

³Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Academic Medical Center, Amsterdam, The Netherlands.

⁴Division of Gastroenterology, Mayo Clinic, Jacksonville, FL, USA.

⁵Pfizer Inc, Collegeville, PA, USA.

⁶Pfizer Inc, New York, NY, USA.

⁷IBD Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy.

⁸Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Patients with inflammatory bowel disease are susceptible to Clostridium difficile infection (CDI). Here, we evaluate CDI in the tofacitinib UC clinical program.

Methods: Events from 4 randomized, placebo-controlled studies (phase [P] 2 or P3 induction [NCT00787202; NCT01465763; NCT01458951], P3 maintenance [NCT01458574]) and an open-label, long-term extension (OLE) study (NCT01470612), were analyzed as 3 cohorts: Induction (P2/P3 induction), Maintenance (P3 maintenance), and Overall (patients receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, and OLE studies; including final data from the OLE study, as of August 24, 2020). Proportions and incidence rates (unique patients with events per 100 patient-years of exposure) of CDI were evaluated.

Results: The overall cohort comprised 1157 patients who received ≥1 dose of tofacitinib 5 or 10 mg BID, with a total of 2814.4 patient-years of tofacitinib exposure and up to 7.8 years of treatment. A total of 82.6% of patients received predominantly tofacitinib 10 mg BID. In the induction, maintenance, and overall cohorts, 3 (2 tofacitinib treated, 1 placebo treated), 3 (all placebo treated), and 9 patients had CDI, respectively; the overall cohort incidence rate was 0.31 (95% confidence interval, 0.14-0.59). CDI were all mild-moderate in severity and resolved with treatment in 8 patients. Six of 9 patients continued tofacitinib treatment without interruption. Two patients had events reported as serious due to hospitalization. Two patients were receiving corticosteroids when the CDI occurred.

Conclusion: CDIs among patients with UC receiving tofacitinib were infrequent, cases were mild-moderate in severity, and most resolved with treatment.