Inflamm Bowel Dis. 2022 Feb 1;28(2):234-245.doi: 10.1093/ibd/izab056.

Bruce E Sands ¹, Millie D Long ², Walter Reinisch ³, Julian Panés ⁴, Edward V Loftus ⁵, Chudy I Nduaka ⁶, Arif Soonasra ⁶, Rajiv Mundayat ⁷, Nervin Lawendy ⁶, Gary Chan ⁶, Gary S Friedman ⁶, Chinyu Su ⁶

Author information

¹Icahn School of Medicine at Mount Sinai, New York, New York, USA.

²University of North Carolina, Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina, USA.

³Medical University of Vienna, Vienna, Austria.

⁴§Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.

⁵¶Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

⁶aPfizer Inc, Collegeville, Pennsylvania, USA.

⁷*Pfizer Inc, New York, New York, USA.

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We present integrated analyses of nonmelanoma skin cancer (NMSC) incidence in the tofacitinib UC clinical program.

Methods: Nonmelanoma skin cancer events were evaluated from 3 randomized, placebo-controlled studies: 2 identical, 8-week induction studies (NCT01465763, NCT01458951), a 52-week maintenance study (NCT01458574), and an open-label, long-term extension study (NCT01470612). Cohorts analyzed were: Induction, Maintenance, and Overall (patients receiving ≥1 dose of tofacitinib 5 mg or 10 mg twice daily [BID]). An independent adjudication committee reviewed potential NMSC. Proportions and incidence rates (IRs; unique patients with events per 100 patient-years of exposure) for NMSC were evaluated. A Cox proportional hazards model was used for risk factor analysis.

Results: Nonmelanoma skin cancer was evaluated for 1124 patients (2576.4 patient-years of tofacitinib exposure; ≤6.8 years' treatment). In the Induction Cohort, NMSC IR was 0.00 for placebo and 1.26 for 10 mg BID. Nonmelanoma skin cancer IR was 0.97 for placebo, 0.00 for 5 mg BID and 1.91 for 10 mg BID in the Maintenance Cohort, and 0.73 (n = 19) in the Overall Cohort. No NMSC was metastatic or led to discontinuation. In the Overall Cohort, Cox regression identified prior NMSC (hazard ratio [HR], 9.09; P = 0.0001), tumor necrosis factor inhibitor (TNFi) failure (3.32; P = 0.0363), and age (HR per 10-year increase, 2.03; P = 0.0004) as significant independent NMSC risk factors.

Conclusions: For patients receiving tofacitinib, NMSC occurred infrequently. Older age, prior NMSC, and TNFi failure, which are previously reported NMSC risk factors in patients with UC, were associated with increased NMSC risk.