P334 Tofacitinib for the treatment of Ulcerative Colitis: Analysis of malignancy rates from the Ulcerative Colitis clinical programme

Ungaro, R.C.(1);Ciorba, M.A.(2);Rogler, G.(3);Sharara, A.I.(4);Sunna, N.(5);Connelly, S.B.(6);Mundayat, R.(7);Lawendy, N.(6);Panés, J.(8);

(1)Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York- New York, United States;(2)Division of Gastroenterology, Washington University in St. Louis, St. Louis- Missouri, United States;(3)Department of Gastroenterology and Hepatology, University of Zürich, Zürich, Switzerland;(4)Division of Gastroenterology, American University of Beirut Medical Center, Beirut, Lebanon;(5)-, Pfizer Inc, Amman, Jordan;(6)Pfizer Inc, Collegeville, Pennsylvania, United States;(7)Pfizer Inc, New York, New York, United States;(8)Department of Gastroenterology, Hospital Clínic de Barcelona- IDIBAPS- CIBERehd, Barcelona, Spain


Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated analysis of adjudicated malignancies in the tofacitinib UC clinical programme, including final data from the open-label, long-term extension (OLE) study (as of 24 Aug 2020).


Malignancies were evaluated from 3 randomised, placebo-controlled studies (2 Phase [P]3 induction studies [NCT01465763; NCT01458951]; 1 P3 maintenance study [NCT01458574]) and an OLE study (NCT01470612). Three cohorts were analysed: Induction (P3 induction studies), Maintenance (P3 maintenance study) and Overall (patients receiving tofacitinib 5 or 10 mg twice daily [BID] in P3 or OLE studies; data from the previous data cut [May 2019] are also reported for comparison). Analysis was by predominant dose (PD) 5 or 10 mg BID, based on average daily dose <15 mg or ≥15 mg, respectively (82.1% of patients received PD 10 mg BID). An independent adjudication committee reviewed potential malignancies. Proportions and incidence rates (IRs; unique patients with events per 100 patient-years of exposure) were evaluated for malignancies (excluding non-melanoma skin cancer [NMSC]) and NMSC.


1124 patients were evaluated for malignancies (2809.4 patient-years of tofacitinib exposure; up to 7.8 years of treatment; median duration of 685.5 days). No malignancies (excluding NMSC) occurred in Induction Cohort patients. Malignancies (excluding NMSC) occurred in 1 Maintenance Cohort patient (who was receiving placebo) and in 25 Overall Cohort patients (IR 0.86 [95% confidence interval (CI) 0.56, 1.27]: PD tofacitinib 5 mg BID n=5, IR 0.63 [95% CI 0.20, 1.47]; PD tofacitinib 10 mg BID n=20, IR 0.95 [95% CI 0.58, 1.46]); 5 new cases since May 2019 (Table).1 NMSC events in the Induction and Maintenance Cohorts were previously reported (Table).1 NMSC events occurred in 21 Overall Cohort patients (IR 0.73 [95% CI 0.45, 1.12]): PD tofacitinib 5 mg BID n=5, IR 0.63 (95% CI 0.21, 1.48); PD tofacitinib 10 mg BID n=16, IR 0.77 (95% CI 0.44, 1.25); 2 new cases since May 2019 (Table).1


There was no apparent clustering of types of malignancy, excluding NMSC. Malignancies (excluding NMSC) and NMSC IRs remained stable over time, being comparable to those previously reported in the tofacitinib UC clinical programme.1 In this analysis, malignancies (excluding NMSC) and NMSC IRs were similar to those in patients with UC treated with tumour necrosis factor inhibitors, as reported from claims data (IRs of 0.63 and 1.69, respectively).2


1. Lichtenstein et al. United European Gastroenterol J 2020;8(S):OP106
2. Curtis et al. Inflamm Bowel Dis 2020;Epub ahead of print