Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across the Ulcerative Colitis Clinical Program

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we performed an integrated analysis of malignancy events from the tofacitinib phase 3 UC clinical development program (excluding nonmelanoma skin cancer [NMSC]).

Methods: Data (up to May 2019) were pooled from two phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension (OLE) study, and analyzed as 3 cohorts: induction (N = 1139), maintenance (N = 592), and overall (induction, maintenance, and ongoing OLE study; N = 1124). Proportions and incidence rates (IRs; unique patients with events per 100 patient-years [PY] of exposure) for malignancies confirmed by adjudication were calculated.

Results: The overall cohort consisted of patients who received at least 1 dose of tofacitinib at 5 or 10 mg twice daily, for up to 6.8 years, with an exposure of 2576.4 PY. Of the 1124 overall cohort tofacitinib-treated patients, 20 developed a malignancy (excluding NMSC; IR, 0.75; 95% confidence interval, 0.46-1.16), of which 17 occurred in patients treated with tofacitinib 10 mg twice daily; importantly, more than 80% of patients predominantly received this dose. Furthermore, there was no apparent clustering of malignancy types, and IRs were stable over time.

Conclusions: In the tofacitinib UC clinical development program, malignancy events were infrequent, and rates were comparable with those in the tofacitinib rheumatoid arthritis and psoriatic arthritis clinical development programs, and for biologic UC treatments. ClinicalTrials.gov: NCT01465763, NCT01458951, NCT01458574, and NCT01470612.

Keywords: cancer; inflammatory bowel disease; ulcerative colitis.

© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.

Figures

FIGURE 1.

Overview of the tofacitinib UC clinical development program. aFinal complete efficacy assessment at week 8 of 52. Treatment continued up to week 9 of 53. bClinical response in OCTAVE Induction 1 and 2 was defined as a decrease from induction study baseline total Mayo score of ≥3 points and ≥30%, plus a decrease in rectal bleeding subscore of >1 point or an absolute rectal bleeding subscore of 0 or 1. cRemission was defined as a total Mayo score of ≤2 with no individual subscore >1, and a rectal bleeding subscore of 0. dStudy A3921139 (OCTAVE Open) is ongoing. Abbreviations: N, number of patients included in the cohort analysis; UC, ulcerative colitis.

FIGURE 2.

Proportions and IRs of adjudicated malignancies (excluding nonmelanoma skin cancer) in the maintenance and overall cohorts. Abbreviations: CI, confidence interval; IR, incidence rate (unique patients with events per 100 PY of exposure); N, number of patients; PD, predominant dose; PY, patient-years.

FIGURE 3.

Incidence rates for malignancies (excluding nonmelanoma skin cancer) in the overall cohort, by 6-monthly intervals. Abbreviations: CI, confidence interval; IR, incidence rate (unique patients with events per 100 PY of exposure); PY patient-years.

FIGURE 4.

Incidence rates for malignancies (excluding nonmelanoma skin cancer) in the overall cohort, by subgroup. Abbreviations: CI, confidence interval; IR, incidence rate (unique patients with event per 100 PY of exposure); PY, patient-years; TNFi, tumor necrosis factor inhibitor.