Tofacitinib Treatment Safety in Moderate to Severe Ulcerative Colitis: Comparison of Observational Population Cohort Data From the IBM MarketScan® Administrative Claims Database With Tofacitinib Trial Data

Jeffrey R Curtis, Miguel Regueiro, Huifeng Yun, Chinyu Su, Marco DiBonaventura, Nervin Lawendy, Chudy I Nduaka, Nana Koram, Joseph C Cappelleri, Gary Chan, Irene Modesto, Gary R Lichtenstein, Jeffrey R Curtis, Miguel Regueiro, Huifeng Yun, Chinyu Su, Marco DiBonaventura, Nervin Lawendy, Chudy I Nduaka, Nana Koram, Joseph C Cappelleri, Gary Chan, Irene Modesto, Gary R Lichtenstein

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We aimed to estimate the overall incidence of safety events in patients with UC in a real-life population cohort for comparison with the tofacitinib UC clinical trial program.

Methods: Clinical trial-like criteria were applied to an IBM MarketScan® claims database population-based cohort (n = 22,967) of patients with UC (October 2010 to September 2015) to identify a UC trial-like cohort treated with tumor necrosis factor inhibitors (TNFi; n = 6366) to compare with the tofacitinib UC clinical trial cohort (n = 1157).

Results: Incidence rates (events per 100 patient-years; [95% confidence interval]) in the UC trial-like cohort were as follows: serious infections, 3.33 (2.73-4.02); opportunistic infections (OIs; excluding herpes zoster [HZ]), 1.45 (1.06-1.93); HZ, 1.77 (1.34-2.29); malignancies (excluding nonmelanoma skin cancer [NMSC]), 0.63 (0.43-0.90); NMSC, 1.69 (1.35-2.10); major adverse cardiovascular events (MACE), 0.51 (0.31-0.79); pulmonary embolism (PE), 0.54 (0.30-0.89); deep vein thrombosis (DVT), 1.41 (1.00-1.93); and gastrointestinal perforations, 0.31 (0.16-0.54). Compared with the UC trial-like cohort, tofacitinib-treated patients had numerically lower incidence rates for serious infections (1.75 [1.27-2.36]), OIs (excluding HZ; 0.16 [0.04-0.42]), NMSC (0.78 [0.47-1.22]), PE (0.16 [0.04-0.41]), and DVT (0.04 [0.00-0.23]), and a higher rate for HZ (3.57 [2.84-4.43]); rates for malignancies (excluding NMSC), MACE, and gastrointestinal perforations were similar.

Conclusions: When acknowledging limitations of comparing claims data with controlled clinical trial data, incidence rates for HZ among TNFi-treated patients in the UC trial-like cohort were lower than in the tofacitinib UC clinical trial cohort; rates for serious infections, OIs, NMSC, PE, and DVT were numerically higher.

Clinicaltrials.gov: NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612.

Keywords: indirect comparison; safety; ulcerative colitis.

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

Figures

FIGURE 1.
FIGURE 1.
Selection of the UC trial-like cohort. aAdalimumab, infliximab, golimumab, and vedolizumab. bAzathioprine, 6-mercaptopurine, methotrexate, tacrolimus (oral or IV), and cyclosporine (oral or IV). cA patient could only be counted as a new user once per drug category; however, it was possible for a patient to be considered a new user for multiple drug categories. Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; N, number of patients; NE, number of treatment episodes.
FIGURE 2.
FIGURE 2.
Incidence rates (patients with events per 100 PY) for serious infections, OIs (excluding HZ), HZ, malignancies (excluding NMSC), NMSC, MACE, PE, DVT, and GI perforations in the tofacitinib UC maintenance cohort (ie, data from the 52-week OCTAVE Sustain study) and the 12-month UC trial-like cohort of the MarketScan® analysis for patients receiving any TNFi.

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