Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases

Claudia A Salinas; Anthony Louder; Jennifer Polinski; Tancy C Zhang; Hannah Bower; Syd Phillips; Yufei Song; Emaan Rashidi; Rafia Bosan; Hsiu-Ching Chang; Nicole Foster; Bernice Gershenson; Hisashi Yamanaka; Mitsumasa Kishimoto; Yoshiya Tanaka; Peter Fischer; Baojin Zhu; Douglas Faries; Xiaodan Mai; Brett T Doherty; Angela Grelaud; Nicolas H Thurin; Johan Askling; Walter Deberdt; B023 Study Consortium

doi:10.1007/s40744-022-00505-1

Evaluation of VTE, MACE, and Serious Infections Among Patients with RA Treated with Baricitinib Compared to TNFi: A Multi-Database Study of Patients in Routine Care Using Disease Registries and Claims Databases

Rheumatol Ther. 2023 Feb;10(1):201-223. doi: 10.1007/s40744-022-00505-1. Epub 2022 Nov 13.

Authors

Claudia A Salinas¹, Anthony Louder², Jennifer Polinski², Tancy C Zhang², Hannah Bower³, Syd Phillips⁴, Yufei Song⁴, Emaan Rashidi⁴, Rafia Bosan⁴, Hsiu-Ching Chang⁴, Nicole Foster⁵, Bernice Gershenson⁵, Hisashi Yamanaka⁶, Mitsumasa Kishimoto⁷, Yoshiya Tanaka⁸, Peter Fischer⁹, Baojin Zhu⁹, Douglas Faries⁹, Xiaodan Mai¹⁰, Brett T Doherty¹⁰, Angela Grelaud¹¹, Nicolas H Thurin¹¹, Johan Askling³, Walter Deberdt⁹; B023 Study Consortium

Affiliations

¹ Eli Lilly and Company Corporate Center, 893 Delaware St., Indianapolis, IN, 46225, USA. claudia.salinas@lilly.com.
² Aetion, New York, NY, USA.
³ Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
⁴ IQVIA, Epidemiology and Drug Safety, IQVIA, Durham, NC, USA.
⁵ CorEvitas, Waltham, MA, USA.
⁶ Rheumatology, Sanno Medical Center, Tokyo, Japan.
⁷ Department of Nephrology and Rheumatology, Kyorin University School of Medicine, Tokyo, Japan.
⁸ The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan.
⁹ Eli Lilly and Company Corporate Center, 893 Delaware St., Indianapolis, IN, 46225, USA.
¹⁰ HealthCore Inc., Wilmington, DE, USA.
¹¹ Bordeaux PharmacoEpi, INSERM CIC-P 1401, Univ. Bordeaux, Bordeaux, France.

Abstract

Introduction: The aim of this work is to evaluate baricitinib safety with respect to venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and serious infection relative to tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis (RA).

Methods: Patients with RA from 14 real-world data sources (three disease registries, eight commercial and three government health insurance claims databases) in the United States (n = 9), Europe (n = 3), and Japan (n = 2) were analyzed using a new user active comparator design. Propensity score matching (1:1) controlled for potential confounding. Meta-analysis of incidence rate ratios (IRR) and incidence rate differences (IRD) for each outcome, from each data source was executed using modified Poisson regression and Cochran-Mantel-Haenszel analysis.

Results: Of 9013 eligible baricitinib-treated patients, 7606 were propensity score-matched with TNFi-treated patients, contributing 5879 and 6512 person-years of baricitinib and TNFi exposure, respectively. Across data sources, 97 patients (56 baricitinib) experienced VTE during follow-up, 93 experienced MACE (54 baricitinib), and 321 experienced serious infection (176 baricitinib). Overall IRRs comparing baricitinib with TNFi treatment were 1.51 (95% CI 1.10, 2.08) for VTE, 1.54 (95% CI 0.93, 2.54) for MACE, and 1.36 (95% CI 0.86, 2.13) for serious infection. IRDs for VTE, MACE, and serious infection, respectively, were 0.26 (95% CI -0.04, 0.57), 0.22 (95% CI -0.07, 0.52), and 0.57 (95% CI -0.07, 1.21) per 100 person-years greater for baricitinib than TNFi.

Conclusions: Overall results suggest increased risk of VTE with baricitinib versus TNFi, with consistent point estimates from the two largest data sources. A numerically greater risk was observed for MACE and serious infection when comparing baricitinib versus TNFi, with different point estimates from the two largest data sources. Findings from this study and their impact on clinical practice should be considered in context of limitations and other evidence regarding the safety and efficacy of baricitinib and other Janus kinase inhibitors.

Trial registration: EU PAS Register ( http://encepp.eu ), identifier #32271.

Keywords: Baricitinib; JAK inhibitors; Major adverse cardiovascular event; Rheumatoid arthritis; Serious infection; Tumor necrosis factor inhibitors; Venous thromboembolism.