Potential Adverse Events Reported With the Janus Kinase Inhibitors Approved for the Treatment of Rheumatoid Arthritis Using Spontaneous Reports and Online Patient Reviews.

Yun-Kyoung Song,Junu Song,Kyungim Kim,Jin-Won Kwon

doi:10.3389/fphar.2021.792877

Abstract

The aim of this study was to analyze the potential adverse events (AEs) caused by Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and upadacitinib, used to treat rheumatoid arthritis using spontaneous AE reports from the FDA (FAERS) and interpreting them in correlation with those from Korea (KAERS) and an online patient review (WebMD). Potential AEs were identified based on a disproportionality analysis using the proportional reporting ratio (PRR), reporting odds ratio (ROR), and the information component (IC). A total of 23,720 reports were analyzed from FAERS database, of which 91.5% were reports on tofacitinib. Potentially important medical AEs related to infections were reported frequently, as well as thromboembolism-related AEs. The AEs, such as malignancy, interstitial lung diseases, myocardial infarction, and gastrointestinal disorder, also reported. In an online patient review report, the ineffectiveness of the drug and gastrointestinal AEs were frequently reported. Infection with baricitinib and symptoms related to pain or edema due to upadacitinib were the main discomfort experienced by patients. In conclusion, the results of this study highlight the possible safety issues associated with JAK inhibitors. Routine clinical observations and further research using various real-world databases are needed.

Highlights

Janus kinase (JAK) inhibitors are small molecules that block the activity of one or more intracellular tyrosine kinases (JAK1, JAK2, JAK3, and tyrosine-protein kinase TYK2)
Tofacitinib, baricitinib, and upadacitinib were reported in 91.5% (n 21,708), 4.1% (n 980), and 4.4% (n 1,032), respectively
The mean age of patients with adverse events (AEs) related to JAK inhibitors was 59.9 years, and 54.3% (n 12,890) of the patients were in their 50’s and 60’s

Summary

Introduction

Janus kinase (JAK) inhibitors are small molecules that block the activity of one or more intracellular tyrosine kinases (JAK1, JAK2, JAK3, and tyrosine-protein kinase TYK2). Tofacitinib is the first JAK inhibitor commercially approved for the treatment of RA, Adverse Events of JAK Inhibitors gaining approval by the United States Food and Drug Association (FDA) in 2012 and the Korean Ministry of Food and Drug Safety (MFDS) in 2014. Increasing evidence suggests that JAK inhibitors may not be suitable for patients at risk for infection and thromboembolic events because the drugs block intracellular signaling pathways of inflammatory cytokines, which are relevant to host defense mechanisms, and may affect thrombopoietin signaling and platelet homeostasis adversely (Bechman et al, 2019; Gadina et al, 2019; Harigai, 2019)

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