Analysis of Adverse Events With Janus Kinase Inhibitors Reported to Spontaneous Reporting System

Background: Janus kinase (JAK) inhibitors are recently launched treatments with a new mechanism of action, so their safety needs to be verified through long-term usage. Objectives: This study aimed to determine the clinical characteristics of JAK inhibitor-related adverse events (AEs) in a real-world setting, using data from the Japanese adverse drug event report (JADER) database. Methods: AEs are defined using the preferred terms from the dictionary of medical terms for regulatory agencies and include pneumonia, herpes zoster (HZ), hematopoietic erythropenia, hematopoietic leukopenia, hematopoietic thrombocytopenia, liver disorder, renal impairment, interstitial lung disease (ILD), cardiac failure, embolic and thrombotic events, gastrointestinal perforation, and hyperglycemia. Adjusted reported odds ratios (ROR) are used to assess disproportionality in the pharmacovigilance data, and time-to-onset analysis is performed using Weibull shape parameters. Results: The JADER database contained ۸۲۳۶۶۲ reports published between April ۲۰۰۴ and March ۲۰۲۳. Pneumonia and HZ are associated with all JAK inhibitors except filgotinib. Adjusted RORs for pneumonia with peficitinib, tofacitinib, baricitinib, ruxolitinib, filgotinib, and upadacitinib are ۴.۴ (۹۵% CI, ۳.۳۶%, ۵.۷۵%), ۶.۹۳ (۹۵% CI, ۶.۱۸%, ۷.۷۷%), ۶.۵۱ (۹۵% CI, ۵.۵۲%, ۷.۶۷%), ۳.۳ (۹۵% CI, ۲.۷۶%, ۳.۹۵%), ۴.۳۹ (۹۵% CI, ۲.۵۵%, ۷.۵۸%), and ۶.۱۱ (۹۵% CI, ۴.۵۳%, ۸.۲۳%), respectively. Adjusted RORs for HZ with peficitinib, tofacitinib, baricitinib, ruxolitinib, and upadacitinib are ۸.۹۴ (۹۵% CI, ۵.۶۹%, ۱۴.۰۵%), ۳۱.۸۲ (۹۵% CI, ۲۷.۵۸%, ۳۶.۷۱%), ۳۴.۹۶ (۹۵% CI, ۲۸.۹۲%, ۴۲.۲۶%), ۵.۲۴ (۹۵% CI, ۳.۵۷%, ۷.۷%), and ۳۳.۱۹ (۹۵% CI, ۲۳.۸۱%, ۴۶.۲۷%), respectively. The median time-to-onset of pneumonia and HZ with JAK inhibitor usage ranged from ۲ to ۶ months and ۴ to ۷ months, respectively. Conclusion: We demonstrated the potential risks of JAK inhibitor use with real-world data. The present analysis shows that patients receiving peficitinib, tofacitinib, baricitinib, ruxolitinib, filgotinib, or upadacitinib should be closely monitored for AEs. The most common AEs associated with JAK inhibitors were pneumonia and HZ.

کلیدواژه ها:

Pharmacovigilance ، Tofacitinib ، Janus kinase (JAK) ، Pneumonia ، Herpes zoster (HZ)