# Association Between the Dose of Tofacitinib and Risk of Herpes Zoster in Patients With Rheumatoid Arthritis: Analysis of Japanese Adverse Drug Event Report Data

## TL;DR

This study found that a lower dose of tofacitinib (5 mg/day) may reduce the risk of herpes zoster compared to a higher dose (10 mg/day) in rheumatoid arthritis patients.

## Contribution

The study provides new evidence on the dose-dependent risk of herpes zoster with tofacitinib in rheumatoid arthritis patients.

## Key findings

- Tofacitinib 5 mg/day was associated with a lower risk of herpes zoster compared to 10 mg/day.
- Female patients and methotrexate users had a higher risk of herpes zoster.
- The risk reduction with 5 mg/day was statistically significant in multivariable analysis.

## Abstract

Background: Tofacitinib is one of the Janus kinase inhibitors approved for the treatment of rheumatoid arthritis. The major adverse event of this drug is herpes zoster, which can lead to death in severe cases. The risk of herpes zoster has been studied at 10 mg/day of tofacitinib; however, 5 mg/day, which is recommended in patients with chronic kidney disease, is unclear.

Objective: To investigate whether 5 mg/day of tofacitinib reduced the risk of herpes zoster compared with 10 mg/day in rheumatoid arthritis patients.

Methods: We analyzed the Japanese Adverse Drug Event Report Data (JADER) database and compared the frequency of herpes zoster in rheumatoid arthritis patients treated with tofacitinib 5 mg/day and 10 mg/day. Multivariable logistic regression analysis was performed to identify the risk factors for herpes zoster in tofacitinib users.

Results: A total of 812 tofacitinib users with rheumatoid arthritis were identified, including 131 with herpes zoster. Disproportionality for herpes zoster was observed between 5 mg/day and 10 mg/day (reporting odds ratio (OR): 0.68, 95% confidence interval (CI): 0.47-0.98, P = 0.045). Multivariable logistic regression analysis showed that the risk of herpes zoster was significantly increased in female patients (OR: 1.87, 95% CI: 1.12-3.12, P = 0.016) and methotrexate users (OR: 1.69, 95% CI: 1.12-2.54, P = 0.013) and significantly decreased with tofacitinib 5 mg/day compared with 10 mg/day (OR: 0.62, 95% CI: 0.40-0.96, P = 0.032).

Conclusion: We suggest that tofacitinib 5 mg/day may decrease the risk of herpes zoster compared with 10 mg/day in rheumatoid arthritis patients.