Background: Herpes zoster (HZ) is a viral infection caused by the reactivation of the varicella-zoster virus. Approximately half of individuals over the age of 50 experience HZ, and 20% of these patients develop postherpetic neuralgia, which is significantly impacts their quality of life [1]. Previous studies have identified various several risk factors for HZ, including older age, gender, race, and the use of immunosuppressive drugs [2]. Among immunosuppressive drugs, glucocorticoids and Janus kinase (JAK) inhibitors are well-known contributors to HZ [3]. One meta-analysis reported that filgotinib, a selective JAK1 inhibitor, may pose a lower risk of HZ compared to other JAK inhibitors in patients with rheumatoid arthritis (RA) [4]. However, this hypothesis has not yet been validated using real world data.

Objectives: The primary objective of this study was to evaluate the association between the types of JAK inhibitor, with a specific focus on filgotinib compared to other JAK inhibitors, and the incidence of HZ in RA patients treated with JAK inhibitors using administrative claims database. The analysis specifically targeted a high-risk elderly population aged 75 years and older.

Methods: This study is retrospective cohort study using Japan Medical Data Center database between March 2018 and April 2023. Following the target trial emulation framework, patients were included if they met the following criteria: 1) at least one claim for RA (ICD-10 code M05, 06) and 2) initiation of JAK inhibitors without any prescriptions for these medications in the preceding three months (defined as the index date). The primary outcome measure was the incidence of HZ, identified through claims (ICD-10 code B02) and prescriptions for antiviral medications for HZ treatment. A Cox proportional hazard model, adjusted for confounders such as age, sex, and chronic kidney disease, was used to assess the impact of JAK inhibitor type on HZ risk.

Results: Among 220,158 RA patients aged 75 years and older, 1,163 (0.5%) initiated JAK inhibitors during the study period. The cohort included tofacitinib (145 [12%]), baricitinib (524 [45%]), peficitinib (91 [8%]), Upadacitinib (217 [19%]), and filgotinib (186 [16%]). Mean (standard deviation [SD]) age of the patients was 81 (6.3), and 846 (73%) were female. During a mean (SD) follow-up period of 11 (9.8) months, 120 patients (10%) developed HZ. Although the incidence of HZ in patients with filgotinib appeared lower than in those with other JAK inhibitors, the difference was not statistically significant (adjusted hazards ratio: 0.66, 95% confidence interval: 0.33 - 1.31, P = 0.24).

Conclusion: In this real-world data for elderly RA patients aged 75 years and older treated, filgotinib did not demonstrate a significant benefit over other JAK inhibitors in reducing the risk of HZ. The observed advantage of filgotinib in previous network meta-analyses may be influenced by biases in the target population.

REFERENCES: [1] Johnson RW, Bouhassira D, Kassianos G, et al. The impact of herpes zoster and post-herpetic neuralgia on quality-of-life. BMC Med . 2010;8:37.

[2] Marra F, Parhar K, Huang B, et al. Risk factors for herpes zoster infection: A meta-analysis. Open Forum Infect Dis . 2020;7:ofaa005.

[3] Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open . 2020;6:e001395.

[4] Alves C, Penedones A, Mendes D, et al. The risk of infections associated with JAK inhibitors in rheumatoid arthritis: A systematic review and network meta-analysis. J Clin Rheumatol . 2022;28:e407–14.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.