Risk of herpes zoster in patients with rheumatoid arthritis in the biologics era from 2011 to 2015 and its association with methotrexate, biologics, and corticosteroids

Rei Yamaguchi; Eiichi Tanaka; Ayako Nakajima; Eisuke Inoue; Mai Abe; Eri Sugano; Naohiro Sugitani; Kumiko Saka; Moeko Ochiai; Yoko Higuchi; Naoki Sugimoto; Katsunori Ikari; Hisashi Yamanaka; Masayoshi Harigai

doi:10.1093/mr/roab026

Risk of herpes zoster in patients with rheumatoid arthritis in the biologics era from 2011 to 2015 and its association with methotrexate, biologics, and corticosteroids

Mod Rheumatol. 2022 Apr 18;32(3):522-527. doi: 10.1093/mr/roab026.

Authors

Rei Yamaguchi^{1

2}, Eiichi Tanaka^{1

2}, Ayako Nakajima^{1

3}, Eisuke Inoue^{1

4}, Mai Abe^{1

2}, Eri Sugano^{1

2}, Naohiro Sugitani^{1

2}, Kumiko Saka^{1

2}, Moeko Ochiai^{1

2}, Yoko Higuchi^{1

2}, Naoki Sugimoto^{1

2}, Katsunori Ikari^{1

5

6}, Hisashi Yamanaka^{1

7

8}, Masayoshi Harigai^{1

2}

Affiliations

¹ Department of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
² Department of Rheumatology, Institute of Rheumatology, Tokyo Women's Medical University Hospital, Tokyo, Japan.
³ Center for Rheumatic Disease, Mie University Hospital, Mie, Japan.
⁴ Research Administration Center, Showa University, Tokyo, Japan.
⁵ Department of Orthopedic Surgery, Institute of Rheumatology, Tokyo Women's Medical University Hospital, Tokyo, Japan.
⁶ Division of Multidisciplinary Management of Rheumatic Diseases, Department of Orthopedic Surgery, Tokyo Women's Medical University, Tokyo, Japan.
⁷ Rheumatology, Sanno Medical Center, Tokyo, Japan.
⁸ Department of Rheumatology, International University of Health and Welfare, Tokyo, Japan.

PMID: 34897494
DOI: 10.1093/mr/roab026

Abstract

Objectives: To elucidate the incidence and risk factors of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) in the biologics era.

Methods: We determined the rate of HZ occurrence among the RA patients that participated in the Institute of Rheumatology, Rheumatoid Arthritis surveys from 2011 to 2015, by assessing medical records. The standardised incidence rate per 1000 patient-years with a 95% confidence interval (CI) was calculated, and risk factors for HZ were analysed using a time-dependent Cox regression analysis.

Results: Among 7815 patients (female, 84.7%) contributing to 25,863 patient-years of observation, 340 HZ events in 309 patients were confirmed. The standardised incidence rate (95% CI) per 1000 patient-years was 8.5 (6.9-10.5) in total, 6.0 (3.7-9.2) in men, and 11.0 (8.7-13.7) in women. Risk factors for HZ were age per 10 years (hazard ratio 1.14, 95% CI 1.03-1.26, p < .05), Japanese version of the Health Assessment Questionnaire (J-HAQ) score of 0.5-1.5 (versus J-HAQ = 0; 1.51, 1.09-2.10, p < .05), methotrexate use (1.58, 1.06-2.36, p < .05), and biologic use (1.88, 1.44-2.47, p < .01).

Conclusions: In the era when biologics were frequently used and corticosteroid use and doses were decreasing, methotrexate and biologics increased the risk for HZ.

Keywords: Biologic disease-modifying antirheumatic drug; corticosteroid; herpes zoster; methotrexate; rheumatoid arthritis.

MeSH terms

Adrenal Cortex Hormones / therapeutic use
Antirheumatic Agents* / adverse effects
Arthritis, Rheumatoid* / complications
Arthritis, Rheumatoid* / drug therapy
Arthritis, Rheumatoid* / epidemiology
Biological Products* / adverse effects
Child
Female
Herpes Zoster* / epidemiology
Herpes Zoster* / etiology
Herpesvirus 3, Human
Humans
Male
Methotrexate / adverse effects

Substances

Adrenal Cortex Hormones
Antirheumatic Agents
Biological Products
Methotrexate

Grants and funding

Ministry of Health, Labour and Welfare