Abstract

This study aimed to determine whether the long-term use of biologic agents increases serious infections in elderly patients with rheumatoid arthritis (RA) and to determine the risk factors of serious infections in biologics-treated elderly RA patients. We retrospectively analyzed the incidence rate of serious infections that required hospitalization between biologics-treated and non-biologic disease-modifying antirheumatic drug (DMARD)-treated elderly RA patients (aged over 65 years). We examined the risk factors for serious infections in biologics-treated elderly RA patients. We found that, during a 3-year observation period, the incidence rate of serious infections was not significantly different between biologics-treated and non-biologic DMARD-treated elderly RA patients [8.0 (95% CI 4.7–13.5) and 6.3 (95% CI 4.1–9.5) events per 100 person-years of follow-up, respectively, P = 0.78]. The time to the first serious infection did not significantly differ between the two groups by the analysis of the Kaplan–Meier curves, either (P = 0.46). We then found that prednisolone doses alone were significantly associated with serious infections in biologics-treated elderly RA patients. Furthermore, we found that prednisolone at 1–4 mg/day was associated with serious infections in biologics-treated patients, but not non-biologic DMARD-treated patients. On the other hand, prednisolone at greater than 5 mg/day was associated with serious infections in both biologics-treated and non-biologics-treated patients. We show that there is not a significant difference between the incidence of serious infections between biologics group and non-biologics group in elderly RA patients (≧65 years) and that even very low-dose glucocorticoid use (prednisolone 1–4 mg/day) is a risk factor for serious infections in biologics-treated elderly RA patients.

Highlights

  • Methotrexate (MTX) is an immunosuppressive non-biologic disease-modifying antirheumatic drug (DMARD), which is used as a first-line drug for the treatment of rheumatoid arthritis (RA) [1, 2]

  • PSL (≧5 mg/day) use, but not PSL (1–4 mg/day) use, was significantly associated with serious infections in the non-biologics group of elderly RA patients (Table 4). These results suggest that even lower doses of glucocorticoid (PSL 1–4 mg/day) cause serious infections in biologics-treated patients than those do in the patients without biologics

  • In this retrospective cohort study, we show that there is not a significant difference in the incidence of serious infections between the biologics and non-biologics groups in elderly RA patients (≧65 years; Table 2 and Fig. 1)

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Summary

Introduction

Methotrexate (MTX) is an immunosuppressive non-biologic disease-modifying antirheumatic drug (DMARD), which is used as a first-line drug for the treatment of rheumatoid arthritis (RA) [1, 2]. Biologic agents that block the effects of pro-inflammatory cytokines such as tumor necrosis factor (TNF) and IL-6 are used for the treatment of RA when disease activity can not be controlled with conventional DMARDs including MTX and substantially improve outcomes of RA [1, 2]. Biologic agents, due to their immunological properties, may increase the risk of serious infections in RA patients. Previous studies have reported that biologic agents increase the risk of serious infections in RA patients [7,8,9,10]. Other studies have not found an increased risk of serious infections with biologic agents in RA patients [6, 11, 12]. Conflicting information still exists regarding the risk of serious infections with biologic therapy for RA

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