Nonserious Infections in Patients With Rheumatoid Arthritis: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Kapil Halai,Sam Norton,Mark Yates,James B Galloway,Andrew P Cope,Katie Bechman,Kimme L Hyrich

doi:10.1002/art.41754

Abstract

To describe the frequency and predictors of nonserious infections (NSI) and compare incidence across biologic agents within the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA). The BSRBR-RA is a prospective observational cohort study. An NSI was defined as an infection that did not require hospitalization or intravenous therapy. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered "at risk" from the date of initiation of biologic treatment for up to 3 years. Drug exposure was defined by agent: tumor necrosis factor inhibitor (TNFi), interleukin-6 (IL-6) inhibitor, B cell depletion (rituximab), or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone. A multiple-failure Cox model was used with multivariable adjustment. Missing data were addressed using multiple imputation. There were 17,304 NSI in 8,145 patients, with an event rate of 27.0 per person per year (95% confidence interval [95% CI] 26.6-27.4). Increasing age, female sex, comorbidity burden, glucocorticoid therapy, higher Disease Activity Score in 28 joints, and higher Health Assessment Questionnaire disability index were associated with an increased risk of NSI. There was a significant reduction in NSI risk with csDMARDs compared to biologic treatments. Compared to TNFi, IL-6 inhibition and rituximab were associated with a higher NSI risk (adjusted hazard ratio 1.45 [95% CI 1.29-1.63] and adjusted hazard ratio 1.28 [95% CI 1.14-1.45], respectively), while the csDMARD cohort had a lower risk (adjusted hazard ratio 0.64 [95% CI 0.59-0.70]). Within the TNFi class, adalimumab was associated with a higher NSI risk than etanercept (adjusted hazard ratio 1.11 [95% CI 1.05-1.17]). NSI occur frequently in RA, and predictors mirror those reported with serious infections. All biologics are associated with a greater risk of NSI, with differences observed between agents. While unmeasured confounding must be considered, the magnitude of effect is large, and a relationship between NSI and targeted immunomodulatory therapy likely exists.

Highlights

Patients with rheumatoid arthritis (RA) experience a greater number of infections compared to the background population
Compared to tumor necrosis factor inhibitor (TNFi), IL-6 inhibition and rituximab were associated with a higher Nonserious infections (NSI) risk, while the csDMARD cohort had a lower risk
Within the TNFi class, adalimumab was associated with a higher NSI risk than etanercept

Summary

Introduction

Patients with rheumatoid arthritis (RA) experience a greater number of infections compared to the background population. These infections are frequent and contribute to substantial morbidity and mortality [1,2]. Infection susceptibility is a combination of disease-related immunologic dysfunction, immunocompromising comorbidities, and the use of immunomodulatory drugs. It is determined by patient lifestyle and other factors beyond the RA disease. Differences in risk observed between biologic agents have particular clinical relevance for patients considered to be “high risk” [8,10,11]

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Discussion

Conclusion