Herpes Zoster Reactivation in Patients With Rheumatoid Arthritis: Analysis of Disease Characteristics and Disease‐Modifying Antirheumatic Drugs

Abstract

Objective. To identify the rheumatoid arthritis (RA) characteristics associated with increased herpes zoster (HZ) risk in the Corrona registry RA patients, and to evaluate the risk in initiators of tumor necrosis factor inhibitors (TNFi) or non-TNFi biologic agents or (among those who were currently on or had been previously treated with methotrexate [MTX]) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) other than MTX. Methods. Cox regression modeling estimated the association between first HZ incidence and selected RA characteristics, including disease activity. Medication-related risk for HZ in RA patients taking current or past MTX (to exclude milder RA disease) were categorized by treatment initiation (TNFi versus non-TNFi versus csDMARD). Hazard ratios (HRs) estimated HZ risk of each treatment initiation category after stratification on trimmed propensity score (PS) quintiles to control for potential confounders. Results. A total of 28,852 patients contributed 95,287 person-years. Seven hundred twenty-nine observed HZ cases yielded a 7.7 (95% confidence interval [95% CI] 7.1-8.2) per 1,000 patient-years crude incidence rate, lower than found in prior RA cohorts. However, consistent with prior studies, increasing age (HR 1.14, 95% CI 1.09-1.19 per 5 years) and prednisone therapy ‡7.5 mg/day (HR 1.81, 95% CI 1.23-2.67) were associated with a higher HZ risk. Referent to TNFi exposure, PS-stratified analysis showed an HR for csDMARDs of 1.36 (95% CI 0.82-2.25) and for non-TNFi of 0.83 (95% CI 0.51-1.38). Conclusion. In the Corrona registry, the HZ risk in RA patients taking prior or current MTX increased with older age and higher prednisone dose. The HZ risk among these patients with RA was comparable after initiation of TNFi versus non-TNFi versus csDMARDs.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis

“…One study comparing bDMARDs with the general population reported standardised incidence rates of 16–20 for tumour necrosis factor-α inhibitor (TNFi) and even higher for RTX (table 1). 15 In total, six studies,21 44–48 performed in European and American datasets, of which four were at low risk of bias, focused on the occurrence of herpes zoster, most of them reporting no increased risk for this type of infection in patients on TNFi (no studies for other bDMARDs), particularly the studies at low risk of bias and/or those that had been adjusted for dropouts 21 44–46…”

Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis

“…However, despite using validated methods to identify cases of HZ,11 we did not have access to medical records to confirm events, nor do we know of the existence of a validation study for incident HSV. While we were unable to adjust for RA disease activity and severity, we made abatacept our referent exposure group given that it is often used as a second or later line agent in patients that may be more comparable with tofacitinib-treated patients 20. Finally, we recognise the potential for surveillance bias if patients initiating tofacitinib were counselled about zoster risk and thus might be more likely to present for evaluation of suspected HZ to a physician.…”

Infection Risk and Safety of Corticosteroid Use

“…In the SABER collaboration, a baseline use of 10 mg/day or more was associated with an increased risk of HZ among rheumatic disease patients compared to no baseline steroid use (aHR 2.13 [95% CI 1.64, 2.75]) [60]. In the CORRONA registry, a prednisone dose of at least 7.5 mg/day was associated with increased risk of HZ among RA patients (HR 1.78 [95% CI 1.20, 2.63]) compared to no glucocorticoid use [61]. …”