Risks of Herpes Zoster in Patients With Rheumatoid Arthritis According to Biologic Disease‐Modifying Therapy

Abstract

Objective To evaluate whether the risks of herpes zoster (HZ) differed by biologic agents with different mechanisms of action (MOAs) in older rheumatoid arthritis (RA) patients. Methods Using Medicare data from 2006–2011, among RA patients with prior biologic agent use and no history of cancer or other autoimmune diseases, this retrospective cohort study identified new treatment episodes of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Followup started on initiation of the new biologic agent and ended at any of the following: first incidence of HZ, a 30‐day gap in current exposure, death, a diagnosis of other autoimmune disease or cancer, loss of insurance coverage, or December 31, 2011. We calculated the proportion of RA patients vaccinated for HZ in each calendar year prior to biologic agent initiation and HZ incidence rate for each biologic agent. We compared HZ risks among therapies using Cox regression adjusted for potential confounders. Results Of 29,129 new biologic treatment episodes, 28.7% used abatacept, 15.9% adalimumab, 14.8% rituximab, 12.4% infliximab, 12.2% etanercept, 6.1% tocilizumab, 5.8% certolizumab, and 4.4% golimumab. The proportion of RA patients vaccinated for HZ prior to biologic agent initiation ranged from 0.4% in 2007 to 4.1% in 2011. We identified 423 HZ diagnoses with the highest HZ incidence rate for certolizumab (2.45 per 100 person‐years) and the lowest for golimumab (1.61 per 100 person‐years). Neither the crude incidence rate nor the adjusted hazard ratio differed significantly among biologic agents. Glucocorticoid use had a significant association with HZ. Conclusion Among older patients with RA, the HZ risk was similar across biologic agents, including those with different MOAs.

Differential risk of herpes zoster infection with biologic agent use in rheumatoid arthritis: comment on the article by Yun et al

“…There was no difference in the risk of HZ between patients in group 2 (hazard ratio [HR] 1.34, 95% confidence interval [95% CI] 1.13-1.59) and group 3 (HR 1.38, 95% CI 1.08-1.77). Among TNF antagonists, we found a lower risk for HZ with the use of etanercept (HR 0.62, 95% CI 0.40-0.95) and adalimumab (HR 0.53, 95% CI 0.31-0.91) compared to infliximab, similar to findings by Galloway et al (4), but in contrast to those from the German biologics registry RABBIT (Rheumatoid Arthritis Observation of Biologic Therapy) (4) and the current study by Yun et al (1). One common and important risk factor for HZ in RA that emerged from all these studies was glucocorticoid use.…”

“…The study by Yun et al (1) in a recent issue of Arthritis Care & Research examining the risk of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) initiated on biologic disease-modifying antirheumatic drugs revealed that the incidence of HZ was similar among the patient groups treated with the different biologic agents, which included the 5 anti-tumor necrosis factor (anti-TNF) agents, abatacept, rituximab, and tocilizumab.…”

“…This algorithm has been validated and shown to have a high positive predictive value (PPV; .85%) (1,2). Despite this already high PPV, in order to eliminate potential false positives, we started with this approach and additionally required, for the outpatient HZ cases identified, a filled prescription for an antiviral medication within 30 days of the diagnosis, which presumably conferred greater specificity and PPV to our outcome definition.…”

Safety and Efficacy of Baricitinib Through 128 Weeks in an Open-label, Longterm Extension Study in Patients with Rheumatoid Arthritis

“…Event types such as malignancies or opportunistic infections did not emerge with prolonged treatment. Herpes zoster infections were reported without evidence of a dose effect during the OLE period at incidence rates (2.3/100 patient-yrs) similar to those described in association with biologic DMARD in RA 7,8 . Laboratory abnormalities leading to discontinuation were uncommon.…”

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy

“…We considered that the relationship between HZ and biologics was significant when the HZ events occurred during the biologic treatment or within the recommended dosing intervals after the discontinuance of biologics. The recommended dosing intervals were defined as follows: 30 days for abatacept, golimumab, and tocilizumab; 56 days for infliximab; and 180 days for rituximab [16].…”