Use of disease-modifying antirheumatic drugs and the subsequent risk of herpes zoster in older adults

Abstract

Objectives: To examine the association between DMARD use and subsequent risk of herpes zoster in a large, heterogeneous and prospective population-based cohort.

Methods: Using data from a cohort of adults (45 and Up Study) recruited between 2006 and 2009 and linked to pharmaceutical, hospital and death data (2004-2015), the effect of DMARD use on zoster risk was analysed using Cox proportional hazards models, adjusting for sociodemographic characteristics, comorbidities and corticosteroid use.

Results: Among 254 065 eligible participants, over 1 826 311 person-years follow-up, there were 6295 new DMARD users and 17 024 incident herpes zoster events. Compared with non-users, the risk of zoster was higher in those who used biologic (b)DMARDs, either alone or in combination with conventional synthetic (cs)DMARDs than in those who only used csDMARDs (adjusted hazard ratio [aHR] 2.53 [95% CI: 2.03, 3.16]) for bDMARDs vs 1.48 [95% CI: 1.33, 1.66] for csDMARDs, P-heterogeneity < 0.001; reference: non-users). Among users of csDMARDs, compared with non-users, zoster risks were highest in those using exclusively cyclophosphamide (aHR 2.69 [95% CI: 1.89, 3.83]), more moderate in those using azathioprine (aHR 1.57 [95% CI: 1.07, 2.30]) and hydroxychloroquine (aHR 1.43 [95%CI: 1.11, 1.83]) and not elevated in users of methotrexate (aHR 1.24 [95% CI: 0.98, 1.57]), sulfasalazine (aHR 1.00 [95% CI: 0.71, 1.42]) and leflunomide (aHR 0.41 [95% CI: 0.06, 2.88]).

Conclusions: The risk of zoster was high among bDMARD and cyclophosphamide users. Also, the risk was increased in those using hydroxychloroquine alone and in combination with methotrexate but not methotrexate alone. Preventative strategies such as zoster vaccination or antiviral therapies should be considered in these populations if not contraindicated.

Keywords: DMARDs; herpes zoster; hydroxychloroquine.