Risk of herpes zoster in individuals on biologics, DMARDS and/or corticosteroids for autoimmune diseases: A systematic review and meta-analysis

Background: Studies examining the risk of herpes zoster (HZ) associated with immunosuppressants, such as biologics, non-biological disease modifying agents (nbDMARDs) or corticosteroids, have generated conflicting results.

Methods: We conducted a systematic literature search from Jan 1946 to Feb 2016. Search terms related to HZ, rheumatoid arthritis, psoriasis, psoriatic arthritis, systemic lupus erythematous or inflammatory bowel disease, biologics, nbDMARDS and corticosteroids were used. We included randomized controlled trials (RCTs) and observational studies reporting associations between immunosuppressants and HZ outcomes in adults. For RCTs, we used the Mantel-Haenszel fixed-effects model to estimate pooled odds ratios (OR) and 95% confidence intervals (CI) for HZ risk. For observational studies, adjusted ORs were pooled separately using random-effects inverse variance models.

Findings: Data were pooled from 40 eligible RCTs (20,136 patients) and 19 observational studies (810,939 patients). Biologics were associated with a greater risk of HZ than control (RCTs: OR 1.71, 95% CI 1.11-2.64; Observational studies: OR OR 1.58, 95% CI 1.39-1.81). In RCTs, the OR of non-TNF blockers was 2.19 (95% CI 1.20-4.02), but that of TNF blockers was not significantly different from control. Increased risks of HZ with nbDMARDs (OR 1.21, 95% CI 1.15-1.28) and corticosteroids (OR 1.73, 95% CI 1.57-1.89) were observed in observational studies, but few RCTs examined these comparisons.

Conclusions: Immunocompromized patients receiving biologics were associated with an increased risk of HZ. The risk is also increased with corticosteroids and nbDMARDs. These findings raise the issue of prophylaxis with zoster vaccine in patients initiating immunosuppressive therapy for autoimmune diseases.