Risk of Herpes Zoster in Individuals on Biologics, Disease-Modifying Antirheumatic Drugs, and/or Corticosteroids for Autoimmune Diseases: A Systematic Review and Meta-Analysis

Abstract

Background.Studies examining the risk of herpes zoster (HZ) associated with immunosuppressants, such as biologics, nonbiological disease-modifying antirheumatic drugs (nbDMARDs), or corticosteroids, have generated conflicting results.Methods.We conducted a systematic literature search from January 1946 to February 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 (ORs) and 95% confidence intervals (CIs) for HZ risk. For observational studies, adjusted ORs were pooled separately using random-effects inverse variance models.Results.Data were pooled from 40 eligible RCTs (20136 patients) and 19 observational studies (810939 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 = 1.58, 95% CI = 1.39–1.81). In RCTs, the OR of non-tumor necrosis factor (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.Immunocompromised 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.

Risk of cutaneous herpes zoster in patients with spondyloarthritis treated with conventional and biologic disease‐modifying antirheumatic drugs

“…Other studies have found that MTX was associated with HR of 3.02 for HZ in RA patients and HR of 3 in SpA patients . The use of DMARDs in general was associated with increased risk of HZ, as shown in a meta‐analysis by Marra et al, and with adjusted odds ratio of 1.27 and 1.37 in RA patients from two retrospective studies . Nonetheless, a recent population‐based cohort in Taiwan failed to show the increased risk of HZ in patients with SpA .…”

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo‐controlled phase 3 trial

“…These findings should be considered alongside reports of an increased risk of HZ infection in patients with inflammatory disease, including psoriasis, treated with some biologics. [43][44][45][46][47] Although there has been some controversy around the level of HZ risk associated with biologics for inflammatory disease, 44,[48][49][50] there appears to be strong evidence suggesting an increased risk with monoclonal tumor necrosis factor-a inhibitors, 46,47 and particularly with infliximab. 43 However, an analysis of US health plan data suggested that the HZ risk associated with tofacitinib in rheumatoid arthritis patients was approximately double that with biologics.…”

Impfen bei Immundefizienz

“…B. im höheren Alter oder unter immunsuppressiver Therapie) hervorgerufen. Das Risiko für das Auftreten eines Herpes zoster ist bei Immunsupprimierten deutlich erhöht [50,[68][69][70][71]. Diese Personen sollten daher gegen Herpes zoster geimpft werden.…”