Incidence of herpes zoster infections in juvenile idiopathic arthritis patients

Rheumatol Int. 2015 Mar;35(3):465-70. doi: 10.1007/s00296-014-3197-6. Epub 2015 Jan 13.


The risk of herpes zoster among patients with juvenile idiopathic arthritis (JIA) exposed to biologics has not been evaluated. We determined incidence rates of herpes zoster among children with JIA in correlation with medication at time of occurrence and total drug exposure. The German biologics register database was used to identify patients with herpes zoster. Crude infection rates and incidence ratios (IRR) were compared to published rates. Demographics and overall exposure and particular exposure time to corticosteroids, immunosuppressive drugs and biologics were analyzed. The JIA cohort included 3,042 patients with 5,557.9 person-years of follow-up; 1,628 have used corticosteroids, 2,930 methotrexate and 1,685 etanercept. In total, 17 herpes zoster events have been documented [6/1,000 patients (3.5-9.0); 3.1/1,000 patient-years (1.9-4.9)]. Thus, the incidence rate in JIA patients was higher than expected [IRR 2.9 (1.8-4.5), p < 0.001]. In all patients, the event resolved completely. There were two complications, one patient developed intercostal neuralgia, and one had a recurrent herpes zoster. Compared to the healthy population, a significant higher IRR is observed in JIA patients who received a monotherapy with etanercept or in combination with steroids and methotrexate, but not in JIA patients exposed to methotrexate without biologics. In comparison with our control group of patients treated with methotrexate, the IRR was higher for exposure to etanercept monotherapy and combination of etanercept and corticosteroids irrespective of methotrexate use. A generally higher incidence rate in JIA patients treated with etanercept was observed. No serious or refractory manifestations occurred.

Publication types

  • Observational Study

MeSH terms

  • Adalimumab / adverse effects
  • Adalimumab / therapeutic use
  • Adolescent
  • Adrenal Cortex Hormones / adverse effects
  • Adrenal Cortex Hormones / therapeutic use
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / epidemiology
  • Arthritis, Juvenile / immunology
  • Azathioprine / adverse effects
  • Azathioprine / therapeutic use
  • Child
  • Cohort Studies
  • Cyclosporine / adverse effects
  • Cyclosporine / therapeutic use
  • Drug Therapy, Combination
  • Etanercept / adverse effects
  • Etanercept / therapeutic use
  • Female
  • Herpes Zoster / epidemiology*
  • Herpes Zoster / etiology
  • Herpes Zoster / immunology
  • Humans
  • Immunocompromised Host*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Incidence
  • Longitudinal Studies
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Prospective Studies
  • Risk Factors


  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Cyclosporine
  • Adalimumab
  • tocilizumab
  • Azathioprine
  • Etanercept
  • Methotrexate