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Incidence of herpes zoster infections in juvenile idiopathic arthritis patients

  • Original Article - Safety and Pharmacovigillance
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Abstract

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.

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References

  1. Beukelman T, Xie F, Chen L, Baddley JW, Delzell E, Grijalva CG et al (2012) SABER collaboration. Rates of hospitalized bacterial infection associated with juvenile idiopathic arthritis and its treatment. Arthritis Rheum 64(8):2773–2780

    Article  PubMed Central  PubMed  Google Scholar 

  2. Pérez-Zafrilla B, Carmona L, Gómez-Reino JJ (2012) Infections in patients with rheumatic diseases treated with TNF antagonists. Curr Pharm Biotechnol 13(8):1418–1425

    Article  PubMed  Google Scholar 

  3. Winthrop KL, Chiller T (2009) Preventing and treating biologic-associated opportunistic infections. Nat Rev Rheumatol 5(7):405–410

    Article  CAS  PubMed  Google Scholar 

  4. Winthrop KL, Baddley JW, Chen L, Liu L, Grijalva CG, Delzell E et al (2013) Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster. JAMA 309(9):887–895

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Smitten AL, Choi HK, Hochberg MC, Suissa S, Simon TA, Testa MA et al (2007) The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom. Arthritis Rheum 57(8):1431–1438

    Article  PubMed  Google Scholar 

  6. Insinga RP, Itzler RF, Pellissier JM, Saddier P, Nikas AA (2005) The incidence of herpes zoster in a United States administrative database. J Gen Intern Med 20(8):748–753

    Article  PubMed Central  PubMed  Google Scholar 

  7. Meier JL, Strauss SE (1992) Comparative biology of latent varicella-zoster virus and herpes simplex virus infections. J Infect Dis 166(Suppl 1):S13–S23

    Article  PubMed  Google Scholar 

  8. Horneff G, Schmeling H, Biedermann T, Foeldvari I, Ganser G, Girschick HJ et al (2004) The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 63(12):1638–1644

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Horneff G, De Bock F, Foeldvari I, Girschick HJ, Michels H, Moebius D et al (2009) German and Austrian Paediatric Rheumatology Collaborative Study Group. Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis 68(4):2–519

    Article  Google Scholar 

  10. Comar M, Delbue S, Lepore L, Martelossi S, Radillo O, Ronfani L et al (2013) Latent viral infections in young patients with inflammatory diseases treated with biological agents: prevalence of JC virus genotype. J Med Virol 85(4):716–722

    Article  CAS  PubMed  Google Scholar 

  11. Kerensky TA, Gottlieb AB, Yaniv S, Au SC (2012) Etanercept: efficacy and safety for approved indications. Expert Opin Drug Saf. 11(1):121–139

    Article  CAS  PubMed  Google Scholar 

  12. Bracaglia C, Buonuomo PS, Tozzi AE, Pardeo M, Nicolai R, Campana A et al (2012) Safety and efficacy of etanercept in a cohort of patients with juvenile idiopathic arthritis under 4 years of age. J Rheumatol 39(6):1287–1290

    Article  CAS  PubMed  Google Scholar 

  13. Shimizu M, Nakagishi Y, Kasai K, Yamasaki Y, Miyoshi M, Takei S et al (2012) Tocilizumab masks the clinical symptoms of systemic juvenile idiopathic arthritis-associated macrophage activation syndrome: the diagnostic significance of interleukin-18 and interleukin-6. Cytokine. 58(2):287–294. doi:10.1016/j.cyto.2012.02.006

    Article  CAS  PubMed  Google Scholar 

  14. Beukelman T, Xie F, Baddley JW, Chen L, Delzell E, Grijalva CG et al (2013) SABER Collaboration. Brief report: incidence of selected opportunistic infections among children with juvenile idiopathic arthritis. Arthritis Rheum 65(5):1384–1389

    Article  PubMed Central  PubMed  Google Scholar 

  15. Strangfeld A, Listing J, Herzer P, Liebhaber A, Rockwitz K, Richter C et al (2009) Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents. JAMA 301(7):737–744. doi:10.1001/jama.2009.146

    Article  CAS  PubMed  Google Scholar 

  16. Zhang N, Wilkinson S, Riaz M, Östör AJ, Nisar MK (2012) Does Methotrexate increase the risk of varicella or herpes zoster infection in patients with rheumatoid arthritis? A systematic literature review. Clin Exp Rheumatol 30(6):962–971

    CAS  PubMed  Google Scholar 

  17. Kilic O, Kasapcopur O, Camcioglu Y, Cokugras H, Arisoy N, Akcakaya N (2012) Is it safe to use anti-TNF-α agents for tuberculosis in children suffering with chronic rheumatic disease? Rheumatol Int 32(9):2675–2679. doi:10.1007/s00296-011-2030-8

    Article  CAS  PubMed  Google Scholar 

  18. Glynn C, Crockford G, Garaghan D et al (1990) Epidemiology of shingles. J R Soc Med 83(10):617–619

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Kost RG, Straus SE (1996) Postherpetic neuralgia—pathogenesis, treatment and prevention. N Engl J Med 335(1):32–42

    Article  CAS  PubMed  Google Scholar 

  20. Guess HA, Broughton DD, Melton LJ, Kurland LJ III (1985) Epidemiology of herpes zoster in children and adolescents: a population-based study. Pediatrics 76(4):512–517

    CAS  PubMed  Google Scholar 

  21. Balfour HH Jr (1988) Varicella zoster virus infections in immunocompromised hosts. Am J Med 85(2A):68–73

    PubMed  Google Scholar 

  22. Locksley RM, Flournoy N, Sullivan KM, Meyers JD (1985) Infection with varicella-zoster virus after marrow transplantation. J Infect Dis 152(6):1172–1181

    Article  CAS  PubMed  Google Scholar 

  23. Veenstra J, Krol A, van Praag RM, Frissen PH, Schellekens PT, Lange JM et al (1995) Herpes zoster, immunological deterioration and disease progression in HIV-1 infection. AIDS. 9(10):1153–1158

    Article  CAS  PubMed  Google Scholar 

  24. Schöfer H et al (1991) Frühsymptome der HIV-Erkrankung an Haut und Schleimhäuten. AIDS-Forschung (AIFO) 6:633–648

    Google Scholar 

  25. Cohen, Beltriani, Grossman et al (1988) Disseminated herpes zoster in patients with human immunodeficiency virus infection. Am J Med 84(6):1076–1080

    Article  CAS  PubMed  Google Scholar 

  26. Rusthoven JJ, Ahlgren P, Elhakim T, Pinfold P, Reid J, Stewart L et al (1988) Varizella zoster infection in adult cancer patients: a population study. Arch Intern Med 148(7):1561–1566

    Article  CAS  PubMed  Google Scholar 

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Nimmrich, S., Horneff, G. Incidence of herpes zoster infections in juvenile idiopathic arthritis patients. Rheumatol Int 35, 465–470 (2015). https://doi.org/10.1007/s00296-014-3197-6

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  • DOI: https://doi.org/10.1007/s00296-014-3197-6

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