Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents

  • Strangfeld A
  • Listing J
  • Herzer P
 et al. 
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Context The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor alpha (TNF-alpha). Little is known about the reactivation of latent viral infections during treatment with TNF-alpha inhibitors. Objective To investigate whether TNF-alpha inhibitors together as a class, or separately as either monoclonal anti-TNF-alpha antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis. Design, Setting, and Patients Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatmentwith infliximab, etanercept, adalimumab, oranakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up. Main Outcome Measures Hazard ratio (HR) of herpes zoster episodes following anti-TNF-alpha treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF-alpha inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF-alpha inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs. Results Among 5040 patients receiving TNF-alpha inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti-TNF-alpha antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.613.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.732.55]) or for anti-TNF-alpha treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class. Conclusion Treatment with monoclonal anti-TNF-alpha antibodies may be associated with increased risk of herpes zoster, but this requires further study. copyright 2009 American Medical Association. All rights reserved.

Author-supplied keywords

  • adalimumab/ae [Adverse Drug Reaction]
  • adalimumab/dt [Drug Therapy]
  • article
  • azathioprine
  • clinical examination
  • controlled study
  • corticosteroid therapy
  • disease modifying antirheumatic drug/ae [Adverse D
  • disease modifying antirheumatic drug/dt [Drug Ther
  • disease severity
  • esophagitis/si [Side Effect]
  • etanercept/ae [Adverse Drug Reaction]
  • etanercept/dt [Drug Therapy]
  • female
  • follow up
  • glucocorticoid/dt [Drug Therapy]
  • herpes zoster/ep [Epidemiology]
  • herpes zoster/et [Etiology]
  • herpes zoster/si [Side Effect]
  • human
  • incidence
  • infliximab/ae [Adverse Drug Reaction]
  • infliximab/dt [Drug Therapy]
  • leflunomide
  • major clinical study
  • male
  • multidermatomal herpes zoster/si [Side Effect]
  • postherpetic neuralgia/si [Side Effect]
  • prednisolone
  • priority journal
  • prospective study
  • recombinant interleukin 1 receptor blocking agent
  • rheumatoid arthritis/dt [Drug Therapy]
  • rheumatology
  • risk factor
  • tumor necrosis factor alpha inhibitor/dt [Drug The
  • virus reactivation

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  • A Strangfeld

  • J Listing

  • P Herzer

  • A Liebhaber

  • K Rockwitz

  • C Richter

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