German scientists found that some arthritis drugs may be linked to an increased risk of developing shingles (herpes zoster), an infection that causes painful blisters.

The research was the work of Dr Anja Strangfeld of the German Rheumatism Research Center in Berlin, and colleagues, and is published in the 18 February issue of JAMA, Journal of the American Medical Association.

They found that use of certain drugs classed as monoclonal anti-tumor necrosis factor α (TNF-α) antibodies which are used to treat rheumatoid arthritis may be linked to a higher risk of developing herpes zoster (shingles).

Previous studies have suggested that treatment with anti-TNF-α agents puts rheumatoid arthritis patients at higher risk of bacterial infections but there have been few investigations into how they affect the risk of infection by viruses like shingles.

There are a number of anti-TNF-α drugs used to treat rheumatoid arthritis. They all act on the cytokine TNF (tumor necrosis factor), a chemical messenger in the immune system that sends signals to increase inflammation. TNF does other things as well (such as trigger cell death), but as far as rheumatoid arthritis is concerned it is its role in the promotion of inflammation that is important.

Anti-TNF-α agents stop TNF from binding to particular receptors on certain cells and prevents them from triggering an inflammatory response. Many arthritis patients produce too much TNF.

For this study the researchers looked at data on over 5,000 rheumatoid arthritis patients who were registed with RABBIT, a German biologics register, between May 2001 and December 2006. They enrolled on the register when they started treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed to a conventional disease-modifying antirheumatic drug (DMARD).

Infliximab and adalimumab are monoclonal antibodies and etanercept is a fusion protein and all three work by inhibiting TNF-α. Anakinra is not a TNF-α inhibitor, it blocks another inflammation signalling path that uses the interleukin-1 (IL-1) receptor.

Rheumatologists regularly assessed participants’ treatment, clinical status and adverse events during follow up.

The aim of the study was to compare the number of times shingles was observed in patients receiving the various different treatments. In particular the researchers wanted to see if the TNF-α inhibitors together as a class, or separately either as anti-TNF-α antibodies (infliximab and adalimumab), or a fusion protein (etanercept), were related to higher rates of herpes zoster (shingles).

The results showed that:

  • There were 86 episodes of herpes zoster (shingles) recorded among 82 patients.
  • 39 of the episodes were attributed to treatment with monoclonal anti-TNF-α antibodies, 23 to the fusion protein etanercept, and 24 to conventional DMARDs.
  • The crude incidence rate was 11.1 per 1,000 patient years for monoclonal anti-TNF-α antibodies, 8.9 for etanercept, and 5.6 for conventional DMARDs.
  • After adjusting for age, severity of disease, and use of glucocorticoid, the increased risk for treatment with monoclonal anti-TNF-α antibodies was a significant 1.82, but this was not high enough to reach clinical significance.
  • No significant links were found for use of etanercept (fusion protein) or for TNF-α inhibitors together as a class.

The authors concluded that:

“Treatment with monoclonal anti-TNF-{alpha} antibodies may be associated with increased risk of herpes zoster, but this requires further study.”

They added that:

“Based on our data, we recommend careful monitoring of patients treated with monoclonal anti-TNF-α antibodies for early signs and symptoms of herpes zoster.”

In an accompanying editorial, Drs Richard J. Whitley and John W. Gnann of the University of Alabama at Birmingham, commented on the findings:

“The TNF-α inhibitors provide tremendous benefit to a broad spectrum of patients with systemic inflammatory diseases. As with any therapy, time is required for all of the safety concerns related to these potent medications to become apparent. TNF-α inhibitors have revolutionized the management of a number of difficult diseases, especially inflammatory arthritis, but clinicians must continue to remain aware of the potential for serious infectious complications, which now include herpes zoster.”

“Risk of Herpes Zoster in Patients With Rheumatoid Arthritis Treated With Anti-TNF-{alpha} Agents.”
Anja Strangfeld; Joachim Listing; Peter Herzer; Anke Liebhaber; Karin Rockwitz; Constanze Richter; Angela Zink
JAMA. Vol. 301 No. 7, pp 737-744, February 18, 2009.

Click here for Abstract.

Sources: JAMA media and journal abstract.

Written by: Catharine Paddock, PhD