Anti-TNF therapy increases risk of varicella zoster virus infections

American College of RheumatologyNov 9 2010

Anti tumor necrosis factor therapy increases the risk of developing varicella zoster virus infections, including shingles and chicken pox, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

Varicella zoster virus is a common viral infection. The initial infection typically occurs in childhood, causing chicken pox, and reactivation later in life results in herpes zoster (shingles). The body's immune defense against both chicken pox and herpes zoster relies on immune pathways that may be impaired by anti-TNF therapy ¬- theoretically predisposing people who take anti-TNF therapy to varicella zoster-associated infection.

Using the British Society for Rheumatology Biologics Register—a registry that tracks the progress of patients with severe rheumatoid arthritis and other rheumatic conditions who are taking anti-TNF therapy—researchers recently looked at the association between anti-TNF therapy and varicella zoster infections.

They studied 11,864 people with RA who were undergoing anti-TNF therapy and compared them to 3,666 patients who were undergoing treatment with disease-modifying antirheumatic drugs (commonly called DMARDs). They began recruiting patients in October 2001 and continued to monitor them until the first episode of herpes zoster infection (which is caused by varicella zoster virus), death, or the end of 2009, whichever came first. A patient's health was monitored through questionnaires filled out by the patients and their physicians, and a varicella zoster infection was attributed to anti-TNF therapy if diagnosed while a patient was actively receiving the drug (up to the date of the first missed dose).

During the study, 322 herpes zoster infections occurred in the patients taking anti-TNF therapy and 46 infections occurred in the DMARD group. A greater proportion of the cases in the anti-TNF group were severe (defined as herpes zoster being a primary reason for hospitalization, requiring intravenous anti-viral medication, or being multi-dermatomal). Furthermore, 12 cases of chicken pox, presumably initial infection with the varicella zoster virus, were reported in the anti-TNF group and none in the DMARD group. These results suggest that anti-TNF therapy may be associated with both primary and recurrent infections with the varicella zoster virus.

"Anti-TNF therapy conferred more than a twofold increase in the risk of developing shingles in our dataset when compared to traditional DMARD therapy," explains James Galloway, MD, MBChB, MRCP, MSc; clinical research fellow; BSR Biologics Register; ARC unit; University of Manchester, Manchester, United Kingdom, and lead investigator in the study."Chicken pox was also observed more frequently in the anti-TNF cohort, although absolute numbers were small. This supports a recent similar observation from the Spanish Registry - BIOBADASER." Dr. Galloway adds. "The clinical message from this study is to be vigilant for shingles with anti-TNF therapy."

Dr. Galloway also suggests that the study's findings raise two important questions that warrant further research: Is there any value in screening people for immunity to the varicella zoster virus, and what role does vaccination have in preventing the VZV-associated infections?

TNF-antagonists (anti-TNF therapy; among drugs called biologics) are a class of drugs that have been used since 1998. Overall, they have been given to more than 600,000 people worldwide. These drugs are given to lessen inflammation by interfering with biologic substances that cause or worsen inflammation.