Rheumatic disease patients who are exposed to tumor necrosis factor antagonists have a 10-fold increased risk of hospitalization for varicella zoster virus infections, compared with the general population, according to a secondary analysis of two large databases.
Nonetheless, the absolute incidence of varicella-related hospitalizations remains low at about three cases per 10,000 person-years of exposure, and the risks of using vaccination for prevention likely outweigh the benefits, Dr. Ignacio Garcia-Doval of Complexo Hospitalario de Pontevedra (Spain) and colleagues have reported in the October issue of the Annals of the Rheumatic Diseases.
The estimated incidence rate of hospitalization for shingles in the rheumatic population was 32 cases per 100,000 patient years, compared with an expected rate of 3.4 in the general population, and the estimated incidence of hospitalization for chickenpox in the rheumatic patients was 26 per 100,000, compared with 1.9 in the general population. This finding is based on analysis of data from a national registry of rheumatic disease patients who were treated with TNF agents (BIOBADASER database) and from an administrative database of all hospital admissions in public centers in Spain (Conjunto Mínimo Básico de Datos al Alta Hospitalaria, or CMBD), which together represent more than 114 million patient-years.
The estimated age- and sex-standardized incidence rate per 100,000 person-years, and the estimated standardized incidence difference were 9 and 26, respectively, for shingles, and 19 and 33, respectively, for chickenpox, they said (Ann. Rheum. Dis. 2010;69:1751-5).
TNF antagonists are known to be associated with an increased risk of tuberculosis in particular and of opportunistic infections in general. There is a biological basis for an increased risk of viral infections, the investigators said, noting that although some studies have shown an increased rate of viral infection in TNF antagonist–treated patients, the clinical relevance of the increase is uncertain.
The current study does not allow differentiation of the causes for the increased risk, but it does show that the absolute rate is low.
The investigators said it is unlikely that the cohorts received systematic vaccination against varicella zoster virus, since the general health mandate in Spain was given in 2005 and only for children aged 11-14 years.
"Standard guidelines for chickenpox vaccination probably apply to the population included in our study," they wrote.
However, shingles vaccine, which is an attenuated vaccine with a higher dose of antigen, could potentially lead to more side effects in an immunosuppressed population, they said.
For example, in a randomized trial of adults older than age 60 years, shingles vaccine was associated with 7 cases of severe adverse events and 14 cases of vaccine-related adverse events per 10,000 vaccinations, they noted.
"These vaccination-associated risks are similar in rate and severity to the risks of hospitalized infections in our study. Hence, shingles vaccination before starting a TNF antagonist may not be warranted at present," they wrote, concluding that although vaccination in healthy children is warranted, it is not warranted in adults with "immunosuppression secondary to the baseline inflammatory disease and its complications."
Disclosures: Various study authors reported serving on the advisory board for, and/or receiving lecture fees or honoraria from, Wyeth, Abbott, Schering-Plough, Roche, and/or Bristol-Myers Squibb.