A Spanish study on varicella zoster virus (VZV) infections has shown that patients with rheumatic diseases who are on anti–tumor necrosis factor (anti-TNF) drugs had a 10-fold increase in the rate of hospitalization due to shingles and chickenpox compared with the general population.1 However, the authors note that the absolute numbers for the increase were low (about three cases per 10,000 person-years of exposure) and “the benefits of vaccination do not clearly outweigh the risks with regard to preventing serious or hospitalized herpes zoster infection.”
According to study co-author Loreto Carmona, MD, PhD, the message to rheumatologists is that, “the rate of infections or re-infections by VZV in patients treated with anti-TNFs may or may not be clearly increased; we cannot really tell. But the severity of infections may be increased. “
He adds that the decision to vaccinate a patient should be made on an individual basis. “Massive VZV vaccination has not shown to clearly prevent serious cases of VZV infection,” Dr. Carmona says, “and thus it is unclear that it will prevent serious cases in anti–TNF-exposed patients. The best vaccination should be offered before any immunosuppression (even before the use of corticoids) occurs.”
The study used estimates from the Registro Español de Acontecimientos Adversos de Terapias Biológicas en Enfermedades Reumaticas (BIOBADASER), a national active registry of Spanish patients with rheumatic diseases treated with TNF antagonists, and an administrative database of all hospital admissions in public centers in Spain. For each condition, the incidence rate (IR), the age and gender standardized incidence ratio, and the standardized incidence difference were estimated.
In patients exposed to anti-TNF drugs, the estimated IR of hospitalization due to shingles was 32 cases per 100,000 patient-years, whereas the expected rate in the general population was 3.4 cases. The estimated IR of hospitalization due to chickenpox in patients exposed to TNF antagonists was 26 cases per 100,000, the while expected rate in the general population was 1.9 cases.
The authors note that, given the low overall risk, their study was underpowered to separate the effect of drugs and disease and to compare the risks associated with different drugs. They suggest that future research would require large cohorts.
Additionally, the researchers note that shingles vaccine has a higher dose of antigen that could potentially lead to more side effects in an immunosuppressed population. “Hence, shingles vaccination before starting a TNF antagonist may not be warranted at present,” they say, adding that, “in Spain the rate of severe cases (admission) has not decreased with vaccination, so vaccination should clearly be recommended in healthy children but not in adults with immunosuppression secondary to the baseline inflammatory disease and its complications.”
Dr. Carmona tells The Rheumatologist that, “effective preventive measures are more effective before any immunosuppression at all, not only before anti-TNF treatment.”
- García-Doval I, Pérez-Zafrilla B, Descalzo MA, et al. Incidence and risk of hospitalization due to shingles and chickenpox in patients with rheumatic diseases treated with TNF antagonists. Ann Rheum Dis. 2010;69:1751-1755.