Zoster and Pneumococcal Vaccines May Be Given Concomitantly

Laurie Barclay, MD

May 12, 2011

May 12, 2011 — Giving pneumococcal and herpes zoster vaccines to patients during the same visit may be beneficial without compromising the protective effect of the zoster vaccine, according to the results of an observational study reported in the May 9 issue of Vaccine. These findings challenge information in a 2009 revision to the zoster vaccine package insert stating that the zoster vaccine and the pneumococcal vaccine should not be given concurrently because concomitant use resulted in reduced immunogenicity of the zoster vaccine.

"Our study found no evidence that receiving the zoster vaccine and pneumococcal vaccine on the same day would compromise the immune response necessary to protect against herpes zoster, also known as shingles," said lead author Hung Fu Tseng, PhD, MPH, from the Kaiser Permanente Department of Research & Evaluation in Pasadena, California, in a news release. "Ideally, when a new vaccine is introduced to the public, one should consider giving it at the same time as other vaccines to increase coverage levels and minimize administration costs, if there are no immune response issues or safety concerns."

At Kaiser Permanente Southern California in 2009, the investigators used electronic health records to compare the incidence of herpes zoster after vaccination with a zoster vaccine in patients 60 years or older who received both vaccines on the same day (n = 7187) vs that in patients receiving a pneumococcal vaccine within 1 year to 30 days before receiving zoster vaccine (n = 7179). A Cox proportional hazard model allowed estimation of the hazard ratio (HR) for incident herpes zoster.

Of 114 herpes zoster cases identified, 56 cases were in the concomitant vaccination group, and 58 cases were in the nonconcomitant group. The incidence of herpes zoster was 4.54 (95% confidence interval [CI], 3.43 - 5.89) per 1000 person-years in the concomitant vaccination cohort and 4.51 (95% CI, 3.42 - 5.83) per 1000 person-years in the nonconcomitant vaccination cohort. After adjustment, the HR was 1.19 (95% CI, 0.81 - 1.74).

"In this study, we found no evidence of an increased risk of [herpes zoster] in the population receiving zoster vaccine and pneumococcal vaccine concomitantly," the study authors write. "The revision of the product information needs to be carefully assessed to avoid introducing barriers to patients and providers who are interested in these two important vaccines."

Limitations of this study include lack of validation of the completeness of pneumococcal or zoster vaccine data captured within the system; reliance on the electronic heath record; and limited power to detect a difference in herpes zoster incidence of the 2 cohorts, especially in the age and sex subgroups.

Albeit Observational, Study Well Done

"Although this was an observational study, it was very well done, and the findings support the current [US Centers for Disease Control (CDC)] recommendation that persons eligible for both vaccines receive the zoster vaccine and the pneumococcal vaccine at the same visit," Rafael Harpaz, MD, MPH, a CDC medical epidemiologist on the Herpes virus team, told Medscape Medical News in an independent comment. "It has been the general recommendation of the [Advisory Committee on Immunization Practices] that giving a live vaccine and an attenuated vaccine together should not be a problem."

Dr. Harpaz also noted that an additional strength of this study is that the investigators looked at 13 other conditions and found the groups to be well balanced.

On the basis of an earlier research study by Merck showing that antibody levels to the herpes zoster virus were lowered if the vaccine was given concomitantly with pneumococcal vaccine, the US Food and Drug Administration (FDA) approved the zoster vaccine package labeling change in 2009. However, that study assessed antibody levels, whereas it is the cell-mediated immunity against the herpes virus that protects against contracting herpes zoster.

"The CDC was also concerned about the label change because baseline serology was different in the 2 randomized groups in the Merck study, and the FDA and Merck couldn't explain why even after studying the data again," Dr. Harpaz said. "The CDC was delighted that in the present observational study, there appeared to be no problem with giving the 2 vaccines at the same visit. This practice should help to minimize barriers to giving the herpes vaccine."

Expertise From Outside Sources Needed

An accompanying editorial by Michael N. Oxman, MD, from the University of California, San Diego, and Department of Veterans Affairs San Diego Healthcare System, and colleagues note the importance of using a clinically valid correlate of protection.

"The selection and evaluation of such clinically valid and reliable correlates of protection, and the design of suitable phase IV clinical studies, will need to be accomplished in advance of their deployment," the editorialists write. "Since this will often require more expertise than is likely to be found in a single federal agency or pharmaceutical company, it may require new paradigms to ensure that the expertise and experience of the dedicated personnel at the [FDA] and industry are routinely augmented by appropriate external expertise from other government agencies and academia. While there may be barriers, both legal and cultural, to introducing such a broad-based and integrated process, the potential benefits to the public health warrant its careful consideration and the effort required."

No funding information has been reported for this study. The study authors have disclosed no relevant financial relationships. One of the editorialists (Anne A. Gershon, MD) has received research support from Merck, consulting for and serving as chair of a data and safety monitoring board for a zoster vaccine produced by GlaxoSmithKline, and receiving lecture fees from GlaxoSmithKline. Dr. Harpaz has disclosed no relevant financial relationships.

Vaccine. 2011;29:3625-3627, 3628-3632. Abstract