ACIP approves MMRV vaccine revision

April 2008

ATLANTA – Taking into consideration the recent developments regarding the measles-mumps-rubella-varicella vaccine supply and safety, the Advisory Committee on Immunization Practices has voted to revise the wording for its recommendation on use of this vaccine.

Mona Marin, MD, of the National Center for Immunization and Respiratory Diseases’ division of viral diseases, presented a brief update on the current MMRV (Proquad, Merck) vaccine supply and safety data at the February ACIP meeting.

“MMRV vaccine has not been widely distributed in the United States since June 2007 and is not expected to be available again until 2009; however, some providers might still have some supply in stock,” she said. “As far as postvaccination safety monitoring, in October 2007 following FDA review of adverse event reports submitted to VAERS and Merck’s worldwide adverse experience system, MMRV vaccine labeling was updated to include convulsion and febrile seizures among adverse reactions postvaccination.”

Marin also presented the proposed vote to revise the committee’s previous recommendation for MMRV vaccine use.

Currently, consistent with the ACIP General Recommendations on Immunizations, ACIP officials describe the use of MMRV vaccine as preferable to separate injections of equivalent components whenever any of the components of the combination vaccine are indicated and the other components are not contraindicated.

“In light of the recent findings from post-licensure safety surveillance, the CDC proposes that the committee consider replacing the preference for use of MMRV vaccine over simultaneous administration of MMR and varicella vaccines with no preference, the varicella ACIP statement from last year,” Marin said.

Post-licensure safety data

Nicola P. Klein, MD, PhD, a research scientist from Northern California Kaiser Permanente and co-director of the Kaiser Permanente Vaccine Study Center, spoke on behalf of the CDC’s Vaccine Safety Datalink investigators and the MMRV Rapid Cycle Analysis team to present preliminary data regarding the association between MMRV and febrile seizures.

Klein and colleagues began a rapid cycle analysis in June 2007 among children aged 12 to 23 months and monitored several outcomes, including seizures, ataxia and encephalitis. The investigators opted for a postvaccination observation window of 42 days to allow enough time to monitor all outcomes.

“The MMRV rapid cycle analysis study generated a seizure signal within 42 days post-MMRV vaccine,” Klein said. “What that means is that the number of observed seizures of any etiology in the 42-day postvaccination time window first exceeded the number of expected seizures based on historical MMR recipients by enough to justify a signal.”

They observed 59 seizures instead of the 38 seizures they expected based on historical rates.

Through temporal distribution of seizures scans, the investigators found similar, statistically significant clusters of seizures among patients seven to 10 days after vaccination with either MMRV or with simultaneous MMR, according to Klein.

MMR vaccine without varicella vaccine resulted in clustering of cases between days six through 10, whereas varicella vaccine alone resulted in clustering between days 21 and 24 postvaccination.

“Chart review data confirmed that greater than 90% of seizures were febrile,” Klein said. “Among children aged 12 to 23 months, the adjusted odds ratio was 2.3 for having confirmed febrile seizures seven-to-10 days post-MMRV compared with MMR and varicella vaccines administered simultaneously.”

She added that the attributable risk for febrile seizures on days seven to 10 postvaccination with MMRV translates into one additional febrile seizure case per every 2,000 doses when compared with MMR vaccine and varicella vaccine administered simultaneously. The increased risk for febrile seizure following vaccination with MMRV cannot be explained through concomitant vaccines, temporal trends in seizures, Vaccine Safety Datalink site, age or influenza season.

New wording

The ACIP voted 10-2 in favor of approving the proposed change to the current MMRV recommendation, with some revision.

The recommendation language will now read: “Combination MMRV vaccine is approved for use among healthy children aged 12 months to 12 years. MMRV vaccine is indicated for simultaneous vaccination against measles, mumps, rubella and varicella. ACIP does not express a preference for use of combination MMRV vaccine over separate injections of equivalent component vaccines MMR and varicella vaccine.”

According to Marin, the CDC has developed several communication materials, including a fact sheet for providers to inform them of the preliminary findings and the policy change, as well as updated the Vaccine Information Statement with the new MMRV vaccine information.

Marin said that the CDC will develop a Morbidity and Mortality Weekly Report (57(10);258-260) and encourages the ACIP to develop a work group that would evaluate the results presented and would discuss future policy options.

For more information:

• Klein NP. Vaccine Safety Datalink Project: evaluation of MMRV and febrile seizures.
• Marin M. Immunization safety update: combination measles, mumps, rubella and varicella (MMRV) vaccine – proposed vote.
• Both presented at: ACIP meeting; Feb. 27-28, 2008; Atlanta.