Pharmacology Consult

Trivalent influenza vaccine: It may be 
time to step up our game

A hot topic among hospitals across the country is whether they will purchase one of the new quadrivalent influenza vaccines or a traditional trivalent influenza vaccine for the 2013-2014 influenza season.

The 2012-2013 influenza season was more severe than other recent influenza seasons, with the exception of the 2009-2010 H1N1 pandemic. This prompted several drug manufacturers to revamp the trivalent influenza vaccine to include an additional strain of influenza virus, converting it to a quadrivalent vaccine. With the quadrivalent influenza vaccines being so new, it is difficult to truly assess their efficacy compared with the trivalent vaccines. A recent article in American Journal of Health-System Pharmacy describes several pharmacists’ opinions regarding the quadrivalent vaccine.

Influenza A vs. influenza B

Since 1977, influenza viruses have circulated the globe and caused infection in humans. Influenza B is more specific to causing disease in humans, whereas influenza A causes disease in humans as well as other animal species. When drug manufacturers create their seasonal influenza vaccine, they include one variant strain that is most likely to circulate and cause disease from each of the following subtypes: influenza A(H1N1), A(H3N2) and B virus. Since 1985, two strains of influenza B have circulated globally, but only one of these strains could be included in the influenza vaccine.

Unfortunately, in just five of the previous 10 influenza seasons have the circulating lineage of influenza B been the one chosen to be included in the vaccine. This means patients have suboptimal protection against the influenza virus during the years in which the circulating B virus is different from the B lineage included in the vaccine for that season.

Across the country, the 2012-2013 influenza season was “early and intense,” according to the CDC. However, many clinicians said the past influenza season was particularly worse compared with other recent years because the circulating strain of influenza B was not protected against by the seasonal influenza vaccine. In Ohio, less than 40% of the influenza type B viruses isolated from patients matched the strain in the trivalent vaccine.

Kati Shihadeh

Kati Shihadeh

From Oct. 1, 2012, to May 18, 2013, the CDC antigenically characterized 2,452 influenza viruses, including 252 influenza A(H1N1) viruses, 1,324 influenza A(H3N2) viruses and 876 influenza B viruses. Of the 252 influenza A(H1N1) viruses, 98.8% were characterized as A/California/7/2009-like, the strain included in the vaccine. Of the 1,324 influenza A(H3N2) viruses, 99.6% were characterized as A/Victoria/361/2011-like, the influenza A(H3N2) component included in the vaccine. Of the 876 influenza B viruses characterized, just 66.3% belonged to the B/Yamagata lineage of viruses and were characterized as B/Wisconsin/1/2010-like, the influenza B component included in the vaccine. The remaining 33.7% of the tested influenza B viruses belonged to the B/Victoria lineage of viruses that were not protected against by the vaccine.

Move to quadrivalent

Because of last year’s awful influenza season and the ongoing influenza B mismatch contained in the vaccine, several drug manufacturers have decided to include strains from both influenza B lineages along with the two strains of influenza A to create a quadrivalent influenza vaccine. Currently, three drug companies, GlaxoSmithKline, Sanofi-Pasteur and ID Biomedical Corporation, are manufacturing the injectable quadrivalent vaccine. Strains included in the quadrivalent vaccine are A/California/07/2009 X-179A H1N1, A/Texas/50/2012 X-8 223A H3N2, B/Massachusetts/02/2012 (B Yamagata 9 lineage) and B/Brisbane/60/2008 (B Victoria lineage). MedImmune is also manufacturing a quadrivalent intranasal influenza vaccine for patients aged 2 to 49 years.

The Advisory Committee on Immunization Practices and CDC do not offer a preferential recommendation between the trivalent or quadrivalent influenza vaccines for the 2013-2014 influenza season. The quadrivalent vaccine is more expensive than the trivalent by approximately $5/dose. The quadrivalent vaccine is thought to be more effective in preventing the influenza, as it protects against an additional strain of influenza virus, but this is yet to be determined.

Investigators from the University of Pittsburgh developed a Monte Carlo simulation to predict the economic value of the quadrivalent vaccine compared with the trivalent vaccine. They published the results in Vaccine in December 2012 and suggested that the addition of the second influenza B strain to the seasonal vaccine could result in substantial cost-savings to society and third-party payers, even though the cost of the quadrivalent vaccine is significantly higher.

A recent article published in the American Journal of Health-System Pharmacy described buy-in from pharmacists for the quadrivalent vaccine. Several pharmacists quoted in the article said their hospitals would be purchasing the quadrivalent vaccine for the 2013-2014 influenza season hoping that it provides broader protection against influenza. Throughout the spring and summer, there were discussions circulating through infectious diseases pharmacists’ listservs discussing the best approach for their patients regarding which vaccine to provide at their hospital. Responses were rather divided. Some hospitals are attempting to risk-stratify patients and offer the quadrivalent to those at highest risk of being infected with influenza or those at highest risk of having substantial morbidity or mortality from the virus. Other hospitals are sticking with the traditional trivalent vaccine until more efficacy data are available for the quadrivalent vaccine or until the CDC recommends the quadrivalent over the trivalent.

With the continued mismatch of the circulating influenza B lineage compared with the B lineage selected for the seasonal vaccine, some hospitals have decided to spend more money on the quadrivalent vaccine with hopes of better protecting their patients from the influenza. Theoretically, the quadrivalent vaccine should offer better protection because it provides coverage against an additional strain of influenza. After the 2013-2014 influenza season, more data on the quadrivalent vaccine should be available. Hopefully then the CDC and ACIP can help guide clinicians in choosing which vaccine to carry in subsequent years.

References:

Ambrose CS. Hum Vaccin Immunother. 2012;8:81-88.
CDC. CDC Vaccine price list. 2013. Available at: www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/index.html#adflu. Accessed Sept. 11, 2013.
CDC. Seasonal influenza activity surveillance reports: 1999-2000 to 2010-2011 seasons. Available at: www.cdc.gov/flu/weekly/pastreports.htm. Accessed Sept. 10, 2013.
CDC. Seasonal influenza (flu). 2013. Available at: www.cdc.gov/flu/weekly/summary.htm. Accessed Sept. 10, 2013.
Lee BY. Vaccine. 2012;30:7443-7446.
Rota PA. Virology. 1990;175:59-68.
Traynor K. Am J Health Syst Pharm. 2013;70:1461-1464.

For more information::

Kati Shihadeh, PharmD, is a PGY2 infectious diseases resident at the University of Minnesota Medical Center. She can be reached at the University of Minnesota Medical Center, Fairview, Pharmacy Services, C-365 MMC 611, 420 Delaware St. SE; Minneapolis, MN 55455; email: kshihad1@fairview.org.

Disclosure: Shihadeh reports no relevant financial disclosures.

A hot topic among hospitals across the country is whether they will purchase one of the new quadrivalent influenza vaccines or a traditional trivalent influenza vaccine for the 2013-2014 influenza season.

The 2012-2013 influenza season was more severe than other recent influenza seasons, with the exception of the 2009-2010 H1N1 pandemic. This prompted several drug manufacturers to revamp the trivalent influenza vaccine to include an additional strain of influenza virus, converting it to a quadrivalent vaccine. With the quadrivalent influenza vaccines being so new, it is difficult to truly assess their efficacy compared with the trivalent vaccines. A recent article in American Journal of Health-System Pharmacy describes several pharmacists’ opinions regarding the quadrivalent vaccine.

Influenza A vs. influenza B

Since 1977, influenza viruses have circulated the globe and caused infection in humans. Influenza B is more specific to causing disease in humans, whereas influenza A causes disease in humans as well as other animal species. When drug manufacturers create their seasonal influenza vaccine, they include one variant strain that is most likely to circulate and cause disease from each of the following subtypes: influenza A(H1N1), A(H3N2) and B virus. Since 1985, two strains of influenza B have circulated globally, but only one of these strains could be included in the influenza vaccine.

Unfortunately, in just five of the previous 10 influenza seasons have the circulating lineage of influenza B been the one chosen to be included in the vaccine. This means patients have suboptimal protection against the influenza virus during the years in which the circulating B virus is different from the B lineage included in the vaccine for that season.

Across the country, the 2012-2013 influenza season was “early and intense,” according to the CDC. However, many clinicians said the past influenza season was particularly worse compared with other recent years because the circulating strain of influenza B was not protected against by the seasonal influenza vaccine. In Ohio, less than 40% of the influenza type B viruses isolated from patients matched the strain in the trivalent vaccine.

Kati Shihadeh

Kati Shihadeh

From Oct. 1, 2012, to May 18, 2013, the CDC antigenically characterized 2,452 influenza viruses, including 252 influenza A(H1N1) viruses, 1,324 influenza A(H3N2) viruses and 876 influenza B viruses. Of the 252 influenza A(H1N1) viruses, 98.8% were characterized as A/California/7/2009-like, the strain included in the vaccine. Of the 1,324 influenza A(H3N2) viruses, 99.6% were characterized as A/Victoria/361/2011-like, the influenza A(H3N2) component included in the vaccine. Of the 876 influenza B viruses characterized, just 66.3% belonged to the B/Yamagata lineage of viruses and were characterized as B/Wisconsin/1/2010-like, the influenza B component included in the vaccine. The remaining 33.7% of the tested influenza B viruses belonged to the B/Victoria lineage of viruses that were not protected against by the vaccine.

Move to quadrivalent

Because of last year’s awful influenza season and the ongoing influenza B mismatch contained in the vaccine, several drug manufacturers have decided to include strains from both influenza B lineages along with the two strains of influenza A to create a quadrivalent influenza vaccine. Currently, three drug companies, GlaxoSmithKline, Sanofi-Pasteur and ID Biomedical Corporation, are manufacturing the injectable quadrivalent vaccine. Strains included in the quadrivalent vaccine are A/California/07/2009 X-179A H1N1, A/Texas/50/2012 X-8 223A H3N2, B/Massachusetts/02/2012 (B Yamagata 9 lineage) and B/Brisbane/60/2008 (B Victoria lineage). MedImmune is also manufacturing a quadrivalent intranasal influenza vaccine for patients aged 2 to 49 years.

The Advisory Committee on Immunization Practices and CDC do not offer a preferential recommendation between the trivalent or quadrivalent influenza vaccines for the 2013-2014 influenza season. The quadrivalent vaccine is more expensive than the trivalent by approximately $5/dose. The quadrivalent vaccine is thought to be more effective in preventing the influenza, as it protects against an additional strain of influenza virus, but this is yet to be determined.

Investigators from the University of Pittsburgh developed a Monte Carlo simulation to predict the economic value of the quadrivalent vaccine compared with the trivalent vaccine. They published the results in Vaccine in December 2012 and suggested that the addition of the second influenza B strain to the seasonal vaccine could result in substantial cost-savings to society and third-party payers, even though the cost of the quadrivalent vaccine is significantly higher.

A recent article published in the American Journal of Health-System Pharmacy described buy-in from pharmacists for the quadrivalent vaccine. Several pharmacists quoted in the article said their hospitals would be purchasing the quadrivalent vaccine for the 2013-2014 influenza season hoping that it provides broader protection against influenza. Throughout the spring and summer, there were discussions circulating through infectious diseases pharmacists’ listservs discussing the best approach for their patients regarding which vaccine to provide at their hospital. Responses were rather divided. Some hospitals are attempting to risk-stratify patients and offer the quadrivalent to those at highest risk of being infected with influenza or those at highest risk of having substantial morbidity or mortality from the virus. Other hospitals are sticking with the traditional trivalent vaccine until more efficacy data are available for the quadrivalent vaccine or until the CDC recommends the quadrivalent over the trivalent.

With the continued mismatch of the circulating influenza B lineage compared with the B lineage selected for the seasonal vaccine, some hospitals have decided to spend more money on the quadrivalent vaccine with hopes of better protecting their patients from the influenza. Theoretically, the quadrivalent vaccine should offer better protection because it provides coverage against an additional strain of influenza. After the 2013-2014 influenza season, more data on the quadrivalent vaccine should be available. Hopefully then the CDC and ACIP can help guide clinicians in choosing which vaccine to carry in subsequent years.

References:

Ambrose CS. Hum Vaccin Immunother. 2012;8:81-88.
CDC. CDC Vaccine price list. 2013. Available at: www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/index.html#adflu. Accessed Sept. 11, 2013.
CDC. Seasonal influenza activity surveillance reports: 1999-2000 to 2010-2011 seasons. Available at: www.cdc.gov/flu/weekly/pastreports.htm. Accessed Sept. 10, 2013.
CDC. Seasonal influenza (flu). 2013. Available at: www.cdc.gov/flu/weekly/summary.htm. Accessed Sept. 10, 2013.
Lee BY. Vaccine. 2012;30:7443-7446.
Rota PA. Virology. 1990;175:59-68.
Traynor K. Am J Health Syst Pharm. 2013;70:1461-1464.

For more information::

Kati Shihadeh, PharmD, is a PGY2 infectious diseases resident at the University of Minnesota Medical Center. She can be reached at the University of Minnesota Medical Center, Fairview, Pharmacy Services, C-365 MMC 611, 420 Delaware St. SE; Minneapolis, MN 55455; email: kshihad1@fairview.org.

Disclosure: Shihadeh reports no relevant financial disclosures.