Statin therapy reduces influenza vaccine effectiveness

Issue: December 2015

Statins, which are prescribed to large numbers of adults to prevent cardiovascular disease, may inadvertently lower the immune response and reduce influenza vaccine effectiveness, according to two studies published in the Journal of Infectious Diseases.

The CDC estimated that up to 26% of adults aged older than 40 years in the United States in 2012 were prescribed statins, and these findings appear to support the use of high-dose or adjuvanted influenza vaccines in older adults to counteract the immunosuppressive effect of statin therapy.

“Although the primary goal of statin therapy has been to lower cholesterol levels, it has been recognized that this drug class has other effects, including suppression of T-cell activation and immunomodulatory anti-inflammatory effects,”Steven Black, MD, of Cincinnati Children’s Hospital Medical Center, and colleagues wrote in one of the studies.

Steven Black

In a post hoc cross-sectional observational analysis, Black and colleagues evaluated the influence of statin therapy on immune response to influenza vaccination in nearly 7,000 adults aged older than 65 years during the 2009-2010 and 2010-2011 influenza seasons.

The researchers found that among the statin group, geometric mean titer ratios were reduced by 38% (95% CI, 27-50) for A(H1N1), 67% (95% CI, 54-80) for A(H3N2) and 38% (95% CI, 28-29) for influenza B.

“The thought is that statins, which interfere with the inflammatory response, may indeed blunt the immune mechanism,” William Schaffner, MD, professor of preventive medicine at Vanderbilt University School of Medicine and an Infectious Disease News Editorial Board member, said in an interview. “That’s the current thinking, although I don’t think people have thought very profoundly about it, yet.”

William Schaffner

In the second study, a retrospective cohort analysis, Saad B. Omer, MBBS, MPH, PhD, of Emory University, and colleagues evaluated the effectiveness of influenza vaccine against medically attended acute respiratory illness over nine influenza seasons from 2002 to 2011. The study included 137,488 patients, most aged younger than 65 years, and compared incidence rate ratios estimating vaccines effectiveness in statin users before and after influenza circulation. The researchers adjusted their analysis for age, diabetes, cardiovascular disease, well-care visits during influenza season, previous chronic obstructive pulmonary disease and prior receipt of Pneumovax 23 (23-valent pneumococcal polysaccharide vaccine, Merck).

Saad B. Omer

For statin users, vaccine effectiveness against influenza was reduced during periods of local and widespread flu circulation, with mean differences of 13.1% (95% CI, 0.4%-27.6%) and 20.3% (5.1%-37.6%), respectively. Even in the adjusted analysis, vaccine effectiveness was reduced during periods of widespread flu circulation, with a mean difference of 18.4% (95% CI, 2.9%-36.2%), and there was a nonsignificant trend toward reduced vaccine effectiveness during periods of local flu circulation, with a mean difference of 11.4% (95% CI, –1.7% to 26.1%).

Robert L. Atmar

Wendy A. Keitel

“We recognize that the influenza vaccine is a good vaccine, but a far from perfect vaccine,” Schaffner said. “Another potentially good effect of these studies is it will get companies and the NIH and investigators committed even more to develop a better influenza vaccine.”

In a related commentary, Robert L. Atmar, MD, and Wendy A. Keitel, MD, of Baylor College of Medicine, said that while the results are biologically plausible, they should not affect a physician’s care of patients.

“Instead, the results of these two studies should be viewed as hypothesis-generating and should prompt further investigations into whether statins reduce inactivated influenza vaccine immunogenicity and, if so, the mechanisms by which immune responses and associated vaccine effectiveness are adversely affected,” they wrote.

A CDC representative told Infectious Disease News that the CDC is looking deeper into the issue, but for now, its recommendation for vaccination remains unchanged.

“With rare exception, CDC recommends an annual flu vaccine for everyone 6 months and older, with no preferential recommendation for one vaccine over another,” the representative said. “For people 65 and older, the high-dose vaccine — which is intended to create a stronger immune response (more antibody) in the person getting the vaccine — is a vaccination option. Some studies have shown the high-dose vaccine to be more effective than the regular-dose vaccine in people for whom it is approved.”

The high-dose vaccine contains four times the amount of antigen as the standard dose, and is associated with higher antibody production after vaccination, according to the CDC. Studies have shown that the high-dose vaccine was cost-effective, reduced hospitalizations in the elderly, and was more effective in preventing laboratory-confirmed influenza.

“While we’re in this position, certainly, of reviewing the data and trying to find out more information, I would think that that would make the high-dose vaccine more attractive for people aged 65 and older,” Schaffner said. “I think providers, as they become aware of these data and the discussions that are going on, might well become even more committed to using the high-dose vaccine.” – by Will Offit and Stephanie Viguers

References:
Atmar RL, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv459.
Black S, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv456.
Omer SB, et al. et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv457.

Disclosures: Atmar reports receiving grants from Takeda Vaccines. Black reports serving as a consultant for Novartis Vaccines, which funded the study. Keitel, Omer, Schaffner and colleagues report no relevant financial disclosures. Please see the full studies for the lists of all other authors’ relevant financial disclosures.