Statin use associated with reduced influenza vaccine effectiveness

Statins may inadvertently lower the immune response to influenza vaccines and reduce effectiveness in older adults at risk for serious illness, according to a pair of studies published in The Journal of Infectious Diseases.

“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. “We have shown that elderly individuals who receive this class of drugs, especially synthetically derived statins, have apparent lower immune responses to both adjuvanted and unadjuvanted influenza vaccines.”

Steven Black

For a post hoc cross-sectional observational analysis, Black and colleagues assessed the association between statins and influenza vaccine immune responses in nearly 7,000 aged adults older than 65 years during the 2009 to 2010 and 2010 to 2011 influenza seasons. More than 1,300 patients received statins at least 28 days before vaccination and continued the therapy for 22 days after receipt of vaccination. Seventy-six percent of statin users who received the adjuvanted trivalent influenza vaccine (aIIV3) and 74% who received the unadjuvanted IIV3 vaccine received fermentation-derived statins; the remaining participants received synthetic statins.

The researchers compared hemagglutination-inhibiting (HAI) geometric mean titers (GMTs) between the statin and control groups against influenza A(H1N1)/California, influenza A(H3N2)/Perth and influenza B (Brisbane) using blood samples obtained each day during the observation period. Among statin users, GMT ratios were 38% (95% CI, 27-50) lower for A(H1N1), 67% (95% CI, 54-80) lower for A(H3N2) and 38% (95% CI, 28-29) lower for influenza B compared with patients in the control arm. The detrimental effect of statins on immune response was more evident in patients receiving synthetic statins for both aIIV3 and IIV3 vaccines.

“Antibody levels achieved with adjuvanted vaccine were higher, so more individuals would reach an arbitrary threshold of protection on statin with aIIV than with IIV,” Black and colleagues wrote. “If … confirmed by other studies, these results could support preferential use of adjuvanted vaccines or high-dose influenza vaccines in elderly individuals to counteract statin-induced immunosuppression.”

Another study also concluded that, if confirmed through additional research, their findings may have potential implications for guidelines on statin use during routine vaccinations.

Saad B. Omer

Saad B. Omer, MBBS, MPH, PhD, and colleagues from Emory University conducted a retrospective cohort study over nine influenza seasons from 2002 to 2011 to determine the effectiveness of influenza vaccines against medically attended acute respiratory illnesses. The researchers collected data on 137,488 patients from a large managed care organization in the Southeastern United States. The majority were aged younger than 65 years.

Incidence rate ratios estimating vaccines effectiveness were evaluated before influenza circulation and compared with incidence rate ratios during times of increased transmission, which was based on state health department reports. The analysis was adjusted for age, well-care visits during influenza season, prior receipt of 23-valent pneumococcal polysaccharide vaccine, prior chronic obstructive pulmonary disease, cardiovascular disease and diabetes.

More than 52,000 cases of medically attended acute respiratory illnesses were reported. The mean vaccine effectiveness was 11.4% (95% CI, –1.7 to 26.1) lower during local influenza circulation and 18.4% (95% CI, 2.9-36.2) lower during widespread circulation in statin users vs. nonstatin users.

Robert L. Atmar

Wendy A. Keitel

In a related commentary, Robert L. Atmar, MD, and Wendy A. Keitel, MD, of Baylor College of Medicine in Houston, 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. – by 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: Black reports serving as a consultant for Novartis Vaccines, which funded the study. Atmar reports receiving grants from Takeda Vaccines. Please see the full studies for a full list of all other authors’ disclosures.