High-dose flu vaccine in rheumatoid arthritis beats standard dose

The administration of high-dose vs. standard-dose influenza vaccine provided substantially better immune responses in seropositive rheumatoid arthritis patients in a randomized, active-controlled trial.

High-dose trivalent influenza vaccine is known to improve immune responses in the elderly, but the current findings, are the first to document a successful intervention to enhance vaccine responses in immunocompromised patients.

Researchers assessed antibody responses to either standard-dose (15 mcg of hemagglutinin per strain) quadrivalent inactivated influenza vaccine (SD-QIV) or high-dose (60 mcg of hemagglutinin per strain) trivalent inactivated influenza vaccine (HD-TIV) in 140 and 139 patients, respectively.

Seroprotection rates prior to vaccination were comparable in the two groups, but the high-dose recipients had consistently higher overall responses to vaccination.

Seroconversion rates were 22.3 percent vs. 8.6 percent (odds ratio, 2.93) for the H3N2 strain (A/HongKong/4801/2014), and 44.6 percent vs. 28.6 percent (OR, 1.93) for the B Victoria Lin strain (B/Brisbane/60/2008). For the H1N1 strain A/California/7/2009 in 2016-2017 and closely related A/Michigan/45/2015 in 2017-2018, the seroconversion rates were 51.1 percent vs. 30.0 percent (OR, 2.91) and 46.4 percent vs. 24.6 percent (OR, 2.79), respectively. Seroprotection rates for the H3N2 strain were 48.5 percent vs. 30.9 percent, and for the B Victoria Lin strain, 60.0 percent vs. 50.7 percent. The seroprotection rates for the H1N1 strains together were and 80.4 percent vs. 73.5 percent.

Seroconversion was defined as at least a fourfold serum hemagglutination inhibition (HI) antibody increase from prevaccination level (day 0), and seroprotection was defined as percent with HI titers of 1:40 or greater at postvaccination day 28.

After the researchers controlled for age, vaccine type, treatment type in the 3 months prior to vaccination and during the study period, Charlson comorbidity index, and RA duration, the only significant predictors of vaccine seroresponse were vaccine dose and age.

The findings are notable because RA patients have a nearly threefold increase in the risk of contracting influenza infection or related illness, compared with age-matched healthy controls, because of “inherent immune dysfunction associated with RA, comorbidities, the age of our patients, and immunosuppressive therapy.”

For this reason, RA patients are a priority group for annual vaccination. However, while vaccination remains the most effective method for preventing influenza and its associated complications, vaccine-induced antibody responses and protection in RA are suboptimal, she explained, noting that this puts them at increased risk for severe influenza.

“There is a high priority to develop new approaches to try to decrease this risk.”

It was unknown whether HD-TIV – the only currently available high-dose influenza vaccine – would safely enhance antibody production in RA as it does in the elderly, researchers recruited patients from a tertiary care center during the 2016-2017 and 2017-2018 Northern Hemisphere influenza seasons for this study.

The mean age of the patients was 61 years, and 80 percent were women. All were on stable treatment with either disease-modifying antirheumatic drugs (DMARDs) or biologics for at least 3 months prior to vaccination; treatment types included DMARDs in 138 patients (49.5 percent), anticytokine therapy in 92 patients (33 percent), and anti-B-cell therapy and small molecules in 49 patients (17.6 percent). 

Treatment in all groups was safe, with no differences in adverse events between those receiving high- or standard-dose vaccine, and none of the adverse events were related to treatment.