A high dose flu vaccine is better than standard dose ones for protecting people with rheumatoid arthritis against influenza, a Canadian randomised controlled trial has suggested.

The use of a high dose trivalent flu vaccine containing four times the standard dose of antigen (60 μg vs 15 μg) produced superior immunogenicity to standard seasonal influenza vaccine without any increase in adverse events nor worsening in RA disease activity, according to findings published in Lancet Rheumatology.

In a prospective trial, 279 patients with RA (positive for rheumatoid factor and/or anti-cyclic citrullinated peptide) were followed up after being randomly assigned to vaccination with standard quadrivalent Fluzone or high dose Fluzone trivalent vaccine during the 2016–17 and 2017–18 influenza seasons in Montreal.

Patients who received high dose vaccine were about two to three times more likely to seroconvert than those who received standard vaccine (odds ratios 2.44-3.21 for different influenza serotypes).

Seroconversion and seroprotection rates as measured by haemagglutination-inhibition and microneutralisation assays were higher after administration of high dose than standard dose vaccines and  the increased antibody titres persisted for at least 186 days after vaccination.

Local and systemic adverse events were similar in both vaccine groups, no serious adverse events were reported up to a month after immunisation in any group, and neither vaccine increased RA disease activity as measured by Routine Assessment of Patient Index Data (RAPID3).

In post hoc analyses, the benefit of the high dose vaccine over standard vaccine was seen regardless of whether patients were taking conventional or biological DMARDs.

The study authors said the results backed the use of high dose vaccine – which was originally designed for older people – in all rheumatoid arthritis patients.

An accompanying commentary said the findings showed that “more is better” for the high-dose flu vaccine in patients with RA.

This was an important message since people with RA were more likely to have influenza, have more severe influenza symptoms and more likely to have influenza-related complications, including pneumonia, stroke, and myocardial infarctions, they said.

“This vulnerable group represents a sizable population at risk for serious infections because of the disease itself and the therapies used to treat it.”

They also noted the possibility that vaccines could worsen underlying autoimmune conditions because of immune stimulation had been a persistent worry for physicians and patients.

“It is thus reassuring that [the study] noted no increase in disease activity with the HD-TIV vaccination,” they wrote.