By Marilynn Larkin
NEW YORK (Reuters Health) - In patients with rheumatoid arthritis (RA), a high-dose trivalent inactivated influenza vaccine (HD-TIV) is safe and potentially more immunogenic than a standard-dose quadrivalent vaccine (SD-QIV), a randomized controlled, active-comparator trial suggests.
"By the nature of their underlying disease and frequent use of immunomodulatory therapies, RA patients are at increased risk of influenza and its complications," Dr. Ines Colmegna of McGill University in Montreal told Reuters Health by email. While this justifies current recommendations for influenza vaccination, in such patients "the generation of vaccine-induced antibodies - considered a surrogate for influenza protection - is suboptimal."
"The results of this trial show that participants who received the HD-TIV were two to three times more likely to generate antibodies against each of the three influenza strains contained in the vaccine compared to those who received the standard-dose vaccine," she said. "The immunogenicity advantage of the high-dose vaccine was demonstrated in patients on either conventional synthetic DMARDs alone or in combination with anti-TNF or anti-IL-6 drugs."
"Moreover, the benefit of the high-dose vaccine . . . was also present in those younger than 65 years old," she noted. "Importantly, the standard-dose and the high-dose influenza vaccines had similar frequency and profile of side effects, and neither vaccine increased (RA) activity."
The study compared the immunogenicity and safety of SD-QIV (15 mcgs of hemagglutinin per strain) versus HD-TIV (60 mcgs per strain) in adults with RA at three hospitals affiliated with McGill University.
Participants were stratified into one of three groups according to RA treatment. Group 1 took conventional or targeted synthetic DMARDs (methotrexate, hydroxychloroquine, and sulfasalazine) as monotherapy or in combination; group 2 took a biological DMARD (anti-tumor necrosis factor or anti-interleukin 6), with or without methotrexate, hydroxychloroquine, or sulfasalazine, or a combination thereof; and group 3 took abatacept, tofacitinib, or rituximab, with or without methotrexate, hydroxychloroquine, or sulfasalazine, or a combination.
As reported online November 20 in The Lancet Rheumatology, 279 participants (mean age, about 60; about 80% women and 79% white) were randomly assigned to SD-QIV or HD-TIV.
Overall, patients who received HD-TIV were more likely to seroconvert than those who received SD-QIV: the odds ratio was 2.99 for seroconversion to strain A/H3N2; 1.95 to strain B/Bris; 3.21 to strain A/H1N1 in 2016-2017; and 2.44 to strain A/H1N1 in 2017-2018.
Similar results were observed when comparing groups 1 and 2. The number of individuals in group 3 was insufficient to draw conclusions.
Local and systemic adverse events were similar in both vaccine groups. No serious adverse events were reported through day 28 in any treatment group, and as Dr. Colmegna noted, neither vaccine increased RA disease activity.
The authors state, "Our data suggest that in patients with seropositive rheumatoid arthritis, HD-TIV is safe and more immunogenic than SD-QIV."
Rheumatologist Dr. Francis Luk, an assistant professor at Wake Forest Baptist Health in Winston-Salem North Carolina, called the study "compelling." However, he said in an email, "I do not think it will be practice changing yet, due to the need for further studies to reproduce the results. However, it could change (guidelines) in the future."
Side effects were no greater with the high-dose vaccine, he noted. "However, side effects of muscle aches, headaches, fevers can still occur with either vaccine. So (treatment) must be tailored to the individual patient."
"In general," he said, "the benefit of increased protection from influenza infection will be worth the risk of side effects."
"I think it is a great idea to consider using the high-dose vaccine among patients who are on immunosuppressive medications, even if they are less than age 65," he added. "Currently, the high-dose influenza vaccine is approved for all adults 65 and older."
Lancet Rheumatol 2019.