Rituximab, Abatacept May Interfere With Influenza Vaccine

Janis C. Kelly

January 14, 2014

Most arthritis treatments have no effect on the immunogenicity of adjuvanted pandemic H1N1 influenza (pH1N1) vaccine in patients with rheumatoid arthritis (RA) or spondyloarthropathy (SpA), but rituximab severely reduced antibody responses, according to an article published online January 2 in Arthritis Research & Therapy.

Meliha C. Kapetanovic, MD, PhD, an associate professor in the Department of Rheumatology, Skåne University Hospital, Lund, Sweden, and colleagues write that protective antibody titers persisted for up to 22 months after vaccination in those who were not treated with rituximab.

"Rituximab treatment severely reduced antibody response to pH1N1 influenza vaccine. The other treatment groups showed acceptable responses," the authors write.

The researchers studied antibody response a mean of 8.3 months after pH1N1 vaccination in 291 patients with arthritis. A positive immune response was a postvaccination H1 titer of 40 or higher or an increase of 4-fold or more in H1 titer in a patient with negative prevaccination serum.

The authors found protective antibody titers in 42% of patients with RA treated with methotrexate (MTX), 53% of patients with RA who are receiving anti-tumor necrosis factor (TNF) monotherapy, and 43% of patients with RA treated with anti-TNF plus MTX. In patients with RA who are receiving other biologics, protective antibody titers developed in 50% of patients receiving tocilizumab, but in only 10% of patients receiving rituximab and 20% of patients receiving abatacept.

"Compared to a single dose, immunization with two doses of the vaccine overall resulted in more patients with a positive immune response in all treatment groups except for RA patients on MTX and RA [patients] on rituximab," the authors write.

Among the patients with SpA, protective antibody responses developed in 76% of those treated with anti-TNF monotherapy, in 47% treated with anti-TNF plus MTX, and in 59% treated with nonsteroidal anti-inflammatory drugs/analgesics.

The authors report that the patients with RA had significantly lower response rates when receiving rituximab (P < .001) compared with other RA treatment groups and that patients with SpA who were receiving anti-TNF monotherapy had significantly better responses than other treatment groups.

The authors note that their findings differ from those reported by Franco et al ( Rheumatology (Oxford). 2012;51:2091-2098) but suggest this might reflect the fact that patients in that study were immunized with a single dose of nonadjuvanted pH1N1 vaccine, whereas those in the current study received both an adjuvanted vaccine and a booster dose of vaccine.

Most patients (except those receiving rituximab) vaccinated with adjuvanted pH1N1 would reach antibody levels that should protect against infection, Dr. Kapetanovic told Medscape Medical News.

"If it is practically possible, patients planning to start rituximab should get immunized against influenza before treatment initiation. In patients who have been taking rituximab, the probability of initiating a protective immune response is best if H1N1 vaccination is performed a few weeks before the next rituximab course," Dr. Kapetanovic explained.

Dr. Kapetanovic added, "The antibody response is a surrogate measure of vaccine efficacy. Although good immune response is correlated with a protection against infection, in order to know whether the vaccine is efficacious in these immunosuppressed patients, I would like to perform a study investigating whether the occurrence of influenza is lower in vaccinated patients compared to unvaccinated matched controls."

The study was supported by grants from the Swedish Rheumatism Association, the Swedish Research Council, The Medical Faculty of the University of Lund, Alfred Österlund’s Foundation, the Crafoord Foundation, Greta and Johan Kock’s Foundation, the King Gustaf V Foundation, and Lund University Hospital. The authors have disclosed no relevant financial relationships.

Arthritis Res Therapy. Published online January 2, 2014. Full text


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