Ann Rheum Dis 67:937-941 doi:10.1136/ard.2007.077461
  • Extended reports

Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response

Open Access
  1. O Elkayam1,4
  1. 1 Department of Rheumatology, Tel Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  2. 2 Central Virology Laboratory, Ministry of Health, Chaim Sheba Medical Centre, Tel Hashomer, Israel; Tel Aviv Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  3. 3 B Shine Department of Rheumatology, Rambam Health Care Centre, The Ruth and Bruce Rapaport School of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
  4. 4 Department of Internal Medicine “F”, Tel Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  5. 5 Statistic Unit, Tel Aviv Sourasky Medical Centre, Tel Aviv, Israel
  1. Dr O Elkayam, Department of Rheumatology, Tel Aviv Sourasky Medical Centre, 6 Weizmann Street, Tel Aviv 64239, Israel; oribe14{at}
  • Accepted 13 October 2007
  • Published Online First 2 November 2007


Objective: To assess the effect of rituximab on the efficacy and safety of influenza virus vaccine in patients with rheumatoid arthritis (RA).

Methods: The study group comprised patients with RA treated with conventional disease-modifying drugs with or without rituximab. Split-virion inactivated vaccine containing 15 μg haemagglutinin/dose of B/Shanghai/361/02 (SHAN), A/New Caledonian/20/99 (NC) (H1N1) and A/California/7/04 (CAL) (H3N2) was used. Disease activity was assessed by the number of tender and swollen joints, duration of morning stiffness and evaluation of pain on the day of vaccination and 4 weeks later. CD19-positive cell levels were assessed in rituximab-treated patients. Haemagglutination inhibition (HI) antibodies were tested and response was defined as a greater than fourfold rise 4 weeks after vaccination or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated in all subjects.

Results: The participants were divided into three groups: RA (n = 29, aged 64 (12) years), rituximab-treated RA (n = 14, aged 53 (15) years) and healthy controls (n = 21, aged 58 (15) years). All baseline protective levels of HI antibodies and GMT were similar. Four weeks after vaccination, there was a significant increase in GMT for NC and CAL antigens in all subjects, but not for the SHAN antigen in the rituximab group. In rituximab-treated patients, the percentage of responders was low for all three antigens tested, achieving statistical significance for the CAL antigen. Measures of disease activity remained unchanged.

Conclusion: Influenza virus vaccine generated a humoral response in all study patients with RA and controls. Although the response was significantly lower among rituximab-treated patients, treatment with rituximab does not preclude administration of vaccination against influenza.


  • Competing interests: None declared.

  • Ethics approval: Approved by the ethics committees of Tel Aviv Sourasky Medical Centre and the Rambam Health Care Centre.

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