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

Ann Rheum Dis. 2008 Jul;67(7):937-41. doi: 10.1136/ard.2007.077461. Epub 2007 Nov 2.

Abstract

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 microg 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.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Viral / biosynthesis
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Female
  • Hemagglutination Inhibition Tests / methods
  • Humans
  • Influenza A virus / immunology
  • Influenza B virus / immunology
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Male
  • Middle Aged
  • Rituximab
  • Severity of Illness Index
  • Vaccination

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antibodies, Viral
  • Antirheumatic Agents
  • Influenza Vaccines
  • Rituximab