Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis

Arthritis Res Ther. 2013 Oct 30;15(5):R171. doi: 10.1186/ar4358.

Abstract

Introduction: The objective of the study was to investigate the impact of newer biologic treatments including rituximab, abatacept and tocilizumab on antibody response following pneumococcal vaccination using a 7-valent conjugate vaccine in patients with established rheumatoid arthritis (RA).

Methods: Patients with RA receiving rituximab, abatacept or tocilizumab as monotherapy or combined with methotrexate (MTX) participated in the study. Specific IgG antibodies against 23F and 6B serotypes were measured at vaccination and 4 to 6 weeks after vaccination using standardised ELISA. Geometric mean antibody levels (GML) were calculated. Antibody response (AR) was defined as the ratio between post- and pre-vaccination antibody levels and a positive antibody response (posAR) was AR ≥ 2.

Results: In total, 88 patients were enrolled in the study. Of 55 patients treated with rituximab, 26 (46%) were on concomitant MTX. Of patients receiving abatacept (n = 17) and tocilizumab (n = 16) biologic treatment was given in combination with MTX in 13 (76%) and 9 (56%) patients, respectively. Patients treated with rituximab had significantly lower AR compared to those on tocilizumab, as well as compared to previously reported RA patients on MTX and controls (spondylarthropathy patients treated with NSAIDs and/or analgesics). In total, 10.3% of patients on rituximab monotherapy and no patient on rituximab + MTX had posAR for both serotypes. For abatacept and tocilizumab the corresponding figures were 17.6% and 50%.

Conclusion: In this cohort of patients with established RA, treatment with rituximab and abatacept was associated with diminished antibody response but this was most pronounced for rituximab. Pneumococcal conjugate vaccine administrated during ongoing tocilizumab treatment seems to be associated with sufficient antibody response. Pneumococcal vaccination should preferably be encouraged before initiation of rituximab or abatacept treatment.

Trial registration: NCT00828997 and EudraCT EU 2007-006539-29.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bacterial / immunology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antibody Formation / drug effects*
  • Antibody Formation / immunology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Drug Therapy, Combination
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Immunoconjugates / therapeutic use*
  • Immunoglobulin G / immunology
  • Logistic Models
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Pneumococcal Vaccines / immunology
  • Pneumococcal Vaccines / therapeutic use*
  • Rituximab
  • Serotyping
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Immunoconjugates
  • Immunoglobulin G
  • Pneumococcal Vaccines
  • Rituximab
  • Abatacept
  • tocilizumab
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT00828997