Reduced antibody formation after influenza vaccination in patients with neuromyelitis optica spectrum disorder treated with rituximab

Eur J Neurol. 2013 Jun;20(6):975-80. doi: 10.1111/ene.12132. Epub 2013 Mar 22.


Background and purpose: Vaccination against infection becomes important in patients with neuromyelitis optica spectrum disorder (NMOSD) because they are at an increased risk of infection due to long-term immunosuppressive therapy. However, it is unclear whether NMOSD patients under immunosuppression therapy show proper antibody formation after vaccination. Thus the antibody formation after influenza A (H1N1) vaccination in patients with NMOSD receiving rituximab was evaluated.

Methods: The study enrolled 26 patients with NMOSD, nine with multiple sclerosis and eight healthy controls. The enrolled patients had been treated with rituximab (n = 16), mycophenolate mofetil (n = 5), azathioprine (n = 6) and interferon-β (IFN-β) (n = 8). Antibodies against the H1N1 influenza virus were measured in the serum drawn just before (T0) and between 3 and 5 weeks after (T1) vaccination. The immunization states for hepatitis B virus surface antigen, measles and tetanus during the treatment period were also tested.

Results: The rituximab group showed significantly lower geometric mean titer, seroprotection rate and mean fold increase than the azathioprine group, IFN-β group and healthy controls, and a lower seroconversion rate than the IFN-β group. This decrease in vaccination efficacy was also shown in patients receiving mycophenolate mofetil. The immunization state for hepatitis B virus surface antigen, measles and tetanus remained the same during the treatment period with each drug, suggesting that these treatments do not affect previously formed immunity.

Conclusion: This study shows a severely hampered humoral immune response to H1N1 influenza vaccine in patients with NMOSD treated with rituximab, although the vaccination itself is safe in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antibody Formation / drug effects
  • Antibody Formation / immunology*
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H1N1 Subtype / metabolism*
  • Influenza Vaccines / blood*
  • Influenza Vaccines / immunology
  • Influenza Vaccines / therapeutic use
  • Male
  • Middle Aged
  • Neuromyelitis Optica / blood*
  • Neuromyelitis Optica / drug therapy
  • Neuromyelitis Optica / immunology
  • Rituximab
  • Treatment Outcome
  • Vaccination* / trends
  • Young Adult


  • Antibodies, Monoclonal, Murine-Derived
  • Influenza Vaccines
  • Rituximab