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


Correspondence: H. J. Kim, Department of Neurology, Research Institute and Hospital of National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Korea (tel.: +82-31-920-2438; fax: +82-31-905-5524; e-mail:


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.


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.


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.


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.