Article Text

Download PDFPDF

Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response
  1. S Oren1,
  2. M Mandelboim2,
  3. Y Braun-Moscovici3,
  4. D Paran1,
  5. J Ablin1,4,
  6. I Litinsky1,
  7. D Comaneshter5,
  8. D Levartovsky1,
  9. E Mendelson2,
  10. R Azar2,
  11. I Wigler1,
  12. A Balbir-Gurman3,
  13. D Caspi1,
  14. 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}


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.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

View Full Text

Statistics from


  • Competing interests: None declared.

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

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.