Giuseppe
Emeritus
Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. (Wiley InterScience, abstract, edited)
Rheumatoid Arthritis Clinical Studies
Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab
Sander van Assen 1 *, Albert Holvast 1, Cornelis A. Benne 2, Marcel D. Posthumus 1, Miek A. van Leeuwen 1, Alexandre E. Voskuyl 3, Marlies Blom 4, Anke P. Risselada 5, Aalzen de Haan 1, Johanna Westra 1, Cees G. M. Kallenberg 1, Marc Bijl 1
1University Medical Center Groningen, Groningen, The Netherlands
2Laboratory for Infectious Diseases, Groningen, The Netherlands
3VU University Medical Center Amsterdam, Amsterdam, The Netherlands
4Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
5University Medical Center Utrecht, Utrecht, The Netherlands
email: Sander van Assen (s.van.assen@int.umcg.nl)
*Correspondence to Sander van Assen, Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
Registered in the Dutch Trial Register: NTR1137.
Funded by: Roche Nederland, Woerden, The Netherlands - Solvay Pharmaceuticals, Weesp, The Netherlands
Abstract
Objective
For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination.
Methods
Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4-8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity.
Results
Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for no strains in the rituximab-treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination.
Conclusion
Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6-10 months after rituximab administration. Previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. RA activity was not influenced.
Received: 24 February 2009; Accepted: 8 September 2009
Digital Object Identifier (DOI)10.1002/art.25033
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<cite cite="http://www3.interscience.wiley.com/journal/123227146/abstract?CRETRY=1&SRETRY=0">Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Sander van Assen. 2009; Arthritis & Rheumatism - Wiley InterScience</cite>Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab
Sander van Assen 1 *, Albert Holvast 1, Cornelis A. Benne 2, Marcel D. Posthumus 1, Miek A. van Leeuwen 1, Alexandre E. Voskuyl 3, Marlies Blom 4, Anke P. Risselada 5, Aalzen de Haan 1, Johanna Westra 1, Cees G. M. Kallenberg 1, Marc Bijl 1
1University Medical Center Groningen, Groningen, The Netherlands
2Laboratory for Infectious Diseases, Groningen, The Netherlands
3VU University Medical Center Amsterdam, Amsterdam, The Netherlands
4Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
5University Medical Center Utrecht, Utrecht, The Netherlands
email: Sander van Assen (s.van.assen@int.umcg.nl)
*Correspondence to Sander van Assen, Department of Internal Medicine, Division of Infectious Diseases, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands
Registered in the Dutch Trial Register: NTR1137.
Funded by: Roche Nederland, Woerden, The Netherlands - Solvay Pharmaceuticals, Weesp, The Netherlands
Abstract
Objective
For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination.
Methods
Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4-8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity.
Results
Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for no strains in the rituximab-treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination.
Conclusion
Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6-10 months after rituximab administration. Previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. RA activity was not influenced.
Received: 24 February 2009; Accepted: 8 September 2009
Digital Object Identifier (DOI)10.1002/art.25033
-