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Published in: Arthritis Research & Therapy 5/2013

Open Access 01-10-2013 | Research article

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

Authors: Meliha Crnkic Kapetanovic, Tore Saxne, Göran Jönsson, Lennart Truedsson, Pierre Geborek

Published in: Arthritis Research & Therapy | Issue 5/2013

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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

Appendix
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Literature
1.
go back to reference Lexau CA, Lynfield R, Danila R, Pilishvili T, Facklam R, Farley MM, Harrison LH, Schaffner W, Reingold A, Bennett NM, Hadler J, Cieslak PR, Whitney CG: Active Bacterial Core Surveillance Team. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA. 2005, 294: 2043-2051. 10.1001/jama.294.16.2043.CrossRefPubMed Lexau CA, Lynfield R, Danila R, Pilishvili T, Facklam R, Farley MM, Harrison LH, Schaffner W, Reingold A, Bennett NM, Hadler J, Cieslak PR, Whitney CG: Active Bacterial Core Surveillance Team. Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA. 2005, 294: 2043-2051. 10.1001/jama.294.16.2043.CrossRefPubMed
2.
3.
go back to reference van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, Emery P, Geborek P, Ioannidis JP, Jayne DR, Kallenberg CG, Müller-Ladner U, Shoenfeld Y, Stojanovich L, Valesini G, Wulffraat NM, Bijl M: EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2011, 70: 414-422. 10.1136/ard.2010.137216.CrossRefPubMed van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, Emery P, Geborek P, Ioannidis JP, Jayne DR, Kallenberg CG, Müller-Ladner U, Shoenfeld Y, Stojanovich L, Valesini G, Wulffraat NM, Bijl M: EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2011, 70: 414-422. 10.1136/ard.2010.137216.CrossRefPubMed
4.
go back to reference Kapetanovic MC, Roseman C, Jönsson G, Truedsson L, Saxne T, Geborek P: Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors. Arthritis Rheum. 2011, 63: 3723-3732. 10.1002/art.30580.CrossRefPubMed Kapetanovic MC, Roseman C, Jönsson G, Truedsson L, Saxne T, Geborek P: Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors. Arthritis Rheum. 2011, 63: 3723-3732. 10.1002/art.30580.CrossRefPubMed
6.
go back to reference Wernette CM, Frasch CE, Madore D, Carlone G, Goldblatt D, Plikaytis B, Benjamin W, Quataert SA, Hildreth S, Sikkema DJ, Käyhty H, Jonsdottir I, Nahm MH: Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clin Diagn Lab Immunol. 2003, 10: 514-519.PubMedCentralPubMed Wernette CM, Frasch CE, Madore D, Carlone G, Goldblatt D, Plikaytis B, Benjamin W, Quataert SA, Hildreth S, Sikkema DJ, Käyhty H, Jonsdottir I, Nahm MH: Enzyme-linked immunosorbent assay for quantitation of human antibodies to pneumococcal polysaccharides. Clin Diagn Lab Immunol. 2003, 10: 514-519.PubMedCentralPubMed
7.
go back to reference Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed
9.
go back to reference van Assen S, Holvast A, Benne CA, Posthumus MD, van Leeuwen MA, Voskuyl AE, Blom M, Risselada AP, Voskuyl A, de Haan A, Westra J, Kallenberg CG, Bijl M: Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum. 2010, 62: 75-81. 10.1002/art.25033.CrossRefPubMed van Assen S, Holvast A, Benne CA, Posthumus MD, van Leeuwen MA, Voskuyl AE, Blom M, Risselada AP, Voskuyl A, de Haan A, Westra J, Kallenberg CG, Bijl M: Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum. 2010, 62: 75-81. 10.1002/art.25033.CrossRefPubMed
10.
go back to reference Bingham CO, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, Trzaskoma B, Martin F, Agarwal S, Kelman A: Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010, 62: 64-74. 10.1002/art.25034.CrossRefPubMed Bingham CO, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, Trzaskoma B, Martin F, Agarwal S, Kelman A: Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010, 62: 64-74. 10.1002/art.25034.CrossRefPubMed
11.
go back to reference Keystone E, Fleischmann R, Emery P, Furst DE, van Vollenhoven R, Bathon J, Dougados M, Baldassare A, Ferraccioli G, Chubick A, Udell J, Cravets MW, Agarwal S, Cooper S, Magrini F: Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: an open label extension analysis. Arthritis Rheum. 2007, 56: 3896-3908. 10.1002/art.23059.CrossRefPubMed Keystone E, Fleischmann R, Emery P, Furst DE, van Vollenhoven R, Bathon J, Dougados M, Baldassare A, Ferraccioli G, Chubick A, Udell J, Cravets MW, Agarwal S, Cooper S, Magrini F: Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: an open label extension analysis. Arthritis Rheum. 2007, 56: 3896-3908. 10.1002/art.23059.CrossRefPubMed
12.
go back to reference Tay L, Leon F, Vratsanos G, Raymond R, Corbo M: Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects. Arthritis Res Ther. 2007, 9: R38-10.1186/ar2174.PubMedCentralCrossRefPubMed Tay L, Leon F, Vratsanos G, Raymond R, Corbo M: Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects. Arthritis Res Ther. 2007, 9: R38-10.1186/ar2174.PubMedCentralCrossRefPubMed
13.
go back to reference Ribeiro AC, Laurindo IM, Guedes LK, Saad CG, Moraes JC, Silva CA, Bonfa E: Abatacept severely reduces the immune response to pandemic 2009 influenza A/H1N1 vaccination in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013, 65: 476-480. 10.1002/acr.21838.CrossRef Ribeiro AC, Laurindo IM, Guedes LK, Saad CG, Moraes JC, Silva CA, Bonfa E: Abatacept severely reduces the immune response to pandemic 2009 influenza A/H1N1 vaccination in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013, 65: 476-480. 10.1002/acr.21838.CrossRef
14.
go back to reference Kapetanovic MC, Saxne T, Sjöholm A, Truedsson L, Jönsson G, Geborek P: Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology (Oxford). 2006, 45: 106-111. 10.1093/rheumatology/kei193.CrossRef Kapetanovic MC, Saxne T, Sjöholm A, Truedsson L, Jönsson G, Geborek P: Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology (Oxford). 2006, 45: 106-111. 10.1093/rheumatology/kei193.CrossRef
15.
go back to reference Cope AP, Londei M, Chu NR, Cohen SB, Elliott MJ, Brennan FM, Maini RN, Feldmann M: Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis. J Clin Invest. 1994, 94: 749-760. 10.1172/JCI117394.PubMedCentralCrossRefPubMed Cope AP, Londei M, Chu NR, Cohen SB, Elliott MJ, Brennan FM, Maini RN, Feldmann M: Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis. J Clin Invest. 1994, 94: 749-760. 10.1172/JCI117394.PubMedCentralCrossRefPubMed
16.
go back to reference Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T: The essential role of B cell stimulatory factor (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988, 167: 332-344. 10.1084/jem.167.2.332.CrossRefPubMed Muraguchi A, Hirano T, Tang B, Matsuda T, Horii Y, Nakajima K, Kishimoto T: The essential role of B cell stimulatory factor (BSF-2/IL-6) for the terminal differentiation of B cells. J Exp Med. 1988, 167: 332-344. 10.1084/jem.167.2.332.CrossRefPubMed
17.
go back to reference Mori S, Ueki Y, Hirakata N, Oribe M, Hidaka T, Oishi K: Impact of tocilizumab therapy on antibody response to influenza vaccine in patients with rheumatoid arthritis. Ann Rheum Dis. 2012, 71: 2006-2010. 10.1136/annrheumdis-2012-201950.PubMedCentralCrossRefPubMed Mori S, Ueki Y, Hirakata N, Oribe M, Hidaka T, Oishi K: Impact of tocilizumab therapy on antibody response to influenza vaccine in patients with rheumatoid arthritis. Ann Rheum Dis. 2012, 71: 2006-2010. 10.1136/annrheumdis-2012-201950.PubMedCentralCrossRefPubMed
18.
go back to reference Costelloe KE, Smith SH, Callard RE: Interleukin 6 is not required for antigen-specific antibody responses by human B cells. Eur J Immunol. 1993, 23: 984-987. 10.1002/eji.1830230436.CrossRefPubMed Costelloe KE, Smith SH, Callard RE: Interleukin 6 is not required for antigen-specific antibody responses by human B cells. Eur J Immunol. 1993, 23: 984-987. 10.1002/eji.1830230436.CrossRefPubMed
20.
go back to reference Henriques Normark B, Kalin M, Ortqvist A, Akerlund T, Olsson Liljeqvist B, Hedlund J: Dynamics of penicillin-susceptible clones in invasive pneumococcal disease. J Infect Dis. 2001, 184: 861-869. 10.1086/323339.CrossRefPubMed Henriques Normark B, Kalin M, Ortqvist A, Akerlund T, Olsson Liljeqvist B, Hedlund J: Dynamics of penicillin-susceptible clones in invasive pneumococcal disease. J Infect Dis. 2001, 184: 861-869. 10.1086/323339.CrossRefPubMed
Metadata
Title
Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis
Authors
Meliha Crnkic Kapetanovic
Tore Saxne
Göran Jönsson
Lennart Truedsson
Pierre Geborek
Publication date
01-10-2013
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 5/2013
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4358

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