Vaccinations for Rheumatoid Arthritis

  • Lisa M. Perry
  • Kevin L. Winthrop
  • Jeffrey R. CurtisEmail author
Part of the following topical collections:
  1. Topical Collection on Rheumatoid Arthritis


Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious disease-related morbidity and mortality and have twice the risk of acquiring a severe infection compared to the general population. This increased risk is not only a result of the autoimmune disease but is also attributed to the immunosuppressive therapies that are commonly used in this patient population. Given the increase in infection-related risks in RA, there is great interest in mitigating such risk. A number of vaccines are available to the rheumatologist, with a handful that are of importance for RA patients in the United States. The goal of this paper is to highlight the most recent literature on the key vaccines and the specific considerations for the rheumatologist and their RA patients, with a particular focus on influenza, pneumococcal, and herpes zoster vaccines. It is important for rheumatologist to understand and be aware of which vaccines are live and what potential contraindications exist for giving vaccines to RA patients.


Vaccination Rheumatoid arthritis RA Influenza Pneumococcal vaccination Herpes zoster vaccination Biologics DMARDs 


Compliance with Ethics Guidelines

Conflict of Interest

Lisa Perry declares that she has no conflict of interest. Kevin Winthrop declares that he received a grant from Pfizer, consulting for Abbvie, Pfizer, UCB, Genentech. Jeffrey Curtis declares that he received consulting fees and research grants from Amgen, Abbott, BMS, Pfizer, Eli Lilly, Janssen, UCB, Roche/Genentech and CORRONA, and that he receives support from the NIH (AR064172). The authors jointly declare that this work was supported by the Agency for Healthcare Research and Quality (AHRQ) (R01HS018517).

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37(4):481–94.PubMedCrossRefGoogle Scholar
  2. 2.
    Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Predictors of infection in rheumatoid arthritis. Arthritis Rheum. 2002;46(9):2294–300.PubMedCrossRefGoogle Scholar
  3. 3.
    Gluck T, Muller-Ladner U. Vaccination in patients with chronic rheumatic or autoimmune diseases. Clin Infect Dis Off Publ Infect Dis Soc Am. 2008;46(9):1459–65.CrossRefGoogle Scholar
  4. 4.
    Grijalva CG, Chen L, Delzell E, Baddley JW, Beukelman T, Winthrop KL, et al. Initiation of tumor necrosis factor-alpha antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA J Am Med Assoc. 2011;306(21):2331–9.CrossRefGoogle Scholar
  5. 5.
    Crowson CS, Hoganson DD, Fitz-Gibbon PD, Matteson EL. Development and validation of a risk score for serious infection in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64(9):2847–55.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res. 2012;64(5):625–39.CrossRefGoogle Scholar
  7. 7.
    Immunization Schedules: Recommended Vaccinations Indicated for Adults Based on Medical and Other Indications. 2013.Google Scholar
  8. 8.
    Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2013–2014 2013 [01/06/2014]. Available from:
  9. 9.
    Couch RB, Atmar RL, Franco LM, Quarles JM, Wells J, Arden N, et al. Antibody correlates and predictors of immunity to naturally occurring influenza in humans and the importance of antibody to the neuraminidase. J Infect Dis. 2013;207(6):974–81.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.•
    Franca IL, Ribeiro AC, Aikawa NE, Saad CG, Moraes JC, Goldstein-Schainberg C, et al. TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients. Rheumatology. 2012;51(11):2091–8. Shows that methotrexate but not TNF blockage therapy has a deleterious effect on the influenza vaccine in RA patients.PubMedCrossRefGoogle Scholar
  11. 11.
    Kobie JJ, Zheng B, Bryk P, Barnes M, Ritchlin CT, Tabechian DA, et al. Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor. Arthritis Res Ther. 2011;13(6):R209.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.•
    Ribeiro AC, Laurindo IM, Guedes LK, Saad CG, Moraes JC, Silva CA, et al. Abatacept and reduced immune response to pandemic 2009 influenza A/H1N1 vaccination in patients with rheumatoid arthritis. Arthritis Care Res. 2013;65(3):476–80. Describes the effects of abatacept on the influenza vaccine response.CrossRefGoogle Scholar
  13. 13.
    Salemi S, Picchianti-Diamanti A, Germano V, Donatelli I, Di Martino A, Facchini M, et al. Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFalpha blockers: safety and immunogenicity. Clin Immunol. 2010;134(2):113–20.PubMedCrossRefGoogle Scholar
  14. 14.
    Gelinck LB, van der Bijl AE, Beyer WE, Visser LG, Huizinga TW, van Hogezand RA, et al. The effect of anti-tumour necrosis factor alpha treatment on the antibody response to influenza vaccination. Ann Rheum Dis. 2008;67(5):713–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Elkayam O, Bashkin A, Mandelboim M, Litinsky I, Comaheshter D, Levartovsky D, et al. The effect of infliximab and timing of vaccination on the humoral response to influenza vaccination in patients with rheumatoid arthritis and ankylosing spondylitis. Semin Arthritis Rheum. 2010;39(6):442–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Gabay C, Bel M, Combescure C, Ribi C, Meier S, Posfay-Barbe K, et al. Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: a prospective, open-label, parallel-cohort, single-center study. Arthritis Rheum. 2011;63(6):1486–96.PubMedCrossRefGoogle Scholar
  17. 17.
    Kaine JL, Kivitz AJ, Birbara C, Luo AY. Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab. J Rheumatol. 2007;34(2):272–9.PubMedGoogle Scholar
  18. 18.
    Fomin I, Caspi D, Levy V, Varsano N, Shalev Y, Paran D, et al. Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNF alpha blockers. Ann Rheum Dis. 2006;65(2):191–4.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.•
    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(12):2006–10. Evaluates the effects of tocilizumab on the influenza vaccine and pneumococcal vaccine response showing no deleterious effects.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Adler S, Krivine A, Weix J, Rozenberg F, Launay O, Huesler J, et al. Protective effect of A/H1N1 vaccination in immune-mediated disease–a prospectively controlled vaccination study. Rheumatology. 2012;51(4):695–700.PubMedCrossRefGoogle Scholar
  21. 21.
    Arad U, Tzadok S, Amir S, Mandelboim M, Mendelson E, Wigler I, et al. The cellular immune response to influenza vaccination is preserved in rheumatoid arthritis patients treated with rituximab. Vaccine. 2011;29(8):1643–8.PubMedCrossRefGoogle Scholar
  22. 22.•
    Rehnberg M, Brisslert M, Amu S, Zendjanchi K, Hawi G, Bokarewa MI. Vaccination response to protein and carbohydrate antigens in patients with rheumatoid arthritis after rituximab treatment. Arthritis Res Ther. 2010;12(3):R111. Describes the response to the influenza and pnemococcal vaccines as greater in patients on rituximab if given before rather than after treatment.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    van Assen S, Holvast A, Benne CA, Posthumus MD, van Leeuwen MA, Voskuyl AE, et al. Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum. 2010;62(1):75–81.PubMedCrossRefGoogle Scholar
  24. 24.
    Oren S, Mandelboim M, Braun-Moscovici Y, Paran D, Ablin J, Litinsky I, et al. Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response. Ann Rheum Dis. 2008;67(7):937–41.PubMedCrossRefGoogle Scholar
  25. 25.
    Kapetanovic MC, Roseman C, Jonsson 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(12):3723–32.PubMedCrossRefGoogle Scholar
  26. 26.
    Kapetanovic MC, Roseman C, Jonsson G, Truedsson L. Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs. Clin Rheumatol. 2011;30(12):1555–61.PubMedCrossRefGoogle Scholar
  27. 27.
    Kapetanovic MC, Saxne T, Sjoholm A, Truedsson L, Jonsson G, Geborek P. Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology. 2006;45(1):106–11.PubMedCrossRefGoogle Scholar
  28. 28.
    Visvanathan S, Keenan GF, Baker DG, Levinson AI, Wagner CL. Response to pneumococcal vaccine in patients with early rheumatoid arthritis receiving infliximab plus methotrexate or methotrexate alone. J Rheumatol. 2007;34(5):952–7.PubMedGoogle Scholar
  29. 29.
    Elkayam O, Caspi D, Reitblatt T, Charboneau D, Rubins JB. The effect of tumor necrosis factor blockade on the response to pneumococcal vaccination in patients with rheumatoid arthritis and ankylosing spondylitis. Semin Arthritis Rheum. 2004;33(4):283–8.PubMedCrossRefGoogle Scholar
  30. 30.•
    Bingham CO, 3rd, Rizzo W, Kivitz A, Hassanali A, Upmanyu R, Klearman M. Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA). Ann Rheum Dis. 2014 Jan 21. Newest study evaluating the response to vaccines in RA patients treated with tocilizumab. Google Scholar
  31. 31.
    Bingham 3rd CO, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010;62(1):64–74.PubMedCrossRefGoogle Scholar
  32. 32.•
    Clutterbuck EA, Lazarus R, Yu LM, Bowman J, Bateman EA, Diggle L, et al. Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells. J Infect Dis. 2012;205(9):1408–16. Explains diminished immune responses with additional vaccinations given to patients.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.•
    Jackson LA, Gurtman A, van Cleeff M, Frenck RW, Treanor J, Jansen KU, et al. Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older. Vaccine. 2013;31(35):3594–602. Describes that the response to the PPSV-23 vaccine might be more robust if the vaccine is given after an initial vaccination with PCV-13.PubMedCrossRefGoogle Scholar
  34. 34.
    Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine for Adults with Immunocompromising Conditions: Recommendations of the Advisory Committee on Immunization Practices (ACIP). 2012 Contract No.: 40.Google Scholar
  35. 35.
    Morrison VA, Oxman MN, Levin MJ, Schmader KE, Guatelli JC, Betts RF, et al. Safety of zoster vaccine in elderly adults following documented herpes zoster. J Infect Dis. 2013;208(4):559–63.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Prevention of Herpes Zoster Recommendations of the Advisory Committee on Immunization Practices (ACIP). 2008 Contract No.: RR-5.Google Scholar
  37. 37.
    Zhang J, Delzell E, Xie F, Baddley JW, Spettell C, McMahan RM, et al. The use, safety, and effectiveness of herpes zoster vaccination in individuals with inflammatory and autoimmune diseases: a longitudinal observational study. Arthritis Res Ther. 2011;13(5):R174.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.•
    Zhang J, Xie F, Delzell E, Chen L, Winthrop KL, Lewis JD, et al. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA J Am Med Assoc. 2012;308(1):43–9. Describes that when the live zoster vaccine is given in the setting of current biologic use may not be associated with a short-term increase in the risk for varicella or herpes zoster.CrossRefGoogle Scholar
  39. 39.
    Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352(22):2271–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Yun H, Yang S, Chen L, Winthrop K, Xie F, Baddley JW, et al. Herpes Zoster Infection Across Auto-Immune and Inflammatory Dieseases: Implications for vaccination. 2014 To be presented at EULAR 2014:To be presented at EULAR 2014.Google Scholar
  41. 41.•
    Winthrop KL, Furst DE. Rheumatoid arthritis and herpes zoster: risk and prevention in those treated with anti-tumour necrosis factor therapy. Ann Rheum Dis. 2010;69(10):1735–7. Shows that there may not be an increase in the incidence of herpes zoster cases after initiation of an anti-TNF or non-biologic DMARD therapy.PubMedCrossRefGoogle Scholar
  42. 42.
    Schmader KE, Oxman MN, Levin MJ, Johnson G, Zhang JH, Betts R, et al. Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012;55(10):1320–8.CrossRefGoogle Scholar
  43. 43.
    Curtis JR, Arora T, Narongroeknawin P, Taylor A, Bingham 3rd CO, Cush J, et al. The delivery of evidence-based preventive care for older Americans with arthritis. Arthritis Res Ther. 2010;12(4):R144.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Desai SP, Lu B, Szent-Gyorgyi LE, Bogdanova AA, Turchin A, Weinblatt M, et al. Increasing pneumococcal vaccination for immunosuppressed patients: a cluster quality improvement trial. Arthritis Rheum. 2013;65(1):39–47.PubMedCrossRefGoogle Scholar
  45. 45.
    McCarthy EM, Azeez MA, Fitzpatrick FM, Donnelly S. Knowledge, attitudes, and clinical practice of rheumatologists in vaccination of the at-risk rheumatology patient population. J Clin Rheumatol Pract Rep Rheum Musculoskelet Dis. 2012;18(5):237–41.Google Scholar
  46. 46.
    Ledwich LJ, Harrington TM, Ayoub WT, Sartorius JA, Newman ED. Improved influenza and pneumococcal vaccination in rheumatology patients taking immunosuppressants using an electronic health record best practice alert. Arthritis Rheum. 2009;61(11):1505–10.PubMedCrossRefGoogle Scholar
  47. 47.
    Rothholz MC. The role of community pharmacies/pharmacists in vaccine delivery in the United States. Available from:

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Lisa M. Perry
    • 1
  • Kevin L. Winthrop
    • 2
  • Jeffrey R. Curtis
    • 3
    Email author
  1. 1.Division of Arthritis & Rheumatic DiseasesOregon Health and Science UniversityPortlandUSA
  2. 2.Division of Infectious DiseaseOregon Health and Science UniversityPortlandUSA
  3. 3.Division of Clinical Immunology and RheumatologyUniversity of Alabama at BirminghamBirminghamUSA

Personalised recommendations