Vaccine Efficacy in Rheumatoid Arthritis

April 9, 2018

How to ensure your patients with RA receive the vaccines they need when immunosuppressive therapy complicates the picture.

References1. Singh JA, Furst DE, Bharat A, 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;64:625-639.2. van Assen S, Agmon-Levin N, Elkayam O, et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2011;70:414-422.3. Friedman MA, Winthrop K. Vaccines and disease-modifying antirheumatic drugs: practical implications for the rheumatologist. Rheum Dis Clin North Am. 2017;43:1-13.4. Perry LM, Winthrop KL, Curtis JR. Vaccinations for rheumatoid arthritis. Curr Rheumatol Rep. 2014;16:431.5. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep. 2018;67:103-108.6. Hales CM, Harpaz R, Ortega-Sanchez I, et al. Centers for Disease Control and Prevention (CDC). Update on recommendations for use of herpes zoster vaccine. MMWR Morb Mortal Wkly Rep. 2014;63:729-731.

Rheumatoid arthritis (RA) is associated with higher rates of infectious disease–related morbidity and mortality. The risk of a severe infection is double that of the general population, because of both patients’ autoimmune status and the medications used to treat RA. For these reasons, vaccines are especially important in this population.

The advent of biologic disease-modifying antirheumatic drugs (DMARDs) for the treatment of RA-which amplify immunosuppressive effects of traditional DMARDs-suggests potentially greater impact on the safety and efficacy profiles of vaccines.
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The most recent and widely used guidelines for vaccines in patients with RA are:

• 2012 American College of Rheumatology (ACR)¹
• 2011 European League Against Rheumatism (EULAR)²

Studies of vaccines in the RA population are limited, and many evidence gaps exist, particularly regarding interactions between immunosuppressive RA therapies and vaccine immunogenicity.

Vaccines recommended for all patients with RA are influenza, pneumococcal pneumonia, and herpes zoster. Human papillomavirus (HPV), hepatitis B virus (HBV), and yellow fever vaccines are recommended for patients at high risk for these infections.^3,4

The influenza vaccine changes annually according to predictions of the most likely circulating variations of influenza virus. In addition to a trivalent vaccine, a quadrivalent formulation was added in 2013. Patients with RA have a 1.5 to 2 times greater risk of hospitalization and a higher risk of death due to influenza. Thus, annual vaccination is recommended for all patients with RA.⁴
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Live vaccine is contraindicated in patients with RA. Only attenuated, intramuscular vaccinations should be given. In cases of severe egg allergy, a recombinant form can be substituted. Patients over age 65 should receive high-dose trivalent vaccine for higher efficacy, although this has not been demonstrated specifically in RA. DMARDs, particularly rituximab, may interfere with efficacy; schedule the vaccine before initiation or wait as long as possible after most recent treatment.^3,4

The pneumococcal pneumonia vaccine is available in both conjugated and polysaccharide formulations. Studies have not yet shown a clear advantage to either, although conjugate vaccines are known to confer greater immunogenicity.³

The 13-valent conjugated vaccine (PVC13) is a once-in-a-lifetime vaccine; doses of PVC13 must be spread 5 years apart. For these reasons, schedules vary by individual.^3,4

The two available formulations of herpes zoster vaccine are the live, attenuated vaccine and the recombinant zoster vaccine (RZV), which was approved by the FDA in October 2017. The CDC recommends that adults with chronic medical conditions such as RA should receive RZV.⁵

The ACR guidelines recommend that patients with RA and other immune disorders be vaccinated at age 50.¹ Biologic therapies interfere with the efficacy of the vaccine and should be discontinued before the vaccine is given.^3,4

Human papillomavirus (HPV) infection is the most common STD; it affects mostly sexually active teenagers and young adults. HPV can cause genital warts or lead to genital cancers.
(©Katyrena Kan/Shutterstock.com)

Hepatitis B virus (HBV) infection is often acute but can become chronic and cause serious liver damage or cancer. HBV can be reactivated by biologic therapies for RA.
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Yellow fever presents risks for patients with RA who live in or are traveling to an endemic area (eg, tropical countries with high mosquito populations).
(©mycteria/Shutterstock.com)

TNF, tumor necrosis factor.
^a Anti-TNF drugs may inhibit response to the HBV vaccine.
^b Prednisone showed acceptable response to the yellow fever vaccine.

Because of their immunosuppressive action, many therapies for RA may interfere with vaccine efficacy.^3,4

Live vaccines for herpes zoster and yellow fever are contraindicated in patients who take biologic therapies.

Despite recommendations by multiple agencies, vaccination rates among patients with RA remain very low: 45.8% (influenza), 28.5% (pneumococcal pneumonia), and 4% (herpes zoster).³

A number of evidence gaps for the three major vaccine responses in RA populations still remain to be explored in order to improve vaccination rates⁴:
• Controlled trials in RA have not been done for any vaccine
• Safety of the herpes zoster vaccine needs to be confirmed
• Optimal vaccination schedules and revaccination intervals are not clear