Vaccination Strategies for Patients With Rheumatoid Arthritis
A session titled “Vaccines: Shingles, Pneumonia & Flu” was presented on November 10, 2019, by Leonard H. Calabrese, DO, of the Cleveland Clinic. This topic was part of a broader discussion on vaccination and infection prophylaxis at the 2019 ACR/ARP Annual Meeting being held in Atlanta, GA, November 8-13. Noting the heightened risk of common, vaccine-preventable infections in rheumatoid arthritis (RA), Dr Calabrese suggested several strategies to help individualize the vaccine schedule for patients with RA.
“This presentation pointed out the study by Park et al that found benefit from withholding MTX for 2 weeks following influenza vaccination. Dr Calabrese has implemented this approach at the Cleveland Clinic, and I plan to do the same at my institution.”
Dr Calabrese commented that there is a fact that is frequently left unsaid, but probably should be stated more often and with greater emphasis: vaccination is the best mode of infection prevention. The 3 most relevant vaccines for all adult patients with RA are those for influenza, pneumococcal disease, and herpes zoster (HZ). As noted in this presentation, influenza is likely the most feared of these infections because of the potential for serious morbidity and mortality. However, pneumococcal disease and HZ are also of concern for patients with RA.
Dr Calabrese began his remarks by mentioning recently published guidance from the European League Against Rheumatism about vaccination. This addresses several important principles in individualizing the approach to vaccination, including preferentially administering vaccines during quiescent disease. There is widespread agreement that patients preferably should be vaccinated several weeks prior to the planned initiation of immunosuppression, especially when using B-cell–depleting agents such as rituximab. Because influenza is seasonal, one cannot necessarily vaccinate prior to starting immunosuppressive therapy. The inactivated influenza vaccine may be administered to patients on immunosuppressive therapy, but this may reduce the immunogenicity of the vaccine. This reduced immunogenicity is the most marked with rituximab, but methotrexate (MTX) also may suppress the immunogenicity of the seasonal influenza vaccine by 10% to 20%. Thus, the temporary discontinuation of MTX has been shown to significantly improve immunogenicity in patients with RA. Park et al have found benefit from withholding MTX for 2 weeks following influenza vaccination. Dr Calabrese has implemented this approach at the Cleveland Clinic, and I plan to do the same at my institution. There is a theoretical concern that the discontinuation of MTX might result in RA flares, but clinical experience, such as in patients who withheld MTX prior to undergoing surgery, has shown the risk of such flares to be quite low.
Regarding pneumococcal vaccination, markedly reduced immunogenicity is also observed in patients treated with rituximab and reduced immunogenicity is seen in those receiving MTX. Since this is not an annually administered vaccine, the concerns regarding the timing of vaccination are different from those for the influenza vaccine. My current approach to pneumococcal vaccination is the same as that of Dr Calabrese: I prime patients with PCV13 and then boost them using PPSV23.
Finally, the individualized approach to HZ vaccination is informed by HZ risk, which increases with age and with treatment with Janus kinase inhibitors such as tofacitinib. The risk of HZ infection is also higher in older patients receiving corticosteroids. Patients should be vaccinated against HZ before initiating treatment with any immunosuppressive agent, but especially with a Janus kinase inhibitor. My current approach to HZ vaccination is also the same as that of Dr Calabrese: I recommend using the recombinant HZ vaccine. Although it avoids the theoretical risk of HZ infection from the live vaccine, the recombinant vaccine is more costly and may not be available in all countries. A presentation at the 2019 ACR/ARP Annual Meeting by Curtis et al of the results from the VERVE trial provides reassurance regarding the safety of the live HZ vaccine. Thus, although the use of live vaccines is generally contraindicated in patients receiving immunosuppressive therapy, the live HZ vaccine may still be used to immunize patients if the recombinant HZ vaccine is unavailable.
Bechman K, Subesinghe S, Norton S, et al. A systematic review and meta-analysis of infection risk with small molecule JAK inhibitors in rheumatoid arthritis. Rheumatology (Oxford). 2019;58(10):1755-1766.
Calabrese LH, Abud-Mendoza C, Lindsey SM, et al. Live zoster vaccine in patients with rheumatoid arthritis treated with tofacitinib with or without methotrexate, or adalimumab with methotrexate. Arthritis Care Res (Hoboken). 2019 Jun 17. doi: 10.1002/acr.24010. [Epub ahead of print]
Calabrese LH. Vaccines: shingles, pneumonia & flu. Session presented at: 2019 American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting; November 10, 2019; Atlanta, GA.
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Winthrop KL, Wouters AG, Choy EH, et al. The safety and immunogenicity of live zoster vaccination in patients with rheumatoid arthritis before starting tofacitinib: a randomized phase II trial. Arthritis Rheumatol. 2017;69(10):1969-1977.
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