PHILADELPHIA—The treatment of rheumatic diseases is often a double-edged sword: immunosuppressive regimens can be very effective in reducing disease activity, but the cost of such treatments may be seen in the form of increased risk of infection. At ACR Convergence 2022, the session titled ACR Guidelines for Vaccination in Patients with Rheumatic and Musculoskeletal Diseases sought to update clinicians on the best evidence-based recommendations regarding how to protect patients from infection.
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The first speaker in the session was Anne Bass, MD, professor of clinical medicine, Hospital for Special Surgery, Weill Cornell Medicine, New York City, and she began her presentation by discussing the rationale for creating such guidelines. Dr. Bass noted that patients with rheumatic and musculoskeletal diseases (RMDs) may see higher rates of infection in general and more serious infections than the general population, and the immunogenicity and safety of vaccines may differ in RMD patients. In addition, there may be modified vaccine indications for these patients and a need to consider vaccination timing and scheduling of medications around dates of vaccination.
Dr. Bass described a few guiding principles with respect to vaccination for patients with RMDs, namely that indicated vaccinations should be given whenever possible, decisions to hold a medication around vaccination should take into account many factors (e.g., disease type, disease activity, risk for vaccine-preventable infection) and shared decision making with patients is key.
Vaccines & Immunosuppression
The second speaker in the session was Clifton O. “Bing” Bingham, MD, professor of medicine and director of the Arthritis Center at Johns Hopkins University School of Medicine, Baltimore. Dr. Bingham discussed expanded indications for specific vaccines in patients with RMDs on immunosuppression. With respect to influenza vaccination, high-dose vaccination or adjuvanted vaccination is conditionally recommended over regular-dose vaccination for all patients with RMDs age 65 and older and for patients with RMDs between the ages of 18 and 65 who are on an immunosuppressive medication.
Some of the data supporting this recommendation includes the observation that a higher seroconversion rate occurs with high dose vs. standard dose in patients with rheumatoid arthritis without an increased rate of adverse events.1,2 If high-dose or adjuvanted influenza vaccination is not available in a clinician’s office on the day they are seeing a patient, then any vaccine is preferred over no vaccine and vaccination that day is preferred over delaying vaccination.
Pneumococcal vaccination is strongly recommended for all patients younger than age 65 with RMDs who are on immunosuppressive medication. Dr. Bingham explained the sequence of vaccination for patients who have or have not received prior pneumococcal vaccination. For patients who have not previously received any pneumococcal vaccination, the Centers for Disease Control and Prevention (CDC) recommends giving one dose of either PCV15 or PCV20. If PCV20 is given, then PPSV23 is not needed after this dose. If PCV15 is given, then this should be followed by a dose of PPSV23 at least one year later. For patients who have received PPSV23 in the past, the CDC notes that one dose of PCV15 or PCV20 may be given. For patients who have received PCV13 with or without PPSV23, the CDC recommends following previously published guidelines on how to give PPSV23 to these patients.3
Dr. Bingham went on to state that recombinant varicella zoster (VZV) vaccination (Shingrix) is strongly recommended for all patients who have an RMD, are older than 18 and are on immunosuppressive medication. This recommendation is for several reasons. First, patients with RMDs are at higher risk of zoster than the older adults in the general population. Second, the VZV vaccine is safe and effective even in patients who are more profoundly immunosuppressed than patients with RMDs (e.g., due to therapies used to manage renal transplant, stem cell transplant or hematologic malignancies). Third, the Advisory Committee on Immunization Practices recommends recombinant VZV vaccination to individuals between the ages of 18 and 50 who are immunocompromised.
The final vaccination discussed by Dr. Bingham was human papilloma virus vaccination (Gardasil, Cerevix), which is conditionally recommended for patients with RMD aged 26 to 45 who are on immunosuppressive medication and have not previously been vaccinated. This is largely because patients on immunosuppressive therapy are at increased risk of cervical dysplasia and cervical cancer.4
Hold Immunosuppressive Medication?
The third speaker in the session was Kevin Winthrop, MD, MPH, professor of infectious diseases and public health, Oregon Health and Science University, Portland, and his talk focused on whether to hold immunosuppressive medication at the time of non-live attenuated vaccination to maximize immunogenicity. Dr. Winthrop noted that patients on treatment with methotrexate typically have a diminished response to pneumococcal vaccination, influenza vaccination and other vaccinations.
A landmark paper on this topic is from Park et al., who in 2017 studied the effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis. Patients were randomly assigned to one of four groups: 1) continuing methotrexate without interruption during vaccination, 2) suspending methotrexate for four weeks before vaccination, 3) suspending methotrexate for two weeks before and two weeks after vaccination, or 4) suspending methotrexate for four weeks after vaccination. In this trial, the third and fourth groups saw increased rates of immunogenicity as compared to group one, and this finding has laid the groundwork for recommendations since that time.5
Dr. Winthrop noted that further work has shown that holding methotrexate for two weeks as opposed to four weeks after vaccination results in fewer disease flares with no significant difference in immunogenicity. This has played into the rationale for guidelines, such as those around COVID-19 vaccination, which advise holding methotrexate for two weeks after each dose.6
With regard to patients on rituximab, Dr. Winthrop noted that it is advisable to administer vaccinations prior to initiation of rituximab whenever possible. He also stated that clinicians should delay the start of rituximab therapy for at least two weeks after any vaccination to allow time for the patient to develop an immune response. For patients receiving glucocorticoids at a dose of 20 mg of prednisone per day or more, Dr. Winthrop explained how it is advisable to attempt to wean patients below this dose prior to providing vaccination to increase immunogenicity.
At the end of the session, Dr. Bass provided several general comments about medication management at the time of live-attenuated vaccines. First, Dr. Bass noted that for patients with RMDs who are on immunosuppressive medication, deferring live-attenuated vaccines is conditionally recommended. Second, for these same patients, holding immunosuppressive medication for an appropriate period before and four weeks after live-attenuated virus vaccination is conditionally recommended. Dr. Bass went into more detail on these subjects with regard to specific medications and indicated that expanded guidance can be found in the ACR guidance document.
Jason Liebowitz, MD, completed his fellowship in rheumatology at Johns Hopkins University, Baltimore, where he also earned his medical degree. He is currently in practice with Skylands Medical Group, N.J.
- Colmegna I, Useche ML, Rodriguez K, et al. Immunogenicity and safety of high-dose vs. standard-dose inactivated influenza vaccine in rheumatoid arthritis patients: A randomized, double-blind, active-comparator trial. Lancet Rheumatol. 2019 Nov 20;2(1):e14–e23.
- Stapleton JT, Wagner N, Tuetken R, et al. High dose trivalent influenza vaccine compared to standard dose vaccine in patients with rheumatoid arthritis receiving TNF-alpha inhibitor therapy and healthy controls: Results of the DMID 10-0076 randomized clinical trial. Vaccine. 2020 May 13;38(23):3934–3941.
- Centers for Disease Control and Prevention. Pneumococcal Vaccine Timing for Adults. 2022 April 1. https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf
- Feldman CH, Liu J, Feldman S, et al. Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs. Lupus. 2017 June;26(7):682–689.
- Park JK, Min AL, Lee EY, et al. Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: A randomized clinical trial. Ann Rheum Dis. 2017 Sep;76(9):1559–1565.
- Curtis JR, Johnson SR, Anthony DD, et al. American College of Rheumatology guidance for COVID-19 vaccination in patients with rheumatic and musculoskeletal diseases – Version 4. Arthritis Rheumatol. 2022 May 7;74(5):e21–e36.