Delayed methotrexate start improves pneumococcal vaccine response in rheumatoid arthritis
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WASHINGTON — Delaying methotrexate initiation for 1 month after pneumococcal vaccination improves humoral response in patients with rheumatoid arthritis, according to data presented at ACR Convergence 2024.
“As you know, vaccination against pneumococcus is recommended in patients with RA being treated with methotrexate,” Jacques Morel, MD, of the University Hospital of Montpellier, in France, told attendees. “The objective of our study was to compare the humoral response rate of different techniques regarding the PCV13 vaccine, administered either one month before methotrexate initiation or simultaneous with methotrexate.”
To address this question of vaccine management in RA, Morel and colleagues recruited an initial cohort of 276 patients with RA who all were vaccinated with PCV13 at randomization, and then 2 months later with the 23-valent pneumococcal polysaccharide vaccine (PPV23).
At 1 month after PCV13 vaccination, the researchers randomly assigned participants to either initiate methotrexate immediately or delay initiation for 1 month. Patients were assessed for at least a two-fold IgG antibody response, as determined by enzyme-linked immunosorbent assay (ELISA) and opsonic pneumococcal antibody (OPA). The researchers additionally evaluated PCV13 response for at least three positive antibody responses of the five target serotypes.
Women comprised 70% of the cohort, which had a mean age of 55.6 years and an RA duration of 2 months. Anti-citrullinated protein antibodies (ACPA) were present in 69% of the cohort.
Primary endpoint results, as assessed by ELISA, demonstrated that 88% of patients in the delay group responded to the vaccine, compared with 75% in the immediate initiation group (P < .01), according to the researchers.
“In responders for the five target serotypes, we also see that the rate is much greater in the delay treatment group,” Morel said.
Patients in the delay group also mounted higher rates of OPA response — 96% vs. 88% (P = .02), the researchers added.
“PCV13 administered one month prior to starting methotrexate allows a significantly higher immunological response at 1 month in comparison to patients vaccinated simultaneously with methotrexate initiation,” Morel said. “This is the first study to show it is better to vaccinate RA patients with PCV13 1 month before methotrexate initiation with no impact on RA disease activity.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Immunosuppression resulting from the disease process or immunosuppressive therapies is a common challenge in patients with autoimmune rheumatic diseases. Specific medications significantly influence immune responses, particularly vaccination efficacy.
Glucocorticoids have a dose-dependent negative impact on humoral immune responses, especially at daily doses exceeding 7.5 to 10 mg. According to the American College of Rheumatology guidelines, lowering glucocorticoid doses below 20 mg per day is recommended for most vaccinations. However, this does not apply to the influenza vaccine. Reducing the steroid dose annually to administer the influenza vaccine can complicate disease management. Thus, the ACR conditionally recommends “high-dose or adjuvanted influenza vaccination” for patients receiving immunosuppression.
Methotrexate is also linked to reduced humoral immune responses, especially at doses above 0.4 mg per kg per week. The 2022 ACR guidelines recommend withholding methotrexate for at least 2 weeks after receiving the influenza vaccine if disease activity allows.
For other non-live attenuated vaccines, methotrexate should be continued. In the case of live attenuated vaccines, the ACR advises stopping methotrexate for 4 weeks before, and up to 4 weeks after, vaccination.
The present abstract suggests that delaying methotrexate for 4 weeks may also improve the immunogenicity of the pneumonia vaccine.
Sulfasalazine and hydroxychloroquine do not adversely affect vaccine responses. Notably, in patients with systemic lupus erythematosus on steroids or immunosuppressants, the addition of hydroxychloroquine resulted in seroconversion rates following influenza A/H1N1 vaccination comparable to those in patients not on immunosuppressive therapy.
Azathioprine at doses greater than 3 mg per kg per day, mycophenolate mofetil and cyclophosphamide significantly reduce vaccine immunogenicity. Limited data exist on the impact of leflunomide on vaccine responses. The ACR guidelines recommend continuing azathioprine, mycophenolate mofetil, cyclophosphamide and leflunomide during administration of all non-live attenuated vaccines.
For live attenuated vaccines, azathioprine, mycophenolate mofetil and oral cyclophosphamide should be stopped for 4 weeks before, and up to 4 weeks after, vaccination. For intravenous cyclophosphamide, it is recommended to pause treatment one dosing interval before vaccination and resume 4 weeks after.
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Morel J. Abstract #2676. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
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