Lowered antibody response to vaccination for some methotrexate users
In the newer study, led by Rebecca H. Haberman, MD, of New York University Langone Health, researchers examined COVID-19 vaccine response in cohorts in New York City and Erlangen, Germany.
The New York cohort included 25 patients with IMID who were taking methotrexate by itself or with other immunomodulatory medications (mean age, 63.2 years), 26 with IMID who were on anticytokine therapy and/or other oral immunomodulators (mean age, 49.1 years) and 26 healthy controls (mean age, 49.2 years). Most patients with IMID had psoriasis/psoriatic arthritis or RA.
The German validation cohort included 182 healthy subjects (mean age, 45.0 years), 11 subjects with IMID who received TNF inhibitor monotherapy (mean age, 40.8 years), and 20 subjects with IMID on methotrexate monotherapy (mean age, 54.5 years).
In the New York cohort, 96.1% of healthy controls showed “adequate humoral immune response,” along with 92.3% of patients with IMID who weren’t taking methotrexate. However, those on methotrexate had a lower rate of adequate response (72.0%), and the gap persisted even after researchers removed those who showed signs of previous COVID-19 infection (P = .045).
In the German cohort, 98.3% of healthy cohorts and 90.9% of patients with IMID who didn’t receive methotrexate reached an “adequate” humoral response versus just half (50.0%) of those who were taking methotrexate.
When both cohorts are combined, over 90% of the healthy subjects and the patients with IMID on biologic treatments (mainly TNF blockers, n = 37) showed “robust” antibody response. However, only 62% of patients with IMID who took methotrexate (n = 45) reached an “adequate” level of response. The methotrexate gap remained after researchers accounted for differences in age among the cohorts.
What’s going on? “We think that the underlying chronic immune stimulation in autoimmune patients may cause T-cell exhaustion and thus blunts the immune response,” said Dr. Schett, who’s also a coauthor of this study. “In addition, specific drugs such as methotrexate could additionally impair the immune response.”
Still, the findings “reiterate that vaccinations are safe and effective, which is what the recommendations state,” he said, adding that more testing of vaccination immune response is wise.
Insights into vaccine response while on rituximab
Two more reports, also published in Annals of the Rheumatic Diseases, offer insight into vaccine response in patients with IMID who take rituximab.
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In one report, published May 11, U.S. researchers retrospectively tracked 89 rheumatic disease patients (76% female; mean age, 61) at a single clinic who’d received at least one dose of a COVID-19 vaccine. Of those, 21 patients showed no sign of vaccine antibody response, and 20 of them were in the group taking rituximab. (The other patient was taking belimumab.) Another 10 patients taking rituximab did show a response.
“Longer duration from most recent rituximab exposure was associated with a greater likelihood of response,” the report’s authors wrote. “The results suggest that time from last rituximab exposure is an important consideration in maximizing the likelihood of a serological response, but this likely is related to the substantial variation in the period of B-cell depletion following rituximab.”
Finally, an Austrian report published May 6 examined COVID-19 vaccine immune response in five patients who were taking rituximab (four with other drugs such as methotrexate and prednisone). Researchers compared them with eight healthy controls, half who’d been vaccinated.
The researchers found evidence that rituximab “may not have to preclude SARS-CoV-2 vaccination, since a cellular immune response will be mounted even in the absence of circulating B cells. Alternatively, in patients with stable disease, delaying [rituximab] treatment until after the second vaccination may be warranted and, therefore, vaccines with a short interval between first and second vaccination or those showing full protection after a single vaccination may be preferable. Importantly, in the presence of circulating B cells also a humoral immune response may be expected despite prior [rituximab] therapy.”
Dr. Bass said the findings reflect growing awareness that “patients with autoimmune disease, especially when they’re on immunosuppressant medications, don’t quite have as optimal responses to the vaccinations.” However, she said, the vaccines are so potent that they’re likely to still have significant efficacy in these patients even if there’s a reduction in response.
What’s next? Dr. Schett said “testing immune response to vaccination is important for patients with autoimmune disease. Some of them may need a third vaccination.”
The American College of Rheumatology’s COVID-19 vaccination guidelines do not recommend third vaccinations or postvaccination immune testing at this time. However, Dr. Bass, one of the coauthors of the recommendations, said it’s likely that postvaccination immune testing and booster shots will become routine.
Dr. Bass reported no relevant disclosures. Dr. Schett reported receiving consulting fees from AbbVie. The May 6 German vaccine study was funded by Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, the ERC Synergy grant 4D Nanoscope, the IMI funded project RTCure, the Emerging Fields Initiative MIRACLE of the Friedrich-Alexander-Universität Erlangen-Nürnberg, the Schreiber Stiftung, and the Else Kröner-Memorial Scholarship. The study authors reported no disclosures. The May 25 study of German and American cohorts was funded by the National Institute of Arthritis and Musculoskletal and Skin Diseases, National Institute of Allergy and Infectious Diseases, Rheumatology Research Foundation, Bloomberg Philanthropies COVID-19 Initiative, Pfizer COVID-19 Competitive Grant Program, Beatrice Snyder Foundation, Riley Family Foundation, National Psoriasis Foundation, and Deutsche Forschungsgemeinschaft. The authors reported a range of financial relationships with pharmaceutical companies. No specific funding was reported for the other two studies mentioned.