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In patients with rheumatoid arthritis receiving rituximab, a positive humoral response following COVID-19 vaccination persists regardless of continued rituximab infusion, according to data published in Rheumatology.
The researchers added that repeated vaccine doses administered “as late as possible” after the lowest possible rituximab (Rituxan, Genentech) dose appears to be the optimal COVID-19 vaccination strategy for this population.
“Rheumatoid arthritis (RA) patients treated with rituximab (RTX) have both an increased risk of COVID-19 hospitalization and a reduced humoral response after two-dose vaccination, when compared to other disease modifying antirheumatic drugs (DMARDs),” Celeste J.T. van der Togt, MD, of the Radboud University Medical Center, in Nijmegen, the Netherlands, and co-authors wrote. “Therefore, to optimize management of COVID-19 risk in these patients, it is important to identify strategies for increasing response in this population.”
To investigate the interactions between rituximab and the effectiveness of a third COVID-19 vaccine dose in patients with RA, van der Togt and colleagues conducted a monocenter, observational study following up on the RTC-COVAC study. The present study featured two analyses. First, patients from the COVAC cohort who failed to respond to the first two vaccine doses but then demonstrated a humoral response 2 to 6 weeks after a third dose were included in the “third vaccine” analysis. Meanwhile, those who achieved a follow-up humoral response prior to the third dose were included in the “persistence” analysis. The study was conducted from June 2021 through January 2022.
All included patients had received two doses of either the Pfizer-BioNTech, the AstraZeneca or the Moderna vaccine. For the third dose, patients received either the Pfizer-BioNTech or Moderna formulations. The researchers examined demographic and disease information, as well as treatment details, including the use of conventional synthetic disease-modifying antirheumatic drugs, prednisolone biologic DMARDs, cumulative rituximab dose and the date and dose of the last rituximab dose.
Main outcomes included the proportion of patients achieving seroconversion following a third vaccination dose, as well as the proportion of patients who achieve a persistent humoral response following a second vaccine dose.
The current study included a total of 196 patients, of whom 98 were part of the “third vaccine” analysis, and 23 were part of “persistence” analysis.
According to the researchers, 19% of patients in the “third vaccine” analysis achieved a vaccination response. In addition, the percent of patients achieving a vaccine response was higher among those receiving rituximab 200 mg, compared with 500 mg or 1,000 mg — 38% vs. 19% and 15%, respectively. Meanwhile, in the “persistence” analysis, humoral response persisted in 96% and 89% of patients who received rituximab between the two measurements, the researchers wrote.
“Our main results illustrate that humoral response after third vaccination occurs in a relevant proportion of patients who did not respond to earlier vaccination,” van der Togt and colleagues wrote. “Also, with a similar OR as in our first study — although not significantly so due to a smaller study population — humoral response was associated with 200mg RTX and a longer time between RTX infusion and vaccination. Additionally, we have shown that the persistence of humoral response is very high even in the context of intercurrent RTX infusions.
“Based on the results of our study, repeated vaccination as late as possible after the lowest RTX dose possible seems the best vaccination strategy,” they added. “Once seroconversion is achieved, humoral response persists despite RTX continuation.”
References:
Avouac J, et al. Lancet Rheumatol. 2021;doi: 10.1016/S2665-9913(21)00059-X.
Furer V, et al. Ann Rheum Dis. 2021;doi: 10.1136/annrheumdis-2021-220647.