Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis.

OBJECTIVES: In patients with rheumatoid arthritis (RA) treated with (ultra-)low dose rituximab (RTX), we investigated (1) the association of dosing and timing of rituximab (RTX) on seroconversion after third COVID-19 vaccination, and (2) persistence of humoral response after two-dose vaccination. METHODS: In this monocentre observational study, patients from the COVAC-cohort were included in the third vaccine analysis if humoral response was obtained 2-6 weeks after third vaccination in previous non-responders, and in the persistence analysis if a follow-up humoral response was obtained before third vaccination in previous responders. Dichotomization between 'positive' and 'negative' response was based on the assay cut-off. The association between latest RTX dose before first vaccination, timing between latest rituximab and vaccination, and response was analysed with univariable logistic regression. RESULTS: Of the 196 patients in the cohort, 98 were included in the third vaccine analysis and 23 in the persistence analysis. Third vaccination response was 19/98 (19%) and higher for 200 mg RTX users (5/13, 38%) than 500 and 1000 mg (7/37, 19% and 7/48, 15%). Non-significant trends were seen for higher response with lower dosing (200 versus 1000 mg: OR 3.66, 95% CI 0.93-14.0) and later timing (per month since infusion: OR 1.16, 0.97-1.35). Humoral response persisted in 96% (22/23) and in 89% (8/9) of patients who received RTX between the two measurements. CONCLUSION: Repeated vaccination as late as possible after the lowest RTX dose possible seems the best vaccination strategy. A once positive humoral response after COVID-19 vaccination persists irrespective of intercurrent rituximab infusion. TRIAL REGISTRATION: Netherlands Trial Register, https://www.trialregister.nl/, NL9342.

Humoral response to coronavirus disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis.

OBJECTIVES: Humoral response to vaccines in RA patients treated with rituximab (RTX) in standard dosages (≥1000 mg) is decreased. Ultra-low dosages (500 or 200 mg) may have better response. Also, timing after latest RTX infusion may be an important variable. We aimed to investigate the influence of RTX dosage and timing on response to COVID-19 vaccination in RA patients. METHODS: A single-centre observational study (n = 196) investigated the humoral response, measured by total Ig anti-COVID-19 assay (positive response ≥1.1), 2-6 weeks after complete COVID-19 vaccination. A multivariable logistic regression model was built to study the effect of RTX dosage and time between latest rituximab and vaccination on response, adjusting for age and methotrexate use. RESULTS: After two-dose vaccination, the response rate was significantly better for patients receiving 200 mg (n = 31, 45%) rituximab compared with 1000 mg (n = 98, 26%; odds ratio 3.07, 95% CI 1.14-8.27) and for each additional month between latest rituximab and vaccination (OR 1.67, 1.39-2.01). CONCLUSION: Both increased time between latest rituximab infusion and complete vaccination, and 200 mg as latest dose were associated with a better response to COVID-19 vaccination and should be considered when trying to increase vaccine response after rituximab in RA patients. TRIAL REGISTRATION: Netherlands Trial Register, https://www.trialregister.nl/, NL9342.

Identification of Risk Factors for COVID-19 Hospitalization in Patients With Anti-Rheumatic Drugs: Results From a Multicenter Nested Case Control Study.

Patients with inflammatory rheumatic diseases (IRDs) do not have an increased risk for coronavirus disease 2019 (COVID-19) compared with the general population. However, it remains uncertain whether subgroups of patients with IRD using different immunosuppressive antirheumatic drugs carry a higher risk for severe COVID-19 compared with other patients with IRD. The aim of this study is to identify risk factors for severe COVID-19, requiring hospitalization in patients with IRD. This is a multicenter nested case control study conducted in the Netherlands. Cases are hospital known patients with IRD requiring hospitalization for COVID-19 between March 1, 2020, and May 31, 2020. Controls are hospital known patients with IRD not requiring hospitalization for COVID-19 in this period, included at a 4:1 ratio. Patient, disease, and treatment characteristics were extracted from electronic medical records and a questionnaire. Potential risk factors were analyzed using unconditional logistic regression, corrected for confounders and multiple testing. Eighty-one cases and 396 controls were included. General risk factors of older age and obesity apply to patients with IRD as well (odds ratio (OR) for age ≥ 75 3.5, 95% confidence interval (CI) 1.9-6.3, OR for body mass index ≥ 40 4.5, 95% CI 1.5-14). No significantly increased ORs for COVID-19 hospitalization were found for any antirheumatic agent or IRD. A protective effect was found for use of methotrexate (OR 0.53, 95% CI 0.31-0.92). In conclusion, similar to the general population, elderly and obese patients with IRD have a higher risk for hospitalization for COVID-19. We did not identify a specific antirheumatic agent or IRD to increase the risk of COVID-19 hospitalization in patients with IRD, except for a possible protective effect of methotrexate.