Research into the effect of the COVID-19 vaccines on patients with rheumatoid arthritis, treated with rituximab

Many vaccines are being deployed to prevent corona virus disease 2019 (COVID-19) infections. Although these vaccines appear to be safe and effective in the general population, less is known about the effectiveness of these vaccines in patients with rheumatoid arthritis (RA), treated with rituximab (RTX). Previous studies into influenza and pneumococcal vaccines showed a decreased vaccination response to these vaccinations in RA patients treated with RTX, compared to other antirheumatic drugs. However, all these studies have been performed with registered high dose RTX (2x 1000 mg), whereas optimal efficacy in RA can be reached with low-dose (1x 1000 mg) RTX or even ultra-low dose (1x 500 mg or 1x 200 mg) RTX. Therefore, we want to investigate the response to the COVID-19 vaccine in patients with RA treated with different doses of RTX in our clinic (200, 500 and 1000 mg) and the relation to the time between previous RTX administration and vaccination.
We will perform a prospective (usual care) cohort study in which we will determine total immunoglobulin (IgT) titre against COVID-19 at two points in time: the first 2-6 weeks after the last vaccine dose and the second 3-6 months after (combined with the next RTX administration, if possible). In addition to these antibody titre measurements, we will collect vaccination details (type of vaccine, date(s), batch number), information about a prior COVID-19 infection (if applicable) and general information about the RA and the treatment with RTX.

Amendment:
In the autumn of 2021, the Dutch government made a third vaccination available for patients treated with rituximab, because of the decreased humoral response after two vaccines. Therefore, we made an amendment to the existing study, with the aim to investigate humoral response in patients treated with (ultra-)low dose RTX 2-6 weeks after the third vaccine, and the relation between timing and dosing.

We hypothesize that the % responders 2-6 weeks after the last vaccine dose in patients with ultra-low dose RTX (1x 500 mg or 1x 200 mg every 6 months) is significantly higher compared to patients treated with low-dose or registered dose RTX. We also hypothesize that the % responders 2-6 weeks after the last vaccine dose in patients that received the vaccine in the two months prior to the next RTX administration, is significantly higher compared to patients who received the vaccine early (first 4 months) after RTX administration.

Amendment:
We hypothesize that the % responders 2-6 weeks after the third vaccine dose in patients with 200 mg RTX is significantly higher compared to patients treated with 500 or 1000 mg RTX as last dose before first vaccination. We also hypothesize that time since latest RTX is a significantly associated variable with humoral response in univariable logistic regression.

First blood sample: 2-4 weeks after last vaccine dose;
Second blood sample: 3-6 months after last vaccine dose.
After the second blood sample, the study ends.

Amendment:
Third blood sample: 2-6 weeks after third vaccine dose.
After the third blood sample, the study ends.