Extending rituximab dosing intervals in patients with MS during the COVID-19 pandemic and beyond?

Abstract

ObjectiveTo evaluate disease activity in patients with relapsing-remitting MS (RRMS) receiving rituximab with an extended dosing interval.MethodsIn the context of COVID-19 pandemic, this was an interim analysis of an ongoing prospective observational study of patients who were stable on rituximab for at least 6 months and who had a planned extended dosing interval of 24 months. Only data for patients with active RRMS before rituximab were analyzed.ResultsAmong 177 patients receiving rituximab, 33 had RRMS and MRI activity before rituximab and at least 8 months of follow-up after the last infusion. The mean (SD) age was 40 (14) years, 25 were females, the mean disease duration was 10 (6.8) years, the mean annual relapse rate (ARR) before rituximab was 1.7 (1.3), and the median Expanded Disability Status Scale (EDSS) score before rituximab was 4.5 (1–7). Before extended dosing, when rituximab was infused every 6 months, the mean (SD) ARR decreased to 0.04 (0.1) (p < 0.0001) and the EDSS score to 4 (0–7) (p = 0.04). At the time of this analysis, the median follow-up since the last infusion was 11 (8–31) months. No patient showed relapse or disability progression. In total, 30 patients had at least 1 MRI performed since the last infusion (median time between the last MRI and the last infusion 10 [8–31] months). No MRI showed activity. The CD19+ cell proportion was >1% for 10 of 25 patients at the last count (median time 8 [6–25] months).ConclusionsAn extended dosing interval for rituximab for patients with stable MS during the COVID-19 pandemic may be associated with a low risk of disease activity.

Rituximab-Induced Hypogammaglobulinemia and Infections in AQP4 and MOG Antibody–Associated Diseases

“…In AQP4-positive NMOSD, intensive maintenance regimen with anti-CD20 agents seems necessary because relapses can occur when memory B cells are slightly repopulated, 8 , 19 – 21 but in MS, extending dosing of RTX is associated with a low risk of relapse or MRI activity, as suggested by recent studies. 22 , 23 Future prospective studies performed in large sample are required to confirm that extending dosing of anti-CD20 agents could improve safety in MS without significant loss of efficacy.…”

COVID-19 Vaccination in Patients With Multiple Sclerosis on Disease-Modifying Therapy

“…As there is data that the therapeutic effects of rituximab can extend for months beyond the timing of humoral immune reconstitution, it may be possible to extend the dosing interval to create a window to administer the COVD-19 vaccine and allow for immunological response. 24 To maximize the immunological response, it is suggested by the Canadian Network of MS Clinics (https://cnmsc.ca/Covid19VaccineGuidance) to wait 4 weeks after the 2 nd mRNA vaccine dose for new or repeat infusion of anti-CD20 DMT. For patients already on anti-CD20 DMT, waiting 12 weeks (as in the VELOCE study) after infusion to start the vaccination process is recommended.…”

Rituximab and risk of COVID-19 infection and its severity in patients with MS and NMOSD

“…Regarding the general approach of using DMTs during the pandemic, recommendations are categorized into initiation, continuing, delaying, and stopping DMTs. The International Federation (MSIF) along with MS Society have recommended not to initiate Rituximab [35][36][37] In this respect, Dr. Brownlee [38] has endorsed delaying the initiation of Rituximab or considering an alternative for patients along with extended interval dosing guided by intermittent assay for CD19 lymphocyte counts for patients already on treatment. In our study, since none of the confirmed COVID-19 patients who were seriously ill had experienced delayed scheduled infusion dates, we cautiously recommend extended interval dosing if there is an immediate need for doing so.…”