Longitudinal humoral response after SARS-CoV-2 vaccination in ocrelizumab treated MS patients: To wait and repopulate?

Zoé L E Van Kempen ,Alyssa A Toorop ,Maurice Steenhuis ,Anja Ten Brinke ,Taco W Kuijpers ,Pieter-Jan Van Dam ,Eva Strijbis ,Gertjan Wolbink ,Carolien Van De Sandt ,Filip Eftimov ,S Marieke Van Ham ,Niels J M Verstegen ,Luuk Wieske ,Theo Rispens ,Mark Löwenberg ,Laura Kummer ,Laura Boekel ,Eileen W Stalman ,Adriaan Volkers ,Sander W Tas ,Joep Killestein

doi:10.1016/j.msard.2021.103416

Abstract

ObjectiveThe objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count. MethodsOCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70. Results87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL). ConclusionsLow B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.

Highlights

In patients with multiple sclerosis (MS), ocrelizumab (OCR) is a risk factor for a severe course of COVID-19 (Simpson-Yap et al, 2021)
Sixty-two patients were treated with ocrelizumab and 25 pa tients were not treated with disease modifying therapies (DMTs)
We found a clear difference in the humoral response after SARS-CoV-2 vaccination between OCR treated MS patients and MS patients without DMTs, which is in agreement with other reports (Achiron et al, 2021; Bigaut et al, 2021; Louapre et al, 2021)

Summary

Introduction

In patients with multiple sclerosis (MS), ocrelizumab (OCR) is a risk factor for a severe course of COVID-19 (Simpson-Yap et al, 2021). OCR negatively influences the humoral response after vaccination, as previously shown for pneumococcal and tetanus vaccination (Bar-Or et al, 2020). It has been suggested that the humoral response after SARS-CoV-2 vaccination can improve by adjusting timing of vaccination to OCR infusion or repopulation of B-cells (Otero-Romero et al, 2021). In the updated advice (October 13th 2021) of the MS International Federation, it is advised to schedule SARS-CoV-2 vaccination minimally 12 weeks after the last OCR infusion to optimize vaccination response. Data supporting this advice are currently lacking

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