Ocrelizumab Extended Interval Dosing in Multiple Sclerosis in Times of COVID-19

Abstract

ObjectiveTo evaluate the clinical consequences of extended interval dosing (EID) of ocrelizumab in relapsing-remitting multiple sclerosis (RRMS) during the coronavirus disease 2019 (COVID-19) pandemic.MethodsIn our retrospective, multicenter cohort study, we compared patients with RRMS on EID (defined as ≥4-week delay of dose interval) with a control group on standard interval dosing (SID) at the same period (January to December 2020).ResultsThree hundred eighteen patients with RRMS were longitudinally evaluated in 5 German centers. One hundred sixteen patients received ocrelizumab on EID (median delay [interquartile range 8.68 [5.09–13.07] weeks). Three months after the last ocrelizumab infusion, 182 (90.1%) patients following SID and 105 (90.5%) EID patients remained relapse free (p = 0.903). Three-month confirmed progression of disability was observed in 18 SID patients (8.9%) and 11 EID patients (9.5%, p = 0.433). MRI progression was documented in 9 SID patients (4.5%) and 8 EID patients (6.9%) at 3-month follow-up (p = 0.232). Multivariate logistic regression showed no association between treatment regimen and no evidence of disease activity status at follow-up (OR: 1.266 [95% CI: 0.695–2.305]; p = 0.441). Clinical stability was accompanied by persistent peripheral CD19+ B-cell depletion in both groups (SID vs EID: 82.6% vs 83.3%, p = 0.463). Disease activity in our cohort was not associated with CD19+ B-cell repopulation.ConclusionOur data support EID of ocrelizumab as potential risk mitigation strategy in times of the COVID-19 pandemic.Classification of EvidenceThis study provides Class IV evidence that for patients with RRMS, an EID of at least 4 weeks does not diminish effectiveness of ocrelizumab.

Preserved T cell responses to SARS-CoV-2 in anti-CD20 treated multiple sclerosis

“…Furthermore, if clinically justified, one may consider prolonging the infusion interval between anti-CD20 infusions to increase chances of successful SARS-CoV-2 vaccinations. 25 Finally, the reduced SARS-CoV-2 antibody responses in anti-CD20 treated pwMS suggest that an additional booster vaccination should be considered in this patient population.…”

CD19 B cell repopulation after ocrelizumab, alemtuzumab and cladribine: Implications for SARS-CoV-2 vaccinations in multiple sclerosis

“…During the COVID-19 pandemic ocrelizumab infusions were delayed by 1-3 months, with no apparent major rebound in disease activity, suggesting the potential safety of an delayed-dosing scheme ( Maarouf et al, 2020 , Rolfes et al, 2021 , van Lierop et al, 2021 , Baker et al, 2021 ). The importance of mounting a sterilising response relates not only to clinical severity of infection, but also that immunosuppressed individuals may harbour prolonged SARS-CoV-2 infection allowing serial mutations to develop, impacting on infectivity and immune escape ( Khoury et al, 2021 , Corey et al, 2021 ).…”

The wearing-off phenomenon of ocrelizumab in patients with multiple sclerosis

“…4 EID is rapidly evolving for patients using monoclonal antibodies. [8][9][10][11][12] Recently, patients using ocrelizumab received personalized EID at our center to limit This study has several strengths. It is the first study reporting about the wearing-off phenomenon in patients with MS using ocrelizumab.…”

“…Furthermore, as personalized extended interval dosing (EID) of monoclonal antibodies is gaining ground, and an increasing number of trials on EID are conducted, studying the effect of EID on the wearing-off phenomenon is a timely matter. [8][9][10][11][12] Abbreviations: MS = Multiple Sclerosis; BMI = Body Mass Index; COVID= Coronavirus Disease; MSIS = Multiple Sclerosis Impact Scale; MRI = Magnetic Resonance Imaging; EDSS = Expanded Disability Status Scale; sNfL = serum Neurofilament Light; OCR = Ocrelizumab.…”