Personalizing ocrelizumab treatment in Multiple Sclerosis: What can we learn from Sars-Cov2 pandemic?

Abstract

During SARS-CoV-2 pandemic, we adopted a personalized delayed protocol for ocrelizumab infusions in Relapsing Remitting Multiple Sclerosis (RRMS) patients according to the national recommendations. Out of the 83 RRMS patients whose infusion was scheduled between March and December 2020, 56 patients experienced a delay in treatment based on MS severity and SARS-CoV2 infection risk profile. In most cases, the immunophenotype was performed monthly to guide re-infusions. Specifically, B CD19 + cells repopulation rate was monitored. Mean infusion delay was 103,1 [SD 40,6] days, and none of the patients presented relapses or active disease at MRI at the end of the observation period. Treatment naïve status and the interval between immunophenotyping and the last ocrelizumab infusion were predictors of earlier B CD19 + cells repopulation. Two patients contracted SARS-CoV2 with complete recovery. Definitive data about Sars-Cov2 vaccine efficacy in patients treated with ocrelizumab are still lacking. Our findings suggest that a personalized treatment with a delayed infusion schedule does not compromise ocrelizumab short-term efficacy and may help to lengthen the therapeutic window for an effective response to SARS-CoV2 vaccine.

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.…”

Multiple Sclerosis Patients and Disease Modifying Therapies: Impact on Immune Responses against COVID-19 and SARS-CoV-2 Vaccination

“…Although CD19+ B-cell subsets, including memory (CD19+CD27+CD38low) B-cells are completely depleted during active treatment with ocrelizumab, amount of CD4+ and CD8+ T-cells is relatively stable. The repopulation time for cladribine and alemtuzumab is shorter, as the recovery of CD19 naive B-cells takes place within a median of 30 weeks and 6 months, respectively [25,27,34,35,[70][71][72][73]. Accordingly, the National Multiple Sclerosis Society advises waiting at least 12 weeks after the last dose of B-cell-depleting therapies before vaccination.…”

“…The results of a study by Disanto and his colleagues show that there is a progressive increase in SARS-CoV-2 IgG levels with an increase in CD19+ B-cell count and time since last anti-CD20 antibody infusion. In treatment-naive patients or patients who were under treatment with first-line immunomodulators, vaccines should be given at least 2 weeks prior to administration of immunosuppressive drugs [25,34,35,70,71,73]. Currently, there are some studies demonstrating the efficacy of vaccine boosters on antibody responses in immuno-compromised patients on anti-CD20 therapies.…”

Stable multiple sclerosis patients on anti-CD20 therapy should go on extended interval dosing: NO

“…The primary aim of EID should be retaining maximal drug efficacy. Although data on EID of anti-CD20 therapies is expanding, 1–5 all (mostly retrospective) cohorts have short durations of follow-up and lack control groups. Furthermore, these studies investigated various strategies of EID, some investigating a set interval extension and others only re-dosing based on percentage or absolute number of CD19+ or CD27+ B-cells.…”