ABSTRACT
Introduction: In patients with Multiple Sclerosis (pwMS) disease- modifying therapies (DMTs) are known to affect immune response to antigens and possibly to SARS-CoV2 vaccine. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. Objectives and aims: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARSCov- 2 vaccination with mRNA vaccines (BNT162b2, Pfizer/ BioNTech, Inc or mRNA-1273, Moderna Tx, Inc) to evaluate their effect on SARS-CoV-2 antibody response. Methods: A blood collection for the measure of SARS-CoV-2 antibody before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized and blinded serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche Diagnostics). Results: Preliminary data were collected on 780 pwMS (76% BNT162b2 and 24% mRNA-1273) who had pre- and 4-week post-vaccination blood assessments. 87 (11.2%) were untreated, 154 (19.7%) on ocrelizumab, 25 (3.2%) on rituximab, 85 (10.9%) on fingolimod, 25 (3.2%) on cladribine and 404 (51.7%) on other DMTs. 677 patients (86.8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariate analysis, the antibody levels of patients on ocrelizumab (178-fold decrease, p<0.001), fingolimod (26-fold decrease, p<0.001) and rituximab (17-fold decrease, p<0.001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3.5-fold higher antibody level than with the BNT162b2 vaccine (p<0.001). Interpretation: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3.5-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those that will be produced by studying the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. At the time of the ECTRIMS presentation data on the full sample (about 2000 subjects) will be presented.
ABSTRACT
Objective: To evaluate efficacy and Safety of multiple sclerosis (MS) patients (pts) who switched to ocrelizumab (OCR) due to persistence of disease activity after two courses of alemtuzumab (ALM) Background: The management of MS pts who show disease activity after 2 ALM courses represents an unsolved issue Design/Methods: MS patients who switched from ALM to OCR from March 2019 to March 2020 were retro-A nd prospectively recruited from different Italian MS Centers. Clinical, immunological and neuroradiological data about ALM treatment period, ALM-OCR interval and OCR treatment period were collected Results: 23 MS pts [mean age: 35.7(6.8);female, 40.1%;Relapsing Remitting, (RR): 75.8%, active Secondary progressive, (aSP): 24.2%;mean time interval (days) from II ALM course 87.4(108);cumulative number of relapses: 21;mean number of new T2 and Gd+ lesions: 4.1(4.5) and 1.6(3.1);median EDSS:3(range 1-7)]. The mean follow-up (FU) from OCR start: 7.9±7.4 months. 4 (17.4%) pts had a relapse after OCR start (1 during the interval between first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start. 4 (17.4%) pts showed only radiological activity at 3 (n=2), 4 (n=1) and 9 months (n=1). Infusion Associated Reactions occurrence was lower than ALM courses (p<0.05) ;mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1). No pts showed T CD4+ cell count <200 cell/mm3 at 3, 6-months and 1-year FU;B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU with the exception of 1 pt (B CD19+ count 12 cells/mm3 at 6 month FU (n=12 pts)). 10 (43.4%) pts developed hypogammaglobulinemia without infectious events. No ALM-related new complications occurred. Conclusions: Short-term FU suggests that the switch to OCR in MS after 2 ALM courses is characterized by a good safety and efficacy profile.
ABSTRACT
Background: the management of MS patients (pts) who show disease activity after 2 alemtuzumab (ALM) courses represents an unsolved issue. No real-life data about the switch to ocrelizumab (OCR) have been reported yet. Objectives: To describe efficacy and safety outcome of OCR patients switching from ALM due to persistence of disease activity after ALM Methods: MS pts who switched from ALM to OCR from March 2019 to March 2020 were retro- and prospectively recruited from different Italian MS Centers. Clinical, immunological and neuroradiological data about ALM treatment period, ALM-OCR interval and OCR treatment period were collected. Results: we recruited 23 MS pts [mean age: 35.7(SD±6.8);female, 40.1%;Relapsing Remitting, (RR): 75.8%, active Secondary progressive, (aSP): 24.2%;mean time interval (days) from II ALM course: 87.4(SD±108);cumulative number of relapses: 21;mean number of new T2 and Gd+ lesions: 4.1(SD±4.5) and 1.6(SD±3.1);median EDSS:3(range 1-7)]. The mean follow-up (FU) from OCR start was 7.9±7.4 months. Efficacy: 4 (17.4%) pts had a relapse after OCR start (1 pt relapsed between the first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start respectively), with complete recovery after steroid treatment. 4 (17.4%) pts showed radiological activity with no clinical correlates at 3 months (n=2), 4 months (n=1) and 9 months (n=1). EDSS was stable except for 1 aSP patient who showed 1-year disability progression. Safety: I) Infusion Associated Reactions (IARs) occurrence was significantly lower with respect to alemtuzumab courses (p<0.05);(ii) infections: mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1). For 12 pts, data about immunophenotype were available. Of them, no pts showed T CD4+ cell count decrease <200 cell/mm3 at 3, 6-months and 1-year FU;complete B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU. 10 (43.4%) pts developed hypogammaglobulinemia without developing associated infectious events. C) Autoimmunity: no alemtuzumab-related new complications occurred. Conclusions: short-term FU seems to suggest that the switch to OCR in MS patients who showed disease activity after 2 ALM courses is characterized by a good safety and efficacy profile, although clinical and neuroradiological activity can be detected both in an early and in a later phase of treatment. Longer followup is warranted and recruitment is still ongoing.