Did the introduction of the Sars-Cov-2 vaccine influence the choices of therapy in patients with a new diagnosis of multiple sclerosis?

Introduction: Since the beginning of the Sars-Cov-2 pandemic, several evidences have been gathered on the use of Disease Modifying Drugs (DMTs) in patients with Multiple Sclerosis (MS) .The introduction of the Sars-Cov-2 vaccine marked a turning point for MS patients, considered fragile patients. Aim(s):The objective of this study is to describe changes about the use of first-line DMTs in patients with a new diagnosis of MS, comparing the semester before and after the start of vaccination campaign for Sars-Cov-2. Method(s): The study included patients newly diagnosed with MS according to McDonald's 2017 criteria. The proportion of patients initiated into the use of Interferon Beta (IFN), Dimethylfumarate (DMF) and Teriflunamide (TERI) was defined as a proportion for the previous semester (October 2020- March 2021) and subsequent (April 2021-September 2021) to the avaibility of Sars- Cov-2 vaccine. The determinants of the choice of first-line DMTs were evaluated through regression analysis. Result(s): The study included 134 patients, including 40 (29.9%) male, average age of 38.3 +/- 12.3 years, disease duration of 3.0 +/- 4.6 years, average EDSS of 1.7 +/- 1.1. Among these, 75 (56%) patients started a first-line DMTs in the semester before the start of vaccination campaign [IFN 13 (9.7%), TERI 6 (4.5%), GA 28 (20.9%), DMF 28 (20.9%)], while 59 (44%) in the following semester [IFN 4 (3%), TERI 11(8.2%), GA 12 (8.9%) and DMF 32 (23.9%)]. A reduction of 40% and 53% respectively in the use of GA and IFN was observed in the semester following the start of the vaccination campaign. In contrast, an increase of 29 % in the use of TERI and 6% in the use of DMF respectively was reported in the same semester. The regression analysis shows the use of injection therapies (IFN, GA) being associated with female gender (p= 0.032) and with the previous semester to the availability of Sars- Cov-2 vaccine (p=0.006). In contrast, the use of TERI is associated with male gender (p=0.031) and with the following semester the introduction of the vaccine (p=0.05). About the use of DMF, a relationship with the post-introduction semester of the vaccine has been observed (p=0.037) the relapse rate in the previous 2 years is the strongest determinant in the choice of this treatment (p=0.001). Conclusion(s): Our data show how the start of the vaccination campaign for Sars-Cov-2 influenced the use of first-line immunotheraphies in patients with new diagnosis of MS.

Evolution of teriflunomide use in multiple sclerosis: A real-world experience.

OBJECTIVES: The present study aims to describe the evolution of teriflunomide use for multiple sclerosis (MS) in the clinical setting, in particular for naïve patients and young women. Predictors of treatment response were also investigated. METHODS: This was an independent, retrospective, real-world monocentric study. We analysed the use of teriflunomide from 2016 to 2020 in patients categorized as naïve or switchers, and assessed the variations in its use in men and women by age group. Clinical and MRI data of treated patients were evaluated, and NEDA-3 status at 24 and 36 months was defined. Determinants of therapeutic response were examined using regression analysis. RESULTS: The study included 319 MS patients exposed to teriflunomide [209 women (65.5%)]. Of these, 67 (21%) were naïve and 252 (79%) were switchers. A 20% increase of teriflunomide use in the naïve group in the past two years, particularly in 2020, the first year of global Sars-Cov-2 spread, was observed. An increase of teriflunomide use of more than 10% in young women under age 45 was also reported. NEDA-3 status was calculated for 204 patients after 24 months and was achieved in 120 (58.8%) of these ones. NEDA-3 was also achieved in 92/160 (56.8%) patients at 36 months. A lower ARR in the two years prior to teriflunomide treatment (p = 0.026), lower baseline age (p = 0.05), and lower EDSS score (p = 0.009) were associated with achievement of the NEDA-3. CONCLUSIONS: Our study confirms a major evolution in teriflunomide use in clinical settings, particularly for naïve patients and young women.

Effect of SARS-CoV-2 mRNA vaccination in multiple sclerosis patients treated with disease modifying therapies

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.

Short-term evaluation of alemtuzumab to ocrelizumab switch in MS patients with disease activity after alemtuzumab: An Italian multicentric study

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.

Short-term evaluation of alemtuzumab to ocrelizumab switch in MS patients with disease activity after alemtuzumab: An italian multicentric study

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.