Moderator of 2 Sessions
Presenter of 3 Presentations
IS016 - MULTIPLE SCLEROSIS, COVID-19 AND VACCINES (ID 815)
Abstract
Abstract Body
Disease-modifying therapies (DMTs) for multiple sclerosis (MS) either modulate or suppress the immune system. In patients with MS (PwMS), infection with SARS-CoV-2 and the effects of Covid-19 vaccination are concerns complicated by an increased risk of severe disease in some, and by the effects of DMTs on immune responses to both the virus and the vaccine. We evaluated the effects of DMTs on humoral and cell-mediated immune responses to 2 and 3 mRNA vaccinations and the longevity of SARS-Cov-2 spike IgG levels in 522 PwMS and 68 healthy controls.
Patients treated with most DMTs were seropositive post 2nd and 3rd vaccinations, however only 38% and 44% of ocrelizumab-treated patients and 54% and 46% of fingolimod-treated patients, respectively, were seropositive. IgG levels decreased by 82% within 6 months from 2nd vaccination (p<0.0001), but were boosted 10.3 fold by the 3rd vaccination (p<0.0001), and 1.8 fold compared to ≤3m post 2nd vaccination (p=0.025). Vaccination ≥5 months after ocrelizumab infusion was associated with higher IgG levels (p=0.039 and 0.036 post-2nd and 3rd vaccination), and higher rates of seropositivity. T-cell responses were detected in 89% and 63% of PwMS post 2nd and 3rd vaccination, but in only 25% and 0% of fingolimod-treated patients, while in 100% and 86% of ocrelizumab-treated patients, respectively. We conclude that PwMS treated with most DMTs develop humoral and T-cell responses following 2 and 3 mRNA SARS-CoV-2 vaccinations, however, fingolimod or ocrelizumab blunt humoral responses, while fingolimod compromises also the cellular responses, with no improvement after a 3rd booster.
IS027 - EARLY HIGH-EFFICACY TREATMENT FOR MULTIPLE SCLEROSIS (ID 865)
Abstract
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Multiple sclerosis (MS) can be a devastating disease causing significant physical, cognitive and mental disabilities. With currently available disease modifying therapies (DMTs) for MS, in particular the higher efficacy ones (namely natalizumab, alemtizimab, cladribine, ocrelizumab and ofatumumab), the bar for modern treatment goals has been raised from reducing relapse frequency, delaying disability progression and preventing new or enhancing MRI lesions to freedom from clinical and MRI disease activity (NEDA), stabilizing function and/or improving pre-existing disability, reducing brain atrophy and allowing for healthy aging. The best treatment strategy for MS is still debated. However, multiple lines of evidence support the approach of using high efficacy therapies (HET) early in the course of the disease in order to achieve these goals. Early aggressive therapy has been shown to slow disability accumulation and improve the course of MS; Comparative studies demonstrate the superiority of early treatment with HET over platform therapies or later treatment; Real world cohort studies confirm the superiority of HET in delaying disability progression and secondary progressive MS; and patients also prefer more efficacious therapies and tend to underestimate therapy risks and overestimate benefits. Accumulating clinical experience, appropriate individualized treatment selection, risk mitigation strategies and risk-management programs make risk profile of most HET predictable and manageable and help reduce risks and increase benefits of early HET for MS. Two ongoing large pragmatic randomized clinical trials, TREAT-MS and DELIVER-MS will help to evaluate the place of early aggressive therapy in the treatment algorithm of MS
IS041 - TARGETING B CELLS IN MULTIPLE SCLEROSIS (ID 909)
Abstract
Abstract Body
Increasing evidence suggests that B cells contribute to both regulation of normal autoimmunity and the pathogenesis of immune mediated diseases including multiple sclerosis (MS). B cells in MS are skewed towards a pro-inflammatory profile and contribute to its pathogenesis by antibody production, antigen presentation, stimulation and activation of T cells, production of pro-inflammatory cytokines, formation of ectopic germinal centers under the meninges that drive cortical pathology and contribute to neurological disability, and probably by carrying the Epstein-Barr virus (EBV).
The recent interest in the key role of B cells in MS has primarily been evoked by the profound anti-inflammatory effects of rituximab observed in patients with relapsing MS. This has been reaffirmed by clinical trials with less immunogenic and more potent humanized and fully human B cell-depleting mAbs targeting CD20, namely ocrelizumab and ofatumumab, and the novel glycoengineered mAb ublituximab. Ocrelizumab is the first disease-modifying drug that has shown efficacy also in primary-progressive MS, and is currently approved for both indications. Another promising approach is the inhibition of Bruton's tyrosine kinase (BTK), a key cytoplasmic enzyme that mediates B and myeloid cell activation and survival, by agents such as evobrutinib, tolebrutinib, phenebrutinib and orelabrutinib. On the other hand, targeting B cell cytokines with the fusion protein atacicept paradoxically increased MS disease activity, probably by augmenting memory B cells. Finally, essentially all other approved therapies for MS, some of which have been designed to target T cells, have some effects on B cells that may contribute to their therapeutic activity.