Relapsing-remitting and primary progressive multiple sclerosis treated with ocrelizumab: A comparative study.

OBJECTIVES: To compare the clinical and radiological effectiveness of ocrelizumab in primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) in a clinical practice setting and describe its tolerability and adverse events. METHODS: A retrospective observational cohort study was conducted comparing clinical and magnetic resonance imaging (MRI) data of all patients with (pw)PPMS and RRMS who had received treatment with ocrelizumab at least one cycle and have been followed up for one year at minimum. RESULTS: 42 patients (27 women) treated with ocrelizumab: 29 had RRMS and 13 PPMS. The follow-up period was 26.4 ± 8.4 months. The proportion of pwRRMS with no evidence of disease activity (NEDA) in the first year was 69.2% and in the second was 80%. In the first year, radiological activity was reduced by 80.0% in pwRRMS and 91.7% in pwPPMS. In the second year, radiological activity was completely reduced in both groups. A statistically significant difference (p<0.05) was observed between the pre-ocrelizumab rate of disability progression vs. the first year rate of progression for pwRRMS and pwPPMS. However, an increase in the disability progression rate in the second year of treatment was found in pwPPMS. Ocrelizumab was mostly well tolerated and some adverse effects were reported: infusion-related reactions (IRRs) were the most frequent adverse event, followed by infections and hematological side effects. Discontinuations were due to infections, hematological complications, and perception of ineffectiveness. CONCLUSIONS: Ocrelizumab was very effective in reducing relapses and MRI activity. The rate of progression was slowed down; however, the effect was more evident for pwRRMS than for pwPPMS over time.

Expert opinion on COVID-19 vaccines and cladribine tablets in MS: A plain language summary.

WHAT IS THIS SUMMARY ABOUT?: People with multiple sclerosis (shortened to MS) who are taking cladribine tablets may have concerns about whether they can be vaccinated against COVID-19. This summary details the findings from a previously published article, in which an international committee of 10 MS experts developed recommendations to answer some important questions about COVID-19 vaccines in people with MS (including relapsingremitting or active secondary progressive disease) taking cladribine tablets. WHAT WERE THE RESULTS?: The committee identified 13 recommendations, which were all agreed upon by at least three-quarters (75%) of the 38 voting MS experts. Generally, they recommended that people with MS taking cladribine tablets should be vaccinated for COVID-19 as soon as possible, because the vaccine is thought to be both safe and effective, and vaccine responses were not likely to be affected by cladribine tablets. WHAT DO THE RESULTS MEAN?: Overall, people with MS taking cladribine tablets should receive the COVID-19 vaccine to protect themselves, unless advised differently by their healthcare provider.

Anti-SARS-CoV-2 vaccination in people with multiple sclerosis: Lessons learnt a year in.

It has been over a year since people with multiple sclerosis (pwMS) have been receiving vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a negligible number of cases in which vaccination led to a relapse or new onset MS, experts around the world agree that the potential consequences of COVID-19 in pwMS by far outweigh the risks of vaccination. This article reviews the currently available types of anti-SARS-CoV-2 vaccines and the immune responses they elicit in pwMS treated with different DMTs. Findings to date highlight the importance of vaccine timing in relation to DMT dosing to maximize protection, and of encouraging pwMS to get booster doses when offered.

The risk of infections for multiple sclerosis and neuromyelitis optica spectrum disorder disease-modifying treatments: Eighth European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop Review. April 2021.

Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.

Multiple sclerosis in the era of COVID-19: disease course, DMTs and SARS-CoV2 vaccinations.

PURPOSE OF REVIEW: As of January 21st 2022, over 340 million are confirmed cases of coronavirus disease 2019 (COVID-19), including nearly 5.6 million deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is neurotropic and affects the neural parenchyma through direct viral invasion from the nasal mucosa and postinfectious cytokine storm. Further challenges of SARS-CoV-2 infection are nowadays linked to variants of concern. Multiple sclerosis is an inflammatory and progressive degenerative disorder of the central nervous system commonly affecting young adults and potentially generating irreversible disability. Since the beginning of the SARS-CoV-2 pandemic, people with multiple sclerosis (pwMS) have been considered 'extra' vulnerable because of the immune-mediated nature of the disease, the disability status, and the immunomodulatory therapies potentially increasing the risk for viral infection. Today multiple sclerosis neurologists are faced with several challenges in the management of pwMS to both prevent SARS-CoV-2 infection and protection from disease worsening. We aimed to highlight today's most relevant facts about the complex management of pwMS in the COVID-19 era. RECENT FINDINGS: The incidence of COVID-19 among pwMS does not differ from the general population. The prognosis of COVID-19 among pwMS is driven by older age, male sex, nonambulatory status, comorbidity as in the general population, as well as by corticosteroid treatment and B-cell depleting agents which decrease seropositivity from SARS-CoV-2 infection and immune responses to SARS-CoV-2 vaccination. SUMMARY: Disease modifying treatments (DMTs) should be regularly continued in relation to SARS-CoV-2 vaccination, but an ad hoc timing is required with B-cell depleting agents. SARS-CoV-2 vaccination is recommended in pwMS with willingness improving through health education programs. Multiple sclerosis does not seem to worsen after SARS-Cov2 vaccination but COVID-19 may enhance disease activity.

Expert opinion on COVID-19 vaccination and the use of cladribine tablets in clinical practice.

BACKGROUND: Gaps in current evidence and guidance leave clinicians with unanswered questions on the use of cladribine tablets for the treatment of multiple sclerosis (MS) in the era of the COVID-19 pandemic, in particular relating to COVID-19 vaccination. OBJECTIVE: We describe a consensus-based program led by international MS experts with the aim of supplementing current guidelines and treatment labels by providing timely recommendations relating to COVID-19 vaccination and the use of cladribine tablets in clinical practice. METHODS: A steering committee (SC) of 10 international MS experts identified 7 clinical questions to answer concerning the use of cladribine tablets and COVID-19 vaccination, which addressed issues relating to patient selection, timing and efficacy, and safety. Clinical recommendations to address each question were drafted using available evidence combined with expert opinion from the SC. An extended faculty of 28 MS experts, representing 19 countries, in addition to the 10 SC members, voted on the recommendations. Consensus on recommendations was achieved when ⩾75% of respondents expressed an agreement score of 7-9, on a 9-point scale. RESULTS: Consensus was achieved on all 13 recommendations. Clinical recommendations are provided on whether all patients with MS receiving cladribine tablets should be vaccinated against COVID-19, and whether they should be prioritized; the timing of vaccination around dosing of cladribine tablets (i.e. before and after a treatment course); and the safety of COVID-19 vaccination for these patients. CONCLUSION: These expert recommendations provide timely guidance on COVID-19 vaccination in patients receiving cladribine tablets, which is relevant to everyday clinical practice.

SARS-CoV-2 Infection in Multiple Sclerosis: Results of the Spanish Neurology Society Registry.

OBJECTIVE: To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. METHODS: Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. RESULTS: Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. CONCLUSIONS: This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal disease.

Risk and outcomes of COVID-19 in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Limited information is available on incidence and outcomes of COVID-19 in patients with multiple sclerosis (MS). This study investigated the risks of SARS-CoV-2 infection and COVID-19-related outcomes in patients with MS, and compared these with the general population. METHODS: A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit admission, and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison. The study was conducted at 14 specialist MS treatment centers in Madrid, Spain, between February and May 2020. RESULTS: Two-hundred nineteen patients were included in the registry, 51 of whom were hospitalized with COVID-19. The mean age ± standard deviation was 45.3 ± 12.4 years, and the mean duration of MS was 11.9 ± 8.9 years. The infection incidence rate was lower in patients with MS than the general population (adjusted incidence rate ratio = 0.78, 95% confidence interval [CI] = 0.70-0.80), but hospitalization rates were higher (relative risk = 5.03, 95% CI = 3.76-6.62). Disease severity was generally low, with only one admission to an intensive care unit and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying treatment and hospitalization risk. CONCLUSIONS: Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue disease-modifying treatment should be based on a careful risk-benefit assessment.

Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus.

Coronavirus disease (COVID-19) appeared in December 2019 in the Chinese city of Wuhan and has quickly become a global pandemic. The disease is caused by the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), an RNA beta coronavirus phylogenetically similar to SARS coronavirus. To date, more than 132 million cases of COVID19 have been recorded in the world, of which over 2.8 million were fatal ( https://coronavirus.jhu.edu/map.html ). A huge vaccination campaign has started around the world since the end of 2020. The availability of vaccines has raised some concerns among neurologists regarding the safety and efficacy of vaccination in patients with multiple sclerosis (MS) taking immunomodulatory or immunosuppressive therapies.

A plea for equitable global access to COVID-19 diagnostics, vaccination and therapy: The NeuroCOVID-19 Task Force of the European Academy of Neurology.

Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.