OBJECTIVE: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). METHODS: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. RESULTS: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. INTERPRETATION: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis.

Importance Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS. Observations MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid–specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease. Conclusions and Relevance MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.

https://jamanetwork.com/journals/jama/articlepdf/2776694/jama_mcginley_2021_rv_200019_1622223670.83305.pdf

Diagnosis and Treatment of Multiple Sclerosis: A Review.

Background and Aims:The National Multiple Sclerosis Society and other expert organizations recommended that all patients with multiple sclerosis (MS) should be vaccinated against COVID-19. However,...

Humoral immune response to COVID-19 mRNA vaccine in patients with multiple sclerosis treated with high-efficacy disease-modifying therapies

The current Coronavirus disease 2019 or COVID-19 pandemic has infected over two million people and resulted in the death of over one hundred thousand people at the time of writing this review. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though multiple vaccines and treatments are under development so far, the disease is only slowing down under extreme social distancing measures that are difficult to maintain. SARS-COV-2 is an enveloped virus that is surrounded by a lipid bilayer. Lipids are fundamental cell components that play various biological roles ranging from being a structural building block to a signaling molecule as well as a central energy store. The role lipids play in viral infection involves the fusion of the viral membrane to the host cell, viral replication, and viral endocytosis and exocytosis. Since lipids play a crucial function in the viral life cycle, we asked whether drugs targeting lipid metabolism, such as statins, can be utilized against SARS-CoV-2 and other viruses. In this review, we discuss the role of lipid metabolism in viral infection as well as the possibility of targeting lipid metabolism to interfere with the viral life cycle.

https://www.mdpi.com/1422-0067/21/10/3544/pdf

The Role of Lipid Metabolism in COVID-19 Virus Infection and as a Drug Target.

Summary Background Pharmacological prevention against relapses in patients with neuromyelitis optica spectrum disorder (NMOSD) is developing rapidly. We aimed to investigate the safety and efficacy of rituximab, an anti-CD20 monoclonal antibody, against relapses in patients with NMOSD. Methods We did a multicentre, randomised, double-blind, placebo-controlled clinical trial at eight hospitals in Japan. Patients aged 16–80 years with NMOSD who were seropositive for aquaporin 4 (AQP4) antibody, were taking 5–30 mg/day oral steroids, and had an Expanded Disability Status Scale (EDSS) score of 7·0 or less were eligible for the study. Individuals taking any other immunosuppressants were excluded. Participants were randomly allocated (1:1) either rituximab or placebo by a computer-aided dynamic random allocation system. The doses of concomitant steroid (converted to equivalent doses of prednisolone) and relapses in previous 2 years were set as stratification factors. Participants and those assessing outcomes were unaware of group assignments. Rituximab (375 mg/m2) was administered intravenously every week for 4 weeks, then 6-month interval dosing was done (1000 mg every 2 weeks, at 24 weeks and 48 weeks after randomisation). A matching placebo was administered intravenously. Concomitant oral prednisolone was gradually reduced to 2–5 mg/day, according to the protocol. The primary outcome was time to first relapse within 72 weeks. Relapses were defined as patient-reported symptoms or any new signs consistent with CNS lesions and attributable objective changes in MRI or visual evoked potential. The primary analysis was done in the full analysis set (all randomly assigned patients) and safety analyses were done in the safety analysis set (all patients who received at least one infusion of assigned treatment). The primary analysis was by intention-to-treat principles. This trial is registered with the UMIN clinical trial registry, UMIN000013453. Findings Between May 10, 2014, and Aug 15, 2017, 38 participants were recruited and randomly allocated either rituximab (n=19) or placebo (n=19). Three (16%) patients assigned rituximab discontinued the study and were analysed as censored cases. Seven (37%) relapses occurred in patients allocated placebo and none were recorded in patients assigned rituximab (group difference 36·8%, 95% CI 12·3–65·5; log-rank p=0·0058). Eight serious adverse events were recorded, four events in three (16%) patients assigned rituximab (lumbar compression fracture and infection around nail of right foot [n=1], diplopia [n=1], and uterine cancer [n=1]) and four events in two (11%) people allocated to placebo (exacerbation of glaucoma and bleeding in the right eye chamber after surgery [n=1], and visual impairment and asymptomatic white matter brain lesion on MRI [n=1]); all patients recovered. No deaths were reported. Interpretation Rituximab prevented relapses for 72 weeks in patients with NMOSD who were AQP4 antibody-positive. This study is limited by its small sample size and inclusion of participants with mild disease activity. However, our results suggest that rituximab could be useful maintenance therapy for individuals with NMOSD who are AQP4 antibody-positive. Funding Japanese Ministry of Health, Labour and Welfare, Japan Agency for Medical Research and Development, and Zenyaku Kogyo.

Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial

Importance: Although highly effective disease-modifying therapies for multiple sclerosis (MS) have been associated with an increased risk of infections vs injectable therapies interferon beta and g ...

https://jamanetwork.com/journals/jamaneurology/articlepdf/2752284/jamaneurology_luna_2019_oi_190084_1630696216.93896.pdf

Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies.

Objectives To evaluate a dermatologist-centred screening tool followed by a structured rheumatological examination including MRI of sacroiliac joints and spine for the recognition of psoriatic arthritis with axial involvement (axPsA). Methods This was a prospective multicentre study. Adult patients with a confirmed diagnosis of psoriasis who had chronic back pain (≥3 months), onset <45 years and had not been treated with any biologic or targeted synthetic disease-modifying antirheumatic drug in the 12 weeks before screening were referred to a specialised rheumatology clinic. A rheumatological investigation including clinical, laboratory and genetic assessments as well as imaging with conventional radiography and MRI of sacroiliac joints and spine was performed. The primary outcome of the study was the proportion of patients diagnosed with axPsA among all referred patients with PsO. Results Rheumatologists examined 100 patients of those who qualified for referral. 14 patients (including 3 with both axial and peripheral involvement) were diagnosed with axPsA and 5 were diagnosed with peripheral PsA solely. All patients diagnosed with axPsA had active inflammatory and/or structural (post)inflammatory changes in the sacroiliac joints and/or spine on imaging. In five patients, MRI changes indicative of axial involvement were found only in the spine. All but one patient with PsA (13/14 with axPsA and 5/5 with pPsA) fulfilled the Classification Criteria for Psoriatic Arthritis criteria for PsA. The Assessment of SpondyloArthritis International Society criteria for axSpA were fulfilled in 9 (64.3%) patients diagnosed with axPsA. Conclusions Applying a dermatologist-centred screening tool may be useful for the early detection of axPsA in at-risk patients with psoriasis .

/pdf/early-identification-of-axial-psoriatic-arthritis-among-1unzak7g.pdf

Gustavo Luna

Papers

Infection Risks Among Patients With Multiple Sclerosis Treated With Fingolimod, Natalizumab, Rituximab, and Injectable Therapies.

Early identification of axial psoriatic arthritis among patients with psoriasis: a prospective multicentre study