Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study.

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, is approved in several countries for relapsing multiple sclerosis (RMS).

Objective: To demonstrate the bioequivalence of ofatumumab administered by an autoinjector versus a pre-filled syringe (PFS) and to explore the effect of ofatumumab on B-cell depletion.

Methods: APLIOS (NCT03560739) is a 12-week, open-label, parallel-group, phase-2 study in patients with RMS receiving subcutaneous ofatumumab 20 mg every 4 weeks (q4w) (from Week 4, after initial doses on Days 1, 7, and 14).

Validation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in the Russian Population.

Objective: Cognitive dysfunction is common in multiple sclerosis (MS). The Brief International Cognitive Assessment for MS (BICAMS) battery of tests has been suggested as a measure for the evaluation of the cognitive status of MS patients. This study aims to validate the BICAMS battery in the Russian population of MS patients.

COVID-19 Immunopathology and the Central Nervous System: Implication for Multiple Sclerosis and Other Autoimmune Diseases with Associated Demyelination.

In the frame of the coronavirus disease 2019 (COVID-19) pandemic, recent reports on SARS-CoV-2 potential neuroinvasion placed neurologists on increased alertness in order to assess early neurological manifestations and their potentially prognostic value for the COVID-19 disease. Moreover, the management of chronic neurological diseases, such as Multiple Sclerosis (MS), underwent guided modifications, such as an Extended Interval Dose (EID) of Disease-Modifying Treatment (DMT) administration, in order to minimize patients' exposure to the health system, thus reducing the risk of SARS-CoV-2 infection. In this review, we summarize existing evidence of key immune pathways that the SARS-CoV-2 modifies during COVID-19 and the relevant implication for MS and other autoimmune diseases with associated demyelination (such as Systemic lupus erythematosus and Antiphospholipid syndrome), including the context of potential neuroinvasion by SARS-Cov-2 and the alterations that DMT induces to the immune system.

Real-world study of efficacy, risk management and reasons for discontinuation of natalizumab for treatment of multiple sclerosis in Russia.

Background: NTZ is approved in Russia for the treatment of highly active relapsing remitting multiple sclerosis and is reimbursed via federal budget program. However, no data about NTZ treatment in Russia and the effect of federal reimbursement have been performed so far.

Objective: To characterize the population of patients receiving natalizumab and assess the efficacy and risk-management plan (RMP) implementation of NTZ therapy in routine clinical practice in Russia.

Concentrations of immunoglobulin free light chains in cerebrospinal fluid predict increased level of brain atrophy in multiple sclerosis.

Recent studies showed that B cells play a major role in the pathogenesis of neurodegeneration in multiple sclerosis (MS). In this study, we aimed to determine the possible link between immunoglobulin free light chains (FLC) and brain atrophy in patients with MS. Ninety-two patients (32 males and 60 females) with MS were included.

Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay.

Leptomeningeal Contrast Enhancement Is Associated with Disability Progression and Grey Matter Atrophy in Multiple Sclerosis.

Leptomeningeal contrast enhancement (LMCE) on magnetic resonance imaging (MRI) is a newly recognized possible biomarker in multiple sclerosis (MS), associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. 54 patients with MS were included in the study.

CD206-Targeted Liposomal Myelin Basic Protein Peptides in Patients with Multiple Sclerosis Resistant to First-Line Disease-Modifying Therapies: A First-in-Human, Proof-of-Concept Dose-Escalation Study.

Previously, we showed that CD206-targeted liposomal delivery of co-encapsulated immunodominant myelin basic protein (MBP) sequences MBP, MBP and MBP (Xemys) suppressed experimental autoimmune encephalomyelitis in dark Agouti rats. The objective of this study was to assess the safety of Xemys in the treatment of patients with relapsing-remitting multiple sclerosis (MS) and secondary progressive MS, who failed to achieve a sustained response to first-line disease-modifying therapies. In this phase I, open-label, dose-escalating, proof-of-concept study, 20 patients with relapsing-remitting or secondary progressive MS received weekly subcutaneously injections with ascending doses of Xemys up to a total dose of 2.

The effects of intrathecal rituximab on biomarkers in multiple sclerosis.

Objectives: Clinical trials of IV-rituximab have proved successful. It is unclear whether intrathecal (IT)-rituximab is more efficacious at lower doses. We examine its effects on B-cell biomarkers.

Diagnostic and Prognostic Value of the Cerebrospinal Fluid Concentration of Immunoglobulin Free Light Chains in Clinically Isolated Syndrome with Conversion to Multiple Sclerosis.

Background And Objective: In this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS).

Methods: We compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values.

Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome.

Background: Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls.

Methods: We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79-139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.

Immunoglobulin M oligoclonal bands: biomarker of targetable inflammation in primary progressive multiple sclerosis.

Objective: To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy.

Methods: The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity.

Results: Using both cross-sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo-controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF-restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients.

Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.

Background. Mitoxantrone (MTX) and Rituximab (RTX) are successfully used for treatment of multiple sclerosis (MS) and can be combined to increase efficacy. Objective.