Targeting the neonatal Fc receptor (FcRn) is not beneficial in an animal model of chronic neuritis.

The inhibition of the neonatal Fc receptor (FcRn) is a promising therapeutic pathway in certain autoimmune disorders to reduce the amount of circulating pathogenic IgG autoantibodies by interfering with their recycling system. FcRn antibodies are currently being tested in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). This study aimed to investigate the therapeutic potential of an antibody targeting FcRn in the intracellular adhesion molecule 1 (ICAM1)-deficient NOD mouse-a model representative for many aspects of human CIDP.

Prognostic factors for worsening and improvement in multiple sclerosis using a multistate model.

Background: The long-term disease trajectory of people living with multiple sclerosis (MS) can be improved by initiating efficacious treatment early. More quantitative evidence is needed on factors that affect a patient's risk of disability worsening or possibility of improvement to inform timely treatment decisions.

Methods: We developed a multistate model to quantify the influence of demographic, clinical, and imaging factors on disability worsening and disability improvement simultaneously across the disability spectrum as measured by the Expanded Disability Status Scale (EDSS).

Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis.

Background And Objectives: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083).

Methods: In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions.

A review of Bruton's tyrosine kinase inhibitors in multiple sclerosis.

Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation.

Immunomodulatory potential of anti-IFN-beta antibodies on monocyte-derived macrophages.

Multiple sclerosis (MS) is a disabling neurological disease with an unknown etiology, where the recombinant interferon beta (rIFNβ) is the most established treatment. However, the development of anti-IFNβ antibodies has posed a significant therapeutic drawback. In this study, the interaction between anti-IFNβ antibodies and macrophages was investigated to assess the effects on the immune system.

Fatigue, depression, and product tolerability during long-term treatment with intravenous immunoglobulin (Gamunex® 10%) in patients with chronic inflammatory demyelinating polyneuropathy.

Introduction/aims: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is characterized by progressive weakness and sensory loss, often affecting patient's ability to walk and perform activities of daily living independently. Furthermore, patients often report fatigue and depression which can affect their quality of life. These symptoms were assessed in CIDP patients receiving long-term intravenous immunoglobulin (IVIG) treatment.

Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial.

Introduction: Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by magnetic resonance imaging (MRI) at the group level and evaluate the potential of sNfL as a biomarker for capturing subclinical disease activity in individual RMS patients.

Methods: In the 12-week APLIOS study, patients (N = 284) received subcutaneous ofatumumab 20 mg.

Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years.

Background: Ofatumumab is approved for the treatment of relapsing multiple sclerosis (RMS). Ongoing safety reporting is crucial to understand its long-term benefit-risk profile.

Objective: Report the safety and tolerability of ofatumumab in RMS after extended treatment up to 3.

How patients with multiple sclerosis acquire disability.

Patients with multiple sclerosis acquire disability either through relapse-associated worsening (RAW) or progression independent of relapse activity (PIRA). This study addresses the relative contribution of relapses to disability worsening over the course of the disease, how early progression begins and the extent to which multiple sclerosis therapies delay disability accumulation. Using the Novartis-Oxford multiple sclerosis (NO.

Effect of ofatumumab on pregnancy, parturition, and lactation in cynomolgus monkeys.

Knowledge of the impacts of the anti-CD20 monoclonal antibody ofatumumab on the developing immune system is limited. This study examined the effects of intravenous ofatumumab on pregnancy, parturition, and lactation, and on pre- and postnatal survival and development in cynomolgus monkeys, an established model for developmental toxicity assessment. Pregnant cynomolgus monkeys (n = 42) were randomized to receive vehicle only (control group; n = 14), low-dose ofatumumab (n = 14), or high-dose ofatumumab (n = 14).

Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study.

Background: Ofatumumab, the first fully human anti-CD20 monoclonal antibody, has been developed as a treatment for relapsing multiple sclerosis (RMS) which can be self-administered at home.

Objective: To investigate the efficacy and safety of ofatumumab in RMS patients from Japan and Russia.

Methods: APOLITOS included a 24-week, double-blind, placebo-controlled core-part followed by an open-label extension-part.

Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy.

Background: Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea.

Temporal profile of serum neurofilament light in multiple sclerosis: Implications for patient monitoring.

Objective: To understand how longitudinal serum neurofilament light chain (sNfL) patterns can inform its use as a prognostic biomarker in multiple sclerosis (MS) and evaluate whether sNfL reflects MS disease activity and disease-modifying therapy usage.

Methods: This was a post hoc analysis of longitudinal data and samples from the ADVANCE trial (NCT00906399) of patients with relapsing-remitting MS (RRMS). sNfL was measured every 3 months for 2 years, then every 6 months for 4 years.

Association of Serum Neurofilament Light Levels With Long-term Brain Atrophy in Patients With a First Multiple Sclerosis Episode.

Importance: Data are needed on the potential long-term prognostic association of serum neurofilament light in multiple sclerosis (MS).

Objective: To evaluate serum neurofilament light as a biomarker associated with long-term disease outcomes in clinically isolated syndrome.

Design, Setting, And Participants: This post hoc cohort study used data from the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study, a 36-month, multicenter, placebo-controlled interferon β-1a randomized clinical trial conducted from April 1996 to March 2000, and its long-term (5- and 10-year) extension study from February 2001 to March 2009.

NK cell markers predict the efficacy of IV immunoglobulins in CIDP.

Objective: To assess whether IV immunoglobulins (IVIgs) as a first-line treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) have a regulative effect on natural killer (NK) cells that is related to clinical responsiveness to IVIg.

Methods: In a prospective longitudinal study, we collected blood samples of 29 patients with CIDP before and after initiation of IVIg treatment for up to 6 months. We used semiquantitative PCR and flow cytometry in the peripheral blood to analyze the effects of IVIg on the NK cells.

Harnessing Real-World Data to Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS).

Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is the first example of a learning health system in multiple sclerosis (MS). This paper describes the initial implementation of MS PATHS and initial patient characteristics. MS PATHS is an ongoing initiative conducted in 10 healthcare institutions in three countries, each contributing standardized information acquired during routine care.

Corneal Confocal Microscopy Demonstrates Corneal Nerve Loss in Patients With Trigeminal Neuralgia.

The diagnosis of trigeminal neuralgia (TN) is challenging due to the lack of objective diagnostics. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique, which allows quantification of corneal nerve fibers arising from the trigeminal ganglion and may allow the assessment of neurodegeneration in TN. CCM was undertaken in 11 patients with TN and 11 age-matched healthy controls.

Blood neurofilament light levels segregate treatment effects in multiple sclerosis.

Objective: To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS).

Methods: Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide).

Results: The baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs.

Predicting disability progression in multiple sclerosis: Insights from advanced statistical modeling.

Background: There is an unmet need for precise methods estimating disease prognosis in multiple sclerosis (MS).

Objective: Using advanced statistical modeling, we assessed the prognostic value of various clinical measures for disability progression.

Methods: Advanced models to assess baseline prognostic factors for disability progression over 2 years were applied to a pooled sample of patients from placebo arms in four different phase III clinical trials.

Neurofilament light levels are associated with long-term outcomes in multiple sclerosis.

Background: Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear.

Objective: We measured NfL from a phase 3 trial in relapsing-remitting MS and investigated its association with outcomes after 8 and 15 years.

Methods: NfL concentrations were measured by single molecule array assay in cerebrospinal fluid (CSF) from MS patients ( = 235) in a 2-year randomized clinical trial (RCT) of intramuscular interferon β-1a, and in serum ( = 164) from the extension study.

A proof-of-concept application of a novel scoring approach for personalized medicine in multiple sclerosis.

Background: Stratified medicine methodologies based on subgroup analyses are often insufficiently powered. More powerful personalized medicine approaches are based on continuous scores.

Objective: We deployed a patient-specific continuous score predicting treatment response in patients with relapsing-remitting multiple sclerosis (RRMS).

Immune-mediated neuropathies.

Since the discovery of an acute monophasic paralysis, later coined Guillain-Barré syndrome, almost 100 years ago, and the discovery of chronic, steroid-responsive polyneuropathy 50 years ago, the spectrum of immune-mediated polyneuropathies has broadened, with various subtypes continuing to be identified, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). In general, these disorders are speculated to be caused by autoimmunity to proteins located at the node of Ranvier or components of myelin of peripheral nerves, although disease-associated autoantibodies have not been identified for all disorders. Owing to the numerous subtypes of the immune-mediated neuropathies, making the right diagnosis in daily clinical practice is complicated.

Trapped in the epineurium: early entry into the endoneurium is restricted to neuritogenic T cells in experimental autoimmune neuritis.

Background: Autoimmune polyneuropathies are acquired inflammatory disorders of the peripheral nervous system (PNS) characterized by inflammation, demyelination, and axonal degeneration. Although the pathogenesis has not been fully elucidated, T cells recognizing self-antigens are believed to initiate inflammation in a subgroup of patients. However, the route and time of T cell entry into the PNS have not yet been described in detail.