Neurologic Outcomes in People With Multiple Sclerosis Treated With Immune Checkpoint Inhibitors for Oncologic Indications.

Background And Objectives: Immune checkpoint inhibitors (ICIs) are increasingly used against various cancers but are associated with immune-related adverse events (irAEs). Risk of irAEs may be higher in patients with certain preexisting autoimmune diseases, and these patients may also experience exacerbation of the underlying autoimmune disease following ICI initiation. People with multiple sclerosis (MS) have mostly been excluded from clinical trials of ICIs, so data on the safety of ICIs in MS are limited.

Cost Per Relapse Avoided for Ozanimod Versus Other Selected Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis in the United States.

Introduction: This study assessed the cost-effectiveness of ozanimod compared with commonly used disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS).

Methods: Annualized relapse rate (ARR) and safety data were obtained from a network meta-analysis (NMA) of clinical trials of RRMS treatments including ozanimod, fingolimod, dimethyl fumarate, teriflunomide, interferon beta-1a, interferon beta-1b, and glatiramer acetate. ARR-related number needed to treat (NNT) relative to placebo and annual total MS-related healthcare costs was used to estimate the incremental annual cost per relapse avoided with ozanimod vs each DMT.

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: open-label extension study.

Baclofen, a racemic γ-aminobutyric acid B receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the γ-aminobutyric acid B receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets allow a dosing interval of 12 h and have shown a favourable safety and efficacy profile in early clinical development.

Arbaclofen extended-release tablets for spasticity in multiple sclerosis: randomized, controlled clinical trial.

Baclofen, a racemic GABA-B (GABA) receptor agonist, is commonly used for the management of multiple sclerosis-related spasticity but is associated with frequent dosing and poor tolerability. Arbaclofen, the active R-enantiomer of baclofen, exhibits 100- to 1000-fold greater specificity for the GABA receptor compared with the S-enantiomer and ∼5-fold greater potency compared with racemic baclofen. Arbaclofen extended-release tablets have a dosing interval of 12 hours and have shown a favourable safety and efficacy profile in early-phase clinical development.

Digital Scientific Platform for Independent Content in Neurology: Rigorous Quality Guideline Development and Implementation.

Background: Digital communication has emerged as a major source of scientific and medical information for health care professionals. There is a need to set up an effective and reliable methodology to assess and monitor the quality of content that is published on the internet.

Objective: The aim of this project was to develop content quality guidelines for Neurodiem, an independent scientific information platform dedicated to neurology for health care professionals and neuroscientists.

Confirmed 6-Month Disability Improvement and Worsening Correlate with Long-term Disability Outcomes in Alemtuzumab-Treated Patients with Multiple Sclerosis: Post Hoc Analysis of the CARE-MS Studies.

Introduction: In the 2-year CARE-MS trials (NCT00530348; NCT00548405) in patients with relapsing-remitting multiple sclerosis, alemtuzumab showed superior efficacy versus subcutaneous interferon beta-1a. Efficacy was maintained in two consecutive extensions (NCT00930553; NCT02255656). This post hoc analysis compared disability outcomes over 9 years among alemtuzumab-treated patients according to whether they experienced confirmed disability improvement (CDI) or worsening (CDW) or neither CDI nor CDW.

Treatment Patterns and Relapses Among Newly Treated Multiple Sclerosis Patients From a Retrospective Claims Analysis.

Purpose: Although all disease-modifying therapies (DMTs) reduce risk of relapse in multiple sclerosis (MS), many factors, including route of administration, influence selection of first-line DMT. Knowledge of real-world treatment patterns and effectiveness in reducing relapses across DMTs is important to understanding factors influencing this choice. This study sought to describe treatment patterns and relapses among newly treated adults with MS and by DMT route of administration (oral, injectable, and infusion).

Multiple sclerosis relapse rates and healthcare costs of two versions of glatiramer acetate.

To compare relapse rates and healthcare costs in MS patients treated with Glatopa 20 mg (generic glatiramer acetate) versus Copaxone 20 mg in a US managed care population. A retrospective claims study was conducted using the HealthCore Integrated Research Database. Patients with ≥1 Glatopa or Copaxone claim between 01 April 2015 (Glatopa) or 01 January 2013 (Copaxone) and 30 April 2018 were included.

Two Sides to Every Story: Perspectives from Four Patients and a Healthcare Professional on Multiple Sclerosis Disease Progression.

Multiple sclerosis (MS) is a chronic progressive disease and many patients transition from an initial relapsing-remitting course to a secondary progressive pattern. Accurate classification of disease status is critical to ensure that patients are treated appropriately and kept informed of their prognosis. Consensus terms defining the different forms of MS are available but were developed primarily for healthcare professionals (HCPs) and may be of limited value to patients.

Effectiveness of alternative dose fingolimod for multiple sclerosis.

Background: Fingolimod is a daily oral medication used to treat relapsing multiple sclerosis (MS). Clinicians often adopt less frequent dosing for patients with profound drug-induced lymphopenia or other adverse events. Data on the effectiveness of alternate dose fingolimod are limited.

Real-world persistence with fingolimod for the treatment of multiple sclerosis: A systematic review and meta-analysis.

Objective: To systematically review reports of fingolimod persistence in the treatment of relapsing-remitting multiple sclerosis (RRMS) across data sources and practice settings, and to develop a consensus estimate of the 1-year real-world persistence rate.

Methods: A systematic literature review was conducted (MEDLINE, EMBASE, and abstracts from selected conferences [2013-2015]) to identify observational studies reporting 1-year fingolimod persistence among adult patients with RRMS (sample size ≥50). A random-effects meta-analysis was performed to estimate a synthesized 1-year persistence rate and to assess heterogeneity across studies.

Perspectives from the Patient and the Healthcare Professional in Multiple Sclerosis: Social Media and Patient Education.

A diagnosis of multiple sclerosis (MS) is life-altering. Because the course of MS is heterogeneous, patients may face uncertainty in terms of long-term physical and cognitive challenges, potential loss of employment, and the risk of social isolation. Patients often turn to the Internet and social media for information about MS and its management, and to seek out fellow patients and support groups.

Perspectives from the Patient and the Healthcare Professional in Multiple Sclerosis: Social Media and Participatory Medicine.

When faced with a diagnosis of multiple sclerosis (MS), patients often turn to the Internet and social media to find support groups, read about the experiences of other people affected by MS and seek their advice, and research their condition and treatment options to discuss with their healthcare professionals (HCPs). Here, we examine the use of social media and the Internet among patients with MS, considering its impact on patient empowerment and patient participation in treatment decision-making and MS research. These themes are exemplified with first-hand experiences of the patient author.

Development of Glatopa® (Glatiramer Acetate): The First FDA-Approved Generic Disease-Modifying Therapy for Relapsing Forms of Multiple Sclerosis.

The multiple sclerosis (MS) treatment landscape in the United States has changed dramatically over the past decade. While many disease-modifying therapies (DMTs) have been approved by the US Food and Drug Administration (FDA) for the treatment of relapsing forms of MS, DMT costs continue to rise. The availability of generics and biosimilars in the MS-treatment landscape is unlikely to have a major impact on clinical benefit.

Safety and efficacy of dual-lead thalamic deep brain stimulation for patients with treatment-refractory multiple sclerosis tremor: a single-centre, randomised, single-blind, pilot trial.

Background: Efficacy in previous studies of surgical treatments of refractory multiple sclerosis tremor using lesioning or deep brain stimulation (DBS) has been variable. The aim of this study was to investigate the safety and efficacy of dual-lead thalamic DBS (one targeting the ventralis intermedius-ventralis oralis posterior nucleus border [the VIM lead] and one targeting the ventralis oralis anterior-ventralis oralis posterior border [the VO lead]) for the treatment of multiple sclerosis tremor.

Methods: We did a single centre, single-blind, prospective, randomised pilot trial at the University of Florida Center for Movement Disorders and Neurorestoration clinic (Gainesville, FL, USA).

Two decades of glatiramer acetate: From initial discovery to the current development of generics.

Multiple sclerosis (MS) is a chronic, incurable, inflammatory disease of the central nervous system (CNS). In the United States, several US Food and Drug Administration (FDA)-approved disease-modifying treatments (DMTs) are available, including glatiramer acetate (GA; Copaxone®), one of the most longstanding treatments. GA was discovered serendipitously in the late 1960s/early 1970s while attempting to produce a synthetic antigen capable of inducing experimental autoimmune encephalomyelitis (EAE), an animal model of autoimmune inflammatory CNS disorders, including MS.

Demonstration of Biological and Immunological Equivalence of a Generic Glatiramer Acetate.

Background: In April 2015, the US Food and Drug Administration approved the first generic glatiramer acetate, Glatopa® (M356), as fully substitutable for Copaxone® 20 mg/mL for relapsing forms of multiple sclerosis (MS). This approval was accomplished through an Abbreviated New Drug Application that demonstrated equivalence to Copaxone.

Method: This article will provide an overview of the methods used to establish the biological and immunological equivalence of the two glatiramer acetate products, including methods evaluating antigenpresenting cell (APC) biology, T-cell biology, and other immunomodulatory effects.

Demonstration of equivalence of a generic glatiramer acetate (Glatopa™).

Glatiramer acetate (GA) has been available under the brand name Copaxone® for nearly two decades. Recently, the US Food and Drug Administration (FDA) approved the first generic GA, Glatopa™, as fully substitutable for all indications for which Copaxone 20mg is approved; Glatopa also represents the first FDA-approved "AP-rated," substitutable generic for treating patients with MS. Glatiramer acetate is a complex mixture of polypeptides and, consequently, its characterization presented challenges not generally encountered in drug development.

Equivalent Gene Expression Profiles between Glatopa™ and Copaxone®.

Glatopa™ is a generic glatiramer acetate recently approved for the treatment of patients with relapsing forms of multiple sclerosis. Gene expression profiling was performed as a means to evaluate equivalence of Glatopa and Copaxone®. Microarray analysis containing 39,429 unique probes across the entire genome was performed in murine glatiramer acetate--responsive Th2-polarized T cells, a test system highly relevant to the biology of glatiramer acetate.

Treatment of Postherpetic Neuralgia With Gastroretentive Gabapentin: Interaction of Patient Demographics, Disease Characteristics, and Efficacy Outcomes.

Unlabelled: To understand how patient demographics and patient-reported disease characteristics relate to successful management of postherpetic neuralgia (PHN), integrated data from phase 3 and phase 4 studies of patients with PHN (n = 546) who received once-daily gastroretentive gabapentin (G-GR, 1800 mg) were analyzed. There were widespread, networked, positive correlations among efficacy end points--pain qualities on the visual analog scale (VAS) and Brief Pain Inventory (BPI), measures of pain interference on the BPI, and Patient Global Impression of Change (PGIC)--most likely characterized by positive feedback loops, in which pain interferes with patient functioning, and poor functioning enhances pain. VAS scores at baseline or at week 2 were the strongest predictors of being "much" or "very much" improved on the PGIC; BPI sleep interference scores were the strongest predictors of percent changes in BPI pain qualities and in the average of BPI interference scores, whereas age, sex, and race were not important predictors.

First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis.

Background: In pivotal phase 3 studies, fingolimod treatment initiation was associated with a transient reduction in heart rate (HR). Atrioventricular (AV) conduction delays, which were typically asymptomatic, were detected in a small minority of patients.

Objective: We report the first-dose effects of fingolimod in patients who switched from injectable therapies during the Evaluate Patient OutComes (EPOC) study (ClinicalTrials.

Assessment of confirmed urinary tract infection in patients treated with dalfampridine for multiple sclerosis.

Urinary tract infections (UTIs) were reported frequently with dalfampridine extended-release (dalfampridine-ER) 10 mg relative to placebo in previous multiple sclerosis (MS) studies. The objective of this study was to determine whether dalfampridine-ER is associated with increased incidence of confirmed UTIs in MS patients. This post hoc analysis used UTI data from a study comparing the 4-week safety and efficacy of 5 mg (n = 144) and 10 mg (n = 142) twice-daily dalfampridine-ER versus placebo (n = 143).