Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial.

Background: In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline.

Methods: Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2.

Alemtuzumab outcomes by age: Post hoc analysis from the randomized CARE-MS studies over 8 years.

Background: Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]).

Methods: Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years).

Efficacy of alemtuzumab in relapsing-remitting MS patients who received additional courses after the initial two courses: Pooled analysis of the CARE-MS, extension, and TOPAZ studies.

Background: Alemtuzumab is given as two annual courses. Patients with continued disease activity may receive as-needed additional courses.

Objective: To evaluate efficacy and safety of additional alemtuzumab courses in the CARE-MS (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) studies and their extensions.

Best Practices for Intrathecal Baclofen Therapy: Troubleshooting.

Introduction: Troubleshooting helps optimize intrathecal baclofen (ITB) therapy in cases of underdose, overdose, and infection.

Methods: An expert panel of 21 multidisciplinary physicians currently managing >3200 ITB patients was convened, and using standard methodologies for guideline development, created an organized approach to troubleshooting ITB. They conducted a structured literature search that identified 263 peer-reviewed papers, and used results from an online survey of 42 physicians currently managing at least 25 ITB patients each.

Best Practices for Intrathecal Baclofen Therapy: Patient Selection.

Introduction: When spasticity interferes with comfort, function, activities of daily living, mobility, positioning, or caregiver assistance, patients should be considered for intrathecal baclofen (ITB) therapy.

Methods: An expert panel consulted on best practices.

Results: ITB can be considered for problematic spasticity involving muscles/muscle groups during all phases of diseases, including progressive neurologic diseases.

Best Practices for Intrathecal Baclofen Therapy: Screening Test.

Introduction: Intrathecal baclofen (ITB) screening assesses response to a test dose of ITB on spasticity and function and identifies adverse reactions.

Method: An expert panel consulted on best practices after conducting an extensive literature search and conducting an online survey.

Results: A successful trial may confirm predetermined goals, which may include improved mobility/positioning, decreased time/improved independence for activities, less home exercise, better wheelchair tolerance, decreased caregiver time, improved sleep, and reduced pain, or may modify goals and expectations.

Best Practices for Intrathecal Baclofen Therapy: Dosing and Long-Term Management.

Introduction: Intrathecal baclofen (ITB) therapy aims to reduce spasticity and provide functional control.

Method: An expert panel consulted on best practices.

Results: Pump fill and drug delivery can be started intraoperatively, with monitoring for at least eight hours.

Glatiramer acetate: long-term safety and efficacy in relapsing-remitting multiple sclerosis.

Glatiramer acetate (GA) is approved for relapsing-remitting multiple sclerosis in 57 countries worldwide, with more than 2 million patient-years of exposure and over 20 years of continuous clinical use without new safety concerns. GA has an overall favorable risk-benefit profile: 30% reduced annual relapse rate and decreased brain lesion activity. In clinically definite MS or clinically isolated syndrome, GA slows brain atrophy, which may be related to its unique anti-inflammatory and neuroprotective mechanisms of action.

Concise review: modeling multiple sclerosis with stem cell biological platforms: toward functional validation of cellular and molecular phenotypes in inflammation-induced neurodegeneration.

In recent years, tremendous progress has been made in identifying novel mechanisms and new medications that regulate immune cell function in multiple sclerosis (MS). However, a significant unmet need is the identification of the mechanisms underlying neurodegeneration, because patients continue to manifest brain atrophy and disability despite current therapies. Neural and mesenchymal stem cells have received considerable attention as therapeutic candidates to ameliorate the disease in preclinical and phase I clinical trials.

Design of oral agents for the management of multiple sclerosis: benefit and risk assessment for dimethyl fumarate.

Dimethyl fumarate (DMF) is the most recent oral disease-modifying therapy approved by the US Food and Drug Administration and is indicated for the treatment of relapsing forms of multiple sclerosis (MS). Prior to approval for use in MS, DMF and its active metabolite, monomethyl fumarate, had been used for decades as two of the fumaric acid esters in Fumaderm, a medication used in Europe for the treatment of psoriasis. The unique mechanism of action of DMF remains under evaluation; however, it has been shown to act through multiple pathways leading to shifts away from the Th1 proinflammatory response to the less inflammatory Th2 response.

First-line natalizumab in multiple sclerosis: rationale, patient selection, benefits and risks.

Natalizumab (NTZ) is a highly effective disease modifying therapy for the treatment of relapsing forms of multiple sclerosis (MS). Despite evidence to support its use as first-line therapy, risk of NTZ-associated progressive multifocal leukoencephalopathy (PML) has largely contributed to it being relegated to a second-line position. Recent preliminary data may allow for a more accurate analysis of JC virus (JCV) risk stratification of a given patient's PML risk.

Multiple sclerosis: Five new things.

Preliminary studies have suggested that a high salt diet may play a role in the development of autoimmune disease and possibly multiple sclerosis (MS). Promising clinical trial results for 2 new therapies for MS have been reported. Dimethyl fumarate, also known by its investigational name BG-12, became the third oral disease-modifying therapy for MS to be Food and Drug Administration (FDA)-approved in March 2013.

Lessons learned from fatal progressive multifocal leukoencephalopathy in a patient with multiple sclerosis treated with natalizumab.

Objective: To describe the clinical, radiological, and histopathological features of a fatal case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple sclerosis treated with natalizumab. We will use this case to review PML risk stratification and diagnosis.

Design: Case report.

Pediatric-onset multiple sclerosis in African-American black and European-origin white patients.

Pediatric-onset multiple sclerosis is now recognized, but the association with ethnicity has not been well studied. In a retrospective review at a major teaching facility, 46 pediatric-onset multiple sclerosis patients were identified; of these, 24 were African-American black and 19 were European-origin white. Both groups were similar in mean age at onset (black, 13.