Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis.

Background: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.

Methods: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.

Relapse Rate and MRI Activity in Young Adult Patients With Multiple Sclerosis: A Post Hoc Analysis of Phase 3 Fingolimod Trials.

Background: Disease activity differs in young patients with multiple sclerosis (MS) compared with the overall adult MS population.

Objective: The objective of this paper is to evaluate the effect of fingolimod 0.5 mg on disease activity in young adults with MS from three randomized, double-blind Phase 3 trials.

Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study.

Objective: To investigate the relationship between brain volume and disability worsening over ≥3 years in the natural history of primary progressive multiple sclerosis using data from the placebo group of the INFORMS trial ( = 487; clinicaltrials.gov NCT00731692).

Methods: Magnetic resonance imaging scans were collected annually.

A comparison of multiple sclerosis disease activity after discontinuation of fingolimod and placebo.

Background: Cases of higher-than-expected disease activity have been reported following fingolimod discontinuation.

Objective: The objective of this paper is to assess the risk of substantially higher-than-expected disease activity post-study drug discontinuation (SDD) at the individual patient level using data from the Phase III, placebo-controlled FREEDOMS and FREEDOMS II trials.

Methods: Baseline gadolinium-enhancing T1-lesion volumes were used to statistically model the expected level of MRI disease activity post-SDD.

Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial.

Background: No treatments have been approved for primary progressive multiple sclerosis. Fingolimod, an oral sphingosine 1-phosphate receptor modulator, is effective in relapse-onset multiple sclerosis, but has not been assessed in primary progressive multiple sclerosis. We assessed the safety and efficacy of fingolimod in patients with primary progressive multiple sclerosis.

Longitudinal changes in self-reported walking ability in multiple sclerosis.

Background: Patient-reported outcomes are increasingly used to understand the clinical meaningfulness of multiple sclerosis disability and its treatments. For example, the 12-item Multiple Sclerosis Walking Scale (MSWS-12) measures the patient-reported impact of the disease on walking ability.

Objective: We studied longitudinal changes in walking ability using the MSWS-12 in a cohort of 108 patients with relapsing-remitting multiple sclerosis and moderate-to-severe disability from a single US center cohort study investigating multiple sclerosis symptoms and physical activity.

Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management.

Importance: Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity.

Objective: To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management.

Design, Setting, And Participants: Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants).

Timed 25-foot walk: direct evidence that improving 20% or greater is clinically meaningful in MS.

Objective: In this study, we used data from clinical trials of dalfampridine (fampridine outside the United States) to re-examine the clinical meaningfulness of Timed 25-Foot Walk (T25FW) changes.

Methods: Pooled data were analyzed from 2 phase III randomized placebo-controlled clinical trials of dalfampridine in multiple sclerosis (MS) (n = 533). Walking speed (T25FW) and patient-reported walking ability (MS Walking Scale-12 [MSWS-12]) were measured, concurrently, multiple times before and during treatment.

Historical overview of the rationale for the pharmacological use of prolonged-release fampridine in multiple sclerosis.

Multiple sclerosis is a progressive demyelinating neurological disease resulting in long-term disability, commonly manifesting in walking impairment and reduced quality of life. The use of the potassium channel blocker fampridine, chemically 4-aminopyridine, as an immediate-release formulation to improve action potential conduction in demyelinated axons was hampered by adverse events, including seizures. The prolonged-release formulation of fampridine (known as modified- or sustained-release fampridine in some countries and dalfampridine extended release in the USA) has a longer apparent half-life and a lower peak plasma concentration versus immediate-release fampridine formulations, sustaining its duration of action and reducing the incidence of adverse events.

The interferon beta therapies for treatment of relapsing-remitting multiple sclerosis: are they equally efficacious? A comparative review of open-label studies evaluating the efficacy, safety, or dosing of different interferon beta formulations alone or in combination.

Interferon beta preparations are the most widely used initial therapies prescribed for patients with relapsing-remitting multiple sclerosis. Phase III studies have demonstrated comparable efficacy on clinical measures of disease activity, variable benefits on radiological measures, and good overall tolerability. Subsequent clinical studies have attempted to compare directly the three available interferon beta preparations, reporting both safety and efficacy data.

Fatigue and progression of corpus callosum atrophy in multiple sclerosis.

Fatigue is one of the most disabling symptoms in multiple sclerosis (MS) patients. There is no or only weak correlation between conventional magnetic resonance imaging (MRI) parameters and level of fatigue. The aim of this study was to investigate the relationship between progression of corpus callosum (CC) atrophy and fatigue in MS patients.

Vitamin D levels in Swiss multiple sclerosis patients.

Background: Vitamin D levels have not been previously published for Swiss multiple sclerosis (MS) patients. An association between vitamin D status and disease activity in MS has been suggested.

Aim: To define 25-hydroxy-vitamin D (25(OH)D) levels in Swiss multiple sclerosis patients.

Headache in multiple sclerosis.

Pain, including headache, is a frequent complaint of individuals with multiple sclerosis (MS). Prevalence of headache in patients with MS was reported to be higher than 50%, but it is uncertain if this is different than what is seen in the general population. Nonetheless, it is possible that MS and headaches are comorbid.

Effects of natalizumab on circulating B cells, T regulatory cells and natural killer cells.

Background: Natalizumab is a humanized monoclonal antibody directed against very late activation antigen 4 (VLA-4) and has a potent effect on disease activity in multiple sclerosis. Blockade of VLA-4 with natalizumab may not only interfere with autoimmunological mechanisms but also with central nervous system immune surveillance.

Methods: Longitudinal ex vivo and in vitro study to determine the effect of natalizumab on the frequency of distinct immune cells and on the frequency and suppressive function of natural CD4+CD25+ regulatory T cells (Tregs).

Corpus callosum index and long-term disability in multiple sclerosis patients.

Prediction of long-term disability in patients with multiple sclerosis (MS) is essential. Magnetic resonance imaging (MRI) measurement of brain volume may be of predictive value but sophisticated MRI techniques are often inaccessible in clinical practice. The corpus callosum index (CCI) is a normalized measurement that reflects changes of brain volume.

Natalizumab reduces clinical and MRI activity in multiple sclerosis patients with high disease activity: results from a multicenter study in Switzerland.

Background: Natalizumab has been recommended for the treatment of relapsing-remitting multiple sclerosis (RRMS) in patients with insufficient response to interferon-beta or glatiramer acetate (disease-modifying treatments-DMT) or in aggressive MS. The pivotal trials were not designed to investigate natalizumab monotherapy in these patient populations.

Aim: To investigate the efficacy of natalizumab after treatment failure of previous DMT and in highly active MS.

Fatigue is not associated with impaired function of regulatory T cells in untreated patients with multiple sclerosis.

Background: The pathophysiology of multiple sclerosis (MS)-associated fatigue is poorly understood. Immunological mechanisms may play a role. Alterations in immunological profile indicate a chronic immune activation in MS patients with fatigue.

Multiple sclerosis associated fatigue during natalizumab treatment.

Objective: To assess multiple sclerosis (MS) associated fatigue after the first 6 months of natalizumab treatment.

Methods: Prospective, open-label, uncontrolled study. Fatigue was measured before treatment initiation and at month 6 with the Modified Fatigue Impact Scale (MFIS) and the Fatigue Severity Scale (FSS) in 42 patients.

Natalizumab in the treatment of multiple sclerosis.

Natalizumab reduced the rate of clinical relapse at one year by 68% and the risk of sustained progression of disability by 42-54% over 2 years in its pivotal phase III trial (AFFIRM) in relapsing-remitting multiple sclerosis (RRMS). Natalizumab is generally well tolerated, but due to rare and potentially fatal side-effects, it was approved with a restricted-distribution format in 2006. Expert statements and the European Medical Agency recommend the use of natalizumab after failure of first-line disease-modifying therapies in patients with relapsing forms of MS.

Mitoxantrone does not restore the impaired suppressive function of natural regulatory T cells in patients suffering from multiple sclerosis. A longitudinal ex vivo and in vitro study.

CD4+CD25+ regulatory T (T(reg)) cells play a major role in controlling autoimmunity by suppressing self-reactive T cells. Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system, where T cells are of major importance. T(reg) cell frequency and function are potential therapeutic targets of MS treatment.

Habituation of the auditory startle response in cervical dystonia and Parkinson's disease.

The auditory startle response (ASR) is a brainstem reflex elicited by an unexpected acoustic stimulus. In focal dystonia (FD), the excitability of brainstem neurons is abnormally enhanced. To identify a possible impact of this pathology on the processing of acoustic stimuli, we studied the habituation of the ASR in patients (n = 11) with FD and compared the findings to those of patients with Parkinson's disease (PD; n = 11) and controls (n = 11).