Identification and validation of clinically meaningful benchmarks in the 12-item Multiple Sclerosis Walking Scale.

BACKGROUND: The 12-item Multiple Sclerosis Walking Scale (12-MSWS) is a validated questionnaire which assessed walking function; it has been widely adopted in multiple sclerosis (MS) clinical research. OBJECTIVE: Identify and validate clinically meaningful 12-MSWS benchmarks in MS. METHODS: Cross-sectional study of 159 MS patients permitted identification of clinically meaningful 12-MSWS benchmarks based on their relationship to real-life anchors. Identified 12-MSWS benchmarks were then validated in a second population of 96 subjects using measures of ambulation, cognition, and patient-reported outcomes. RESULTS: 12-MSWS score of 0-24.99 was associated with working outside the home and assistance-free mobility; 25-49.99 was associated with gait disability and difficulty doing housework; 50-74.99 was associated with unemployment, government healthcare, cane use, and difficulty performing instrumental activities of daily living (IADLs); and 75-100 was associated with change in occupation due to walking, mobility impairment requiring bilateral assistance, and inability to perform IADLs. During the validation step, strong linear associations were identified between 12-MSWS benchmarks and other MS-related disability outcome measures, including ambulatory and non-ambulatory measures. CONCLUSION: We have identified clinically meaningful 12-MSWS benchmarks which define four groups differentiated by increasing levels of mobility impairment and associated loss of functional independence. These data provide insight into how 12-MSWS translate to meaningful functional limitations in MS.

Cryptococcal meningitis after fingolimod discontinuation in a patient with multiple sclerosis.

Fingolimod (Gilenya, Novartis) is an oral sphingosine-1-phosphate analogue used in the treatment of relapsing multiple sclerosis (MS). Fingolimod treatment is associated with relative lymphopenia and was associated with an increased risk of herpes infection in clinical trials. In the post-marketing setting, fingolimod has been associated with several cases of cryptococcal meningitis, recently prompting an update to its prescribing information. To date, all cases have been associated with active treatment with fingolimod. In this report, we describe the first case of cryptococcal meningitis diagnosed after fingolimod discontinuation.

Overview and safety of fingolimod hydrochloride use in patients with multiple sclerosis.

INTRODUCTION: Fingolimod (Gilenya®, FTY720) is an oral sphingosine-1-phosphate analogue that was approved by the FDA in 2010 for the treatment of relapsing forms of multiple sclerosis (MS). Fingolimod's mechanism of action is primarily related to lymphocyte sequestration in primary and secondary lymphoid tissues. Phase III trials demonstrated a reduction in annualized relapse rate and MRI progression in fingolimod-treated subjects compared with both placebo and IFN-ß-treated subjects. Frequent adverse effects include fatigue, gastrointestinal disturbance, headache and upper respiratory tract infection. More serious, but rare, adverse events associated with fingolimod include atrioventricular block, symptomatic bradycardia, herpetic viral infections and macular edema. AREAS COVERED: We discuss the mechanism of action, pharmacokinetics, clinical efficacy and safety profile of fingolimod in patients with relapsing MS. EXPERT OPINION: Fingolimod is an effective treatment for relapsing MS and its oral route of administration may be preferred by some. Fingolimod is generally well tolerated but requires diligence in patient selection and monitoring. Additional information is needed regarding risk of infection, malignancy and rebound disease with long-term use of fingolimod.