ABSTRACT
BACKGROUND: Walking impairment causes disability and reduced quality of life in patients with multiple sclerosis (MS). OBJECTIVE: Characterize the safety and efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered once daily at bedtime in patients with MS with walking impairment. METHODS: This randomized, double-blind, placebo-controlled, 4-week study was conducted at 14 trial sites in the United States. Study objectives included safety and tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW), Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale-12). Fatigue, depression, and cognition also were assessed. RESULTS: A total of 60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were treated. The most frequent adverse events (AEs) were dry mouth, constipation, and insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment due to AEs. One patient in the ADS-5102 group experienced a serious AE-suspected serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW test ( p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No changes in fatigue, depression, or cognition were observed. CONCLUSION: ADS-5102 was generally well tolerated. These data demonstrate an effect of ADS-5102 on walking speed. Further studies are warranted to confirm these observations.
Subject(s)
Amantadine/pharmacology , Dopamine Agents/pharmacology , Dyskinesias/drug therapy , Multiple Sclerosis/drug therapy , Outcome Assessment, Health Care , Walking , Adult , Aged , Amantadine/administration & dosage , Amantadine/adverse effects , Delayed-Action Preparations , Dopamine Agents/administration & dosage , Dopamine Agents/adverse effects , Double-Blind Method , Dyskinesias/etiology , Dyskinesias/physiopathology , Exercise Test , Female , Humans , Male , Middle Aged , Multiple Sclerosis/complications , Multiple Sclerosis/physiopathology , Proof of Concept StudyABSTRACT
OBJECTIVE: To establish whether the analysis of whole-blood gene expression is useful in predicting or monitoring response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). METHODS: Whole-blood RNA (using a PAXgene system to stabilize whole-blood RNA in the collection tube) was obtained at baseline and at 14 weeks from 3 independent cohorts, consisting of a combined total of 240 RA patients who were beginning therapy with anti-TNF. We used an approach to gene expression analysis that is based on modular patterns of gene expression, or modules. RESULTS: Good and moderate responders according to the European League Against Rheumatism criteria exhibited highly significant and consistent changes in multiple gene expression modules after 14 weeks of therapy, as demonstrated by hypergeometric analysis. Strikingly, nonresponders exhibited very little change in any modules, despite exposure to TNF blockade. These patterns of change were highly consistent across all 3 cohorts, indicating that immunologic changes after TNF treatment are specific to the combination of both drug exposure and responder status. In contrast, modular patterns of gene expression did not exhibit consistent differences between responders and nonresponders at baseline in the 3 study cohorts. CONCLUSION: These data provide evidence that using gene expression modules related to inflammatory disease may provide a valuable method for objective monitoring of the response of RA patients who are treated with TNF inhibitors.
Subject(s)
Antirheumatic Agents/pharmacology , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/genetics , Gene Expression Regulation/drug effects , RNA/blood , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adult , Aged , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology , Antibodies, Monoclonal, Humanized/therapeutic use , Arthritis, Rheumatoid/blood , Cohort Studies , Dose-Response Relationship, Drug , Etanercept , Female , Gene Expression Regulation/genetics , Humans , Immunoglobulin G/pharmacology , Immunoglobulin G/therapeutic use , Infliximab , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , RNA/genetics , Receptors, Tumor Necrosis Factor/therapeutic use , Treatment OutcomeABSTRACT
Quantification of HIV-1 RNA levels is a vital tool in the medical management of individuals infected with HIV. The commercially available US Federal Drug Administration (FDA)-approved assays vary in their ability to accurately measure and detect significant changes in plasma viral load. A more precise assay can accurately distinguish true clinically significant biologic changes in viral plasma load from background noise, or systematic variation. These differences in precision between assays are profound at low, near-cutoff levels, but also occur throughout the dynamic range of the assays. This review examines the precision specifications, expressed as fold changes in test and retesting, across the dynamic ranges of the Bayer Versant bDNA assay, and the two available versions of the Roche Amplicor Monitor PCR assays. Highly validated data from their respective package inserts are analyzed to confirm each assay's performance throughout its dynamic range. The precision of a viral load assay is critical to patient management, and gives the clinician a clearer picture of the patient's true virologic status that is attributable to infection or treatment as opposed to systematic variation in assays.
