Dataset Information

Analysis of IL-6, IL-1? and TNF-? production in monocytes isolated from multiple sclerosis patients treated with disease modifying drugs.

ABSTRACT: OBJECTIVE AND DESIGN:The etiology of multiple sclerosis (MS) is unknown, but blood derived monocytes/macrophages are believed to be involved in the pathogenesis through phagocytosis of myelin and production of inflammatory mediators. The objective of this study is to examine inflammatory cytokines that are present at elevated levels in active MS lesions to determine whether there are differences between classically stimulated monocytes isolated from healthy control (HC) and relapsing-remitting MS (RRMS) subjects taking disease modifying drugs (DMDs), including dimethyl fumarate (DMF). SUBJECTS:Thirty-nine veterans of the US Armed Forces were enrolled, 21 health controls (HC), and 18 with relapsing-remitting MS (RRMS), all taking DMDs. METHODS:Use ELISAs to measure production of IL-6, IL-1? and TNF-? by LPS-stimulated peripheral monocytes. RESULTS:Activation of monocytes from MS subjects produced significantly more IL-6 than healthy controls (49531 ± 20795 vs 10526 ± 4845), and IL-6 production trended higher in MS subjects taking DMF than those taking other DMDs (72186.9 ± 35156.2 vs 32585.8 ± 17135.4). There were no significant differences in IL-1? or TNF-? secretion. CONCLUSIONS:Our data suggest that not all DMDs may provide disease modification by suppressing monocyte/macrophage production of pro-inflammatory mediators.

SUBMITTER: Fiedler SE

PROVIDER: S-EPMC5621757 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Analysis of IL-6, IL-1β and TNF-α production in monocytes isolated from multiple sclerosis patients treated with disease modifying drugs.

Fiedler Sarah E SE George Joshua D JD Love Haley N HN Kim Edward E Spain Rebecca R Bourdette Dennis D Salinthone Sonemany S

Journal of systems and integrative neuroscience 20170501 3

<h4>Objective and design</h4>The etiology of multiple sclerosis (MS) is unknown, but blood derived monocytes/macrophages are believed to be involved in the pathogenesis through phagocytosis of myelin and production of inflammatory mediators. The objective of this study is to examine inflammatory cytokines that are present at elevated levels in active MS lesions to determine whether there are differences between classically stimulated monocytes isolated from healthy control (HC) and relapsing-rem ...[more]

PMID: 28966794

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Project description:OBJECTIVE:To summarize major clinical trials which evaluate the efficacy and safety data of approved disease modifying agents for the treatment of various types of multiple sclerosis. DATA SOURCES:A MEDLINE (1966 to August 2008) search of clinical trials using the terms multiple sclerosis, interferon, glatiramer, mitoxantrone and natalizumab was performed. A manual bibliographic search was also conducted. English-language articles identified from the searches were evaluated. New agents under investigation in phase 3 clinical trials were identified using www.clinicaltrials.gov. STUDY SELECTION #ENTITYSTARTX00026; DATA EXTRACTION:Relevant information was identified and selected based on clinical relevance and evidence-based strength. Prescribing information leaflets were used to provide usual dosage, contraindications, precautions, monitoring parameters and other relevant drug-specific information. DATA SYNTHESIS:Interferon beta products are more efficacious for the treatment of relapsing-remitting multiple sclerosis. Interferon beta 1-b also delayed the time to diagnosis of definite multiple sclerosis and reduced brain lesion burden in patients with clinical isolated syndrome. Glatiramer and natalizumab have both established efficacy in relapsing forms of multiple sclerosis; whereas mitoxantrone is more commonly used in patients with advanced disease. There are limited data the comparative efficacy among different disease modifying agents. New agents currently under investigation have showed promising results and may offer more treatment options in the future. CONCLUSIONS:MS is a complex and devastating disease with challenging treatment considerations and approaches. Interferon beta products continue to be the mainstay of therapy in many patients, however, other treatments are proving to be at least as effective in the management of various types of MS. Newer compounds are being developed and studied with much anticipation and promise for the clinical management of the disease.

Project description:BackgroundAdministrative healthcare claims data provide a mechanism for assessing and monitoring multiple sclerosis (MS) disease status across large, clinically representative "real-world" populations. The estimation of MS disease status using administrative claims can be a challenge, however, due to a lack of detailed clinical information. Retrospective claims analyses in MS have traditionally used rates of MS relapses to approximate disease status. Healthcare costs may be alternate, broader claims-based indicators of disease activity because costs reflect multiple facets of care of patients with MS, and there is a strong correlation between quality of life of patients with MS and costs of the disease. This study developed, tested, and validated a healthcare cost-based measure to serve as an indicator of overall disease status in patients with MS treated with disease-modifying drugs (DMDs) utilizing administrative claims.MethodsUsing IMS Health Real World Data Adjudicated Claims - US data (January 2006-June 2013), a negative binomial regression predicted annual all-cause medical costs. Coefficients reaching statistical significance (p < 0.05) and increasing costs by ?5% were selected for inclusion into an MS-specific severity score (scale of 0 to 100). Components of the score included rehabilitation services, altered mental state, pain, disability, stiffness, balance disorder, urinary incontinence, numbness, malaise/fatigue, and infections. Coefficient weights represented each predictor's contribution. The predictive model was derived using 50% of a random sample and tested/validated using the remaining 50%.ResultsAverage overall predicted annual total medical cost was $11,134 (development sample, n = 11,384, vs. $10,528 actual) and $11,303 (validation sample, n = 11,385, vs. $10,620 actual). The model had consistent bias (approximately +$600 or +6% of actual costs) for both samples. In the validation sample, mean MS disease status scores were 0.24, 8.95, and 21.77 for low, medium, and high tertiles, respectively. Mean costs were most accurately predicted among less severe patients ($5243 predicted vs. $5233 actual cost for lowest tertile).ConclusionThe algorithm developed in this study provides an initial step to helping understand and potentially predict cost changes for a commercially insured MS population.

Dataset Information

Analysis of IL-6, IL-1? and TNF-? production in monocytes isolated from multiple sclerosis patients treated with disease modifying drugs.

Publications

Analysis of IL-6, IL-1β and TNF-α production in monocytes isolated from multiple sclerosis patients treated with disease modifying drugs.

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