Dataset Information

Immunotherapy of experimental and human stroke with agents approved for multiple sclerosis: a systematic review.

ABSTRACT: Background:'Thromboinflammation' describes a novel concept in stroke pathophysiology that has opened up the possibility of immunotherapeutic approaches which could become promising strategies for targeted stroke therapies in the future. Methods:We reviewed current evidence for agents approved for multiple sclerosis in preclinical and clinical stroke studies. A systematic review was performed in accordance with the PRISMA statement, searching MEDLINE, the Cochrane Central Register of Controlled Trials, and reference lists of articles published until 16 October 2017. Results:The review included 52 of 629 identified studies, consisting of 5 clinical and 47 preclinical trials. Most of the studies showed beneficial effects of the evaluated immunotherapeutic drugs in terms of reduction in morphological lesion size and improvement in functional outcome. Nevertheless, the significance of these findings is limited due to the high degree of heterogeneity. Conclusions:Immunotherapy of stroke might be effective and could become a promising treatment strategy, but larger clinical trials with standardized interventions and outcome measures are needed.

SUBMITTER: Dreikorn M

PROVIDER: S-EPMC5949925 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immunotherapy of experimental and human stroke with agents approved for multiple sclerosis: a systematic review.

Dreikorn Mirjam M Milacic Zeljko Z Pavlovic Vladimir V Meuth Sven G SG Kleinschnitz Christoph C Kraft Peter P

Therapeutic advances in neurological disorders 20180420

<h4>Background</h4>'Thromboinflammation' describes a novel concept in stroke pathophysiology that has opened up the possibility of immunotherapeutic approaches which could become promising strategies for targeted stroke therapies in the future.<h4>Methods</h4>We reviewed current evidence for agents approved for multiple sclerosis in preclinical and clinical stroke studies. A systematic review was performed in accordance with the PRISMA statement, searching MEDLINE, the Cochrane Central Register ...[more]

PMID: 29774055

Similar Datasets

Project description:BackgroundMultiple sclerosis (MS) and stroke are two common causes of death and disability worldwide. The relationship between these two diseases remains unclear. Effective early preventative measures and treatments are available to reduce the morbidity and mortality of acute stroke. The objectives of our systematic review are to estimate the risk of stroke in patients with MS and to collate related studies to draw preliminary conclusions that may improve clinical practice.MethodRelevant studies were systematically searched in MEDLINE, Embase, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure and the VIP database of Chinese periodicals from January 1983 to May 2017, with no restrictions on language. Patients included in this review were adults who suffered from MS. Review Manager 5.3 software program was used to pool data and calculate the risk ratio (RR) and its 95% confidence interval (CI). We also performed heterogeneity and sensitivity analyses and evaluated bias in the meta-analysis.ResultsNine studies including more than 380,000 participants that met our inclusion criteria were incorporated into the meta-analysis. During different follow-up periods, patients with MS had an increased risk of any type of stroke [RR = 3.48, 95% CI (1.59, 7.64), P = 0.002 for 1 year; RR = 2.45, 95% CI (1.90, 3.16), P < 0.00001 for 10-13 years]. The total prevalence of stroke (any type) in patients with MS exceeded expectations compared to different groups [Comparing with general veteran: RR = 2, 95% CI (1.19, 3.38), P = 0.009. Comparing with general population: RR = 2.93, 95% CI (1.13, 7.62), P = 0.03]. Furthermore, ischemic stroke was particularly more common in the MS population than in people without MS [RR = 6.09, 95% CI (3.44, 10.77), P < 0.00001].ConclusionCompared with the general population, people with MS have an increased risk of developing any type of stroke and ischemic stroke in particular. Consistent results were obtained from patients of different sexes and age groups. Preventative measures and treatments should be administered at earlier time points to improve patient outcomes.

Project description:Background: Over the past two decades, various novel disease-modifying drugs for multiple sclerosis (MS) have been approved. However, there is high variability in the patient response to the available medications, which is hypothesized to be partly attributed to genetics. Objectives: To conduct a systematic review of the current literature on the pharmacogenomics of MS therapy. Methods: A systematic literature search was conducted using PubMed/MEDLINE database searching for articles investigating a role of genetic variation in response to disease-modifying MS treatments, published in the English language up to October 9th, 2018. PRISMA guidelines for systematic reviews were applied. Studies were included if they investigated response or nonresponse to MS treatment defined as relapse rate, by expanded disability status scale score or based on magnetic resonance imaging. The following data were extracted: first author's last name, year of publication, PMID number, sample size, ethnicity of patients, method, genes, and polymorphisms tested, outcome, significant associations with corresponding P-values and confidence intervals, response criteria, and duration of the follow-up period. Results: Overall, 48 articles published up to October 2018, evaluating response to interferon-beta, glatiramer acetate, mitoxantrone, and natalizumab, met our inclusion criteria and were included in this review. Among those, we identified 42 (87.5%) candidate gene studies and 6 (12.5%) genome-wide association studies. Existing pharmacogenomic evidence is mainly based on the results of individual studies, or on results of multiple studies, which often lack consistency. In recent years, hypothesis-free approaches identified novel candidate genes that remain to be validated. Various study designs, including the definition of clinical response, duration of the follow-up period, and methodology as well as moderate sample sizes, likely contributed to discordances between studies. However, some of the significant associations were identified in the same genes, or in the genes involved in the same biological pathways. Conclusions: At the moment, there is no available clinically actionable pharmacogenomic biomarker that would enable more personalized treatment of MS. More large-scale studies with uniform design are needed to identify novel and validate existing pharmacogenomics findings. Furthermore, studies investigating associations between rare variants and treatment response in MS patients, using next-generation sequencing technologies are warranted.

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.

Dataset Information

Immunotherapy of experimental and human stroke with agents approved for multiple sclerosis: a systematic review.

Publications

Immunotherapy of experimental and human stroke with agents approved for multiple sclerosis: a systematic review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets