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      Oral versus intravenous methylprednisolone for the treatment of multiple sclerosis relapses: A meta-analysis of randomized controlled trials

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          Abstract

          Background

          Intravenous glucocorticoids are recommended for multiple sclerosis (MS). However, they can be inconvenient and expensive. Due to their convenience and low cost, oral glucocorticoids may be an alternative treatment. Recently, several studies have shown that there is no difference in efficacy and safety between oral methylprednisolone (oMP) and intravenous methylprednisolone (ivMP).

          Objectives

          We sought to assess the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses in this meta-analysis.

          Methods

          Randomized controlled trials (RCTs) evaluating the clinical efficacy, safety and tolerability of oral methylprednisolone versus intravenous methylprednisolone for MS relapses were searched in PubMed, Cochrane Library, Medline, EMBASE and China Biology Medicine until October 25, 2016, without language restrictions. The proportion of patients who had improved by day 28 was chosen as the efficacy outcome. We chose the risk ratio (RR) to analyze each trial with the 95% confidence interval (95% CI). We also used the fixed-effects model (Mantel–Haenszel approach) to calculate the pooled relative effect estimates.

          Results

          A total of 5 trials were identified, which included 369 patients. The results of our meta-analysis revealed that no significant difference existed in relapse improvement at day 28 between oMP and ivMP (RR 0.96, 95% CI 0.84 to 1.10). No evidence of heterogeneity existed among the trials (P = 0.45, I 2 = 0%). Both treatments were equally safe and well tolerated except that insomnia was more likely to occur in the oMP group compared to the ivMP group.

          Conclusion

          Our meta-analysis reveals strong evidence that oMP is not inferior to ivMP in increasing the proportion of patients experiencing clinical improvement at day 28. In addition, both routes of administration are equally well tolerated and safe. These findings suggest that we may be able to replace ivMP with oMP to treat MS relapses.

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          Most cited references25

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          Multiple Sclerosis

          New England Journal of Medicine, 343(13), 938-952
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            Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.

            Glucocorticoids have pleiotropic effects that are used to treat diverse diseases such as asthma, rheumatoid arthritis, systemic lupus erythematosus and acute kidney transplant rejection. The most commonly used systemic glucocorticoids are hydrocortisone, prednisolone, methylprednisolone and dexamethasone. These glucocorticoids have good oral bioavailability and are eliminated mainly by hepatic metabolism and renal excretion of the metabolites. Plasma concentrations follow a biexponential pattern. Two-compartment models are used after intravenous administration, but one-compartment models are sufficient after oral administration.The effects of glucocorticoids are mediated by genomic and possibly nongenomic mechanisms. Genomic mechanisms include activation of the cytosolic glucocorticoid receptor that leads to activation or repression of protein synthesis, including cytokines, chemokines, inflammatory enzymes and adhesion molecules. Thus, inflammation and immune response mechanisms may be modified. Nongenomic mechanisms might play an additional role in glucocorticoid pulse therapy. Clinical efficacy depends on glucocorticoid pharmacokinetics and pharmacodynamics. Pharmacokinetic parameters such as the elimination half-life, and pharmacodynamic parameters such as the concentration producing the half-maximal effect, determine the duration and intensity of glucocorticoid effects. The special contribution of either of these can be distinguished with pharmacokinetic/pharmacodynamic analysis. We performed simulations with a pharmacokinetic/pharmacodynamic model using T helper cell counts and endogenous cortisol as biomarkers for the effects of methylprednisolone. These simulations suggest that the clinical efficacy of low-dose glucocorticoid regimens might be increased with twice-daily glucocorticoid administration.
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              Diagnosis and treatment of multiple sclerosis.

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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Project administration
                Role: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Supervision
                Role: ConceptualizationRole: Project administrationRole: Supervision
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                27 November 2017
                2017
                : 12
                : 11
                : e0188644
                Affiliations
                [1 ] Neurology Department, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China
                [2 ] Shantou University Medical College, Shantou, Guangdong, China
                Karolinska Institutet, SWEDEN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-0723-9447
                Article
                PONE-D-17-29987
                10.1371/journal.pone.0188644
                5703548
                29176905
                1239dcc6-1f23-41cd-8b70-c01aa5366e2f
                © 2017 Liu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 August 2017
                : 10 November 2017
                Page count
                Figures: 5, Tables: 1, Pages: 13
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Immunology
                Autoimmune Diseases
                Multiple Sclerosis
                Biology and Life Sciences
                Immunology
                Clinical Immunology
                Autoimmune Diseases
                Multiple Sclerosis
                Medicine and Health Sciences
                Immunology
                Clinical Immunology
                Autoimmune Diseases
                Multiple Sclerosis
                Medicine and Health Sciences
                Neurology
                Demyelinating Disorders
                Multiple Sclerosis
                Medicine and Health Sciences
                Neurology
                Neurodegenerative Diseases
                Multiple Sclerosis
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Research and Analysis Methods
                Research Design
                Clinical Research Design
                Adverse Events
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Medicine and Health Sciences
                Neurology
                Sleep Disorders
                Dyssomnias
                Insomnia
                Medicine and Health Sciences
                Pharmacology
                Routes of Administration
                Oral Administration
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Trials
                Randomized Controlled Trials
                Medicine and Health Sciences
                Pharmacology
                Drug Research and Development
                Clinical Trials
                Randomized Controlled Trials
                Research and Analysis Methods
                Clinical Trials
                Randomized Controlled Trials
                Medicine and Health Sciences
                Pulmonology
                Chronic Obstructive Pulmonary Disease
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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