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Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.

ABSTRACT: Objective:To perform a meta-analysis of randomized, blinded, multiple sclerosis (MS) clinical trials, to test the hypothesis that efficacy of immunomodulatory disease-modifying therapies (DMTs) on MS disability progression is strongly dependent on age. Methods:We performed a literature search with pre-defined criteria and extracted relevant features from 38 clinical trials that assessed efficacy of DMTs on disability progression. We fit a linear regression, weighted for trial sample size, and duration, to examine the hypothesis that age has a defining effect on the therapeutic efficacy of immunomodulatory DMTs. Results:More than 28,000 MS subjects participating in trials of 13 categories of immunomodulatory drugs are included in the meta-analysis. The efficacy of immunomodulatory DMTs on MS disability strongly decreased with advancing age (R2?=?0.6757, p?=?6.39e-09). Inclusion of baseline EDSS did not significantly improve the model. The regression predicts zero efficacy beyond approximately age 53?years. The comparative efficacy rank derived from the regression residuals differentiates high- and low-efficacy drugs. High-efficacy drugs outperform low-efficacy drugs in inhibiting MS disability only for patients younger than 40.5?years. Conclusion:The meta-analysis supports the notion that progressive MS is simply a later stage of the MS disease process and that age is an essential modifier of a drug efficacy. Higher efficacy treatments exert their benefit over lower efficacy treatments only during early stages of MS, and, after age 53, the model suggests that there is no predicted benefit to receiving immunomodulatory DMTs for the average MS patient.

SUBMITTER: Weideman AM

PROVIDER: S-EPMC5686062 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.

Weideman Ann Marie AM Tapia-Maltos Marco Aurelio MA Johnson Kory K Greenwood Mark M Bielekova Bibiana B

Frontiers in neurology 20171110

<h4>Objective</h4>To perform a meta-analysis of randomized, blinded, multiple sclerosis (MS) clinical trials, to test the hypothesis that efficacy of immunomodulatory disease-modifying therapies (DMTs) on MS disability progression is strongly dependent on age.<h4>Methods</h4>We performed a literature search with pre-defined criteria and extracted relevant features from 38 clinical trials that assessed efficacy of DMTs on disability progression. We fit a linear regression, weighted for trial samp ...[more]

PMID: 29176956

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Project description:INTRODUCTION:Cognitive impairment is prevalent and debilitating among persons with multiple sclerosis (MS). While many pharmacologic treatments have shown good efficacy in reducing clinical relapses, brain lesions, and improving certain physical symptoms, their efficacy for improving cognitive function is not well understood. OBJECTIVES:The current systematic review aimed to evaluate the efficacy of pharmacologic treatments for improving cognitive function among persons with MS. METHODS:A literature search was conducted through the PubMed and PsycINFO databases. Two independent reviewers assessed each paper, and a third reviewer weighed in if the two reviewers could not reach a consensus. Classification of evidence was determined using the 2017 American Academy of Neurology (AAN) criteria for therapeutic trials. Standardized effect sizes (Cohen's d) were calculated to compare across studies. RESULTS:Eighty-seven journal articles published between 1990 and January 2020 were included in the current review. Overall, there is insufficient evidence to support the use of pharmacologic treatments to improve cognitive function in persons with MS. There were many contradictory findings observed in this review, which may be due to possible unidentified moderating treatment response variables and/or lack of standardization in assessment procedures. There was also an overreliance on statistical significance (most papers did not provide sizes of treatment effects), which may not be clinically meaningful. CONCLUSIONS:Higher-quality randomized controlled trials are needed to establish the cognitive efficacy of pharmacologic treatments for MS-related cognitive dysfunction, with cognition as the primary endpoint. Researchers are urged to use standardized criteria (such as the AAN criteria) to guide their research designs. Clinicians should consider effect sizes of studies before deciding whether to prescribe certain medications to ameliorate cognitive symptoms.

Project description:ObjectiveThe aim of this study is to create a rank order of the comparative efficacy and acceptability (risk of all-cause discontinuation) of antidepressant treatment in poststroke depression (PSD) by integrating direct and indirect evidence.DesignMultiple-treatments meta-analysis of randomised controlled trials.ParticipantsPatients with depression following stroke.Interventions10 antidepressants and placebo in the acute treatment of PSD.Outcome measuresThe primary outcomes were the overall efficacy, defined as the mean change of the total depression score. The secondary outcome was the acceptability, defined as risk of all-cause discontinuation. These estimates as standardised mean differences or ORs with 95% CIs.ResultsWe identified 12 suitable trials, with data from 707 participants. All drugs were significantly more effective than placebo apart from sertraline, nefiracetam and fluoxetine. Most of the comparisons for acceptability revealed no significant differences except that paroxetine had significantly lower all-cause discontinuation than doxepin, citalopram and fluoxetine. Standardised mean differences compared with placebo for efficacy varied from -6.54 for the best drug (reboxetine) to 0.51 for the worst drug (nefiracetam). ORs compared with placebo for acceptability ranged from 0.09 for the best drug (paroxetine) to 3.42 for the worst drug (citalopram). For the efficacy rank, reboxetine, paroxetine, doxepin and duloxetine were among the most efficacious treatments, the cumulative probabilities of which were 100%, 85.7%, 83.2%, 62.4%, respectively. With respect to the acceptability rank, paroxetine, placebo, sertraline and nortriptyline were among the most acceptable treatments, the cumulative probabilities of which were 92.4%, 63.5%, 57.3%, 56.3%.ConclusionAfter weighing the efficacy and acceptability, we conclude that paroxetine might be the best choice when starting acute treatment for PSD, and fluoxetine might be the worst choice.Trial registration numberThis systematic review has been registered in the Prospective Register of Systematic Review Protocols (PROSPERO) public database (CRD42017054741; http://www.crd.york.ac.uk/PROSPERO).

Dataset Information

Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.

Publications

Meta-analysis of the Age-Dependent Efficacy of Multiple Sclerosis Treatments.

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