Trends in Efficacy, Safety, and Tolerability of Approved Multiple Sclerosis Disease Modifying Treatments

Abstract

AbstractBackgroundDisease-modifying therapies (DMTs) have become the mainstay of treatment for relapsing forms of multiple sclerosis (MS), reducing relapse rates and slowing disease progression.ObjectivesTo determine whether or not available MS DMTs have demonstrated an increase in safety, efficacy, and tolerability over time.MethodsResults from pivotal phase III trials of approved MS DMTs were used to create a dataset of relevant outcomes. Common endpoints analyzed include annualized relapse rates (ARR), rates of serious adverse events (SAE), and rates of discontinuation due to adverse events. Trial comparator, active or placebo, was also documented. Descriptive statistics and Fisher exact tests were performed on outcomes stratified by recency of pivotal trials.ResultsOn visual inspection, there was a trend of decrease in ARR. A significant relationship was seen between recent approvals and trial design with an active comparator (p=0.004), as well as between recent approvals and ARR (p=0.020). No significance was found between recent approvals and SAE (p=0.138), formulation and discontinuation (p=0.559), or recent approvals and formulation (p=0.352).ConclusionDMTs for relapsing forms of MS increased in efficacy over time. Oral therapies offered similar tolerability to other routes of administration. Further research is warranted to identify if these clinical trial findings translate to real world evidence.What was already knownThe number of FDA approved disease-modifying therapies for multiple sclerosis has been steadily increasing. Available routes of administration include injectable, oral, and infusions.These medications are proven to be effective in reducing MS relapse rates and slowing overall disease progression, with varying degrees of safety and tolerability.The comparative efficacy of these therapies varies, with certain medications often deemed high efficacy.What this study addsWe used published phase III trial results for each medication to provide a direct comparison between each medication’s efficacy, safety, and tolerability at time of approval.Our analysis demonstrates a trend in increasing efficacy of available therapies along with the use of active comparators for controls in disease modifying treatments for multiple sclerosis.