Glatiramer acetate (Copaxone ® Glatopa ®)Įurope: second-line treatment or rapidly evolving severe RRMS Oral DMTs such as teriflunomide, dimethyl fumarate, and fingolimod offer a convenient route of administration, while peginterferon beta, daclizumab beta, ocrelizumab, and alemtuzumab provide a lower dosing frequency, being dosed once every 2 weeks, monthly, every 6 months, and annually, respectively. While there may be differences in their relative efficacy, additional head-to-head clinical trials, particularly comparator studies between oral DMTs, are required to confirm and quantify this assertion. Several of the new DMTs have demonstrated superior efficacy over either interferon beta or glatiramer acetate in Phase III studies of patients with RMS (Table 3). Since 2010, new disease-modifying therapies (DMTs) have emerged 13 approved DMTs are currently available to treat RMS worldwide (Table 1), which target different pathways of the immune system (Table 2).
For this reason, historically, natalizumab was generally reserved for patients requiring higher efficacy than interferon beta and glatiramer acetate, and, more recently in the US, only when the expected benefit is sufficient to offset PML risk. Natalizumab is more efficacious than interferon beta and glatiramer acetate, but has a complex safety profile due to the risk of progressive multifocal leukoencephalopathy (PML). Conversely, the safety of interferon beta and glatiramer acetate over two decades is highly favorable and the relative risk for immunologic complications is low. However, a high proportion of patients experience breakthrough disease or have persistent clinical or radiologic disease activity within 2 years of treatment initiation of these agents. The beta interferons and glatiramer acetate have comparable long-term safety profiles and efficacy, reducing the frequency of relapses by ~30% over a 2- to 3-year treatment period, as evaluated in clinical trials. ĭespite the heterogeneity in MS disease course, selecting an appropriate therapy for relapsing forms of MS (RMS) before the approval of fingolimod in 2010 was relatively simple because neurologists had two main treatment options: interferon beta/glatiramer acetate or natalizumab. A range of genetic, immunopathologic, and environmental/epigenetic factors drive the tremendous variability in the type, frequency, and severity of signs and symptoms that may present during the course of MS. The unpredictable nature of multiple sclerosis (MS) clinical manifestations within and between patients with apparently similar characteristics is brought about by a complex and dynamic pathophysiology involving inflammatory-based mechanisms of demyelination and axon loss.
This review is intended to help neurologists make informed decisions when treating RMS by summarizing the known data for each DMT and raising awareness of the multiple considerations involved in treating people with RMS throughout the entire course of their disease.
A comprehensive benefit–risk assessment can only be achieved by evaluating the immunologic, safety, and efficacy data for DMTs in the controlled clinical trial environment and the postmarketing clinical practice setting. When customizing a treatment program, a benefit–risk assessment must consider multiple factors, including the efficacy of the DMT to reduce disease activity, the short- and long-term safety and immunologic profiles of each DMT, the criteria used to define switching treatment, and the risk tolerance of each patient. However, some DMTs are associated with long-lasting effects on the immune system and/or serious adverse events, both of which may complicate the use of subsequent therapies. All DMTs for RMS are believed to reduce central nervous system immune-mediated inflammatory processes, which translate into demonstrable improvement in clinical and radiologic outcomes. The treatment landscape for relapsing forms of multiple sclerosis (RMS) has expanded considerably over the last 10 years with the approval of multiple new disease-modifying therapies (DMTs), and others in late-stage clinical development.