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The first disease-modifying therapy for relapsing–remitting multiple sclerosis — interferon‑β 1b — was approved by the FDA in 1993. The following 25 years have seen rapid expansion of the therapeutic options as an evolving understanding of the disease has enabled development of therapies with different modes of action. As a result, we now have a complex treatment landscape that includes various injectables, oral drugs and monoclonal antibodies, each of which has its own advantages and risks. This Milestone tracks the development of the treatment of multiple sclerosis on an interactive Timeline, from the approval of the first disease-modifying therapy to the latest breakthroughs that have seen unprecedented efficacy and approval of the first drug for primary progressive multiple sclerosis.
This Milestone is editorially independent, produced with financial support from a third party.
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The development of treatment for multiple sclerosis over the past 25 years is a success of translational medicine. In this Timeline article, Tintore et al. chart major developments and discuss the implications for current and future patient management.
In clinical trials, outcome measures might determine whether a drug is worthy of further development; in the clinic, they might guide important treatment decisions. Here, Tur and colleagues help clinicians and researchers navigate the maze of options for clinical, neuroimaging, patient-reported and composite outcome measures in multiple sclerosis.
The benefits of early treatment for multiple sclerosis (MS) place pressure on physicians to make the diagnosis early, thereby increasing the risk of misdiagnosis, which can have considerable consequences for patients and health-care systems. Solomon and Corboy examine the problem of MS misdiagnosis, including the probable causes and associated risks, and discuss how the tension between early diagnosis and misdiagnosis might be addressed.
Autologous haematopoietic stem cell transplantation has produced striking results in patients with aggressive multiple sclerosis in small trials. In this Review, Muraro et al. provide an overview of the procedure, detail evidence for its high efficacy in multiple sclerosis, and provide recommendations for its clinical use and future trials.
Real-world observational studies have the potential to answer questions about multiple sclerosis (MS) treatment that randomized controlled trials cannot. Trojano and colleagues discuss the pitfalls and necessary safeguards in observational studies, and the insights that such studies have provided into treatment decisions for patients with MS.
The range of immunomodulatory therapies to treat multiple sclerosis (MS) has widened markedly in recent years, and MS treatments have become more efficient. This improvement in efficacy has been accompanied by an increased risk of treatment-associated infections. In this Review, Winkelman et al. discuss the modes of action of the currently available MS therapies and detail the specific infections associated with each treatment. They consider how this information can influence the daily clinical use of MS therapies, so as to minimize the associated infectious risk.
In this Review, Mishra and Yong consider how myeloid cells — monocytes, macrophages, microglia and dendritic cells — contribute to the pathology of multiple sclerosis (MS). The authors also consider how current multiple sclerosis treatments might directly and indirectly affect these cells.
A subset of patients with multiple sclerosis (MS) demonstrate rapid accumulation of disability, and symptoms that are refractory to standard disease-modifying therapies. Rush and colleagues present criteria for identifying patients with so-called aggressive MS, and outline the efficacy of various therapies in this group of patients. The authors emphasize the need to act quickly with these patients, and propose a treatment algorithm to aid clinical decision-making.
As the range of therapeutic options for multiple sclerosis (MS) continues to expand, the ability to select the most appropriate treatment for each patient becomes increasingly important. In this Review, Sormani and De Stefano assess the studies that have attempted to classify patients with MS on the basis of their response to IFN-β treatment. The authors also discuss the development and use of scoring systems that combine different clinical and MRI markers to aid definition of an early response to this drug.
Increasing evidence supports a role for B cells and antibodies in the pathogenesis of multiple sclerosis (MS). Here, Meinl and colleagues discuss the proinflammatory contribution of B-cell signalling in MS, and consider potential targets of autoantibodies. The B-cell response to various MS therapies is also summarized.
Only moderately effective therapies are currently available for the treatment of multiple sclerosis (MS). New treatments for MS that have neuroprotective properties as well as anti-inflammatory effects are needed. Fingolimod could be one such potential treatment. In this article, Aktas et al. examine the underlying biological actions of this prospective new therapy, review the data from phase II and phase III oral fingolimod clinical trials and provide an update on the emerging field of sphingosine-1-phosphate receptor-mediated therapies for MS.