Diagnosis and treatment of progressive multiple sclerosis: A position paper

Background and Purpose Multiple sclerosis (MS) is an unpredictable disease characterised by a highly variable disease onset and clinical course. Three main clinical phenotypes have been described. However, distinguishing between the two progressive forms of MS can be challenging for clinicians. This article examines how the diagnostic definitions of progressive MS impact clinical research, the design of clinical trials and, ultimately, treatment decisions. Methods We carried out an extensive review of the literature highlighting differences in the definition of progressive forms of MS, and the importance of assessing the extent of the ongoing inflammatory component in MS when making treatment decisions. Results Inconsistent results in phase III clinical studies of treatments for progressive MS, may be attributable to differences in patient characteristics (e.g., age, clinical and radiological activity at baseline) and endpoint definitions. In both primary and secondary progressive MS, patients who are younger and have more active disease will derive the greatest benefit from the available treatments. Conclusions We recommend making treatment decisions based on the individual patient's pattern of disease progression, as well as functional, clinical and imaging parameters, rather than on their clinical phenotype. Because the definition of progressive MS differs across clinical studies, careful selection of eligibility criteria and study endpoints is needed for future studies in patients with progressive MS.

Automated summary

This article examines the impact of diagnostic definitions of progressive multiple sclerosis (MS) on clinical research, clinical trial design, and treatment decisions. The results show that inconsistent results in clinical studies of treatments for progressive MS may be attributed to differences in patient characteristics and endpoint definitions. Younger patients with more active disease are likely to benefit the most from available treatments. Therefore, treatment decisions should be based on individual patient's disease progression pattern and parameters, rather than their clinical phenotype. Careful selection of eligibility criteria and study endpoints is necessary for future studies in patients with progressive MS.