The importance of long-term data in multiple sclerosis

Abstract

■ Abstract Natural history studies provide important information on the prognosis of multiple sclerosis and on risk factors for long-term outcome and thus help orientate treatment decisions and design clinical trials. Before the introduction of disease-modifying treatment, large longitudinal natural history studies described the typical clinical course of multiple sclerosis and identified landmark events in disease progression, for example that 50 % of patients with relapsing-remitting multiple sclerosis are unable to walk unaided 15 years after disease onset. A large observational natural history study performed in Barcelona following outcome after the first presentation with a clinically isolated syndrome revealed that patients presenting initially with optic neuritis were less likely to progress to clinically definite multiple sclerosis than other patients. This finding could be explained by a lower lesion load on cranial MRI. Initial lesion load also appeared to be an important determinant of future disability. These and other similar data suggest that the development of lesions early in the disease process has an important influence on long-term disability. Since the advent of disease-modifying treatments in multiple sclerosis, this natural history can also help define criteria for determining treatment failure. An analysis of a cohort of patients treated with β-interferons revealed that progression of EDSS disability scores during the first two years of treatment could predict treatment failure at six years (three points worsening in EDSS score since treatment initiation) with an accuracy of 92 %. Early progression of EDSS scores was itself associated with early accumulation of lesion load visible on MRI. Rate of accumulation of lesion load after first symptom presentation may thus be a useful marker of poor prognosis that could be considered an indicator of the need for intensive treatment. Initial long-term outcome data obtained with immunomodulatory treatments is consistent with the notion that these treatments improve the long-term prognosis. If this is confirmed, then a first step towards the goal of limiting irreversible disability in patients with multiple sclerosis will have been made.