What is disease progression?

Abstract

The clinical course of multiple sclerosis (MS) represents a spectrum. The subdivision of MS, according to the clinical course, has become increasingly important in recent years, since therapeutic clinical trials have shown demonstrable reductions in the frequency of clinical relapses and of inflammatory lesions as demonstrated on magnetic resonance imaging (MRI). Measures of disease progression are more resistant to change and in patients with progressive MS, it has been more difficult to demonstrate positive benefits from therapeutic interventions. It has long been recognized that although patients may essentially share the diagnostic label of MS, there is considerable variation across a spectrum in terms of clinical phenotype, prognosis, MRI appearances, immunological characteristics, and pathology. The nature of the clinical course may also determine the response to disease-modifying therapy and the course itself may be influenced by underlying genetic heterogeneity. In approximately 85-90% of cases, the onset of MS is marked by relapses and remissions-relapsing-remitting MS (RRMS). With time, an increasing proportion of these patients enter a secondary progressive phase (SPMS), 40% within 10 years and 65% within 25 years. SPMS represents a phase during which there are generally fewer relapses. It is characterized by gradual progression in disability. A minority of patients, 10-15%, do not have relapses at the onset of the disease, but rather, steadily accumulate disability over time. This has come to be described as primary progressive MS (PPMS). How does the clinician know whether a patient with MS has progressive disease? In a similar way to the initial diagnosis of MS, although paraclinical measures and biomarkers (imaging and otherwise) can help, the diagnosis of progressive disease still remains firmly a clinical one. Neurologists will usually be able to classify the disease subtype of an individual patient based on clinical history and examination, although patients experiencing transition from relapsing-remitting MS to secondary progressive MS may be difficult to fully classify, as will patients experiencing significant numbers of relapses. In reality, disease progression is often not confidently diagnosed until time has passed in these patients and, thus, defining onset of disease progression is often a retrospective exercise.