Background:
Primary progressive MS (PPMS) affects 10-20% of people with MS and differs in many ways from relapsing-remitting MS (RRMS), such as in age of onset, gender ratios, and physiological characteristics. PPMS is harder to study than RRMS due to the lower proportion of cases and thus information on disease course and treatment options remain is scarce. Currently, there are no therapies for treating progressive forms of MS.
Evidence has shown that in RRMS, disability is likely to accumulate in two stages, known as “early” and “late” phases. Whether there are similar stages in PPMS is unknown. Results from a study recently published in the Journal of Neurology, Neurosurgery & Psychiatry may provide new insight into disability accumulation in PPMS, offering evidence that may help better understand how PPMS can be diagnosed, treated, and monitored.
The Study:
Dr. Marcus Koch and colleagues at the University of Calgary analyzed demographic and medical data collected at the Calgary MS clinic between 1976 and 2012. The data includes information from 446 patients with primary progressive MS, such as date of birth, gender, disease onset, diagnosis, disease course and disability.
Statistical analyses were done in order to examine how factors such as gender and age at disease onset influenced the amount of time it would take for an individual’s disability to worsen, and to determine if there are phases of early and late disability accumulation in people with primary progressive MS. To measure changes in disability, the researchers looked specifically at the Expanded Disability Status Scale (EDSS) scores for each person. The research team also analyzed whether or not there are different risk factors for rapid versus slow accumulation of disability.
Results:
From the MS Clinic database, researchers analyzed data from 446 people with primary progressive MS. The median time from onset of MS to reaching an EDSS score of 4 (the person is can walk despite severe disability) was 5 years, and the median time from onset of MS to reaching an EDSS score of 6 (the person requires a cane for walking) was 9 years. Those who were at EDSS 4 were around 51 years old, and those who were at EDSS 6 were around 55 years old. This data is consistent with similar studies from France and Canada, however the researchers note other population studies report longer times to disability, likely because they did not include people with rapid disease progression. This highlights the importance of accurately defining disability in people with progressive MS.
The researchers concluded that age at which a person is diagnosed with MS is the most significant predictor of disability accumulation in PPMS. Findings indicate that being diagnosed with PPMS at an older age is associated with a quicker time to both EDSS 4 and EDSS 6. The research team found that gender did not appear to influence the course of PPMS, in accordance with findings from previous similar studies. The analyses also showed that experiencing mobility problems on both sides of the body is associated with quicker disease progression. This finding agrees with what is observed by neurologists in the clinic, which is that spinal cord damage in MS results in bilateral motor symptoms, which is often associated with a worse prognosis.
Comment:
The results from this study offer implications for clinical trial design. The knowledge of time from disease onset in PPMS to specific disability milestones, notably EDSS 4 and EDSS 6, may help when considering the best way to establish eligibility criteria for participation in progressive MS trials in the future. By including as many people who are affected by progressive MS as possible, whether their disease course progresses quickly or slowly, researchers may accurately gage the benefits and harms of therapies for progressive MS.
Source:
Koch MW et al. The natural history of early versus late disability accumulation in primary progressive MS. J Neurol Neurosurg Psychiatry 2014 August 4 [Epub ahead of print].