You can’t predict progressive MS risk factors with EDSS

Stellmann JP, Neuhaus A, Lederer C, Daumer M, Heesen C. Validating predictors of disease progression in a large cohort of primary-progressive multiple sclerosis based on a systematic literature review. PLoS One. 2014 Mar 20;9(3):e92761. doi: 10.1371/journal.pone.0092761. eCollection 2014.

BACKGROUND: New agents with neuroprotective or neuroregenerative potential might be explored in primary-progressive Multiple Sclerosis (PPMS) – the MS disease course with leading neurodegenerative pathology. Identification of patients with a high short-term risk for progression may minimize study duration and sample size. Cohort studies reported several variables as predictors of EDSS disability progression but findings were partially contradictory.
OBJECTIVE: To analyse the impact of published predictors on EDSS disease progression in a large cohort of PPMS patients.
METHODS: A systematic literature research was performed to identify predictors for disease progression in PPMS. Individual case data from the Sylvia Lawry Centre (SLC) and the Hamburg MS patient database (HAPIMS) was pooled for a retrospective validation of these predictors on the annualized EDSS change.
RESULTS: The systematic literature analysis revealed heterogeneous data from 3 prospective and 5 retrospective natural history cohort studies. Age at onset, gender, type of first symptoms and early EDSS changes were available for validation. Our pooled cohort of 597 PPMS patients (54% female) had a mean follow-up of 4.4 years and mean change of EDSS of 0.35 per year based on 2503 EDSS assessments. There was no significant association between the investigated variables and the EDSS-change.
CONCLUSION: None of the analysed variables were predictive for the disease progression measured by the annualized EDSS change. Whether PPMS is still unpredictable or our results may be due to limitations of cohort assessments or selection of predictors cannot be answered. Large systematic prospective studies with new endpoints are needed.

There are clearly risk factors that help predict whether you may be more likely to develop progressive MS, but the best indicator is the clinical course. EDSS is a measure of disability that will progress with PPMS and SPMS but for the purposes of early clinical trials the EDSS is not sensitive enough for short studies. The International Collaborative on Progressive MS recently published a research agenda for progressive MS, which claimed new outcome parameters and new phase II clinical trial strategies as 2 out of 5 major research needs.

This study could not validate gender, age at onset, type of first symptoms or early EDSS-progression as predictive for the EDSS dynamic in PPMS. Prospective cohort data of PPMS are yet very limited. Besides larger cohorts, new outcome measures for progressive MS are needed, as the EDSS seems to be too imprecise to detect disease progression.

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  • How do these results comport with what Dr G reported as results of Daclizumab study which showed EDSs impact on progression

    • We are talking two different things this study is about Primary Progressive MS,ProfG's study is relapsing remitting MS and is looking at progression. This is measured by changes in EDSS but the point being made here is that it is an insensitive tool.

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