A multiple sclerosis disease progression measure based on rate of cumulative disability
ECTRIMS Online Library. Ramanujam R. Sep 12, 2019; 279499; 218
Ryan Ramanujam
Ryan Ramanujam

Abstract: 218

Type: Scientific Session

Abstract Category: Clinical aspects of MS - Natural course

A. Manouchehrinia, J. Hillert, R. Ramanujam

Karolinska Institutet, Stockholm, Sweden

Introduction: Current disability measures in multiple sclerosis (MS), such as the Multiple Sclerosis Severity Score (MSSS), use current Expanded Disability Status Scale (EDSS) and disease duration. This disregards the overall course, wherein a patient may have had long periods of high severity.
Aims: Create a disease progression measure based on cumulative disability. Determine if patients with extreme progression after 10 years of monitoring can be identified after 2 and 4 years.
Methods: We created a disability measure called ARMSS-rate based on the time rate of change of the ARMSS (Age Related Multiple Sclerosis Severity Score). Data was extracted for 15,831 patients from the Swedish MS registry including age at visit and EDSS at each neurological visit. ARMSS-rate was calculated by differencing the integral of serial gARMSS scores and the expected curve, namely a stable gARMSS score of 5.
Patients were included if serial EDSS scores were available for 10 years (n=4514). Individuals in the lowest and highest quartiles were considered those in the extremes of cumulative disability after 10 years. ARMSS-rates at the first EDSS measurement after 2 and 4 years of monitoring were investigated for patients with sufficiently spaced EDSS available.
Results: The 10-year ARMSS-rate for the entire cohort followed a left-skewed distribution with median -7.5 (range [-82.0, 117.0], Q1=-27.7, Q3=17.0). Analysis of 2-years of follow up (n=3326) included 831 and 779 of patients in 10-year Q1 and Q4, respectively. The corresponding Q1 and Q4 numbers for the 4-year analysis (n=4174) were 1028 and 1026.
Using 2-years of follow up, ARMSS-rates over 8.65 classified patients with most severe 10-year disease with 100% accuracy (n=167). Patients with ARMSS-rate >5 were 93.3% likely to be in the 10-year Q4 (499 of 535). Conversely, patients with an ARMSS-rate < 1 only had a 10-year Q4 rate of 3.1% (69 of 2212).
For ARMSS-rates at 4 years, the 100% classification rate of most cumulative disability at 10-years corresponded to a value of 5.7 (n=394). An ARMSS-rate above 7.5 yielded 90.2% of patients (863 of 956) in the Q4 10-year group.
Conclusion: The ARMSS-rate provides an objective measure of cumulative progression. Early ARMSS-rate corresponds well to future disability, and even after 2 years correctly classifies a large proportion of patients in the upper quartile of future progression. It may have the potential to function as an early warning indicator of disability risk.
Disclosure: AM is supported by Margaretha af Ugglas foundation. He has received consultancy fees from Biogen and speaker honoraria and/or travel expenses from Biogen and ECTRIMS.
Ryan Ramanujam has nothing to disclose. Jan Hillert has received honoraria for serving on advisory boards for Biogen, Sanofi-Genzyme and Novartis and speaker´s fees from Biogen, Novartis, Merck-Serono, Bayer-Schering, Teva and Sanofi-Genzyme. He has served as P.I. for projects, or received unrestricted research support from, Biogen, Merck-Serono, TEVA, Sanofi-Genzyme and Bayer-Schering.

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