Assessment of clinical definitions of conversion of relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (P4.402)

Objective: To assess the accuracy of different definitions of conversion from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS). Background: A standardized definition to identify the conversion from RRMS to SPMS is lacking. An accurate definition is required to optimize patient treatment and to identify subjects for studies designed to discover biomarkers of the conversion. Design/Methods: 29,392 visits from 2,236 subjects in the Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women’s Hospital (CLIMB) were screened. Patients with primary progressive MS were excluded. We evaluated 30 SPMS definitions by combining three features: expanded disability status scale (EDSS) cut-off score (3, 3.5, 4, 5, or 6) reached by a patient who previously was below this level, time interval (TI) during which EDSS was required to remain at or above the cut-off value (12, 24, or 36 months), and presence/absence of relapses during this TI. To assess the accuracy of each definition, we calculated the proportion of subjects maintaining the baseline EDSS (i.e. reached at the end of the TI) during two additional years of follow-up. For each definition, we calculated the proportion of patients designated as SPMS by their treating neurologist. Results: 196 patients satisfied at least one definition. For definitions using an EDSS cut-off of 4, 5, or 6, the proportion of patients maintaining the EDSS at or above baseline level during follow-up ranged from 78% to 91%. Definitions combining cut-off values of 3 or 3.5 with TIs of 24 or 36 months showed a similar accuracy. Excluding patients who had relapses did not cause large changes in accuracy. In all definitions, the proportion of patients designated as SPMS by neurologists was lower than the proportion maintaining an elevated EDSS during follow-up. Conclusions: Reaching and maintaining an EDSS score of 4 for at least 12 months may provide a reasonable definition for SPMS. Study Supported by: EMD-Serono, Nancy Davis Center without Walls. Disclosure: Dr. Diaz-Cruz has received research support from EMD Serono and Verily. Dr. Healy has received personal compensation for activities with Biogen Idec Worldwide Medical Biostatistics MS Advisory Board. Dr. Healy has received research support from Merck Serono SA, Verily Life Sciences, Genentech, and Novartis. Dr. Chua has nothing to disclose. Dr. Bhattacharyya has received personal compensation for activities with Advance Medical. Dr. Kimbrough has nothing to disclose. Dr. Severson has received personal compensation for activities with Biogen Idec and Novartis. Dr. Stankiewicz has received personal compensation for activities with Teva Neuroscience, Novartis, Sanofi Genzyme, Biogen Idec, Genentech, and Bayer as a consultant. Dr. Sattarnezhad has received research support from EMD Serono and Verily. Dr. Glanz has received research support from Merck Serono. Dr. Weiner has received personal compensation for activities with Genentech and Tiziana Life Sciences. Dr. Weiner has received research support from EMD Serono, Miragen, Sanofi, Teva and Verily. Dr. Chitnis received personal compensation for activities with Roche-Genentech and Sanofi-Genzyme. Dr. Chitnis received research support from EMD Serono, Biogen, Novartis and Verily.