Transition to secondary progression in relapsing-onset multiple sclerosis: Definitions and risk factors.

BACKGROUND No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. OBJECTIVE To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). METHODS Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. RESULTS SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p  40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. CONCLUSION A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.