Sub-optimal Response to Therapy in Disease-free MS Patients: A Paradox? (P6.113)

Objective: Axonal loss is an early finding in multiple sclerosis (MS) and relates to disability. So we propose its use as a marker for treatment optimization. Background: Current MS therapies target inflammatory activity of disease, defined by clinical relapses and EDSS progression, besides with absent T1W contrast enhancing lesions as well as no new or enlarging T2W lesions on MRI, in a way to impact disability development. So, the absence of clinical and MRI activity are accepted paradigms of disease free status in treated patients. Nevertheless, axonal loss seems to be a major determinant of disability, and may occur with lacking clinical expression and sophisticated MRI requirements. In this paper, we discuss current concept of disease free applied in real world, and propose that measures of atrophy be used in daily practice as a tool for optimal therapy. Design/Methods: Our group studied 206 consecutive non-selected patients with relapsing-remitting MS diagnosed according to 2001 McDonald criteria, on regular immunomodulatory treatment. They were submitted to serial clinical examinations and conventional MRI evaluation focus on relapses, EDSS progression and the presence of T1W Gd enhancing or T2W new/enlarging lesions. On conventional MRI sequences, we studied brain parenchymal fraction (BPF) and corpus callosum index (CCI), annually comparing results with data from a control group, composed by non-inflammatory diseases. Results: After 5 year, 56.7% patients presented with some evidence of disease activity: all but two patients showed worsening scores in BPF and CCI. On the other hand, 43.2% fulfilled accepted criteria for free of disease status, despite 48.3% of them showed a progressive reduction on BPF and CCI, comparable with those stratified as suboptimal responders. Conclusions: Our data demonstrates that axonal loss can be detected using corpus callosum index on routine follow up conventional MRI sequences, even among apparently stable patients. We propose axonal loss to be included as a requirement to consider a patient "disease free", during MS therapy. Disclosure: Dr. Figueira has received personal compensation for activities with Merck Serono, Genzyme Corp., and Novartis. Dr. Figueira has nothing to disclose. Dr. Soares has nothing to disclose.