Active and non-active progression independent of relapse activity within the first 20 years of relapsing multiple sclerosis

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BACKGROUND: Progression independent of relapse activity (PIRA) has been described since the early stage of relapsing multiple sclerosis (RMS). However, little is known about the relation between PIRA and inflammatory activity that is particularly important at this stage of the disease. METHOD: We included 110 patients in a prospective study within 18 months of RMS onset. MRI examinations and clinical visits were scheduled on the same day for months 0, 6, 12, 24, 36, 60, 84, 120, 180 and 240. RESULTS: The mean (SD) age of patients was 30 (6.7) years at inclusion and median (range) follow-up 15 (9-20) years. Analysis of 1118 between-visit intervals revealed 93 confirmed disability accumulation events in 68 (62%) patients: 50 (54%) events related to relapse activity worsening and 43 (46%) PIRA events, including 17 (18%) with MRI activity. The risk of PIRA between two visits (stable event as the reference category) was associated with Expanded Disability Status Scale (EDSS) score (HR: 1.41; 95% CI: 1.18 to 1.69; p<0.001), disease duration (HR: 0.75; 95% CI: 0.62 to 0.90; p<0.005) and new lesions between the visits (HR: 1.09 per lesion; 95% CI: 1.01 to 1.17; p<0.05). As compared with PIRA events with MRI activity, PIRA events without such activity occurred in patients with more disability (mean EDSS score 3, p<0.05), longer disease duration (mean 11 years, p<0.001) and greater number of T2-weighted lesions (p<0.05). CONCLUSION: This study evidenced that inflammatory activity increases the risk of PIRA in early RMS, arguing that a significant part of PIRA is accessible to treatment targeting inflammation in these patients.

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