Whole brain volume loss is associated with a short-term disability progression in relapse-activity free multiple...

Reliable biomarkers for disability progression independent of relapse activity (PIRA) in multiple sclerosis (MS) applicable in routine patient care are urgently needed. This study reports results from an ongoing multicenter, prospective, observational study with the primary objective of investigating the association of change in brain MRI biomarkers and PIRA.

In total 453 active relapsing remitting patients from 19 sites with baseline (BL) and one-year follow-up (FU) visits were included. At each visit, medication, relapse activity, and EDSS were recorded. MRI included 3D-T1 and 2D/3D-FLAIR. BL and FU scans enabled extraction of new/enlarged T2-lesions and brain volume loss (BVL) (annualized). Correlations and logistic regression assessed associations between EDSS progression and BVL/year.

At BL an EDSS (25%/50%/75%) of 1.5/2.0/2.5 and a time since first MS diagnosis of 2.1/5.7/11.4 years were observed. Change (FU-BL): ΔEDSS was 0.0/0.0/0.0, BVL/year was $-$ 0.5/ $-$ 0.3/ $-$ 0.0%, age-adjusted BVL/year was $-$ 0.4/ $-$ 0.1/0.2%, and number of new/enlarged T2-lesions per year was 0.0/0.0/0.6. 75% of patients were relapse activity-free during the observation period, 72% had no new/enlarged T2-lesions, and 56% were free of both. BVL/year (adjusted for age) correlated with ΔEDSS (r = $-$ 0.14, p = 0.002) for all patients, but also for sub-cohorts of patients without new/enlarged T2-lesions and without relapses (r = $-$ 0.17, p = 0.008). BVL/year was significantly associated with EDSS progression in the logistic regression model (p < 0.001). The risk of EDSS progression increases from 15% to 19% (relative risk increase of 26%), when BVL/year declines from $-$ 0.5% to $-$ 1.0%.

BVL over one year was significantly associated with EDSS progression in the absence of relapses or new lesions, confirming its value as a short-term risk marker for disability progression in MS.