A lesion topography-based approach to predict the outcomes of patients with multiple sclerosis treated with...

With increasing availability of effective disease-modifying treatments for multiple sclerosis (MS), an early identification of patients who do not adequately respond to Interferon Beta (IFNB) is relevant to decide the future strategy.

To investigate the predictive role of new lesion location on the risk of breakthrough disease in IFNB-treated patients with MS.

We analysed data from 392 patients starting IFNB and regularly followed up to 5 years. Before and after one year of IFNB treatment, all patients underwent a conventional brain and spinal cord magnetic resonancer imaging (MRI) scan with the same 1.5T magnet to obtain the count and location of new MRI lesions. Relapses and MRI activity occurred in the first year of IFNB treatment (year 0-1) were included in the set of potential predictors for relapses and disability worsening in the subsequent four years (year 2-5).

We found that 96 (24.5%) patients had relapses and/or MRI activity in the first year of IFNB treatment, while 41.6% of the patients experienced relapses and 17.8% experienced disability worsening. from year 2 to 5. The risk of relapses (year 2-5) was associated with ≥2 relapses (HR=5.65, p<0.001) and new T2-hyperintense lesions (for 2 new lesions: HR=1.96, p=0.011; for ≥3 new lesions: HR=3.55, p<0.001) in the first year of treatment. Other than male sex (HR=2.01, p=0.01) and higher EDSS score (HR=2.17, p<0.001), the risk of disability worsening (year 2-5) was associated with ≥2 relapses (HR=4.33, p<0.001) and new spinal cord or infratentorial lesions (HR=4.45,p<0.001) in the first year of treatment.

Our findings suggest a dose-effect relationship between the lesion count and the risk of future relapses, while the occurrence of new MRI lesions in sites representing anatomical bottle-necks was better than lesion count at predicting the future risk of disability worsening despite IFNB treatment.