Targeting progression in multiple sclerosis — an update

In 2018, the distinguishing pathological features of white matter lesions in patients with progressive multiple sclerosis (MS) were refined, and serological and MRI biomarkers of clinical worsening and evolution to progressive MS were identified. We also saw therapeutic advances in progressive MS with the emergence of new neuroprotective strategies and putative markers of neurodegeneration.

Key advances

• A pathological study showed that substantial white matter lesion activity, in the form of mixed active–inactive, smouldering and slowly expanding lesions, persists and correlates with disease severity in patients with long-standing progressive multiple sclerosis (MS)¹.

• Levels of serum neurofilament light chain, a marker of neuroaxonal damage, were found to be higher in progressive MS than in relapsing MS, to correlate with current and future clinical disability, and to predict accelerated brain and spinal cord atrophy⁴.

• In patients with relapse-onset MS, a high cortical lesion count at disease onset predicted conversion to secondary progressive MS⁵, and in patients with primary progressive MS, baseline grey matter damage was predictive of clinical worsening after 15 years⁶.

• Integration of MRI measures into the clinical evaluation of patients with MS would allow earlier prognostication of long-term clinical outcomes⁶, leading to possible improvements in treatment decision-making and optimization of overall costs.

• In a phase II trial in patients with progressive MS, ibudilast treatment was associated with slower progression of brain atrophy but also had some adverse effects¹⁰; this study provides the impetus for future trials of neuroprotection in progressive MS.