Multiple Sclerosis Research Repository

1. “Late-Onset MS: Disease Course and Safety-Efficacy of DMTS: Maria Chaira Buscarinu et al

-In AFFIRM (NCT00027300) and SENTINEL (NCT00030966) studies, Natalizumab failed to reduce progression in patients with MS older than 40 years; in this case factors such as male sex, EDSS score higher than 3.5 and fewer than 9 baseline T2 lesions turn out to be predictors of non-responsiveness (30). Fingolimod showed similar results in the FREEDOMS trial (NCT00289978), being not able to reduce disability progression and relapses in patients older than 40 years, compared to placebo

-Among the other first-line DMT, dimethyl fumarate (CONFIRM trial; NCT00451451) (26), peginterferon-β-1a (ADVANCE trial; NCT00906399) (27), and teriflunomide (TEMSO trial; NCT00134563) (28) reduced annual relapses rate (ARR) in both young and old patients (threshold of 38 years for teriflunomide and 40 years for the others); however, all these DMTs failed to reduce the risk of disability accumulation.

-they found that IFN-β use was not statistically related with a slowing of disability progression

-ozanimod failed to reduce both relapses and disability progression. (NCT02047734; NCT02294058)

-Among the more recent DMTs, Ocrelizumab, a B cell-depleting anti-CD20 antibody, failed to reduce ARR in patients older than 40 years (33)

-The age-related changes that take place in the immune system, a process known as immunosenescence generally result in a higher susceptibility to infections, a reduced response to vaccines and a higher prevalence of autoimmunity and neurodegenerative disorders. These processes may affect the safety of DMT, so that potentially severe adverse events are more common in elderly patients.

-A pressing problem in clinical practice is the safety of certain DMT in LOMS people: especially the depleting drugs seem to pose older subjects at higher risk of serious infections or cancer.