Discontinuing
How would you characterize the prevalence of MS in the elderly?
DR. CORBOY: A recent large demographic study put together by the National MS Society found that there’s almost a million individuals diagnosed with MS over the course of the last 40 to 50 years. The largest population segment was those aged 55 to 64 years. People with MS aged 55 or older constituted 46% of all those with MS.
What disease-modifying therapies (DMTs) are approved by the FDA for the elderly?
DR. CORBOY: Of the drugs that have received FDA approval, most are for individuals over the age of 18 and there’s no specific age cutoff. However, there’s no data supporting DMT use in people over the age of 55 because they were excluded from the studies.
There’s one DMT, fingolimod, that was approved for use in patients under the age of 18; all others are approved for 18 and above. However, none of them are explicitly approved for people over the age of 55, because there is no data to support it.
What is the goal of your study, the DISCO MS trial?
DR. CORBOY: The DISCO MS trial will be the first randomized, controlled, blinded discontinuation trial in the MS space. The objective is to assess the benefit of DMTs in patients over the age of 55.
Part of the rationale for the trial is that prior subgroup analyses have shown that the vast majority of the benefit that we’ve been able to measure with all of these DMTs is seen in those who are under age 45.
A number of studies have examined existing databases and individuals who were either randomly or deliberately taken off of their medication as they age, including people who were felt to be stable with no recent relapses and no recent changes on their MRI brain. These studies reinforced that when discontinuing medications, the individuals who were much more likely to have recurrence of disease activity were younger patients.
Pathological studies clearly show the number of acutely inflamed plaques in the white matter is dramatically lower in autopsies of older vs younger patients. There are different changes in older patients, with lymphocytic nodules in the meninges, gray matter plaques related to these meningeal nodules, microglial activation, and smaller numbers of active, or mostly, inactive, white matter plaques. It’s been difficult to show any substantial benefit in slowing disability progression, much of which is felt to not be associated with acute inflammatory disease in the aging patient. All of these medicines, which can be thought of as anti-inflammatory medicines, are very beneficial when patients are young but less so as they age.
Would you describe the DISCO MS study design?
DR. CORBOY: Our study looks at individuals who are 55 and older who have not had a relapse for at least 5 years, and who’ve not had a change on their brain scan for at least 3 years.