Corboy

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.

Individuals will be randomized to either stay on the medication that they’re currently taking or discontinue that medicine. They will be followed then for 2 years. The primary outcome will be either a new relapse or a new scan change. The examining investigators are blinded to whether the patient is currently taking a MS disease modifying therapy.

Secondary outcomes include progression of disability as measured by confirmed change on the Extended Disability Status Scale (EDSS).

The enrollment goal is about 300 patients. There are presently 15 sites. The goal is to have the study completed in about 3 years. We’re presently over halfway through enrollment.

We also have a number of patient-reported outcomes because we’re particularly interested in the patient’s view of what’s going on in terms of how they feel. Understanding that dynamic will be extremely important.

We are including both patients with relapsing MS and progressive forms of MS, noting that they should have no relapse and no scan change at study entry.

What are the challenges with this study?

DR. CORBOY: One challenge is interpreting the information with the assumption that the hypothesis is validated. The hypothesis is that in a stable population of older patients that we can safely discontinue DMTs.

If that is found to be true, the question is how many people will be affected? We know that about 46% of people with MS are 55 and older, but there are not really good estimates of the number of individuals 55 and older who remain on a DMT and who are stable by the definition I just described.

It can be safely said, I think, that a substantial number of the individuals 55 and older are still on DMTs. If there’s almost a million people with MS and 46% are 55 and older, that means around 400,000 people with MS in the United States are aged 55 and older. If only half of those are on a DMT, that leaves 200,000. If only half of those are stable and could go off therapy, that would mean perhaps 100,000 people could discontinue DMTs in the United States. If all those assumptions are true, that would be a substantial savings in the health care burden of the United States from a relatively small population of individuals.

Beyond the cost, there are adverse events associated with using these medications. Older patients are more likely to be at risk of complications of MS DMTs. There also are doctor visits, blood monitoring, and other things that are done over time, and the inconvenience of taking a medicine on a routine basis if, indeed, it’s really not necessary because there is no benefit. Moreover, older individuals have other conditions (eg diabetes, hypertension, arrhythmias, cancer, etc) that may limit their ability to use medications due to risk. We’re very interested to see the outcome.

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.

Individuals will be randomized to either stay on the medication that they’re currently taking or discontinue that medicine. They will be followed then for 2 years. The primary outcome will be either a new relapse or a new scan change. The examining investigators are blinded to whether the patient is currently taking a MS disease modifying therapy.

Secondary outcomes include progression of disability as measured by confirmed change on the Extended Disability Status Scale (EDSS).

The enrollment goal is about 300 patients. There are presently 15 sites. The goal is to have the study completed in about 3 years. We’re presently over halfway through enrollment.

We also have a number of patient-reported outcomes because we’re particularly interested in the patient’s view of what’s going on in terms of how they feel. Understanding that dynamic will be extremely important.

We are including both patients with relapsing MS and progressive forms of MS, noting that they should have no relapse and no scan change at study entry.

What are the challenges with this study?

DR. CORBOY: One challenge is interpreting the information with the assumption that the hypothesis is validated. The hypothesis is that in a stable population of older patients that we can safely discontinue DMTs.

If that is found to be true, the question is how many people will be affected? We know that about 46% of people with MS are 55 and older, but there are not really good estimates of the number of individuals 55 and older who remain on a DMT and who are stable by the definition I just described.

It can be safely said, I think, that a substantial number of the individuals 55 and older are still on DMTs. If there’s almost a million people with MS and 46% are 55 and older, that means around 400,000 people with MS in the United States are aged 55 and older. If only half of those are on a DMT, that leaves 200,000. If only half of those are stable and could go off therapy, that would mean perhaps 100,000 people could discontinue DMTs in the United States. If all those assumptions are true, that would be a substantial savings in the health care burden of the United States from a relatively small population of individuals.

Beyond the cost, there are adverse events associated with using these medications. Older patients are more likely to be at risk of complications of MS DMTs. There also are doctor visits, blood monitoring, and other things that are done over time, and the inconvenience of taking a medicine on a routine basis if, indeed, it’s really not necessary because there is no benefit. Moreover, older individuals have other conditions (eg diabetes, hypertension, arrhythmias, cancer, etc) that may limit their ability to use medications due to risk. We’re very interested to see the outcome.

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.

Individuals will be randomized to either stay on the medication that they’re currently taking or discontinue that medicine. They will be followed then for 2 years. The primary outcome will be either a new relapse or a new scan change. The examining investigators are blinded to whether the patient is currently taking a MS disease modifying therapy.

Secondary outcomes include progression of disability as measured by confirmed change on the Extended Disability Status Scale (EDSS).

The enrollment goal is about 300 patients. There are presently 15 sites. The goal is to have the study completed in about 3 years. We’re presently over halfway through enrollment.

We also have a number of patient-reported outcomes because we’re particularly interested in the patient’s view of what’s going on in terms of how they feel. Understanding that dynamic will be extremely important.

We are including both patients with relapsing MS and progressive forms of MS, noting that they should have no relapse and no scan change at study entry.

What are the challenges with this study?

DR. CORBOY: One challenge is interpreting the information with the assumption that the hypothesis is validated. The hypothesis is that in a stable population of older patients that we can safely discontinue DMTs.

If that is found to be true, the question is how many people will be affected? We know that about 46% of people with MS are 55 and older, but there are not really good estimates of the number of individuals 55 and older who remain on a DMT and who are stable by the definition I just described.

It can be safely said, I think, that a substantial number of the individuals 55 and older are still on DMTs. If there’s almost a million people with MS and 46% are 55 and older, that means around 400,000 people with MS in the United States are aged 55 and older. If only half of those are on a DMT, that leaves 200,000. If only half of those are stable and could go off therapy, that would mean perhaps 100,000 people could discontinue DMTs in the United States. If all those assumptions are true, that would be a substantial savings in the health care burden of the United States from a relatively small population of individuals.

Beyond the cost, there are adverse events associated with using these medications. Older patients are more likely to be at risk of complications of MS DMTs. There also are doctor visits, blood monitoring, and other things that are done over time, and the inconvenience of taking a medicine on a routine basis if, indeed, it’s really not necessary because there is no benefit. Moreover, older individuals have other conditions (eg diabetes, hypertension, arrhythmias, cancer, etc) that may limit their ability to use medications due to risk. We’re very interested to see the outcome.