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Prospective MS Trial Proves Ocrelizumab Efficacy in Under-Represented Populations
NASHVILLE, Tennessee — , according to the results of a 1-year analysis of the CHIMES trial. The study is the first-ever prospective study of an MS disease-modifying therapy (DMT) exclusively performed in under-represented populations, and offers lessons to researchers aiming to design more inclusive clinical trials to bolster participation by under-represented populations.
“The goal was to better understand efficacy of therapy in under-represented populations because we typically have very low numbers of these patients in our clinical trials, although there are multiple studies over the past decades suggesting that there may be poorer outcomes in Black and Hispanic individuals, particularly in the United States, and that there also may be more aggressive disease,” said Mitzi Williams, MD, who presented the study in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.
The team recruited 113 Black participants and 69 Hispanic participants, and, in fact, over-recruited the target number by 25%, and did so 2 months before the launch of the study in July 2020, which just happened to be in the midst of a global pandemic.
After 48 weeks of ocrelizumab treatment, 46.0% of Black participants and 58.0% of Hispanic participants achieved no evidence of disease activity in three components (NEDA-3), while 94.7% and 95.7% were free from relapses, respectively, and 94.7% and 94.2% were free from disease worsening. Serious adverse events occurred in 6.2% and 4.3% of each group, respectively, and there were no new safety signals in either group.
“The good news is that the efficacy and safety was very similar to what we saw in other clinical trials. I don’t think we really expected it to be much different, because when we think about race, it’s a social construct, not a biologic construct. What we do hope to find out is more about some of the interplay of social determinants of health, and how getting on high efficacy treatment can improve and increase productivity and outcomes in the long term,” said Dr. Williams, who is medical director of Joi Life Wellness Group, Smyrna, Georgia.
The researchers succeeded by involving patient advocates and advocacy organizations at the very earliest stages of the trial design. “We were very intentional about looking at things like social determinants of health, childcare, transportation, and things like that to ease some of the burden of participating in the trial, obviously in a legal and compliant way,” said Dr. Williams. The team also ensured complete and accurate translation of patient materials into Spanish.
The study was also a phase 4 trial, which may have simplified recruitment. “So it’s a therapy that’s already approved, which may make people feel more comfortable, but obviously the goal is for our phase 3 trials to make sure that we are recruiting represented populations. We’re taking these learnings and applying them to the broader clinical trial population so that hopefully we won’t have to come back and do phase 4 studies like this,” said Dr. Williams.
She noted that the results of more inclusive studies don’t just benefit underserved populations. “You have groups of people that are suffering and having more disability from a condition, and you need to understand why. When we broaden the population to understand those that are most vulnerable and underserved and [having the worst outcomes], it really helps us to better treat everybody. Because if we can get a hold of those factors that make us do the worst, then we can also better understand the factors that make us do the best,” said Dr. Williams.
Inclusive Recruitment in Clinical Trials
Asked for comment, Ahmed Obeidat, MD, PhD, highlighted the importance of inclusive recruitment. “The study is very important because historically and even in most recent clinical trials, these groups were markedly under-represented and most completed clinical trials derive conclusions based on the study of a nondiverse, White-non-Hispanic predominant population,” said Dr. Obeidat, who is an associate professor at the Medical College of Wisconsin, Milwaukee. He pointed to a systematic review showing that the median percentage of White participants in MS clinical trials was 93% and ranged from 86% to 98%.
“Several factors may contribute to the disparity in clinical trial participation, and solutions must be explored and developed. CHIMES is a first step in this direction where the study itself is designed to address disparity in MS clinical trial participation,” said Dr. Obeidat.
Dr. Obeidat also pointed to the need to consider other forms of diversity in clinical trials, such as older patients and those with advanced disability. “Investigators, coordinators, and other staff should all strive to be as inclusive as possible in clinical trials,” he said.
Dr. Williams has received consulting fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech Inc., Janssen, Novartis, Sanofi, and TG Therapeutics, and serves on speakers bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Janssen, Genentech, and TG Therapeutics. Dr. Ahmed Z. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio.
NASHVILLE, Tennessee — , according to the results of a 1-year analysis of the CHIMES trial. The study is the first-ever prospective study of an MS disease-modifying therapy (DMT) exclusively performed in under-represented populations, and offers lessons to researchers aiming to design more inclusive clinical trials to bolster participation by under-represented populations.
“The goal was to better understand efficacy of therapy in under-represented populations because we typically have very low numbers of these patients in our clinical trials, although there are multiple studies over the past decades suggesting that there may be poorer outcomes in Black and Hispanic individuals, particularly in the United States, and that there also may be more aggressive disease,” said Mitzi Williams, MD, who presented the study in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.
The team recruited 113 Black participants and 69 Hispanic participants, and, in fact, over-recruited the target number by 25%, and did so 2 months before the launch of the study in July 2020, which just happened to be in the midst of a global pandemic.
After 48 weeks of ocrelizumab treatment, 46.0% of Black participants and 58.0% of Hispanic participants achieved no evidence of disease activity in three components (NEDA-3), while 94.7% and 95.7% were free from relapses, respectively, and 94.7% and 94.2% were free from disease worsening. Serious adverse events occurred in 6.2% and 4.3% of each group, respectively, and there were no new safety signals in either group.
“The good news is that the efficacy and safety was very similar to what we saw in other clinical trials. I don’t think we really expected it to be much different, because when we think about race, it’s a social construct, not a biologic construct. What we do hope to find out is more about some of the interplay of social determinants of health, and how getting on high efficacy treatment can improve and increase productivity and outcomes in the long term,” said Dr. Williams, who is medical director of Joi Life Wellness Group, Smyrna, Georgia.
The researchers succeeded by involving patient advocates and advocacy organizations at the very earliest stages of the trial design. “We were very intentional about looking at things like social determinants of health, childcare, transportation, and things like that to ease some of the burden of participating in the trial, obviously in a legal and compliant way,” said Dr. Williams. The team also ensured complete and accurate translation of patient materials into Spanish.
The study was also a phase 4 trial, which may have simplified recruitment. “So it’s a therapy that’s already approved, which may make people feel more comfortable, but obviously the goal is for our phase 3 trials to make sure that we are recruiting represented populations. We’re taking these learnings and applying them to the broader clinical trial population so that hopefully we won’t have to come back and do phase 4 studies like this,” said Dr. Williams.
She noted that the results of more inclusive studies don’t just benefit underserved populations. “You have groups of people that are suffering and having more disability from a condition, and you need to understand why. When we broaden the population to understand those that are most vulnerable and underserved and [having the worst outcomes], it really helps us to better treat everybody. Because if we can get a hold of those factors that make us do the worst, then we can also better understand the factors that make us do the best,” said Dr. Williams.
Inclusive Recruitment in Clinical Trials
Asked for comment, Ahmed Obeidat, MD, PhD, highlighted the importance of inclusive recruitment. “The study is very important because historically and even in most recent clinical trials, these groups were markedly under-represented and most completed clinical trials derive conclusions based on the study of a nondiverse, White-non-Hispanic predominant population,” said Dr. Obeidat, who is an associate professor at the Medical College of Wisconsin, Milwaukee. He pointed to a systematic review showing that the median percentage of White participants in MS clinical trials was 93% and ranged from 86% to 98%.
“Several factors may contribute to the disparity in clinical trial participation, and solutions must be explored and developed. CHIMES is a first step in this direction where the study itself is designed to address disparity in MS clinical trial participation,” said Dr. Obeidat.
Dr. Obeidat also pointed to the need to consider other forms of diversity in clinical trials, such as older patients and those with advanced disability. “Investigators, coordinators, and other staff should all strive to be as inclusive as possible in clinical trials,” he said.
Dr. Williams has received consulting fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech Inc., Janssen, Novartis, Sanofi, and TG Therapeutics, and serves on speakers bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Janssen, Genentech, and TG Therapeutics. Dr. Ahmed Z. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio.
NASHVILLE, Tennessee — , according to the results of a 1-year analysis of the CHIMES trial. The study is the first-ever prospective study of an MS disease-modifying therapy (DMT) exclusively performed in under-represented populations, and offers lessons to researchers aiming to design more inclusive clinical trials to bolster participation by under-represented populations.
“The goal was to better understand efficacy of therapy in under-represented populations because we typically have very low numbers of these patients in our clinical trials, although there are multiple studies over the past decades suggesting that there may be poorer outcomes in Black and Hispanic individuals, particularly in the United States, and that there also may be more aggressive disease,” said Mitzi Williams, MD, who presented the study in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.
The team recruited 113 Black participants and 69 Hispanic participants, and, in fact, over-recruited the target number by 25%, and did so 2 months before the launch of the study in July 2020, which just happened to be in the midst of a global pandemic.
After 48 weeks of ocrelizumab treatment, 46.0% of Black participants and 58.0% of Hispanic participants achieved no evidence of disease activity in three components (NEDA-3), while 94.7% and 95.7% were free from relapses, respectively, and 94.7% and 94.2% were free from disease worsening. Serious adverse events occurred in 6.2% and 4.3% of each group, respectively, and there were no new safety signals in either group.
“The good news is that the efficacy and safety was very similar to what we saw in other clinical trials. I don’t think we really expected it to be much different, because when we think about race, it’s a social construct, not a biologic construct. What we do hope to find out is more about some of the interplay of social determinants of health, and how getting on high efficacy treatment can improve and increase productivity and outcomes in the long term,” said Dr. Williams, who is medical director of Joi Life Wellness Group, Smyrna, Georgia.
The researchers succeeded by involving patient advocates and advocacy organizations at the very earliest stages of the trial design. “We were very intentional about looking at things like social determinants of health, childcare, transportation, and things like that to ease some of the burden of participating in the trial, obviously in a legal and compliant way,” said Dr. Williams. The team also ensured complete and accurate translation of patient materials into Spanish.
The study was also a phase 4 trial, which may have simplified recruitment. “So it’s a therapy that’s already approved, which may make people feel more comfortable, but obviously the goal is for our phase 3 trials to make sure that we are recruiting represented populations. We’re taking these learnings and applying them to the broader clinical trial population so that hopefully we won’t have to come back and do phase 4 studies like this,” said Dr. Williams.
She noted that the results of more inclusive studies don’t just benefit underserved populations. “You have groups of people that are suffering and having more disability from a condition, and you need to understand why. When we broaden the population to understand those that are most vulnerable and underserved and [having the worst outcomes], it really helps us to better treat everybody. Because if we can get a hold of those factors that make us do the worst, then we can also better understand the factors that make us do the best,” said Dr. Williams.
Inclusive Recruitment in Clinical Trials
Asked for comment, Ahmed Obeidat, MD, PhD, highlighted the importance of inclusive recruitment. “The study is very important because historically and even in most recent clinical trials, these groups were markedly under-represented and most completed clinical trials derive conclusions based on the study of a nondiverse, White-non-Hispanic predominant population,” said Dr. Obeidat, who is an associate professor at the Medical College of Wisconsin, Milwaukee. He pointed to a systematic review showing that the median percentage of White participants in MS clinical trials was 93% and ranged from 86% to 98%.
“Several factors may contribute to the disparity in clinical trial participation, and solutions must be explored and developed. CHIMES is a first step in this direction where the study itself is designed to address disparity in MS clinical trial participation,” said Dr. Obeidat.
Dr. Obeidat also pointed to the need to consider other forms of diversity in clinical trials, such as older patients and those with advanced disability. “Investigators, coordinators, and other staff should all strive to be as inclusive as possible in clinical trials,” he said.
Dr. Williams has received consulting fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech Inc., Janssen, Novartis, Sanofi, and TG Therapeutics, and serves on speakers bureaus for Biogen, Bristol Myers Squibb, EMD Serono, Janssen, Genentech, and TG Therapeutics. Dr. Ahmed Z. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio.
FROM CMSC 2024
Pediatric Ocrelizumab Dose Established for MS
NASHVILLE, Tennessee — , according to pharmacokinetic/pharmacodynamic (PK/PD) data from the OPERETTA 1 phase 2 clinical trial. The safety profile was similar to adult patients.
“While we believe the disease to be the same in children and adolescents, [MS] is distinguished by its very inflammatory nature, oftentimes causing two to three times the number of relapses per year as their adult-onset colleagues,” said Teri Schreiner, MD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Approved therapies for pediatric MS include fingolimod in the United States and Europe, as well as dimethyl fumarate in Europe. “There’s a real need for high-efficacy treatment [in pediatric patients], again referring back to this disease being very inflammatory in children and adolescents. We oftentimes will use medications off label but this is clearly suboptimal as we lack safety data, and oftentimes run into difficulty with insurance approval of off-label use of medicine,” said Dr. Schreiner, who is an associate professor of neurology at University of Colorado School of Medicine, Aurora.
To determine the dose in pediatric patients that would produce comparable PK and PD to adults, the researchers dosed six patients aged 10-18 with 300 mg ocrelizumab, and 17 such patients with 600 mg ocrelizumab during a 24-week dose-exploration period, followed by a 264-week optional extension period. The cohorts were separated based on weight of less than or more than 40 kg. The mean ages were 11.2 years (mean weight, 34.9 kg) and 15.3 years (mean weight, 62.3 kg), respectively.
During the dose-exploration period, seven blood draws were performed to characterize PK. “When the PK data was analyzed, we saw that the proper cut-off point was 35 kilos. At less than 35 kilos, the appropriate dose was half of that adult dose, so 300 milligrams every 6 months, whereas above 35 kilos, the proper dose was actually 600, or the adult dose. Given the rarity of pediatric-onset MS patients less than 35 kilos, most patients will benefit from the adult dose of 600 milligrams twice yearly,” said Dr. Schreiner.
PD data were also encouraging. “The primary PD was the absence of CD-19 B cells, and that was tracked over time. While there were a few patients in both cohorts that had modest reconstitution, there was no patient in our study that crossed the retreatment threshold, and all blood samples were negative for anti-drug antibodies,” said Dr. Schreiner.
Adverse events occurred in five of six patients in the 300 mg group (83%; 4 grade 2, 1 grade 3) and 100% of patients in the 600 mg group (1 grade 1, 9 grade 2, 6 grade 3, 1 grade 4). There was one serious adverse event in the 300 mg group (16.7%) and four serious adverse events in the 600 mg group (23.5%). None led to treatment discontinuation. “This is largely consistent with what was seen in the adult studies of ocrelizumab,” said Dr. Schreiner.
Roche is now recruiting for the phase 3 OPERETTA 2 trial, which will use the 600 mg dose and compare outcomes to a fingolimod arm.
Establishing Safety in the Pediatric Population
“In [pediatric onset MS] it’s an important piece of information to design OPERETTA 2 and to dose ocrelizumab in pediatric-onset MS in general,” said Jeffrey A Cohen, MD, professor of neurology at the Cleveland Clinic, who was asked for comment.
During the Q&A period, Dr. Schreiner was asked whether it is possible to extrapolate experience from rituximab to the pediatric population. “They’re very similar molecules, and we know the mechanisms of action, but I think part of the importance of doing these studies is to get the safety data so that we actually can say with certainty, we are giving you a drug that has this list of side effects and we know about them definitively. We all use other high-efficacy medications, but I don’t think we can exactly extrapolate,” said Dr. Schreiner.
Session moderator Amy Perrin Ross, APN, noted the lack of approved pediatric therapies for MS. “This is an extremely important study, because we at least in the lower 48 are quite limited in our resources for approved pediatric cases. Information like this will make it easier for a potential pediatric indication, which would then make it easier on us to go after [treatment of the disease in this population]. The weight-based dosing, I think, is really a good thing. Patients have been asking for weight-based dosing on everything for many years,” she said.
Ahmed Obeidat, MD, PhD, associate professor at the Medical College of Wisconsin, also praised the study. “While pediatric MS is rare, it is an area of unmet need when it comes to disease-modifying therapies as only fingolimod is FDA-approved, and many use B cell–depleting therapy, such as rituximab, off label to treat children with MS with good outcomes. The need for guidance on the dosing of B cell–depleting therapy is a main priority for research in pediatric MS,” he said.
The study was funded by Roche. Dr. Schreiner has consulted for Roche and Cycle Pharmaceuticals. Dr. Cohen has consulted for Astoria, Bristol Myers Squibb, Convelo, EMD Serono Inc, FiND, INMune, and Sandoz. Dr. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Ms. Ross has consulted for EMD Serono, BMS, Horizon, Alexion, TG Therapeutics, Novartis, Roche, and Sanofi.
NASHVILLE, Tennessee — , according to pharmacokinetic/pharmacodynamic (PK/PD) data from the OPERETTA 1 phase 2 clinical trial. The safety profile was similar to adult patients.
“While we believe the disease to be the same in children and adolescents, [MS] is distinguished by its very inflammatory nature, oftentimes causing two to three times the number of relapses per year as their adult-onset colleagues,” said Teri Schreiner, MD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Approved therapies for pediatric MS include fingolimod in the United States and Europe, as well as dimethyl fumarate in Europe. “There’s a real need for high-efficacy treatment [in pediatric patients], again referring back to this disease being very inflammatory in children and adolescents. We oftentimes will use medications off label but this is clearly suboptimal as we lack safety data, and oftentimes run into difficulty with insurance approval of off-label use of medicine,” said Dr. Schreiner, who is an associate professor of neurology at University of Colorado School of Medicine, Aurora.
To determine the dose in pediatric patients that would produce comparable PK and PD to adults, the researchers dosed six patients aged 10-18 with 300 mg ocrelizumab, and 17 such patients with 600 mg ocrelizumab during a 24-week dose-exploration period, followed by a 264-week optional extension period. The cohorts were separated based on weight of less than or more than 40 kg. The mean ages were 11.2 years (mean weight, 34.9 kg) and 15.3 years (mean weight, 62.3 kg), respectively.
During the dose-exploration period, seven blood draws were performed to characterize PK. “When the PK data was analyzed, we saw that the proper cut-off point was 35 kilos. At less than 35 kilos, the appropriate dose was half of that adult dose, so 300 milligrams every 6 months, whereas above 35 kilos, the proper dose was actually 600, or the adult dose. Given the rarity of pediatric-onset MS patients less than 35 kilos, most patients will benefit from the adult dose of 600 milligrams twice yearly,” said Dr. Schreiner.
PD data were also encouraging. “The primary PD was the absence of CD-19 B cells, and that was tracked over time. While there were a few patients in both cohorts that had modest reconstitution, there was no patient in our study that crossed the retreatment threshold, and all blood samples were negative for anti-drug antibodies,” said Dr. Schreiner.
Adverse events occurred in five of six patients in the 300 mg group (83%; 4 grade 2, 1 grade 3) and 100% of patients in the 600 mg group (1 grade 1, 9 grade 2, 6 grade 3, 1 grade 4). There was one serious adverse event in the 300 mg group (16.7%) and four serious adverse events in the 600 mg group (23.5%). None led to treatment discontinuation. “This is largely consistent with what was seen in the adult studies of ocrelizumab,” said Dr. Schreiner.
Roche is now recruiting for the phase 3 OPERETTA 2 trial, which will use the 600 mg dose and compare outcomes to a fingolimod arm.
Establishing Safety in the Pediatric Population
“In [pediatric onset MS] it’s an important piece of information to design OPERETTA 2 and to dose ocrelizumab in pediatric-onset MS in general,” said Jeffrey A Cohen, MD, professor of neurology at the Cleveland Clinic, who was asked for comment.
During the Q&A period, Dr. Schreiner was asked whether it is possible to extrapolate experience from rituximab to the pediatric population. “They’re very similar molecules, and we know the mechanisms of action, but I think part of the importance of doing these studies is to get the safety data so that we actually can say with certainty, we are giving you a drug that has this list of side effects and we know about them definitively. We all use other high-efficacy medications, but I don’t think we can exactly extrapolate,” said Dr. Schreiner.
Session moderator Amy Perrin Ross, APN, noted the lack of approved pediatric therapies for MS. “This is an extremely important study, because we at least in the lower 48 are quite limited in our resources for approved pediatric cases. Information like this will make it easier for a potential pediatric indication, which would then make it easier on us to go after [treatment of the disease in this population]. The weight-based dosing, I think, is really a good thing. Patients have been asking for weight-based dosing on everything for many years,” she said.
Ahmed Obeidat, MD, PhD, associate professor at the Medical College of Wisconsin, also praised the study. “While pediatric MS is rare, it is an area of unmet need when it comes to disease-modifying therapies as only fingolimod is FDA-approved, and many use B cell–depleting therapy, such as rituximab, off label to treat children with MS with good outcomes. The need for guidance on the dosing of B cell–depleting therapy is a main priority for research in pediatric MS,” he said.
The study was funded by Roche. Dr. Schreiner has consulted for Roche and Cycle Pharmaceuticals. Dr. Cohen has consulted for Astoria, Bristol Myers Squibb, Convelo, EMD Serono Inc, FiND, INMune, and Sandoz. Dr. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Ms. Ross has consulted for EMD Serono, BMS, Horizon, Alexion, TG Therapeutics, Novartis, Roche, and Sanofi.
NASHVILLE, Tennessee — , according to pharmacokinetic/pharmacodynamic (PK/PD) data from the OPERETTA 1 phase 2 clinical trial. The safety profile was similar to adult patients.
“While we believe the disease to be the same in children and adolescents, [MS] is distinguished by its very inflammatory nature, oftentimes causing two to three times the number of relapses per year as their adult-onset colleagues,” said Teri Schreiner, MD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
Approved therapies for pediatric MS include fingolimod in the United States and Europe, as well as dimethyl fumarate in Europe. “There’s a real need for high-efficacy treatment [in pediatric patients], again referring back to this disease being very inflammatory in children and adolescents. We oftentimes will use medications off label but this is clearly suboptimal as we lack safety data, and oftentimes run into difficulty with insurance approval of off-label use of medicine,” said Dr. Schreiner, who is an associate professor of neurology at University of Colorado School of Medicine, Aurora.
To determine the dose in pediatric patients that would produce comparable PK and PD to adults, the researchers dosed six patients aged 10-18 with 300 mg ocrelizumab, and 17 such patients with 600 mg ocrelizumab during a 24-week dose-exploration period, followed by a 264-week optional extension period. The cohorts were separated based on weight of less than or more than 40 kg. The mean ages were 11.2 years (mean weight, 34.9 kg) and 15.3 years (mean weight, 62.3 kg), respectively.
During the dose-exploration period, seven blood draws were performed to characterize PK. “When the PK data was analyzed, we saw that the proper cut-off point was 35 kilos. At less than 35 kilos, the appropriate dose was half of that adult dose, so 300 milligrams every 6 months, whereas above 35 kilos, the proper dose was actually 600, or the adult dose. Given the rarity of pediatric-onset MS patients less than 35 kilos, most patients will benefit from the adult dose of 600 milligrams twice yearly,” said Dr. Schreiner.
PD data were also encouraging. “The primary PD was the absence of CD-19 B cells, and that was tracked over time. While there were a few patients in both cohorts that had modest reconstitution, there was no patient in our study that crossed the retreatment threshold, and all blood samples were negative for anti-drug antibodies,” said Dr. Schreiner.
Adverse events occurred in five of six patients in the 300 mg group (83%; 4 grade 2, 1 grade 3) and 100% of patients in the 600 mg group (1 grade 1, 9 grade 2, 6 grade 3, 1 grade 4). There was one serious adverse event in the 300 mg group (16.7%) and four serious adverse events in the 600 mg group (23.5%). None led to treatment discontinuation. “This is largely consistent with what was seen in the adult studies of ocrelizumab,” said Dr. Schreiner.
Roche is now recruiting for the phase 3 OPERETTA 2 trial, which will use the 600 mg dose and compare outcomes to a fingolimod arm.
Establishing Safety in the Pediatric Population
“In [pediatric onset MS] it’s an important piece of information to design OPERETTA 2 and to dose ocrelizumab in pediatric-onset MS in general,” said Jeffrey A Cohen, MD, professor of neurology at the Cleveland Clinic, who was asked for comment.
During the Q&A period, Dr. Schreiner was asked whether it is possible to extrapolate experience from rituximab to the pediatric population. “They’re very similar molecules, and we know the mechanisms of action, but I think part of the importance of doing these studies is to get the safety data so that we actually can say with certainty, we are giving you a drug that has this list of side effects and we know about them definitively. We all use other high-efficacy medications, but I don’t think we can exactly extrapolate,” said Dr. Schreiner.
Session moderator Amy Perrin Ross, APN, noted the lack of approved pediatric therapies for MS. “This is an extremely important study, because we at least in the lower 48 are quite limited in our resources for approved pediatric cases. Information like this will make it easier for a potential pediatric indication, which would then make it easier on us to go after [treatment of the disease in this population]. The weight-based dosing, I think, is really a good thing. Patients have been asking for weight-based dosing on everything for many years,” she said.
Ahmed Obeidat, MD, PhD, associate professor at the Medical College of Wisconsin, also praised the study. “While pediatric MS is rare, it is an area of unmet need when it comes to disease-modifying therapies as only fingolimod is FDA-approved, and many use B cell–depleting therapy, such as rituximab, off label to treat children with MS with good outcomes. The need for guidance on the dosing of B cell–depleting therapy is a main priority for research in pediatric MS,” he said.
The study was funded by Roche. Dr. Schreiner has consulted for Roche and Cycle Pharmaceuticals. Dr. Cohen has consulted for Astoria, Bristol Myers Squibb, Convelo, EMD Serono Inc, FiND, INMune, and Sandoz. Dr. Obeidat has financial relationships with Alexion Pharmaceuticals, Banner Life Sciences, BD Biosciences, Biogen, Biologix Solutions, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharmaceuticals, Horizon Therapeutics, Jazz Pharmaceuticals, Novartis, Sandoz, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Ms. Ross has consulted for EMD Serono, BMS, Horizon, Alexion, TG Therapeutics, Novartis, Roche, and Sanofi.
FROM CMSC 2024
The Positive Effects of Exercise in MS
NASHVILLE, TENNESSEE — Exercise has a long history in multiple sclerosis (MS). In 1838, the Scottish physician John Abercrombie reported that a patient with “a diminution of muscular power,” who could walk but only unsteadily, decided after various failed treatments like “evacuations and spare diet” to try “violent exercise.” He walked 5-6 miles on a warm evening, as quickly as he was able, and returned home “much fatigued, and considerably heated. Next morning he had severe pains in the calves of his legs, but his other complaints were much diminished, and in a few days disappeared. He has ever since enjoyed good health,” Dr. Abercrombie was quoted in Multiple Sclerosis: The History of a Disease by T. Jock Murray.
The first randomized, controlled trial of an exercise intervention for MS didn’t appear in the literature until 1988, but more than 200 have been published in the years since, according to Robert Motl, PhD, who spoke about exercise interventions for MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In fact, the evidence shows that exercise can improve walking performance and quality of life. “When we look at what we might call the unseen symptoms, we can see the exercise training is very effective at reducing fatigue in people with MS. It’s very effective at reducing depressive mood in individuals living with MS. There is moderate evidence that it can improve mobility, particularly lower extremity mobility and walking performance in individuals living with multiple sclerosis, as well as balance. And lastly, we see consistent evidence that exercise training can improve quality of life,” said Dr. Motl, who is a professor of kinesiology and nutrition at University of Illinois, Chicago.
There is less evidence that exercise training helps mobility, anxiety, pain, and participation, he said.
Dr. Motl showed the results of various meta-analyses that he co-authored of randomized, controlled trials (RCTs) of exercise training. One meta-analysis of 20 trials that examined the effect on fitness found an effect size of 0.47, which was about one-half of a standard deviation, and is considered to be a clinically meaningful effect. There was also about a 20% improvement in aerobic capacity, and this improves the capacity for maintaining independence, according to Dr. Motl. “That’s huge as individuals who are living with MS over a long-term period of time are aging with this chronic disease and independence does become an issue later in life. We maybe can forestall some of that,” he said.
Another meta-analysis of 17 RCTs examining exercise training and fatigue found a similar effect size of 0.452. When the authors limited the analysis to studies that used the Fatigue Severity Score and its benchmark of clinically significant fatigue of 4.0, “they were able to reduce the mean fatigue severity score below 4.0, meaning you’re taking individuals who have severe fatigue and reducing their fatigue below a threshold of severity that impacts everyday life. So this is something that is clinically meaningful and relevant to the lives of individuals with MS,” he said.
With respect to depression, a meta-analysis of 14 randomized, controlled trials found an effect size of 0.55 standard deviations. The researchers found that the effect size was associated with the number of days per week: The effect was size was doubled among individuals who exercised 3 or more times per week. Another meta-analysis of walking found an average 2-second improvement in walking speed and about a 40-meter improvement in walking endurance. “I believe that’s pretty comparable to what you see with Ampyra (dalfampridine) and its effects on walking speeds, so we’re seeing something that’s as good as a pharmacological agent for managing walking in MS,” said Dr. Motl.
Another meta-analysis of health-related quality of life found that the effect on the physical domain was about twice as large as the effect on mental health–related quality of life. “I think that makes sense because when you are engaging in exercise, it’s a physically invoking stimulus. As you see adaptations, your perceptions of your physical health improve,” said Dr. Motl.
Dr. Motl also addressed safety. There have been some concerns that exercise could lead to temporary worsening of symptoms, “but it was blown up into a major, major problem when it is only 5% of individuals who have these sorts of severe problems,” said Dr. Motl. A systematic review in 2023 found an adverse event rate of 1.2% in the control groups and 2.0% in the exercise groups. This was about the same rates that are seen in the general population, according to Dr. Motl. A consistent adverse event was lower back pain, but further analysis showed it was only reported with resistance training. “The beauty of that is that we have incredible people in the field of MS, who know how to deliver resistance training more safely. And if we do that more effectively, we can avoid this very common injury with exercise training,” said Dr. Motl.
The review also found a 25% reduction in relapses. “It was very interesting. I don’t know if we want to say exercise is a disease-modifying behavior yet, but that effect at the time that these studies were done was about the same as some of the early disease-modifying therapies, showing the same degree of reduction of relapse rate,” said Dr. Motl.
Dr. Motl also discussed updated guidelines for exercise in patients with mild to moderate MS, as well as Parkinson’s disease and stroke survivors. The general advice is for 2-3 days of moderate aerobic exercise per week, beginning at 10 minutes and gradually increasing to 30 minutes per session. The newer guidelines added an option for advanced aerobic exercise, which can be up to 5 times per week and up to 40 minutes per session. Activities include ergometry, walking, aquatics, and elliptical machines for general aerobic exercise, while advanced exercise can also include running or road cycling. Resistance exercise can be done 2-3 times per week with 1-3 sets of 8-15 repetitions, with a total of 5-10 exercises. The authors recommend weight machines, free weights, or resistance bands.
Dr. Motl has received funding from the Department of Defense, National Institutes of Health, Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, and Bristol Myers Squibb Foundation.
NASHVILLE, TENNESSEE — Exercise has a long history in multiple sclerosis (MS). In 1838, the Scottish physician John Abercrombie reported that a patient with “a diminution of muscular power,” who could walk but only unsteadily, decided after various failed treatments like “evacuations and spare diet” to try “violent exercise.” He walked 5-6 miles on a warm evening, as quickly as he was able, and returned home “much fatigued, and considerably heated. Next morning he had severe pains in the calves of his legs, but his other complaints were much diminished, and in a few days disappeared. He has ever since enjoyed good health,” Dr. Abercrombie was quoted in Multiple Sclerosis: The History of a Disease by T. Jock Murray.
The first randomized, controlled trial of an exercise intervention for MS didn’t appear in the literature until 1988, but more than 200 have been published in the years since, according to Robert Motl, PhD, who spoke about exercise interventions for MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In fact, the evidence shows that exercise can improve walking performance and quality of life. “When we look at what we might call the unseen symptoms, we can see the exercise training is very effective at reducing fatigue in people with MS. It’s very effective at reducing depressive mood in individuals living with MS. There is moderate evidence that it can improve mobility, particularly lower extremity mobility and walking performance in individuals living with multiple sclerosis, as well as balance. And lastly, we see consistent evidence that exercise training can improve quality of life,” said Dr. Motl, who is a professor of kinesiology and nutrition at University of Illinois, Chicago.
There is less evidence that exercise training helps mobility, anxiety, pain, and participation, he said.
Dr. Motl showed the results of various meta-analyses that he co-authored of randomized, controlled trials (RCTs) of exercise training. One meta-analysis of 20 trials that examined the effect on fitness found an effect size of 0.47, which was about one-half of a standard deviation, and is considered to be a clinically meaningful effect. There was also about a 20% improvement in aerobic capacity, and this improves the capacity for maintaining independence, according to Dr. Motl. “That’s huge as individuals who are living with MS over a long-term period of time are aging with this chronic disease and independence does become an issue later in life. We maybe can forestall some of that,” he said.
Another meta-analysis of 17 RCTs examining exercise training and fatigue found a similar effect size of 0.452. When the authors limited the analysis to studies that used the Fatigue Severity Score and its benchmark of clinically significant fatigue of 4.0, “they were able to reduce the mean fatigue severity score below 4.0, meaning you’re taking individuals who have severe fatigue and reducing their fatigue below a threshold of severity that impacts everyday life. So this is something that is clinically meaningful and relevant to the lives of individuals with MS,” he said.
With respect to depression, a meta-analysis of 14 randomized, controlled trials found an effect size of 0.55 standard deviations. The researchers found that the effect size was associated with the number of days per week: The effect was size was doubled among individuals who exercised 3 or more times per week. Another meta-analysis of walking found an average 2-second improvement in walking speed and about a 40-meter improvement in walking endurance. “I believe that’s pretty comparable to what you see with Ampyra (dalfampridine) and its effects on walking speeds, so we’re seeing something that’s as good as a pharmacological agent for managing walking in MS,” said Dr. Motl.
Another meta-analysis of health-related quality of life found that the effect on the physical domain was about twice as large as the effect on mental health–related quality of life. “I think that makes sense because when you are engaging in exercise, it’s a physically invoking stimulus. As you see adaptations, your perceptions of your physical health improve,” said Dr. Motl.
Dr. Motl also addressed safety. There have been some concerns that exercise could lead to temporary worsening of symptoms, “but it was blown up into a major, major problem when it is only 5% of individuals who have these sorts of severe problems,” said Dr. Motl. A systematic review in 2023 found an adverse event rate of 1.2% in the control groups and 2.0% in the exercise groups. This was about the same rates that are seen in the general population, according to Dr. Motl. A consistent adverse event was lower back pain, but further analysis showed it was only reported with resistance training. “The beauty of that is that we have incredible people in the field of MS, who know how to deliver resistance training more safely. And if we do that more effectively, we can avoid this very common injury with exercise training,” said Dr. Motl.
The review also found a 25% reduction in relapses. “It was very interesting. I don’t know if we want to say exercise is a disease-modifying behavior yet, but that effect at the time that these studies were done was about the same as some of the early disease-modifying therapies, showing the same degree of reduction of relapse rate,” said Dr. Motl.
Dr. Motl also discussed updated guidelines for exercise in patients with mild to moderate MS, as well as Parkinson’s disease and stroke survivors. The general advice is for 2-3 days of moderate aerobic exercise per week, beginning at 10 minutes and gradually increasing to 30 minutes per session. The newer guidelines added an option for advanced aerobic exercise, which can be up to 5 times per week and up to 40 minutes per session. Activities include ergometry, walking, aquatics, and elliptical machines for general aerobic exercise, while advanced exercise can also include running or road cycling. Resistance exercise can be done 2-3 times per week with 1-3 sets of 8-15 repetitions, with a total of 5-10 exercises. The authors recommend weight machines, free weights, or resistance bands.
Dr. Motl has received funding from the Department of Defense, National Institutes of Health, Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, and Bristol Myers Squibb Foundation.
NASHVILLE, TENNESSEE — Exercise has a long history in multiple sclerosis (MS). In 1838, the Scottish physician John Abercrombie reported that a patient with “a diminution of muscular power,” who could walk but only unsteadily, decided after various failed treatments like “evacuations and spare diet” to try “violent exercise.” He walked 5-6 miles on a warm evening, as quickly as he was able, and returned home “much fatigued, and considerably heated. Next morning he had severe pains in the calves of his legs, but his other complaints were much diminished, and in a few days disappeared. He has ever since enjoyed good health,” Dr. Abercrombie was quoted in Multiple Sclerosis: The History of a Disease by T. Jock Murray.
The first randomized, controlled trial of an exercise intervention for MS didn’t appear in the literature until 1988, but more than 200 have been published in the years since, according to Robert Motl, PhD, who spoke about exercise interventions for MS at the annual meeting of the Consortium of Multiple Sclerosis Centers.
In fact, the evidence shows that exercise can improve walking performance and quality of life. “When we look at what we might call the unseen symptoms, we can see the exercise training is very effective at reducing fatigue in people with MS. It’s very effective at reducing depressive mood in individuals living with MS. There is moderate evidence that it can improve mobility, particularly lower extremity mobility and walking performance in individuals living with multiple sclerosis, as well as balance. And lastly, we see consistent evidence that exercise training can improve quality of life,” said Dr. Motl, who is a professor of kinesiology and nutrition at University of Illinois, Chicago.
There is less evidence that exercise training helps mobility, anxiety, pain, and participation, he said.
Dr. Motl showed the results of various meta-analyses that he co-authored of randomized, controlled trials (RCTs) of exercise training. One meta-analysis of 20 trials that examined the effect on fitness found an effect size of 0.47, which was about one-half of a standard deviation, and is considered to be a clinically meaningful effect. There was also about a 20% improvement in aerobic capacity, and this improves the capacity for maintaining independence, according to Dr. Motl. “That’s huge as individuals who are living with MS over a long-term period of time are aging with this chronic disease and independence does become an issue later in life. We maybe can forestall some of that,” he said.
Another meta-analysis of 17 RCTs examining exercise training and fatigue found a similar effect size of 0.452. When the authors limited the analysis to studies that used the Fatigue Severity Score and its benchmark of clinically significant fatigue of 4.0, “they were able to reduce the mean fatigue severity score below 4.0, meaning you’re taking individuals who have severe fatigue and reducing their fatigue below a threshold of severity that impacts everyday life. So this is something that is clinically meaningful and relevant to the lives of individuals with MS,” he said.
With respect to depression, a meta-analysis of 14 randomized, controlled trials found an effect size of 0.55 standard deviations. The researchers found that the effect size was associated with the number of days per week: The effect was size was doubled among individuals who exercised 3 or more times per week. Another meta-analysis of walking found an average 2-second improvement in walking speed and about a 40-meter improvement in walking endurance. “I believe that’s pretty comparable to what you see with Ampyra (dalfampridine) and its effects on walking speeds, so we’re seeing something that’s as good as a pharmacological agent for managing walking in MS,” said Dr. Motl.
Another meta-analysis of health-related quality of life found that the effect on the physical domain was about twice as large as the effect on mental health–related quality of life. “I think that makes sense because when you are engaging in exercise, it’s a physically invoking stimulus. As you see adaptations, your perceptions of your physical health improve,” said Dr. Motl.
Dr. Motl also addressed safety. There have been some concerns that exercise could lead to temporary worsening of symptoms, “but it was blown up into a major, major problem when it is only 5% of individuals who have these sorts of severe problems,” said Dr. Motl. A systematic review in 2023 found an adverse event rate of 1.2% in the control groups and 2.0% in the exercise groups. This was about the same rates that are seen in the general population, according to Dr. Motl. A consistent adverse event was lower back pain, but further analysis showed it was only reported with resistance training. “The beauty of that is that we have incredible people in the field of MS, who know how to deliver resistance training more safely. And if we do that more effectively, we can avoid this very common injury with exercise training,” said Dr. Motl.
The review also found a 25% reduction in relapses. “It was very interesting. I don’t know if we want to say exercise is a disease-modifying behavior yet, but that effect at the time that these studies were done was about the same as some of the early disease-modifying therapies, showing the same degree of reduction of relapse rate,” said Dr. Motl.
Dr. Motl also discussed updated guidelines for exercise in patients with mild to moderate MS, as well as Parkinson’s disease and stroke survivors. The general advice is for 2-3 days of moderate aerobic exercise per week, beginning at 10 minutes and gradually increasing to 30 minutes per session. The newer guidelines added an option for advanced aerobic exercise, which can be up to 5 times per week and up to 40 minutes per session. Activities include ergometry, walking, aquatics, and elliptical machines for general aerobic exercise, while advanced exercise can also include running or road cycling. Resistance exercise can be done 2-3 times per week with 1-3 sets of 8-15 repetitions, with a total of 5-10 exercises. The authors recommend weight machines, free weights, or resistance bands.
Dr. Motl has received funding from the Department of Defense, National Institutes of Health, Patient-Centered Outcomes Research Institute, National Multiple Sclerosis Society, and Bristol Myers Squibb Foundation.
FROM CMSC 2024
Advice, Support for Entrepreneurs at AGA Tech 2024
CHICAGO — Have a great tech idea to improve gastroenterology? Start-up companies have the potential to transform the practice of medicine, and to make founders a nice pot of money, but it is a difficult road. At the 2024 AGA Tech Summit, held at the Chicago headquarters of MATTER, a global healthcare startup incubator, investors and gastroenterologists discussed some of the key challenges and opportunities for GI startups.
The road is daunting, and founders must be dedicated to their companies but also maintain life balance. “It is very easy, following your passion, for your life to get out of check. I don’t know what the divorce rate is for entrepreneurs, but I personally was a victim of that. The culture that we built was addictive and it became all encompassing, and at the same time [I neglected] my home life,” Scott Fraser, managing director of the consulting company Fraser Healthcare, said during a “Scars and Stripes” panel at the summit.
For those willing to navigate those waters, there is help. Investors are prepared to provide seed money for companies with good ideas and a strong market. AGA itself has stepped into the investment field with its GI Opportunity Fund, which it launched in 2022 through a partnership with Varia Ventures. The fund’s capital comes from AGA members, with a minimum investment of $25,000. To date, AGA has made investments in six companies, at around $100,000 per company. “It’s not a large amount that we’re investing. We’re a lead investor that signals to other venture capital companies that this is a viable company,” Tom Serena, CEO of AGA, said in an interview.
The fund grew out of AGA’s commitment to boosting early-stage companies in the gastroenterology space. AGA has always supported GI device and tech companies through its Center for GI Innovation and Technology, which sponsored the AGA Tech Summit. The center now provides resources and advice for GI innovators and startups. The AGA Tech Summit has created a gathering place for entrepreneurs and innovators to share their experiences and learn from one another. “But what we were missing was the last mile, which is getting funding to the companies,” said Mr. Serena. The summit itself has been modified to increase the venture capital presence. “That’s the networking we’re trying to [create] here. Venture capitalists are well acquainted with these companies, but we feel that AGA can bring clinical due diligence, and the startups want to be exposed to venture capital,” said Mr. Serena.
During the “Learn from VC Strategists” panel, investors shared advice for entrepreneurs. The emphasis throughout was on marketable ideas that can fundamentally change healthcare practice, though inventions may not have the whiz-bang appeal of some new technologies of years past.
“We’re particularly focused on clinical models that actually work. There were a lot of companies for many years that were doing things that had minimal impact, or very incremental impact. Maybe they were helping identify certain patients, but they weren’t actually engaging those patients. We’re now looking very end-to-end and trying to make sure that it’s not just a good idea, but one that you can actually roll out, engage patients, and see the [return on investment] in that patient data,” said Kelsey Maguire, managing director of the Blue Venture Fund, which is a collaborative effort across Blue Cross Blue Shield companies.
Part of the reason for that shift is that healthcare has evolved in a way that has put more pressure on physicians, according to Barbara H. Jung, MD, AGAF, past president of AGA, who was present for the session. “I think that there’s huge burnout among gastroenterologists, [partly because] some of the systems have been optimized to get the most out of each specialist. I think we just have to get back to making work more enjoyable. [It could be less] fighting with the insurance companies, it could be that you spend less time typing after hours. It could be that it helps the team work more seamlessly, or it could be something that helps the patient prepare, so they have everything ready when they see the doctors. It’s thinking about how healthcare is delivered, and really in a patient and physician-centric way,” Dr. Jung said in an interview.
Anna Haghgooie, managing director of Valtruis, noted that, historically, new technology has been rewarded by the healthcare system. “It’s part of why we find ourselves where we are as an industry: There was nobody in the marketplace that was incented to roll out a cost-reducing technology, and those weren’t necessarily considered grand slams. But [I think] we’re at a tipping point on cost, and as a country will start purchasing in pretty meaningfully different ways, which opens up a lot of opportunities for those practical solutions to be grand slams. Everything that we look at has a component of virtual care, leveraging technology, whether it’s AI or just better workflow tools, better data and intelligence to make business decisions,” said Ms. Haghgooie. She did note that Valtruis does not work much with medical devices.
Specifically in the GI space, one panelist called for a shift away from novel colonoscopy technology. “I don’t know how many more bells and whistles we can ask for colonoscopy, which we’re very dependent on. Not that it’s not important, but I don’t think that’s where the real innovation is going to come. When you think about the cognitive side of the GI business: New diagnostics, things that are predictive of disease states, things that monitor disease, things that help you to know what people’s disease courses will be. I think as more and more interventions are done by endoscopists, you need more tools,” said Thomas Shehab, MD, managing partner at Arboretum Ventures.
Finally, AI has become a central component to investment decisions. Ms. Haghgooie said that Valtruis is focused on the infrastructure surrounding AI, such as the data that it requires to make or help guide decisions. That data can vary widely in quality, is difficult to index, exists in various silos, and is subject to a number of regulatory constraints on how to move or aggregate it. “So, a lot of what we’re focused on are the systems and tools that can enable the next gen application of AI. That’s one piece of the puzzle. The other is, I’d say that every company that we’ve either invested in or are looking at investing in, we ask the question: How are you planning to incorporate and leverage this next gen technology to drive your marginal cost-to-deliver down? In many cases you have to do that through business model redesign, because there is no fee-for-service code to get paid for leveraging AI to reduce your costs. You’ve got to have different payment structures in order to get the benefit of leveraging those types of technologies. When we’re sourcing and looking at deals, we’re looking at both of those angles,” she said.
CHICAGO — Have a great tech idea to improve gastroenterology? Start-up companies have the potential to transform the practice of medicine, and to make founders a nice pot of money, but it is a difficult road. At the 2024 AGA Tech Summit, held at the Chicago headquarters of MATTER, a global healthcare startup incubator, investors and gastroenterologists discussed some of the key challenges and opportunities for GI startups.
The road is daunting, and founders must be dedicated to their companies but also maintain life balance. “It is very easy, following your passion, for your life to get out of check. I don’t know what the divorce rate is for entrepreneurs, but I personally was a victim of that. The culture that we built was addictive and it became all encompassing, and at the same time [I neglected] my home life,” Scott Fraser, managing director of the consulting company Fraser Healthcare, said during a “Scars and Stripes” panel at the summit.
For those willing to navigate those waters, there is help. Investors are prepared to provide seed money for companies with good ideas and a strong market. AGA itself has stepped into the investment field with its GI Opportunity Fund, which it launched in 2022 through a partnership with Varia Ventures. The fund’s capital comes from AGA members, with a minimum investment of $25,000. To date, AGA has made investments in six companies, at around $100,000 per company. “It’s not a large amount that we’re investing. We’re a lead investor that signals to other venture capital companies that this is a viable company,” Tom Serena, CEO of AGA, said in an interview.
The fund grew out of AGA’s commitment to boosting early-stage companies in the gastroenterology space. AGA has always supported GI device and tech companies through its Center for GI Innovation and Technology, which sponsored the AGA Tech Summit. The center now provides resources and advice for GI innovators and startups. The AGA Tech Summit has created a gathering place for entrepreneurs and innovators to share their experiences and learn from one another. “But what we were missing was the last mile, which is getting funding to the companies,” said Mr. Serena. The summit itself has been modified to increase the venture capital presence. “That’s the networking we’re trying to [create] here. Venture capitalists are well acquainted with these companies, but we feel that AGA can bring clinical due diligence, and the startups want to be exposed to venture capital,” said Mr. Serena.
During the “Learn from VC Strategists” panel, investors shared advice for entrepreneurs. The emphasis throughout was on marketable ideas that can fundamentally change healthcare practice, though inventions may not have the whiz-bang appeal of some new technologies of years past.
“We’re particularly focused on clinical models that actually work. There were a lot of companies for many years that were doing things that had minimal impact, or very incremental impact. Maybe they were helping identify certain patients, but they weren’t actually engaging those patients. We’re now looking very end-to-end and trying to make sure that it’s not just a good idea, but one that you can actually roll out, engage patients, and see the [return on investment] in that patient data,” said Kelsey Maguire, managing director of the Blue Venture Fund, which is a collaborative effort across Blue Cross Blue Shield companies.
Part of the reason for that shift is that healthcare has evolved in a way that has put more pressure on physicians, according to Barbara H. Jung, MD, AGAF, past president of AGA, who was present for the session. “I think that there’s huge burnout among gastroenterologists, [partly because] some of the systems have been optimized to get the most out of each specialist. I think we just have to get back to making work more enjoyable. [It could be less] fighting with the insurance companies, it could be that you spend less time typing after hours. It could be that it helps the team work more seamlessly, or it could be something that helps the patient prepare, so they have everything ready when they see the doctors. It’s thinking about how healthcare is delivered, and really in a patient and physician-centric way,” Dr. Jung said in an interview.
Anna Haghgooie, managing director of Valtruis, noted that, historically, new technology has been rewarded by the healthcare system. “It’s part of why we find ourselves where we are as an industry: There was nobody in the marketplace that was incented to roll out a cost-reducing technology, and those weren’t necessarily considered grand slams. But [I think] we’re at a tipping point on cost, and as a country will start purchasing in pretty meaningfully different ways, which opens up a lot of opportunities for those practical solutions to be grand slams. Everything that we look at has a component of virtual care, leveraging technology, whether it’s AI or just better workflow tools, better data and intelligence to make business decisions,” said Ms. Haghgooie. She did note that Valtruis does not work much with medical devices.
Specifically in the GI space, one panelist called for a shift away from novel colonoscopy technology. “I don’t know how many more bells and whistles we can ask for colonoscopy, which we’re very dependent on. Not that it’s not important, but I don’t think that’s where the real innovation is going to come. When you think about the cognitive side of the GI business: New diagnostics, things that are predictive of disease states, things that monitor disease, things that help you to know what people’s disease courses will be. I think as more and more interventions are done by endoscopists, you need more tools,” said Thomas Shehab, MD, managing partner at Arboretum Ventures.
Finally, AI has become a central component to investment decisions. Ms. Haghgooie said that Valtruis is focused on the infrastructure surrounding AI, such as the data that it requires to make or help guide decisions. That data can vary widely in quality, is difficult to index, exists in various silos, and is subject to a number of regulatory constraints on how to move or aggregate it. “So, a lot of what we’re focused on are the systems and tools that can enable the next gen application of AI. That’s one piece of the puzzle. The other is, I’d say that every company that we’ve either invested in or are looking at investing in, we ask the question: How are you planning to incorporate and leverage this next gen technology to drive your marginal cost-to-deliver down? In many cases you have to do that through business model redesign, because there is no fee-for-service code to get paid for leveraging AI to reduce your costs. You’ve got to have different payment structures in order to get the benefit of leveraging those types of technologies. When we’re sourcing and looking at deals, we’re looking at both of those angles,” she said.
CHICAGO — Have a great tech idea to improve gastroenterology? Start-up companies have the potential to transform the practice of medicine, and to make founders a nice pot of money, but it is a difficult road. At the 2024 AGA Tech Summit, held at the Chicago headquarters of MATTER, a global healthcare startup incubator, investors and gastroenterologists discussed some of the key challenges and opportunities for GI startups.
The road is daunting, and founders must be dedicated to their companies but also maintain life balance. “It is very easy, following your passion, for your life to get out of check. I don’t know what the divorce rate is for entrepreneurs, but I personally was a victim of that. The culture that we built was addictive and it became all encompassing, and at the same time [I neglected] my home life,” Scott Fraser, managing director of the consulting company Fraser Healthcare, said during a “Scars and Stripes” panel at the summit.
For those willing to navigate those waters, there is help. Investors are prepared to provide seed money for companies with good ideas and a strong market. AGA itself has stepped into the investment field with its GI Opportunity Fund, which it launched in 2022 through a partnership with Varia Ventures. The fund’s capital comes from AGA members, with a minimum investment of $25,000. To date, AGA has made investments in six companies, at around $100,000 per company. “It’s not a large amount that we’re investing. We’re a lead investor that signals to other venture capital companies that this is a viable company,” Tom Serena, CEO of AGA, said in an interview.
The fund grew out of AGA’s commitment to boosting early-stage companies in the gastroenterology space. AGA has always supported GI device and tech companies through its Center for GI Innovation and Technology, which sponsored the AGA Tech Summit. The center now provides resources and advice for GI innovators and startups. The AGA Tech Summit has created a gathering place for entrepreneurs and innovators to share their experiences and learn from one another. “But what we were missing was the last mile, which is getting funding to the companies,” said Mr. Serena. The summit itself has been modified to increase the venture capital presence. “That’s the networking we’re trying to [create] here. Venture capitalists are well acquainted with these companies, but we feel that AGA can bring clinical due diligence, and the startups want to be exposed to venture capital,” said Mr. Serena.
During the “Learn from VC Strategists” panel, investors shared advice for entrepreneurs. The emphasis throughout was on marketable ideas that can fundamentally change healthcare practice, though inventions may not have the whiz-bang appeal of some new technologies of years past.
“We’re particularly focused on clinical models that actually work. There were a lot of companies for many years that were doing things that had minimal impact, or very incremental impact. Maybe they were helping identify certain patients, but they weren’t actually engaging those patients. We’re now looking very end-to-end and trying to make sure that it’s not just a good idea, but one that you can actually roll out, engage patients, and see the [return on investment] in that patient data,” said Kelsey Maguire, managing director of the Blue Venture Fund, which is a collaborative effort across Blue Cross Blue Shield companies.
Part of the reason for that shift is that healthcare has evolved in a way that has put more pressure on physicians, according to Barbara H. Jung, MD, AGAF, past president of AGA, who was present for the session. “I think that there’s huge burnout among gastroenterologists, [partly because] some of the systems have been optimized to get the most out of each specialist. I think we just have to get back to making work more enjoyable. [It could be less] fighting with the insurance companies, it could be that you spend less time typing after hours. It could be that it helps the team work more seamlessly, or it could be something that helps the patient prepare, so they have everything ready when they see the doctors. It’s thinking about how healthcare is delivered, and really in a patient and physician-centric way,” Dr. Jung said in an interview.
Anna Haghgooie, managing director of Valtruis, noted that, historically, new technology has been rewarded by the healthcare system. “It’s part of why we find ourselves where we are as an industry: There was nobody in the marketplace that was incented to roll out a cost-reducing technology, and those weren’t necessarily considered grand slams. But [I think] we’re at a tipping point on cost, and as a country will start purchasing in pretty meaningfully different ways, which opens up a lot of opportunities for those practical solutions to be grand slams. Everything that we look at has a component of virtual care, leveraging technology, whether it’s AI or just better workflow tools, better data and intelligence to make business decisions,” said Ms. Haghgooie. She did note that Valtruis does not work much with medical devices.
Specifically in the GI space, one panelist called for a shift away from novel colonoscopy technology. “I don’t know how many more bells and whistles we can ask for colonoscopy, which we’re very dependent on. Not that it’s not important, but I don’t think that’s where the real innovation is going to come. When you think about the cognitive side of the GI business: New diagnostics, things that are predictive of disease states, things that monitor disease, things that help you to know what people’s disease courses will be. I think as more and more interventions are done by endoscopists, you need more tools,” said Thomas Shehab, MD, managing partner at Arboretum Ventures.
Finally, AI has become a central component to investment decisions. Ms. Haghgooie said that Valtruis is focused on the infrastructure surrounding AI, such as the data that it requires to make or help guide decisions. That data can vary widely in quality, is difficult to index, exists in various silos, and is subject to a number of regulatory constraints on how to move or aggregate it. “So, a lot of what we’re focused on are the systems and tools that can enable the next gen application of AI. That’s one piece of the puzzle. The other is, I’d say that every company that we’ve either invested in or are looking at investing in, we ask the question: How are you planning to incorporate and leverage this next gen technology to drive your marginal cost-to-deliver down? In many cases you have to do that through business model redesign, because there is no fee-for-service code to get paid for leveraging AI to reduce your costs. You’ve got to have different payment structures in order to get the benefit of leveraging those types of technologies. When we’re sourcing and looking at deals, we’re looking at both of those angles,” she said.
FROM THE 2024 AGA TECH SUMMIT
MS in Men: Unusual, and Unusually Challenging
NASHVILLE, TENNESSEE — Disease course, mental health, and social function may be different in male patients.
Among the clinical differences: Men may be diagnosed at an older age, often closer to 30 years of age, and they more often experience memory problems, spinal cord lesions, and motor symptoms. They are at higher risk of progressive-onset disease, but have lower relapse rates. Disability rates are higher in men than in women, but long-term survival is no different. Brain atrophy is also more common among men.
Not all MRI facilities will include brain atrophy assessment, so it is a good idea to put an order in for brain atrophy when there are reasons to be concerned, such as cognitive effects or issues with walking, according to Jeffrey Hernandez, DNP, during a talk at the annual meeting of the Consortium of Multiple Sclerosis Centers. Dr. Hernandez is affiliated with the University of Miami Multiple Sclerosis Center.
Addressing Sensitive Topics
Men may be less willing to discuss their symptoms, in part because they may have been raised to be tough and stoic. “Looking for help might make them feel more vulnerable,” said Dr. Hernandez. That’s not a feeling that most men are familiar with, he said. Men “don’t want to be deemed or seem weak or dependent on anyone.” Consequently, men are less likely to complain about any symptom, said Dr. Hernandez.
He advised asking more open-ended questions in an effort to draw men out. “Just ask how they’re doing. See if anything has changed from their usual habits, have their activities of daily living changed, has their work performance changed? That can give you an indication. One of my patients [said he] was demoted from [his] position, that the demotion was related to cognitive impairment and the way that he was working. That gives you an idea as to where you can help intervene and perhaps make an improvement for that patient’s quality of life, or consider switching treatments,” said Dr. Hernandez.
Men are less likely to report symptoms such as tingling, physical complaints, cognitive difficulties, mood changes, and sexual dysfunction. That doesn’t mean they’re not experiencing issues, though, especially when it comes to sexual problems. Dr. Hernandez recalled one patient who just stared out the window when asked about his sex life. “Then I said, the next time I want your wife to be here, and then she spilled the beans on everything. So it’s important sometimes to include other members of the family or their partners in the conversation to give you some insight. And perhaps that day it wasn’t a priority for him, but then the next time it was a priority for his wife,” he said.
He pointed out that erectile dysfunction could be due to a physiological response to MS, or to psychological effects.
Low testosterone levels may also play a role in MS, since it is a natural anti-inflammatory hormone. Hypogonadism has been found to be high among men with MS in some studies. MS in men is associated with more enhancing lesions, greater cognitive decline, and increased risk of disability, while high levels of testosterone are linked to neuroprotective effects and lower risk of developing MS.
Men with MS are more likely than women to report suicidal thoughts when depressed, and mental health can be taboo, as men may try to solve problems on their own before seeking help. “But a lot of the times they can use a little bit of help, whether it be from talk therapy or meds. With the expansion of telemedicine, virtual care has skyrocketed in psychiatry. I advocate strongly for it. Psychologytoday.com is a very common portal that I recommend so they can look up providers with their insurances, and they can see who gives in person versus virtual care. They can do it from the comfort of their car. I’ve had people in their car crying because they don’t want to be in their house when they talk to me,” said Dr. Hernandez.
Physical struggles can lead men to feel they’ve lost their independence, and that they are no longer the protector of the household. Divorce is common, which can lead to social isolation. One patient wanted to see Dr. Hernandez monthly, a request that he had to decline. “Sometimes they want to discuss these things and they just don’t have someone to talk to,” said Dr. Hernandez. Social support programs through the National MS Society, the MS Foundation, or the Multiple Sclerosis Association of America may sponsor local programs that could be beneficial.
Dr. Hernandez has no relevant financial disclosures.
NASHVILLE, TENNESSEE — Disease course, mental health, and social function may be different in male patients.
Among the clinical differences: Men may be diagnosed at an older age, often closer to 30 years of age, and they more often experience memory problems, spinal cord lesions, and motor symptoms. They are at higher risk of progressive-onset disease, but have lower relapse rates. Disability rates are higher in men than in women, but long-term survival is no different. Brain atrophy is also more common among men.
Not all MRI facilities will include brain atrophy assessment, so it is a good idea to put an order in for brain atrophy when there are reasons to be concerned, such as cognitive effects or issues with walking, according to Jeffrey Hernandez, DNP, during a talk at the annual meeting of the Consortium of Multiple Sclerosis Centers. Dr. Hernandez is affiliated with the University of Miami Multiple Sclerosis Center.
Addressing Sensitive Topics
Men may be less willing to discuss their symptoms, in part because they may have been raised to be tough and stoic. “Looking for help might make them feel more vulnerable,” said Dr. Hernandez. That’s not a feeling that most men are familiar with, he said. Men “don’t want to be deemed or seem weak or dependent on anyone.” Consequently, men are less likely to complain about any symptom, said Dr. Hernandez.
He advised asking more open-ended questions in an effort to draw men out. “Just ask how they’re doing. See if anything has changed from their usual habits, have their activities of daily living changed, has their work performance changed? That can give you an indication. One of my patients [said he] was demoted from [his] position, that the demotion was related to cognitive impairment and the way that he was working. That gives you an idea as to where you can help intervene and perhaps make an improvement for that patient’s quality of life, or consider switching treatments,” said Dr. Hernandez.
Men are less likely to report symptoms such as tingling, physical complaints, cognitive difficulties, mood changes, and sexual dysfunction. That doesn’t mean they’re not experiencing issues, though, especially when it comes to sexual problems. Dr. Hernandez recalled one patient who just stared out the window when asked about his sex life. “Then I said, the next time I want your wife to be here, and then she spilled the beans on everything. So it’s important sometimes to include other members of the family or their partners in the conversation to give you some insight. And perhaps that day it wasn’t a priority for him, but then the next time it was a priority for his wife,” he said.
He pointed out that erectile dysfunction could be due to a physiological response to MS, or to psychological effects.
Low testosterone levels may also play a role in MS, since it is a natural anti-inflammatory hormone. Hypogonadism has been found to be high among men with MS in some studies. MS in men is associated with more enhancing lesions, greater cognitive decline, and increased risk of disability, while high levels of testosterone are linked to neuroprotective effects and lower risk of developing MS.
Men with MS are more likely than women to report suicidal thoughts when depressed, and mental health can be taboo, as men may try to solve problems on their own before seeking help. “But a lot of the times they can use a little bit of help, whether it be from talk therapy or meds. With the expansion of telemedicine, virtual care has skyrocketed in psychiatry. I advocate strongly for it. Psychologytoday.com is a very common portal that I recommend so they can look up providers with their insurances, and they can see who gives in person versus virtual care. They can do it from the comfort of their car. I’ve had people in their car crying because they don’t want to be in their house when they talk to me,” said Dr. Hernandez.
Physical struggles can lead men to feel they’ve lost their independence, and that they are no longer the protector of the household. Divorce is common, which can lead to social isolation. One patient wanted to see Dr. Hernandez monthly, a request that he had to decline. “Sometimes they want to discuss these things and they just don’t have someone to talk to,” said Dr. Hernandez. Social support programs through the National MS Society, the MS Foundation, or the Multiple Sclerosis Association of America may sponsor local programs that could be beneficial.
Dr. Hernandez has no relevant financial disclosures.
NASHVILLE, TENNESSEE — Disease course, mental health, and social function may be different in male patients.
Among the clinical differences: Men may be diagnosed at an older age, often closer to 30 years of age, and they more often experience memory problems, spinal cord lesions, and motor symptoms. They are at higher risk of progressive-onset disease, but have lower relapse rates. Disability rates are higher in men than in women, but long-term survival is no different. Brain atrophy is also more common among men.
Not all MRI facilities will include brain atrophy assessment, so it is a good idea to put an order in for brain atrophy when there are reasons to be concerned, such as cognitive effects or issues with walking, according to Jeffrey Hernandez, DNP, during a talk at the annual meeting of the Consortium of Multiple Sclerosis Centers. Dr. Hernandez is affiliated with the University of Miami Multiple Sclerosis Center.
Addressing Sensitive Topics
Men may be less willing to discuss their symptoms, in part because they may have been raised to be tough and stoic. “Looking for help might make them feel more vulnerable,” said Dr. Hernandez. That’s not a feeling that most men are familiar with, he said. Men “don’t want to be deemed or seem weak or dependent on anyone.” Consequently, men are less likely to complain about any symptom, said Dr. Hernandez.
He advised asking more open-ended questions in an effort to draw men out. “Just ask how they’re doing. See if anything has changed from their usual habits, have their activities of daily living changed, has their work performance changed? That can give you an indication. One of my patients [said he] was demoted from [his] position, that the demotion was related to cognitive impairment and the way that he was working. That gives you an idea as to where you can help intervene and perhaps make an improvement for that patient’s quality of life, or consider switching treatments,” said Dr. Hernandez.
Men are less likely to report symptoms such as tingling, physical complaints, cognitive difficulties, mood changes, and sexual dysfunction. That doesn’t mean they’re not experiencing issues, though, especially when it comes to sexual problems. Dr. Hernandez recalled one patient who just stared out the window when asked about his sex life. “Then I said, the next time I want your wife to be here, and then she spilled the beans on everything. So it’s important sometimes to include other members of the family or their partners in the conversation to give you some insight. And perhaps that day it wasn’t a priority for him, but then the next time it was a priority for his wife,” he said.
He pointed out that erectile dysfunction could be due to a physiological response to MS, or to psychological effects.
Low testosterone levels may also play a role in MS, since it is a natural anti-inflammatory hormone. Hypogonadism has been found to be high among men with MS in some studies. MS in men is associated with more enhancing lesions, greater cognitive decline, and increased risk of disability, while high levels of testosterone are linked to neuroprotective effects and lower risk of developing MS.
Men with MS are more likely than women to report suicidal thoughts when depressed, and mental health can be taboo, as men may try to solve problems on their own before seeking help. “But a lot of the times they can use a little bit of help, whether it be from talk therapy or meds. With the expansion of telemedicine, virtual care has skyrocketed in psychiatry. I advocate strongly for it. Psychologytoday.com is a very common portal that I recommend so they can look up providers with their insurances, and they can see who gives in person versus virtual care. They can do it from the comfort of their car. I’ve had people in their car crying because they don’t want to be in their house when they talk to me,” said Dr. Hernandez.
Physical struggles can lead men to feel they’ve lost their independence, and that they are no longer the protector of the household. Divorce is common, which can lead to social isolation. One patient wanted to see Dr. Hernandez monthly, a request that he had to decline. “Sometimes they want to discuss these things and they just don’t have someone to talk to,” said Dr. Hernandez. Social support programs through the National MS Society, the MS Foundation, or the Multiple Sclerosis Association of America may sponsor local programs that could be beneficial.
Dr. Hernandez has no relevant financial disclosures.
FROM CMSC 2024
Strategies for MS Fatigue and Sleep Issues
NASHVILLE, TENNESSEE —
Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.
It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
Fatigue
When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.
“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.
It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.
A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.
Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.
The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
Sleep
Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.
One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.
Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.
As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.
Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.
Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.
Dr. Tworek did not report any disclosures or conflicts of interest.
NASHVILLE, TENNESSEE —
Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.
It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
Fatigue
When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.
“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.
It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.
A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.
Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.
The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
Sleep
Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.
One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.
Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.
As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.
Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.
Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.
Dr. Tworek did not report any disclosures or conflicts of interest.
NASHVILLE, TENNESSEE —
Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.
It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
Fatigue
When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.
“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.
It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.
A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.
Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.
The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
Sleep
Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.
One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.
Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.
As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.
Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.
Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.
Dr. Tworek did not report any disclosures or conflicts of interest.
FROM CMSC 2024
In MS With Mild Symptoms, Non-Motor Symptoms Predict Later Mobility Problems
NASHVILLE, TENNESSEE — However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.
The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.
“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
Focusing on Non-Motor Symptoms
When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).
Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.
A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R2 adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R2 value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R2 value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R2 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).
“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.
She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
Perception May Differ From Actual Function
During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.
She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.
Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.
Dr. Williams and Dr. Fritz have no relevant financial disclosures.
NASHVILLE, TENNESSEE — However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.
The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.
“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
Focusing on Non-Motor Symptoms
When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).
Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.
A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R2 adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R2 value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R2 value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R2 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).
“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.
She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
Perception May Differ From Actual Function
During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.
She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.
Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.
Dr. Williams and Dr. Fritz have no relevant financial disclosures.
NASHVILLE, TENNESSEE — However, these associations fall away among patients with more severe disease, according to a new study performed in Australia. The findings could eventually help tailor physical activity interventions.
The research grew out of frustrations with developing interventions focused on strength. “There are many systematic reviews showing stronger and stronger evidence that exercise is beneficial. It does change your walking. It does improve your balance,” said Katrina Williams, PhD, during a presentation of the results at the annual meeting of the Consortium of Multiple Sclerosis Centers.
However, when her group’s intervention studies yielded no statistically significant improvements, she began to search for explanations, and began to suspect heterogeneity among MS patients. Their clinic took all comers, regardless of disability level. “[Our attitude was] we will make it work. We’ll get you actively moving and exercising. But when you break down a lot of those systematic reviews, there’s not a lot of teasing out of disability levels. So, potentially, it is the disability level that might be leading to why some people don’t change or why we’re not getting the statistically significant benefits, because we’re not addressing the individual at their level of disease progression,” said Dr. Williams, who is a senior lecturer in physiotherapy at the University of Queensland, Brisbane, Australia.
“Physiotherapists, we love exercise, we love movement, but we’re a bit unidimensional. It’s some strength training, [or] let’s get on that bike and do cardiovascular. But that may not be enough for individuals who have different symptoms profiles. We’re assuming that the motor profile is the most important, and the one that needs to be addressed in these individuals,” said Dr. Williams.
Focusing on Non-Motor Symptoms
When she searched the literature, she could find little evidence of non-motor symptoms correlating to walking, balance, or even quality of life. To dig deeper, her group studied 220 MS patients in Australia who self-reported symptoms of dizziness, vision problems, fatigue, and spasticity. The population had a mean age of 42 years, and 82% were female. They ranged in disease severity from disease step (DS) 0 to DS 6. The researchers categorized respondents as between DS 0 (mild symptoms that were mostly sensory) to DS 3 (MS interferes with walking) and from DS 4 (early cane use) to DS 6 (requiring bilateral walking support).
Deficits were more commonly reported in the DS 4-6 group than the DS 0-3 group with respect to light touch (88% vs 72%), proprioception (63% vs 41%), fatigue (100% vs 96%), and spasticity (78% vs 69%). There were no significant differences in dizziness, vision, or memory/cognition/emotion.
A linear regression model incorporating sensory worsening, age, social participation, perceived deficit, and spasticity showed an R2 adjusted value of 0.73. However, when they looked only at DS 0-3 patients, the R2 value strengthened to 0.86. Among the DS 4-6 group, the correlation largely disappeared with an R2 value of 0.16. Specifically, there were stronger associations in the DS 0-3 group than the overall group (DS 0-6) between perceived walking deficit and sensory worsening (R2 0.45 vs 0.31), fatigue (0.67 vs 0.05), spasticity (0.47 vs 0.16), and balance (0.8 vs 0.16).
“Most non-motor symptoms do have moderate to weak correlations to walking confidence and walking balance, and quality of life, and the correlations do decline as disability worsens. Those with less disability had more correlations that were stronger, particularly for the walking and balance confidence. So [among those] walking without an aid, there are more non-motor correlations aligned to the actual outcomes. In more disabled, they fell away, so there’s something else going on that we do have to look at,” said Dr. Williams.
She called for other clinicians to explore non-motor symptoms in patients with less disability, and the relationships of those symptoms to gait, balance, and overall MS impact, in the hopes that such observations could improve the tailoring of physiotherapy programs.
Perception May Differ From Actual Function
During the Q&A session, Nora Fritz, PhD, an associate professor of neurology at Wayne State University, Detroit, Michigan, asked about the lack of correlations seen in more disabled patients. “It’s not exactly what you would expect to happen,” said Dr. Fritz, in an interview.
She asked Dr. Williams if the study had sufficient power to detect associations in patients with more severe disability, since the study had a relatively small sample size and many predictors in its regression model. Dr. Fritz also noted that perceptions may differ from actual function, so actual function can’t be captured using a survey. Dr. Williams responded that the group is now working to incorporate more clinical measures to their correlations.
Another audience member said she was “perplexed” by the drop-off of correlation in the most severe group. She suggested the possibility that as patients become more disabled, they may be less likely to perceive the relatively less severe non-motor symptoms and therefore did not report them.
Dr. Williams and Dr. Fritz have no relevant financial disclosures.
FROM CMSC 2024
A Simple Stress Intervention for MS
NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.
Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.
She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).
Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.
“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.
That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.
The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.
Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.
They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.
In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.
The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.
The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).
In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.
The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.
The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.
During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.
Dr. Sullivan did not report any relevant disclosures.
NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.
Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.
She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).
Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.
“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.
That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.
The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.
Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.
They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.
In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.
The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.
The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).
In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.
The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.
The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.
During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.
Dr. Sullivan did not report any relevant disclosures.
NASHVILLE, TENNESSEE — Stress in patients with multiple sclerosis (MS) can have serious effects on quality of life, but there is some evidence that it could worsen inflammation through activation of pro-inflammatory cytokines, leading to more relapses.
Observational studies have suggested that stress may lead to relapses, according to Amy Sullivan, PsyD, who spoke during a session at the annual meeting of the Consortium of Multiple Sclerosis Centers.
She cited a study conducted during the 34-day war between Israel and Lebanon in 2006, which found more exacerbations among 156 Israeli patients with relapsing-remitting MS patients during the period of hostilities. There were 18 relapses that occurred during the war, and 44% of those who experienced a relapse reported experience intense subjective stress, versus 20% of those who did not experience a relapse, and 67% of relapsers reported high levels of distress linked to rocket attack exposure, versus 42% of those who did not have a relapse (P = .05).
Another study of 216 Lebanese MS patients found 23 relapses during the 2-month war period, compared with a mean of 8.4 during other 2-month periods.
“So we have two observational studies that are showing us that there’s a pretty strong link or correlation between war, a very stressful life event, and MS relapses,” said Dr. Sullivan.
That relationship has prompted development of interventions to reduce stress in MS patients in hopes of improving clinical outcomes. One that “shaped our practice,” according to Dr. Sullivan, was published in 2012. It was the first high-quality randomized controlled trial of such an intervention, she said.
The program was based on cognitive behavioral therapy (CBT) and lasted 24 weeks and 16 psychotherapy sessions. Compared with controls, participants had fewer MRI brain lesions, but there were no differences after week 24. “[That] tells us that when people stopped the stress management techniques, the intervention did not give them protection,” said Dr. Sullivan.
Her group aimed to build on that work by developing a program that would be easier for busy patients to learn and incorporate into their lives. “Being in a psychotherapist office for 24 weeks to me was not feasible. I didn’t think that this was something that individuals would have interest in,” said Dr. Sullivan.
They focused on skills to manage stress, delivered over four sessions and designed to be employed in their private life. “We want them to go into the world for 4 to 6 weeks to do the skills that we taught them in that particular session, and then they come back and they tell us how that worked. We also recognize that each skill is not going to work. It’s not a one-size-fits-all for each person,” said Dr. Sullivan.
In addition to patient self-reports, the team measured physiological indicators of stress like pulse (beats per minute), breath rate (breaths per minute), and saturated oxygen (%SpO2). The measures were taken before and after stress management exercises.
The first session included psychoeducation and diaphragmatic breathing for relaxation. The second reviewed the nervous system and the stress response. The third introduced visualization and guided imagery that was individualized for each patient. The fourth focused on mindfulness and distress tolerance.
The study included 195 individuals (mean age, 44.4 years; 72.0% female, 71.5% White).
In all four sessions, patients achieved significant in-session improvements in breath rate, pulse, and saturated oxygen, as well as improvements from the first to the final session: Among 124 patients who completed at least 2 sessions, Patient Health Questionnaire-9 (PHQ-9) scores improved by 1.61 (P < .001), Generalized Anxiety Disorder (GAD) scores by 1.08 (P = .004), breaths per minute by 3.38 (P = .001), and SpO2 by 1.67 (P = .016). There was no significant change in pulse.
The high dropout rate could be seen as a weakness, but it was actually designed into the program. “We encouraged people to drop out when they were done. Our program is built on feasibility, and it’s built based on wanting our patients to get what they need out of our treatment, and then go live their lives. We don’t want them to feel tied to our offices, so they voluntarily discontinued after they felt they had sufficiently mastered stress management skills,” said Dr. Sullivan.
The results “suggest that short-term treatment with stress management skills can impact physiological and emotional stress in MS. [The] stress management protocol is likely a great adjunctive treatment to bolster skills traditionally taught during psychotherapy sessions,” said Dr. Sullivan.
During the Q&A period, an audience member asked why the group deviated from traditional cognitive behavioral therapy and moved into more right-brain activities. “In our practice, we’re very eclectic. We don’t believe that just CBT helps, or just behavioral therapy helps, or just [dialectical behavior therapy] helps. We want to teach the skills which we believe are the most important skills to train people on,” said Dr. Sullivan.
Dr. Sullivan did not report any relevant disclosures.
FROM CMSC 2024
DMTs in Aging MS Patients: When and How to Stop
NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.
This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.
said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
MS in Older Patients
Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.
“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.
The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.
On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.
Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.
Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.
Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
What Does the Literature Say?
There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.
A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.
The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.
One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.
The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).
Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
Other Concerns and Options
During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.
Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.
Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.
Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”
Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.
Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.
This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.
said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
MS in Older Patients
Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.
“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.
The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.
On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.
Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.
Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.
Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
What Does the Literature Say?
There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.
A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.
The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.
One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.
The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).
Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
Other Concerns and Options
During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.
Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.
Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.
Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”
Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.
Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.
This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.
said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
MS in Older Patients
Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.
“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.
The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.
On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.
Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.
Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.
Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
What Does the Literature Say?
There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.
A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.
The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.
One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.
The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).
Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
Other Concerns and Options
During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.
Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.
Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.
Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”
Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.
Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
FROM CMSC 2024
AI Wins AGA’s Shark Tank Competition
CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.
After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.
The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.
Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.
When they decided to try a start-up, the two initiated conversations with healthcare providers to identify a key unmet need. “The common recurring theme was that medical billing was a problem, because of [insufficient] institutional knowledge, staff shortage, and inconsistencies with the payers,” said Dr. Elango. During their presentation, the two noted that about 80% of claims include at least one coding error, and this leads to an estimated $125 billion in annual losses.
Generative AI presented a solution. “Automating the medical billing code [determination] from a clinical record became 10 times easier than what it was before. So I thought, I can build a product that actually brings in augmented analytics and generative AI and do something that is tremendously useful to physicians,” he said.
The future goal is to make life easier for healthcare providers, according to Dr. Dhanasekaran. “As physicians, we went into medicine to talk with patients, but a lot of us are just typing away when patients are sitting in the room, because there are all of these requirements for documentation to get the billing so that we can get paid at the end of the day,” she said.
Arithmedics aims to initially target small-group medical practices that are tech savvy. They will analyze a year’s worth of claims for errors and resubmit claims for the past 3 months and split any additional revenue that ensues. They plan to expand to revenue cycle management companies and hospital systems. On the technology side, they will expand to data intelligence and integrate with electronic health records, and ultimately plan to charge 1%-2% of revenue.
The other Shark Tank finalists were:
- Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
- Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
- Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
- Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.
The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.
“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.
The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.
Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.
Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.
He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”
Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.
The summit was sponsored by the AGA Center for GI Innovation and Technology.
Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.
CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.
After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.
The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.
Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.
When they decided to try a start-up, the two initiated conversations with healthcare providers to identify a key unmet need. “The common recurring theme was that medical billing was a problem, because of [insufficient] institutional knowledge, staff shortage, and inconsistencies with the payers,” said Dr. Elango. During their presentation, the two noted that about 80% of claims include at least one coding error, and this leads to an estimated $125 billion in annual losses.
Generative AI presented a solution. “Automating the medical billing code [determination] from a clinical record became 10 times easier than what it was before. So I thought, I can build a product that actually brings in augmented analytics and generative AI and do something that is tremendously useful to physicians,” he said.
The future goal is to make life easier for healthcare providers, according to Dr. Dhanasekaran. “As physicians, we went into medicine to talk with patients, but a lot of us are just typing away when patients are sitting in the room, because there are all of these requirements for documentation to get the billing so that we can get paid at the end of the day,” she said.
Arithmedics aims to initially target small-group medical practices that are tech savvy. They will analyze a year’s worth of claims for errors and resubmit claims for the past 3 months and split any additional revenue that ensues. They plan to expand to revenue cycle management companies and hospital systems. On the technology side, they will expand to data intelligence and integrate with electronic health records, and ultimately plan to charge 1%-2% of revenue.
The other Shark Tank finalists were:
- Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
- Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
- Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
- Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.
The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.
“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.
The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.
Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.
Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.
He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”
Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.
The summit was sponsored by the AGA Center for GI Innovation and Technology.
Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.
CHICAGO — At the 2024 AGA Tech Summit, held April 11-12 at the Chicago headquarters of MATTER, a global healthcare startup incubator, five companies made their pitch to be the winner of the Shark Tank competition that recognizes an outstanding tech start up in the gastroenterology field.
After the companies’ rapid-fire pitches and Q&A sessions, four judges convened to determine a winner and returned to make an announcement.
The winner was Arithmedics, which uses AI technology to automate billing codes. Founder Venthan Elango, PhD, has worked as a software engineer at Google, Urban Engines, and Georgia Tech, and his wife of 17 years is Renumathy Dhanasekaran, MD, PhD, a gastroenterologist and assistant professor of medicine at Stanford (California) University.
Their marriage has brought a unique perspective, according to Dr. Elango. “There isn’t a single day that goes by when she talks to me about the inefficiencies in healthcare, and then I say, ‘this can be easily solved with a software solution,’ ” he said.
When they decided to try a start-up, the two initiated conversations with healthcare providers to identify a key unmet need. “The common recurring theme was that medical billing was a problem, because of [insufficient] institutional knowledge, staff shortage, and inconsistencies with the payers,” said Dr. Elango. During their presentation, the two noted that about 80% of claims include at least one coding error, and this leads to an estimated $125 billion in annual losses.
Generative AI presented a solution. “Automating the medical billing code [determination] from a clinical record became 10 times easier than what it was before. So I thought, I can build a product that actually brings in augmented analytics and generative AI and do something that is tremendously useful to physicians,” he said.
The future goal is to make life easier for healthcare providers, according to Dr. Dhanasekaran. “As physicians, we went into medicine to talk with patients, but a lot of us are just typing away when patients are sitting in the room, because there are all of these requirements for documentation to get the billing so that we can get paid at the end of the day,” she said.
Arithmedics aims to initially target small-group medical practices that are tech savvy. They will analyze a year’s worth of claims for errors and resubmit claims for the past 3 months and split any additional revenue that ensues. They plan to expand to revenue cycle management companies and hospital systems. On the technology side, they will expand to data intelligence and integrate with electronic health records, and ultimately plan to charge 1%-2% of revenue.
The other Shark Tank finalists were:
- Aspero Medical: Balloon overtube that maximizes frictional properties to improve mucosal wall traction and anchoring consistency. (Voted ‘fan favorite’ by AGA Tech Summit attendees)
- Aurora Medical Technologies: Minimally invasive, guided, tissue-anchoring suturing system for complex endoscopic procedures.
- Ergami Endoscopy: Flexible overtube capable of automatic insertion and fixation in the colon, which could potentially eliminate sedation and prevent endoscopic injuries to the physician.
- Lazurite: Wireless surgical camera that eliminates the need for light or video cables, avoiding the associated fire, trip, and contamination hazards.
The judges were swayed by Arithmedics’ practical solution to a widespread problem. “There is for sure a need in terms of inaccurate billing and billing codes that are wrong. There’s lost revenue for physicians around that. So I think we were really focused from a judging standpoint on the fact that their solution was filling truly an unmet need,” said judge Andrea Vossler, a managing director of Varia Ventures, which has partnered with AGA to launch and manage the GI Opportunity Fund, an AGA-member venture fund.
“We were really focused on how to assist physicians in terms of supporting their practices, and really changing what you’re doing. I think AI has the ability to do that, so we liked that about the company,” she added.
The company is an example of how AI is poised to alter healthcare, according to Ms. Vossler. “I think it’s massive. I think we’re at the very beginning of its impact on healthcare,” she said.
Another judge had a similar view. “They won because there is a screaming need to fix billing. So, it’s well known that lots of money is indeed lost in billing practices, which are stressful for office personnel and stressful for physicians. They can fulfill a long-standing need, and we thought that that was the success story,” said Christopher Gostout, MD, emeritus professor of medicine at Mayo Clinic in Rochester, Minnesota.
Dr. Gostout offered advice for gastroenterologists and other physicians interested in starting tech companies. It’s imperative to be a realist, he said. “Is there a real market for it, or [is it just] a niche market? Does your device have legs — can it expand and can evolve into other [spin-off] products? These are things you need to think about because one-offs or single-trick ponies are pretty hard to move along now,” said Dr. Gostout.
He recommended that entrepreneurs apply for Small Business Innovation Research (SBIR) grants. “I think it’s a great opportunity to bring in money and get the ball rolling.”
Finally, he advised entrepreneurs to be thoughtful about their advisory groups. Founders may be tempted to find the highest profile names they can to give the business gravitas, but those big names may not have the best knowledge base to understand the problems that the technology is meant to address. “I’ve seen businesses fail because they went for marquee names that really were not helpful, and they didn’t do their due diligence in seeking out really useful value. You don’t need a lot of advisers, just a couple of really good ones,” said Dr. Gostout.
The summit was sponsored by the AGA Center for GI Innovation and Technology.
Dr. Gostout has founded and advises AdaptivEndo and Lean Medical. He is a consultant to Boston Scientific. Dr. Dhanasekaran has no financial disclosures. Ms. Vossler is an employee of Varia Ventures, which is an investment partner to AGA. Dr. Elango is an employee of Arithmedics.
FROM THE 2024 AGA TECH SUMMIT