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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
High-Dose Vitamin D Linked to Lower Disease Activity in CIS
COPENHAGEN — , results of a randomized, controlled trial suggest. In addition, cholecalciferol had a favorable safety profile and was well tolerated.
“These data support high-dose vitamin D supplementation in early MS and make vitamin D the best candidate for add-on therapy evaluation in the therapeutic strategy for multiple sclerosis [MS],” said study author Eric Thouvenot, MD, PhD, University Hospital of Nimes, Neurology Department, Nimes, France.
The study was presented at the 2024 ECTRIMS annual meeting.
Vitamin D Supplementation Versus Placebo
Research shows vitamin D deficiency is a risk factor for MS. However, results of previous research investigating vitamin D supplementation in MS, with different regimens and durations, have been contradictory.
The current double-blind study included 303 adults newly diagnosed with CIS (within 90 days) and a serum 25-hydroxy vitamin D concentration of less than 100 nmol/L at baseline. Participants had a median age of 34 years, and 70% were women.
About one third of participants had optic neuritis, two thirds had oligoclonal bands from cerebrospinal fluid analysis, and the median Expanded Disability Status Scale (EDSS) score was 1.0. Of the total, 89% fulfilled 2017 McDonald criteria for the diagnosis of relapsing-remitting MS (RRMS).
Participants were randomly assigned to receive high-dose (100,000 international units) oral cholecalciferol or placebo every 2 weeks for 24 months. Participants had a clinical visit at 3, 6, 12, 18, and 24 months, and brain and spinal cord MRI with and without gadolinium at 3, 12, and 24 months.
The primary outcome was occurrence of disease activity — relapse, new or enlarging T2 lesions, and presence of contrast-enhancing lesions.
Significant Difference
During follow-up, 60.3% in the vitamin group showed evidence of disease activity versus 74.1% in the placebo group (hazard ratio [HR], 0.66; 95% CI, 0.50-0.87; P = .004). In addition, the median time to evidence of disease activity was 432 days in the vitamin D group versus 224 days in the placebo group (P = .003).
“As you can see, the difference is really, really significant,” said Dr. Thouvenot, referring to a Kaplan-Meier curve. He said he was somewhat surprised by the “very rapid” effect of vitamin D.
He noted that the 34% reduction in relative risk for disease activity is “similar to that of some published platform therapies for CIS patients.”
An analysis of the 247 patients who met 2017 McDonald criteria for RRMS at baseline showed the same results.
Secondary analyses showed no significant reduction in relapses and no significant differences for annual change in EDSS, quality of life, fatigue, anxiety, or depression.
Additional analyses showed the HR was unchanged after adjusting for known prognostic factors including age, sex, number of lesions (< 9 vs ≥ 9), EDSS score at baseline, and delay between CIS and treatment onset.
Results showed vitamin D3 supplementation was safe and well tolerated. Dr. Thouvenot noted that 95% of participants completed the trial, and none of the 33 severe adverse events in 30 patients suggested hypercalcemia or were related to the study drug.
These encouraging new data support further studies of high-dose vitamin D supplementation as an add-on therapy in early MS, said Dr. Thouvenot. He noted that animal models suggest vitamin D added to interferon beta has a synergistic effect on the immune system.
‘Fabulous’ Research
During a question-and-answer session, delegates praised the study, with some describing it as “fantastic” or “fabulous.”
Addressing a query about why this study succeeded in showing the benefits of vitamin D while numerous previous studies did not, Dr. Thouvenot said it may be due to the longer duration or a design that was better powered to show differences.
Asked if researchers examined vitamin D blood levels during the study, Dr. Thouvenot said these measures are “ongoing.”
Responding to a question of whether high-dose vitamin D could be a lifelong treatment, he referred again to the “excellent” safety of the intervention. Not only is it well tolerated, but vitamin D benefits bones and the risk for hypercalcemia is low except perhaps for patients with tuberculosis or sarcoidosis, he said.
“When you exclude those patients, the safety is huge, so I don’t know why we should stop it once it’s started.”
This study was funded in part by the French Ministry of Health. Dr. Thouvenot reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
COPENHAGEN — , results of a randomized, controlled trial suggest. In addition, cholecalciferol had a favorable safety profile and was well tolerated.
“These data support high-dose vitamin D supplementation in early MS and make vitamin D the best candidate for add-on therapy evaluation in the therapeutic strategy for multiple sclerosis [MS],” said study author Eric Thouvenot, MD, PhD, University Hospital of Nimes, Neurology Department, Nimes, France.
The study was presented at the 2024 ECTRIMS annual meeting.
Vitamin D Supplementation Versus Placebo
Research shows vitamin D deficiency is a risk factor for MS. However, results of previous research investigating vitamin D supplementation in MS, with different regimens and durations, have been contradictory.
The current double-blind study included 303 adults newly diagnosed with CIS (within 90 days) and a serum 25-hydroxy vitamin D concentration of less than 100 nmol/L at baseline. Participants had a median age of 34 years, and 70% were women.
About one third of participants had optic neuritis, two thirds had oligoclonal bands from cerebrospinal fluid analysis, and the median Expanded Disability Status Scale (EDSS) score was 1.0. Of the total, 89% fulfilled 2017 McDonald criteria for the diagnosis of relapsing-remitting MS (RRMS).
Participants were randomly assigned to receive high-dose (100,000 international units) oral cholecalciferol or placebo every 2 weeks for 24 months. Participants had a clinical visit at 3, 6, 12, 18, and 24 months, and brain and spinal cord MRI with and without gadolinium at 3, 12, and 24 months.
The primary outcome was occurrence of disease activity — relapse, new or enlarging T2 lesions, and presence of contrast-enhancing lesions.
Significant Difference
During follow-up, 60.3% in the vitamin group showed evidence of disease activity versus 74.1% in the placebo group (hazard ratio [HR], 0.66; 95% CI, 0.50-0.87; P = .004). In addition, the median time to evidence of disease activity was 432 days in the vitamin D group versus 224 days in the placebo group (P = .003).
“As you can see, the difference is really, really significant,” said Dr. Thouvenot, referring to a Kaplan-Meier curve. He said he was somewhat surprised by the “very rapid” effect of vitamin D.
He noted that the 34% reduction in relative risk for disease activity is “similar to that of some published platform therapies for CIS patients.”
An analysis of the 247 patients who met 2017 McDonald criteria for RRMS at baseline showed the same results.
Secondary analyses showed no significant reduction in relapses and no significant differences for annual change in EDSS, quality of life, fatigue, anxiety, or depression.
Additional analyses showed the HR was unchanged after adjusting for known prognostic factors including age, sex, number of lesions (< 9 vs ≥ 9), EDSS score at baseline, and delay between CIS and treatment onset.
Results showed vitamin D3 supplementation was safe and well tolerated. Dr. Thouvenot noted that 95% of participants completed the trial, and none of the 33 severe adverse events in 30 patients suggested hypercalcemia or were related to the study drug.
These encouraging new data support further studies of high-dose vitamin D supplementation as an add-on therapy in early MS, said Dr. Thouvenot. He noted that animal models suggest vitamin D added to interferon beta has a synergistic effect on the immune system.
‘Fabulous’ Research
During a question-and-answer session, delegates praised the study, with some describing it as “fantastic” or “fabulous.”
Addressing a query about why this study succeeded in showing the benefits of vitamin D while numerous previous studies did not, Dr. Thouvenot said it may be due to the longer duration or a design that was better powered to show differences.
Asked if researchers examined vitamin D blood levels during the study, Dr. Thouvenot said these measures are “ongoing.”
Responding to a question of whether high-dose vitamin D could be a lifelong treatment, he referred again to the “excellent” safety of the intervention. Not only is it well tolerated, but vitamin D benefits bones and the risk for hypercalcemia is low except perhaps for patients with tuberculosis or sarcoidosis, he said.
“When you exclude those patients, the safety is huge, so I don’t know why we should stop it once it’s started.”
This study was funded in part by the French Ministry of Health. Dr. Thouvenot reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
COPENHAGEN — , results of a randomized, controlled trial suggest. In addition, cholecalciferol had a favorable safety profile and was well tolerated.
“These data support high-dose vitamin D supplementation in early MS and make vitamin D the best candidate for add-on therapy evaluation in the therapeutic strategy for multiple sclerosis [MS],” said study author Eric Thouvenot, MD, PhD, University Hospital of Nimes, Neurology Department, Nimes, France.
The study was presented at the 2024 ECTRIMS annual meeting.
Vitamin D Supplementation Versus Placebo
Research shows vitamin D deficiency is a risk factor for MS. However, results of previous research investigating vitamin D supplementation in MS, with different regimens and durations, have been contradictory.
The current double-blind study included 303 adults newly diagnosed with CIS (within 90 days) and a serum 25-hydroxy vitamin D concentration of less than 100 nmol/L at baseline. Participants had a median age of 34 years, and 70% were women.
About one third of participants had optic neuritis, two thirds had oligoclonal bands from cerebrospinal fluid analysis, and the median Expanded Disability Status Scale (EDSS) score was 1.0. Of the total, 89% fulfilled 2017 McDonald criteria for the diagnosis of relapsing-remitting MS (RRMS).
Participants were randomly assigned to receive high-dose (100,000 international units) oral cholecalciferol or placebo every 2 weeks for 24 months. Participants had a clinical visit at 3, 6, 12, 18, and 24 months, and brain and spinal cord MRI with and without gadolinium at 3, 12, and 24 months.
The primary outcome was occurrence of disease activity — relapse, new or enlarging T2 lesions, and presence of contrast-enhancing lesions.
Significant Difference
During follow-up, 60.3% in the vitamin group showed evidence of disease activity versus 74.1% in the placebo group (hazard ratio [HR], 0.66; 95% CI, 0.50-0.87; P = .004). In addition, the median time to evidence of disease activity was 432 days in the vitamin D group versus 224 days in the placebo group (P = .003).
“As you can see, the difference is really, really significant,” said Dr. Thouvenot, referring to a Kaplan-Meier curve. He said he was somewhat surprised by the “very rapid” effect of vitamin D.
He noted that the 34% reduction in relative risk for disease activity is “similar to that of some published platform therapies for CIS patients.”
An analysis of the 247 patients who met 2017 McDonald criteria for RRMS at baseline showed the same results.
Secondary analyses showed no significant reduction in relapses and no significant differences for annual change in EDSS, quality of life, fatigue, anxiety, or depression.
Additional analyses showed the HR was unchanged after adjusting for known prognostic factors including age, sex, number of lesions (< 9 vs ≥ 9), EDSS score at baseline, and delay between CIS and treatment onset.
Results showed vitamin D3 supplementation was safe and well tolerated. Dr. Thouvenot noted that 95% of participants completed the trial, and none of the 33 severe adverse events in 30 patients suggested hypercalcemia or were related to the study drug.
These encouraging new data support further studies of high-dose vitamin D supplementation as an add-on therapy in early MS, said Dr. Thouvenot. He noted that animal models suggest vitamin D added to interferon beta has a synergistic effect on the immune system.
‘Fabulous’ Research
During a question-and-answer session, delegates praised the study, with some describing it as “fantastic” or “fabulous.”
Addressing a query about why this study succeeded in showing the benefits of vitamin D while numerous previous studies did not, Dr. Thouvenot said it may be due to the longer duration or a design that was better powered to show differences.
Asked if researchers examined vitamin D blood levels during the study, Dr. Thouvenot said these measures are “ongoing.”
Responding to a question of whether high-dose vitamin D could be a lifelong treatment, he referred again to the “excellent” safety of the intervention. Not only is it well tolerated, but vitamin D benefits bones and the risk for hypercalcemia is low except perhaps for patients with tuberculosis or sarcoidosis, he said.
“When you exclude those patients, the safety is huge, so I don’t know why we should stop it once it’s started.”
This study was funded in part by the French Ministry of Health. Dr. Thouvenot reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM ECTRIMS 2024
Guidance Will Aid Pediatric to Adult Diabetes Care Transfer
MADRID — A new consensus statement in development will aim to advise on best practices for navigating the transition of youth with diabetes from pediatric to adult diabetes care, despite limited data.
Expected to be released in early 2025, the statement will be a joint effort of the International Society for Pediatric and Adolescent Diabetes (ISPAD), the American Diabetes Association (ADA), and the European Association for the Study of Diabetes (EASD). It will provide guidance on advance transition planning, the care transfer itself, and follow-up. Writing panel members presented an update on the statement’s development on September 13, 2024, at EASD’s annual meeting.
The care transition period is critical because “adolescents and young adults are the least likely of all age groups to achieve glycemic targets for a variety of physiological and psychosocial reasons ... Up to 60% of these individuals don’t transfer successfully from pediatric to adult care, with declines in attendance, adverse medical outcomes, and mental health challenges,” Frank J. Snoek, PhD, emeritus professor of medical psychology at Amsterdam University Medical College, Amsterdam, the Netherlands, said in introductory remarks at the EASD session.
Session chair Carine De Beaufort, MD, a pediatric endocrinologist in Luxembourg City, Luxembourg, told this news organization, “We know it’s a continuing process, which is extremely important for young people to move into the world. The last formal recommendations were published in 2011, so we thought it was time for an update. What we realized in doing a systematic review and scoping review is that there are a lot of suggestions and ideas not really associated with robust data, and it’s not so easy to get good outcome indicators.”
The final statement will provide clinical guidance but, at the same time, “will be very transparent where more work is needed,” she said.
Sarah Lyons, MD, associate professor of pediatrics at Baylor College of Medicine, Houston, broadly outlined the document. Pre-transition planning will include readiness assessments for transfer from pediatric to adult care. The transfer phase will include measures to prevent gaps in care. And the post-transition phase will cover incorporation into adult care, with follow-up of the individual’s progress for a period.
Across the three stages, the document is expected to recommend a multidisciplinary team approach including psychological support, education and assessment, family and peer support, and care coordination. It will also address practical considerations for patients and professionals including costs and insurance.
It will build upon previous guidelines, including those of ADA and general guidance on transition from pediatric to adult healthcare from the American Academy of Pediatrics. “Ideally, this process will be continuous, comprehensive, coordinated, individualized, and developmentally appropriate,” Dr. Lyons said.
‘It Shouldn’t Be Just One Conversation ... It Needs to Be a Process’
Asked to comment, ISPAD president David Maahs, MD, the Lucile Salter Packard Professor of Pediatrics and Division Chief of Pediatric Endocrinology at Stanford University, Palo Alto, California, told this news organization, “It shouldn’t be just one conversation and one visit. It needs to be a process where you talk about the need to transition to adult endocrine care and prepare the person with diabetes and their family for that transition. One of the challenges is if they don’t make it to that first appointment and you assume that they did, and then that’s one place where there can be a gap that people fall through the two systems.”
Dr. Maahs added, “Another issue that’s a big problem in the United States is that children lose their parents’ insurance at 26 ... Some become uninsured after that, or their insurance plan isn’t accepted by the adult provider.”
‘There Does Not Appear to Be Sufficient Data’
Steven James, PhD, RN, of the University of the Sunshine Coast, Brisbane, Australia, presented the limited data upon which the statement will be based. A systematic literature review yielded just 26 intervention trials looking at care transition for youth with type 1 or type 2 diabetes, including seven clinical trials with only one randomized.
In that trial, in which 205 youth aged 17-20 years were randomized to a structured 18-month transition program with a transition coordinator, the intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but the benefits weren’t maintained 12 months after completion of the intervention.
The other trials produced mixed results in terms of metabolic outcomes, with improvements in A1c and reductions in diabetic ketoacidosis and hospitalizations seen in some but not others. Healthcare outcomes and utilization, psychosocial outcomes, transition-related knowledge, self-care, and care satisfaction were only occasionally assessed, Dr. James noted.
“The field is lacking empirically supported interventions that can improve patient physiologic and psychologic outcomes, prevent poor clinic attendance, and improve patient satisfaction in medical care ... There still does not appear to be sufficient data related to the impact of transition readiness or transfer-to-adult care programs.”
‘Quite a Lot of Variation in Practices Worldwide’
Dr. James also presented results from two online surveys undertaken by the document writing panel. One recently published survey in Diabetes Research and Clinical Practice examined healthcare professionals’ experiences and perceptions around diabetes care transitions. Of 372 respondents (75% physicians) from around the world — including a third in low-middle-income countries — fewer than half reported using transition readiness checklists (32.8%), provided written transition information (29.6%), or had a dedicated staff member to aid in the process (23.7%).
Similarly, few involved a psychologist (25.3%) or had a structured transition education program (22.6%). Even in high-income countries, fewer than half reported using these measures. Overall, a majority (91.9%) reported barriers to offering patients a positive transition experience.
“This shows to me that there is quite a lot of variation in practices worldwide ... There is a pressing need for an international consensus transition guideline,” Dr. James said.
Among the respondents’ beliefs, 53.8% thought that discussions about transitioning should be initiated at ages 15-17 years, while 27.8% thought 12-14 years was more appropriate. Large majorities favored use of a transition readiness checklist (93.6%), combined transition clinics (80.6%), having a dedicated transition coordinator/staff member available (85.8%), and involving a psychologist in the transition process (80.6%).
A similar survey of patients and carers will be published soon and will be included in the new statement’s evidence base, Dr. James said.
Dr. Maahs said that endorsement of the upcoming guidance from three different medical societies should help raise the profile of the issue. “Hopefully three professional organizations are able to speak with a united and louder voice than if it was just one group or one set of authors. I think this consensus statement can raise awareness, improve care, and help advocate for better care.”
Dr. De Beaufort, Dr. James, and Dr. Lyons had no disclosures. Dr. Snoek is an adviser/speaker for Abbott, Lilly, Novo Nordisk, and Sanofi and receives funding from Breakthrough T1D, Sanofi, and Novo Nordisk. Dr. Maahs has had research support from the National Institutes of Health, Breakthrough T1D, National Science Foundation, and the Helmsley Charitable Trust, and his institution has had research support from Medtronic, Dexcom, Insulet, Bigfoot Biomedical, Tandem, and Roche. He has consulted for Abbott, Aditxt, the Helmsley Charitable Trust, LifeScan, MannKind, Sanofi, Novo Nordisk, Eli Lilly, Medtronic, Insulet, Dompe, BioSpex, Provention Bio, Kriya, Enable Biosciences, and Bayer.
A version of this article first appeared on Medscape.com.
MADRID — A new consensus statement in development will aim to advise on best practices for navigating the transition of youth with diabetes from pediatric to adult diabetes care, despite limited data.
Expected to be released in early 2025, the statement will be a joint effort of the International Society for Pediatric and Adolescent Diabetes (ISPAD), the American Diabetes Association (ADA), and the European Association for the Study of Diabetes (EASD). It will provide guidance on advance transition planning, the care transfer itself, and follow-up. Writing panel members presented an update on the statement’s development on September 13, 2024, at EASD’s annual meeting.
The care transition period is critical because “adolescents and young adults are the least likely of all age groups to achieve glycemic targets for a variety of physiological and psychosocial reasons ... Up to 60% of these individuals don’t transfer successfully from pediatric to adult care, with declines in attendance, adverse medical outcomes, and mental health challenges,” Frank J. Snoek, PhD, emeritus professor of medical psychology at Amsterdam University Medical College, Amsterdam, the Netherlands, said in introductory remarks at the EASD session.
Session chair Carine De Beaufort, MD, a pediatric endocrinologist in Luxembourg City, Luxembourg, told this news organization, “We know it’s a continuing process, which is extremely important for young people to move into the world. The last formal recommendations were published in 2011, so we thought it was time for an update. What we realized in doing a systematic review and scoping review is that there are a lot of suggestions and ideas not really associated with robust data, and it’s not so easy to get good outcome indicators.”
The final statement will provide clinical guidance but, at the same time, “will be very transparent where more work is needed,” she said.
Sarah Lyons, MD, associate professor of pediatrics at Baylor College of Medicine, Houston, broadly outlined the document. Pre-transition planning will include readiness assessments for transfer from pediatric to adult care. The transfer phase will include measures to prevent gaps in care. And the post-transition phase will cover incorporation into adult care, with follow-up of the individual’s progress for a period.
Across the three stages, the document is expected to recommend a multidisciplinary team approach including psychological support, education and assessment, family and peer support, and care coordination. It will also address practical considerations for patients and professionals including costs and insurance.
It will build upon previous guidelines, including those of ADA and general guidance on transition from pediatric to adult healthcare from the American Academy of Pediatrics. “Ideally, this process will be continuous, comprehensive, coordinated, individualized, and developmentally appropriate,” Dr. Lyons said.
‘It Shouldn’t Be Just One Conversation ... It Needs to Be a Process’
Asked to comment, ISPAD president David Maahs, MD, the Lucile Salter Packard Professor of Pediatrics and Division Chief of Pediatric Endocrinology at Stanford University, Palo Alto, California, told this news organization, “It shouldn’t be just one conversation and one visit. It needs to be a process where you talk about the need to transition to adult endocrine care and prepare the person with diabetes and their family for that transition. One of the challenges is if they don’t make it to that first appointment and you assume that they did, and then that’s one place where there can be a gap that people fall through the two systems.”
Dr. Maahs added, “Another issue that’s a big problem in the United States is that children lose their parents’ insurance at 26 ... Some become uninsured after that, or their insurance plan isn’t accepted by the adult provider.”
‘There Does Not Appear to Be Sufficient Data’
Steven James, PhD, RN, of the University of the Sunshine Coast, Brisbane, Australia, presented the limited data upon which the statement will be based. A systematic literature review yielded just 26 intervention trials looking at care transition for youth with type 1 or type 2 diabetes, including seven clinical trials with only one randomized.
In that trial, in which 205 youth aged 17-20 years were randomized to a structured 18-month transition program with a transition coordinator, the intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but the benefits weren’t maintained 12 months after completion of the intervention.
The other trials produced mixed results in terms of metabolic outcomes, with improvements in A1c and reductions in diabetic ketoacidosis and hospitalizations seen in some but not others. Healthcare outcomes and utilization, psychosocial outcomes, transition-related knowledge, self-care, and care satisfaction were only occasionally assessed, Dr. James noted.
“The field is lacking empirically supported interventions that can improve patient physiologic and psychologic outcomes, prevent poor clinic attendance, and improve patient satisfaction in medical care ... There still does not appear to be sufficient data related to the impact of transition readiness or transfer-to-adult care programs.”
‘Quite a Lot of Variation in Practices Worldwide’
Dr. James also presented results from two online surveys undertaken by the document writing panel. One recently published survey in Diabetes Research and Clinical Practice examined healthcare professionals’ experiences and perceptions around diabetes care transitions. Of 372 respondents (75% physicians) from around the world — including a third in low-middle-income countries — fewer than half reported using transition readiness checklists (32.8%), provided written transition information (29.6%), or had a dedicated staff member to aid in the process (23.7%).
Similarly, few involved a psychologist (25.3%) or had a structured transition education program (22.6%). Even in high-income countries, fewer than half reported using these measures. Overall, a majority (91.9%) reported barriers to offering patients a positive transition experience.
“This shows to me that there is quite a lot of variation in practices worldwide ... There is a pressing need for an international consensus transition guideline,” Dr. James said.
Among the respondents’ beliefs, 53.8% thought that discussions about transitioning should be initiated at ages 15-17 years, while 27.8% thought 12-14 years was more appropriate. Large majorities favored use of a transition readiness checklist (93.6%), combined transition clinics (80.6%), having a dedicated transition coordinator/staff member available (85.8%), and involving a psychologist in the transition process (80.6%).
A similar survey of patients and carers will be published soon and will be included in the new statement’s evidence base, Dr. James said.
Dr. Maahs said that endorsement of the upcoming guidance from three different medical societies should help raise the profile of the issue. “Hopefully three professional organizations are able to speak with a united and louder voice than if it was just one group or one set of authors. I think this consensus statement can raise awareness, improve care, and help advocate for better care.”
Dr. De Beaufort, Dr. James, and Dr. Lyons had no disclosures. Dr. Snoek is an adviser/speaker for Abbott, Lilly, Novo Nordisk, and Sanofi and receives funding from Breakthrough T1D, Sanofi, and Novo Nordisk. Dr. Maahs has had research support from the National Institutes of Health, Breakthrough T1D, National Science Foundation, and the Helmsley Charitable Trust, and his institution has had research support from Medtronic, Dexcom, Insulet, Bigfoot Biomedical, Tandem, and Roche. He has consulted for Abbott, Aditxt, the Helmsley Charitable Trust, LifeScan, MannKind, Sanofi, Novo Nordisk, Eli Lilly, Medtronic, Insulet, Dompe, BioSpex, Provention Bio, Kriya, Enable Biosciences, and Bayer.
A version of this article first appeared on Medscape.com.
MADRID — A new consensus statement in development will aim to advise on best practices for navigating the transition of youth with diabetes from pediatric to adult diabetes care, despite limited data.
Expected to be released in early 2025, the statement will be a joint effort of the International Society for Pediatric and Adolescent Diabetes (ISPAD), the American Diabetes Association (ADA), and the European Association for the Study of Diabetes (EASD). It will provide guidance on advance transition planning, the care transfer itself, and follow-up. Writing panel members presented an update on the statement’s development on September 13, 2024, at EASD’s annual meeting.
The care transition period is critical because “adolescents and young adults are the least likely of all age groups to achieve glycemic targets for a variety of physiological and psychosocial reasons ... Up to 60% of these individuals don’t transfer successfully from pediatric to adult care, with declines in attendance, adverse medical outcomes, and mental health challenges,” Frank J. Snoek, PhD, emeritus professor of medical psychology at Amsterdam University Medical College, Amsterdam, the Netherlands, said in introductory remarks at the EASD session.
Session chair Carine De Beaufort, MD, a pediatric endocrinologist in Luxembourg City, Luxembourg, told this news organization, “We know it’s a continuing process, which is extremely important for young people to move into the world. The last formal recommendations were published in 2011, so we thought it was time for an update. What we realized in doing a systematic review and scoping review is that there are a lot of suggestions and ideas not really associated with robust data, and it’s not so easy to get good outcome indicators.”
The final statement will provide clinical guidance but, at the same time, “will be very transparent where more work is needed,” she said.
Sarah Lyons, MD, associate professor of pediatrics at Baylor College of Medicine, Houston, broadly outlined the document. Pre-transition planning will include readiness assessments for transfer from pediatric to adult care. The transfer phase will include measures to prevent gaps in care. And the post-transition phase will cover incorporation into adult care, with follow-up of the individual’s progress for a period.
Across the three stages, the document is expected to recommend a multidisciplinary team approach including psychological support, education and assessment, family and peer support, and care coordination. It will also address practical considerations for patients and professionals including costs and insurance.
It will build upon previous guidelines, including those of ADA and general guidance on transition from pediatric to adult healthcare from the American Academy of Pediatrics. “Ideally, this process will be continuous, comprehensive, coordinated, individualized, and developmentally appropriate,” Dr. Lyons said.
‘It Shouldn’t Be Just One Conversation ... It Needs to Be a Process’
Asked to comment, ISPAD president David Maahs, MD, the Lucile Salter Packard Professor of Pediatrics and Division Chief of Pediatric Endocrinology at Stanford University, Palo Alto, California, told this news organization, “It shouldn’t be just one conversation and one visit. It needs to be a process where you talk about the need to transition to adult endocrine care and prepare the person with diabetes and their family for that transition. One of the challenges is if they don’t make it to that first appointment and you assume that they did, and then that’s one place where there can be a gap that people fall through the two systems.”
Dr. Maahs added, “Another issue that’s a big problem in the United States is that children lose their parents’ insurance at 26 ... Some become uninsured after that, or their insurance plan isn’t accepted by the adult provider.”
‘There Does Not Appear to Be Sufficient Data’
Steven James, PhD, RN, of the University of the Sunshine Coast, Brisbane, Australia, presented the limited data upon which the statement will be based. A systematic literature review yielded just 26 intervention trials looking at care transition for youth with type 1 or type 2 diabetes, including seven clinical trials with only one randomized.
In that trial, in which 205 youth aged 17-20 years were randomized to a structured 18-month transition program with a transition coordinator, the intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but the benefits weren’t maintained 12 months after completion of the intervention.
The other trials produced mixed results in terms of metabolic outcomes, with improvements in A1c and reductions in diabetic ketoacidosis and hospitalizations seen in some but not others. Healthcare outcomes and utilization, psychosocial outcomes, transition-related knowledge, self-care, and care satisfaction were only occasionally assessed, Dr. James noted.
“The field is lacking empirically supported interventions that can improve patient physiologic and psychologic outcomes, prevent poor clinic attendance, and improve patient satisfaction in medical care ... There still does not appear to be sufficient data related to the impact of transition readiness or transfer-to-adult care programs.”
‘Quite a Lot of Variation in Practices Worldwide’
Dr. James also presented results from two online surveys undertaken by the document writing panel. One recently published survey in Diabetes Research and Clinical Practice examined healthcare professionals’ experiences and perceptions around diabetes care transitions. Of 372 respondents (75% physicians) from around the world — including a third in low-middle-income countries — fewer than half reported using transition readiness checklists (32.8%), provided written transition information (29.6%), or had a dedicated staff member to aid in the process (23.7%).
Similarly, few involved a psychologist (25.3%) or had a structured transition education program (22.6%). Even in high-income countries, fewer than half reported using these measures. Overall, a majority (91.9%) reported barriers to offering patients a positive transition experience.
“This shows to me that there is quite a lot of variation in practices worldwide ... There is a pressing need for an international consensus transition guideline,” Dr. James said.
Among the respondents’ beliefs, 53.8% thought that discussions about transitioning should be initiated at ages 15-17 years, while 27.8% thought 12-14 years was more appropriate. Large majorities favored use of a transition readiness checklist (93.6%), combined transition clinics (80.6%), having a dedicated transition coordinator/staff member available (85.8%), and involving a psychologist in the transition process (80.6%).
A similar survey of patients and carers will be published soon and will be included in the new statement’s evidence base, Dr. James said.
Dr. Maahs said that endorsement of the upcoming guidance from three different medical societies should help raise the profile of the issue. “Hopefully three professional organizations are able to speak with a united and louder voice than if it was just one group or one set of authors. I think this consensus statement can raise awareness, improve care, and help advocate for better care.”
Dr. De Beaufort, Dr. James, and Dr. Lyons had no disclosures. Dr. Snoek is an adviser/speaker for Abbott, Lilly, Novo Nordisk, and Sanofi and receives funding from Breakthrough T1D, Sanofi, and Novo Nordisk. Dr. Maahs has had research support from the National Institutes of Health, Breakthrough T1D, National Science Foundation, and the Helmsley Charitable Trust, and his institution has had research support from Medtronic, Dexcom, Insulet, Bigfoot Biomedical, Tandem, and Roche. He has consulted for Abbott, Aditxt, the Helmsley Charitable Trust, LifeScan, MannKind, Sanofi, Novo Nordisk, Eli Lilly, Medtronic, Insulet, Dompe, BioSpex, Provention Bio, Kriya, Enable Biosciences, and Bayer.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Positive Stem Cell Transplant Data Is Increasing Its Use
COPENHAGEN —
With only one completed randomized trial available, HSCT remains experimental but the number of patients treated with this approach has now reached substantial numbers over 20 years of experience at multiple centers, according to two representative real-world studies presented at the 2024 ECTRIMS annual meeting.
The latest data are wholly consistent with a 2019 multinational randomized trial that found HSCT, which is a one-time intervention, to be relatively well tolerated and more effective than disease-modifying therapy (DMT) for median time to progression in patients refractory to DMT.
Relative to 24 months in the DMT group, median time to relapse was not reached among those randomized to HSCT because there were too few events. The hazard ratio (HR) reduction for progression was greater than 90% (HR, 0.07; P < 0.001). Other endpoints, such as EDSS, which improved in the group receiving HSCT but declined on DMT, also favored the single-treatment therapy.
Two Real-World Experiences With HSCT Reported
Of the two multicenter real world studies presented at ECTRIMS, one included 363 patients treated at one of 14 participating public hospitals in the United Kingdom since 2002. This analysis was uncontrolled. The other, with 97 patients treated at one of 20 participating centers in Italy since 1999, compared HSCT to alemtuzumab retrospectively.
In the UK data, presented by Paolo Muraro, MD, PhD, Senior Consultant, Division of Brain Sciences, Imperial College, London, England, 94.6% were in relapse-free survival (RFS) at 2 years and 88.6% at 5 years after undergoing HSCT. He called these numbers “impressive.”
In addition, MRI-free activity survival (MFS) was 88.2% and 78.8% at 2 and 5 years, respectively, Dr. Muraro said.
On the Expanded Disability Status Scale (EDSS), the cumulative incidence of improvement was 24.6% at 2 years and 28.6% at 5 years. There was no evidence of disease activity on the endpoints of symptoms, relapse, and MRI (NEDA-3) in 72% of patients at 2 years and 48.5% at 5 years.
Relative to historical response rates in a refractory population, Dr. Muraro considered these results favorable. Although there were four deaths, producing a treatment-related mortality of 1.1%, all occurred at an early stage of the HSCT program when there was limited experience in the management of cytopenias and other acute complications of HSCT.
“In this real-world cohort, stem cell transplant led to a durable remission of inflammatory activity and to clinical stability even though this included patients with a high EDSS at baseline [median 6.0] and a substantial proportion [39%) with progressive disease,” Dr. Muraro said.
In the Italian data, presented by Alessio Signori, MD, PhD, associate professor, Department of Health Sciences, University of Genoa, Italy, the 97 HSCT patients were matched with 314 treated with alemtuzumab over the same period and compared with propensity score overlap weighting. Baseline features were comparable.
HSCT Outperforms Alemtuzumab on All Measures
After a median follow-up of 62 months in the HSCT group and 30 months in the alemtuzumab group, HSCT outperformed drug therapy on all efficacy measures. When translated into HR, HSCT relative to alemtuzumab was associated with a 50% reduction in the probability of disability progression (HR, 0.50; P = 0.025), a 66% reduction in probability of relapse (HR, 0.34; P < 0.001), and a 62% reduction in the probability of MRI activity (HR, 0.38; P < 0.001).
“At 5 years, 58.3% of patients in the HSCT group versus 22.3% of the patients in the alemtuzumab group maintained NEDA-3,” said Dr. Signori, who reported that this difference represented a greater than 50% reduction (HR, 0.48; P < 0.001).
In this study there were two treatment-related deaths. Both occurred within 30 days of HSCT and, again, were confined to the early experience with HSCT.
There are questions that remain unanswered, such as whether there are predictors of response to HSCT. Although sustained responses have been greater on HSCT than drug therapy on average, poor responses appeared to be more common among those with a progressive phenotype in the UK experience.
Although patients with progressive disease were excluded from the Italian study, a real-world experience published 2 years ago also indicated that patients with progressive forms of MS respond less well to HSCT. Conducted in the United States at a single center (Northwestern University, Chicago) with 414 patients of whom 93 had progressive disease, EDSS progressively declined over the 5 years of follow-up among those with secondary progressive MS even as it improved in those with relapsing-remitting multiple sclerosis.
HSCT Considered on Compassionate Basis
Overall, the HSCT experience as a rescue therapy for MS patients with an inadequate response to DMT has led a growing number of centers active in this area to offer this option on a compassionate basis, according to Dr. Muraro and Dr. Signori. Joachim Burman, MD, PhD, who was the moderator of the scientific session at ECTRIMS and the leader of a research program into HSCT for MS at Uppsala University, Uppsala, Sweden, agreed.
The increasing number of centers offering HSCT to MS patients does not preclude the need or the value of the ongoing phase 3 trials, according to Dr. Burman, but he suggested that there is a growing focus of how it should be used, not whether it will be used.
Ultimately, he speculated that HSCT, once accepted as a mainstream option for MS, will probably be confined to the 5%-10% of patients with very aggressive disease. This is not for lack of safety or efficacy, but he sees several barriers to using this approach first-line, outside of special situations.
“You need a team of several different specialists to offer HSCT,” he said, suggesting that this approach to MS is much more complicated than a visit to a neurologist’s office for a DMT prescription. However, he thinks other barriers, such as concern about safety, are dissipating.
HSCT “is still being characterized as a high-risk procedure, but I would object to that,” he said. “The deaths associated with HSCT largely occurred 20 years ago when the field was new.”
Dr. Muraro reported a financial relationship with Cellerys AG that is unrelated to this study. Dr. Signori reported financial relationships with Chiesi, Horizon, and Novartis. Dr. Burman reports no potential conflicts of interest.
COPENHAGEN —
With only one completed randomized trial available, HSCT remains experimental but the number of patients treated with this approach has now reached substantial numbers over 20 years of experience at multiple centers, according to two representative real-world studies presented at the 2024 ECTRIMS annual meeting.
The latest data are wholly consistent with a 2019 multinational randomized trial that found HSCT, which is a one-time intervention, to be relatively well tolerated and more effective than disease-modifying therapy (DMT) for median time to progression in patients refractory to DMT.
Relative to 24 months in the DMT group, median time to relapse was not reached among those randomized to HSCT because there were too few events. The hazard ratio (HR) reduction for progression was greater than 90% (HR, 0.07; P < 0.001). Other endpoints, such as EDSS, which improved in the group receiving HSCT but declined on DMT, also favored the single-treatment therapy.
Two Real-World Experiences With HSCT Reported
Of the two multicenter real world studies presented at ECTRIMS, one included 363 patients treated at one of 14 participating public hospitals in the United Kingdom since 2002. This analysis was uncontrolled. The other, with 97 patients treated at one of 20 participating centers in Italy since 1999, compared HSCT to alemtuzumab retrospectively.
In the UK data, presented by Paolo Muraro, MD, PhD, Senior Consultant, Division of Brain Sciences, Imperial College, London, England, 94.6% were in relapse-free survival (RFS) at 2 years and 88.6% at 5 years after undergoing HSCT. He called these numbers “impressive.”
In addition, MRI-free activity survival (MFS) was 88.2% and 78.8% at 2 and 5 years, respectively, Dr. Muraro said.
On the Expanded Disability Status Scale (EDSS), the cumulative incidence of improvement was 24.6% at 2 years and 28.6% at 5 years. There was no evidence of disease activity on the endpoints of symptoms, relapse, and MRI (NEDA-3) in 72% of patients at 2 years and 48.5% at 5 years.
Relative to historical response rates in a refractory population, Dr. Muraro considered these results favorable. Although there were four deaths, producing a treatment-related mortality of 1.1%, all occurred at an early stage of the HSCT program when there was limited experience in the management of cytopenias and other acute complications of HSCT.
“In this real-world cohort, stem cell transplant led to a durable remission of inflammatory activity and to clinical stability even though this included patients with a high EDSS at baseline [median 6.0] and a substantial proportion [39%) with progressive disease,” Dr. Muraro said.
In the Italian data, presented by Alessio Signori, MD, PhD, associate professor, Department of Health Sciences, University of Genoa, Italy, the 97 HSCT patients were matched with 314 treated with alemtuzumab over the same period and compared with propensity score overlap weighting. Baseline features were comparable.
HSCT Outperforms Alemtuzumab on All Measures
After a median follow-up of 62 months in the HSCT group and 30 months in the alemtuzumab group, HSCT outperformed drug therapy on all efficacy measures. When translated into HR, HSCT relative to alemtuzumab was associated with a 50% reduction in the probability of disability progression (HR, 0.50; P = 0.025), a 66% reduction in probability of relapse (HR, 0.34; P < 0.001), and a 62% reduction in the probability of MRI activity (HR, 0.38; P < 0.001).
“At 5 years, 58.3% of patients in the HSCT group versus 22.3% of the patients in the alemtuzumab group maintained NEDA-3,” said Dr. Signori, who reported that this difference represented a greater than 50% reduction (HR, 0.48; P < 0.001).
In this study there were two treatment-related deaths. Both occurred within 30 days of HSCT and, again, were confined to the early experience with HSCT.
There are questions that remain unanswered, such as whether there are predictors of response to HSCT. Although sustained responses have been greater on HSCT than drug therapy on average, poor responses appeared to be more common among those with a progressive phenotype in the UK experience.
Although patients with progressive disease were excluded from the Italian study, a real-world experience published 2 years ago also indicated that patients with progressive forms of MS respond less well to HSCT. Conducted in the United States at a single center (Northwestern University, Chicago) with 414 patients of whom 93 had progressive disease, EDSS progressively declined over the 5 years of follow-up among those with secondary progressive MS even as it improved in those with relapsing-remitting multiple sclerosis.
HSCT Considered on Compassionate Basis
Overall, the HSCT experience as a rescue therapy for MS patients with an inadequate response to DMT has led a growing number of centers active in this area to offer this option on a compassionate basis, according to Dr. Muraro and Dr. Signori. Joachim Burman, MD, PhD, who was the moderator of the scientific session at ECTRIMS and the leader of a research program into HSCT for MS at Uppsala University, Uppsala, Sweden, agreed.
The increasing number of centers offering HSCT to MS patients does not preclude the need or the value of the ongoing phase 3 trials, according to Dr. Burman, but he suggested that there is a growing focus of how it should be used, not whether it will be used.
Ultimately, he speculated that HSCT, once accepted as a mainstream option for MS, will probably be confined to the 5%-10% of patients with very aggressive disease. This is not for lack of safety or efficacy, but he sees several barriers to using this approach first-line, outside of special situations.
“You need a team of several different specialists to offer HSCT,” he said, suggesting that this approach to MS is much more complicated than a visit to a neurologist’s office for a DMT prescription. However, he thinks other barriers, such as concern about safety, are dissipating.
HSCT “is still being characterized as a high-risk procedure, but I would object to that,” he said. “The deaths associated with HSCT largely occurred 20 years ago when the field was new.”
Dr. Muraro reported a financial relationship with Cellerys AG that is unrelated to this study. Dr. Signori reported financial relationships with Chiesi, Horizon, and Novartis. Dr. Burman reports no potential conflicts of interest.
COPENHAGEN —
With only one completed randomized trial available, HSCT remains experimental but the number of patients treated with this approach has now reached substantial numbers over 20 years of experience at multiple centers, according to two representative real-world studies presented at the 2024 ECTRIMS annual meeting.
The latest data are wholly consistent with a 2019 multinational randomized trial that found HSCT, which is a one-time intervention, to be relatively well tolerated and more effective than disease-modifying therapy (DMT) for median time to progression in patients refractory to DMT.
Relative to 24 months in the DMT group, median time to relapse was not reached among those randomized to HSCT because there were too few events. The hazard ratio (HR) reduction for progression was greater than 90% (HR, 0.07; P < 0.001). Other endpoints, such as EDSS, which improved in the group receiving HSCT but declined on DMT, also favored the single-treatment therapy.
Two Real-World Experiences With HSCT Reported
Of the two multicenter real world studies presented at ECTRIMS, one included 363 patients treated at one of 14 participating public hospitals in the United Kingdom since 2002. This analysis was uncontrolled. The other, with 97 patients treated at one of 20 participating centers in Italy since 1999, compared HSCT to alemtuzumab retrospectively.
In the UK data, presented by Paolo Muraro, MD, PhD, Senior Consultant, Division of Brain Sciences, Imperial College, London, England, 94.6% were in relapse-free survival (RFS) at 2 years and 88.6% at 5 years after undergoing HSCT. He called these numbers “impressive.”
In addition, MRI-free activity survival (MFS) was 88.2% and 78.8% at 2 and 5 years, respectively, Dr. Muraro said.
On the Expanded Disability Status Scale (EDSS), the cumulative incidence of improvement was 24.6% at 2 years and 28.6% at 5 years. There was no evidence of disease activity on the endpoints of symptoms, relapse, and MRI (NEDA-3) in 72% of patients at 2 years and 48.5% at 5 years.
Relative to historical response rates in a refractory population, Dr. Muraro considered these results favorable. Although there were four deaths, producing a treatment-related mortality of 1.1%, all occurred at an early stage of the HSCT program when there was limited experience in the management of cytopenias and other acute complications of HSCT.
“In this real-world cohort, stem cell transplant led to a durable remission of inflammatory activity and to clinical stability even though this included patients with a high EDSS at baseline [median 6.0] and a substantial proportion [39%) with progressive disease,” Dr. Muraro said.
In the Italian data, presented by Alessio Signori, MD, PhD, associate professor, Department of Health Sciences, University of Genoa, Italy, the 97 HSCT patients were matched with 314 treated with alemtuzumab over the same period and compared with propensity score overlap weighting. Baseline features were comparable.
HSCT Outperforms Alemtuzumab on All Measures
After a median follow-up of 62 months in the HSCT group and 30 months in the alemtuzumab group, HSCT outperformed drug therapy on all efficacy measures. When translated into HR, HSCT relative to alemtuzumab was associated with a 50% reduction in the probability of disability progression (HR, 0.50; P = 0.025), a 66% reduction in probability of relapse (HR, 0.34; P < 0.001), and a 62% reduction in the probability of MRI activity (HR, 0.38; P < 0.001).
“At 5 years, 58.3% of patients in the HSCT group versus 22.3% of the patients in the alemtuzumab group maintained NEDA-3,” said Dr. Signori, who reported that this difference represented a greater than 50% reduction (HR, 0.48; P < 0.001).
In this study there were two treatment-related deaths. Both occurred within 30 days of HSCT and, again, were confined to the early experience with HSCT.
There are questions that remain unanswered, such as whether there are predictors of response to HSCT. Although sustained responses have been greater on HSCT than drug therapy on average, poor responses appeared to be more common among those with a progressive phenotype in the UK experience.
Although patients with progressive disease were excluded from the Italian study, a real-world experience published 2 years ago also indicated that patients with progressive forms of MS respond less well to HSCT. Conducted in the United States at a single center (Northwestern University, Chicago) with 414 patients of whom 93 had progressive disease, EDSS progressively declined over the 5 years of follow-up among those with secondary progressive MS even as it improved in those with relapsing-remitting multiple sclerosis.
HSCT Considered on Compassionate Basis
Overall, the HSCT experience as a rescue therapy for MS patients with an inadequate response to DMT has led a growing number of centers active in this area to offer this option on a compassionate basis, according to Dr. Muraro and Dr. Signori. Joachim Burman, MD, PhD, who was the moderator of the scientific session at ECTRIMS and the leader of a research program into HSCT for MS at Uppsala University, Uppsala, Sweden, agreed.
The increasing number of centers offering HSCT to MS patients does not preclude the need or the value of the ongoing phase 3 trials, according to Dr. Burman, but he suggested that there is a growing focus of how it should be used, not whether it will be used.
Ultimately, he speculated that HSCT, once accepted as a mainstream option for MS, will probably be confined to the 5%-10% of patients with very aggressive disease. This is not for lack of safety or efficacy, but he sees several barriers to using this approach first-line, outside of special situations.
“You need a team of several different specialists to offer HSCT,” he said, suggesting that this approach to MS is much more complicated than a visit to a neurologist’s office for a DMT prescription. However, he thinks other barriers, such as concern about safety, are dissipating.
HSCT “is still being characterized as a high-risk procedure, but I would object to that,” he said. “The deaths associated with HSCT largely occurred 20 years ago when the field was new.”
Dr. Muraro reported a financial relationship with Cellerys AG that is unrelated to this study. Dr. Signori reported financial relationships with Chiesi, Horizon, and Novartis. Dr. Burman reports no potential conflicts of interest.
FROM ECTRIMS 2024
Comorbidity Control Might Slow MS Activity
COPENHAGEN — The largest and perhaps most rigorous study to demonstrate an association between the presence of comorbidities and accelerated progression of multiple sclerosis (MS) is sufficiently compelling that both the study author and an independent expert maintained clinical practice should be adjusted.
Even while acknowledging that “it is hard to make causative statements” on the basis of these types of data, the findings are sufficiently compelling to suggest that comorbidities “should be a pressing concern” in MS management, according to Amber Salter, PhD, an associate professor of biostatistics at the University of Texas Southwestern Medical School, Dallas.
The strong association in this meta-analysis, presented at the 2024 ECTRIMS annual meeting, were drawn from 15 multicenter phase 3 treatment trials with 16,794 participants followed for at least 2 years, Dr. Salter reported. Her data were published simultaneously in JAMA Neurology.
“One of the strengths of this study is that the data on comorbidities were collected prospectively as part of these trials,” explained Mark S. Freedman, MD, director of the Multiple Sclerosis Research Center at Ottawa Hospital in Canada. He agreed with Dr. Salter that it is reasonable to apply these findings to clinical practice given their consistency with numerous other studies and the value of what he termed as “a holistic approach” to improving outcomes in MS.
Meta-Analysis Avoids Weaknesses of Previous Data
There are many potential weaknesses of past observational studies that the authors of this meta-analysis hoped to avoid. These include the possibility that MS patients with comorbidities might be less likely to take or adhere to disease-modifying therapies (DMT) or that comorbidity burden might masquerade or be misinterpreted as MS progression. By employing data from phase 3 DMT trials, Dr. Salter maintained that prospectively collected data monitored carefully over an extended follow-up allows the impact of comorbidities on outcome to be evaluated in a more controlled fashion.
Dr. Freedman liked the design of this study, but he admitted that he was surprised by the result.
“Phase 3 trials typically include exclusion criteria for significant comorbidities, so I did not think they would be able to show any meaningful differences,” Dr. Freedman said in an interview.
For the main outcome of evidence of disease activity (EDA), defined as confirmed disability worsening measured with the Expanded Disability Status Scale (EDSS), relapse activity, or any new or enlarging lesions on MRI, the differences reached significance even after adjustments for multiple potentially confounding factors.
MS Activity Increases Significantly with More Comorbidities
Compared with no comorbidity, the presence of three or more comorbidities were associated with a significant 14% increase in the adjusted hazard ratio (aHR) of EDA (aHR, 1.14; 95% CI, 1.02-1.28), Dr. Salter reported. If there were two or more cardiometabolic comorbidities, the risk of EDA was increased 21% (aHR, 1.21; 95% CI 1.08-1.37).
The list of comorbidities considered in this study was drawn from the International Advisory Committee on Clinical Trials in MS. It included numerous cardiometabolic comorbidities, such as hypertension, hyperlipidemia, diabetes, ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. It also included chronic lung diseases, such as asthma and chronic obstructive pulmonary disease; psychiatric diseases, such as depression and anxiety; and miscellaneous autoimmune conditions.
The number of comorbidities was categorized for analysis as zero, one, two, or three or more. However, Dr. Salter acknowledged that these phase 3 trials did include comorbidity exclusion criteria. In fact, severe forms of most of these comorbidities were exclusion criteria in at least some studies. Yet, the prevalence of one or more comorbidities was still 45.4% in the total population from this meta-analysis.
By themselves alone, ischemic heart disease (aHR, 1.63), cerebrovascular disease (aHR, 1.70) and at least one psychiatric disorder (aHR, 1.14) were all significant for increased MS activity at the end of 2 years by a 95% confidence interval that did not cross the line of unity.
When the EDA endpoints were evaluated individually, not even three or more comorbidities was associated with an increased rate of active lesions on MRI at the end of follow-up, but two or more and three or more comorbidities were associated with a significantly increased risk of disability worsening (aHR, 1.16 and aHR, 1.31, respectively) and relapse (aHR, 1.16 for both).
An Underestimation of Associations?
Prospective trials are still needed to show that treating comorbidities improves outcome in MS, but randomization will be problematic if it means withholding treatment for conditions with risks independent of MS, Dr. Salter said. Although the data from this analysis did not permit an analysis of how relative severity of comorbidities affected MS outcome, she reiterated that most patients with severe comorbidities were likely excluded from inclusion in the studies anyway.
“We think that we are probably seeing an underestimation of an associations between comorbidity and increased MS activity,” Dr. Salter said. While she reported that confounding cannot be ruled out, the robust associations identified in a meta-analysis “limit the possibility of bias or chance findings.”
Asked if the message that clinicians should treat comorbidities to reduce MS activity is a reasonable conclusion in the absence of proof that treatment is beneficial, Dr. Freedman looked both to the body of evidence and to the common sense behind the recommendation.
Basically, Dr. Freedman believes that comorbidities should be addressed routinely and rigorously even if there was no evidence that they improve MS outcome. These data provide just one other source of support for a practice that should be conducted anyway.
Dr. Salter reported financial relationships with Abata Therapeutics, Gryphon Bio, and Owl Therapeutics. Dr. Freedman reported financial relationships with more than 10 pharmaceutical companies.
COPENHAGEN — The largest and perhaps most rigorous study to demonstrate an association between the presence of comorbidities and accelerated progression of multiple sclerosis (MS) is sufficiently compelling that both the study author and an independent expert maintained clinical practice should be adjusted.
Even while acknowledging that “it is hard to make causative statements” on the basis of these types of data, the findings are sufficiently compelling to suggest that comorbidities “should be a pressing concern” in MS management, according to Amber Salter, PhD, an associate professor of biostatistics at the University of Texas Southwestern Medical School, Dallas.
The strong association in this meta-analysis, presented at the 2024 ECTRIMS annual meeting, were drawn from 15 multicenter phase 3 treatment trials with 16,794 participants followed for at least 2 years, Dr. Salter reported. Her data were published simultaneously in JAMA Neurology.
“One of the strengths of this study is that the data on comorbidities were collected prospectively as part of these trials,” explained Mark S. Freedman, MD, director of the Multiple Sclerosis Research Center at Ottawa Hospital in Canada. He agreed with Dr. Salter that it is reasonable to apply these findings to clinical practice given their consistency with numerous other studies and the value of what he termed as “a holistic approach” to improving outcomes in MS.
Meta-Analysis Avoids Weaknesses of Previous Data
There are many potential weaknesses of past observational studies that the authors of this meta-analysis hoped to avoid. These include the possibility that MS patients with comorbidities might be less likely to take or adhere to disease-modifying therapies (DMT) or that comorbidity burden might masquerade or be misinterpreted as MS progression. By employing data from phase 3 DMT trials, Dr. Salter maintained that prospectively collected data monitored carefully over an extended follow-up allows the impact of comorbidities on outcome to be evaluated in a more controlled fashion.
Dr. Freedman liked the design of this study, but he admitted that he was surprised by the result.
“Phase 3 trials typically include exclusion criteria for significant comorbidities, so I did not think they would be able to show any meaningful differences,” Dr. Freedman said in an interview.
For the main outcome of evidence of disease activity (EDA), defined as confirmed disability worsening measured with the Expanded Disability Status Scale (EDSS), relapse activity, or any new or enlarging lesions on MRI, the differences reached significance even after adjustments for multiple potentially confounding factors.
MS Activity Increases Significantly with More Comorbidities
Compared with no comorbidity, the presence of three or more comorbidities were associated with a significant 14% increase in the adjusted hazard ratio (aHR) of EDA (aHR, 1.14; 95% CI, 1.02-1.28), Dr. Salter reported. If there were two or more cardiometabolic comorbidities, the risk of EDA was increased 21% (aHR, 1.21; 95% CI 1.08-1.37).
The list of comorbidities considered in this study was drawn from the International Advisory Committee on Clinical Trials in MS. It included numerous cardiometabolic comorbidities, such as hypertension, hyperlipidemia, diabetes, ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. It also included chronic lung diseases, such as asthma and chronic obstructive pulmonary disease; psychiatric diseases, such as depression and anxiety; and miscellaneous autoimmune conditions.
The number of comorbidities was categorized for analysis as zero, one, two, or three or more. However, Dr. Salter acknowledged that these phase 3 trials did include comorbidity exclusion criteria. In fact, severe forms of most of these comorbidities were exclusion criteria in at least some studies. Yet, the prevalence of one or more comorbidities was still 45.4% in the total population from this meta-analysis.
By themselves alone, ischemic heart disease (aHR, 1.63), cerebrovascular disease (aHR, 1.70) and at least one psychiatric disorder (aHR, 1.14) were all significant for increased MS activity at the end of 2 years by a 95% confidence interval that did not cross the line of unity.
When the EDA endpoints were evaluated individually, not even three or more comorbidities was associated with an increased rate of active lesions on MRI at the end of follow-up, but two or more and three or more comorbidities were associated with a significantly increased risk of disability worsening (aHR, 1.16 and aHR, 1.31, respectively) and relapse (aHR, 1.16 for both).
An Underestimation of Associations?
Prospective trials are still needed to show that treating comorbidities improves outcome in MS, but randomization will be problematic if it means withholding treatment for conditions with risks independent of MS, Dr. Salter said. Although the data from this analysis did not permit an analysis of how relative severity of comorbidities affected MS outcome, she reiterated that most patients with severe comorbidities were likely excluded from inclusion in the studies anyway.
“We think that we are probably seeing an underestimation of an associations between comorbidity and increased MS activity,” Dr. Salter said. While she reported that confounding cannot be ruled out, the robust associations identified in a meta-analysis “limit the possibility of bias or chance findings.”
Asked if the message that clinicians should treat comorbidities to reduce MS activity is a reasonable conclusion in the absence of proof that treatment is beneficial, Dr. Freedman looked both to the body of evidence and to the common sense behind the recommendation.
Basically, Dr. Freedman believes that comorbidities should be addressed routinely and rigorously even if there was no evidence that they improve MS outcome. These data provide just one other source of support for a practice that should be conducted anyway.
Dr. Salter reported financial relationships with Abata Therapeutics, Gryphon Bio, and Owl Therapeutics. Dr. Freedman reported financial relationships with more than 10 pharmaceutical companies.
COPENHAGEN — The largest and perhaps most rigorous study to demonstrate an association between the presence of comorbidities and accelerated progression of multiple sclerosis (MS) is sufficiently compelling that both the study author and an independent expert maintained clinical practice should be adjusted.
Even while acknowledging that “it is hard to make causative statements” on the basis of these types of data, the findings are sufficiently compelling to suggest that comorbidities “should be a pressing concern” in MS management, according to Amber Salter, PhD, an associate professor of biostatistics at the University of Texas Southwestern Medical School, Dallas.
The strong association in this meta-analysis, presented at the 2024 ECTRIMS annual meeting, were drawn from 15 multicenter phase 3 treatment trials with 16,794 participants followed for at least 2 years, Dr. Salter reported. Her data were published simultaneously in JAMA Neurology.
“One of the strengths of this study is that the data on comorbidities were collected prospectively as part of these trials,” explained Mark S. Freedman, MD, director of the Multiple Sclerosis Research Center at Ottawa Hospital in Canada. He agreed with Dr. Salter that it is reasonable to apply these findings to clinical practice given their consistency with numerous other studies and the value of what he termed as “a holistic approach” to improving outcomes in MS.
Meta-Analysis Avoids Weaknesses of Previous Data
There are many potential weaknesses of past observational studies that the authors of this meta-analysis hoped to avoid. These include the possibility that MS patients with comorbidities might be less likely to take or adhere to disease-modifying therapies (DMT) or that comorbidity burden might masquerade or be misinterpreted as MS progression. By employing data from phase 3 DMT trials, Dr. Salter maintained that prospectively collected data monitored carefully over an extended follow-up allows the impact of comorbidities on outcome to be evaluated in a more controlled fashion.
Dr. Freedman liked the design of this study, but he admitted that he was surprised by the result.
“Phase 3 trials typically include exclusion criteria for significant comorbidities, so I did not think they would be able to show any meaningful differences,” Dr. Freedman said in an interview.
For the main outcome of evidence of disease activity (EDA), defined as confirmed disability worsening measured with the Expanded Disability Status Scale (EDSS), relapse activity, or any new or enlarging lesions on MRI, the differences reached significance even after adjustments for multiple potentially confounding factors.
MS Activity Increases Significantly with More Comorbidities
Compared with no comorbidity, the presence of three or more comorbidities were associated with a significant 14% increase in the adjusted hazard ratio (aHR) of EDA (aHR, 1.14; 95% CI, 1.02-1.28), Dr. Salter reported. If there were two or more cardiometabolic comorbidities, the risk of EDA was increased 21% (aHR, 1.21; 95% CI 1.08-1.37).
The list of comorbidities considered in this study was drawn from the International Advisory Committee on Clinical Trials in MS. It included numerous cardiometabolic comorbidities, such as hypertension, hyperlipidemia, diabetes, ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. It also included chronic lung diseases, such as asthma and chronic obstructive pulmonary disease; psychiatric diseases, such as depression and anxiety; and miscellaneous autoimmune conditions.
The number of comorbidities was categorized for analysis as zero, one, two, or three or more. However, Dr. Salter acknowledged that these phase 3 trials did include comorbidity exclusion criteria. In fact, severe forms of most of these comorbidities were exclusion criteria in at least some studies. Yet, the prevalence of one or more comorbidities was still 45.4% in the total population from this meta-analysis.
By themselves alone, ischemic heart disease (aHR, 1.63), cerebrovascular disease (aHR, 1.70) and at least one psychiatric disorder (aHR, 1.14) were all significant for increased MS activity at the end of 2 years by a 95% confidence interval that did not cross the line of unity.
When the EDA endpoints were evaluated individually, not even three or more comorbidities was associated with an increased rate of active lesions on MRI at the end of follow-up, but two or more and three or more comorbidities were associated with a significantly increased risk of disability worsening (aHR, 1.16 and aHR, 1.31, respectively) and relapse (aHR, 1.16 for both).
An Underestimation of Associations?
Prospective trials are still needed to show that treating comorbidities improves outcome in MS, but randomization will be problematic if it means withholding treatment for conditions with risks independent of MS, Dr. Salter said. Although the data from this analysis did not permit an analysis of how relative severity of comorbidities affected MS outcome, she reiterated that most patients with severe comorbidities were likely excluded from inclusion in the studies anyway.
“We think that we are probably seeing an underestimation of an associations between comorbidity and increased MS activity,” Dr. Salter said. While she reported that confounding cannot be ruled out, the robust associations identified in a meta-analysis “limit the possibility of bias or chance findings.”
Asked if the message that clinicians should treat comorbidities to reduce MS activity is a reasonable conclusion in the absence of proof that treatment is beneficial, Dr. Freedman looked both to the body of evidence and to the common sense behind the recommendation.
Basically, Dr. Freedman believes that comorbidities should be addressed routinely and rigorously even if there was no evidence that they improve MS outcome. These data provide just one other source of support for a practice that should be conducted anyway.
Dr. Salter reported financial relationships with Abata Therapeutics, Gryphon Bio, and Owl Therapeutics. Dr. Freedman reported financial relationships with more than 10 pharmaceutical companies.
FROM ECTRIMS 2024
Expert Warns of Problems with Large Language Models in Dermatology
HUNTINGTON BEACH, CALIF. — and alarmed.
Of the 134 respondents who completed the survey, 87 (65%) reported using LLMs in a clinical setting. Of those 87 respondents, 17 (20%) used LMMs daily, 28 (32%) weekly, 5 (6%) monthly, and 37 (43%) rarely. That represents “pretty significant usage,” Dr. Daneshjou, assistant professor of biomedical data science and dermatology at Stanford University, Palo Alto, California, said at the annual meeting of the Pacific Dermatologic Association.
Most of the respondents reported using LLMs for patient care (79%), followed by administrative tasks (74%), medical records (43%), and education (18%), “which can be problematic,” she said. “These models are not appropriate to use for patient care.”
When asked about their thoughts on the accuracy of LLMs, 58% of respondents deemed them to be “somewhat accurate” and 7% viewed them as “extremely accurate.”
The overall survey responses raise concern because LLMs “are not trained for accuracy; they are trained initially as a next-word predictor on large bodies of tech data,” Dr. Daneshjou said. “LLMs are already being implemented but have the potential to cause harm and bias, and I believe they will if we implement them the way things are rolling out right now. I don’t understand why we’re implementing something without any clinical trial or showing that it improves care before we throw untested technology into our healthcare system.”
Meanwhile, Epic and Microsoft are collaborating to bring AI technology to electronic health records, she said, and Epic is building more than 100 new AI features for physicians and patients. “I think it’s important for every physician and trainee to understand what is going on in the realm of AI,” said Dr. Daneshjou, who is an associate editor for the monthly journal NEJM AI. “Be involved in the conversation because we are the clinical experts, and a lot of people making decisions and building tools do not have the clinical expertise.”
To further illustrate her concerns, Dr. Daneshjou referenced a red teaming event she and her colleagues held with computer scientists, biomedical data scientists, engineers, and physicians across multiple specialties to identify issues related to safety, bias, factual errors, and/or security issues in GPT-3.5, GPT-4, and GPT-4 with internet. The goal was to mimic clinical health scenarios, ask the LLM to respond, and have the team members review the accuracy of LLM responses.
The participants found that nearly 20% of LLM responses were inappropriate. For example, in one task, an LLM was asked to calculate a RegiSCAR score for Drug Reaction With Eosinophilia and Systemic Symptoms for a patient, but the response included an incorrect score for eosinophilia. “That’s why these tools can be so dangerous because you’re reading along and everything seems right, but there might be something so minor that can impact patient care and you might miss it,” Dr. Daneshjou said.
On a related note, she advised against dermatologists uploading images into GPT-4 Vision, an LLM that can analyze images and provide textual responses to questions about them, and she recommends not using GPT-4 Vision for any diagnostic support. At this time, “GPT-4 Vision overcalls malignancies, and the specificity and sensitivity are not very good,” she explained.
Dr. Daneshjou disclosed that she has served as an adviser to MDalgorithms and Revea and has received consulting fees from Pfizer, L’Oréal, Frazier Healthcare Partners, and DWA and research funding from UCB.
A version of this article first appeared on Medscape.com.
HUNTINGTON BEACH, CALIF. — and alarmed.
Of the 134 respondents who completed the survey, 87 (65%) reported using LLMs in a clinical setting. Of those 87 respondents, 17 (20%) used LMMs daily, 28 (32%) weekly, 5 (6%) monthly, and 37 (43%) rarely. That represents “pretty significant usage,” Dr. Daneshjou, assistant professor of biomedical data science and dermatology at Stanford University, Palo Alto, California, said at the annual meeting of the Pacific Dermatologic Association.
Most of the respondents reported using LLMs for patient care (79%), followed by administrative tasks (74%), medical records (43%), and education (18%), “which can be problematic,” she said. “These models are not appropriate to use for patient care.”
When asked about their thoughts on the accuracy of LLMs, 58% of respondents deemed them to be “somewhat accurate” and 7% viewed them as “extremely accurate.”
The overall survey responses raise concern because LLMs “are not trained for accuracy; they are trained initially as a next-word predictor on large bodies of tech data,” Dr. Daneshjou said. “LLMs are already being implemented but have the potential to cause harm and bias, and I believe they will if we implement them the way things are rolling out right now. I don’t understand why we’re implementing something without any clinical trial or showing that it improves care before we throw untested technology into our healthcare system.”
Meanwhile, Epic and Microsoft are collaborating to bring AI technology to electronic health records, she said, and Epic is building more than 100 new AI features for physicians and patients. “I think it’s important for every physician and trainee to understand what is going on in the realm of AI,” said Dr. Daneshjou, who is an associate editor for the monthly journal NEJM AI. “Be involved in the conversation because we are the clinical experts, and a lot of people making decisions and building tools do not have the clinical expertise.”
To further illustrate her concerns, Dr. Daneshjou referenced a red teaming event she and her colleagues held with computer scientists, biomedical data scientists, engineers, and physicians across multiple specialties to identify issues related to safety, bias, factual errors, and/or security issues in GPT-3.5, GPT-4, and GPT-4 with internet. The goal was to mimic clinical health scenarios, ask the LLM to respond, and have the team members review the accuracy of LLM responses.
The participants found that nearly 20% of LLM responses were inappropriate. For example, in one task, an LLM was asked to calculate a RegiSCAR score for Drug Reaction With Eosinophilia and Systemic Symptoms for a patient, but the response included an incorrect score for eosinophilia. “That’s why these tools can be so dangerous because you’re reading along and everything seems right, but there might be something so minor that can impact patient care and you might miss it,” Dr. Daneshjou said.
On a related note, she advised against dermatologists uploading images into GPT-4 Vision, an LLM that can analyze images and provide textual responses to questions about them, and she recommends not using GPT-4 Vision for any diagnostic support. At this time, “GPT-4 Vision overcalls malignancies, and the specificity and sensitivity are not very good,” she explained.
Dr. Daneshjou disclosed that she has served as an adviser to MDalgorithms and Revea and has received consulting fees from Pfizer, L’Oréal, Frazier Healthcare Partners, and DWA and research funding from UCB.
A version of this article first appeared on Medscape.com.
HUNTINGTON BEACH, CALIF. — and alarmed.
Of the 134 respondents who completed the survey, 87 (65%) reported using LLMs in a clinical setting. Of those 87 respondents, 17 (20%) used LMMs daily, 28 (32%) weekly, 5 (6%) monthly, and 37 (43%) rarely. That represents “pretty significant usage,” Dr. Daneshjou, assistant professor of biomedical data science and dermatology at Stanford University, Palo Alto, California, said at the annual meeting of the Pacific Dermatologic Association.
Most of the respondents reported using LLMs for patient care (79%), followed by administrative tasks (74%), medical records (43%), and education (18%), “which can be problematic,” she said. “These models are not appropriate to use for patient care.”
When asked about their thoughts on the accuracy of LLMs, 58% of respondents deemed them to be “somewhat accurate” and 7% viewed them as “extremely accurate.”
The overall survey responses raise concern because LLMs “are not trained for accuracy; they are trained initially as a next-word predictor on large bodies of tech data,” Dr. Daneshjou said. “LLMs are already being implemented but have the potential to cause harm and bias, and I believe they will if we implement them the way things are rolling out right now. I don’t understand why we’re implementing something without any clinical trial or showing that it improves care before we throw untested technology into our healthcare system.”
Meanwhile, Epic and Microsoft are collaborating to bring AI technology to electronic health records, she said, and Epic is building more than 100 new AI features for physicians and patients. “I think it’s important for every physician and trainee to understand what is going on in the realm of AI,” said Dr. Daneshjou, who is an associate editor for the monthly journal NEJM AI. “Be involved in the conversation because we are the clinical experts, and a lot of people making decisions and building tools do not have the clinical expertise.”
To further illustrate her concerns, Dr. Daneshjou referenced a red teaming event she and her colleagues held with computer scientists, biomedical data scientists, engineers, and physicians across multiple specialties to identify issues related to safety, bias, factual errors, and/or security issues in GPT-3.5, GPT-4, and GPT-4 with internet. The goal was to mimic clinical health scenarios, ask the LLM to respond, and have the team members review the accuracy of LLM responses.
The participants found that nearly 20% of LLM responses were inappropriate. For example, in one task, an LLM was asked to calculate a RegiSCAR score for Drug Reaction With Eosinophilia and Systemic Symptoms for a patient, but the response included an incorrect score for eosinophilia. “That’s why these tools can be so dangerous because you’re reading along and everything seems right, but there might be something so minor that can impact patient care and you might miss it,” Dr. Daneshjou said.
On a related note, she advised against dermatologists uploading images into GPT-4 Vision, an LLM that can analyze images and provide textual responses to questions about them, and she recommends not using GPT-4 Vision for any diagnostic support. At this time, “GPT-4 Vision overcalls malignancies, and the specificity and sensitivity are not very good,” she explained.
Dr. Daneshjou disclosed that she has served as an adviser to MDalgorithms and Revea and has received consulting fees from Pfizer, L’Oréal, Frazier Healthcare Partners, and DWA and research funding from UCB.
A version of this article first appeared on Medscape.com.
FROM PDA 2024
Laser, Radiofrequency Therapies Offer Little Benefit for Genitourinary Syndrome of Menopause
CHICAGO — Use of CO2 lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.
“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”
The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”
The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.
Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.
Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.
But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”
GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.
Most of these have been found effective, according to a recent systematic review Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO2 laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.
Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”
Much of the evidence has focused on CO2 lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.
Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.
The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.
Most of these studies assessed CO2 lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO2 lasers vs radiofrequency treatments.
The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO2 lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO2 laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.
Most CO2 laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.
“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.
“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said.
The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.
The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
A version of this article first appeared on Medscape.com.
CHICAGO — Use of CO2 lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.
“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”
The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”
The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.
Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.
Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.
But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”
GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.
Most of these have been found effective, according to a recent systematic review Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO2 laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.
Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”
Much of the evidence has focused on CO2 lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.
Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.
The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.
Most of these studies assessed CO2 lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO2 lasers vs radiofrequency treatments.
The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO2 lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO2 laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.
Most CO2 laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.
“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.
“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said.
The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.
The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
A version of this article first appeared on Medscape.com.
CHICAGO — Use of CO2 lasers and similar “energy-based” treatments result in little to no benefit for genitourinary syndrome of menopause (GSM) symptoms, according to research presented at the The Menopause Society 2024 Annual Meeting in Chicago on September 12.
“There was a concern that menopausal women are being targeted for treatments that may not have a lot of benefit and might have significant harms,” Elisheva Danan, MD, MPH, a physician at the Minneapolis VA Health Care System and an assistant professor of medicine at the University of Minnesota Medical School in Minneapolis, told this news organization. While she was not surprised to find little evidence of benefit, “we were a little bit surprised that we also didn’t find significant evidence of harms.”
The study was unable to evaluate the potential for financial harms, but Dr. Danan noted that these therapies are often expensive and not typically covered by insurance. The treatments appear to be used primarily in private practice, she said, while “most academic clinicians were not familiar with these and do not use these lasers.”
The American Urological Association had requested the review, Dr. Danan said, “to inform clinical guidelines that they could put out for practitioners about treating genital urinary syndrome from menopause.” Yet the evidence available remains slim. “There’s a lot of outcomes that were not looked at by most of these [trials], or they were looked at in a way that we couldn’t separate out,” she said.
Kamalini Das, MD, a professor of ob.gyn. at the University of Minnesota who was not involved in the research, was surprised by the findings because studies to date have been variable, “but since this looks at multiple studies and they find no benefits, I would take these results as more significant than any of the small studies,” she told this news organization.
Dr. Das said she has patients who ask about using these therapies and have had them done. “So far, I’ve told them the jury is out on whether it will help or not, that there are some studies that say they’re beneficial and some studies that they’re not,” Dr. Das said.
But this new review changes what she will tell patients going forward, she said. “This is a good study because it consolidates lots of little studies, so I think I would use this to say, looking at all the studies together, this treatment is not beneficial.”
GSM occurs due to the body’s reduced production of estrogen and affects anywhere from 27% to 84% of postmenopausal women. It can involve a constellation of symptoms ranging from vaginal discomfort and irritation to painful urination or intercourse. Typical recommended treatments for GSM include systemic hormone therapy, localized hormonal treatments such as vaginal estrogen or dehydroepiandrosterone, nonhormonal creams and moisturizers, and the prescription drug ospemifene.
Most of these have been found effective, according to a recent systematic review Dr. Danan published in the Annals of Internal Medicine that this news organization covered. But recent years have also seen a rapid increase in interest and the availability of energy-based treatments for GSM, such as CO2 laser and radiofrequency interventions, particularly for those who cannot or do not want to use hormonal treatments. The idea behind these newer therapies is that they “heat tissue to cause a denaturation of collagen fibers and induce a wound-healing response,” with the aim of “enhancement of vaginal elasticity, restoration of premenopausal epithelial function, and symptom improvement,” the authors wrote.
Evidence has been scant and uneven for the safety and effectiveness of these treatments, and they have not been evaluated by the US Food and Drug Administration. The agency issued a warning in 2018 with remarks from then Commissioner Scott Gottlieb that the “products have serious risks and don’t have adequate evidence to support their use for these purposes.”
Much of the evidence has focused on CO2 lasers instead of other energy-based treatments, however, and a raft of new studies have been published on these interventions in the past 2 years. Dr. Danan and colleagues, therefore, assessed the most current state of the research with a systematic review of randomized controlled trials (RCTs) and prospective observational studies with control groups published through December 11, 2023.
Included studies needed to evaluate an energy-based treatment for at least 8 weeks in a minimum of 40 postmenopausal women (20 in each group) who had one or more GSM symptoms. The authors also included nonrandomized and uncontrolled studies with a follow-up of a year or more to assess possible adverse events. The studies also needed to assess at least one of eight core outcomes: Dyspareunia; vulvovaginal dryness; vulvovaginal discomfort/irritation; dysuria; change in most bothersome symptom; treatment satisfaction; adverse events; and distress, bother, or interference associated with genitourinary symptoms.
The authors identified 32 studies, including 16 RCTs, one quasi-RCT, and 15 nonrandomized studies. The researchers extracted and analyzed data from the 10 RCTs and one quasi-RCT that were rated as having low to moderate risk for bias.
Most of these studies assessed CO2 lasers alone, while three assessed erbium:yttrium-aluminum-garnet (Er:YAG) laser, and one looked at CO2 lasers vs radiofrequency treatments.
The average age of participants ranged from 56 to 64 years, and most trials were in the United States. Results showed that CO2 lasers led to little or no difference in dysuria, dyspareunia, or quality of life when compared with sham lasers. The CO2 laser therapy also showed little to no difference compared with vaginal estrogen creams for dyspareunia, dryness, discomfort/irritation, dysuria, or quality of life.
Most CO2 laser studies reported on most outcomes, but the Er:YAG studies tended to report only on quality of life and/or one or two other outcomes. The radiofrequency study only assessed dyspareunia and quality of life.
“Treatment effects on other outcomes and effects of Er:YAG laser or radiofrequency on any outcomes are very uncertain,” the authors reported. Few adverse events and no serious adverse events were reported based on 15 studies, including the additional non-RCTs that had follow-up for at least a year.
“There are case reports and other types of studies that have shown some bad outcomes using laser therapies, and we really wanted to be expansive and include anything, especially because this is such a new treatment and all these trials were in the last couple of years,” Dr. Danan said.
The review was limited by inconsistent or nonvalidated outcome reporting in the studies as well as small populations and short follow-up, typically less than 3 months.
The research was funded by the Agency for Healthcare Research and Quality and Patient-Centered Outcomes Research Institute. Dr. Danan and Dr. Das had no disclosures.
A version of this article first appeared on Medscape.com.
FROM THE MENOPAUSE SOCIETY 2024
Short Steroid Treatment May Raise Diabetes Risk: Study
People who received systemic glucocorticoids during short hospital stays were more than twice as likely to develop new onset diabetes than those who didn’t, reported the authors of a large study that analyzed more than a decade’s worth of patient records.
Rajna Golubic, MD, PhD, of the diabetes trials unit at the University of Oxford, United Kingdom, and colleagues did an observational cohort study, using data from electronic healthcare records of more than patients admitted between January 1, 2013, and October 1, 2023.
They looked for patients who didn’t have a diabetes diagnosis at the time of admission and who were not taking a steroid. Their research was presented this month at the 2024 annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain.
About 1.8%, of 316, of the 17,258 patients who received systemic glucocorticoids (tablets, injections, or infusions) during their hospital stay developed new-onset diabetes, while this happened to only 0.8%, or 3450, of the 434,348 who did not get these drugs, according to an abstract of the EASD presentation.
The median length of stay was 3 days (2-8) for the group of patients who took steroids, compared with 1 day (1-3) in those who did not. Further analysis showed that, when age and sex were factored in, patients receiving systemic glucocorticoids were more than twice as likely (2.6 times) to develop diabetes as those not receiving the treatment, Dr. Golubic said.
This research builds on previous studies that looked at smaller groups of patients and the diabetes risk in patients with specific conditions, including rheumatoid arthritis, Dr. Golubic said. It may prove helpful for clinicians considering when to employ steroids, which are useful medications for managing inflammation associated with many conditions.
“This gives them a very good estimate of how much more likely people treated with systemic glucocorticoids are to develop new-onset diabetes,” Dr. Golubic said.
Glucocorticoids have for decades been used for managing acute and chronic inflammatory diseases. The link to diabetes has been previously reported in smaller studies and in ones linked to specific conditions such as respiratory disease and rheumatoid arthritis.
Carolyn Cummins, PhD, an associate professor at the University of Toronto, Canada, who was not part of this study, told this news organization she was pleased to see a study of diabetes and steroids done with the scope that Dr. Golubic and colleagues undertook. Dr. Cummins in 2022 published an article titled “Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions” in Nature Reviews Endocrinology.
“We know that this is an issue, but we didn’t necessarily know numerically how significant it was,” Dr. Cummins said. “I would say it wasn’t a surprising finding, but it’s nice to actually have the numbers from a large study.”
Dr. Golubic and Dr. Cummins reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People who received systemic glucocorticoids during short hospital stays were more than twice as likely to develop new onset diabetes than those who didn’t, reported the authors of a large study that analyzed more than a decade’s worth of patient records.
Rajna Golubic, MD, PhD, of the diabetes trials unit at the University of Oxford, United Kingdom, and colleagues did an observational cohort study, using data from electronic healthcare records of more than patients admitted between January 1, 2013, and October 1, 2023.
They looked for patients who didn’t have a diabetes diagnosis at the time of admission and who were not taking a steroid. Their research was presented this month at the 2024 annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain.
About 1.8%, of 316, of the 17,258 patients who received systemic glucocorticoids (tablets, injections, or infusions) during their hospital stay developed new-onset diabetes, while this happened to only 0.8%, or 3450, of the 434,348 who did not get these drugs, according to an abstract of the EASD presentation.
The median length of stay was 3 days (2-8) for the group of patients who took steroids, compared with 1 day (1-3) in those who did not. Further analysis showed that, when age and sex were factored in, patients receiving systemic glucocorticoids were more than twice as likely (2.6 times) to develop diabetes as those not receiving the treatment, Dr. Golubic said.
This research builds on previous studies that looked at smaller groups of patients and the diabetes risk in patients with specific conditions, including rheumatoid arthritis, Dr. Golubic said. It may prove helpful for clinicians considering when to employ steroids, which are useful medications for managing inflammation associated with many conditions.
“This gives them a very good estimate of how much more likely people treated with systemic glucocorticoids are to develop new-onset diabetes,” Dr. Golubic said.
Glucocorticoids have for decades been used for managing acute and chronic inflammatory diseases. The link to diabetes has been previously reported in smaller studies and in ones linked to specific conditions such as respiratory disease and rheumatoid arthritis.
Carolyn Cummins, PhD, an associate professor at the University of Toronto, Canada, who was not part of this study, told this news organization she was pleased to see a study of diabetes and steroids done with the scope that Dr. Golubic and colleagues undertook. Dr. Cummins in 2022 published an article titled “Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions” in Nature Reviews Endocrinology.
“We know that this is an issue, but we didn’t necessarily know numerically how significant it was,” Dr. Cummins said. “I would say it wasn’t a surprising finding, but it’s nice to actually have the numbers from a large study.”
Dr. Golubic and Dr. Cummins reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People who received systemic glucocorticoids during short hospital stays were more than twice as likely to develop new onset diabetes than those who didn’t, reported the authors of a large study that analyzed more than a decade’s worth of patient records.
Rajna Golubic, MD, PhD, of the diabetes trials unit at the University of Oxford, United Kingdom, and colleagues did an observational cohort study, using data from electronic healthcare records of more than patients admitted between January 1, 2013, and October 1, 2023.
They looked for patients who didn’t have a diabetes diagnosis at the time of admission and who were not taking a steroid. Their research was presented this month at the 2024 annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, Spain.
About 1.8%, of 316, of the 17,258 patients who received systemic glucocorticoids (tablets, injections, or infusions) during their hospital stay developed new-onset diabetes, while this happened to only 0.8%, or 3450, of the 434,348 who did not get these drugs, according to an abstract of the EASD presentation.
The median length of stay was 3 days (2-8) for the group of patients who took steroids, compared with 1 day (1-3) in those who did not. Further analysis showed that, when age and sex were factored in, patients receiving systemic glucocorticoids were more than twice as likely (2.6 times) to develop diabetes as those not receiving the treatment, Dr. Golubic said.
This research builds on previous studies that looked at smaller groups of patients and the diabetes risk in patients with specific conditions, including rheumatoid arthritis, Dr. Golubic said. It may prove helpful for clinicians considering when to employ steroids, which are useful medications for managing inflammation associated with many conditions.
“This gives them a very good estimate of how much more likely people treated with systemic glucocorticoids are to develop new-onset diabetes,” Dr. Golubic said.
Glucocorticoids have for decades been used for managing acute and chronic inflammatory diseases. The link to diabetes has been previously reported in smaller studies and in ones linked to specific conditions such as respiratory disease and rheumatoid arthritis.
Carolyn Cummins, PhD, an associate professor at the University of Toronto, Canada, who was not part of this study, told this news organization she was pleased to see a study of diabetes and steroids done with the scope that Dr. Golubic and colleagues undertook. Dr. Cummins in 2022 published an article titled “Fresh insights into glucocorticoid-induced diabetes mellitus and new therapeutic directions” in Nature Reviews Endocrinology.
“We know that this is an issue, but we didn’t necessarily know numerically how significant it was,” Dr. Cummins said. “I would say it wasn’t a surprising finding, but it’s nice to actually have the numbers from a large study.”
Dr. Golubic and Dr. Cummins reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Will New Obesity Drugs Make Bariatric Surgery Obsolete?
MADRID — In spirited presentations at the annual meeting of the European Association for the Study of Diabetes, Louis J. Aronne, MD, of Weill Cornell Medicine in New York City, made a compelling case that the next generation of obesity medications will make bariatric surgery obsolete, and Francesco Rubino, MD, of King’s College London in England, made an equally compelling case that they will not.
In fact, Dr. Rubino predicted that “metabolic” surgery — new nomenclature reflecting the power of surgery to reduce not only obesity, but also other metabolic conditions, over the long term — will continue and could even increase in years to come.
‘Medical Treatment Will Dominate’
“Obesity treatment is the superhero of treating metabolic disease because it can defeat all of the bad guys at once, not just one, like the other treatments,” Dr. Aronne told meeting attendees. “If you treat somebody’s cholesterol, you’re just treating their cholesterol, and you may actually increase their risk of developing type 2 diabetes (T2D). You treat their blood pressure, you don’t treat their glucose and you don’t treat their lipids — the list goes on and on and on. But by treating obesity, if you can get enough weight loss, you can get all those things at once.”
He pointed to the SELECT trial, which showed that treating obesity with a glucagon-like peptide 1 receptor agonist reduced major adverse cardiovascular events as well as death from any cause, results in line with those from other modes of treatment for cardiovascular disease (CVD) or lipid lowering, he said. “But we get much more with these drugs, including positive effects on heart failure, chronic kidney disease, and a 73% reduction in T2D. So, we’re now on the verge of a major change in the way we manage metabolic disease.”
Dr. Aronne drew a parallel between treating obesity and the historic way of treating hypertension. Years ago, he said, “we waited too long to treat people. We waited until they had severe hypertension that in many cases was irreversible. What would you prefer to do now for obesity — have the patient lose weight with a medicine that is proven to reduce complications or wait until they develop diabetes, high blood pressure, heart disease and then have them undergo surgery to treat that?”
Looking ahead, “the trend could be to treat obesity before it gets out of hand,” he suggested. Treatment might start in people with a body mass index (BMI) of 27 kg/m2, who would be treated to a target BMI of 25. “That’s only a 10% or so change, but our goal would be to keep them in the normal range so they never go above that target. In fact, I think we’re going to be looking at people with severe obesity in a few years and saying, ‘I can’t believe someone didn’t treat that guy earlier.’ What’s going to happen to bariatric surgery if no one gets to a higher weight?”
The plethora of current weight-loss drugs and the large group on the horizon mean that if someone doesn’t respond to one drug, there will be plenty of other choices, Dr. Aronne continued. People will be referred for surgery, but possibly only after they’ve not responded to medical treatment — or just the opposite. “In the United States, it’s much cheaper to have surgery, and I bet the insurance companies are going to make people have surgery before they can get the medicines,” he acknowledged.
A recent report from Morgan Stanley suggests that the global market for the newer weight-loss drugs could increase by 15-fold over the next 5 years as their benefits expand beyond weight loss and that as much as 9% of the US population will be taking the drugs by 2035, Dr. Aronne said, adding that he thinks 9% is an underestimate. By contrast, the number of patients treated by his team’s surgical program is down about 20%.
“I think it’s very clear that medical treatment is going to dominate,” he concluded. “But, it’s also possible that surgery could go up because so many people are going to be coming for medical therapy that we may wind up referring more for surgical therapy.”
‘Surgery Is Saving Lives’
Dr. Rubino is convinced that anti-obesity drugs will not make surgery obsolete, “but it will not be business as usual,” he told meeting attendees. “In fact, I think these drugs will expedite a process that is already ongoing — a transformation of bariatric into metabolic surgery.”
“Bariatric surgery will go down in history as one of the biggest missed opportunities that we, as medical professionals, have seen over the past many years,” he said. “It has been shown beyond any doubt to reduce all-cause mortality — in other words, it saves lives,” and it’s also cost effective and improves quality of life. Yet, fewer than 1% of people globally who meet the criteria actually get the surgery.
Many clinicians don’t inform patients about the treatment and don’t refer them for it, he said. “That would be equivalent to having surgery for CVD [cardiovascular disease], cancer, or other important diseases available but not being accessed as they should be.”
A big reason for the dearth of procedures is that people have unrealistic expectations about diet and exercise interventions for weight loss, he said. His team’s survey, presented at the 26th World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, showed that 43% of respondents believed diet and exercise was the best treatment for severe obesity (BMI > 35). A more recent survey asked which among several choices was the most effective weight-loss intervention, and again a large proportion “believed wrongly that diet and exercise is most effective — more so than drugs or surgery — despite plenty of evidence that this is not the case.”
In this context, he said, “any surgery, no matter how safe or effective, would never be very popular.” If obesity is viewed as a modifiable risk factor, patients may say they’ll think about it for 6 months. In contrast, “nobody will tell you ‘I will think about it’ if you tell them they need gallbladder surgery to get rid of gallstone pain.”
Although drugs are available to treat obesity, none of them are curative, and if they’re stopped, the weight comes back, Dr. Rubino pointed out. “Efficacy of drugs is measured in weeks or months, whereas efficacy of surgery is measured in decades of durability — in the case of bariatric surgery, 10-20 years. That’s why bariatric surgery will remain an option,” he said. “It’s not just preventing disease, it’s resolving ongoing disease.”
Furthermore, bariatric surgery is showing value for people with established T2D, whereas in the past, it was mainly considered to be a weight-loss intervention for younger, healthier patients, he said. “In my practice, we’re operating more often in people with T2D, even those at higher risk for anesthesia and surgery — eg, patients with heart failure, chronic kidney disease, on dialysis — and we’re still able to maintain the same safety with minimally invasive laparoscopic surgery that we had with healthier patients.”
A vote held at the end of the session revealed that the audience was split about half and half in favor of drugs making bariatric surgery obsolete or not.
“I think we may have to duke it out now,” Dr. Aronne quipped.
Dr. Aronne disclosed being a consultant, speaker, and adviser for and receiving research support from Altimmune, Amgen, AstraZeneca, Eli Lilly, Intellihealth, Janssen, Novo Nordisk, Pfizer, Senda, UnitedHealth Group, Versanis, and others; he has ownership interests in ERX, Intellihealth, Jamieson, Kallyope, Skye Bioscience, Veru, and others; and he is on the board of directors of ERX, Jamieson Wellness, and Intellihealth/FlyteHealth. Dr. Rubino disclosed receiving research and educational grants from Novo Nordisk, Ethicon, and Medtronic; he is on the scientific advisory board/data safety advisory board for Keyron, Morphic Medical, and GT Metabolic Solutions; he receives speaking honoraria from Medtronic, Ethicon, Novo Nordisk, and Eli Lilly; and he is president of the nonprofit Metabolic Health Institute.
A version of this article first appeared on Medscape.com.
MADRID — In spirited presentations at the annual meeting of the European Association for the Study of Diabetes, Louis J. Aronne, MD, of Weill Cornell Medicine in New York City, made a compelling case that the next generation of obesity medications will make bariatric surgery obsolete, and Francesco Rubino, MD, of King’s College London in England, made an equally compelling case that they will not.
In fact, Dr. Rubino predicted that “metabolic” surgery — new nomenclature reflecting the power of surgery to reduce not only obesity, but also other metabolic conditions, over the long term — will continue and could even increase in years to come.
‘Medical Treatment Will Dominate’
“Obesity treatment is the superhero of treating metabolic disease because it can defeat all of the bad guys at once, not just one, like the other treatments,” Dr. Aronne told meeting attendees. “If you treat somebody’s cholesterol, you’re just treating their cholesterol, and you may actually increase their risk of developing type 2 diabetes (T2D). You treat their blood pressure, you don’t treat their glucose and you don’t treat their lipids — the list goes on and on and on. But by treating obesity, if you can get enough weight loss, you can get all those things at once.”
He pointed to the SELECT trial, which showed that treating obesity with a glucagon-like peptide 1 receptor agonist reduced major adverse cardiovascular events as well as death from any cause, results in line with those from other modes of treatment for cardiovascular disease (CVD) or lipid lowering, he said. “But we get much more with these drugs, including positive effects on heart failure, chronic kidney disease, and a 73% reduction in T2D. So, we’re now on the verge of a major change in the way we manage metabolic disease.”
Dr. Aronne drew a parallel between treating obesity and the historic way of treating hypertension. Years ago, he said, “we waited too long to treat people. We waited until they had severe hypertension that in many cases was irreversible. What would you prefer to do now for obesity — have the patient lose weight with a medicine that is proven to reduce complications or wait until they develop diabetes, high blood pressure, heart disease and then have them undergo surgery to treat that?”
Looking ahead, “the trend could be to treat obesity before it gets out of hand,” he suggested. Treatment might start in people with a body mass index (BMI) of 27 kg/m2, who would be treated to a target BMI of 25. “That’s only a 10% or so change, but our goal would be to keep them in the normal range so they never go above that target. In fact, I think we’re going to be looking at people with severe obesity in a few years and saying, ‘I can’t believe someone didn’t treat that guy earlier.’ What’s going to happen to bariatric surgery if no one gets to a higher weight?”
The plethora of current weight-loss drugs and the large group on the horizon mean that if someone doesn’t respond to one drug, there will be plenty of other choices, Dr. Aronne continued. People will be referred for surgery, but possibly only after they’ve not responded to medical treatment — or just the opposite. “In the United States, it’s much cheaper to have surgery, and I bet the insurance companies are going to make people have surgery before they can get the medicines,” he acknowledged.
A recent report from Morgan Stanley suggests that the global market for the newer weight-loss drugs could increase by 15-fold over the next 5 years as their benefits expand beyond weight loss and that as much as 9% of the US population will be taking the drugs by 2035, Dr. Aronne said, adding that he thinks 9% is an underestimate. By contrast, the number of patients treated by his team’s surgical program is down about 20%.
“I think it’s very clear that medical treatment is going to dominate,” he concluded. “But, it’s also possible that surgery could go up because so many people are going to be coming for medical therapy that we may wind up referring more for surgical therapy.”
‘Surgery Is Saving Lives’
Dr. Rubino is convinced that anti-obesity drugs will not make surgery obsolete, “but it will not be business as usual,” he told meeting attendees. “In fact, I think these drugs will expedite a process that is already ongoing — a transformation of bariatric into metabolic surgery.”
“Bariatric surgery will go down in history as one of the biggest missed opportunities that we, as medical professionals, have seen over the past many years,” he said. “It has been shown beyond any doubt to reduce all-cause mortality — in other words, it saves lives,” and it’s also cost effective and improves quality of life. Yet, fewer than 1% of people globally who meet the criteria actually get the surgery.
Many clinicians don’t inform patients about the treatment and don’t refer them for it, he said. “That would be equivalent to having surgery for CVD [cardiovascular disease], cancer, or other important diseases available but not being accessed as they should be.”
A big reason for the dearth of procedures is that people have unrealistic expectations about diet and exercise interventions for weight loss, he said. His team’s survey, presented at the 26th World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, showed that 43% of respondents believed diet and exercise was the best treatment for severe obesity (BMI > 35). A more recent survey asked which among several choices was the most effective weight-loss intervention, and again a large proportion “believed wrongly that diet and exercise is most effective — more so than drugs or surgery — despite plenty of evidence that this is not the case.”
In this context, he said, “any surgery, no matter how safe or effective, would never be very popular.” If obesity is viewed as a modifiable risk factor, patients may say they’ll think about it for 6 months. In contrast, “nobody will tell you ‘I will think about it’ if you tell them they need gallbladder surgery to get rid of gallstone pain.”
Although drugs are available to treat obesity, none of them are curative, and if they’re stopped, the weight comes back, Dr. Rubino pointed out. “Efficacy of drugs is measured in weeks or months, whereas efficacy of surgery is measured in decades of durability — in the case of bariatric surgery, 10-20 years. That’s why bariatric surgery will remain an option,” he said. “It’s not just preventing disease, it’s resolving ongoing disease.”
Furthermore, bariatric surgery is showing value for people with established T2D, whereas in the past, it was mainly considered to be a weight-loss intervention for younger, healthier patients, he said. “In my practice, we’re operating more often in people with T2D, even those at higher risk for anesthesia and surgery — eg, patients with heart failure, chronic kidney disease, on dialysis — and we’re still able to maintain the same safety with minimally invasive laparoscopic surgery that we had with healthier patients.”
A vote held at the end of the session revealed that the audience was split about half and half in favor of drugs making bariatric surgery obsolete or not.
“I think we may have to duke it out now,” Dr. Aronne quipped.
Dr. Aronne disclosed being a consultant, speaker, and adviser for and receiving research support from Altimmune, Amgen, AstraZeneca, Eli Lilly, Intellihealth, Janssen, Novo Nordisk, Pfizer, Senda, UnitedHealth Group, Versanis, and others; he has ownership interests in ERX, Intellihealth, Jamieson, Kallyope, Skye Bioscience, Veru, and others; and he is on the board of directors of ERX, Jamieson Wellness, and Intellihealth/FlyteHealth. Dr. Rubino disclosed receiving research and educational grants from Novo Nordisk, Ethicon, and Medtronic; he is on the scientific advisory board/data safety advisory board for Keyron, Morphic Medical, and GT Metabolic Solutions; he receives speaking honoraria from Medtronic, Ethicon, Novo Nordisk, and Eli Lilly; and he is president of the nonprofit Metabolic Health Institute.
A version of this article first appeared on Medscape.com.
MADRID — In spirited presentations at the annual meeting of the European Association for the Study of Diabetes, Louis J. Aronne, MD, of Weill Cornell Medicine in New York City, made a compelling case that the next generation of obesity medications will make bariatric surgery obsolete, and Francesco Rubino, MD, of King’s College London in England, made an equally compelling case that they will not.
In fact, Dr. Rubino predicted that “metabolic” surgery — new nomenclature reflecting the power of surgery to reduce not only obesity, but also other metabolic conditions, over the long term — will continue and could even increase in years to come.
‘Medical Treatment Will Dominate’
“Obesity treatment is the superhero of treating metabolic disease because it can defeat all of the bad guys at once, not just one, like the other treatments,” Dr. Aronne told meeting attendees. “If you treat somebody’s cholesterol, you’re just treating their cholesterol, and you may actually increase their risk of developing type 2 diabetes (T2D). You treat their blood pressure, you don’t treat their glucose and you don’t treat their lipids — the list goes on and on and on. But by treating obesity, if you can get enough weight loss, you can get all those things at once.”
He pointed to the SELECT trial, which showed that treating obesity with a glucagon-like peptide 1 receptor agonist reduced major adverse cardiovascular events as well as death from any cause, results in line with those from other modes of treatment for cardiovascular disease (CVD) or lipid lowering, he said. “But we get much more with these drugs, including positive effects on heart failure, chronic kidney disease, and a 73% reduction in T2D. So, we’re now on the verge of a major change in the way we manage metabolic disease.”
Dr. Aronne drew a parallel between treating obesity and the historic way of treating hypertension. Years ago, he said, “we waited too long to treat people. We waited until they had severe hypertension that in many cases was irreversible. What would you prefer to do now for obesity — have the patient lose weight with a medicine that is proven to reduce complications or wait until they develop diabetes, high blood pressure, heart disease and then have them undergo surgery to treat that?”
Looking ahead, “the trend could be to treat obesity before it gets out of hand,” he suggested. Treatment might start in people with a body mass index (BMI) of 27 kg/m2, who would be treated to a target BMI of 25. “That’s only a 10% or so change, but our goal would be to keep them in the normal range so they never go above that target. In fact, I think we’re going to be looking at people with severe obesity in a few years and saying, ‘I can’t believe someone didn’t treat that guy earlier.’ What’s going to happen to bariatric surgery if no one gets to a higher weight?”
The plethora of current weight-loss drugs and the large group on the horizon mean that if someone doesn’t respond to one drug, there will be plenty of other choices, Dr. Aronne continued. People will be referred for surgery, but possibly only after they’ve not responded to medical treatment — or just the opposite. “In the United States, it’s much cheaper to have surgery, and I bet the insurance companies are going to make people have surgery before they can get the medicines,” he acknowledged.
A recent report from Morgan Stanley suggests that the global market for the newer weight-loss drugs could increase by 15-fold over the next 5 years as their benefits expand beyond weight loss and that as much as 9% of the US population will be taking the drugs by 2035, Dr. Aronne said, adding that he thinks 9% is an underestimate. By contrast, the number of patients treated by his team’s surgical program is down about 20%.
“I think it’s very clear that medical treatment is going to dominate,” he concluded. “But, it’s also possible that surgery could go up because so many people are going to be coming for medical therapy that we may wind up referring more for surgical therapy.”
‘Surgery Is Saving Lives’
Dr. Rubino is convinced that anti-obesity drugs will not make surgery obsolete, “but it will not be business as usual,” he told meeting attendees. “In fact, I think these drugs will expedite a process that is already ongoing — a transformation of bariatric into metabolic surgery.”
“Bariatric surgery will go down in history as one of the biggest missed opportunities that we, as medical professionals, have seen over the past many years,” he said. “It has been shown beyond any doubt to reduce all-cause mortality — in other words, it saves lives,” and it’s also cost effective and improves quality of life. Yet, fewer than 1% of people globally who meet the criteria actually get the surgery.
Many clinicians don’t inform patients about the treatment and don’t refer them for it, he said. “That would be equivalent to having surgery for CVD [cardiovascular disease], cancer, or other important diseases available but not being accessed as they should be.”
A big reason for the dearth of procedures is that people have unrealistic expectations about diet and exercise interventions for weight loss, he said. His team’s survey, presented at the 26th World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders, showed that 43% of respondents believed diet and exercise was the best treatment for severe obesity (BMI > 35). A more recent survey asked which among several choices was the most effective weight-loss intervention, and again a large proportion “believed wrongly that diet and exercise is most effective — more so than drugs or surgery — despite plenty of evidence that this is not the case.”
In this context, he said, “any surgery, no matter how safe or effective, would never be very popular.” If obesity is viewed as a modifiable risk factor, patients may say they’ll think about it for 6 months. In contrast, “nobody will tell you ‘I will think about it’ if you tell them they need gallbladder surgery to get rid of gallstone pain.”
Although drugs are available to treat obesity, none of them are curative, and if they’re stopped, the weight comes back, Dr. Rubino pointed out. “Efficacy of drugs is measured in weeks or months, whereas efficacy of surgery is measured in decades of durability — in the case of bariatric surgery, 10-20 years. That’s why bariatric surgery will remain an option,” he said. “It’s not just preventing disease, it’s resolving ongoing disease.”
Furthermore, bariatric surgery is showing value for people with established T2D, whereas in the past, it was mainly considered to be a weight-loss intervention for younger, healthier patients, he said. “In my practice, we’re operating more often in people with T2D, even those at higher risk for anesthesia and surgery — eg, patients with heart failure, chronic kidney disease, on dialysis — and we’re still able to maintain the same safety with minimally invasive laparoscopic surgery that we had with healthier patients.”
A vote held at the end of the session revealed that the audience was split about half and half in favor of drugs making bariatric surgery obsolete or not.
“I think we may have to duke it out now,” Dr. Aronne quipped.
Dr. Aronne disclosed being a consultant, speaker, and adviser for and receiving research support from Altimmune, Amgen, AstraZeneca, Eli Lilly, Intellihealth, Janssen, Novo Nordisk, Pfizer, Senda, UnitedHealth Group, Versanis, and others; he has ownership interests in ERX, Intellihealth, Jamieson, Kallyope, Skye Bioscience, Veru, and others; and he is on the board of directors of ERX, Jamieson Wellness, and Intellihealth/FlyteHealth. Dr. Rubino disclosed receiving research and educational grants from Novo Nordisk, Ethicon, and Medtronic; he is on the scientific advisory board/data safety advisory board for Keyron, Morphic Medical, and GT Metabolic Solutions; he receives speaking honoraria from Medtronic, Ethicon, Novo Nordisk, and Eli Lilly; and he is president of the nonprofit Metabolic Health Institute.
A version of this article first appeared on Medscape.com.
FROM EASD 2024
Osimertinib/Savolitinib Combo Shows Promise in NSCLC
according to results of the phase 2 FLOWERS study.
Compared with EGFR inhibitor osimertinib alone, the combination demonstrated a clinically meaningful improvement in the objective response rate — the study’s primary endpoint — with a positive trend in progression-free survival and a manageable safety profile.
About 30% patients with EGFR-mutated NSCLC fail to respond well to EGFR–tyrosine kinase inhibitors (TKIs), explained Jin-Ji Yang, MD, with Guangdong Lung Cancer Institute, Guangzhou, China, who reported the study results at the annual meeting of the World Conference on Lung Cancer.
Data suggested that de novo MET amplification occurs in up to 5% patients with treatment-naive, EGFR-mutated advanced NSCLC, and MET overexpression occurs in up to 15% these patients.
Coexistence of EGFR mutation and MET amplification/overexpression reduces sensitivity to EGFR-TKI therapy “and is likely the mechanism for mediating primary resistance to first-line EGFR-TKI monotherapy,” Dr. Yang explained in her presentation.
Osimertinib is a third-generation EGFR-TKI recommended as the first-line treatment for EGFR-mutant advanced NSCLC. Savolitinib is a highly selective MET-TKI which has demonstrated antitumor activity in various cancers with MET alterations.
The FLOWERS study is the first to test whether combining the two agents could improve efficacy and overcome MET-driven primary resistance in these patients.
The phase 2 study enrolled 44 treatment-naive patients with de novo MET-aberrant, EGFR-mutant, stage IIIB-IV NSCLC; 23 were randomly allocated to receive oral osimertinib (80 mg once daily) alone and 21 to receive oral osimertinib (80 mg once daily) plus savolitinib (300 mg twice daily).
At a median follow-up of 8.2 months, the objective response rate was 60.9% with osimertinib monotherapy vs 90.5% with combination therapy. The disease control rate was also better with the combination therapy than with monotherapy (95.2% vs 87%).
Median duration of response (not yet mature) was 8.4 months with monotherapy vs 18.6 months with combination therapy.
Preliminary progression-free survival data also showed a trend in favor of combination therapy over monotherapy (a median of 19.3 vs 9.3 months; hazard ratio, 0.59).
Most treatment-related adverse events were grade 1 or 2, and there were no fatal adverse events.
Treatment-related adverse events of grade 3 or higher were more common with combination therapy (57.1% vs 8.7%). The most common events with monotherapy were diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) and with dual therapy were rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%).
The results showed that the combination therapy has the potential to become a first-line treatment option for patients who do not respond well to EGFR-TKIs alone, Dr. Yang said in a press release.
Discussant for the study Paul Paik, MD, thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York City, said this study “adds to data suggesting high MET expression might be a poor prognostic or predictive marker, the outcomes of which are improved with MET inhibition.”
He cautioned, however, that there appears to be “quality of life, side-effect trade-offs with dual MET plus EGFR TKI upfront.”
Dr. Paik said he looks forward to results from FLOWERS on serial circulating tumor DNA and formal androgen receptor testing, which “might aid in further assessing clonality and characterizing MET as a co-driver in this setting.”
The study was funded by AstraZeneca China. Dr. Yang had no disclosures. Dr. Paik disclosed relationships with EMD Serono, Bicara, Novartis, and Summit.
A version of this article first appeared on Medscape.com.
according to results of the phase 2 FLOWERS study.
Compared with EGFR inhibitor osimertinib alone, the combination demonstrated a clinically meaningful improvement in the objective response rate — the study’s primary endpoint — with a positive trend in progression-free survival and a manageable safety profile.
About 30% patients with EGFR-mutated NSCLC fail to respond well to EGFR–tyrosine kinase inhibitors (TKIs), explained Jin-Ji Yang, MD, with Guangdong Lung Cancer Institute, Guangzhou, China, who reported the study results at the annual meeting of the World Conference on Lung Cancer.
Data suggested that de novo MET amplification occurs in up to 5% patients with treatment-naive, EGFR-mutated advanced NSCLC, and MET overexpression occurs in up to 15% these patients.
Coexistence of EGFR mutation and MET amplification/overexpression reduces sensitivity to EGFR-TKI therapy “and is likely the mechanism for mediating primary resistance to first-line EGFR-TKI monotherapy,” Dr. Yang explained in her presentation.
Osimertinib is a third-generation EGFR-TKI recommended as the first-line treatment for EGFR-mutant advanced NSCLC. Savolitinib is a highly selective MET-TKI which has demonstrated antitumor activity in various cancers with MET alterations.
The FLOWERS study is the first to test whether combining the two agents could improve efficacy and overcome MET-driven primary resistance in these patients.
The phase 2 study enrolled 44 treatment-naive patients with de novo MET-aberrant, EGFR-mutant, stage IIIB-IV NSCLC; 23 were randomly allocated to receive oral osimertinib (80 mg once daily) alone and 21 to receive oral osimertinib (80 mg once daily) plus savolitinib (300 mg twice daily).
At a median follow-up of 8.2 months, the objective response rate was 60.9% with osimertinib monotherapy vs 90.5% with combination therapy. The disease control rate was also better with the combination therapy than with monotherapy (95.2% vs 87%).
Median duration of response (not yet mature) was 8.4 months with monotherapy vs 18.6 months with combination therapy.
Preliminary progression-free survival data also showed a trend in favor of combination therapy over monotherapy (a median of 19.3 vs 9.3 months; hazard ratio, 0.59).
Most treatment-related adverse events were grade 1 or 2, and there were no fatal adverse events.
Treatment-related adverse events of grade 3 or higher were more common with combination therapy (57.1% vs 8.7%). The most common events with monotherapy were diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) and with dual therapy were rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%).
The results showed that the combination therapy has the potential to become a first-line treatment option for patients who do not respond well to EGFR-TKIs alone, Dr. Yang said in a press release.
Discussant for the study Paul Paik, MD, thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York City, said this study “adds to data suggesting high MET expression might be a poor prognostic or predictive marker, the outcomes of which are improved with MET inhibition.”
He cautioned, however, that there appears to be “quality of life, side-effect trade-offs with dual MET plus EGFR TKI upfront.”
Dr. Paik said he looks forward to results from FLOWERS on serial circulating tumor DNA and formal androgen receptor testing, which “might aid in further assessing clonality and characterizing MET as a co-driver in this setting.”
The study was funded by AstraZeneca China. Dr. Yang had no disclosures. Dr. Paik disclosed relationships with EMD Serono, Bicara, Novartis, and Summit.
A version of this article first appeared on Medscape.com.
according to results of the phase 2 FLOWERS study.
Compared with EGFR inhibitor osimertinib alone, the combination demonstrated a clinically meaningful improvement in the objective response rate — the study’s primary endpoint — with a positive trend in progression-free survival and a manageable safety profile.
About 30% patients with EGFR-mutated NSCLC fail to respond well to EGFR–tyrosine kinase inhibitors (TKIs), explained Jin-Ji Yang, MD, with Guangdong Lung Cancer Institute, Guangzhou, China, who reported the study results at the annual meeting of the World Conference on Lung Cancer.
Data suggested that de novo MET amplification occurs in up to 5% patients with treatment-naive, EGFR-mutated advanced NSCLC, and MET overexpression occurs in up to 15% these patients.
Coexistence of EGFR mutation and MET amplification/overexpression reduces sensitivity to EGFR-TKI therapy “and is likely the mechanism for mediating primary resistance to first-line EGFR-TKI monotherapy,” Dr. Yang explained in her presentation.
Osimertinib is a third-generation EGFR-TKI recommended as the first-line treatment for EGFR-mutant advanced NSCLC. Savolitinib is a highly selective MET-TKI which has demonstrated antitumor activity in various cancers with MET alterations.
The FLOWERS study is the first to test whether combining the two agents could improve efficacy and overcome MET-driven primary resistance in these patients.
The phase 2 study enrolled 44 treatment-naive patients with de novo MET-aberrant, EGFR-mutant, stage IIIB-IV NSCLC; 23 were randomly allocated to receive oral osimertinib (80 mg once daily) alone and 21 to receive oral osimertinib (80 mg once daily) plus savolitinib (300 mg twice daily).
At a median follow-up of 8.2 months, the objective response rate was 60.9% with osimertinib monotherapy vs 90.5% with combination therapy. The disease control rate was also better with the combination therapy than with monotherapy (95.2% vs 87%).
Median duration of response (not yet mature) was 8.4 months with monotherapy vs 18.6 months with combination therapy.
Preliminary progression-free survival data also showed a trend in favor of combination therapy over monotherapy (a median of 19.3 vs 9.3 months; hazard ratio, 0.59).
Most treatment-related adverse events were grade 1 or 2, and there were no fatal adverse events.
Treatment-related adverse events of grade 3 or higher were more common with combination therapy (57.1% vs 8.7%). The most common events with monotherapy were diarrhea (56.5%), rash (52.2%), and pruritus (43.5%) and with dual therapy were rash (52.4%), thrombocytopenia (52.4%), and peripheral edema (42.9%).
The results showed that the combination therapy has the potential to become a first-line treatment option for patients who do not respond well to EGFR-TKIs alone, Dr. Yang said in a press release.
Discussant for the study Paul Paik, MD, thoracic oncologist at Memorial Sloan Kettering Cancer Center in New York City, said this study “adds to data suggesting high MET expression might be a poor prognostic or predictive marker, the outcomes of which are improved with MET inhibition.”
He cautioned, however, that there appears to be “quality of life, side-effect trade-offs with dual MET plus EGFR TKI upfront.”
Dr. Paik said he looks forward to results from FLOWERS on serial circulating tumor DNA and formal androgen receptor testing, which “might aid in further assessing clonality and characterizing MET as a co-driver in this setting.”
The study was funded by AstraZeneca China. Dr. Yang had no disclosures. Dr. Paik disclosed relationships with EMD Serono, Bicara, Novartis, and Summit.
A version of this article first appeared on Medscape.com.
FROM WCLC 2024
No Matched Sibling Donor? Sickle Cell Experts Debate Next-Best Option
“If there is an indication for intervention, for a curative therapy, in the absence of a matched sibling donor, gene therapy is the first choice,” Jaap-Jan Boelens, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York City, argued in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) in Houston.
“In the registries, alternative transplant outcomes are pretty poor, although there is some encouraging data coming up. The time is not there yet when this is the [best] choice.”
But Adetola Kassim, MBBS, of Vanderbilt University Medical Center in Nashville, Tennessee, said patients with sickle cell disease (SCD) who don’t qualify for a matched sibling donor transplant can still have good transplant options. And the results can be impressive.
“Once you’re engrafted, and you don’t lose your graft, the effect in transplant is lifelong,” he said. When it comes to long-lasting effects, he added, “we’re not sure yet about gene therapy.”
As Dr. Kassim noted, SCD continues to take a huge toll.
“Median survival for patients with sickle cell anemia remains stuck in the fifth decade of life with no change in 25 years,” he said. Heart, lung, and kidney complications account for 50% of identifiable causes of death, followed by about 26% attributed to cardiovascular disease, he said. “The question here is about which therapy can impact the most debilitating complication in children, which is stroke, and improve survival in adults with progressive organ dysfunction.”
Dr. Boelens said there are “huge barriers” to stem cell transplant in SCD because only 15% of patients eligible for the treatment have a matched related donor, and only 10% have a matched related or unrelated donor.
“There’s also a lack of financial and psychosocial support in many of the families. There is also parental refusal because of the mortality risk, and there’s also physician refusal because hematologists aren’t always in the same hospitals as the transplant programs.”
Dr. Boelens highlighted a 2019 study of data from 2008-2017 that found outcomes in unmatched donor transplantations are “not great,” with higher risk for mortality and graft failure.
As an alternative, he said, two gene therapies, both gene “additions,” are now approved by the US Food and Drug Administration (FDA). They are exagamglogene autotemcel (exa-cel, Casgevy) and betibeglogene autotemcel (LentiGlobin, Zynteglo). There’s also a gene “correction” option in the works, but it’s not yet ready for prime time, he said.
In the two approved gene therapy treatments, stem cells are removed from the patient, modified/manufactured in an outside facility, and then engrafted.
The advantages of gene therapy include no need to find a donor or worry about graft resistance, and there’s no need for immunosuppression, he said. However, the process takes a long time, there’s limited long-term data, and there’s a risk for loss of fertility and other chemotherapy-related adverse effects.
For his part, Dr. Kassim noted how several groups are excluded from the strong outcomes in matched sibling donor stem-cell transplants: Children with strokes and no eligible donors, others without eligible donors, and adults with severe disease and organ dysfunction who are typically excluded.
“We need transplants with less toxicity and alternative donors,” he said. Another challenge: “How do we decrease graft failure without increasing transplant-related mortality?”
Researchers are exploring several strategies to adjust drug therapy during conditioning, Dr. Kassim said, and he led a promising phase II study that explored one approach. The results of that study were recently published in the journal Blood. Graft failures were very low in both adults and children, he said, and 2-year survival among 70 patients was 94.8%. The five deaths were related to infection.
The evidence about the various strategies shows that “virtually all SCD patients, except those with severe heart, lung, or kidney disease” can benefit from a curative transplant, Dr. Kassim said.
Dr. Boelens had no disclosures. Disclosures for Dr. Kassim were not provided, but he recently reported no disclosures in a report about transplants in SCD.
A version of this article appeared on Medscape.com.
“If there is an indication for intervention, for a curative therapy, in the absence of a matched sibling donor, gene therapy is the first choice,” Jaap-Jan Boelens, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York City, argued in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) in Houston.
“In the registries, alternative transplant outcomes are pretty poor, although there is some encouraging data coming up. The time is not there yet when this is the [best] choice.”
But Adetola Kassim, MBBS, of Vanderbilt University Medical Center in Nashville, Tennessee, said patients with sickle cell disease (SCD) who don’t qualify for a matched sibling donor transplant can still have good transplant options. And the results can be impressive.
“Once you’re engrafted, and you don’t lose your graft, the effect in transplant is lifelong,” he said. When it comes to long-lasting effects, he added, “we’re not sure yet about gene therapy.”
As Dr. Kassim noted, SCD continues to take a huge toll.
“Median survival for patients with sickle cell anemia remains stuck in the fifth decade of life with no change in 25 years,” he said. Heart, lung, and kidney complications account for 50% of identifiable causes of death, followed by about 26% attributed to cardiovascular disease, he said. “The question here is about which therapy can impact the most debilitating complication in children, which is stroke, and improve survival in adults with progressive organ dysfunction.”
Dr. Boelens said there are “huge barriers” to stem cell transplant in SCD because only 15% of patients eligible for the treatment have a matched related donor, and only 10% have a matched related or unrelated donor.
“There’s also a lack of financial and psychosocial support in many of the families. There is also parental refusal because of the mortality risk, and there’s also physician refusal because hematologists aren’t always in the same hospitals as the transplant programs.”
Dr. Boelens highlighted a 2019 study of data from 2008-2017 that found outcomes in unmatched donor transplantations are “not great,” with higher risk for mortality and graft failure.
As an alternative, he said, two gene therapies, both gene “additions,” are now approved by the US Food and Drug Administration (FDA). They are exagamglogene autotemcel (exa-cel, Casgevy) and betibeglogene autotemcel (LentiGlobin, Zynteglo). There’s also a gene “correction” option in the works, but it’s not yet ready for prime time, he said.
In the two approved gene therapy treatments, stem cells are removed from the patient, modified/manufactured in an outside facility, and then engrafted.
The advantages of gene therapy include no need to find a donor or worry about graft resistance, and there’s no need for immunosuppression, he said. However, the process takes a long time, there’s limited long-term data, and there’s a risk for loss of fertility and other chemotherapy-related adverse effects.
For his part, Dr. Kassim noted how several groups are excluded from the strong outcomes in matched sibling donor stem-cell transplants: Children with strokes and no eligible donors, others without eligible donors, and adults with severe disease and organ dysfunction who are typically excluded.
“We need transplants with less toxicity and alternative donors,” he said. Another challenge: “How do we decrease graft failure without increasing transplant-related mortality?”
Researchers are exploring several strategies to adjust drug therapy during conditioning, Dr. Kassim said, and he led a promising phase II study that explored one approach. The results of that study were recently published in the journal Blood. Graft failures were very low in both adults and children, he said, and 2-year survival among 70 patients was 94.8%. The five deaths were related to infection.
The evidence about the various strategies shows that “virtually all SCD patients, except those with severe heart, lung, or kidney disease” can benefit from a curative transplant, Dr. Kassim said.
Dr. Boelens had no disclosures. Disclosures for Dr. Kassim were not provided, but he recently reported no disclosures in a report about transplants in SCD.
A version of this article appeared on Medscape.com.
“If there is an indication for intervention, for a curative therapy, in the absence of a matched sibling donor, gene therapy is the first choice,” Jaap-Jan Boelens, MD, PhD, of Memorial Sloan Kettering Cancer Center, New York City, argued in a presentation at the annual meeting of the Society of Hematologic Oncology (SOHO) in Houston.
“In the registries, alternative transplant outcomes are pretty poor, although there is some encouraging data coming up. The time is not there yet when this is the [best] choice.”
But Adetola Kassim, MBBS, of Vanderbilt University Medical Center in Nashville, Tennessee, said patients with sickle cell disease (SCD) who don’t qualify for a matched sibling donor transplant can still have good transplant options. And the results can be impressive.
“Once you’re engrafted, and you don’t lose your graft, the effect in transplant is lifelong,” he said. When it comes to long-lasting effects, he added, “we’re not sure yet about gene therapy.”
As Dr. Kassim noted, SCD continues to take a huge toll.
“Median survival for patients with sickle cell anemia remains stuck in the fifth decade of life with no change in 25 years,” he said. Heart, lung, and kidney complications account for 50% of identifiable causes of death, followed by about 26% attributed to cardiovascular disease, he said. “The question here is about which therapy can impact the most debilitating complication in children, which is stroke, and improve survival in adults with progressive organ dysfunction.”
Dr. Boelens said there are “huge barriers” to stem cell transplant in SCD because only 15% of patients eligible for the treatment have a matched related donor, and only 10% have a matched related or unrelated donor.
“There’s also a lack of financial and psychosocial support in many of the families. There is also parental refusal because of the mortality risk, and there’s also physician refusal because hematologists aren’t always in the same hospitals as the transplant programs.”
Dr. Boelens highlighted a 2019 study of data from 2008-2017 that found outcomes in unmatched donor transplantations are “not great,” with higher risk for mortality and graft failure.
As an alternative, he said, two gene therapies, both gene “additions,” are now approved by the US Food and Drug Administration (FDA). They are exagamglogene autotemcel (exa-cel, Casgevy) and betibeglogene autotemcel (LentiGlobin, Zynteglo). There’s also a gene “correction” option in the works, but it’s not yet ready for prime time, he said.
In the two approved gene therapy treatments, stem cells are removed from the patient, modified/manufactured in an outside facility, and then engrafted.
The advantages of gene therapy include no need to find a donor or worry about graft resistance, and there’s no need for immunosuppression, he said. However, the process takes a long time, there’s limited long-term data, and there’s a risk for loss of fertility and other chemotherapy-related adverse effects.
For his part, Dr. Kassim noted how several groups are excluded from the strong outcomes in matched sibling donor stem-cell transplants: Children with strokes and no eligible donors, others without eligible donors, and adults with severe disease and organ dysfunction who are typically excluded.
“We need transplants with less toxicity and alternative donors,” he said. Another challenge: “How do we decrease graft failure without increasing transplant-related mortality?”
Researchers are exploring several strategies to adjust drug therapy during conditioning, Dr. Kassim said, and he led a promising phase II study that explored one approach. The results of that study were recently published in the journal Blood. Graft failures were very low in both adults and children, he said, and 2-year survival among 70 patients was 94.8%. The five deaths were related to infection.
The evidence about the various strategies shows that “virtually all SCD patients, except those with severe heart, lung, or kidney disease” can benefit from a curative transplant, Dr. Kassim said.
Dr. Boelens had no disclosures. Disclosures for Dr. Kassim were not provided, but he recently reported no disclosures in a report about transplants in SCD.
A version of this article appeared on Medscape.com.
FROM SOHO 2024