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The Patient Knows Best: Integrating Patient-Reported Outcomes in RA Practice and Research
Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide treatment decisions in daily practice and serve as key endpoints for clinical trials.
That’s the informed opinion of Clifton O. Bingham III, MD, director of the Johns Arthritis Center in Baltimore, Maryland, who discussed clinical and research applications of PROs at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
“Integrating PROs into practice settings can enhance the clinician’s ability to understand their patients and monitor disease impact, and they are increasingly available for clinical care and are being qualified for outcome measures for clinical trials,” Dr. Bingham said.
“I posit to you that some of this ability to better characterize things like anxiety and depression levels of patients more precisely may help us to identify those patients who are less likely to respond to therapy and may require different interventions than disease-modifying therapies for their disease,” he told the audience.
PRO Examples
The term PRO encompasses a broad range of measures that may include health-related quality of life measures, symptoms and their affects, patient satisfaction, and the patient’s experience with care.
PROs are important for rheumatology care and research because “we now have the capacity to make what we used to think were the subjective experiences of disease more objective. We now have ways that we can put numbers and measurements to the experiences that patients have about their illness and use that information as a way to understand more about the patients who are in front of us and also how their disease changes over time,” Dr. Bingham said.
Patients are the best — or in some cases, the only — judges of many aspects of their health, and they are best suited to report on certain events and outcomes, he said.
PROs that are currently included in core outcome measures used to guide care and in clinical trials in pain scores as reported by visual analog scales; functioning, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI); and patient global assessment.
In international qualitative studies in which patients with rheumatoid arthritis (RA) were asked what was most important to them, the usual suspects of pain, function, and fatigue were routinely cited across the studies. But patients in studies from these groups (RAPP-PI, RAID, and OMERACT) also said that other factors important to their well-being included good sleep, enjoyment of life, independence, ability to participate in valued activities, and freedom from emotional distress, Dr. Bingham noted.
The Promise of PROMIS
The science of clinical measurement has advanced dramatically during his career, as Dr. Bingham said.
“There have been significant changes in the science behind how you develop and validate outcomes measures. The fields of clinimetrics and psychometrics have evolved substantially. These are now grounded in what we call ‘modern measurement’ approaches, which focus on item-response theory, constructing interval scales of measurement in things that are very precise in their ability to detect change over time,” he said.
One such measurement instrument is the Patient-Reported Outcome Measurement Information System (PROMIS®), developed at the National Institutes of Health using advanced measurement science.
The system, administered through either computer or paper questionnaires, is designed to improve precision of health-related quality of life assessments in multiple domains, including most domains identified by patients with RA. It uses a T-score metric standardized to the US population.
“You can use this in a disease like rheumatoid arthritis, and you can find out how patients are doing in reference to the normative United States populations,” he said.
Dr. Bingham noted that his team has “very good data” to show that PROMIS system significantly outperforms existing instruments such as the HAQ.
How It Works
The system uses item banks, each with multiple items. For example, there are approximately 150 items for the physical function assessment portion. All the items are scored along a continuum, “from people who are completely disabled to those who can run marathons,” Dr. Bingham said.
Each item on the scale has a question and response component, ranging from “are you able to get in and out of bed?” to “are you able to walk from one room to another?” to “are you able to run 5 miles?”
To evaluate the PROMIS scale, Dr. Bingham and colleagues looked at the distribution of PROMIS T-scores for 1029 patients with RA at their center. The scales showed that patients with RA have higher levels of pain, fatigue, and sleep disturbances, as well as worse physical function, than population norms.
Dr. Bingham and colleagues also evaluated the performance of the system in patients with active RA who were starting on or switching to a different disease-modifying antirheumatic drug (DMARD). As they reported in 2019, among 106 participants who completed the 12-week study, all PROMIS scores improved after DMARD initiation (P ≤ .05). In addition, except for the depression domain, changes in all assessed PROMIS measures correlated with changes in Clinical Disease Activity Index scores.
To see whether integrating PROs into routine clinics could have an effect on care, Dr. Bingham and colleagues conducted a prospective cohort study, which showed that with the additional patient-reported data, clinicians changed or adjusted RA treatment in 16%-19% of visits, identified new symptoms in 27%-38%, and suggested nonpharmacologic interventions in 4%-11%.
“This is information that’s being used, and it’s going into changing medical decision making,” he said.
Summarizing his work, Dr. Bingham told the audience “I hope that I have convinced you that patients with RA prioritize domains that are impacted by their disease. PROMIS measures are really state-of-the-science methods to evaluate multiple aspects of health-related quality of life, and what I’ll note to you is that these have been translated into multiple languages internationally. There are Spanish-language versions, there are Chinese language versions, there are versions for every country in the [European Union] that have been validated and can be used.”
It’s a Start
In the Q & A following the presentation, Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston, commented that “the measurement issues and automating measurements seems like it’s a fundamental practice issue — how to manage the system and how to manage patients better, and I feel like we’re kind of scratching the surface.”
He said that artificial intelligence and PROs in clinic offer some promise for improving care but added that “we can do better than this. We can figure out better systems for measuring PROs: Having patients measure PROs, having patients tell us about their PROs so they don’t have to come in, or coming in only when they need to come in, when they’re really flaring. There are lots of innovative ways of thinking about these tools, and it feels like we’re kind of on the cusp of really taking advantage.”
Dr. Bingham’s work is supported by the Patient-Centered Outcomes Research Institute, National Institutes of Health, Ira T. Fine Discovery Fund, Johns Hopkins Arthritis Center Discovery Fund, Camille J. Morgan Arthritis Research and Education Fund, and Scheer Family Foundation and Joanne and John Rogers. He disclosed consulting for AbbVie, Janssen, Lilly, and Sanofi and serving as a board member of the PROMIS health organization, co-chair of the Omeract Technical Advisory Group, and member of the C-PATH RA PRO working group. Dr. Solomon had no relevant disclosures.
A version of this article appeared on Medscape.com.
Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide treatment decisions in daily practice and serve as key endpoints for clinical trials.
That’s the informed opinion of Clifton O. Bingham III, MD, director of the Johns Arthritis Center in Baltimore, Maryland, who discussed clinical and research applications of PROs at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
“Integrating PROs into practice settings can enhance the clinician’s ability to understand their patients and monitor disease impact, and they are increasingly available for clinical care and are being qualified for outcome measures for clinical trials,” Dr. Bingham said.
“I posit to you that some of this ability to better characterize things like anxiety and depression levels of patients more precisely may help us to identify those patients who are less likely to respond to therapy and may require different interventions than disease-modifying therapies for their disease,” he told the audience.
PRO Examples
The term PRO encompasses a broad range of measures that may include health-related quality of life measures, symptoms and their affects, patient satisfaction, and the patient’s experience with care.
PROs are important for rheumatology care and research because “we now have the capacity to make what we used to think were the subjective experiences of disease more objective. We now have ways that we can put numbers and measurements to the experiences that patients have about their illness and use that information as a way to understand more about the patients who are in front of us and also how their disease changes over time,” Dr. Bingham said.
Patients are the best — or in some cases, the only — judges of many aspects of their health, and they are best suited to report on certain events and outcomes, he said.
PROs that are currently included in core outcome measures used to guide care and in clinical trials in pain scores as reported by visual analog scales; functioning, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI); and patient global assessment.
In international qualitative studies in which patients with rheumatoid arthritis (RA) were asked what was most important to them, the usual suspects of pain, function, and fatigue were routinely cited across the studies. But patients in studies from these groups (RAPP-PI, RAID, and OMERACT) also said that other factors important to their well-being included good sleep, enjoyment of life, independence, ability to participate in valued activities, and freedom from emotional distress, Dr. Bingham noted.
The Promise of PROMIS
The science of clinical measurement has advanced dramatically during his career, as Dr. Bingham said.
“There have been significant changes in the science behind how you develop and validate outcomes measures. The fields of clinimetrics and psychometrics have evolved substantially. These are now grounded in what we call ‘modern measurement’ approaches, which focus on item-response theory, constructing interval scales of measurement in things that are very precise in their ability to detect change over time,” he said.
One such measurement instrument is the Patient-Reported Outcome Measurement Information System (PROMIS®), developed at the National Institutes of Health using advanced measurement science.
The system, administered through either computer or paper questionnaires, is designed to improve precision of health-related quality of life assessments in multiple domains, including most domains identified by patients with RA. It uses a T-score metric standardized to the US population.
“You can use this in a disease like rheumatoid arthritis, and you can find out how patients are doing in reference to the normative United States populations,” he said.
Dr. Bingham noted that his team has “very good data” to show that PROMIS system significantly outperforms existing instruments such as the HAQ.
How It Works
The system uses item banks, each with multiple items. For example, there are approximately 150 items for the physical function assessment portion. All the items are scored along a continuum, “from people who are completely disabled to those who can run marathons,” Dr. Bingham said.
Each item on the scale has a question and response component, ranging from “are you able to get in and out of bed?” to “are you able to walk from one room to another?” to “are you able to run 5 miles?”
To evaluate the PROMIS scale, Dr. Bingham and colleagues looked at the distribution of PROMIS T-scores for 1029 patients with RA at their center. The scales showed that patients with RA have higher levels of pain, fatigue, and sleep disturbances, as well as worse physical function, than population norms.
Dr. Bingham and colleagues also evaluated the performance of the system in patients with active RA who were starting on or switching to a different disease-modifying antirheumatic drug (DMARD). As they reported in 2019, among 106 participants who completed the 12-week study, all PROMIS scores improved after DMARD initiation (P ≤ .05). In addition, except for the depression domain, changes in all assessed PROMIS measures correlated with changes in Clinical Disease Activity Index scores.
To see whether integrating PROs into routine clinics could have an effect on care, Dr. Bingham and colleagues conducted a prospective cohort study, which showed that with the additional patient-reported data, clinicians changed or adjusted RA treatment in 16%-19% of visits, identified new symptoms in 27%-38%, and suggested nonpharmacologic interventions in 4%-11%.
“This is information that’s being used, and it’s going into changing medical decision making,” he said.
Summarizing his work, Dr. Bingham told the audience “I hope that I have convinced you that patients with RA prioritize domains that are impacted by their disease. PROMIS measures are really state-of-the-science methods to evaluate multiple aspects of health-related quality of life, and what I’ll note to you is that these have been translated into multiple languages internationally. There are Spanish-language versions, there are Chinese language versions, there are versions for every country in the [European Union] that have been validated and can be used.”
It’s a Start
In the Q & A following the presentation, Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston, commented that “the measurement issues and automating measurements seems like it’s a fundamental practice issue — how to manage the system and how to manage patients better, and I feel like we’re kind of scratching the surface.”
He said that artificial intelligence and PROs in clinic offer some promise for improving care but added that “we can do better than this. We can figure out better systems for measuring PROs: Having patients measure PROs, having patients tell us about their PROs so they don’t have to come in, or coming in only when they need to come in, when they’re really flaring. There are lots of innovative ways of thinking about these tools, and it feels like we’re kind of on the cusp of really taking advantage.”
Dr. Bingham’s work is supported by the Patient-Centered Outcomes Research Institute, National Institutes of Health, Ira T. Fine Discovery Fund, Johns Hopkins Arthritis Center Discovery Fund, Camille J. Morgan Arthritis Research and Education Fund, and Scheer Family Foundation and Joanne and John Rogers. He disclosed consulting for AbbVie, Janssen, Lilly, and Sanofi and serving as a board member of the PROMIS health organization, co-chair of the Omeract Technical Advisory Group, and member of the C-PATH RA PRO working group. Dr. Solomon had no relevant disclosures.
A version of this article appeared on Medscape.com.
Patient-reported outcomes (PROs) in rheumatology are not just personal lists of physical complaints or so-called “organ recitals.” In fact, PROs can both guide treatment decisions in daily practice and serve as key endpoints for clinical trials.
That’s the informed opinion of Clifton O. Bingham III, MD, director of the Johns Arthritis Center in Baltimore, Maryland, who discussed clinical and research applications of PROs at the 2024 Rheumatoid Arthritis Research Summit presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City.
“Integrating PROs into practice settings can enhance the clinician’s ability to understand their patients and monitor disease impact, and they are increasingly available for clinical care and are being qualified for outcome measures for clinical trials,” Dr. Bingham said.
“I posit to you that some of this ability to better characterize things like anxiety and depression levels of patients more precisely may help us to identify those patients who are less likely to respond to therapy and may require different interventions than disease-modifying therapies for their disease,” he told the audience.
PRO Examples
The term PRO encompasses a broad range of measures that may include health-related quality of life measures, symptoms and their affects, patient satisfaction, and the patient’s experience with care.
PROs are important for rheumatology care and research because “we now have the capacity to make what we used to think were the subjective experiences of disease more objective. We now have ways that we can put numbers and measurements to the experiences that patients have about their illness and use that information as a way to understand more about the patients who are in front of us and also how their disease changes over time,” Dr. Bingham said.
Patients are the best — or in some cases, the only — judges of many aspects of their health, and they are best suited to report on certain events and outcomes, he said.
PROs that are currently included in core outcome measures used to guide care and in clinical trials in pain scores as reported by visual analog scales; functioning, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI); and patient global assessment.
In international qualitative studies in which patients with rheumatoid arthritis (RA) were asked what was most important to them, the usual suspects of pain, function, and fatigue were routinely cited across the studies. But patients in studies from these groups (RAPP-PI, RAID, and OMERACT) also said that other factors important to their well-being included good sleep, enjoyment of life, independence, ability to participate in valued activities, and freedom from emotional distress, Dr. Bingham noted.
The Promise of PROMIS
The science of clinical measurement has advanced dramatically during his career, as Dr. Bingham said.
“There have been significant changes in the science behind how you develop and validate outcomes measures. The fields of clinimetrics and psychometrics have evolved substantially. These are now grounded in what we call ‘modern measurement’ approaches, which focus on item-response theory, constructing interval scales of measurement in things that are very precise in their ability to detect change over time,” he said.
One such measurement instrument is the Patient-Reported Outcome Measurement Information System (PROMIS®), developed at the National Institutes of Health using advanced measurement science.
The system, administered through either computer or paper questionnaires, is designed to improve precision of health-related quality of life assessments in multiple domains, including most domains identified by patients with RA. It uses a T-score metric standardized to the US population.
“You can use this in a disease like rheumatoid arthritis, and you can find out how patients are doing in reference to the normative United States populations,” he said.
Dr. Bingham noted that his team has “very good data” to show that PROMIS system significantly outperforms existing instruments such as the HAQ.
How It Works
The system uses item banks, each with multiple items. For example, there are approximately 150 items for the physical function assessment portion. All the items are scored along a continuum, “from people who are completely disabled to those who can run marathons,” Dr. Bingham said.
Each item on the scale has a question and response component, ranging from “are you able to get in and out of bed?” to “are you able to walk from one room to another?” to “are you able to run 5 miles?”
To evaluate the PROMIS scale, Dr. Bingham and colleagues looked at the distribution of PROMIS T-scores for 1029 patients with RA at their center. The scales showed that patients with RA have higher levels of pain, fatigue, and sleep disturbances, as well as worse physical function, than population norms.
Dr. Bingham and colleagues also evaluated the performance of the system in patients with active RA who were starting on or switching to a different disease-modifying antirheumatic drug (DMARD). As they reported in 2019, among 106 participants who completed the 12-week study, all PROMIS scores improved after DMARD initiation (P ≤ .05). In addition, except for the depression domain, changes in all assessed PROMIS measures correlated with changes in Clinical Disease Activity Index scores.
To see whether integrating PROs into routine clinics could have an effect on care, Dr. Bingham and colleagues conducted a prospective cohort study, which showed that with the additional patient-reported data, clinicians changed or adjusted RA treatment in 16%-19% of visits, identified new symptoms in 27%-38%, and suggested nonpharmacologic interventions in 4%-11%.
“This is information that’s being used, and it’s going into changing medical decision making,” he said.
Summarizing his work, Dr. Bingham told the audience “I hope that I have convinced you that patients with RA prioritize domains that are impacted by their disease. PROMIS measures are really state-of-the-science methods to evaluate multiple aspects of health-related quality of life, and what I’ll note to you is that these have been translated into multiple languages internationally. There are Spanish-language versions, there are Chinese language versions, there are versions for every country in the [European Union] that have been validated and can be used.”
It’s a Start
In the Q & A following the presentation, Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital in Boston, commented that “the measurement issues and automating measurements seems like it’s a fundamental practice issue — how to manage the system and how to manage patients better, and I feel like we’re kind of scratching the surface.”
He said that artificial intelligence and PROs in clinic offer some promise for improving care but added that “we can do better than this. We can figure out better systems for measuring PROs: Having patients measure PROs, having patients tell us about their PROs so they don’t have to come in, or coming in only when they need to come in, when they’re really flaring. There are lots of innovative ways of thinking about these tools, and it feels like we’re kind of on the cusp of really taking advantage.”
Dr. Bingham’s work is supported by the Patient-Centered Outcomes Research Institute, National Institutes of Health, Ira T. Fine Discovery Fund, Johns Hopkins Arthritis Center Discovery Fund, Camille J. Morgan Arthritis Research and Education Fund, and Scheer Family Foundation and Joanne and John Rogers. He disclosed consulting for AbbVie, Janssen, Lilly, and Sanofi and serving as a board member of the PROMIS health organization, co-chair of the Omeract Technical Advisory Group, and member of the C-PATH RA PRO working group. Dr. Solomon had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM RA SUMMIT 2024
Temporary Gut Liner Lowers Weight, A1c
LONDON — , showed data.
Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.
Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.
“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.
Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
Convenient, Reversible Procedure
Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.
Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.
The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.
“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.
Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
Over Half Maintained Full Improvement 2 Years Post Removal
A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m2, and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.
Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.
Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m2, A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.
Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).
Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.
Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.
Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.
Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”
Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.
EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m2.
A version of this article appeared on Medscape.com.
LONDON — , showed data.
Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.
Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.
“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.
Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
Convenient, Reversible Procedure
Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.
Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.
The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.
“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.
Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
Over Half Maintained Full Improvement 2 Years Post Removal
A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m2, and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.
Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.
Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m2, A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.
Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).
Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.
Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.
Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.
Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”
Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.
EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m2.
A version of this article appeared on Medscape.com.
LONDON — , showed data.
Two years after the liner’s removal, 80% of patients continued to show significant improvement, while 20% returned to baseline.
Presenting results at the Diabetes UK Professional Conference (DUKPC) 2024, the researchers, led by Bob Ryder, MD, FRCP, from the Department of Diabetes, Birmingham City Hospital, Birmingham, England, aimed to assess the safety and efficacy of EndoBarrier, as well as maintenance of efficacy 24 months after the device removal.
“We think EndoBarrier finds its place between the end of all the earlier measures and the possible option of bariatric surgery, and these data show that it can lead to tremendous weight loss and improvement in A1c,” Dr. Ryder said in an interview.
Commenting on how most patients had responded to use of the device, Dr. Ryder said, “People with obesity are often very unhappy and have tried everything over many years to no effect; however, this gut liner provided the opportunity to shift out of this state, and they often become so happy with the result they were determined to stick with it and continue with a healthier lifestyle including much more exercise.”
Convenient, Reversible Procedure
Ninety consecutive patients from Birmingham, all with longstanding, poorly controlled, type 2 diabetes and obesity, underwent the implantation procedure, and 60 of these attended follow-up visits 2 years post implantation.
Unlike permanent and more invasive weight loss surgeries, the EndoBarrier device is reversible and fitted with a straightforward procedure.
The thin impermeable sleeve is inserted via an approximate 1-hour endoscopy, enabling the patient to return home the same day. It lines the first 60 cm of the small intestine. Digested food passes through it without absorption and then makes contact with pancreatic and bile juices at the other end. This triggers a change in the metabolism of glucose and nutrients through modulating gut hormones and gut bacteria, as well as disrupting bile flow.
“Because the food bypasses the small intestine, the first time the food is encountered is in an area where it is not normally found, and this causes a reaction where signals are sent to the brain to stop eating,” explained Dr. Ryder.
Due to a license for 1 year of use, the gut liner was removed after a year via a 30-minute endoscopy procedure.
Over Half Maintained Full Improvement 2 Years Post Removal
A total of 60/90 (66%) attended follow-up visits and comprised the data presented. Mean age was 51.2 years, 47% were men, 50% were White, mean body mass index (BMI) was 41.5 kg/m2, and mean A1c was 9.3%. Duration of type 2 diabetes was a median of 11 years, and 60% were taking insulin.
Patients followed dietary requirements for the initial phase after implantation. “During the first week, they followed a liquid diet, then during week 2 — mushy food, and then they were told to chew it really well to avoid blockage,” said Dr. Ryder.
Mean weight loss on removal of the liner (at 12 months post implantation) was 16.7 kg (P < .001), while BMI dropped by mean 6 kg/m2, A1c dropped by a mean of 1.8%, and mean systolic blood pressure by 10.9 mm Hg.
Just over half (32/60, 53%) showed maintenance of fully sustained improvement 2 years after removal of the liner — defined as no significant difference after 2 years between weight loss (mean, 96-97 kg) and similarly for A1c improvement (7.6%-7.4%).
Sixteen of 60 (27%) showed partially sustained improvement over the 2 years of follow-up, with BMI increasing from a mean of 116.8 kg to 128.6 kg and A1c increasing from 7.5% to 8.4%. While 20% (12/60) returned to baseline.
Of the 36/60 people using insulin prior to EndoBarrier treatment, 10 (27.8%) were no longer using insulin at 2 years post removal.
Thirteen of 90 (14%) had early removal of the gut liner due to gastrointestinal hemorrhage (five), liver abscess (two), other abscess (one), and gastrointestinal symptoms (five), but they all made a full recovery; after removal, most experienced benefit despite the adverse event, reported Dr. Ryder.
Sarah Davies, MBBCh, a GP at Woodlands Medical Centre, Cardiff, Wales, agreed that EndoBarrier might be a viable option for patients struggling with obesity. “As GPs, we are the first port of call for these patients. It’s very novel, I hadn’t heard of it before. I like how it’s a noninvasive way for my patients to lose weight and maintain that even after EndoBarrier has been removed.”
Outcomes are being monitored in an ongoing global registry to help determine if EndoBarrier is a safe and effective treatment for individuals with type 2 diabetes and obesity. Dr. Ryder noted that a similar study with 3 years of follow-up showed similar results. Further results will be presented by Dr. Ryder at the upcoming meeting of the American Diabetes Association.
EndoBarrier is currently not approved in the United States. It is awaiting United Kingdom and European CE mark, which the manufacturer hope will be granted this summer. The license will be for patients with BMI of 35-50 kg/m2.
A version of this article appeared on Medscape.com.
Pediatric Patients With MS May Do Best on High-Efficacy DMTs
DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.
“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.
The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
Treatment Strategies
“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.
The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.
Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.
Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.
The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
Study Methodology
The researchers analyzed data from 135 POMS patients between 2012 and 2023.
The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.
Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).
Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.
Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.
Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).
Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).
There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).
Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.
Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.
Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.
DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.
“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.
The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
Treatment Strategies
“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.
The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.
Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.
Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.
The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
Study Methodology
The researchers analyzed data from 135 POMS patients between 2012 and 2023.
The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.
Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).
Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.
Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.
Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).
Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).
There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).
Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.
Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.
Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.
DENVER — Patients with pediatric-onset multiple sclerosis (POMS) are often prescribed low-efficacy disease-modifying therapies (DMTs), but a new retrospective analysis suggests that, like adults, this patient population may benefit from early treatment with high-efficacy DMTs.
“I think it’s very important to highlight that we are seeing that traditionally, kids are just started on lower-efficacy treatments and they keep relapsing. If we can show that when they get transitioned to high-efficacy treatments, the relapses are lessening, I’m hoping that can then push for better clinical trials with pediatric patients included,” said Frederick Bassal, DO, who presented the study during a poster session at the 2024 annual meeting of the American Academy of Neurology. He is a pediatric neurologist at University of California, Davis.
The first line for POMS is generally low-efficacy DMTs like interferon-beta and glatiramer acetate, but these medications may not effectively control disease progression, according to the study authors, and this could lead to pediatric patients being changed to more potent therapies. That can include moderate-efficacy drugs like S1P inhibitors and fumarates, or high-efficacy DMTS such as B cell depletors and alpha 4 integrin receptor antibodies.
Treatment Strategies
“Right now what we’re seeing is the conservative approach — starting low and working up with the younger and adolescent patients. I’m speculating, and I want to look more into it. Is [it maybe] because of insurance approval?” said study coauthor Amara Miller, a medical student at the University of Arizona College of Medicine in Phoenix.
The findings aren’t surprising, according to Barbara Giesser, MD, who was asked to comment on the study. “It is in line with what we think we know about people with adult MS — that if you start early on with a more effective therapy, you tend to have better outcomes,” said Dr. Giesser, director of the MS program at the Pacific Neuroscience Institute.
Another reason to consider higher-efficacy DMTs is that children with MS can have cognitive problems and delays. “There’s a suggestion that if you treat with highly-effective DMT that you might be able to abrogate some of that,” said Dr. Giesser.
Among the approximately two dozen FDA-approved disease-modifying therapies for MS, only fingolimod (Gilenya, Novartis) is approved for children and adolescents. “All of the others are used off label, but I think perhaps, if you have more studies that [show] that children do better if you treat with more effective therapies early on, perhaps we might see more on-label indications for use in a pediatric population,” said Dr. Giesser.
The finding that obesity was associated with a higher likelihood of having multiple therapies is also interesting, she said. “We’re beginning to see that obesity in adults as well seems to portend less favorable neurologic outcomes.”
Study Methodology
The researchers analyzed data from 135 POMS patients between 2012 and 2023.
The mean age of participants was 15 years, 60% were female, and 120 of 135 were White, while 76 were of Hispanic ethnicity. Overweight and obesity were common, with 36 and 43 participants in each category. The initial therapy was a low-efficacy DMT in 23.0% of participants, moderate-efficacy in 37.0%, and high-efficacy in 24.4%, while 1.5% received some other kind of medication and 14.1% received no medication. The annualized relapse rate was 0.932, and the mean EDSS score was 0.88.
Patients who underwent three or medication changes had lower EDSS scores than those who underwent zero to 2 (P = .00607).
Over the course of the study, the percentage of patients who received high-efficacy DMTs rose from 25.9% to 48.9%, largely due to changes in medication. Of those initially prescribed low-efficacy DMTs, 77.4% were eventually switched to high-efficacy DMTs.
Every patient who underwent three or more medication changes was initially prescribed a low-efficacy DMT.
Patients started on low-efficacy drugs had a mean of 1.42 medication changes, compared with 0.94 in the moderate-efficacy group and 0.51 in the high-efficacy group. The reasons for changing from the first medication included relapse (36), side effects (11), patient choice or compliance (8), and pregnancy (2).
Patients 10 years or younger were more likely to be initially prescribed a low-efficacy therapy (odds ratio [OR], 5.72; P = .0366), while older patients were more likely to be prescribed moderate- or high-efficacy therapies (OR, 14.44; P = .0012).
There were more total medication changes in the low-efficacy group than the high initial DMT group (P = .000305).
Asked what advice they would give to physicians treating POMS patients, Ms. Miller suggested a top-down approach. “We want to look at if maybe we can start with higher efficacy DMT’s and maybe titering it down. That may be an option,” said Ms. Miller.
Dr. Bassal highlighted the importance of shared decision-making. “We want to go over the options, that we recommend higher-efficacy [DMTs] for these reasons. But every individual is different. And there may be fears that are very reasonable that families have. I think in those cases, it’s also reasonable to make a shared decision. And if that means going with something like an oral, moderate- to lower-efficacy [therapy], that’s okay, because compliance is key, and if you start something where the family is afraid of side effects, or there are side effects, then you kind of lost that opportunity,” he said.
Dr. Bassal, Dr. Giesser, and Ms. Miller have no relevant financial disclosures.
FROM AAN 2024
Which Probiotics Are Effective in Irritable Bowel Syndrome?
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
How Does Moderate to Severe Eczema Affect Growth in Children?
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM AAD 2024
SAN DIEGO — , results from an ongoing 10-year observational study showed.
“We need to sort out whether this is reversed by newer treatments, especially in the 6- to 11-year-olds, as well as the factors that underlie it in atopic dermatitis,” said the study’s first author Amy S. Paller, MD, chair of dermatology, Northwestern University, Chicago, Illinois, following the annual meeting of the American Academy of Dermatology, where the study was presented during a poster session.
Atopic Dermatitis Impacts Growth
In the ongoing international study called PEDISTAD, researchers enrolled 1326 children younger than 12 years with moderate to severe atopic dermatitis inadequately controlled by topical therapies who were candidates to receive systemic medications. They assessed the percentage of patients above the 50th percentile and the mean percentiles for height, weight, and body mass index (BMI) at baseline against the Centers for Disease Control and Prevention’s (CDC’s) Learning Management System reference healthy population, by age in months, and compared results to the CDC’s standardized growth curves for healthy children aged 0-12 years.
The investigators found that at baseline, compared with the age-specific population norms, 50% of men and 51% of women in the PEDISTAD study were above the 50th percentile for weight, but only 38% and 52%, respectively, were above the 50th percentile for height. Among patients aged 5-12 years, only 28% of men and 47% of women were above the 50th percentile for height, while 69% of men and 71% of women were above the 50th percentile for BMI.
Dr. Paller said that she was “not really surprised by the reduction in linear growth, since there are so many factors that may contribute,” including chronic inflammation, poor sleep, and the use of topical and systemic steroids. “But [it’s] good to have this data as an opportunity to see if our improved therapies can reverse this.”
She said that she was “a bit surprised by the increase in weight and body mass index, but this could reflect less physical activity/sports [participation and] deserves more investigation,” and added that the findings “mesh nicely with new attention on bone growth with good control of atopic dermatitis in this age group.”
Dr. Paller acknowledged certain limitations of the study, including the fact that those enrolled are a heterogeneous cohort with variable treatment regimens.
Some Answers, More Questions
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, who was asked to comment on the findings, said that atopic dermatitis “should be considered the cutaneous manifestations of a systemic inflammatory disease, though even if it were not, the impact on daily and nightly activities [such as sleep] could indirectly have systemic medical consequences.”
The data presented “highlights that children with moderate to severe disease have higher BMIs and shorter height than matched counterparts, likely owing to the treasure trove of direct and indirect consequences of uncontrolled type 2 inflammation,” he said. “What I would like to know, and as the authors astutely noted, could treatment, and especially early intervention, prevent or even alter this impact?”
Dr. Paller disclosed that she is a consultant for several pharmaceutical companies, including Sanofi and Regeneron, the study sponsor. She is also an investigator for AbbVie, Dermavant, Eli Lilly, Incyte, Janssen, Krystal, LEO Pharma, and UCB and is a member of the data monitoring safety board for AbbVie, Abeona, Catawba, Galderma, and InMed. Dr. Friedman, who was not involved with the study, had no relevant disclosures.
A version of this article appeared on Medscape.com.
Childhood Loneliness Predictive of Subsequent Psychosis?
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
How Long Should Active Surveillance Last?
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Lidocaine Nerve Block Effective for Severe, Refractory Migraine in Children
DENVER — , results of a randomized controlled trial show.
Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections.
Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.
Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology.
Significant Results
Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments.
All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone.
“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka.
Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported.
On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).
A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.
Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.
The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.
Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
Encouraging Results
Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”
“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”
The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said.
“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.
“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”
The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
A version of this article appeared on Medscape.com.
DENVER — , results of a randomized controlled trial show.
Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections.
Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.
Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology.
Significant Results
Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments.
All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone.
“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka.
Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported.
On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).
A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.
Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.
The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.
Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
Encouraging Results
Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”
“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”
The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said.
“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.
“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”
The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
A version of this article appeared on Medscape.com.
DENVER — , results of a randomized controlled trial show.
Investigators found children receiving bilateral occipital nerve blocks with 2% lidocaine had significantly greater pain relief than that of peers receiving saline injections.
Cases series have shown a benefit of peripheral nerve blocks (PNBs) — injections of local anesthetics over branches of the occipital or trigeminal nerve — for severe, refractory headache in children.
Although 80% of pediatric headache specialists use PNBs, there is “inconsistent insurance coverage” for this treatment, which had not been tested in a randomized controlled trial in children before now, lead investigator Christina Szperka, MD, with the Pediatric Headache Program, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, told delegates attending the 2024 annual meeting of the American Academy of Neurology.
Significant Results
Investigators enrolled 58 children and adolescents with acute status migrainosus. The mean age was 16 years, and reported gender was female for 44 participants, male for 11 participants, and nonbinary or transgender in 3 participants. Participants had a migraine flare duration of 22 days and had not responded to other treatments.
All participants had topical lidocaine cream applied for 30 minutes as a run-in step and could decline injections if they experienced sufficient benefit from cream alone.
“We used a lidocaine cream lead-in for two reasons. One was to try to see if we could address the issue of high placebo response in pediatric trials in particular, and also to see if we could help with blinding to injection,” said Dr. Szperka.
Topical lidocaine cream led to a small decrease in pain score overall (0.2 point on a 0-10 scale), and all participants proceeded to randomized blinded bilateral greater occipital nerve injection with 2% lidocaine or saline, she reported.
On the primary endpoint — change in pain score at 30 minutes — lidocaine was significantly more effective than saline, achieving a 2.3-point decrease on average (on a 0-10 scale) vs a 1.1-point decrease with saline (P = .01).
A 2-point pain reduction was achieved in 69% of patients in the lidocaine group versus 34% in the saline group.
Three quarters (76%) of patients getting lidocaine reported at least partial relief in severity or location of pain compared with 48% of those getting saline (P = .03). Rates of pain freedom at 30 minutes were 17% and 7%, respectively, and at 24 hours were 14% and 0%, respectively.
The majority of adverse events were mild and fairly equal across groups and included anxiety, worsening headache, injection site pain, dizziness, and numbness (more so with lidocaine). There was one case of anaphylaxis after lidocaine injection.
Quite unexpectedly, said Dr. Szperka, patients rated the saline injection as more painful than the lidocaine injection. “This was not what I expected going in, and I think is relevant for future trials,” she said.
Encouraging Results
Reached for comment, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, said that as a neurologist and pain physician, he sees firsthand the “devastating impact of status migrainosus on children.”
“These debilitating headaches can rob them of precious school days, hindering learning and social interaction,” said Dr. Lakhan. “The constant pain and fear of the next attack can also take a toll on their emotional well-being.”
The impact on families is significant as well, highlighting the need to find more effective treatments, Dr. Lakhan said.
“Traditionally, we’ve relied on case studies to see the benefits of nerve blocks for migraine in younger patients. This is the first randomized controlled trial that shows lidocaine injections can be significantly more effective than a placebo for these unrelenting migraines,” he said.
“It’s important to note that this is a relatively small study, and not without safety concerns, including rare but potentially life-threatening anaphylaxis to lidocaine,” Dr. Lakhan added. “More research is needed, but these findings are encouraging. Lidocaine injections could become a valuable tool for managing treatment-resistant migraines in adolescents and young adults.”
The study was supported by a grant from the National Institute of Neurological Disorders and Stroke. Dr. Szperka is a consultant for AbbVie and Teva; serves on a Data Safety Monitoring Board for Eli Lilly and Upsher-Smith; and is a site principal investigator for AbbVie, Amgen, Biohaven/Pfizer, Teva, and Theranica. Dr. Lakhan had no disclosures.
A version of this article appeared on Medscape.com.
FROM AAN 2024
Mining EHRs with AI to Predict RA Outcomes: Coming to You Soon?
Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginning to pay off with the introduction of artificial intelligence (AI) and natural language processing systems that can mine electronic health records (EHRs) for nuggets of research gold and accurately predict short-term rheumatoid arthritis (RA) outcomes.
“I think we have learned from our very early experiments that longitudinal deep learning models can forecast rheumatoid arthritis [RA] outcomes with actually surprising efficiency, with fewer patients than we assumed would be needed,” said Jinoos Yazdany, MD, MPH, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center, and codirector of the University of California San Francisco (UCSF) Quality and Informatics Lab.
At the 2024 Rheumatoid Arthritis Research Summit (RA Summit 2024), presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City, Dr. Yazdany discussed why rheumatologists are well positioned to take advantage of predictive analytics and how natural language processing systems can be used to extract previously hard-to-find data from EHRs, which can then be applied to RA prognostics and research.
Data Galore
EHR data can be particularly useful for RA research because of the large volume of information, clinical data such as notes and imaging, less selection bias compared with other data sources such as cohorts or randomized controlled trials, real-time access, and the fact that many records contain longitudinal data (follow-ups, etc.).
However, EHR data may have gaps or inaccurate coding, and data such as text and images may require significant data processing and scrubbing before it can be used to advance research. In addition, EHR data are subject to patient privacy and security concerns, can be plagued by incompatibility across different systems, and may not represent patients who have less access to care, Dr. Yazdany said.
She noted that most rheumatologists record some measure of RA disease activity and patient physical function, and that patient-reported outcomes have been routinely incorporated into clinical records, especially since the 1980 introduction of the Health Assessment Questionnaire.
“In rheumatology, by achieving consensus and building a national quality measurement program, we have a cohesive national RA outcome measure selection strategy. RA outcomes are available for a majority of patients seen by rheumatologists, and that’s a critical strength of EHR data,” she said.
Spinning Text Into Analytics
The challenge for investigators who want to use this treasure trove of RA data is that more than 80% of the data are in the form of text, which raises questions about how to best extract outcomes data and drug dosing information from the written record.
As described in an article published online in Arthritis Care & Research February 14, 2023, Dr. Yazdany and colleagues at UCSF and Stanford University developed a natural language processing “pipeline” designed to extract RA outcomes from clinical notes on all patients included in the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) registry.
The model used expert-curated terms and a text processing tool to identify patterns and numerical scores linked to outcome measures in the records.
“This was an enormously difficult and ambitious project because we had many, many sites, the data was very messy, we had very complicated [independent review board] procedures, and we actually had to go through de-identification procedures because we were using this data for research, so we learned a lot,” Dr. Yazdany said.
The model processed 34 million notes on 854,628 patients across 158 practices and 24 different EHR systems.
In internal validation studies, the models had 95% sensitivity, 87% positive predictive value (PPV), and an F1 score (a measure of predictive performance) of 91%. Applying the model to an EHR from a large, non-RISE health system for external validation, the natural language processing pipeline had a 92% sensitivity, 69% PPV, and an F1 score of 79%.
The investigators also looked at the use of OpenAI large language models, including GPT 3.5 and 4 to interpret complex prescription orders and found that after training with 100 examples, GPT 4 was able to correctly interpret 95.6% of orders. But this experiment came at a high computational and financial cost, with one experiment running north of $3000, Dr. Yazdany cautioned.
Predicting Outcomes
Experiments to see whether an AI system can forecast RA disease activity at the next clinic visit are in their early stages.
Dr. Yazdany and colleagues used EHR data from UCSF and Zuckerberg San Francisco General Hospital on patients with two RA diagnostic codes at 30 days apart, who had at least one disease-modifying antirheumatic drug prescription and two Clinical Disease Activity Index (CDAI) scores 30 days apart.
One model, designed to predict CDAI at the next visit by “playing the odds” based on clinical experience, showed that about 60% of patients at UCSF achieved treat-to-target goals, while the remaining 40% did not.
This model performed barely better than pure chance, with an area under the receiver operating characteristic curve (AUC) of 0.54.
A second model that included the patient’s last CDAI score also fared little better than a roll of the dice, with an AUC of 0.55.
However, a neural network or “deep learning” model designed to process data akin to the way that the human brain works performed much better at predicting outcomes at the second visit, with an AUC of 0.91.
Applying the UCSF-trained neural network model to the Zuckerberg San Francisco General Hospital population, with different patient characteristics from those of UCSF, the AUC was 0.74. Although this result was not as good as that seen when applied to UCSF patients, it demonstrated that the model retains some predictive capability across different hospital systems, Dr. Yazdany said.
The next steps, she said, are to build more robust models based on vast and varied patient data pools that will allow the predictive models to be generalized across various healthcare settings.
The Here and Now
In the Q & A following the presentation, an audience member said that the study was “very cool stuff.”
“Is there a way to sort of get ahead and think of the technology that we’re starting to pilot? Hospitals are already using AI scribes, for example, to collect the data that is going to make it much easier to feed it to the predictive analytics that we’re going to use,” she said.
Dr. Yazdany replied that “over the last couple of years, one of the projects that we’ve worked on is to interview rheumatologists who are participating in the RISE registry about the ways that they are collecting [patient-reported outcomes], and it has been fascinating: A vast majority of people are still using paper forms.”
“The challenge is that our patient populations are very diverse. Technology, and especially filling out forms via online platforms, doesn’t work for everybody, and in some ways, filling out the paper forms when you go to the doctor’s office is a great equalizer. So, I think that we have some real challenges, and the solutions have to be embedded in the real world,” she added.
Dr. Yazdany’s research was supported by grants from the Agency for Healthcare Research & Quality and the National Institutes of Health. She disclosed consulting fees and/or research support from AstraZeneca, Aurinia, Bristol Myers Squibb, Gilead, and Pfizer.
A version of this article appeared on Medscape.com.
Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginning to pay off with the introduction of artificial intelligence (AI) and natural language processing systems that can mine electronic health records (EHRs) for nuggets of research gold and accurately predict short-term rheumatoid arthritis (RA) outcomes.
“I think we have learned from our very early experiments that longitudinal deep learning models can forecast rheumatoid arthritis [RA] outcomes with actually surprising efficiency, with fewer patients than we assumed would be needed,” said Jinoos Yazdany, MD, MPH, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center, and codirector of the University of California San Francisco (UCSF) Quality and Informatics Lab.
At the 2024 Rheumatoid Arthritis Research Summit (RA Summit 2024), presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City, Dr. Yazdany discussed why rheumatologists are well positioned to take advantage of predictive analytics and how natural language processing systems can be used to extract previously hard-to-find data from EHRs, which can then be applied to RA prognostics and research.
Data Galore
EHR data can be particularly useful for RA research because of the large volume of information, clinical data such as notes and imaging, less selection bias compared with other data sources such as cohorts or randomized controlled trials, real-time access, and the fact that many records contain longitudinal data (follow-ups, etc.).
However, EHR data may have gaps or inaccurate coding, and data such as text and images may require significant data processing and scrubbing before it can be used to advance research. In addition, EHR data are subject to patient privacy and security concerns, can be plagued by incompatibility across different systems, and may not represent patients who have less access to care, Dr. Yazdany said.
She noted that most rheumatologists record some measure of RA disease activity and patient physical function, and that patient-reported outcomes have been routinely incorporated into clinical records, especially since the 1980 introduction of the Health Assessment Questionnaire.
“In rheumatology, by achieving consensus and building a national quality measurement program, we have a cohesive national RA outcome measure selection strategy. RA outcomes are available for a majority of patients seen by rheumatologists, and that’s a critical strength of EHR data,” she said.
Spinning Text Into Analytics
The challenge for investigators who want to use this treasure trove of RA data is that more than 80% of the data are in the form of text, which raises questions about how to best extract outcomes data and drug dosing information from the written record.
As described in an article published online in Arthritis Care & Research February 14, 2023, Dr. Yazdany and colleagues at UCSF and Stanford University developed a natural language processing “pipeline” designed to extract RA outcomes from clinical notes on all patients included in the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) registry.
The model used expert-curated terms and a text processing tool to identify patterns and numerical scores linked to outcome measures in the records.
“This was an enormously difficult and ambitious project because we had many, many sites, the data was very messy, we had very complicated [independent review board] procedures, and we actually had to go through de-identification procedures because we were using this data for research, so we learned a lot,” Dr. Yazdany said.
The model processed 34 million notes on 854,628 patients across 158 practices and 24 different EHR systems.
In internal validation studies, the models had 95% sensitivity, 87% positive predictive value (PPV), and an F1 score (a measure of predictive performance) of 91%. Applying the model to an EHR from a large, non-RISE health system for external validation, the natural language processing pipeline had a 92% sensitivity, 69% PPV, and an F1 score of 79%.
The investigators also looked at the use of OpenAI large language models, including GPT 3.5 and 4 to interpret complex prescription orders and found that after training with 100 examples, GPT 4 was able to correctly interpret 95.6% of orders. But this experiment came at a high computational and financial cost, with one experiment running north of $3000, Dr. Yazdany cautioned.
Predicting Outcomes
Experiments to see whether an AI system can forecast RA disease activity at the next clinic visit are in their early stages.
Dr. Yazdany and colleagues used EHR data from UCSF and Zuckerberg San Francisco General Hospital on patients with two RA diagnostic codes at 30 days apart, who had at least one disease-modifying antirheumatic drug prescription and two Clinical Disease Activity Index (CDAI) scores 30 days apart.
One model, designed to predict CDAI at the next visit by “playing the odds” based on clinical experience, showed that about 60% of patients at UCSF achieved treat-to-target goals, while the remaining 40% did not.
This model performed barely better than pure chance, with an area under the receiver operating characteristic curve (AUC) of 0.54.
A second model that included the patient’s last CDAI score also fared little better than a roll of the dice, with an AUC of 0.55.
However, a neural network or “deep learning” model designed to process data akin to the way that the human brain works performed much better at predicting outcomes at the second visit, with an AUC of 0.91.
Applying the UCSF-trained neural network model to the Zuckerberg San Francisco General Hospital population, with different patient characteristics from those of UCSF, the AUC was 0.74. Although this result was not as good as that seen when applied to UCSF patients, it demonstrated that the model retains some predictive capability across different hospital systems, Dr. Yazdany said.
The next steps, she said, are to build more robust models based on vast and varied patient data pools that will allow the predictive models to be generalized across various healthcare settings.
The Here and Now
In the Q & A following the presentation, an audience member said that the study was “very cool stuff.”
“Is there a way to sort of get ahead and think of the technology that we’re starting to pilot? Hospitals are already using AI scribes, for example, to collect the data that is going to make it much easier to feed it to the predictive analytics that we’re going to use,” she said.
Dr. Yazdany replied that “over the last couple of years, one of the projects that we’ve worked on is to interview rheumatologists who are participating in the RISE registry about the ways that they are collecting [patient-reported outcomes], and it has been fascinating: A vast majority of people are still using paper forms.”
“The challenge is that our patient populations are very diverse. Technology, and especially filling out forms via online platforms, doesn’t work for everybody, and in some ways, filling out the paper forms when you go to the doctor’s office is a great equalizer. So, I think that we have some real challenges, and the solutions have to be embedded in the real world,” she added.
Dr. Yazdany’s research was supported by grants from the Agency for Healthcare Research & Quality and the National Institutes of Health. She disclosed consulting fees and/or research support from AstraZeneca, Aurinia, Bristol Myers Squibb, Gilead, and Pfizer.
A version of this article appeared on Medscape.com.
Rheumatologists and their staff have been dutifully recording disease activity and patient-reported outcomes for decades, and now, all that drudgery is beginning to pay off with the introduction of artificial intelligence (AI) and natural language processing systems that can mine electronic health records (EHRs) for nuggets of research gold and accurately predict short-term rheumatoid arthritis (RA) outcomes.
“I think we have learned from our very early experiments that longitudinal deep learning models can forecast rheumatoid arthritis [RA] outcomes with actually surprising efficiency, with fewer patients than we assumed would be needed,” said Jinoos Yazdany, MD, MPH, chief of rheumatology at Zuckerberg San Francisco General Hospital and Trauma Center, and codirector of the University of California San Francisco (UCSF) Quality and Informatics Lab.
At the 2024 Rheumatoid Arthritis Research Summit (RA Summit 2024), presented by the Arthritis Foundation and the Hospital for Special Surgery in New York City, Dr. Yazdany discussed why rheumatologists are well positioned to take advantage of predictive analytics and how natural language processing systems can be used to extract previously hard-to-find data from EHRs, which can then be applied to RA prognostics and research.
Data Galore
EHR data can be particularly useful for RA research because of the large volume of information, clinical data such as notes and imaging, less selection bias compared with other data sources such as cohorts or randomized controlled trials, real-time access, and the fact that many records contain longitudinal data (follow-ups, etc.).
However, EHR data may have gaps or inaccurate coding, and data such as text and images may require significant data processing and scrubbing before it can be used to advance research. In addition, EHR data are subject to patient privacy and security concerns, can be plagued by incompatibility across different systems, and may not represent patients who have less access to care, Dr. Yazdany said.
She noted that most rheumatologists record some measure of RA disease activity and patient physical function, and that patient-reported outcomes have been routinely incorporated into clinical records, especially since the 1980 introduction of the Health Assessment Questionnaire.
“In rheumatology, by achieving consensus and building a national quality measurement program, we have a cohesive national RA outcome measure selection strategy. RA outcomes are available for a majority of patients seen by rheumatologists, and that’s a critical strength of EHR data,” she said.
Spinning Text Into Analytics
The challenge for investigators who want to use this treasure trove of RA data is that more than 80% of the data are in the form of text, which raises questions about how to best extract outcomes data and drug dosing information from the written record.
As described in an article published online in Arthritis Care & Research February 14, 2023, Dr. Yazdany and colleagues at UCSF and Stanford University developed a natural language processing “pipeline” designed to extract RA outcomes from clinical notes on all patients included in the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) registry.
The model used expert-curated terms and a text processing tool to identify patterns and numerical scores linked to outcome measures in the records.
“This was an enormously difficult and ambitious project because we had many, many sites, the data was very messy, we had very complicated [independent review board] procedures, and we actually had to go through de-identification procedures because we were using this data for research, so we learned a lot,” Dr. Yazdany said.
The model processed 34 million notes on 854,628 patients across 158 practices and 24 different EHR systems.
In internal validation studies, the models had 95% sensitivity, 87% positive predictive value (PPV), and an F1 score (a measure of predictive performance) of 91%. Applying the model to an EHR from a large, non-RISE health system for external validation, the natural language processing pipeline had a 92% sensitivity, 69% PPV, and an F1 score of 79%.
The investigators also looked at the use of OpenAI large language models, including GPT 3.5 and 4 to interpret complex prescription orders and found that after training with 100 examples, GPT 4 was able to correctly interpret 95.6% of orders. But this experiment came at a high computational and financial cost, with one experiment running north of $3000, Dr. Yazdany cautioned.
Predicting Outcomes
Experiments to see whether an AI system can forecast RA disease activity at the next clinic visit are in their early stages.
Dr. Yazdany and colleagues used EHR data from UCSF and Zuckerberg San Francisco General Hospital on patients with two RA diagnostic codes at 30 days apart, who had at least one disease-modifying antirheumatic drug prescription and two Clinical Disease Activity Index (CDAI) scores 30 days apart.
One model, designed to predict CDAI at the next visit by “playing the odds” based on clinical experience, showed that about 60% of patients at UCSF achieved treat-to-target goals, while the remaining 40% did not.
This model performed barely better than pure chance, with an area under the receiver operating characteristic curve (AUC) of 0.54.
A second model that included the patient’s last CDAI score also fared little better than a roll of the dice, with an AUC of 0.55.
However, a neural network or “deep learning” model designed to process data akin to the way that the human brain works performed much better at predicting outcomes at the second visit, with an AUC of 0.91.
Applying the UCSF-trained neural network model to the Zuckerberg San Francisco General Hospital population, with different patient characteristics from those of UCSF, the AUC was 0.74. Although this result was not as good as that seen when applied to UCSF patients, it demonstrated that the model retains some predictive capability across different hospital systems, Dr. Yazdany said.
The next steps, she said, are to build more robust models based on vast and varied patient data pools that will allow the predictive models to be generalized across various healthcare settings.
The Here and Now
In the Q & A following the presentation, an audience member said that the study was “very cool stuff.”
“Is there a way to sort of get ahead and think of the technology that we’re starting to pilot? Hospitals are already using AI scribes, for example, to collect the data that is going to make it much easier to feed it to the predictive analytics that we’re going to use,” she said.
Dr. Yazdany replied that “over the last couple of years, one of the projects that we’ve worked on is to interview rheumatologists who are participating in the RISE registry about the ways that they are collecting [patient-reported outcomes], and it has been fascinating: A vast majority of people are still using paper forms.”
“The challenge is that our patient populations are very diverse. Technology, and especially filling out forms via online platforms, doesn’t work for everybody, and in some ways, filling out the paper forms when you go to the doctor’s office is a great equalizer. So, I think that we have some real challenges, and the solutions have to be embedded in the real world,” she added.
Dr. Yazdany’s research was supported by grants from the Agency for Healthcare Research & Quality and the National Institutes of Health. She disclosed consulting fees and/or research support from AstraZeneca, Aurinia, Bristol Myers Squibb, Gilead, and Pfizer.
A version of this article appeared on Medscape.com.
FROM RA SUMMIT 2024
Adding ACEI to Chemotherapy Does Not Prevent Cardiotoxicity
a new randomized trial showed.
The results suggested adding an ACE inhibitor doesn’t affect cardiac injury or cardiac function outcomes “and should not be used as a preventative strategy” in these patients, David Austin, MD, consultant cardiologist, Academic Cardiovascular Unit, The James Cook University Hospital, Middlesbrough, England, and chief investigator for the PROACT study, told this news organization.
But while these negative results are disappointing, he said, “we now have a definitive result in a robustly conducted trial that will take the field forward.”
The findings were presented on April 8, 2024, at the American College of Cardiology (ACC) Scientific Session 2024.
Anthracyclines, which are extracted from Streptomyces bacterium, are chemotherapy drugs widely used to treat several types of cancer. Doxorubicin is among the most clinically important anthracyclines.
While extremely effective, anthracyclines can cause irreversible damage to cardiac cells and ultimately impair cardiac function and even cause heart failure, which may only be evident years after exposure. “Cardiac injury is very common in patients treated with high dose anthracyclines,” noted Dr. Austin.
The open-label PROACT study included 111 adult patients, mean age 58 years and predominantly White and women, being treated for breast cancer (62%) or NHL (38%) at National Health Service hospitals in England with high-dose anthracycline-based chemotherapy.
Patients were randomized to standard care (six cycles of high-dose doxorubicin-equivalent anthracycline-based chemotherapy) plus the ACE inhibitor enalapril maleate or standard care alone. The mean chemotherapy dose was 328 mg/m2; any dose greater than 300 is considered high.
The starting dose of enalapril was 2.5 mg twice a day, which was titrated up to a maximum of 10 mg twice a day. The ACE inhibitor was started at least 2 days before chemotherapy began and finished 3 weeks after the last anthracycline dose.
During the study, enalapril was titrated to 20 mg in more than 75% of patients, with the mean dose being 17.7 mg.
Myocardial Injury Outcome
The primary outcome was myocardial injury measured by the presence (≥ 14 ng/L) of high sensitivity cardiac troponin T (cTnT) during anthracycline treatment and 1 month after the last dose of anthracycline.
cTnT is highly expressed in cardiomyocytes and has become a preferred biomarker for detecting acute myocardial infarction and other causes of myocardial injury.
Blood sampling for cTnT and cardiac troponin I (cTnI) was performed at baseline, within 72 hours prior to chemotherapy and at trial completion. All patients had negative troponin results at baseline, indicating no heart damage.
A majority of patients experienced elevations in troponin (78% in the enalapril group and 83% in the standard of care group), but there was no statistically significant difference between groups (adjusted odds ratio [OR], 0.65; 95% CI, 0.23-1.78; P = .405).
There was also no significant difference between groups in terms of cTnI, a secondary endpoint. However, the proportion of patients testing positive for cTnI (47% in the enalapril group and 45% in controls) was substantially lower than that for cTnT.
Large Discrepancy
The “large discrepancy in the rate of injury” with cTnT “has implications for the clinical interpretation of cardiac biomarkers in routine practice, and we should proceed with caution,” Dr. Austin told this news organization.
The finding has implications because guidelines don’t currently differentiate based on the type of troponin, Dr. Austin said in a press release. “I was surprised by the difference, and I think this raises the question of what troponin we should be using.”
Secondary outcomes focused on cardiac function, measured using echocardiography and included left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF). These were measured at baseline, 4 weeks after the last anthracycline dose and 1 year after the final chemotherapy.
There was no between-group difference in LVGLS cardiac function (21% for enalapril vs 22% for standard of care; adjusted OR, 0.95; 95% CI, 0.33-2.74; P = .921). This was also true for LVEF (4% for enalapril vs 0% for standard of care group; adjusted OR, 4.89; 95% CI, 0.40-674.62; P = .236).
Asked what the research team plans to do next, Dr. Austin said “the immediate first step” is to continue following PROACT patients. “We know heart failure events and cardiac dysfunction can occur later down the line.”
Due to the challenge of enrolling patients into trials like PROACT, “we should come together as a sort of a broader cardiovascular/oncology academic community to try to understand how we can better recruit patients into these studies,” said Dr. Austin.
“We need to solve that problem before we then go on to maybe examine other potential preventative therapies.”
He doesn’t think an alternative ACE inhibitor would prove beneficial. “We need to look elsewhere for effective therapies in this area.”
He noted these new findings are “broadly consistent” with other trials that investigated angiotensin receptor blockers.
Tough Population
Commenting on the study during a media briefing, Anita Deswal, chair, medicine, Department of Cardiology, Division of Internal Medicine, The University of Texas, commended the researchers for managing to enroll patients with cancer as this is “a tough” population to get to agree to being in a clinical trial.
“These patients are often overwhelmed financially, physically, and emotionally with the cancer diagnosis, as well as the cancer therapy and, therefore, to enroll them in something to prevent, maybe, some potential cardiac toxicity down the line, is really hard.”
Past trials investigating neuro-hormonal blockers to prevent cardiotoxicity have been criticized for enrolling patients at “too low risk,” said Dr. Deswal. “But investigators here went that step beyond and enrolled patients who were going to receive higher doses of anthracyclines, so kudos to that.”
And she noted investigators managed to get patients on almost the maximum dose of enalapril. “So, the drug was poised to have an effect — if it was there.”
The negative results may have something to do with endpoints. “Maybe we haven’t quite figured out what are the cutoffs for high sensitivity troponin I that identify patients truly at risk” of developing heart failure in the future.
Commenting on the study for this news organization, Anu Lala, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, said the results may come as a surprise to some.
“ACE inhibitors are considered cardioprotective and for this reason are often used prophylactically in patients receiving chemotherapy.”
Dr. Lala agrees troponin may not be the right endpoint. “Another question is whether clinical outcomes should be followed in addition to symptoms or onset of any heart failure symptoms, which may hold greater prognostic significance.”
The study was funded by the National Institute for Health and Care Research.
A version of this article appeared on Medscape.com.
a new randomized trial showed.
The results suggested adding an ACE inhibitor doesn’t affect cardiac injury or cardiac function outcomes “and should not be used as a preventative strategy” in these patients, David Austin, MD, consultant cardiologist, Academic Cardiovascular Unit, The James Cook University Hospital, Middlesbrough, England, and chief investigator for the PROACT study, told this news organization.
But while these negative results are disappointing, he said, “we now have a definitive result in a robustly conducted trial that will take the field forward.”
The findings were presented on April 8, 2024, at the American College of Cardiology (ACC) Scientific Session 2024.
Anthracyclines, which are extracted from Streptomyces bacterium, are chemotherapy drugs widely used to treat several types of cancer. Doxorubicin is among the most clinically important anthracyclines.
While extremely effective, anthracyclines can cause irreversible damage to cardiac cells and ultimately impair cardiac function and even cause heart failure, which may only be evident years after exposure. “Cardiac injury is very common in patients treated with high dose anthracyclines,” noted Dr. Austin.
The open-label PROACT study included 111 adult patients, mean age 58 years and predominantly White and women, being treated for breast cancer (62%) or NHL (38%) at National Health Service hospitals in England with high-dose anthracycline-based chemotherapy.
Patients were randomized to standard care (six cycles of high-dose doxorubicin-equivalent anthracycline-based chemotherapy) plus the ACE inhibitor enalapril maleate or standard care alone. The mean chemotherapy dose was 328 mg/m2; any dose greater than 300 is considered high.
The starting dose of enalapril was 2.5 mg twice a day, which was titrated up to a maximum of 10 mg twice a day. The ACE inhibitor was started at least 2 days before chemotherapy began and finished 3 weeks after the last anthracycline dose.
During the study, enalapril was titrated to 20 mg in more than 75% of patients, with the mean dose being 17.7 mg.
Myocardial Injury Outcome
The primary outcome was myocardial injury measured by the presence (≥ 14 ng/L) of high sensitivity cardiac troponin T (cTnT) during anthracycline treatment and 1 month after the last dose of anthracycline.
cTnT is highly expressed in cardiomyocytes and has become a preferred biomarker for detecting acute myocardial infarction and other causes of myocardial injury.
Blood sampling for cTnT and cardiac troponin I (cTnI) was performed at baseline, within 72 hours prior to chemotherapy and at trial completion. All patients had negative troponin results at baseline, indicating no heart damage.
A majority of patients experienced elevations in troponin (78% in the enalapril group and 83% in the standard of care group), but there was no statistically significant difference between groups (adjusted odds ratio [OR], 0.65; 95% CI, 0.23-1.78; P = .405).
There was also no significant difference between groups in terms of cTnI, a secondary endpoint. However, the proportion of patients testing positive for cTnI (47% in the enalapril group and 45% in controls) was substantially lower than that for cTnT.
Large Discrepancy
The “large discrepancy in the rate of injury” with cTnT “has implications for the clinical interpretation of cardiac biomarkers in routine practice, and we should proceed with caution,” Dr. Austin told this news organization.
The finding has implications because guidelines don’t currently differentiate based on the type of troponin, Dr. Austin said in a press release. “I was surprised by the difference, and I think this raises the question of what troponin we should be using.”
Secondary outcomes focused on cardiac function, measured using echocardiography and included left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF). These were measured at baseline, 4 weeks after the last anthracycline dose and 1 year after the final chemotherapy.
There was no between-group difference in LVGLS cardiac function (21% for enalapril vs 22% for standard of care; adjusted OR, 0.95; 95% CI, 0.33-2.74; P = .921). This was also true for LVEF (4% for enalapril vs 0% for standard of care group; adjusted OR, 4.89; 95% CI, 0.40-674.62; P = .236).
Asked what the research team plans to do next, Dr. Austin said “the immediate first step” is to continue following PROACT patients. “We know heart failure events and cardiac dysfunction can occur later down the line.”
Due to the challenge of enrolling patients into trials like PROACT, “we should come together as a sort of a broader cardiovascular/oncology academic community to try to understand how we can better recruit patients into these studies,” said Dr. Austin.
“We need to solve that problem before we then go on to maybe examine other potential preventative therapies.”
He doesn’t think an alternative ACE inhibitor would prove beneficial. “We need to look elsewhere for effective therapies in this area.”
He noted these new findings are “broadly consistent” with other trials that investigated angiotensin receptor blockers.
Tough Population
Commenting on the study during a media briefing, Anita Deswal, chair, medicine, Department of Cardiology, Division of Internal Medicine, The University of Texas, commended the researchers for managing to enroll patients with cancer as this is “a tough” population to get to agree to being in a clinical trial.
“These patients are often overwhelmed financially, physically, and emotionally with the cancer diagnosis, as well as the cancer therapy and, therefore, to enroll them in something to prevent, maybe, some potential cardiac toxicity down the line, is really hard.”
Past trials investigating neuro-hormonal blockers to prevent cardiotoxicity have been criticized for enrolling patients at “too low risk,” said Dr. Deswal. “But investigators here went that step beyond and enrolled patients who were going to receive higher doses of anthracyclines, so kudos to that.”
And she noted investigators managed to get patients on almost the maximum dose of enalapril. “So, the drug was poised to have an effect — if it was there.”
The negative results may have something to do with endpoints. “Maybe we haven’t quite figured out what are the cutoffs for high sensitivity troponin I that identify patients truly at risk” of developing heart failure in the future.
Commenting on the study for this news organization, Anu Lala, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, said the results may come as a surprise to some.
“ACE inhibitors are considered cardioprotective and for this reason are often used prophylactically in patients receiving chemotherapy.”
Dr. Lala agrees troponin may not be the right endpoint. “Another question is whether clinical outcomes should be followed in addition to symptoms or onset of any heart failure symptoms, which may hold greater prognostic significance.”
The study was funded by the National Institute for Health and Care Research.
A version of this article appeared on Medscape.com.
a new randomized trial showed.
The results suggested adding an ACE inhibitor doesn’t affect cardiac injury or cardiac function outcomes “and should not be used as a preventative strategy” in these patients, David Austin, MD, consultant cardiologist, Academic Cardiovascular Unit, The James Cook University Hospital, Middlesbrough, England, and chief investigator for the PROACT study, told this news organization.
But while these negative results are disappointing, he said, “we now have a definitive result in a robustly conducted trial that will take the field forward.”
The findings were presented on April 8, 2024, at the American College of Cardiology (ACC) Scientific Session 2024.
Anthracyclines, which are extracted from Streptomyces bacterium, are chemotherapy drugs widely used to treat several types of cancer. Doxorubicin is among the most clinically important anthracyclines.
While extremely effective, anthracyclines can cause irreversible damage to cardiac cells and ultimately impair cardiac function and even cause heart failure, which may only be evident years after exposure. “Cardiac injury is very common in patients treated with high dose anthracyclines,” noted Dr. Austin.
The open-label PROACT study included 111 adult patients, mean age 58 years and predominantly White and women, being treated for breast cancer (62%) or NHL (38%) at National Health Service hospitals in England with high-dose anthracycline-based chemotherapy.
Patients were randomized to standard care (six cycles of high-dose doxorubicin-equivalent anthracycline-based chemotherapy) plus the ACE inhibitor enalapril maleate or standard care alone. The mean chemotherapy dose was 328 mg/m2; any dose greater than 300 is considered high.
The starting dose of enalapril was 2.5 mg twice a day, which was titrated up to a maximum of 10 mg twice a day. The ACE inhibitor was started at least 2 days before chemotherapy began and finished 3 weeks after the last anthracycline dose.
During the study, enalapril was titrated to 20 mg in more than 75% of patients, with the mean dose being 17.7 mg.
Myocardial Injury Outcome
The primary outcome was myocardial injury measured by the presence (≥ 14 ng/L) of high sensitivity cardiac troponin T (cTnT) during anthracycline treatment and 1 month after the last dose of anthracycline.
cTnT is highly expressed in cardiomyocytes and has become a preferred biomarker for detecting acute myocardial infarction and other causes of myocardial injury.
Blood sampling for cTnT and cardiac troponin I (cTnI) was performed at baseline, within 72 hours prior to chemotherapy and at trial completion. All patients had negative troponin results at baseline, indicating no heart damage.
A majority of patients experienced elevations in troponin (78% in the enalapril group and 83% in the standard of care group), but there was no statistically significant difference between groups (adjusted odds ratio [OR], 0.65; 95% CI, 0.23-1.78; P = .405).
There was also no significant difference between groups in terms of cTnI, a secondary endpoint. However, the proportion of patients testing positive for cTnI (47% in the enalapril group and 45% in controls) was substantially lower than that for cTnT.
Large Discrepancy
The “large discrepancy in the rate of injury” with cTnT “has implications for the clinical interpretation of cardiac biomarkers in routine practice, and we should proceed with caution,” Dr. Austin told this news organization.
The finding has implications because guidelines don’t currently differentiate based on the type of troponin, Dr. Austin said in a press release. “I was surprised by the difference, and I think this raises the question of what troponin we should be using.”
Secondary outcomes focused on cardiac function, measured using echocardiography and included left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF). These were measured at baseline, 4 weeks after the last anthracycline dose and 1 year after the final chemotherapy.
There was no between-group difference in LVGLS cardiac function (21% for enalapril vs 22% for standard of care; adjusted OR, 0.95; 95% CI, 0.33-2.74; P = .921). This was also true for LVEF (4% for enalapril vs 0% for standard of care group; adjusted OR, 4.89; 95% CI, 0.40-674.62; P = .236).
Asked what the research team plans to do next, Dr. Austin said “the immediate first step” is to continue following PROACT patients. “We know heart failure events and cardiac dysfunction can occur later down the line.”
Due to the challenge of enrolling patients into trials like PROACT, “we should come together as a sort of a broader cardiovascular/oncology academic community to try to understand how we can better recruit patients into these studies,” said Dr. Austin.
“We need to solve that problem before we then go on to maybe examine other potential preventative therapies.”
He doesn’t think an alternative ACE inhibitor would prove beneficial. “We need to look elsewhere for effective therapies in this area.”
He noted these new findings are “broadly consistent” with other trials that investigated angiotensin receptor blockers.
Tough Population
Commenting on the study during a media briefing, Anita Deswal, chair, medicine, Department of Cardiology, Division of Internal Medicine, The University of Texas, commended the researchers for managing to enroll patients with cancer as this is “a tough” population to get to agree to being in a clinical trial.
“These patients are often overwhelmed financially, physically, and emotionally with the cancer diagnosis, as well as the cancer therapy and, therefore, to enroll them in something to prevent, maybe, some potential cardiac toxicity down the line, is really hard.”
Past trials investigating neuro-hormonal blockers to prevent cardiotoxicity have been criticized for enrolling patients at “too low risk,” said Dr. Deswal. “But investigators here went that step beyond and enrolled patients who were going to receive higher doses of anthracyclines, so kudos to that.”
And she noted investigators managed to get patients on almost the maximum dose of enalapril. “So, the drug was poised to have an effect — if it was there.”
The negative results may have something to do with endpoints. “Maybe we haven’t quite figured out what are the cutoffs for high sensitivity troponin I that identify patients truly at risk” of developing heart failure in the future.
Commenting on the study for this news organization, Anu Lala, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, said the results may come as a surprise to some.
“ACE inhibitors are considered cardioprotective and for this reason are often used prophylactically in patients receiving chemotherapy.”
Dr. Lala agrees troponin may not be the right endpoint. “Another question is whether clinical outcomes should be followed in addition to symptoms or onset of any heart failure symptoms, which may hold greater prognostic significance.”
The study was funded by the National Institute for Health and Care Research.
A version of this article appeared on Medscape.com.
FROM THE ACC 2024