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Multidisciplinary Team Develops New Guidelines for Sjögren-Related Neuropathy
New guidelines to manage peripheral neuropathy related to Sjögren disease have been developed by a multidisciplinary team of physicians from across medicine.
The guidelines will provide an evidence-based resource for the assessment, diagnosis, and treatment of various peripheral neuropathies related to the disorder.
Up until now, the field has been “haphazard and chaotic,” lead author George Sarka, MD, DrPH, MPH, director of the CME Committee for MemorialCare, Saddleback Medical Center, Laguna Hills, California, and member of the Sjögren Foundation PNS Guidelines Topic Review Group (TRG), told this news organization.
Dr. Sarka discussed the initiative at the American Academy of Neurology 2024 annual meeting.
Severe, Complex Illness
Sjögren disease is the second most common autoimmune rheumatic disorder after rheumatoid arthritis, affecting an estimated 4 million Americans. Women make up most of the patient population at a ratio of 9:1.
The condition typically affects the mucous membranes and moisture-secreting glands of the eyes and mouth, resulting in decreased tears and saliva. But peripheral nervous system (PNS) manifestations often precede these symptoms and can occur in up to 60% of Sjögren disease cases.
“Traditionally, Sjögren’s was looked at as a dry eye and dry mouth disease, but we realize now that it’s so much broader than that,” said Dr. Sarka. “It’s a severe, systemic, and complex illness that can affect any body organ or system, and the nervous system is frequently affected.”
PNS manifestations cause more than mere discomfort; they can lead to diagnostic and management challenges, costly treatments, and diminished quality of life.
Getting a proper diagnosis goes a long way toward improving the quality of life for these patients, Steven Mandel, MD, clinical professor of neurology at the Zucker School of Medicine at Hofstra-Northwell, adjunct clinical professor of medicine at NY Medical College, New York City, and member of the TRG, told this news organization.
The problem is, doctors don’t always think an autoimmune disorder is causing the symptoms, said Dr. Sarka. “There’s an old adage in neurology that if you don’t think about it, you’re going to miss it; you have to ask, and that’s what we’re trying to get people to do.”
The condition often accompanies other immune system disorders such as rheumatoid arthritis and lupus. But as patients are referred back and forth between ophthalmologists, rheumatologists, and neurologists, the condition is often missed. “It could be 4 or 5 years before a definitive diagnosis of Sjögren’s is made,” said Dr. Sarka.
He believes the education system is partly to blame. “Medical schools have been very deficient in teaching people about recognizing Sjögren disease.”
That leaves many physicians at a loss about “what to do with these patients when they walk in the door,” said Dr. Mandel. “They don’t know how to manage them; they don’t know how to diagnose them; and they don’t know how to treat them.”
Developing guidelines with multispecialty collaboration was “absolutely critical” in addressing this knowledge gap, Dr. Mandel added. That process involved “a very rigorous and transparent methodology so that it would be accepted by all the professionals involved in Sjögren’s,” he said.
The process took 3 years and involved amassing and grading the evidence, getting consensus from committee members, developing recommendations, and getting feedback and external review.
Scant Evidence
An early literature search revealed very little evidence on PNS manifestations in patients with Sjögren disease, so the guideline committee “leaned very heavily on expert opinion” to develop recommendations, Kathy Hammitt, MA, vice president of Medical and Scientific Affairs, Sjögren’s Foundation, told this news organization.
The literature search also showed different terms are used to describe PNS, “which is where the chaos comes in,” said Dr. Sarka.
Experts from different specialties worked together to define and align nomenclature used by various specialists. They developed definitions for seven PNS categories including mononeuropathy, large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, ganglionopathy, vasculitis neuropathy, and autoimmune nervous system neuropathy.
The guidelines pertaining to PNS manifestations encompass a spectrum of neurologic abnormalities, including cranial neuropathies (trigeminal neuropathy or acute facial neuropathy), polyneuropathies (large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, vasculitis neuropathy, or ganglionopathy), and autonomic nervous system (ANS) neuropathies (postural tachycardia, orthostatic hypotension, or autonomic dysfunction).
Key Steps
The guidelines address two key steps for each PNS manifestation — the workup and evaluation of patients with suspected ANS manifestation including standard evaluations, diagnostic tests, and treatment. The experts developed 31 best practices for diagnosis and workup and 20 treatment recommendations.
Initial assessment of potential ANS involvement includes asking patients about orthostatic postural lightheadedness and difficulties with digestion, urination, sweating, and sexual function.
Treatment of autoimmune diseases typically focuses on relieving symptoms and can include steroids, the anticonvulsant gabapentin, the monoclonal antibody rituximab, and intravenous immunoglobulin. “The type of neuropathy will mandate or suggest certain therapies over others,” said Dr. Sarka, adding that a patient can have more than one neuropathy.
Therapeutics for Sjögren disease is another example of an area that has been “very haphazard,” he added.
The guidelines are aimed not just at specialists but also at general practitioners who treat many of these patients. But Dr. Hammitt emphasized that neurologists can be “instrumental” in identifying Sjögren disease in patients with PNS symptoms.
“Our hope is that specialists — in this case, neurologists — will recognize the potential for this condition in their PNS patients and ensure referral to a rheumatologist or knowledgeable family practitioner to manage overall care.”
The committee will soon submit its manuscript to the AAN for publication.
“Once published, we will have a robust dissemination strategy to ensure that providers, patients, and policymakers are aware of, and use, this very valuable resource,” said Dr. Hammitt.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
New guidelines to manage peripheral neuropathy related to Sjögren disease have been developed by a multidisciplinary team of physicians from across medicine.
The guidelines will provide an evidence-based resource for the assessment, diagnosis, and treatment of various peripheral neuropathies related to the disorder.
Up until now, the field has been “haphazard and chaotic,” lead author George Sarka, MD, DrPH, MPH, director of the CME Committee for MemorialCare, Saddleback Medical Center, Laguna Hills, California, and member of the Sjögren Foundation PNS Guidelines Topic Review Group (TRG), told this news organization.
Dr. Sarka discussed the initiative at the American Academy of Neurology 2024 annual meeting.
Severe, Complex Illness
Sjögren disease is the second most common autoimmune rheumatic disorder after rheumatoid arthritis, affecting an estimated 4 million Americans. Women make up most of the patient population at a ratio of 9:1.
The condition typically affects the mucous membranes and moisture-secreting glands of the eyes and mouth, resulting in decreased tears and saliva. But peripheral nervous system (PNS) manifestations often precede these symptoms and can occur in up to 60% of Sjögren disease cases.
“Traditionally, Sjögren’s was looked at as a dry eye and dry mouth disease, but we realize now that it’s so much broader than that,” said Dr. Sarka. “It’s a severe, systemic, and complex illness that can affect any body organ or system, and the nervous system is frequently affected.”
PNS manifestations cause more than mere discomfort; they can lead to diagnostic and management challenges, costly treatments, and diminished quality of life.
Getting a proper diagnosis goes a long way toward improving the quality of life for these patients, Steven Mandel, MD, clinical professor of neurology at the Zucker School of Medicine at Hofstra-Northwell, adjunct clinical professor of medicine at NY Medical College, New York City, and member of the TRG, told this news organization.
The problem is, doctors don’t always think an autoimmune disorder is causing the symptoms, said Dr. Sarka. “There’s an old adage in neurology that if you don’t think about it, you’re going to miss it; you have to ask, and that’s what we’re trying to get people to do.”
The condition often accompanies other immune system disorders such as rheumatoid arthritis and lupus. But as patients are referred back and forth between ophthalmologists, rheumatologists, and neurologists, the condition is often missed. “It could be 4 or 5 years before a definitive diagnosis of Sjögren’s is made,” said Dr. Sarka.
He believes the education system is partly to blame. “Medical schools have been very deficient in teaching people about recognizing Sjögren disease.”
That leaves many physicians at a loss about “what to do with these patients when they walk in the door,” said Dr. Mandel. “They don’t know how to manage them; they don’t know how to diagnose them; and they don’t know how to treat them.”
Developing guidelines with multispecialty collaboration was “absolutely critical” in addressing this knowledge gap, Dr. Mandel added. That process involved “a very rigorous and transparent methodology so that it would be accepted by all the professionals involved in Sjögren’s,” he said.
The process took 3 years and involved amassing and grading the evidence, getting consensus from committee members, developing recommendations, and getting feedback and external review.
Scant Evidence
An early literature search revealed very little evidence on PNS manifestations in patients with Sjögren disease, so the guideline committee “leaned very heavily on expert opinion” to develop recommendations, Kathy Hammitt, MA, vice president of Medical and Scientific Affairs, Sjögren’s Foundation, told this news organization.
The literature search also showed different terms are used to describe PNS, “which is where the chaos comes in,” said Dr. Sarka.
Experts from different specialties worked together to define and align nomenclature used by various specialists. They developed definitions for seven PNS categories including mononeuropathy, large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, ganglionopathy, vasculitis neuropathy, and autoimmune nervous system neuropathy.
The guidelines pertaining to PNS manifestations encompass a spectrum of neurologic abnormalities, including cranial neuropathies (trigeminal neuropathy or acute facial neuropathy), polyneuropathies (large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, vasculitis neuropathy, or ganglionopathy), and autonomic nervous system (ANS) neuropathies (postural tachycardia, orthostatic hypotension, or autonomic dysfunction).
Key Steps
The guidelines address two key steps for each PNS manifestation — the workup and evaluation of patients with suspected ANS manifestation including standard evaluations, diagnostic tests, and treatment. The experts developed 31 best practices for diagnosis and workup and 20 treatment recommendations.
Initial assessment of potential ANS involvement includes asking patients about orthostatic postural lightheadedness and difficulties with digestion, urination, sweating, and sexual function.
Treatment of autoimmune diseases typically focuses on relieving symptoms and can include steroids, the anticonvulsant gabapentin, the monoclonal antibody rituximab, and intravenous immunoglobulin. “The type of neuropathy will mandate or suggest certain therapies over others,” said Dr. Sarka, adding that a patient can have more than one neuropathy.
Therapeutics for Sjögren disease is another example of an area that has been “very haphazard,” he added.
The guidelines are aimed not just at specialists but also at general practitioners who treat many of these patients. But Dr. Hammitt emphasized that neurologists can be “instrumental” in identifying Sjögren disease in patients with PNS symptoms.
“Our hope is that specialists — in this case, neurologists — will recognize the potential for this condition in their PNS patients and ensure referral to a rheumatologist or knowledgeable family practitioner to manage overall care.”
The committee will soon submit its manuscript to the AAN for publication.
“Once published, we will have a robust dissemination strategy to ensure that providers, patients, and policymakers are aware of, and use, this very valuable resource,” said Dr. Hammitt.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
New guidelines to manage peripheral neuropathy related to Sjögren disease have been developed by a multidisciplinary team of physicians from across medicine.
The guidelines will provide an evidence-based resource for the assessment, diagnosis, and treatment of various peripheral neuropathies related to the disorder.
Up until now, the field has been “haphazard and chaotic,” lead author George Sarka, MD, DrPH, MPH, director of the CME Committee for MemorialCare, Saddleback Medical Center, Laguna Hills, California, and member of the Sjögren Foundation PNS Guidelines Topic Review Group (TRG), told this news organization.
Dr. Sarka discussed the initiative at the American Academy of Neurology 2024 annual meeting.
Severe, Complex Illness
Sjögren disease is the second most common autoimmune rheumatic disorder after rheumatoid arthritis, affecting an estimated 4 million Americans. Women make up most of the patient population at a ratio of 9:1.
The condition typically affects the mucous membranes and moisture-secreting glands of the eyes and mouth, resulting in decreased tears and saliva. But peripheral nervous system (PNS) manifestations often precede these symptoms and can occur in up to 60% of Sjögren disease cases.
“Traditionally, Sjögren’s was looked at as a dry eye and dry mouth disease, but we realize now that it’s so much broader than that,” said Dr. Sarka. “It’s a severe, systemic, and complex illness that can affect any body organ or system, and the nervous system is frequently affected.”
PNS manifestations cause more than mere discomfort; they can lead to diagnostic and management challenges, costly treatments, and diminished quality of life.
Getting a proper diagnosis goes a long way toward improving the quality of life for these patients, Steven Mandel, MD, clinical professor of neurology at the Zucker School of Medicine at Hofstra-Northwell, adjunct clinical professor of medicine at NY Medical College, New York City, and member of the TRG, told this news organization.
The problem is, doctors don’t always think an autoimmune disorder is causing the symptoms, said Dr. Sarka. “There’s an old adage in neurology that if you don’t think about it, you’re going to miss it; you have to ask, and that’s what we’re trying to get people to do.”
The condition often accompanies other immune system disorders such as rheumatoid arthritis and lupus. But as patients are referred back and forth between ophthalmologists, rheumatologists, and neurologists, the condition is often missed. “It could be 4 or 5 years before a definitive diagnosis of Sjögren’s is made,” said Dr. Sarka.
He believes the education system is partly to blame. “Medical schools have been very deficient in teaching people about recognizing Sjögren disease.”
That leaves many physicians at a loss about “what to do with these patients when they walk in the door,” said Dr. Mandel. “They don’t know how to manage them; they don’t know how to diagnose them; and they don’t know how to treat them.”
Developing guidelines with multispecialty collaboration was “absolutely critical” in addressing this knowledge gap, Dr. Mandel added. That process involved “a very rigorous and transparent methodology so that it would be accepted by all the professionals involved in Sjögren’s,” he said.
The process took 3 years and involved amassing and grading the evidence, getting consensus from committee members, developing recommendations, and getting feedback and external review.
Scant Evidence
An early literature search revealed very little evidence on PNS manifestations in patients with Sjögren disease, so the guideline committee “leaned very heavily on expert opinion” to develop recommendations, Kathy Hammitt, MA, vice president of Medical and Scientific Affairs, Sjögren’s Foundation, told this news organization.
The literature search also showed different terms are used to describe PNS, “which is where the chaos comes in,” said Dr. Sarka.
Experts from different specialties worked together to define and align nomenclature used by various specialists. They developed definitions for seven PNS categories including mononeuropathy, large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, ganglionopathy, vasculitis neuropathy, and autoimmune nervous system neuropathy.
The guidelines pertaining to PNS manifestations encompass a spectrum of neurologic abnormalities, including cranial neuropathies (trigeminal neuropathy or acute facial neuropathy), polyneuropathies (large fiber neuropathy, small fiber neuropathy, demyelinating polyradiculoneuropathy, vasculitis neuropathy, or ganglionopathy), and autonomic nervous system (ANS) neuropathies (postural tachycardia, orthostatic hypotension, or autonomic dysfunction).
Key Steps
The guidelines address two key steps for each PNS manifestation — the workup and evaluation of patients with suspected ANS manifestation including standard evaluations, diagnostic tests, and treatment. The experts developed 31 best practices for diagnosis and workup and 20 treatment recommendations.
Initial assessment of potential ANS involvement includes asking patients about orthostatic postural lightheadedness and difficulties with digestion, urination, sweating, and sexual function.
Treatment of autoimmune diseases typically focuses on relieving symptoms and can include steroids, the anticonvulsant gabapentin, the monoclonal antibody rituximab, and intravenous immunoglobulin. “The type of neuropathy will mandate or suggest certain therapies over others,” said Dr. Sarka, adding that a patient can have more than one neuropathy.
Therapeutics for Sjögren disease is another example of an area that has been “very haphazard,” he added.
The guidelines are aimed not just at specialists but also at general practitioners who treat many of these patients. But Dr. Hammitt emphasized that neurologists can be “instrumental” in identifying Sjögren disease in patients with PNS symptoms.
“Our hope is that specialists — in this case, neurologists — will recognize the potential for this condition in their PNS patients and ensure referral to a rheumatologist or knowledgeable family practitioner to manage overall care.”
The committee will soon submit its manuscript to the AAN for publication.
“Once published, we will have a robust dissemination strategy to ensure that providers, patients, and policymakers are aware of, and use, this very valuable resource,” said Dr. Hammitt.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
FROM AAN 2024
Satisfactory Results, Less Pain When Surface Anesthesia Used with Thermomechanical Fractional Injury Therapy
BALTIMORE — , a small study of the recently cleared device found.
The study enrolled 12 patients who were undergoing treatment for periorbital rhytides, or wrinkles, around the eyes. Seven of them received topical anesthetic cream 20 minutes before the procedure, while five were given ice packs to self-apply for 5 minutes beforehand. Patients received four treatment sessions with a month between sessions and were then evaluated up to 3 months after their last session. Study results were presented at the annual conference of the American Society for Laser Medicine and Surgery.
“Based on the approach that we had used, which was to keep the device parameters the same for those who received topical anesthetics and those who received ice, when we looked at the pain levels that the patients had relayed to us when we were doing the procedure, we found that both of them were almost exactly the same in terms of discomfort, a level of 3-4 out of 10, with 10 being the highest discomfort level,” lead investigator Jerome M. Garden, MD, said in an interview after the conference.
“In terms of patient satisfaction using a range of 0-5, again it was fairly equivalent” between the two groups, said Dr. Garden, professor of clinical dermatology and biomedical engineering at Northwestern University, Chicago. “And the overall satisfaction rate was high.”
The same device settings were used for all procedures: A pulse duration of 10 milliseconds and a protrusion depth of 400 micrometers. Double passes were applied using the standard device tip, with the smaller tip used in tighter areas, Dr. Garden said. Three patients were Fitzpatrick skin type (FST) I, six were FST II, and three were FST III.
Study Results
The results for the different anesthetic methods were almost identical. Those using ice reported a 0-10 average pain level of 3.95 ± 1.5, while those who received the topical anesthetic reported a pain level of 3.92 ± 1.5. In terms of self-graded improvement at 3-month follow-up, using a scale of 1-4, with 1 representing up to a 25% improvement and 4 a 75%-100% improvement, the patients using ice had a 2.6 ± 0.5 improvement and those using topical cream a 2.8 ± 0.5 improvement, Dr. Garden said during his presentation.
In terms of patient satisfaction, rated on a scale of 1-5, with 5 being very satisfied, the average grade was 3.9 ± 0.9, Dr. Garden added, with 70% rating ≥ 4.
“This is a relatively new device, which uses an approach to help texture changes in wrinkling on the skin in a different fashion than any of the other devices that are currently out there,” Dr. Garden told this news organization after the conference. “I wanted to understand more in depth the different parameters that may impact the outcome” with this device, he added.
The thermomechanical fractional injury device, originally cleared by the US Food and Drug Administration (FDA) in 2021, with a second-generation device cleared in June 2023, deposits heat into the skin, producing controlled thermal injury to promote collagen and elastin production. The device uses only heat, not a laser, which penetrates the skin. A heat sensation on the skin during the procedure can affect patients differently depending on their level of tolerance, Dr. Garden said during his presentation.
Managing Patient Discomfort
Kachiu C. Lee, MD, MPH, of the Main Line Center for Laser Surgery in Ardmore, Pennsylvania, has used the device in her own practice and found that “it can definitely get a little bit uncomfortable for patients,” she said in an interview after the conference.
“I would say that as the doctor, my number one priority is to always make sure my patients are comfortable, especially when treating a sensitive area like the eyes,” added Dr. Lee, who was not involved with the study. “I don’t want them to suddenly jump or move from the discomfort when I have a device right next to their eye. I think that the patient comfort is very important to make sure that we’re managing their discomfort so that the procedure is tolerable.”
She added, “Dr. Garden’s study was effective at showing that surface anesthesia, whether it be with an ice pack 5 minutes before or a topical numbing cream, can be very effective in reducing the pain level while also not interfering with the efficacy of the treatment itself.”
Dr. Garden serves on the medical advisory board for Novoxel, maker of the device. Dr. Lee had no relevant disclosures.
A version of this article appeared on Medscape.com.
BALTIMORE — , a small study of the recently cleared device found.
The study enrolled 12 patients who were undergoing treatment for periorbital rhytides, or wrinkles, around the eyes. Seven of them received topical anesthetic cream 20 minutes before the procedure, while five were given ice packs to self-apply for 5 minutes beforehand. Patients received four treatment sessions with a month between sessions and were then evaluated up to 3 months after their last session. Study results were presented at the annual conference of the American Society for Laser Medicine and Surgery.
“Based on the approach that we had used, which was to keep the device parameters the same for those who received topical anesthetics and those who received ice, when we looked at the pain levels that the patients had relayed to us when we were doing the procedure, we found that both of them were almost exactly the same in terms of discomfort, a level of 3-4 out of 10, with 10 being the highest discomfort level,” lead investigator Jerome M. Garden, MD, said in an interview after the conference.
“In terms of patient satisfaction using a range of 0-5, again it was fairly equivalent” between the two groups, said Dr. Garden, professor of clinical dermatology and biomedical engineering at Northwestern University, Chicago. “And the overall satisfaction rate was high.”
The same device settings were used for all procedures: A pulse duration of 10 milliseconds and a protrusion depth of 400 micrometers. Double passes were applied using the standard device tip, with the smaller tip used in tighter areas, Dr. Garden said. Three patients were Fitzpatrick skin type (FST) I, six were FST II, and three were FST III.
Study Results
The results for the different anesthetic methods were almost identical. Those using ice reported a 0-10 average pain level of 3.95 ± 1.5, while those who received the topical anesthetic reported a pain level of 3.92 ± 1.5. In terms of self-graded improvement at 3-month follow-up, using a scale of 1-4, with 1 representing up to a 25% improvement and 4 a 75%-100% improvement, the patients using ice had a 2.6 ± 0.5 improvement and those using topical cream a 2.8 ± 0.5 improvement, Dr. Garden said during his presentation.
In terms of patient satisfaction, rated on a scale of 1-5, with 5 being very satisfied, the average grade was 3.9 ± 0.9, Dr. Garden added, with 70% rating ≥ 4.
“This is a relatively new device, which uses an approach to help texture changes in wrinkling on the skin in a different fashion than any of the other devices that are currently out there,” Dr. Garden told this news organization after the conference. “I wanted to understand more in depth the different parameters that may impact the outcome” with this device, he added.
The thermomechanical fractional injury device, originally cleared by the US Food and Drug Administration (FDA) in 2021, with a second-generation device cleared in June 2023, deposits heat into the skin, producing controlled thermal injury to promote collagen and elastin production. The device uses only heat, not a laser, which penetrates the skin. A heat sensation on the skin during the procedure can affect patients differently depending on their level of tolerance, Dr. Garden said during his presentation.
Managing Patient Discomfort
Kachiu C. Lee, MD, MPH, of the Main Line Center for Laser Surgery in Ardmore, Pennsylvania, has used the device in her own practice and found that “it can definitely get a little bit uncomfortable for patients,” she said in an interview after the conference.
“I would say that as the doctor, my number one priority is to always make sure my patients are comfortable, especially when treating a sensitive area like the eyes,” added Dr. Lee, who was not involved with the study. “I don’t want them to suddenly jump or move from the discomfort when I have a device right next to their eye. I think that the patient comfort is very important to make sure that we’re managing their discomfort so that the procedure is tolerable.”
She added, “Dr. Garden’s study was effective at showing that surface anesthesia, whether it be with an ice pack 5 minutes before or a topical numbing cream, can be very effective in reducing the pain level while also not interfering with the efficacy of the treatment itself.”
Dr. Garden serves on the medical advisory board for Novoxel, maker of the device. Dr. Lee had no relevant disclosures.
A version of this article appeared on Medscape.com.
BALTIMORE — , a small study of the recently cleared device found.
The study enrolled 12 patients who were undergoing treatment for periorbital rhytides, or wrinkles, around the eyes. Seven of them received topical anesthetic cream 20 minutes before the procedure, while five were given ice packs to self-apply for 5 minutes beforehand. Patients received four treatment sessions with a month between sessions and were then evaluated up to 3 months after their last session. Study results were presented at the annual conference of the American Society for Laser Medicine and Surgery.
“Based on the approach that we had used, which was to keep the device parameters the same for those who received topical anesthetics and those who received ice, when we looked at the pain levels that the patients had relayed to us when we were doing the procedure, we found that both of them were almost exactly the same in terms of discomfort, a level of 3-4 out of 10, with 10 being the highest discomfort level,” lead investigator Jerome M. Garden, MD, said in an interview after the conference.
“In terms of patient satisfaction using a range of 0-5, again it was fairly equivalent” between the two groups, said Dr. Garden, professor of clinical dermatology and biomedical engineering at Northwestern University, Chicago. “And the overall satisfaction rate was high.”
The same device settings were used for all procedures: A pulse duration of 10 milliseconds and a protrusion depth of 400 micrometers. Double passes were applied using the standard device tip, with the smaller tip used in tighter areas, Dr. Garden said. Three patients were Fitzpatrick skin type (FST) I, six were FST II, and three were FST III.
Study Results
The results for the different anesthetic methods were almost identical. Those using ice reported a 0-10 average pain level of 3.95 ± 1.5, while those who received the topical anesthetic reported a pain level of 3.92 ± 1.5. In terms of self-graded improvement at 3-month follow-up, using a scale of 1-4, with 1 representing up to a 25% improvement and 4 a 75%-100% improvement, the patients using ice had a 2.6 ± 0.5 improvement and those using topical cream a 2.8 ± 0.5 improvement, Dr. Garden said during his presentation.
In terms of patient satisfaction, rated on a scale of 1-5, with 5 being very satisfied, the average grade was 3.9 ± 0.9, Dr. Garden added, with 70% rating ≥ 4.
“This is a relatively new device, which uses an approach to help texture changes in wrinkling on the skin in a different fashion than any of the other devices that are currently out there,” Dr. Garden told this news organization after the conference. “I wanted to understand more in depth the different parameters that may impact the outcome” with this device, he added.
The thermomechanical fractional injury device, originally cleared by the US Food and Drug Administration (FDA) in 2021, with a second-generation device cleared in June 2023, deposits heat into the skin, producing controlled thermal injury to promote collagen and elastin production. The device uses only heat, not a laser, which penetrates the skin. A heat sensation on the skin during the procedure can affect patients differently depending on their level of tolerance, Dr. Garden said during his presentation.
Managing Patient Discomfort
Kachiu C. Lee, MD, MPH, of the Main Line Center for Laser Surgery in Ardmore, Pennsylvania, has used the device in her own practice and found that “it can definitely get a little bit uncomfortable for patients,” she said in an interview after the conference.
“I would say that as the doctor, my number one priority is to always make sure my patients are comfortable, especially when treating a sensitive area like the eyes,” added Dr. Lee, who was not involved with the study. “I don’t want them to suddenly jump or move from the discomfort when I have a device right next to their eye. I think that the patient comfort is very important to make sure that we’re managing their discomfort so that the procedure is tolerable.”
She added, “Dr. Garden’s study was effective at showing that surface anesthesia, whether it be with an ice pack 5 minutes before or a topical numbing cream, can be very effective in reducing the pain level while also not interfering with the efficacy of the treatment itself.”
Dr. Garden serves on the medical advisory board for Novoxel, maker of the device. Dr. Lee had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ASLMS 2024
Consider a Four-Step Approach to Shared Decision-Making in Pediatric Dermatology
SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, .
“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”
Conditions such as acne, psoriasis, and atopic dermatitis have multiple treatment options, often without a single best choice. The ideal treatment depends on disease characteristics (extent, sites affected, symptoms, and natural history), the patient (age, comorbidities, overall disease burden), therapies (safety, efficacy, duration, and adverse events), and preferences (logistics, time, shots vs. pills, etc.). “These factors vary between patients and within the same patient over time, and at each step along the course of the condition, SDM approaches are relevant,” she said.
AHRQ’s Five-Step Approach
The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.
“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”
Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:
Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”
Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”
Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”
Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”
In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”
Dr. Cordoro reported having no relevant disclosures.
SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, .
“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”
Conditions such as acne, psoriasis, and atopic dermatitis have multiple treatment options, often without a single best choice. The ideal treatment depends on disease characteristics (extent, sites affected, symptoms, and natural history), the patient (age, comorbidities, overall disease burden), therapies (safety, efficacy, duration, and adverse events), and preferences (logistics, time, shots vs. pills, etc.). “These factors vary between patients and within the same patient over time, and at each step along the course of the condition, SDM approaches are relevant,” she said.
AHRQ’s Five-Step Approach
The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.
“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”
Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:
Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”
Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”
Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”
Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”
In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”
Dr. Cordoro reported having no relevant disclosures.
SAN DIEGO — In the clinical experience of Kelly M. Cordoro, MD, .
“SDM is a cornerstone of person-centered care,” Dr. Cordoro, professor of dermatology and pediatrics at the University of California, San Francisco, said at the Society for Pediatric Dermatology meeting, held in advance of the annual meeting of the American Academy of Dermatology. “We do it all the time. It can be patient-led, clinician-led, or a patient/family dyad approach. If we do it well, it can improve outcomes. Patients report more satisfying interactions with their care team. It brings adolescent patients especially a sense of independence and they adapt faster to their illness.”
Conditions such as acne, psoriasis, and atopic dermatitis have multiple treatment options, often without a single best choice. The ideal treatment depends on disease characteristics (extent, sites affected, symptoms, and natural history), the patient (age, comorbidities, overall disease burden), therapies (safety, efficacy, duration, and adverse events), and preferences (logistics, time, shots vs. pills, etc.). “These factors vary between patients and within the same patient over time, and at each step along the course of the condition, SDM approaches are relevant,” she said.
AHRQ’s Five-Step Approach
The Agency for Healthcare Research and Quality developed a five-step approach to SDM known as SHARE: Seek your patient’s participation; Help your patient explore and compare treatment options; Assess your patient’s values and preferences; Reach a decision with your patient, and Evaluate your patient’s decision. “We do this all the time in practice with adult patients, but may not label it as SDM,” said Dr. Cordoro, chief and fellowship director of pediatric dermatology at UCSF.
“Where it gets a little murkier is in pediatric decision-making, which is a complex type of surrogate decision-making.” In this situation the patient — a minor — does not have full autonomy. The challenge for caregivers is that giving or withholding permission for interventions is a difficult role. “Their job is to protect the patient’s well-being while empowering them toward independence,” she said. “It can be hard for caregivers to understand complex information.” The challenge for clinicians, she continued, is to know when to invite SDM. This requires relational and sharp communication skills. “We must consider our patient’s/family’s health literacy and be sure the information we share is understood,” she said. “What are the social and structural determinants of health that are going to influence decision-making? You want to move into a relationship like this with cultural humility so you can understand what their preferences are and how they’re seeing the problem. Because there’s no universal agreement on the age at which minors should be deemed decision-making competent in health care, the approach is nuanced and depends on each individual patient and family.”
Dr. Cordoro proposed the following four-step approach to SDM to use in pediatric dermatology:
Step 1: Share relevant information about the condition and treatment options in a clear and understandable manner. The average US resident is at the seventh-to eighth-grade level, “so we have to avoid medical jargon and use plain language,” Dr. Cordoro said. Then, use the teach-back approach to assess their understanding. “Ask, ‘What is your understanding of the most important points that we talked about?’ Or, ‘Please share with me what you heard so I’m sure we all understand the plan.’ Using these techniques will reduce the barriers to care such as health literacy.”
Step 2: Solicit and understand patient/patient family perspectives, preferences and priorities. The goal here is to uncover their beliefs, concerns, and assumptions that may influence their decisions. “Be mindful of power asymmetry,” she noted. “Many families still believe the doctor is the boss and they are there to be told what to do. Be clear that the patient has a say. Talk directly to the patient about their interests if developmentally appropriate.”
Step 3: Invite patients/family into a shared decision-making conversation. Consider statements like, “There are many reasonable options here. Let’s work together to come up with the decision that’s right for you.” Or, “Let’s start by exploring your specific goals and concerns. As you think about the options I just talked to you about, what’s important to you?” Or, “Do you want to think about this decision with anyone else?”
Step 4: Check back in frequently. Pause between significant points and check in. “See how they’re doing during the conversation,” she said. “At future appointments, remember to solicit their input on additional decisions.”
In Dr. Cordoro’s opinion, one potential pitfall of SDM is an over-reliance on patient decision aids. “Very few are available in dermatology,” she said. “Some are relevant but none specifically to pediatric dermatology. They are often complex and require a high reading comprehension level. This disadvantages patients and families with low health literacy. Keep it clear and simple. Your patients will appreciate it.”
Dr. Cordoro reported having no relevant disclosures.
FROM AAD 2024
Knee Osteoarthritis Trials Show Promising Results for Several Novel Injectables
VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.
Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.
Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
PTP-001 (MOTYS)
Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.
Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.
Although the changes were only numerically and not statistically different from placebo (n = 71) when looking at the total study population, Ms. Pavesio noted that a key objective of the trial had been to identify populations of patients that may benefit.
When they looked at the effects of PTP-001 solely in those with unilateral knee OA, WOMAC pain scores were decreased to a significantly greater extent with both the high and low doses of PTP-001 vs placebo. Decreases in the least squares mean (LSM) change in WOMAC pain from baseline to week 26 were 26.8 with 100-mg PTP-001, 36.1 with 200-mg PTP-001, and 24.0 with placebo (P = .072). A similarly greater effect for PTP-001 was also seen for LSM change in WOMAC function (26.4, 36.0, and 20.0, respectively; P = .023).
Ms. Pavesio noted that the only real side effect seen during the trial was an initial inflammatory reaction within the first 2 days of IA injection, which resolved within a few days without further problems.
The results are promising enough for Ms. Pavesio and her team to consider a phase 3 trial.
Dr. Lane asked Ms. Pavesio: “So, what’s in the secret sauce? You said it was ground-up placentas?” To which Ms. Pavesio replied that it contained about 300 different molecules which came from amnion, chorion, and umbilical cord tissue obtained from consented placental donation.
Dr. Lane subsequently told this news organization: “It’s probably a bunch of growth factors and cytokines, but if it’s not toxic, and they can standardize it, then it might be good. We remain open minded because we haven’t figured it out.”
Novel Fluticasone Delivery
In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.
Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.
The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.
The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).
These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.
It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.
“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
PPS
Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.
“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”
There are currently two approved formulations: Oral capsules used for the treatment of interstitial cystitis in the European Union, United States, and Australia and an injectable form used in Italy for thromboprophylaxis.
Dr. Ahuja presented data from a phase 2 trial that looked at the effect of once- or twice-weekly subcutaneous injections of PPS vs placebo in 61 people with knee OA pain. Assessments were made after 56, 168, and 365 days of treatment.
Results showed PPS injections resulted in significant improvements in total WOMAC score, WOMAC pain, and WOMAC function, with more PPS- than placebo-treated individuals achieving and then maintaining at least a 30% or greater improvement in pain and a 56% improvement in function.
Rescue medication use was lower in the PPS-treated patients, and Patient Global Impression of Change were significantly higher, Dr. Ahuja said.
Exploratory analyses of synovial fluid biomarkers showed PPS could be having a direct inflammatory effect, with reductions in several proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha.
An assessment of OA disease progression using MRI analysis suggested that there may be an effect on cartilage thickness and volume, as well as bone marrow lesions and overall joint inflammation.
Gene Therapy
Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.
Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.
Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.
However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.
Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (P = .044).
Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.
XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.
The Best Is Yet to Come?
“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.
“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”
Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.
“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
A version of this article appeared on Medscape.com.
VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.
Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.
Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
PTP-001 (MOTYS)
Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.
Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.
Although the changes were only numerically and not statistically different from placebo (n = 71) when looking at the total study population, Ms. Pavesio noted that a key objective of the trial had been to identify populations of patients that may benefit.
When they looked at the effects of PTP-001 solely in those with unilateral knee OA, WOMAC pain scores were decreased to a significantly greater extent with both the high and low doses of PTP-001 vs placebo. Decreases in the least squares mean (LSM) change in WOMAC pain from baseline to week 26 were 26.8 with 100-mg PTP-001, 36.1 with 200-mg PTP-001, and 24.0 with placebo (P = .072). A similarly greater effect for PTP-001 was also seen for LSM change in WOMAC function (26.4, 36.0, and 20.0, respectively; P = .023).
Ms. Pavesio noted that the only real side effect seen during the trial was an initial inflammatory reaction within the first 2 days of IA injection, which resolved within a few days without further problems.
The results are promising enough for Ms. Pavesio and her team to consider a phase 3 trial.
Dr. Lane asked Ms. Pavesio: “So, what’s in the secret sauce? You said it was ground-up placentas?” To which Ms. Pavesio replied that it contained about 300 different molecules which came from amnion, chorion, and umbilical cord tissue obtained from consented placental donation.
Dr. Lane subsequently told this news organization: “It’s probably a bunch of growth factors and cytokines, but if it’s not toxic, and they can standardize it, then it might be good. We remain open minded because we haven’t figured it out.”
Novel Fluticasone Delivery
In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.
Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.
The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.
The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).
These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.
It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.
“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
PPS
Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.
“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”
There are currently two approved formulations: Oral capsules used for the treatment of interstitial cystitis in the European Union, United States, and Australia and an injectable form used in Italy for thromboprophylaxis.
Dr. Ahuja presented data from a phase 2 trial that looked at the effect of once- or twice-weekly subcutaneous injections of PPS vs placebo in 61 people with knee OA pain. Assessments were made after 56, 168, and 365 days of treatment.
Results showed PPS injections resulted in significant improvements in total WOMAC score, WOMAC pain, and WOMAC function, with more PPS- than placebo-treated individuals achieving and then maintaining at least a 30% or greater improvement in pain and a 56% improvement in function.
Rescue medication use was lower in the PPS-treated patients, and Patient Global Impression of Change were significantly higher, Dr. Ahuja said.
Exploratory analyses of synovial fluid biomarkers showed PPS could be having a direct inflammatory effect, with reductions in several proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha.
An assessment of OA disease progression using MRI analysis suggested that there may be an effect on cartilage thickness and volume, as well as bone marrow lesions and overall joint inflammation.
Gene Therapy
Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.
Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.
Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.
However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.
Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (P = .044).
Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.
XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.
The Best Is Yet to Come?
“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.
“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”
Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.
“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
A version of this article appeared on Medscape.com.
VIENNA — Encouraging primary or secondary analyses of trial data for the use of several novel injectables and gene therapy for knee osteoarthritis (OA) were reported at the OARSI 2024 World Congress.
Of all the approaches discussed during the News in Therapies session at OARSI 2024, the most intriguing was the use of the placental extract PTP-001 (MOTYS, Bioventus), session chair Nancy E. Lane, MD, of the University of California Davis School of Medicine, Sacramento, California, told this news organization.
Other notable presentations of data from trials of investigational agents for knee OA included an update from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate; a phase 2 trial of pentosan polysulfate sodium (PPS), a non-opioid, semi-synthetic xylose-based polysaccharide; and an update on phase 2 study results for XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant of interleukin 10 (IL-10).
PTP-001 (MOTYS)
Indeed, promising results were seen in a phase 2 trial testing a single intra-articular (IA) injection of PTP-001 vs an IA saline placebo in just over 200 individuals with symptomatic knee OA. Results of this dose-finding study were presented by Alessandra Pavesio, senior vice president and the chief science officer of Bioventus/Doron Therapeutics, Durham, North Carolina.
Ms. Pavesio reported there were decreases in knee pain and improvements in knee function, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). These changes were seen after 26 weeks of treatment with PTP-001 given at either a low (100 mg, n = 74) or high (200 mg, n = 40) dose.
Although the changes were only numerically and not statistically different from placebo (n = 71) when looking at the total study population, Ms. Pavesio noted that a key objective of the trial had been to identify populations of patients that may benefit.
When they looked at the effects of PTP-001 solely in those with unilateral knee OA, WOMAC pain scores were decreased to a significantly greater extent with both the high and low doses of PTP-001 vs placebo. Decreases in the least squares mean (LSM) change in WOMAC pain from baseline to week 26 were 26.8 with 100-mg PTP-001, 36.1 with 200-mg PTP-001, and 24.0 with placebo (P = .072). A similarly greater effect for PTP-001 was also seen for LSM change in WOMAC function (26.4, 36.0, and 20.0, respectively; P = .023).
Ms. Pavesio noted that the only real side effect seen during the trial was an initial inflammatory reaction within the first 2 days of IA injection, which resolved within a few days without further problems.
The results are promising enough for Ms. Pavesio and her team to consider a phase 3 trial.
Dr. Lane asked Ms. Pavesio: “So, what’s in the secret sauce? You said it was ground-up placentas?” To which Ms. Pavesio replied that it contained about 300 different molecules which came from amnion, chorion, and umbilical cord tissue obtained from consented placental donation.
Dr. Lane subsequently told this news organization: “It’s probably a bunch of growth factors and cytokines, but if it’s not toxic, and they can standardize it, then it might be good. We remain open minded because we haven’t figured it out.”
Novel Fluticasone Delivery
In the same session, James A. Helliwell, MD, cofounder, director, and chief executive officer of Eupraxia Pharmaceuticals in Victoria, British Columbia, Canada, presented updated data from the SPRINGBOARD phase 2B trial of EP-104IAR, a novel long-acting formulation of the corticosteroid fluticasone propionate.
Dr. Helliwell, a cardiothoracic anesthesiologist, explained that EP-104IAR uses proprietary technology to form fluticasone into a crystal that can then be injected directly into the joint. This then slowly diffuses out to provide a highly localized treatment.
The SPRINGBOARD trial recruited just over 300 individuals with moderate knee OA and moderate to severe WOMAC pain and randomly allocated 164 to a single IA injection of EP-104IAR and 164 to a matching vehicle injection as a placebo. The latter was a slightly viscous substance that behaved like hyaluronic acid, Dr. Helliwell said.
The LSM change in total WOMAC score from baseline to week 12 showed a greater improvement with EP-104IAR than with placebo in a per protocol analysis (−2.79 vs −2.07; P = .002). Similar results were seen for the WOMAC subscales of pain (−2.97 vs −2.24; P = .003), function (−2.64 vs −1.99; P = .005), and stiffness (−2.85 vs −2.05; P = .001).
These differences persisted, Dr. Helliwell reported, out to a 20-week assessment for total WOMAC score, function, and stiffness and out to a 15-week assessment for WOMAC pain.
It’s probably no surprise that a steroid works, Dr. Helliwell said, noting that the safety profile of EP-104IAR may be better than that of regular IA steroid injection because it has “few off-target” effects. He reported that there were “minimal, clinically insignificant, and transient effects” of EP-104IAR on serum cortisol. There was no effect on glucose metabolism, even in patients with diabetes, he said.
“There is a group of our patients that we give long-acting steroids to in the joint, so it looked like [the EP-104IAR] safety profile was really good,” Dr. Lane told this news organization. However, she added: “I’m worried about the price tag associated with it.”
PPS
Although it perhaps can’t be described as a novel injectable per se, Mukesh Ahuja, MBBS, global clinical head of osteoarthritis at Paradigm Biopharmaceuticals, presented results of the novel use of PPS.
“PPS is a non-opioid, semi-synthetic xylose-based polysaccharide that is derived from beechwood trees,” Dr. Ahuja said. “It has a long-track record for treating pain, inflammation, and thrombosis in humans.”
There are currently two approved formulations: Oral capsules used for the treatment of interstitial cystitis in the European Union, United States, and Australia and an injectable form used in Italy for thromboprophylaxis.
Dr. Ahuja presented data from a phase 2 trial that looked at the effect of once- or twice-weekly subcutaneous injections of PPS vs placebo in 61 people with knee OA pain. Assessments were made after 56, 168, and 365 days of treatment.
Results showed PPS injections resulted in significant improvements in total WOMAC score, WOMAC pain, and WOMAC function, with more PPS- than placebo-treated individuals achieving and then maintaining at least a 30% or greater improvement in pain and a 56% improvement in function.
Rescue medication use was lower in the PPS-treated patients, and Patient Global Impression of Change were significantly higher, Dr. Ahuja said.
Exploratory analyses of synovial fluid biomarkers showed PPS could be having a direct inflammatory effect, with reductions in several proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha.
An assessment of OA disease progression using MRI analysis suggested that there may be an effect on cartilage thickness and volume, as well as bone marrow lesions and overall joint inflammation.
Gene Therapy
Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.
Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.
Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.
However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.
Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (P = .044).
Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.
XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.
The Best Is Yet to Come?
“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.
“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”
Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.
“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
A version of this article appeared on Medscape.com.
FROM OARSI 2024
The Inconsistency of Preparticipation Sports Evaluations Raises Issues About Their Utility
TORONTO — There is little consistency in the elements and types of information captured in preparticipation physical evaluations (PPE) for sports among school-aged children, which is complicating efforts to determine if they have value, according to a study presented at the Pediatric Academic Societies annual meeting.
The study concept developed when Tammy Ng, MD, a third-year resident in pediatrics at the University of California, Davis, School of Medicine in Sacramento, was surprised to learn that the American Academy of Pediatrics (AAP) had been issuing a standard-of-care PPE for decades.
Dr. Ng had a long-standing interest in pediatric sports medicine and thought that if she was unfamiliar with this form, which was first developed by the AAP in the 1990s in collaboration with other professional organizations, there must be others who were unaware of this resource.
Assuming that this collaborative effort led by the AAP could serve as a standard of care, Dr. Ng evaluated whether PPEs at her own institution were capturing similar information.
In the most recent (5th) edition of the PPE, which was released in 2019 and is available online, medical history is elicited for numerous organ systems relevant to risk. The questions are not directed to any specific sport; the form does not even provide a question about which sports are being considered.
Little Consistency
In evaluating whether PPEs completed at her institution in the previous year elicited similar information, Dr. Ng sought to match 25 elements of patient history from the AAP form to questions posed in the PPEs completed at her institution, some of which had been supplied by school or sports organizations.
Of the 365 PPE forms completed at Dr. Ng’s institution that met study criteria, only 28.6% addressed all 25 elements in the AAP form (range, 0%-78%). Although more than half asked specifically about a history of respiratory symptoms, fewer than half included inquiries about cardiovascular history. There was also little consistency in the capture of information about other relevant medical history.
According to Dr. Ng, these low percentages were observed even when liberally awarding credit. For one example, she said forms that asked any question about syncope with exercise were credited with seeking information about cardiovascular health even though a yes-or-no response might not be helpful.
“We did not distinguish between syncope before or after exercise and this is relevant,” Dr. Ng said. “Syncope during exercise is more likely to be a predictor of sudden cardiac death, whereas syncope after exercise is more likely to be a vasovagal response to exertion.”
Of the 365 PPEs evaluated, about half were completed by pediatricians and half by family medicine clinicians. The average age of the children was about 14 years. Sixty-three percent were male. Only one third of the forms documented the sport for which a pre-participation screen was being submitted.
While almost all states now require PPEs for children considering participation in sports, few specify what information should be elicited, according to Dr. Ng. She further noted that no major study has shown that PPEs have any role in preventing morbidity or mortality related to sports participation.
Does Heterogeneity Negate Worth?
With such diversity across PPEs, evaluating their role is difficult. For example, with such heterogeneity among forms for the information elicited, there is no reasonable approach for testing their sensitivity in predicting medical complications.
Dr. Ng noted that school-created forms were just as likely as forms from other sources to diverge from the AAP-endorsed PPE and ignore organ systems relevant to risk of medical complications. Yet, if the answer is to use the AAP form, Dr. Ng noted that the first sentence on the form reads, “This form should be placed in the athlete’s medical file and should not be shared with schools or sports organizations.”
Although Dr. Ng acknowledged that providing completed PPEs to third parties raises questions about privacy, she questioned how the information should be used by children, parents, and sports organization administrators for discussing risks if not shared.
This concern was seconded in the discussion following Dr. Ng’s presentation.
“You might be signing off on sports participation, but is this for cheerleading or for football?” asked Daniel C. Worthington, MD, a pediatrician in private practice who has a clinical appointment at Case Western Reserve University School of Medicine, Cleveland. “This makes a huge difference when evaluating if participation is safe.”
He has no issue with completing PPEs for the goal of keeping children safe, but he focused on the inconsistency of how information is collected and distributed.
“The major question is: Does it make any difference?” said Dr. Worthington, referring to the completion of PPEs.
Another participant in the discussion that followed Dr. Ng’s presentation pointed out that the urgent care office in a mall near to his office offers a completed PPE form for a price of $20. In their recommendations, the AAP suggests PPEs be completed by the individual’s primary care physician during a well visit, according to Dr. Ng.
Dr. Ng indicated that PPEs and their purpose deserve a closer look. Based on her data, it is reasonable to assume that the priority for some – whether those requiring or those completing the form — is completing the task rather than meaningful screening of risk.
Dr. Ng and Dr. Worthington report no potential conflicts of interest.
TORONTO — There is little consistency in the elements and types of information captured in preparticipation physical evaluations (PPE) for sports among school-aged children, which is complicating efforts to determine if they have value, according to a study presented at the Pediatric Academic Societies annual meeting.
The study concept developed when Tammy Ng, MD, a third-year resident in pediatrics at the University of California, Davis, School of Medicine in Sacramento, was surprised to learn that the American Academy of Pediatrics (AAP) had been issuing a standard-of-care PPE for decades.
Dr. Ng had a long-standing interest in pediatric sports medicine and thought that if she was unfamiliar with this form, which was first developed by the AAP in the 1990s in collaboration with other professional organizations, there must be others who were unaware of this resource.
Assuming that this collaborative effort led by the AAP could serve as a standard of care, Dr. Ng evaluated whether PPEs at her own institution were capturing similar information.
In the most recent (5th) edition of the PPE, which was released in 2019 and is available online, medical history is elicited for numerous organ systems relevant to risk. The questions are not directed to any specific sport; the form does not even provide a question about which sports are being considered.
Little Consistency
In evaluating whether PPEs completed at her institution in the previous year elicited similar information, Dr. Ng sought to match 25 elements of patient history from the AAP form to questions posed in the PPEs completed at her institution, some of which had been supplied by school or sports organizations.
Of the 365 PPE forms completed at Dr. Ng’s institution that met study criteria, only 28.6% addressed all 25 elements in the AAP form (range, 0%-78%). Although more than half asked specifically about a history of respiratory symptoms, fewer than half included inquiries about cardiovascular history. There was also little consistency in the capture of information about other relevant medical history.
According to Dr. Ng, these low percentages were observed even when liberally awarding credit. For one example, she said forms that asked any question about syncope with exercise were credited with seeking information about cardiovascular health even though a yes-or-no response might not be helpful.
“We did not distinguish between syncope before or after exercise and this is relevant,” Dr. Ng said. “Syncope during exercise is more likely to be a predictor of sudden cardiac death, whereas syncope after exercise is more likely to be a vasovagal response to exertion.”
Of the 365 PPEs evaluated, about half were completed by pediatricians and half by family medicine clinicians. The average age of the children was about 14 years. Sixty-three percent were male. Only one third of the forms documented the sport for which a pre-participation screen was being submitted.
While almost all states now require PPEs for children considering participation in sports, few specify what information should be elicited, according to Dr. Ng. She further noted that no major study has shown that PPEs have any role in preventing morbidity or mortality related to sports participation.
Does Heterogeneity Negate Worth?
With such diversity across PPEs, evaluating their role is difficult. For example, with such heterogeneity among forms for the information elicited, there is no reasonable approach for testing their sensitivity in predicting medical complications.
Dr. Ng noted that school-created forms were just as likely as forms from other sources to diverge from the AAP-endorsed PPE and ignore organ systems relevant to risk of medical complications. Yet, if the answer is to use the AAP form, Dr. Ng noted that the first sentence on the form reads, “This form should be placed in the athlete’s medical file and should not be shared with schools or sports organizations.”
Although Dr. Ng acknowledged that providing completed PPEs to third parties raises questions about privacy, she questioned how the information should be used by children, parents, and sports organization administrators for discussing risks if not shared.
This concern was seconded in the discussion following Dr. Ng’s presentation.
“You might be signing off on sports participation, but is this for cheerleading or for football?” asked Daniel C. Worthington, MD, a pediatrician in private practice who has a clinical appointment at Case Western Reserve University School of Medicine, Cleveland. “This makes a huge difference when evaluating if participation is safe.”
He has no issue with completing PPEs for the goal of keeping children safe, but he focused on the inconsistency of how information is collected and distributed.
“The major question is: Does it make any difference?” said Dr. Worthington, referring to the completion of PPEs.
Another participant in the discussion that followed Dr. Ng’s presentation pointed out that the urgent care office in a mall near to his office offers a completed PPE form for a price of $20. In their recommendations, the AAP suggests PPEs be completed by the individual’s primary care physician during a well visit, according to Dr. Ng.
Dr. Ng indicated that PPEs and their purpose deserve a closer look. Based on her data, it is reasonable to assume that the priority for some – whether those requiring or those completing the form — is completing the task rather than meaningful screening of risk.
Dr. Ng and Dr. Worthington report no potential conflicts of interest.
TORONTO — There is little consistency in the elements and types of information captured in preparticipation physical evaluations (PPE) for sports among school-aged children, which is complicating efforts to determine if they have value, according to a study presented at the Pediatric Academic Societies annual meeting.
The study concept developed when Tammy Ng, MD, a third-year resident in pediatrics at the University of California, Davis, School of Medicine in Sacramento, was surprised to learn that the American Academy of Pediatrics (AAP) had been issuing a standard-of-care PPE for decades.
Dr. Ng had a long-standing interest in pediatric sports medicine and thought that if she was unfamiliar with this form, which was first developed by the AAP in the 1990s in collaboration with other professional organizations, there must be others who were unaware of this resource.
Assuming that this collaborative effort led by the AAP could serve as a standard of care, Dr. Ng evaluated whether PPEs at her own institution were capturing similar information.
In the most recent (5th) edition of the PPE, which was released in 2019 and is available online, medical history is elicited for numerous organ systems relevant to risk. The questions are not directed to any specific sport; the form does not even provide a question about which sports are being considered.
Little Consistency
In evaluating whether PPEs completed at her institution in the previous year elicited similar information, Dr. Ng sought to match 25 elements of patient history from the AAP form to questions posed in the PPEs completed at her institution, some of which had been supplied by school or sports organizations.
Of the 365 PPE forms completed at Dr. Ng’s institution that met study criteria, only 28.6% addressed all 25 elements in the AAP form (range, 0%-78%). Although more than half asked specifically about a history of respiratory symptoms, fewer than half included inquiries about cardiovascular history. There was also little consistency in the capture of information about other relevant medical history.
According to Dr. Ng, these low percentages were observed even when liberally awarding credit. For one example, she said forms that asked any question about syncope with exercise were credited with seeking information about cardiovascular health even though a yes-or-no response might not be helpful.
“We did not distinguish between syncope before or after exercise and this is relevant,” Dr. Ng said. “Syncope during exercise is more likely to be a predictor of sudden cardiac death, whereas syncope after exercise is more likely to be a vasovagal response to exertion.”
Of the 365 PPEs evaluated, about half were completed by pediatricians and half by family medicine clinicians. The average age of the children was about 14 years. Sixty-three percent were male. Only one third of the forms documented the sport for which a pre-participation screen was being submitted.
While almost all states now require PPEs for children considering participation in sports, few specify what information should be elicited, according to Dr. Ng. She further noted that no major study has shown that PPEs have any role in preventing morbidity or mortality related to sports participation.
Does Heterogeneity Negate Worth?
With such diversity across PPEs, evaluating their role is difficult. For example, with such heterogeneity among forms for the information elicited, there is no reasonable approach for testing their sensitivity in predicting medical complications.
Dr. Ng noted that school-created forms were just as likely as forms from other sources to diverge from the AAP-endorsed PPE and ignore organ systems relevant to risk of medical complications. Yet, if the answer is to use the AAP form, Dr. Ng noted that the first sentence on the form reads, “This form should be placed in the athlete’s medical file and should not be shared with schools or sports organizations.”
Although Dr. Ng acknowledged that providing completed PPEs to third parties raises questions about privacy, she questioned how the information should be used by children, parents, and sports organization administrators for discussing risks if not shared.
This concern was seconded in the discussion following Dr. Ng’s presentation.
“You might be signing off on sports participation, but is this for cheerleading or for football?” asked Daniel C. Worthington, MD, a pediatrician in private practice who has a clinical appointment at Case Western Reserve University School of Medicine, Cleveland. “This makes a huge difference when evaluating if participation is safe.”
He has no issue with completing PPEs for the goal of keeping children safe, but he focused on the inconsistency of how information is collected and distributed.
“The major question is: Does it make any difference?” said Dr. Worthington, referring to the completion of PPEs.
Another participant in the discussion that followed Dr. Ng’s presentation pointed out that the urgent care office in a mall near to his office offers a completed PPE form for a price of $20. In their recommendations, the AAP suggests PPEs be completed by the individual’s primary care physician during a well visit, according to Dr. Ng.
Dr. Ng indicated that PPEs and their purpose deserve a closer look. Based on her data, it is reasonable to assume that the priority for some – whether those requiring or those completing the form — is completing the task rather than meaningful screening of risk.
Dr. Ng and Dr. Worthington report no potential conflicts of interest.
FROM PAS 2024
Neutrophils Take Center Stage in Growing Understanding of Colchicine’s Role in Treating Atherosclerotic Cardiovascular Disease
NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.
In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.
“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.
The Inflammatory Pathway
Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.
“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation.
Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.
“This is where colchicine can potentially play a role,” she said.
Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.
The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted.
Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.
Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.
What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.
“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.
“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
Slow to Embrace Colchicine
Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.
“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.
Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.
Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.
Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com .
NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.
In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.
“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.
The Inflammatory Pathway
Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.
“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation.
Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.
“This is where colchicine can potentially play a role,” she said.
Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.
The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted.
Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.
Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.
What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.
“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.
“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
Slow to Embrace Colchicine
Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.
“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.
Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.
Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.
Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com .
NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.
Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.
In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.
“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.
The Inflammatory Pathway
Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.
“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation.
Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.
“This is where colchicine can potentially play a role,” she said.
Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.
The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted.
Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.
Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.
What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.
“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.
“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
Slow to Embrace Colchicine
Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.
“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.
Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.
Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.
Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.
A version of this article appeared on Medscape.com .
Novel Treatment Options for Epilepsy
DENVER — , according to new data presented at the 2024 annual meeting of the American Academy of Neurology.
Of the two drugs evaluated in phase 2 trials, one is a highly targeted TARP-8–dependent AMPA receptor antagonist known as ES-481. The other is XEN1101, a novel potassium channel opener that was well tolerated as well as effective.
TARP inhibitors, which act on transmembrane AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) receptor regulatory proteins, are already available for the control of epilepsy, but ES-481 might be different, according to Terrence J. O’Brien, MD, department of neuroscience, Monash University, Melbourne, Australia.
First-in-Class TARP Inhibitor Is Tested
As a “first-in-class, potent and selective antagonist of the TARP-γ8 AMPA receptor,” ES-481 is “predicted to effectively suppress focal seizures arising from the hippocampus and limbic system,” he said. Dr. O’Brien claims that this specificity of action appears to circumvent central nervous system side effects in studies so far.
In the phase 2a multicenter, randomized trial, 22 patients with drug-resistant epilepsy of any type (focal, generalized, or mixed) were randomized to ES-481 or placebo. In the ES-481 arm, the dose was escalated each week, climbing from 25 mg once-daily, to 25 mg twice-daily, 50 mg twice-daily, and then to 75 mg twice daily. At the end of 4 weeks and after a 7-day washout, the randomized groups were crossed over to the opposite therapy for another 4 weeks.
When data were confined to the first treatment period to avoid a carry-over effect, there was a consistent advantage for active treatment over placebo. At the highest 75-mg twice-daily dose of ES-481, the reduction in seizure frequency was 80% vs 49% on placebo ( P < .05).
The rate of complete remission at the end of the study was not greater for ES-481, but higher proportions of patients on active therapy achieved reductions from baseline in seizure activity when defined as greater than 30% (72.77% vs 36.4%) or greater than 50% (36.4% vs 18.2%). P values for these differences were not provided.
Differences in EEG were not observed, but Dr. O’Brien reported that 18 of the subjects had no EEG activity at baseline, diminishing the opportunity to show a difference.
Open-Label Study Supports Controlled Data
Sixteen patients have entered an open-label extension with sustained suppression of seizure activity relative to baseline observed so far, Dr. O’Brien reported.
ES-481 was well tolerated. There were no significant changes in lab values, and all four of the adverse events leading to discontinuation occurred on placebo. There were higher rates of dizziness, insomnia, gait disturbance, and dysarthria associated with ES-481 than placebo, but the rate of serious adverse events was lower (4.8% vs 14.3%).
These response rates are noteworthy because patients had severe disease with diminishing therapeutic options, according to Dr. O’Brien. For entry, patients were required to be taking one to four antiseizure medications while still experiencing seizure activity. The patients averaged one interictal epileptiform discharge and/or seizure per hour on EEG.
Large-scale, double-blind, controlled studies are planned and warranted on the basis of these data, according to Dr. O’Brien, who emphasized that benefit was achieved with a low relative risk of significant adverse events.
New Potassium Channel Opener Shows Promise
Data with the selective potassium channel opener XEN1101 from the previously published phase 2b X-TOLE trial were reported in two parts. The first set of data involved an analysis of response by baseline activity. The other set of data were generated by an ongoing open-label extension (OLE) of X-TOLE.
In X-TOLE, which randomized 325 patients with treatment-resistant focal-onset seizures (FOS) to one of three doses of XEN-1011 or placebo, the median reduction in FOS at the highest dose of 25 mg once-daily XEN-1011 was 52.8% vs placebo (P < .001).
In the new analysis, the goal was to look at efficacy of the 25-mg dose across differences in baseline severity, reported Roger J. Porter, MD, adjunct professor of neurology, University of Pennsylvania, Philadelphia.
Generally, a greater response was observed for those with less severe disease. For example, the response rate defined as greater than 50% reduction in seizure frequency on XEN1101 was higher for those with a baseline seizure activity of 8.5 seizures/month or fewer relative to more (65.5% vs 50.6%) and six or fewer antiseizure medications relative to more (64.2% vs 40.0%).
Pointing out that the study enrolled a challenging group of patients, Dr. Porter said that the data do not rule out efficacy “across the spectrum of epilepsy severity,” but he did suggest that these data will provide context for the coming phase 3 trials.
In the OLE data presented by Jacqueline French, MD, professor of neurology at the Langone School of Medicine of New York University, the efficacy and safety of XEN1101 taken with food has been consistent with what was observed in the double-blind trial. With up to 2 years of follow-up in the planned 5-year OLE, which is evaluating 20 mg once-daily taken with food, 60% are still on therapy,
For those followed for 24 months, 23.6% are completely seizure free, according to Dr. French. For those followed at least 12 months, 31.5% have achieved a median percent reduction in monthly seizure activity of 90% or more; 41.8% a reduction of 75% or more; and 69.7% a reduction of 50% or more.
The side-effect profile has also been consistent with that seen in the phase 2b trial. Dizziness and other mild to moderate side effects that often accompany antiseizure medications have been observed, along with modest weight gain, but there have been no new safety signals over long-term use.
If a planned phase 3 study enrolling patients with localized and general epilepsy confirms these phase 2 data, Dr. French indicated that it has the potential to advance a potassium channel opener that is both efficacious and well tolerated.
First-in-Man Study Performed With Stem Cell Product
The investigational product for treatment-resistant epilepsy has data on just five patients. Yet, the two patients followed the longest, both of which had highly treatment-resistant epilepsy, have had reductions in seizure activity exceeding 95%, according to Cory Nicholas, PhD, the chief executive officer of Neurona Therapeutics.
NRTX-100 is a GABAergic interneuron product derived from human pluripotent stem cells. The NRTX cells are surgically transplanted into the head and body of the hippocampus in patients with unilateral temporal lobe epilepsy with hippocampal sclerosis. The procedure is performed with MRI guidance, and patients are placed on immunosuppression that starts 1 week before surgery and is tapered 1 year later.
In this first-in-man study, the primary outcome of interest was safety. There have been no adverse events associated with this stem cell product in follow-up so far, according to Dr. Nicholas, who presented data on the first 5 of 10 procedures that have been completed so far.
Consistent with the prior work in animal models, it takes several months for the reduction in seizures to be achieved and, in animal models, to see improved functionality. It is notable that the reductions in seizure activity observed over time in those patients followed the longest have been accompanied by evidence of neurocognitive improvement, Dr. Nicholas reported.
“The efficacy has seemed durable so far, and we expect incremental improvement in clinical response over time,” said Dr. Nicholas, who reported that the Food and Drug Administration has already approved a second clinical study.
Are New Antiseizure Therapies Needed?
The value of this and the other emerging therapies is that “no treatment for epilepsy works well in every patient. We continue to need a wide array of treatments to find the one right for the patient in front of us,” said Nassim Zecavati, MD, director of Epilepsy, Children’s Hospital, Virginia Commonwealth University, Richmond.
Asked to comment on the promise of these three therapies, Dr. Zecavati suggested each is intriguing for different reasons. AMPA receptor antagonists have proven to be a promising drug class so far, suggesting that “another could be helpful.” Potassium channel openers appear to have “a great mechanism of action,” but Dr. Zecavati said drugs in this class with a more favorable safety profile are needed.
As for NRTX-1001, she was intrigued with its novelty. She speculated that it might have particular promise for intractable drug-resistant epilepsy in patients who are not candidates for standard surgical strategies but might tolerate a less invasive procedure.
“My question might be who is going to perform this procedure,” Dr. Zecavati said. Noting that experience and skill might be needed to achieve an optimal result with cell transplantation into the brain, she said she will be waiting for more studies that might answer this question and to determine where, if effective, it would fit among current options.
Dr. O’Brien reported financial relationships with Eisai, Kinoxis, Livanova, Supernus, and UCB Pharma. Dr. Porter reported financial relationships with Axonis, Engrail, Longboard, Neurocrine, and Xenon, which provided funding for the study he discussed. Dr. French has financial relationships with more than 20 pharmaceutical companies, including Xenon, which provided funding for the study she discussed. Dr. Nicholas is chief executive officer of Neurona Therapeutics. Dr. Zecavati reported no potential conflicts of interest.
DENVER — , according to new data presented at the 2024 annual meeting of the American Academy of Neurology.
Of the two drugs evaluated in phase 2 trials, one is a highly targeted TARP-8–dependent AMPA receptor antagonist known as ES-481. The other is XEN1101, a novel potassium channel opener that was well tolerated as well as effective.
TARP inhibitors, which act on transmembrane AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) receptor regulatory proteins, are already available for the control of epilepsy, but ES-481 might be different, according to Terrence J. O’Brien, MD, department of neuroscience, Monash University, Melbourne, Australia.
First-in-Class TARP Inhibitor Is Tested
As a “first-in-class, potent and selective antagonist of the TARP-γ8 AMPA receptor,” ES-481 is “predicted to effectively suppress focal seizures arising from the hippocampus and limbic system,” he said. Dr. O’Brien claims that this specificity of action appears to circumvent central nervous system side effects in studies so far.
In the phase 2a multicenter, randomized trial, 22 patients with drug-resistant epilepsy of any type (focal, generalized, or mixed) were randomized to ES-481 or placebo. In the ES-481 arm, the dose was escalated each week, climbing from 25 mg once-daily, to 25 mg twice-daily, 50 mg twice-daily, and then to 75 mg twice daily. At the end of 4 weeks and after a 7-day washout, the randomized groups were crossed over to the opposite therapy for another 4 weeks.
When data were confined to the first treatment period to avoid a carry-over effect, there was a consistent advantage for active treatment over placebo. At the highest 75-mg twice-daily dose of ES-481, the reduction in seizure frequency was 80% vs 49% on placebo ( P < .05).
The rate of complete remission at the end of the study was not greater for ES-481, but higher proportions of patients on active therapy achieved reductions from baseline in seizure activity when defined as greater than 30% (72.77% vs 36.4%) or greater than 50% (36.4% vs 18.2%). P values for these differences were not provided.
Differences in EEG were not observed, but Dr. O’Brien reported that 18 of the subjects had no EEG activity at baseline, diminishing the opportunity to show a difference.
Open-Label Study Supports Controlled Data
Sixteen patients have entered an open-label extension with sustained suppression of seizure activity relative to baseline observed so far, Dr. O’Brien reported.
ES-481 was well tolerated. There were no significant changes in lab values, and all four of the adverse events leading to discontinuation occurred on placebo. There were higher rates of dizziness, insomnia, gait disturbance, and dysarthria associated with ES-481 than placebo, but the rate of serious adverse events was lower (4.8% vs 14.3%).
These response rates are noteworthy because patients had severe disease with diminishing therapeutic options, according to Dr. O’Brien. For entry, patients were required to be taking one to four antiseizure medications while still experiencing seizure activity. The patients averaged one interictal epileptiform discharge and/or seizure per hour on EEG.
Large-scale, double-blind, controlled studies are planned and warranted on the basis of these data, according to Dr. O’Brien, who emphasized that benefit was achieved with a low relative risk of significant adverse events.
New Potassium Channel Opener Shows Promise
Data with the selective potassium channel opener XEN1101 from the previously published phase 2b X-TOLE trial were reported in two parts. The first set of data involved an analysis of response by baseline activity. The other set of data were generated by an ongoing open-label extension (OLE) of X-TOLE.
In X-TOLE, which randomized 325 patients with treatment-resistant focal-onset seizures (FOS) to one of three doses of XEN-1011 or placebo, the median reduction in FOS at the highest dose of 25 mg once-daily XEN-1011 was 52.8% vs placebo (P < .001).
In the new analysis, the goal was to look at efficacy of the 25-mg dose across differences in baseline severity, reported Roger J. Porter, MD, adjunct professor of neurology, University of Pennsylvania, Philadelphia.
Generally, a greater response was observed for those with less severe disease. For example, the response rate defined as greater than 50% reduction in seizure frequency on XEN1101 was higher for those with a baseline seizure activity of 8.5 seizures/month or fewer relative to more (65.5% vs 50.6%) and six or fewer antiseizure medications relative to more (64.2% vs 40.0%).
Pointing out that the study enrolled a challenging group of patients, Dr. Porter said that the data do not rule out efficacy “across the spectrum of epilepsy severity,” but he did suggest that these data will provide context for the coming phase 3 trials.
In the OLE data presented by Jacqueline French, MD, professor of neurology at the Langone School of Medicine of New York University, the efficacy and safety of XEN1101 taken with food has been consistent with what was observed in the double-blind trial. With up to 2 years of follow-up in the planned 5-year OLE, which is evaluating 20 mg once-daily taken with food, 60% are still on therapy,
For those followed for 24 months, 23.6% are completely seizure free, according to Dr. French. For those followed at least 12 months, 31.5% have achieved a median percent reduction in monthly seizure activity of 90% or more; 41.8% a reduction of 75% or more; and 69.7% a reduction of 50% or more.
The side-effect profile has also been consistent with that seen in the phase 2b trial. Dizziness and other mild to moderate side effects that often accompany antiseizure medications have been observed, along with modest weight gain, but there have been no new safety signals over long-term use.
If a planned phase 3 study enrolling patients with localized and general epilepsy confirms these phase 2 data, Dr. French indicated that it has the potential to advance a potassium channel opener that is both efficacious and well tolerated.
First-in-Man Study Performed With Stem Cell Product
The investigational product for treatment-resistant epilepsy has data on just five patients. Yet, the two patients followed the longest, both of which had highly treatment-resistant epilepsy, have had reductions in seizure activity exceeding 95%, according to Cory Nicholas, PhD, the chief executive officer of Neurona Therapeutics.
NRTX-100 is a GABAergic interneuron product derived from human pluripotent stem cells. The NRTX cells are surgically transplanted into the head and body of the hippocampus in patients with unilateral temporal lobe epilepsy with hippocampal sclerosis. The procedure is performed with MRI guidance, and patients are placed on immunosuppression that starts 1 week before surgery and is tapered 1 year later.
In this first-in-man study, the primary outcome of interest was safety. There have been no adverse events associated with this stem cell product in follow-up so far, according to Dr. Nicholas, who presented data on the first 5 of 10 procedures that have been completed so far.
Consistent with the prior work in animal models, it takes several months for the reduction in seizures to be achieved and, in animal models, to see improved functionality. It is notable that the reductions in seizure activity observed over time in those patients followed the longest have been accompanied by evidence of neurocognitive improvement, Dr. Nicholas reported.
“The efficacy has seemed durable so far, and we expect incremental improvement in clinical response over time,” said Dr. Nicholas, who reported that the Food and Drug Administration has already approved a second clinical study.
Are New Antiseizure Therapies Needed?
The value of this and the other emerging therapies is that “no treatment for epilepsy works well in every patient. We continue to need a wide array of treatments to find the one right for the patient in front of us,” said Nassim Zecavati, MD, director of Epilepsy, Children’s Hospital, Virginia Commonwealth University, Richmond.
Asked to comment on the promise of these three therapies, Dr. Zecavati suggested each is intriguing for different reasons. AMPA receptor antagonists have proven to be a promising drug class so far, suggesting that “another could be helpful.” Potassium channel openers appear to have “a great mechanism of action,” but Dr. Zecavati said drugs in this class with a more favorable safety profile are needed.
As for NRTX-1001, she was intrigued with its novelty. She speculated that it might have particular promise for intractable drug-resistant epilepsy in patients who are not candidates for standard surgical strategies but might tolerate a less invasive procedure.
“My question might be who is going to perform this procedure,” Dr. Zecavati said. Noting that experience and skill might be needed to achieve an optimal result with cell transplantation into the brain, she said she will be waiting for more studies that might answer this question and to determine where, if effective, it would fit among current options.
Dr. O’Brien reported financial relationships with Eisai, Kinoxis, Livanova, Supernus, and UCB Pharma. Dr. Porter reported financial relationships with Axonis, Engrail, Longboard, Neurocrine, and Xenon, which provided funding for the study he discussed. Dr. French has financial relationships with more than 20 pharmaceutical companies, including Xenon, which provided funding for the study she discussed. Dr. Nicholas is chief executive officer of Neurona Therapeutics. Dr. Zecavati reported no potential conflicts of interest.
DENVER — , according to new data presented at the 2024 annual meeting of the American Academy of Neurology.
Of the two drugs evaluated in phase 2 trials, one is a highly targeted TARP-8–dependent AMPA receptor antagonist known as ES-481. The other is XEN1101, a novel potassium channel opener that was well tolerated as well as effective.
TARP inhibitors, which act on transmembrane AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) receptor regulatory proteins, are already available for the control of epilepsy, but ES-481 might be different, according to Terrence J. O’Brien, MD, department of neuroscience, Monash University, Melbourne, Australia.
First-in-Class TARP Inhibitor Is Tested
As a “first-in-class, potent and selective antagonist of the TARP-γ8 AMPA receptor,” ES-481 is “predicted to effectively suppress focal seizures arising from the hippocampus and limbic system,” he said. Dr. O’Brien claims that this specificity of action appears to circumvent central nervous system side effects in studies so far.
In the phase 2a multicenter, randomized trial, 22 patients with drug-resistant epilepsy of any type (focal, generalized, or mixed) were randomized to ES-481 or placebo. In the ES-481 arm, the dose was escalated each week, climbing from 25 mg once-daily, to 25 mg twice-daily, 50 mg twice-daily, and then to 75 mg twice daily. At the end of 4 weeks and after a 7-day washout, the randomized groups were crossed over to the opposite therapy for another 4 weeks.
When data were confined to the first treatment period to avoid a carry-over effect, there was a consistent advantage for active treatment over placebo. At the highest 75-mg twice-daily dose of ES-481, the reduction in seizure frequency was 80% vs 49% on placebo ( P < .05).
The rate of complete remission at the end of the study was not greater for ES-481, but higher proportions of patients on active therapy achieved reductions from baseline in seizure activity when defined as greater than 30% (72.77% vs 36.4%) or greater than 50% (36.4% vs 18.2%). P values for these differences were not provided.
Differences in EEG were not observed, but Dr. O’Brien reported that 18 of the subjects had no EEG activity at baseline, diminishing the opportunity to show a difference.
Open-Label Study Supports Controlled Data
Sixteen patients have entered an open-label extension with sustained suppression of seizure activity relative to baseline observed so far, Dr. O’Brien reported.
ES-481 was well tolerated. There were no significant changes in lab values, and all four of the adverse events leading to discontinuation occurred on placebo. There were higher rates of dizziness, insomnia, gait disturbance, and dysarthria associated with ES-481 than placebo, but the rate of serious adverse events was lower (4.8% vs 14.3%).
These response rates are noteworthy because patients had severe disease with diminishing therapeutic options, according to Dr. O’Brien. For entry, patients were required to be taking one to four antiseizure medications while still experiencing seizure activity. The patients averaged one interictal epileptiform discharge and/or seizure per hour on EEG.
Large-scale, double-blind, controlled studies are planned and warranted on the basis of these data, according to Dr. O’Brien, who emphasized that benefit was achieved with a low relative risk of significant adverse events.
New Potassium Channel Opener Shows Promise
Data with the selective potassium channel opener XEN1101 from the previously published phase 2b X-TOLE trial were reported in two parts. The first set of data involved an analysis of response by baseline activity. The other set of data were generated by an ongoing open-label extension (OLE) of X-TOLE.
In X-TOLE, which randomized 325 patients with treatment-resistant focal-onset seizures (FOS) to one of three doses of XEN-1011 or placebo, the median reduction in FOS at the highest dose of 25 mg once-daily XEN-1011 was 52.8% vs placebo (P < .001).
In the new analysis, the goal was to look at efficacy of the 25-mg dose across differences in baseline severity, reported Roger J. Porter, MD, adjunct professor of neurology, University of Pennsylvania, Philadelphia.
Generally, a greater response was observed for those with less severe disease. For example, the response rate defined as greater than 50% reduction in seizure frequency on XEN1101 was higher for those with a baseline seizure activity of 8.5 seizures/month or fewer relative to more (65.5% vs 50.6%) and six or fewer antiseizure medications relative to more (64.2% vs 40.0%).
Pointing out that the study enrolled a challenging group of patients, Dr. Porter said that the data do not rule out efficacy “across the spectrum of epilepsy severity,” but he did suggest that these data will provide context for the coming phase 3 trials.
In the OLE data presented by Jacqueline French, MD, professor of neurology at the Langone School of Medicine of New York University, the efficacy and safety of XEN1101 taken with food has been consistent with what was observed in the double-blind trial. With up to 2 years of follow-up in the planned 5-year OLE, which is evaluating 20 mg once-daily taken with food, 60% are still on therapy,
For those followed for 24 months, 23.6% are completely seizure free, according to Dr. French. For those followed at least 12 months, 31.5% have achieved a median percent reduction in monthly seizure activity of 90% or more; 41.8% a reduction of 75% or more; and 69.7% a reduction of 50% or more.
The side-effect profile has also been consistent with that seen in the phase 2b trial. Dizziness and other mild to moderate side effects that often accompany antiseizure medications have been observed, along with modest weight gain, but there have been no new safety signals over long-term use.
If a planned phase 3 study enrolling patients with localized and general epilepsy confirms these phase 2 data, Dr. French indicated that it has the potential to advance a potassium channel opener that is both efficacious and well tolerated.
First-in-Man Study Performed With Stem Cell Product
The investigational product for treatment-resistant epilepsy has data on just five patients. Yet, the two patients followed the longest, both of which had highly treatment-resistant epilepsy, have had reductions in seizure activity exceeding 95%, according to Cory Nicholas, PhD, the chief executive officer of Neurona Therapeutics.
NRTX-100 is a GABAergic interneuron product derived from human pluripotent stem cells. The NRTX cells are surgically transplanted into the head and body of the hippocampus in patients with unilateral temporal lobe epilepsy with hippocampal sclerosis. The procedure is performed with MRI guidance, and patients are placed on immunosuppression that starts 1 week before surgery and is tapered 1 year later.
In this first-in-man study, the primary outcome of interest was safety. There have been no adverse events associated with this stem cell product in follow-up so far, according to Dr. Nicholas, who presented data on the first 5 of 10 procedures that have been completed so far.
Consistent with the prior work in animal models, it takes several months for the reduction in seizures to be achieved and, in animal models, to see improved functionality. It is notable that the reductions in seizure activity observed over time in those patients followed the longest have been accompanied by evidence of neurocognitive improvement, Dr. Nicholas reported.
“The efficacy has seemed durable so far, and we expect incremental improvement in clinical response over time,” said Dr. Nicholas, who reported that the Food and Drug Administration has already approved a second clinical study.
Are New Antiseizure Therapies Needed?
The value of this and the other emerging therapies is that “no treatment for epilepsy works well in every patient. We continue to need a wide array of treatments to find the one right for the patient in front of us,” said Nassim Zecavati, MD, director of Epilepsy, Children’s Hospital, Virginia Commonwealth University, Richmond.
Asked to comment on the promise of these three therapies, Dr. Zecavati suggested each is intriguing for different reasons. AMPA receptor antagonists have proven to be a promising drug class so far, suggesting that “another could be helpful.” Potassium channel openers appear to have “a great mechanism of action,” but Dr. Zecavati said drugs in this class with a more favorable safety profile are needed.
As for NRTX-1001, she was intrigued with its novelty. She speculated that it might have particular promise for intractable drug-resistant epilepsy in patients who are not candidates for standard surgical strategies but might tolerate a less invasive procedure.
“My question might be who is going to perform this procedure,” Dr. Zecavati said. Noting that experience and skill might be needed to achieve an optimal result with cell transplantation into the brain, she said she will be waiting for more studies that might answer this question and to determine where, if effective, it would fit among current options.
Dr. O’Brien reported financial relationships with Eisai, Kinoxis, Livanova, Supernus, and UCB Pharma. Dr. Porter reported financial relationships with Axonis, Engrail, Longboard, Neurocrine, and Xenon, which provided funding for the study he discussed. Dr. French has financial relationships with more than 20 pharmaceutical companies, including Xenon, which provided funding for the study she discussed. Dr. Nicholas is chief executive officer of Neurona Therapeutics. Dr. Zecavati reported no potential conflicts of interest.
FROM AAN 2024
‘Bread and Butter’: Societies Issue T2D Management Guidance
Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.
On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
The document was also presented simultaneously at the ACP annual meeting.
And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
General Agreement but Some Differences
The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone.
The new ACP document gives two general recommendations:
1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.
*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.
*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.
2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.
Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.
ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.”
The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely.
This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”
Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.”
In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness.
In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”
Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”
However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.
“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”
Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.
A version of this article first appeared on Medscape.com.
Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.
On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
The document was also presented simultaneously at the ACP annual meeting.
And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
General Agreement but Some Differences
The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone.
The new ACP document gives two general recommendations:
1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.
*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.
*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.
2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.
Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.
ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.”
The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely.
This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”
Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.”
In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness.
In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”
Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”
However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.
“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”
Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.
A version of this article first appeared on Medscape.com.
Two professional societies have issued new guidance for type 2 diabetes management in primary care, with one focused specifically on the use of the newer medications.
On April 19, 2024, the American College of Physicians (ACP) published Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. The internal medicine group recommends the use of glucagon-like peptide-1 (GLP-1) agonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors as second-line treatment after metformin. They also advise against the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
The document was also presented simultaneously at the ACP annual meeting.
And on April 15, the American Diabetes Association (ADA) posted its comprehensive Standards of Care in Diabetes—2024 Abridged for Primary Care Professionals as a follow-up to the December 2023 publication of its full-length Standards. Section 9, Pharmacologic Approaches to Glycemic Treatment, covers the same ground as the ACP guidelines.
General Agreement but Some Differences
The recommendations generally agree regarding medication use, although there are some differences. Both societies continue to endorse metformin and lifestyle modification as first-line therapy for glycemic management in type 2 diabetes. However, while ADA also gives the option of initial combination therapy with prioritization of avoiding hypoglycemia, ACP advises adding new medications only if glycemic goals aren’t met with lifestyle and metformin alone.
The new ACP document gives two general recommendations:
1. Add an SGLT2 inhibitor or a GLP-1 agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.
*Use an SGLT2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure.
*Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke.
2. ACP recommends against adding a DPP-4 inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.
Both ADA and ACP advise using SGLT2 inhibitors in patients with congestive heart failure and/or chronic kidney disease, and using GLP-1 agonists in patients for whom weight management is a priority. The ADA also advises using agents of either drug class with proven cardiovascular benefit for people with type 2 diabetes who have established cardiovascular disease or who are at high risk.
ADA doesn’t advise against the use of DPP-4 inhibitors but doesn’t prioritize them either. Both insulin and sulfonylureas remain options for both, but they also are lower priority due to their potential for causing hypoglycemia. ACP says that sulfonylureas and long-acting insulin are “inferior to SGLT2 inhibitors and GLP-1 agonists in reducing all-cause mortality and morbidity but may still have some limited value for glycemic control.”
The two groups continue to differ regarding A1c goals, although both recommend individualization. The ACP generally advises levels between 7% and 8% for most adults with type 2 diabetes, and de-intensification of pharmacologic agents for those with A1c levels below 6.5%. On the other hand, ADA recommends A1c levels < 7% as long as that can be achieved safely.
This is the first time ACP has addressed this topic in a guideline, panel chair Carolyn J. Crandall, MD, told this news organization. “Diabetes treatment, of course, is our bread and butter…but what we had done before was based on the need to identify a target, like glycosylated hemoglobin. What patients and physicians really want to know now is, who should receive these new drugs? Should they receive these new drugs? And what benefits do they have?”
Added Dr. Crandall, who is professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles. “At ACP we have a complicated process that I’m actually very proud of, where we’ve asked a lay public panel, as well at the members of our guideline committee, to rank what’s most important in terms of the health outcomes for this condition…And then we look at how to balance those risks and benefits to make the recommendations.”
In the same Annals of Internal Medicine issue are two systematic reviews/meta-analyses that informed the new document, one on drug effectiveness and the other on cost-effectiveness.
In the accompanying editorial from Fatima Z. Syed, MD, an internist and medical weight management specialist at Duke University Division of General Internal Medicine, Durham, North Carolina, she notes, “the potential added benefits of these newer medications, including weight loss and cardiovascular and renal benefits, motivate their prescription, but cost and prior authorization hurdles can bar their use.”
Dr. Syed cites as “missing” from the ACP guidelines an analysis of comorbidities, including obesity. The reason for that, according to the document, is that “weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis.”
However, Dr. Syed notes that factoring in weight loss could improve the cost-effectiveness of the newer medications. She points out that the ADA Standards suggest a GLP-1 agonist with or without metformin as initial therapy options for people with newly diagnosed type 2 diabetes who might benefit from weight loss.
“The ACP guidelines strengthen the case for metformin as first-line medication for diabetes when comorbid conditions are not present. Metformin is cost-effective and has excellent hemoglobin A1c reduction. The accompanying economic analysis tells us that in the absence of comorbidity, the newer medication classes do not seem to be cost-effective. However, given that many patients with type 2 diabetes have obesity or existing cardiovascular or renal disease, the choice and accessibility of newer medications can be nuanced. The cost-effectiveness of GLP1 agonists and SGLT2 inhibitors as initial diabetes therapy in the setting of various comorbid conditions warrants careful exploration.”
Dr. Crandall has no disclosures. Dr. Syed disclosed that her husband is employed by Blue Cross Blue Shield of North Carolina.
A version of this article first appeared on Medscape.com.
Pediatric Clinic Doubles Well-Visit Data Capture by Going Completely Paperless
TORONTO — , and, of course, it eliminated the work associated with managing paper records.
Due to the efficacy of the pre-visit capture, “all of the information — including individual responses and total scores — is available to the provider at a glance” by the time of the examination encounter, according to Brian T. Ketterman, MD, a third-year resident in pediatrics at the Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee.
Urgent issues, such as suicidality risk, “are flagged so that they are seen first,” he added.
The goal of going paperless was to improve the amount and the consistency of data captured with each well visit, according to Dr. Ketterman. He described a major undertaking involving fundamental changes in the electronic medical record (EMR) system to accommodate the new approach.
Characterizing screening at well visits as “one of the most important jobs of a pediatrician” when he presented these data at the Pediatric Academic Societies annual meeting, he added that a paperless approach comes with many advantages.
Raising the Rate of Complete Data Capture
The American Academy of Pediatrics (AAP) has identified more than 30 screening elements at well-child visits. At his institution several additional screening elements have been added. Prior to going paperless, about 45.6% on average of this well-visit data was being captured in any specific patient encounter, even if the institution was doing well overall in capturing essential information, such as key laboratory values and immunizations.
The vast majority of the information that was missing depended on patient or family input, such as social determinants of health (SDoH), which includes the aspects of home environment, such as nutrition and safety. Dr. Ketterman said that going paperless was inspired by positive experiences reported elsewhere.
“We wanted to build on this work,” he said.
The goal of the program was to raise the rate of complete data capture at well visits to at least 80% and do this across all languages. The first step was to create digital forms in English and Spanish for completion unique to each milestone well-child visit defined by age. For those who speak English or Spanish, these forms were supplied through the patient portal several days before the visit.
For those who spoke one of the more than 40 other languages encountered among patients at Dr. Ketterman’s institution, an interpreter was supplied. If patients arrived at the clinic without completing the digital entry, they completed it on a tablet with the help of an interpreter if one was needed.
Prior to going paperless, all screening data were captured on paper forms completed in the waiting room. The provider then manually reviewed and scored the forms before they were then scanned into the medical records. The paperless approach has eliminated all of these steps and the information is already available for review by the time the pediatrician enters the examination room.
With more than 50,000 well-child checkups captured over a recent 15-month period of paperless questionnaires, the proportion with 100% data capture using what Dr. Ketterman characterized as “strict criteria” was 84%, surpassing the goal at the initiation of the program.
“We improved in almost every screening measure,” Dr. Ketterman said, providing P values that were mostly < .001 for a range of standard tests such as M-CHAT-R (Modified Checklist for Autism in Toddlers), QPA (Quick Parenting Assessment), and PSC-17 (Pediatric Symptom Checklist) when compared to the baseline period.
Additional Advantages
The improvement in well-visit data capture was the goal, but the list of other advantages of the paperless system is long. For one, the EMR system now automatically uses the data to offer guidance that might improve patient outcomes. For example, if the family reports that the child does not see a dentist or does not know how to swim, these lead prompt the EMR to provide resources, such as the names of dentists of swim programs, to address the problem.
As another example, screening questions that reveal food insecurity automatically trigger guidance for enrolling in the U.S. Department of Agriculture’s WIC (Women, Infants, and Children) food program. According to Dr. Ketterman, the proportion of children now enrolled in WIC has increased 10-fold from baseline. He also reported there was a twofold increase in the proportion of patients enrolled in a free book program as a result of a screening questions that ask about reading at home.
The improvement in well-visit data capture was seen across all languages. Even if the gains were not quite as good in languages other than English or Spanish, they were still highly significant relative to baseline.
A ‘Life-Changing’ Improvement
The discussion following his talk made it clear that similar approaches are being actively pursued nationwide. Several in the audience working on similar programs identified such challenges as getting electronic medical record (EMR) systems to cooperate, ensuring patient enrollment in the portals, and avoiding form completion fatigue, but the comments were uniformly supportive of the benefits of this approach.
“This has been life-changing for us,” said Katie E. McPeak, MD, a primary care pediatrician and Medical Director for Health Equity at the Children’s Hospital of Philadelphia. “The information is more accurate in the digital format and it reduces time for the clinician reviewing the data in the exam room.” She also agreed that paperless completion of screen captures better information on more topics, like sleep, nutrition, and mood disorders.
However, Dr. McPeak was one of those who was concerned about form fatigue. Patients have to enter extensive information over multiple screens for each well-child visit. She said this problem might need to be addressed if the success of paperless screening leads to even greater expansion of data requested.
In addressing the work behind creating a system of the depth and scope of the one he described, Dr. Ketterman acknowledged that it involved a daunting development process with substantial coding and testing. Referring to the EMR system used at his hospital, he said the preparation required an “epic guru,” but he said that input fatigue has not yet arisen as a major issue.
“Many of the screens are mandatory, so you cannot advance without completing them, but some are optional,” he noted. “However, we are seeing a high rate of response even on the screens they could click past.”
Dr. Ketterman and Dr. McPeak report no potential conflicts of interest.
TORONTO — , and, of course, it eliminated the work associated with managing paper records.
Due to the efficacy of the pre-visit capture, “all of the information — including individual responses and total scores — is available to the provider at a glance” by the time of the examination encounter, according to Brian T. Ketterman, MD, a third-year resident in pediatrics at the Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee.
Urgent issues, such as suicidality risk, “are flagged so that they are seen first,” he added.
The goal of going paperless was to improve the amount and the consistency of data captured with each well visit, according to Dr. Ketterman. He described a major undertaking involving fundamental changes in the electronic medical record (EMR) system to accommodate the new approach.
Characterizing screening at well visits as “one of the most important jobs of a pediatrician” when he presented these data at the Pediatric Academic Societies annual meeting, he added that a paperless approach comes with many advantages.
Raising the Rate of Complete Data Capture
The American Academy of Pediatrics (AAP) has identified more than 30 screening elements at well-child visits. At his institution several additional screening elements have been added. Prior to going paperless, about 45.6% on average of this well-visit data was being captured in any specific patient encounter, even if the institution was doing well overall in capturing essential information, such as key laboratory values and immunizations.
The vast majority of the information that was missing depended on patient or family input, such as social determinants of health (SDoH), which includes the aspects of home environment, such as nutrition and safety. Dr. Ketterman said that going paperless was inspired by positive experiences reported elsewhere.
“We wanted to build on this work,” he said.
The goal of the program was to raise the rate of complete data capture at well visits to at least 80% and do this across all languages. The first step was to create digital forms in English and Spanish for completion unique to each milestone well-child visit defined by age. For those who speak English or Spanish, these forms were supplied through the patient portal several days before the visit.
For those who spoke one of the more than 40 other languages encountered among patients at Dr. Ketterman’s institution, an interpreter was supplied. If patients arrived at the clinic without completing the digital entry, they completed it on a tablet with the help of an interpreter if one was needed.
Prior to going paperless, all screening data were captured on paper forms completed in the waiting room. The provider then manually reviewed and scored the forms before they were then scanned into the medical records. The paperless approach has eliminated all of these steps and the information is already available for review by the time the pediatrician enters the examination room.
With more than 50,000 well-child checkups captured over a recent 15-month period of paperless questionnaires, the proportion with 100% data capture using what Dr. Ketterman characterized as “strict criteria” was 84%, surpassing the goal at the initiation of the program.
“We improved in almost every screening measure,” Dr. Ketterman said, providing P values that were mostly < .001 for a range of standard tests such as M-CHAT-R (Modified Checklist for Autism in Toddlers), QPA (Quick Parenting Assessment), and PSC-17 (Pediatric Symptom Checklist) when compared to the baseline period.
Additional Advantages
The improvement in well-visit data capture was the goal, but the list of other advantages of the paperless system is long. For one, the EMR system now automatically uses the data to offer guidance that might improve patient outcomes. For example, if the family reports that the child does not see a dentist or does not know how to swim, these lead prompt the EMR to provide resources, such as the names of dentists of swim programs, to address the problem.
As another example, screening questions that reveal food insecurity automatically trigger guidance for enrolling in the U.S. Department of Agriculture’s WIC (Women, Infants, and Children) food program. According to Dr. Ketterman, the proportion of children now enrolled in WIC has increased 10-fold from baseline. He also reported there was a twofold increase in the proportion of patients enrolled in a free book program as a result of a screening questions that ask about reading at home.
The improvement in well-visit data capture was seen across all languages. Even if the gains were not quite as good in languages other than English or Spanish, they were still highly significant relative to baseline.
A ‘Life-Changing’ Improvement
The discussion following his talk made it clear that similar approaches are being actively pursued nationwide. Several in the audience working on similar programs identified such challenges as getting electronic medical record (EMR) systems to cooperate, ensuring patient enrollment in the portals, and avoiding form completion fatigue, but the comments were uniformly supportive of the benefits of this approach.
“This has been life-changing for us,” said Katie E. McPeak, MD, a primary care pediatrician and Medical Director for Health Equity at the Children’s Hospital of Philadelphia. “The information is more accurate in the digital format and it reduces time for the clinician reviewing the data in the exam room.” She also agreed that paperless completion of screen captures better information on more topics, like sleep, nutrition, and mood disorders.
However, Dr. McPeak was one of those who was concerned about form fatigue. Patients have to enter extensive information over multiple screens for each well-child visit. She said this problem might need to be addressed if the success of paperless screening leads to even greater expansion of data requested.
In addressing the work behind creating a system of the depth and scope of the one he described, Dr. Ketterman acknowledged that it involved a daunting development process with substantial coding and testing. Referring to the EMR system used at his hospital, he said the preparation required an “epic guru,” but he said that input fatigue has not yet arisen as a major issue.
“Many of the screens are mandatory, so you cannot advance without completing them, but some are optional,” he noted. “However, we are seeing a high rate of response even on the screens they could click past.”
Dr. Ketterman and Dr. McPeak report no potential conflicts of interest.
TORONTO — , and, of course, it eliminated the work associated with managing paper records.
Due to the efficacy of the pre-visit capture, “all of the information — including individual responses and total scores — is available to the provider at a glance” by the time of the examination encounter, according to Brian T. Ketterman, MD, a third-year resident in pediatrics at the Monroe Carell Jr. Children’s Hospital, Vanderbilt University, Nashville, Tennessee.
Urgent issues, such as suicidality risk, “are flagged so that they are seen first,” he added.
The goal of going paperless was to improve the amount and the consistency of data captured with each well visit, according to Dr. Ketterman. He described a major undertaking involving fundamental changes in the electronic medical record (EMR) system to accommodate the new approach.
Characterizing screening at well visits as “one of the most important jobs of a pediatrician” when he presented these data at the Pediatric Academic Societies annual meeting, he added that a paperless approach comes with many advantages.
Raising the Rate of Complete Data Capture
The American Academy of Pediatrics (AAP) has identified more than 30 screening elements at well-child visits. At his institution several additional screening elements have been added. Prior to going paperless, about 45.6% on average of this well-visit data was being captured in any specific patient encounter, even if the institution was doing well overall in capturing essential information, such as key laboratory values and immunizations.
The vast majority of the information that was missing depended on patient or family input, such as social determinants of health (SDoH), which includes the aspects of home environment, such as nutrition and safety. Dr. Ketterman said that going paperless was inspired by positive experiences reported elsewhere.
“We wanted to build on this work,” he said.
The goal of the program was to raise the rate of complete data capture at well visits to at least 80% and do this across all languages. The first step was to create digital forms in English and Spanish for completion unique to each milestone well-child visit defined by age. For those who speak English or Spanish, these forms were supplied through the patient portal several days before the visit.
For those who spoke one of the more than 40 other languages encountered among patients at Dr. Ketterman’s institution, an interpreter was supplied. If patients arrived at the clinic without completing the digital entry, they completed it on a tablet with the help of an interpreter if one was needed.
Prior to going paperless, all screening data were captured on paper forms completed in the waiting room. The provider then manually reviewed and scored the forms before they were then scanned into the medical records. The paperless approach has eliminated all of these steps and the information is already available for review by the time the pediatrician enters the examination room.
With more than 50,000 well-child checkups captured over a recent 15-month period of paperless questionnaires, the proportion with 100% data capture using what Dr. Ketterman characterized as “strict criteria” was 84%, surpassing the goal at the initiation of the program.
“We improved in almost every screening measure,” Dr. Ketterman said, providing P values that were mostly < .001 for a range of standard tests such as M-CHAT-R (Modified Checklist for Autism in Toddlers), QPA (Quick Parenting Assessment), and PSC-17 (Pediatric Symptom Checklist) when compared to the baseline period.
Additional Advantages
The improvement in well-visit data capture was the goal, but the list of other advantages of the paperless system is long. For one, the EMR system now automatically uses the data to offer guidance that might improve patient outcomes. For example, if the family reports that the child does not see a dentist or does not know how to swim, these lead prompt the EMR to provide resources, such as the names of dentists of swim programs, to address the problem.
As another example, screening questions that reveal food insecurity automatically trigger guidance for enrolling in the U.S. Department of Agriculture’s WIC (Women, Infants, and Children) food program. According to Dr. Ketterman, the proportion of children now enrolled in WIC has increased 10-fold from baseline. He also reported there was a twofold increase in the proportion of patients enrolled in a free book program as a result of a screening questions that ask about reading at home.
The improvement in well-visit data capture was seen across all languages. Even if the gains were not quite as good in languages other than English or Spanish, they were still highly significant relative to baseline.
A ‘Life-Changing’ Improvement
The discussion following his talk made it clear that similar approaches are being actively pursued nationwide. Several in the audience working on similar programs identified such challenges as getting electronic medical record (EMR) systems to cooperate, ensuring patient enrollment in the portals, and avoiding form completion fatigue, but the comments were uniformly supportive of the benefits of this approach.
“This has been life-changing for us,” said Katie E. McPeak, MD, a primary care pediatrician and Medical Director for Health Equity at the Children’s Hospital of Philadelphia. “The information is more accurate in the digital format and it reduces time for the clinician reviewing the data in the exam room.” She also agreed that paperless completion of screen captures better information on more topics, like sleep, nutrition, and mood disorders.
However, Dr. McPeak was one of those who was concerned about form fatigue. Patients have to enter extensive information over multiple screens for each well-child visit. She said this problem might need to be addressed if the success of paperless screening leads to even greater expansion of data requested.
In addressing the work behind creating a system of the depth and scope of the one he described, Dr. Ketterman acknowledged that it involved a daunting development process with substantial coding and testing. Referring to the EMR system used at his hospital, he said the preparation required an “epic guru,” but he said that input fatigue has not yet arisen as a major issue.
“Many of the screens are mandatory, so you cannot advance without completing them, but some are optional,” he noted. “However, we are seeing a high rate of response even on the screens they could click past.”
Dr. Ketterman and Dr. McPeak report no potential conflicts of interest.
FROM PAS 2024
Head and Neck Cancer in Spotlight at AVAHO Regional Meeting
In the US Department of Veterans Affairs (VA) health care system, head and neck cancer is one of the most complex oncologic conditions to treat because so many medical professionals are involved in its care. Specialists in speech therapy, nutrition, lymphedema, and dentistry are all part of the picture.
“It takes a complete team to treat cancer in a comprehensive manner, and specialists work hand-in-hand,” said Cindy Bowman, MSN, RN, OCN, president of the Association of VA Hematology/Oncology (AVAHO).
AVAHO held a regional meeting in Seattle on May 4, 2024, that was entirely devoted to head and neck cancer. “The goal was to help the VA oncology professionals gain a global view of how various team members can seamlessly work together,” said Bowman, an oncology nurse navigator and coordinator of the Cancer Care Navigation Program at Bay Pines VA Healthcare System in the Tampa-St. Petersburg, FL area.
According to a 2017 report, 2031 cases of head and neck cancer were diagnosed in 2010 among VA patients, accounting for 4.4% of all cancers. “Veterans are especially vulnerable to this type of cancer for several reasons, such as high rates of smoking and alcohol use,” Bowman said. In addition, she said veterans who served in parts of Southeast Asia, North Africa, and the Middle East are at higher risk of nasopharyngeal carcinoma, which has been linked to Epstein-Barr virus infections in those regions.
Radiation treatment were a significant topic at the regional meeting, and 1 session was focused on the importance of prompt care. “Head and neck cancers are very aggressive,” Bowman said. “The sooner we identify them, the sooner we get treatment started.”
Attendees also heard from a speech therapist and a dietician, who discussed a collaborative approach to improving treatment outcomes. “These are two very important pieces of the puzzle.” Bowman said.
On the nutrition front, a lot of newly diagnosed patients already have malnutrition because they have been having difficulty swallowing. So right up front, a registered dietician works with them and individualizes their nutrition treatment plans all the way into recovery. Some of these folks will end up with their relationship with their dietitian for many years.
“Speech therapists work with patients to design swallowing and tongue exercises that target their individual cancer.” Bowman said. The goal is to prevent the need for a feeding tube.
Another session at the regional conference focused on lymphedema—swelling that can develop due to radiation treatment. “All patients with head and neck cancer should be sent to a lymphedema specialist prior to starting treatment since the specialists can prevent this from happening by giving the patients tools, such as compression garments,” Bowman said. “This way, we don’t end up with somebody 15 or 20 years from now coming back and saying they’re not able to move their neck or unable to swallow the right way.”
Another session highlighted the important role of dental care for patients with head and neck cancer. “We send patients to the dentist prior to ever starting anything. We know that radiation therapy can cause osteoradionecrosis, in which people’s teeth begin to crumble. Fortunately, the VA is now covering dentures for these patients, and they automatically get dental care coverage.” Bowman said.
“In the big picture,” she said, “Attendees should come out of the regional meeting with new insight into the importance of teamwork in head and neck cancer care. We need to make sure that all the pieces to the puzzle are there, and everybody is working together to expedite care for the veterans so that they have the best outcomes possible.”
In the US Department of Veterans Affairs (VA) health care system, head and neck cancer is one of the most complex oncologic conditions to treat because so many medical professionals are involved in its care. Specialists in speech therapy, nutrition, lymphedema, and dentistry are all part of the picture.
“It takes a complete team to treat cancer in a comprehensive manner, and specialists work hand-in-hand,” said Cindy Bowman, MSN, RN, OCN, president of the Association of VA Hematology/Oncology (AVAHO).
AVAHO held a regional meeting in Seattle on May 4, 2024, that was entirely devoted to head and neck cancer. “The goal was to help the VA oncology professionals gain a global view of how various team members can seamlessly work together,” said Bowman, an oncology nurse navigator and coordinator of the Cancer Care Navigation Program at Bay Pines VA Healthcare System in the Tampa-St. Petersburg, FL area.
According to a 2017 report, 2031 cases of head and neck cancer were diagnosed in 2010 among VA patients, accounting for 4.4% of all cancers. “Veterans are especially vulnerable to this type of cancer for several reasons, such as high rates of smoking and alcohol use,” Bowman said. In addition, she said veterans who served in parts of Southeast Asia, North Africa, and the Middle East are at higher risk of nasopharyngeal carcinoma, which has been linked to Epstein-Barr virus infections in those regions.
Radiation treatment were a significant topic at the regional meeting, and 1 session was focused on the importance of prompt care. “Head and neck cancers are very aggressive,” Bowman said. “The sooner we identify them, the sooner we get treatment started.”
Attendees also heard from a speech therapist and a dietician, who discussed a collaborative approach to improving treatment outcomes. “These are two very important pieces of the puzzle.” Bowman said.
On the nutrition front, a lot of newly diagnosed patients already have malnutrition because they have been having difficulty swallowing. So right up front, a registered dietician works with them and individualizes their nutrition treatment plans all the way into recovery. Some of these folks will end up with their relationship with their dietitian for many years.
“Speech therapists work with patients to design swallowing and tongue exercises that target their individual cancer.” Bowman said. The goal is to prevent the need for a feeding tube.
Another session at the regional conference focused on lymphedema—swelling that can develop due to radiation treatment. “All patients with head and neck cancer should be sent to a lymphedema specialist prior to starting treatment since the specialists can prevent this from happening by giving the patients tools, such as compression garments,” Bowman said. “This way, we don’t end up with somebody 15 or 20 years from now coming back and saying they’re not able to move their neck or unable to swallow the right way.”
Another session highlighted the important role of dental care for patients with head and neck cancer. “We send patients to the dentist prior to ever starting anything. We know that radiation therapy can cause osteoradionecrosis, in which people’s teeth begin to crumble. Fortunately, the VA is now covering dentures for these patients, and they automatically get dental care coverage.” Bowman said.
“In the big picture,” she said, “Attendees should come out of the regional meeting with new insight into the importance of teamwork in head and neck cancer care. We need to make sure that all the pieces to the puzzle are there, and everybody is working together to expedite care for the veterans so that they have the best outcomes possible.”
In the US Department of Veterans Affairs (VA) health care system, head and neck cancer is one of the most complex oncologic conditions to treat because so many medical professionals are involved in its care. Specialists in speech therapy, nutrition, lymphedema, and dentistry are all part of the picture.
“It takes a complete team to treat cancer in a comprehensive manner, and specialists work hand-in-hand,” said Cindy Bowman, MSN, RN, OCN, president of the Association of VA Hematology/Oncology (AVAHO).
AVAHO held a regional meeting in Seattle on May 4, 2024, that was entirely devoted to head and neck cancer. “The goal was to help the VA oncology professionals gain a global view of how various team members can seamlessly work together,” said Bowman, an oncology nurse navigator and coordinator of the Cancer Care Navigation Program at Bay Pines VA Healthcare System in the Tampa-St. Petersburg, FL area.
According to a 2017 report, 2031 cases of head and neck cancer were diagnosed in 2010 among VA patients, accounting for 4.4% of all cancers. “Veterans are especially vulnerable to this type of cancer for several reasons, such as high rates of smoking and alcohol use,” Bowman said. In addition, she said veterans who served in parts of Southeast Asia, North Africa, and the Middle East are at higher risk of nasopharyngeal carcinoma, which has been linked to Epstein-Barr virus infections in those regions.
Radiation treatment were a significant topic at the regional meeting, and 1 session was focused on the importance of prompt care. “Head and neck cancers are very aggressive,” Bowman said. “The sooner we identify them, the sooner we get treatment started.”
Attendees also heard from a speech therapist and a dietician, who discussed a collaborative approach to improving treatment outcomes. “These are two very important pieces of the puzzle.” Bowman said.
On the nutrition front, a lot of newly diagnosed patients already have malnutrition because they have been having difficulty swallowing. So right up front, a registered dietician works with them and individualizes their nutrition treatment plans all the way into recovery. Some of these folks will end up with their relationship with their dietitian for many years.
“Speech therapists work with patients to design swallowing and tongue exercises that target their individual cancer.” Bowman said. The goal is to prevent the need for a feeding tube.
Another session at the regional conference focused on lymphedema—swelling that can develop due to radiation treatment. “All patients with head and neck cancer should be sent to a lymphedema specialist prior to starting treatment since the specialists can prevent this from happening by giving the patients tools, such as compression garments,” Bowman said. “This way, we don’t end up with somebody 15 or 20 years from now coming back and saying they’re not able to move their neck or unable to swallow the right way.”
Another session highlighted the important role of dental care for patients with head and neck cancer. “We send patients to the dentist prior to ever starting anything. We know that radiation therapy can cause osteoradionecrosis, in which people’s teeth begin to crumble. Fortunately, the VA is now covering dentures for these patients, and they automatically get dental care coverage.” Bowman said.
“In the big picture,” she said, “Attendees should come out of the regional meeting with new insight into the importance of teamwork in head and neck cancer care. We need to make sure that all the pieces to the puzzle are there, and everybody is working together to expedite care for the veterans so that they have the best outcomes possible.”