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Monitor Asthma Patients on Biologics for Remission, Potential EGPA Symptoms During Steroid Tapering
VIENNA — , according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.
Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.
Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.
In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
Defining Clinical Remission in Asthma
Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.
To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.
GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.
An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”
He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
Biologics and EGPA
In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.
The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.
The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.
The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — , according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.
Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.
Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.
In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
Defining Clinical Remission in Asthma
Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.
To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.
GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.
An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”
He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
Biologics and EGPA
In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.
The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.
The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.
The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — , according to pulmonary experts presenting at the European Respiratory Society (ERS) 2024 International Congress.
Biologics have revolutionized the treatment of severe asthma, significantly improving patient outcomes. However, the focus has recently shifted toward achieving more comprehensive disease control. Remission, already a well-established goal in conditions like rheumatoid arthritis and inflammatory bowel disease, is now being explored in patients with asthma receiving biologics.
Peter Howarth, medical director at Global Medical, Specialty Medicine, GSK, in Brentford, England, said that new clinical remission criteria in asthma may be overly rigid and of little use. He said that more attainable limits must be created. Meanwhile, clinicians should collect clinical data more thoroughly.
In parallel, studies have also raised questions about the role of biologics in the emergence of EGPA.
Defining Clinical Remission in Asthma
Last year, a working group, including members from the American Thoracic Society and the American College and Academy of Allergy, Asthma, and Immunology, proposed new guidelines to define clinical remission in asthma. These guidelines extended beyond the typical outcomes of no severe exacerbations, no maintenance oral corticosteroid use, good asthma control, and stable lung function. The additional recommendations included no missed work or school due to asthma, limited use of rescue medication (no more than once a month), and reduced inhaled corticosteroid use to low or medium doses.
To explore the feasibility of achieving these clinical remission outcomes, GSK partnered with the Mayo Clinic for a retrospective analysis of the medical records of 700 patients with asthma undergoing various biologic therapies. The study revealed that essential data for determining clinical remission, such as asthma control and exacerbation records, were inconsistently documented. While some data were recorded, such as maintenance corticosteroid use in 50%-60% of cases, other key measures, like asthma control, were recorded in less than a quarter of the patients.
GSK researchers analyzed available data and found that around 30% of patients on any biologic therapy met three components of remission. Mepolizumab performed better than other corticosteroids, with over 40% of those receiving the drug meeting these criteria. However, when stricter definitions were applied, such as requiring four or more remission components, fewer patients achieved remission — less than 10% for four components, with no patients meeting the full seven-point criteria proposed by the working group.
An ongoing ERS Task Force is now exploring what clinical remission outcomes are practical to achieve, as the current definitions may be too aspirational, said Mr. Howarth. “It’s a matter of defying what is practical to achieve because if you can’t achieve it, then it won’t be valuable.”
He also pointed out that biologics are often used for the most severe cases of asthma after other treatments have failed. Evidence suggests that introducing biologics earlier in the disease, before chronic damage occurs, may result in better patient outcomes.
Biologics and EGPA
In a retrospective study, clinical details of 27 patients with adult-onset asthma from 28 countries, all on biologic therapy, were analyzed. The study, a multicounty collaboration, was led by ERS Severe Heterogeneous Asthma Research Collaboration, Patient-centred (SHARP), and aimed to understand the role of biologics in the emergence of EGPA.
The most significant finding presented at the ERS 2024 International Congress was that EGPA was not associated with maintenance corticosteroids; instead, it often emerged when corticosteroid doses were reduced or tapered off. “This might suggest that steroid withdrawal may unmask the underlying disease,” said Hitasha Rupani, MD, a consultant respiratory physician at the University Hospital Southampton, in Southampton, England. Importantly, the rate at which steroids were tapered did not influence the onset of EGPA, indicating that the tapering process, rather than its speed, may be the critical factor. However, due to the small sample size, this remains a hypothesis, Dr. Rupani explained.
The study also found that when clinicians had a clinical suspicion of EGPA before starting biologic therapy, the diagnosis was made earlier than in cases without such suspicion. Dr. Rupani concluded that this underscores the importance of clinical vigilance and the need to monitor patients closely for EGPA symptoms, especially during corticosteroid tapering.
The study was funded by GSK. Mr. Howarth is an employee at GSK. Dr. Rupani reports no relevant financial relationships.
A version of this article appeared on Medscape.com.
Genetic Testing and Novel Biomarkers Important in Cystic Fibrosis Diagnosis and Monitoring
VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.
At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.
Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.
Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
Genetic Testing Picks Up Missed Cases
In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).
Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.
The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.
“The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
Biomarkers for Monitoring Cystic Fibrosis Exacerbations
C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.
Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.
Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).
All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:
- CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
- SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
- NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
- SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
- dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
- In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.
Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.
Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.
At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.
Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.
Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
Genetic Testing Picks Up Missed Cases
In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).
Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.
The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.
“The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
Biomarkers for Monitoring Cystic Fibrosis Exacerbations
C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.
Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.
Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).
All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:
- CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
- SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
- NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
- SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
- dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
- In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.
Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.
Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.
At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.
Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.
Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
Genetic Testing Picks Up Missed Cases
In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).
Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.
The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.
“The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
Biomarkers for Monitoring Cystic Fibrosis Exacerbations
C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.
Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.
Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).
All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:
- CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
- SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
- NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
- SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
- dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
- In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.
Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.
Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Blood Eosinophil Counts Might Predict Childhood Asthma, Treatment Response
VIENNA — Simply relying on clinical symptoms is insufficient to predict which children with wheezing will develop asthma and respond to treatments.
Sejal Saglani, MD, PhD, a professor of pediatric respiratory medicine at the National Heart and Lung Institute, Imperial College, London, England, said that preschool wheezing has long-term adverse consequences through to adulthood. “We need to prevent that downward trajectory of low lung function,” she said, presenting the latest research in the field at the annual European Respiratory Society International Congress.
Wheezing affects up to one third of all infants and preschool children, with one third developing asthma later in life. “It’s important to identify those kids because then we can treat them with the right medication,” said Mariëlle W.H. Pijnenburg, MD, PhD, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands.
“We cannot just use clinical phenotype to decide what treatment a child should get. We need to run tests to identify the endotype of preschool wheeze and intervene appropriately,” Dr. Saglani added.
Eosinophilia as a Biomarker for Predicting Exacerbations and Steroid Responsiveness
In a cluster analysis, Dr. Saglani and colleagues classified preschool children with wheezing into two main subgroups: Those who experience frequent exacerbations and those who experience sporadic attacks. Frequent exacerbators were more likely to develop asthma, use asthma medications, and show signs of reduced lung function and airway inflammation, such as higher fractional exhaled nitric oxide and allergic sensitization. “Severe and frequent exacerbators are the kids that get in trouble,” she said. “They’re the ones we must identify at preschool age and really try to minimize their exacerbations.”
Research has shown that eosinophilia is a valuable biomarker in predicting both asthma exacerbations and responsiveness to inhaled corticosteroids. Children with elevated blood eosinophils are more likely to experience frequent and severe exacerbations. These children often demonstrate an inflammatory profile more responsive to corticosteroids, making eosinophilia a predictor of treatment success. Children with eosinophilia are also more likely to have underlying allergic sensitizations, which further supports the use of corticosteroids as part of their management strategy.
Dr. Saglani said a simple blood test can provide a window into the child’s inflammatory status, allowing physicians to make more targeted and personalized treatment plans.
Traditionally, identifying eosinophilia required venipuncture and laboratory analysis, which can be time consuming and impractical in a busy clinical setting. Dr. Saglani’s research group is developing a point-of-care test designed to quickly and efficiently measure blood eosinophil levels in children with asthma or wheezing symptoms from a finger-prick test. Preliminary data presented at the congress show that children with higher eosinophil counts in the clinic were more likely to experience an asthma attack within 3 months.
“The problem is the majority of the children we see are either not atopic or do not have high blood eosinophils. What are we going to do with those?”
How to Treat Those Who Don’t Have Eosinophilia
Most children with wheezing are not atopic and do not exhibit eosinophilic inflammation, and these children may not respond as effectively to corticosteroids. How to treat them remains the “1-billion-dollar question,” Dr. Saglani said.
Respiratory syncytial virus and rhinovirus play a crucial role in triggering wheezing episodes in these children. Research has shown that viral-induced wheezing is a common feature in this phenotype, and repeated viral infections can lead to an increased severity and frequency of exacerbations. However, there are currently no effective antiviral therapies or vaccines for rhinovirus, which limits the ability to address the viral component of the disease directly.
Up to 50% of children with severe, recurrent wheezing also have bacterial pathogens like Moraxella catarrhalis and Haemophilus influenzae in their lower airways. For these children, addressing the bacterial infection is the best treatment option to mitigate the wheezing. “We now have something that we can target with antibiotics for those who don’t respond to corticosteroids,” Dr. Saglani said.
Dr. Pijnenburg said that this body of research is helping pulmonary specialists and general pediatricians navigate the complexity of childhood wheezing beyond phenotyping and symptoms. “We need to dive more deeply into those kids with preschool wheezing to see what’s happening in their lungs.”
Dr. Pijnenburg and Dr. Saglani reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — Simply relying on clinical symptoms is insufficient to predict which children with wheezing will develop asthma and respond to treatments.
Sejal Saglani, MD, PhD, a professor of pediatric respiratory medicine at the National Heart and Lung Institute, Imperial College, London, England, said that preschool wheezing has long-term adverse consequences through to adulthood. “We need to prevent that downward trajectory of low lung function,” she said, presenting the latest research in the field at the annual European Respiratory Society International Congress.
Wheezing affects up to one third of all infants and preschool children, with one third developing asthma later in life. “It’s important to identify those kids because then we can treat them with the right medication,” said Mariëlle W.H. Pijnenburg, MD, PhD, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands.
“We cannot just use clinical phenotype to decide what treatment a child should get. We need to run tests to identify the endotype of preschool wheeze and intervene appropriately,” Dr. Saglani added.
Eosinophilia as a Biomarker for Predicting Exacerbations and Steroid Responsiveness
In a cluster analysis, Dr. Saglani and colleagues classified preschool children with wheezing into two main subgroups: Those who experience frequent exacerbations and those who experience sporadic attacks. Frequent exacerbators were more likely to develop asthma, use asthma medications, and show signs of reduced lung function and airway inflammation, such as higher fractional exhaled nitric oxide and allergic sensitization. “Severe and frequent exacerbators are the kids that get in trouble,” she said. “They’re the ones we must identify at preschool age and really try to minimize their exacerbations.”
Research has shown that eosinophilia is a valuable biomarker in predicting both asthma exacerbations and responsiveness to inhaled corticosteroids. Children with elevated blood eosinophils are more likely to experience frequent and severe exacerbations. These children often demonstrate an inflammatory profile more responsive to corticosteroids, making eosinophilia a predictor of treatment success. Children with eosinophilia are also more likely to have underlying allergic sensitizations, which further supports the use of corticosteroids as part of their management strategy.
Dr. Saglani said a simple blood test can provide a window into the child’s inflammatory status, allowing physicians to make more targeted and personalized treatment plans.
Traditionally, identifying eosinophilia required venipuncture and laboratory analysis, which can be time consuming and impractical in a busy clinical setting. Dr. Saglani’s research group is developing a point-of-care test designed to quickly and efficiently measure blood eosinophil levels in children with asthma or wheezing symptoms from a finger-prick test. Preliminary data presented at the congress show that children with higher eosinophil counts in the clinic were more likely to experience an asthma attack within 3 months.
“The problem is the majority of the children we see are either not atopic or do not have high blood eosinophils. What are we going to do with those?”
How to Treat Those Who Don’t Have Eosinophilia
Most children with wheezing are not atopic and do not exhibit eosinophilic inflammation, and these children may not respond as effectively to corticosteroids. How to treat them remains the “1-billion-dollar question,” Dr. Saglani said.
Respiratory syncytial virus and rhinovirus play a crucial role in triggering wheezing episodes in these children. Research has shown that viral-induced wheezing is a common feature in this phenotype, and repeated viral infections can lead to an increased severity and frequency of exacerbations. However, there are currently no effective antiviral therapies or vaccines for rhinovirus, which limits the ability to address the viral component of the disease directly.
Up to 50% of children with severe, recurrent wheezing also have bacterial pathogens like Moraxella catarrhalis and Haemophilus influenzae in their lower airways. For these children, addressing the bacterial infection is the best treatment option to mitigate the wheezing. “We now have something that we can target with antibiotics for those who don’t respond to corticosteroids,” Dr. Saglani said.
Dr. Pijnenburg said that this body of research is helping pulmonary specialists and general pediatricians navigate the complexity of childhood wheezing beyond phenotyping and symptoms. “We need to dive more deeply into those kids with preschool wheezing to see what’s happening in their lungs.”
Dr. Pijnenburg and Dr. Saglani reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — Simply relying on clinical symptoms is insufficient to predict which children with wheezing will develop asthma and respond to treatments.
Sejal Saglani, MD, PhD, a professor of pediatric respiratory medicine at the National Heart and Lung Institute, Imperial College, London, England, said that preschool wheezing has long-term adverse consequences through to adulthood. “We need to prevent that downward trajectory of low lung function,” she said, presenting the latest research in the field at the annual European Respiratory Society International Congress.
Wheezing affects up to one third of all infants and preschool children, with one third developing asthma later in life. “It’s important to identify those kids because then we can treat them with the right medication,” said Mariëlle W.H. Pijnenburg, MD, PhD, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands.
“We cannot just use clinical phenotype to decide what treatment a child should get. We need to run tests to identify the endotype of preschool wheeze and intervene appropriately,” Dr. Saglani added.
Eosinophilia as a Biomarker for Predicting Exacerbations and Steroid Responsiveness
In a cluster analysis, Dr. Saglani and colleagues classified preschool children with wheezing into two main subgroups: Those who experience frequent exacerbations and those who experience sporadic attacks. Frequent exacerbators were more likely to develop asthma, use asthma medications, and show signs of reduced lung function and airway inflammation, such as higher fractional exhaled nitric oxide and allergic sensitization. “Severe and frequent exacerbators are the kids that get in trouble,” she said. “They’re the ones we must identify at preschool age and really try to minimize their exacerbations.”
Research has shown that eosinophilia is a valuable biomarker in predicting both asthma exacerbations and responsiveness to inhaled corticosteroids. Children with elevated blood eosinophils are more likely to experience frequent and severe exacerbations. These children often demonstrate an inflammatory profile more responsive to corticosteroids, making eosinophilia a predictor of treatment success. Children with eosinophilia are also more likely to have underlying allergic sensitizations, which further supports the use of corticosteroids as part of their management strategy.
Dr. Saglani said a simple blood test can provide a window into the child’s inflammatory status, allowing physicians to make more targeted and personalized treatment plans.
Traditionally, identifying eosinophilia required venipuncture and laboratory analysis, which can be time consuming and impractical in a busy clinical setting. Dr. Saglani’s research group is developing a point-of-care test designed to quickly and efficiently measure blood eosinophil levels in children with asthma or wheezing symptoms from a finger-prick test. Preliminary data presented at the congress show that children with higher eosinophil counts in the clinic were more likely to experience an asthma attack within 3 months.
“The problem is the majority of the children we see are either not atopic or do not have high blood eosinophils. What are we going to do with those?”
How to Treat Those Who Don’t Have Eosinophilia
Most children with wheezing are not atopic and do not exhibit eosinophilic inflammation, and these children may not respond as effectively to corticosteroids. How to treat them remains the “1-billion-dollar question,” Dr. Saglani said.
Respiratory syncytial virus and rhinovirus play a crucial role in triggering wheezing episodes in these children. Research has shown that viral-induced wheezing is a common feature in this phenotype, and repeated viral infections can lead to an increased severity and frequency of exacerbations. However, there are currently no effective antiviral therapies or vaccines for rhinovirus, which limits the ability to address the viral component of the disease directly.
Up to 50% of children with severe, recurrent wheezing also have bacterial pathogens like Moraxella catarrhalis and Haemophilus influenzae in their lower airways. For these children, addressing the bacterial infection is the best treatment option to mitigate the wheezing. “We now have something that we can target with antibiotics for those who don’t respond to corticosteroids,” Dr. Saglani said.
Dr. Pijnenburg said that this body of research is helping pulmonary specialists and general pediatricians navigate the complexity of childhood wheezing beyond phenotyping and symptoms. “We need to dive more deeply into those kids with preschool wheezing to see what’s happening in their lungs.”
Dr. Pijnenburg and Dr. Saglani reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
AI in Medicine Sparks Excitement, Concerns From Experts
VIENNA — At the European Respiratory Society (ERS) 2024 Congress, experts discussed the benefits and risks of artificial intelligence (AI) in medicine and explored ethical implications and practical challenges.
Joshua Hatherley, PhD, a postdoctoral fellow at the School of Philosophy and History of Ideas at Aarhus University in Denmark, said the traditional bioethical principles — autonomy, beneficence, nonmaleficence, and justice — remain a crucial framework for assessing ethics regarding the use of AI tools in medicine. However, he said the emerging fifth principle of “explainability” has gained attention due to the unique characteristics of AI systems.
“Everyone is excited about AI right now, but there are many open questions about how much we can trust it and to what extent we can use it,” Ana Catalina Hernandez Padilla, a clinical researcher at the Université de Limoges, France, told this news organization.
Joseph Alderman, MBChB, an AI and digital health clinical research fellow at the Institute of Inflammation and Ageing at the University of Birmingham, UK, said these are undoubtedly exciting times to work in AI and health, but he believes clinicians should be “part of the story” and advocate for AI that is safe, effective, and equitable.
The Pros
Dr. Alderman said AI has huge potential to improve healthcare and patients’ experiences.
One interesting area in which AI is being applied is the informed consent process. Conversational AI models, like large language models, can provide patients with a time-unlimited platform to discuss risks, benefits, and recommendations, potentially improving understanding and patient engagement. AI systems can also predict the preferences of noncommunicative patients by analyzing their social media and medical data, which may improve surrogate decision-making and ensure treatment aligns with patient preferences, Dr. Hatherley explained.
Another significant benefit is AI’s capacity to improve patient outcomes through better resource allocation. For example, AI can help optimize the allocation of hospital beds, leading to more efficient use of resources and improved patient health outcomes.
AI systems can reduce medical errors and enhance diagnosis or treatment plans through large-scale data analysis, leading to faster and more accurate decision-making. It can handle administrative tasks, reducing clinician burnout and allowing healthcare professionals to focus more on patient care.
AI also promises to advance health equity by improving access to quality care in underserved areas. In rural hospitals or developing countries, AI can help fill gaps in clinical expertise, potentially leveling the playing field in access to healthcare.
The Cons
Despite its potential, AI in medicine presents several risks that require careful ethical considerations. One primary concern is the possibility of embedded bias in AI systems.
For example, AI-driven advice from an AI agent may prioritize certain outcomes, such as survival, based on broad standards rather than unique patient values, potentially misaligning with the preferences of patients who value quality of life over longevity. “That may interfere with patients’ autonomous decisions,” Dr. Hatherley said.
AI systems also have limited generalizability. Models trained on a specific patient population may perform poorly when applied to different groups due to changes in demographic or clinical characteristics. This can result in less accurate or inappropriate recommendations in real-world settings. “These technologies work on the very narrow population on which the tool was developed but might not necessarily work in the real world,” said Dr. Alderman.
Another significant risk is algorithmic bias, which can worsen health disparities. AI models trained on biased datasets may perpetuate or exacerbate existing inequities in healthcare delivery, leading to suboptimal care for marginalized populations. “We have evidence of algorithms directly discriminating against people with certain characteristics,” Dr. Alderman said.
AI’s Black Box
AI systems, particularly those utilizing deep learning, often function as “black boxes,” meaning their internal decision-making processes are opaque and difficult to interpret. Dr. Hatherley said this lack of transparency raises significant concerns about trust and accountability in clinical decision-making.
While Explainable AI methods have been developed to offer insights into how these systems generate their recommendations, these explanations frequently fail to capture the reasoning process entirely. Dr. Hatherley explained that this is similar to using a pharmaceutical medicine without a clear understanding of the mechanisms for which it works.
This opacity in AI decision-making can lead to mistrust among clinicians and patients, limiting its effective use in healthcare. “We don’t really know how to interpret the information it provides,” Ms. Hernandez said.
She said while younger clinicians might be more open to testing the waters with AI tools, older practitioners still prefer to trust their own senses while looking at a patient as a whole and observing the evolution of their disease. “They are not just ticking boxes. They interpret all these variables together to make a medical decision,” she said.
“I am really optimistic about the future of AI,” Dr. Hatherley concluded. “There are still many challenges to overcome, but, ultimately, it’s not enough to talk about how AI should be adapted to human beings. We also need to talk about how humans should adapt to AI.”
Dr. Hatherley, Dr. Alderman, and Ms. Hernandez have reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — At the European Respiratory Society (ERS) 2024 Congress, experts discussed the benefits and risks of artificial intelligence (AI) in medicine and explored ethical implications and practical challenges.
Joshua Hatherley, PhD, a postdoctoral fellow at the School of Philosophy and History of Ideas at Aarhus University in Denmark, said the traditional bioethical principles — autonomy, beneficence, nonmaleficence, and justice — remain a crucial framework for assessing ethics regarding the use of AI tools in medicine. However, he said the emerging fifth principle of “explainability” has gained attention due to the unique characteristics of AI systems.
“Everyone is excited about AI right now, but there are many open questions about how much we can trust it and to what extent we can use it,” Ana Catalina Hernandez Padilla, a clinical researcher at the Université de Limoges, France, told this news organization.
Joseph Alderman, MBChB, an AI and digital health clinical research fellow at the Institute of Inflammation and Ageing at the University of Birmingham, UK, said these are undoubtedly exciting times to work in AI and health, but he believes clinicians should be “part of the story” and advocate for AI that is safe, effective, and equitable.
The Pros
Dr. Alderman said AI has huge potential to improve healthcare and patients’ experiences.
One interesting area in which AI is being applied is the informed consent process. Conversational AI models, like large language models, can provide patients with a time-unlimited platform to discuss risks, benefits, and recommendations, potentially improving understanding and patient engagement. AI systems can also predict the preferences of noncommunicative patients by analyzing their social media and medical data, which may improve surrogate decision-making and ensure treatment aligns with patient preferences, Dr. Hatherley explained.
Another significant benefit is AI’s capacity to improve patient outcomes through better resource allocation. For example, AI can help optimize the allocation of hospital beds, leading to more efficient use of resources and improved patient health outcomes.
AI systems can reduce medical errors and enhance diagnosis or treatment plans through large-scale data analysis, leading to faster and more accurate decision-making. It can handle administrative tasks, reducing clinician burnout and allowing healthcare professionals to focus more on patient care.
AI also promises to advance health equity by improving access to quality care in underserved areas. In rural hospitals or developing countries, AI can help fill gaps in clinical expertise, potentially leveling the playing field in access to healthcare.
The Cons
Despite its potential, AI in medicine presents several risks that require careful ethical considerations. One primary concern is the possibility of embedded bias in AI systems.
For example, AI-driven advice from an AI agent may prioritize certain outcomes, such as survival, based on broad standards rather than unique patient values, potentially misaligning with the preferences of patients who value quality of life over longevity. “That may interfere with patients’ autonomous decisions,” Dr. Hatherley said.
AI systems also have limited generalizability. Models trained on a specific patient population may perform poorly when applied to different groups due to changes in demographic or clinical characteristics. This can result in less accurate or inappropriate recommendations in real-world settings. “These technologies work on the very narrow population on which the tool was developed but might not necessarily work in the real world,” said Dr. Alderman.
Another significant risk is algorithmic bias, which can worsen health disparities. AI models trained on biased datasets may perpetuate or exacerbate existing inequities in healthcare delivery, leading to suboptimal care for marginalized populations. “We have evidence of algorithms directly discriminating against people with certain characteristics,” Dr. Alderman said.
AI’s Black Box
AI systems, particularly those utilizing deep learning, often function as “black boxes,” meaning their internal decision-making processes are opaque and difficult to interpret. Dr. Hatherley said this lack of transparency raises significant concerns about trust and accountability in clinical decision-making.
While Explainable AI methods have been developed to offer insights into how these systems generate their recommendations, these explanations frequently fail to capture the reasoning process entirely. Dr. Hatherley explained that this is similar to using a pharmaceutical medicine without a clear understanding of the mechanisms for which it works.
This opacity in AI decision-making can lead to mistrust among clinicians and patients, limiting its effective use in healthcare. “We don’t really know how to interpret the information it provides,” Ms. Hernandez said.
She said while younger clinicians might be more open to testing the waters with AI tools, older practitioners still prefer to trust their own senses while looking at a patient as a whole and observing the evolution of their disease. “They are not just ticking boxes. They interpret all these variables together to make a medical decision,” she said.
“I am really optimistic about the future of AI,” Dr. Hatherley concluded. “There are still many challenges to overcome, but, ultimately, it’s not enough to talk about how AI should be adapted to human beings. We also need to talk about how humans should adapt to AI.”
Dr. Hatherley, Dr. Alderman, and Ms. Hernandez have reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — At the European Respiratory Society (ERS) 2024 Congress, experts discussed the benefits and risks of artificial intelligence (AI) in medicine and explored ethical implications and practical challenges.
Joshua Hatherley, PhD, a postdoctoral fellow at the School of Philosophy and History of Ideas at Aarhus University in Denmark, said the traditional bioethical principles — autonomy, beneficence, nonmaleficence, and justice — remain a crucial framework for assessing ethics regarding the use of AI tools in medicine. However, he said the emerging fifth principle of “explainability” has gained attention due to the unique characteristics of AI systems.
“Everyone is excited about AI right now, but there are many open questions about how much we can trust it and to what extent we can use it,” Ana Catalina Hernandez Padilla, a clinical researcher at the Université de Limoges, France, told this news organization.
Joseph Alderman, MBChB, an AI and digital health clinical research fellow at the Institute of Inflammation and Ageing at the University of Birmingham, UK, said these are undoubtedly exciting times to work in AI and health, but he believes clinicians should be “part of the story” and advocate for AI that is safe, effective, and equitable.
The Pros
Dr. Alderman said AI has huge potential to improve healthcare and patients’ experiences.
One interesting area in which AI is being applied is the informed consent process. Conversational AI models, like large language models, can provide patients with a time-unlimited platform to discuss risks, benefits, and recommendations, potentially improving understanding and patient engagement. AI systems can also predict the preferences of noncommunicative patients by analyzing their social media and medical data, which may improve surrogate decision-making and ensure treatment aligns with patient preferences, Dr. Hatherley explained.
Another significant benefit is AI’s capacity to improve patient outcomes through better resource allocation. For example, AI can help optimize the allocation of hospital beds, leading to more efficient use of resources and improved patient health outcomes.
AI systems can reduce medical errors and enhance diagnosis or treatment plans through large-scale data analysis, leading to faster and more accurate decision-making. It can handle administrative tasks, reducing clinician burnout and allowing healthcare professionals to focus more on patient care.
AI also promises to advance health equity by improving access to quality care in underserved areas. In rural hospitals or developing countries, AI can help fill gaps in clinical expertise, potentially leveling the playing field in access to healthcare.
The Cons
Despite its potential, AI in medicine presents several risks that require careful ethical considerations. One primary concern is the possibility of embedded bias in AI systems.
For example, AI-driven advice from an AI agent may prioritize certain outcomes, such as survival, based on broad standards rather than unique patient values, potentially misaligning with the preferences of patients who value quality of life over longevity. “That may interfere with patients’ autonomous decisions,” Dr. Hatherley said.
AI systems also have limited generalizability. Models trained on a specific patient population may perform poorly when applied to different groups due to changes in demographic or clinical characteristics. This can result in less accurate or inappropriate recommendations in real-world settings. “These technologies work on the very narrow population on which the tool was developed but might not necessarily work in the real world,” said Dr. Alderman.
Another significant risk is algorithmic bias, which can worsen health disparities. AI models trained on biased datasets may perpetuate or exacerbate existing inequities in healthcare delivery, leading to suboptimal care for marginalized populations. “We have evidence of algorithms directly discriminating against people with certain characteristics,” Dr. Alderman said.
AI’s Black Box
AI systems, particularly those utilizing deep learning, often function as “black boxes,” meaning their internal decision-making processes are opaque and difficult to interpret. Dr. Hatherley said this lack of transparency raises significant concerns about trust and accountability in clinical decision-making.
While Explainable AI methods have been developed to offer insights into how these systems generate their recommendations, these explanations frequently fail to capture the reasoning process entirely. Dr. Hatherley explained that this is similar to using a pharmaceutical medicine without a clear understanding of the mechanisms for which it works.
This opacity in AI decision-making can lead to mistrust among clinicians and patients, limiting its effective use in healthcare. “We don’t really know how to interpret the information it provides,” Ms. Hernandez said.
She said while younger clinicians might be more open to testing the waters with AI tools, older practitioners still prefer to trust their own senses while looking at a patient as a whole and observing the evolution of their disease. “They are not just ticking boxes. They interpret all these variables together to make a medical decision,” she said.
“I am really optimistic about the future of AI,” Dr. Hatherley concluded. “There are still many challenges to overcome, but, ultimately, it’s not enough to talk about how AI should be adapted to human beings. We also need to talk about how humans should adapt to AI.”
Dr. Hatherley, Dr. Alderman, and Ms. Hernandez have reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Survival Rate in Bilateral Lung and Heart-Lung Transplants Comparable
VIENNA — , said researchers presenting at the European Respiratory Society (ERS) 2024 International Congress.
Transplant for end-stage PAH remains an important treatment option. Heart-lung transplantation plummeted from 91.7% to 21.4% between 1991 and 2014. Yet in the United States and Europe, PAH is the second most common reason to perform a heart-lung transplant, said Baharan Zarrabian, DO, a pulmonologist at the Mayo Clinic in Rochester, Minnesota.
Over the past decades, physicians have debated whether to opt for a bilateral lung or a heart-lung transplant. However, there is currently a lack of definitive cardiac indicators to guide the decision between the two procedures in patients with PAH.
While the lung condition has cardiac ramifications, some experts suggest that the heart can repair itself over time after a bilateral lung transplant.
No Survival Difference Between Bilateral Lung and Heart-Lung Transplants
Researchers compared the outcomes of bilateral lung transplantation with those of combined heart-lung transplantation in patients with PAH. They used data from the Organ Procurement and Transplantation Network, focusing on adult patients with PAH without congenital or structural cardiac abnormalities who underwent transplantation between June 2004 and September 2022.
The study included 918 patients, with the majority (84.6%) receiving bilateral lung transplants and 15.4% receiving heart-lung transplants. Pretransplant mean pulmonary arterial pressure and pulmonary vascular resistance were similar between the two groups. However, those who received bilateral lung transplants had higher cardiac output and lower pulmonary capillary wedge pressure than those who received heart-lung transplants. A higher percentage of heart-lung transplant recipients required extracorporeal membrane oxygenation (ECMO) before transplantation, while bilateral lung transplant recipients had longer median ischemic times.
Despite these differences in pretransplant characteristics and surgical factors, researchers found no significant difference in survival outcomes between the two groups at the 1-year and 5-year marks. Similarly, graft survival rates at 1 and 5 years posttransplant did not differ significantly between the two groups.
A higher proportion of patients who received bilateral lung transplant were on ECMO and remained intubated at 72 hours. “That did not translate into a worse outcome later on,” Dr. Zarrabian said.
Cardiac Recovery Post-Bilateral Lung Transplant
Saskia Bos, MD, PhD, a respiratory consultant, lung transplant physician, and transplant pulmonologist at University Hospitals Leuven, Belgium, who was not involved in the study, told this news organization that doctors have historically preferred combined heart-lung transplantation. The decision was motivated by a lack of understanding regarding whether the heart could remodel on its own. “Now we know that the right ventricle, which is the most affected part of the heart in pulmonary hypertension, has a huge ability to readapt to the new situation after just bilateral lung transplantation,” she said.
Bos suggested that in cases where a patient has pulmonary hypertension without any structural heart defects and where the left side of the heart is functioning normally, doctors can opt for a bilateral lung transplant rather than a combined heart-lung transplant. The right ventricle, typically the only part of the heart affected by the condition, can recover once the pulmonary hypertension is addressed through lung transplantation, she explained.
The advantage of bilateral lung transplantation over a heart-lung transplant is that the donor’s heart remains available for someone else.
“The recommendation is that physicians opt for a bilateral lung transplant,” Dr. Zarrabian concluded. “But we need to make that decision on a case-by-case basis because we still don’t know what are the cardiac parameters that we need to look for before the transplant to decide whether or not they should receive a bilateral lung or a heart-lung.”
Dr. Zarrabian and Dr. Bos reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — , said researchers presenting at the European Respiratory Society (ERS) 2024 International Congress.
Transplant for end-stage PAH remains an important treatment option. Heart-lung transplantation plummeted from 91.7% to 21.4% between 1991 and 2014. Yet in the United States and Europe, PAH is the second most common reason to perform a heart-lung transplant, said Baharan Zarrabian, DO, a pulmonologist at the Mayo Clinic in Rochester, Minnesota.
Over the past decades, physicians have debated whether to opt for a bilateral lung or a heart-lung transplant. However, there is currently a lack of definitive cardiac indicators to guide the decision between the two procedures in patients with PAH.
While the lung condition has cardiac ramifications, some experts suggest that the heart can repair itself over time after a bilateral lung transplant.
No Survival Difference Between Bilateral Lung and Heart-Lung Transplants
Researchers compared the outcomes of bilateral lung transplantation with those of combined heart-lung transplantation in patients with PAH. They used data from the Organ Procurement and Transplantation Network, focusing on adult patients with PAH without congenital or structural cardiac abnormalities who underwent transplantation between June 2004 and September 2022.
The study included 918 patients, with the majority (84.6%) receiving bilateral lung transplants and 15.4% receiving heart-lung transplants. Pretransplant mean pulmonary arterial pressure and pulmonary vascular resistance were similar between the two groups. However, those who received bilateral lung transplants had higher cardiac output and lower pulmonary capillary wedge pressure than those who received heart-lung transplants. A higher percentage of heart-lung transplant recipients required extracorporeal membrane oxygenation (ECMO) before transplantation, while bilateral lung transplant recipients had longer median ischemic times.
Despite these differences in pretransplant characteristics and surgical factors, researchers found no significant difference in survival outcomes between the two groups at the 1-year and 5-year marks. Similarly, graft survival rates at 1 and 5 years posttransplant did not differ significantly between the two groups.
A higher proportion of patients who received bilateral lung transplant were on ECMO and remained intubated at 72 hours. “That did not translate into a worse outcome later on,” Dr. Zarrabian said.
Cardiac Recovery Post-Bilateral Lung Transplant
Saskia Bos, MD, PhD, a respiratory consultant, lung transplant physician, and transplant pulmonologist at University Hospitals Leuven, Belgium, who was not involved in the study, told this news organization that doctors have historically preferred combined heart-lung transplantation. The decision was motivated by a lack of understanding regarding whether the heart could remodel on its own. “Now we know that the right ventricle, which is the most affected part of the heart in pulmonary hypertension, has a huge ability to readapt to the new situation after just bilateral lung transplantation,” she said.
Bos suggested that in cases where a patient has pulmonary hypertension without any structural heart defects and where the left side of the heart is functioning normally, doctors can opt for a bilateral lung transplant rather than a combined heart-lung transplant. The right ventricle, typically the only part of the heart affected by the condition, can recover once the pulmonary hypertension is addressed through lung transplantation, she explained.
The advantage of bilateral lung transplantation over a heart-lung transplant is that the donor’s heart remains available for someone else.
“The recommendation is that physicians opt for a bilateral lung transplant,” Dr. Zarrabian concluded. “But we need to make that decision on a case-by-case basis because we still don’t know what are the cardiac parameters that we need to look for before the transplant to decide whether or not they should receive a bilateral lung or a heart-lung.”
Dr. Zarrabian and Dr. Bos reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — , said researchers presenting at the European Respiratory Society (ERS) 2024 International Congress.
Transplant for end-stage PAH remains an important treatment option. Heart-lung transplantation plummeted from 91.7% to 21.4% between 1991 and 2014. Yet in the United States and Europe, PAH is the second most common reason to perform a heart-lung transplant, said Baharan Zarrabian, DO, a pulmonologist at the Mayo Clinic in Rochester, Minnesota.
Over the past decades, physicians have debated whether to opt for a bilateral lung or a heart-lung transplant. However, there is currently a lack of definitive cardiac indicators to guide the decision between the two procedures in patients with PAH.
While the lung condition has cardiac ramifications, some experts suggest that the heart can repair itself over time after a bilateral lung transplant.
No Survival Difference Between Bilateral Lung and Heart-Lung Transplants
Researchers compared the outcomes of bilateral lung transplantation with those of combined heart-lung transplantation in patients with PAH. They used data from the Organ Procurement and Transplantation Network, focusing on adult patients with PAH without congenital or structural cardiac abnormalities who underwent transplantation between June 2004 and September 2022.
The study included 918 patients, with the majority (84.6%) receiving bilateral lung transplants and 15.4% receiving heart-lung transplants. Pretransplant mean pulmonary arterial pressure and pulmonary vascular resistance were similar between the two groups. However, those who received bilateral lung transplants had higher cardiac output and lower pulmonary capillary wedge pressure than those who received heart-lung transplants. A higher percentage of heart-lung transplant recipients required extracorporeal membrane oxygenation (ECMO) before transplantation, while bilateral lung transplant recipients had longer median ischemic times.
Despite these differences in pretransplant characteristics and surgical factors, researchers found no significant difference in survival outcomes between the two groups at the 1-year and 5-year marks. Similarly, graft survival rates at 1 and 5 years posttransplant did not differ significantly between the two groups.
A higher proportion of patients who received bilateral lung transplant were on ECMO and remained intubated at 72 hours. “That did not translate into a worse outcome later on,” Dr. Zarrabian said.
Cardiac Recovery Post-Bilateral Lung Transplant
Saskia Bos, MD, PhD, a respiratory consultant, lung transplant physician, and transplant pulmonologist at University Hospitals Leuven, Belgium, who was not involved in the study, told this news organization that doctors have historically preferred combined heart-lung transplantation. The decision was motivated by a lack of understanding regarding whether the heart could remodel on its own. “Now we know that the right ventricle, which is the most affected part of the heart in pulmonary hypertension, has a huge ability to readapt to the new situation after just bilateral lung transplantation,” she said.
Bos suggested that in cases where a patient has pulmonary hypertension without any structural heart defects and where the left side of the heart is functioning normally, doctors can opt for a bilateral lung transplant rather than a combined heart-lung transplant. The right ventricle, typically the only part of the heart affected by the condition, can recover once the pulmonary hypertension is addressed through lung transplantation, she explained.
The advantage of bilateral lung transplantation over a heart-lung transplant is that the donor’s heart remains available for someone else.
“The recommendation is that physicians opt for a bilateral lung transplant,” Dr. Zarrabian concluded. “But we need to make that decision on a case-by-case basis because we still don’t know what are the cardiac parameters that we need to look for before the transplant to decide whether or not they should receive a bilateral lung or a heart-lung.”
Dr. Zarrabian and Dr. Bos reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Controversy Surrounds Optimal Treatment for High-Risk Pulmonary Embolism
VIENNA — The optimal course of treatment when managing acute, high-risk pulmonary embolism (PE) remains a contentious topic among respiratory specialists.
Systemic thrombolysis, specifically using recombinant tissue plasminogen activator (rtPA), is the current gold standard treatment for high-risk PE. However, the real-world application is less straightforward due to patient complexities.
Here at the European Respiratory Society (ERS) 2024 Congress, respiratory specialists presented contrasting viewpoints and the latest evidence on each side of the issue to provide a comprehensive framework for navigating the complex decision-making process required for effective treatment.
“High-risk PE is a mechanical problem and thus needs a mechanical solution,” said Parth M. Rali, MD, an associate professor in thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.
“The marketing on some of the mechanical techniques is very impressive,” said Olivier Sanchez, MD, a pulmonologist in the Department of Pneumology and Intensive Care at the Georges Pompidou European Hospital in France. “But what is the evidence of such treatment in the setting of pulmonary embolism?”
The Case Against rtPA as the Standard of Care
High-risk PE typically involves hemodynamically unstable patients presenting with conditions such as low blood pressure, cardiac arrest, or the need for mechanical circulatory support. There is a spectrum of severity within high-risk PE, making it a complex condition to manage, especially since many patients have comorbidities like anemia or active cancer, complicating treatment. “It’s a very dynamic and fluid condition, and we can’t take for granted that rtPA is a standard of care,” Dr. Rali said.
Alternative treatments such as catheter-directed therapies, extracorporeal membrane oxygenation (ECMO), and surgical embolectomy are emerging as promising options, especially for patients who do not respond to or cannot receive rtPA. Mechanical treatments offer benefits in reducing clot burden and stabilizing patients, but they come with their own challenges.
ECMO can stabilize patients who are in shock or cardiac arrest, buying time for the clot to resolve or for further interventions like surgery or catheter-based treatments, said Dr. Rali. However, it is an invasive procedure requiring cannulation of large blood vessels, often involving significant resources and expertise.
Catheter-directed thrombolysis is a minimally invasive technique where a catheter is inserted directly into the pulmonary artery to deliver thrombolytic drugs at lower doses. This method allows for more targeted treatment of the clot, reducing the risk for systemic bleeding that comes with higher doses of thrombolytic agents used in systemic therapy, Dr. Rali explained.
Dr. Rali reported results from the FLAME study, which investigated the effectiveness of FlowTriever mechanical thrombectomy compared with conventional therapies for high-risk PE. This prospective, multicenter observational study enrolled 53 patients in the FlowTriever arm and 61 in the context arm, which included patients treated with systemic thrombolysis or anticoagulation. The primary endpoint, a composite of adverse in-hospital outcomes, was reached in 17% of FlowTriever patients, significantly lower than the 32% performance goal and the 63.9% rate in the context arm. In-hospital mortality was dramatically lower in the FlowTriever arm (1.9%) compared to the context arm (29.5%).
When catheter-based treatment fails, surgical pulmonary embolectomy is a last-resort option. “Only a minority of the high-risk PE [patients] would qualify for rtPA without harmful side effects,” Dr. Rali concluded. “So think wise before you pull your trigger.”
rtPA Not a Matter of the Past
In high-risk PE, the therapeutic priority is rapid hemodynamic stabilization and restoration of pulmonary blood flow to prevent cardiovascular collapse. Systemic thrombolysis acts quickly, reducing pulmonary vascular resistance and obstruction within hours, said Dr. Sanchez.
Presenting at the ERS Congress, he reported numerous studies, including 15 randomized controlled trials that demonstrated its effectiveness in high-risk PE. The PEITHO trial, in particular, demonstrated the ability of systemic thrombolysis to reduce all-cause mortality and hemodynamic collapse within 7 days.
However, this benefit comes at the cost of increased bleeding risk, including a 10% rate of major bleeding and a 2% risk for intracranial hemorrhage. “These data come from old studies using invasive diagnostic procedures, and with current diagnostic procedures, the rate of bleeding is probably lower,” Dr. Sanchez said. The risk of bleeding is also related to the type of thrombolytic agent, with tenecteplase being strongly associated with a higher risk of bleeding, while alteplase shows no increase in the risk of major bleeding, he added. New strategies like reduced-dose thrombolysis offer comparable efficacy and improved safety, as demonstrated in ongoing trials like PEITHO-3, which aim to optimize the balance between efficacy and bleeding risk. Dr. Sanchez is the lead investigator of the PEITHO-3 study.
While rtPA might not be optimal for all patients, Dr. Sanchez thinks there is not enough evidence to replace it as a first-line treatment.
Existing studies on catheter-directed therapies often focus on surrogate endpoints, such as right-to-left ventricular ratio changes, rather than clinical outcomes like mortality, he said. Retrospective data suggest that catheter-directed therapies may reduce in-hospital mortality compared with systemic therapies, but they also increase the risk of intracranial bleeding, post-procedure complications, and device-related events.
Sanchez mentioned the same FLAME study described by Dr. Rali, which reported a 23% rate of device-related complications and 11% major bleeding in patients treated with catheter-directed therapies.
“Systemic thrombolysis remains the first treatment of choice,” Dr. Sanchez concluded. “The use of catheter-directed treatment should be discussed as an alternative in case of contraindications.”
The Debate Continues
Numerous ongoing clinical studies, such as the FLARE trial, will address gaps in evidence and refine treatment protocols, potentially reshaping the standard of care in high-risk PE in the near future by providing new data on the efficacy and safety of existing and emerging therapies.
“The coming data will make it clearer what the best option is,” said Thamer Al Khouzaie, MD, a pulmonary medicine consultant at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia. For now, he said, systemic thrombolysis remains the best option for most patients because it is widely available, easily administered with intravenous infusion, and at a limited cost. Catheter-directed treatment and surgical options are only available in specialized centers, require expertise and training, and are also very expensive.
Dr. Rali, Dr. Sanchez, and Dr. Khouzaie report no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — The optimal course of treatment when managing acute, high-risk pulmonary embolism (PE) remains a contentious topic among respiratory specialists.
Systemic thrombolysis, specifically using recombinant tissue plasminogen activator (rtPA), is the current gold standard treatment for high-risk PE. However, the real-world application is less straightforward due to patient complexities.
Here at the European Respiratory Society (ERS) 2024 Congress, respiratory specialists presented contrasting viewpoints and the latest evidence on each side of the issue to provide a comprehensive framework for navigating the complex decision-making process required for effective treatment.
“High-risk PE is a mechanical problem and thus needs a mechanical solution,” said Parth M. Rali, MD, an associate professor in thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.
“The marketing on some of the mechanical techniques is very impressive,” said Olivier Sanchez, MD, a pulmonologist in the Department of Pneumology and Intensive Care at the Georges Pompidou European Hospital in France. “But what is the evidence of such treatment in the setting of pulmonary embolism?”
The Case Against rtPA as the Standard of Care
High-risk PE typically involves hemodynamically unstable patients presenting with conditions such as low blood pressure, cardiac arrest, or the need for mechanical circulatory support. There is a spectrum of severity within high-risk PE, making it a complex condition to manage, especially since many patients have comorbidities like anemia or active cancer, complicating treatment. “It’s a very dynamic and fluid condition, and we can’t take for granted that rtPA is a standard of care,” Dr. Rali said.
Alternative treatments such as catheter-directed therapies, extracorporeal membrane oxygenation (ECMO), and surgical embolectomy are emerging as promising options, especially for patients who do not respond to or cannot receive rtPA. Mechanical treatments offer benefits in reducing clot burden and stabilizing patients, but they come with their own challenges.
ECMO can stabilize patients who are in shock or cardiac arrest, buying time for the clot to resolve or for further interventions like surgery or catheter-based treatments, said Dr. Rali. However, it is an invasive procedure requiring cannulation of large blood vessels, often involving significant resources and expertise.
Catheter-directed thrombolysis is a minimally invasive technique where a catheter is inserted directly into the pulmonary artery to deliver thrombolytic drugs at lower doses. This method allows for more targeted treatment of the clot, reducing the risk for systemic bleeding that comes with higher doses of thrombolytic agents used in systemic therapy, Dr. Rali explained.
Dr. Rali reported results from the FLAME study, which investigated the effectiveness of FlowTriever mechanical thrombectomy compared with conventional therapies for high-risk PE. This prospective, multicenter observational study enrolled 53 patients in the FlowTriever arm and 61 in the context arm, which included patients treated with systemic thrombolysis or anticoagulation. The primary endpoint, a composite of adverse in-hospital outcomes, was reached in 17% of FlowTriever patients, significantly lower than the 32% performance goal and the 63.9% rate in the context arm. In-hospital mortality was dramatically lower in the FlowTriever arm (1.9%) compared to the context arm (29.5%).
When catheter-based treatment fails, surgical pulmonary embolectomy is a last-resort option. “Only a minority of the high-risk PE [patients] would qualify for rtPA without harmful side effects,” Dr. Rali concluded. “So think wise before you pull your trigger.”
rtPA Not a Matter of the Past
In high-risk PE, the therapeutic priority is rapid hemodynamic stabilization and restoration of pulmonary blood flow to prevent cardiovascular collapse. Systemic thrombolysis acts quickly, reducing pulmonary vascular resistance and obstruction within hours, said Dr. Sanchez.
Presenting at the ERS Congress, he reported numerous studies, including 15 randomized controlled trials that demonstrated its effectiveness in high-risk PE. The PEITHO trial, in particular, demonstrated the ability of systemic thrombolysis to reduce all-cause mortality and hemodynamic collapse within 7 days.
However, this benefit comes at the cost of increased bleeding risk, including a 10% rate of major bleeding and a 2% risk for intracranial hemorrhage. “These data come from old studies using invasive diagnostic procedures, and with current diagnostic procedures, the rate of bleeding is probably lower,” Dr. Sanchez said. The risk of bleeding is also related to the type of thrombolytic agent, with tenecteplase being strongly associated with a higher risk of bleeding, while alteplase shows no increase in the risk of major bleeding, he added. New strategies like reduced-dose thrombolysis offer comparable efficacy and improved safety, as demonstrated in ongoing trials like PEITHO-3, which aim to optimize the balance between efficacy and bleeding risk. Dr. Sanchez is the lead investigator of the PEITHO-3 study.
While rtPA might not be optimal for all patients, Dr. Sanchez thinks there is not enough evidence to replace it as a first-line treatment.
Existing studies on catheter-directed therapies often focus on surrogate endpoints, such as right-to-left ventricular ratio changes, rather than clinical outcomes like mortality, he said. Retrospective data suggest that catheter-directed therapies may reduce in-hospital mortality compared with systemic therapies, but they also increase the risk of intracranial bleeding, post-procedure complications, and device-related events.
Sanchez mentioned the same FLAME study described by Dr. Rali, which reported a 23% rate of device-related complications and 11% major bleeding in patients treated with catheter-directed therapies.
“Systemic thrombolysis remains the first treatment of choice,” Dr. Sanchez concluded. “The use of catheter-directed treatment should be discussed as an alternative in case of contraindications.”
The Debate Continues
Numerous ongoing clinical studies, such as the FLARE trial, will address gaps in evidence and refine treatment protocols, potentially reshaping the standard of care in high-risk PE in the near future by providing new data on the efficacy and safety of existing and emerging therapies.
“The coming data will make it clearer what the best option is,” said Thamer Al Khouzaie, MD, a pulmonary medicine consultant at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia. For now, he said, systemic thrombolysis remains the best option for most patients because it is widely available, easily administered with intravenous infusion, and at a limited cost. Catheter-directed treatment and surgical options are only available in specialized centers, require expertise and training, and are also very expensive.
Dr. Rali, Dr. Sanchez, and Dr. Khouzaie report no relevant financial relationships.
A version of this article appeared on Medscape.com.
VIENNA — The optimal course of treatment when managing acute, high-risk pulmonary embolism (PE) remains a contentious topic among respiratory specialists.
Systemic thrombolysis, specifically using recombinant tissue plasminogen activator (rtPA), is the current gold standard treatment for high-risk PE. However, the real-world application is less straightforward due to patient complexities.
Here at the European Respiratory Society (ERS) 2024 Congress, respiratory specialists presented contrasting viewpoints and the latest evidence on each side of the issue to provide a comprehensive framework for navigating the complex decision-making process required for effective treatment.
“High-risk PE is a mechanical problem and thus needs a mechanical solution,” said Parth M. Rali, MD, an associate professor in thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.
“The marketing on some of the mechanical techniques is very impressive,” said Olivier Sanchez, MD, a pulmonologist in the Department of Pneumology and Intensive Care at the Georges Pompidou European Hospital in France. “But what is the evidence of such treatment in the setting of pulmonary embolism?”
The Case Against rtPA as the Standard of Care
High-risk PE typically involves hemodynamically unstable patients presenting with conditions such as low blood pressure, cardiac arrest, or the need for mechanical circulatory support. There is a spectrum of severity within high-risk PE, making it a complex condition to manage, especially since many patients have comorbidities like anemia or active cancer, complicating treatment. “It’s a very dynamic and fluid condition, and we can’t take for granted that rtPA is a standard of care,” Dr. Rali said.
Alternative treatments such as catheter-directed therapies, extracorporeal membrane oxygenation (ECMO), and surgical embolectomy are emerging as promising options, especially for patients who do not respond to or cannot receive rtPA. Mechanical treatments offer benefits in reducing clot burden and stabilizing patients, but they come with their own challenges.
ECMO can stabilize patients who are in shock or cardiac arrest, buying time for the clot to resolve or for further interventions like surgery or catheter-based treatments, said Dr. Rali. However, it is an invasive procedure requiring cannulation of large blood vessels, often involving significant resources and expertise.
Catheter-directed thrombolysis is a minimally invasive technique where a catheter is inserted directly into the pulmonary artery to deliver thrombolytic drugs at lower doses. This method allows for more targeted treatment of the clot, reducing the risk for systemic bleeding that comes with higher doses of thrombolytic agents used in systemic therapy, Dr. Rali explained.
Dr. Rali reported results from the FLAME study, which investigated the effectiveness of FlowTriever mechanical thrombectomy compared with conventional therapies for high-risk PE. This prospective, multicenter observational study enrolled 53 patients in the FlowTriever arm and 61 in the context arm, which included patients treated with systemic thrombolysis or anticoagulation. The primary endpoint, a composite of adverse in-hospital outcomes, was reached in 17% of FlowTriever patients, significantly lower than the 32% performance goal and the 63.9% rate in the context arm. In-hospital mortality was dramatically lower in the FlowTriever arm (1.9%) compared to the context arm (29.5%).
When catheter-based treatment fails, surgical pulmonary embolectomy is a last-resort option. “Only a minority of the high-risk PE [patients] would qualify for rtPA without harmful side effects,” Dr. Rali concluded. “So think wise before you pull your trigger.”
rtPA Not a Matter of the Past
In high-risk PE, the therapeutic priority is rapid hemodynamic stabilization and restoration of pulmonary blood flow to prevent cardiovascular collapse. Systemic thrombolysis acts quickly, reducing pulmonary vascular resistance and obstruction within hours, said Dr. Sanchez.
Presenting at the ERS Congress, he reported numerous studies, including 15 randomized controlled trials that demonstrated its effectiveness in high-risk PE. The PEITHO trial, in particular, demonstrated the ability of systemic thrombolysis to reduce all-cause mortality and hemodynamic collapse within 7 days.
However, this benefit comes at the cost of increased bleeding risk, including a 10% rate of major bleeding and a 2% risk for intracranial hemorrhage. “These data come from old studies using invasive diagnostic procedures, and with current diagnostic procedures, the rate of bleeding is probably lower,” Dr. Sanchez said. The risk of bleeding is also related to the type of thrombolytic agent, with tenecteplase being strongly associated with a higher risk of bleeding, while alteplase shows no increase in the risk of major bleeding, he added. New strategies like reduced-dose thrombolysis offer comparable efficacy and improved safety, as demonstrated in ongoing trials like PEITHO-3, which aim to optimize the balance between efficacy and bleeding risk. Dr. Sanchez is the lead investigator of the PEITHO-3 study.
While rtPA might not be optimal for all patients, Dr. Sanchez thinks there is not enough evidence to replace it as a first-line treatment.
Existing studies on catheter-directed therapies often focus on surrogate endpoints, such as right-to-left ventricular ratio changes, rather than clinical outcomes like mortality, he said. Retrospective data suggest that catheter-directed therapies may reduce in-hospital mortality compared with systemic therapies, but they also increase the risk of intracranial bleeding, post-procedure complications, and device-related events.
Sanchez mentioned the same FLAME study described by Dr. Rali, which reported a 23% rate of device-related complications and 11% major bleeding in patients treated with catheter-directed therapies.
“Systemic thrombolysis remains the first treatment of choice,” Dr. Sanchez concluded. “The use of catheter-directed treatment should be discussed as an alternative in case of contraindications.”
The Debate Continues
Numerous ongoing clinical studies, such as the FLARE trial, will address gaps in evidence and refine treatment protocols, potentially reshaping the standard of care in high-risk PE in the near future by providing new data on the efficacy and safety of existing and emerging therapies.
“The coming data will make it clearer what the best option is,” said Thamer Al Khouzaie, MD, a pulmonary medicine consultant at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia. For now, he said, systemic thrombolysis remains the best option for most patients because it is widely available, easily administered with intravenous infusion, and at a limited cost. Catheter-directed treatment and surgical options are only available in specialized centers, require expertise and training, and are also very expensive.
Dr. Rali, Dr. Sanchez, and Dr. Khouzaie report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Research Promises Better Diabetic Retinopathy Management
STOCKHOLM — At the American Society of Retina Specialists (ASRS) 2024 Annual Meeting, researchers discussed how insights into potential risk factors and new treatments could improve outcomes for patients with diabetic retinopathy.
Jennifer Lim, MD, an ophthalmologist and director of the Retina Service at the University of Illinois Hospital & Health Sciences System in Chicago, told this news organization that emerging approaches to treating diabetic retinopathy offer hope because they address the root causes of the disease beyond just targeting vascular endothelial growth factor (VEGF). She said innovative methods and add-on treatments could lead to more durable and effective drugs.
Exploration of risk factors and treatment options for diabetic retinopathy could lead to more effective management strategies for the condition, agreed David Boyer, MD, an ophthalmologist at Retina Vitreous Associates Medical Group in Los Angeles, speaking with this news organization.
Risk Factors for Diabetic Retinopathy
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have gained popularity because of their benefits beyond glycemic control, including weight loss, and cardiovascular and kidney protection. However, the impact of these medications on vision-threatening retinal complications is not fully understood. “There has always been a question about whether these newer diabetes medications might exacerbate diabetic eye disease,” said Dr. Boyer.
In a retrospective observational study, researchers included adults with type 2 diabetes and moderate cardiovascular disease risk who had no history of advanced diabetic retinal complications. These patients initiated treatment with GLP-1 RA, SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas. The study used inverse probability of treatment weighting to mimic randomization and compared the time to the first treatment for diabetic macular edema or proliferative diabetic retinopathy across the treatment groups.
Results, presented by Andrew J. Barkmeier, MD, an associate professor of ophthalmology at the Mayo Clinic, showed that among 371,698 patients, those who initiated therapy with SGLT2 inhibitors had a lower risk of requiring treatment for sight-threatening retinopathy compared with those using other medication classes. GLP-1 RA did not increase retinopathy risk relative to dipeptidyl peptidase 4 inhibitors and sulfonylurea medications.
“[This study] told us that we do have to keep an eye on patients’ retinopathy when they start on these new inhibitors. But the progression is minimal and, overall, I think most people today favor keeping blood sugar levels as good as possible,” said Dr. Boyer, who was not involved in the study.
Another factor that might increase diabetic retinopathy progression is obstructive sleep apnea. This underdiagnosed condition is linked to several health issues, including dementia, stroke, and myocardial infarctions. Although not easily treated, obstructive sleep apnea is manageable, Dr. Boyer explained.
Researchers utilized the TriNetX electronic health records research network to identify patients with nonproliferative diabetic retinopathy, both with and without obstructive sleep apnea.
The results, presented by Ehsan Rahimy, MD, a retinal specialist at Palo Alto Medical Foundation and a professor at Stanford University, showed that patients with obstructive sleep apnea had a significantly higher risk of progressing to proliferative diabetic retinopathy and developing new-onset diabetic macular edema. These patients were more likely to require ocular interventions, such as intravitreal injections and laser photocoagulation. They also had greater risks for stroke, myocardial infarction, and death compared with those who did not have obstructive sleep apnea.
“It was good to bring this to everybody’s attention,” said Dr. Boyer, who was not involved in the study. “It’s an easy question to ask someone if they snore.”
New Treatments on the Horizon
In another presentation, Nathan C. Steinle, MD, of California Retina Consultants, presented a study that assessed the durability of response to sozinibercept in patients with retinal vascular diseases. This novel therapeutic agent is designed to inhibit VEGF-C and VEGF-D in conditions where VEGF-A suppression alone is insufficient.
Sozinibercept was combined with standard anti–VEGF-A therapies such as ranibizumab or aflibercept. It involved a prospective, post hoc analysis of two phase 1b, open-label, dose-escalation studies, including 40 patients with neovascular age-related macular degeneration (nAMD; 31 patients) or diabetic macular edema (nine patients). These patients, either treatment-naive or previously treated, received three intravitreal injections of ranibizumab or aflibercept in combination with sozinibercept at various doses.
Results indicated that sozinibercept combination therapy was well tolerated, with no dose-limiting toxicities. In treatment-naive nAMD patients, the mean best-corrected visual acuity (BCVA) improved significantly from baseline at months 3 and 6. Previously treated nAMD patients also showed BCVA improvements, although to a lesser extent. For patients with persistent diabetic macular edema, switching to sozinibercept plus aflibercept resulted in notable BCVA gains. The mean time to requiring retreatment was longer in treatment-naive patients than in those previously treated, indicating a durable response.
“Combination therapy with sozinibercept is going to be really important,” said Dr. Lim, who was not involved in the study, “because it attacks with a dual mechanism of action.”
Oral agents promise a potentially easier alternative for patients compared with frequent injections. CU06-1004 is a novel orally administered endothelial dysfunction blocker that has shown promise in stabilizing damaged capillaries, reducing abnormal angiogenesis, and inhibiting inflammatory activation in preclinical studies. “CU06 is very interesting to me because by preventing endothelial loss, it gets to the pathophysiology of why the blood vessels break down,” Dr. Lim said.
In a proof-of-concept phase 2a, multicenter, open-label, parallel-group trial, investigators randomly assigned 67 patients with diabetic macular edema to receive 100 mg, 200 mg, or 300 mg of CU06-1004 once daily for 12 weeks, followed by a 4-week follow-up.
Results presented by Victor Gonzalez, MD, of Valley Retina Institute in Texas, indicated that the oral agent improved BCVA, stabilized central subfield thickness, and showed positive anatomical changes in optical coherence tomography images. CU06-1004 was well tolerated, with no drug-related serious adverse events.
“The number [of patients] was very small, and we will need a much longer, larger trial to see if [CU06-1004] has benefits long term,” said Dr. Boyer, who was not involved in the study. “But I think we’re all very excited if we can find an oral agent for treating diabetic retinopathy. It would be easier for the patient to take a pill than having to come in for injections.”
The sustained-release axitinib implant, OTX-TKI, is also generating significant interest, particularly for nonproliferative diabetic retinopathy. Axitinib, a tyrosine kinase inhibitor (TKI), targets signaling pathways crucial in cellular processes, providing a novel approach to managing diseases where traditional therapies might fall short. Unlike traditional anti-VEGF treatments that focus solely on cytokine levels, TKIs block the activation of signaling pathways, preventing downstream signaling regardless of cytokine levels. This mechanism is particularly important because it effectively inhibits disease progression even if levels of VEGF are high, Dr. Lim explained.
In the phase 1 HELIOS trial, OTX-TKI was assessed in patients with nonproliferative diabetic retinopathy. This multicenter, double-masked, parallel-group clinical study included 21 patients who had not received anti-VEGF treatment, dexamethasone intravitreal implants in the previous 12 months, or intraocular steroid injections in the prior 4 months. Patients were randomly assigned to receive either OTX-TKI or sham treatment.
Results presented by Dilsher S. Dhoot, MD, of California Retina Consultants, indicated that OTX-TKI was generally well tolerated, with no serious ocular adverse events. At 48 weeks, 46.2% of eyes treated with OTX-TKI showed a 1- or 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) compared with none in the sham arm. Additionally, no eyes treated with OTX-TKI experienced a worsening on the DRSS, whereas 25% of eyes in the sham arm did. Vision-threatening complications, such as proliferative diabetic retinopathy or diabetic macular edema, developed in 37.5% of the sham group but in none of the OTX-TKI treated eyes. A single injection of OTX-TKI provided durable DRSS improvement for up to 48 weeks, with no patients in either arm requiring rescue therapy.
“This is a really exciting add-on treatment,” Dr. Lim said, who was not involved in the study. She explained that it is initially necessary to control the disease with standard treatments, because TKIs may take longer to exhibit their effects. Once the disease is stabilized, TKIs can be used alongside other therapies, potentially reducing the reliance on frequent anti-VEGF injections. “These are preliminary results, but that’s the hope going forward.”
Dr. Lim and Dr. Boyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM — At the American Society of Retina Specialists (ASRS) 2024 Annual Meeting, researchers discussed how insights into potential risk factors and new treatments could improve outcomes for patients with diabetic retinopathy.
Jennifer Lim, MD, an ophthalmologist and director of the Retina Service at the University of Illinois Hospital & Health Sciences System in Chicago, told this news organization that emerging approaches to treating diabetic retinopathy offer hope because they address the root causes of the disease beyond just targeting vascular endothelial growth factor (VEGF). She said innovative methods and add-on treatments could lead to more durable and effective drugs.
Exploration of risk factors and treatment options for diabetic retinopathy could lead to more effective management strategies for the condition, agreed David Boyer, MD, an ophthalmologist at Retina Vitreous Associates Medical Group in Los Angeles, speaking with this news organization.
Risk Factors for Diabetic Retinopathy
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have gained popularity because of their benefits beyond glycemic control, including weight loss, and cardiovascular and kidney protection. However, the impact of these medications on vision-threatening retinal complications is not fully understood. “There has always been a question about whether these newer diabetes medications might exacerbate diabetic eye disease,” said Dr. Boyer.
In a retrospective observational study, researchers included adults with type 2 diabetes and moderate cardiovascular disease risk who had no history of advanced diabetic retinal complications. These patients initiated treatment with GLP-1 RA, SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas. The study used inverse probability of treatment weighting to mimic randomization and compared the time to the first treatment for diabetic macular edema or proliferative diabetic retinopathy across the treatment groups.
Results, presented by Andrew J. Barkmeier, MD, an associate professor of ophthalmology at the Mayo Clinic, showed that among 371,698 patients, those who initiated therapy with SGLT2 inhibitors had a lower risk of requiring treatment for sight-threatening retinopathy compared with those using other medication classes. GLP-1 RA did not increase retinopathy risk relative to dipeptidyl peptidase 4 inhibitors and sulfonylurea medications.
“[This study] told us that we do have to keep an eye on patients’ retinopathy when they start on these new inhibitors. But the progression is minimal and, overall, I think most people today favor keeping blood sugar levels as good as possible,” said Dr. Boyer, who was not involved in the study.
Another factor that might increase diabetic retinopathy progression is obstructive sleep apnea. This underdiagnosed condition is linked to several health issues, including dementia, stroke, and myocardial infarctions. Although not easily treated, obstructive sleep apnea is manageable, Dr. Boyer explained.
Researchers utilized the TriNetX electronic health records research network to identify patients with nonproliferative diabetic retinopathy, both with and without obstructive sleep apnea.
The results, presented by Ehsan Rahimy, MD, a retinal specialist at Palo Alto Medical Foundation and a professor at Stanford University, showed that patients with obstructive sleep apnea had a significantly higher risk of progressing to proliferative diabetic retinopathy and developing new-onset diabetic macular edema. These patients were more likely to require ocular interventions, such as intravitreal injections and laser photocoagulation. They also had greater risks for stroke, myocardial infarction, and death compared with those who did not have obstructive sleep apnea.
“It was good to bring this to everybody’s attention,” said Dr. Boyer, who was not involved in the study. “It’s an easy question to ask someone if they snore.”
New Treatments on the Horizon
In another presentation, Nathan C. Steinle, MD, of California Retina Consultants, presented a study that assessed the durability of response to sozinibercept in patients with retinal vascular diseases. This novel therapeutic agent is designed to inhibit VEGF-C and VEGF-D in conditions where VEGF-A suppression alone is insufficient.
Sozinibercept was combined with standard anti–VEGF-A therapies such as ranibizumab or aflibercept. It involved a prospective, post hoc analysis of two phase 1b, open-label, dose-escalation studies, including 40 patients with neovascular age-related macular degeneration (nAMD; 31 patients) or diabetic macular edema (nine patients). These patients, either treatment-naive or previously treated, received three intravitreal injections of ranibizumab or aflibercept in combination with sozinibercept at various doses.
Results indicated that sozinibercept combination therapy was well tolerated, with no dose-limiting toxicities. In treatment-naive nAMD patients, the mean best-corrected visual acuity (BCVA) improved significantly from baseline at months 3 and 6. Previously treated nAMD patients also showed BCVA improvements, although to a lesser extent. For patients with persistent diabetic macular edema, switching to sozinibercept plus aflibercept resulted in notable BCVA gains. The mean time to requiring retreatment was longer in treatment-naive patients than in those previously treated, indicating a durable response.
“Combination therapy with sozinibercept is going to be really important,” said Dr. Lim, who was not involved in the study, “because it attacks with a dual mechanism of action.”
Oral agents promise a potentially easier alternative for patients compared with frequent injections. CU06-1004 is a novel orally administered endothelial dysfunction blocker that has shown promise in stabilizing damaged capillaries, reducing abnormal angiogenesis, and inhibiting inflammatory activation in preclinical studies. “CU06 is very interesting to me because by preventing endothelial loss, it gets to the pathophysiology of why the blood vessels break down,” Dr. Lim said.
In a proof-of-concept phase 2a, multicenter, open-label, parallel-group trial, investigators randomly assigned 67 patients with diabetic macular edema to receive 100 mg, 200 mg, or 300 mg of CU06-1004 once daily for 12 weeks, followed by a 4-week follow-up.
Results presented by Victor Gonzalez, MD, of Valley Retina Institute in Texas, indicated that the oral agent improved BCVA, stabilized central subfield thickness, and showed positive anatomical changes in optical coherence tomography images. CU06-1004 was well tolerated, with no drug-related serious adverse events.
“The number [of patients] was very small, and we will need a much longer, larger trial to see if [CU06-1004] has benefits long term,” said Dr. Boyer, who was not involved in the study. “But I think we’re all very excited if we can find an oral agent for treating diabetic retinopathy. It would be easier for the patient to take a pill than having to come in for injections.”
The sustained-release axitinib implant, OTX-TKI, is also generating significant interest, particularly for nonproliferative diabetic retinopathy. Axitinib, a tyrosine kinase inhibitor (TKI), targets signaling pathways crucial in cellular processes, providing a novel approach to managing diseases where traditional therapies might fall short. Unlike traditional anti-VEGF treatments that focus solely on cytokine levels, TKIs block the activation of signaling pathways, preventing downstream signaling regardless of cytokine levels. This mechanism is particularly important because it effectively inhibits disease progression even if levels of VEGF are high, Dr. Lim explained.
In the phase 1 HELIOS trial, OTX-TKI was assessed in patients with nonproliferative diabetic retinopathy. This multicenter, double-masked, parallel-group clinical study included 21 patients who had not received anti-VEGF treatment, dexamethasone intravitreal implants in the previous 12 months, or intraocular steroid injections in the prior 4 months. Patients were randomly assigned to receive either OTX-TKI or sham treatment.
Results presented by Dilsher S. Dhoot, MD, of California Retina Consultants, indicated that OTX-TKI was generally well tolerated, with no serious ocular adverse events. At 48 weeks, 46.2% of eyes treated with OTX-TKI showed a 1- or 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) compared with none in the sham arm. Additionally, no eyes treated with OTX-TKI experienced a worsening on the DRSS, whereas 25% of eyes in the sham arm did. Vision-threatening complications, such as proliferative diabetic retinopathy or diabetic macular edema, developed in 37.5% of the sham group but in none of the OTX-TKI treated eyes. A single injection of OTX-TKI provided durable DRSS improvement for up to 48 weeks, with no patients in either arm requiring rescue therapy.
“This is a really exciting add-on treatment,” Dr. Lim said, who was not involved in the study. She explained that it is initially necessary to control the disease with standard treatments, because TKIs may take longer to exhibit their effects. Once the disease is stabilized, TKIs can be used alongside other therapies, potentially reducing the reliance on frequent anti-VEGF injections. “These are preliminary results, but that’s the hope going forward.”
Dr. Lim and Dr. Boyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM — At the American Society of Retina Specialists (ASRS) 2024 Annual Meeting, researchers discussed how insights into potential risk factors and new treatments could improve outcomes for patients with diabetic retinopathy.
Jennifer Lim, MD, an ophthalmologist and director of the Retina Service at the University of Illinois Hospital & Health Sciences System in Chicago, told this news organization that emerging approaches to treating diabetic retinopathy offer hope because they address the root causes of the disease beyond just targeting vascular endothelial growth factor (VEGF). She said innovative methods and add-on treatments could lead to more durable and effective drugs.
Exploration of risk factors and treatment options for diabetic retinopathy could lead to more effective management strategies for the condition, agreed David Boyer, MD, an ophthalmologist at Retina Vitreous Associates Medical Group in Los Angeles, speaking with this news organization.
Risk Factors for Diabetic Retinopathy
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have gained popularity because of their benefits beyond glycemic control, including weight loss, and cardiovascular and kidney protection. However, the impact of these medications on vision-threatening retinal complications is not fully understood. “There has always been a question about whether these newer diabetes medications might exacerbate diabetic eye disease,” said Dr. Boyer.
In a retrospective observational study, researchers included adults with type 2 diabetes and moderate cardiovascular disease risk who had no history of advanced diabetic retinal complications. These patients initiated treatment with GLP-1 RA, SGLT2 inhibitors, DPP-4 inhibitors, or sulfonylureas. The study used inverse probability of treatment weighting to mimic randomization and compared the time to the first treatment for diabetic macular edema or proliferative diabetic retinopathy across the treatment groups.
Results, presented by Andrew J. Barkmeier, MD, an associate professor of ophthalmology at the Mayo Clinic, showed that among 371,698 patients, those who initiated therapy with SGLT2 inhibitors had a lower risk of requiring treatment for sight-threatening retinopathy compared with those using other medication classes. GLP-1 RA did not increase retinopathy risk relative to dipeptidyl peptidase 4 inhibitors and sulfonylurea medications.
“[This study] told us that we do have to keep an eye on patients’ retinopathy when they start on these new inhibitors. But the progression is minimal and, overall, I think most people today favor keeping blood sugar levels as good as possible,” said Dr. Boyer, who was not involved in the study.
Another factor that might increase diabetic retinopathy progression is obstructive sleep apnea. This underdiagnosed condition is linked to several health issues, including dementia, stroke, and myocardial infarctions. Although not easily treated, obstructive sleep apnea is manageable, Dr. Boyer explained.
Researchers utilized the TriNetX electronic health records research network to identify patients with nonproliferative diabetic retinopathy, both with and without obstructive sleep apnea.
The results, presented by Ehsan Rahimy, MD, a retinal specialist at Palo Alto Medical Foundation and a professor at Stanford University, showed that patients with obstructive sleep apnea had a significantly higher risk of progressing to proliferative diabetic retinopathy and developing new-onset diabetic macular edema. These patients were more likely to require ocular interventions, such as intravitreal injections and laser photocoagulation. They also had greater risks for stroke, myocardial infarction, and death compared with those who did not have obstructive sleep apnea.
“It was good to bring this to everybody’s attention,” said Dr. Boyer, who was not involved in the study. “It’s an easy question to ask someone if they snore.”
New Treatments on the Horizon
In another presentation, Nathan C. Steinle, MD, of California Retina Consultants, presented a study that assessed the durability of response to sozinibercept in patients with retinal vascular diseases. This novel therapeutic agent is designed to inhibit VEGF-C and VEGF-D in conditions where VEGF-A suppression alone is insufficient.
Sozinibercept was combined with standard anti–VEGF-A therapies such as ranibizumab or aflibercept. It involved a prospective, post hoc analysis of two phase 1b, open-label, dose-escalation studies, including 40 patients with neovascular age-related macular degeneration (nAMD; 31 patients) or diabetic macular edema (nine patients). These patients, either treatment-naive or previously treated, received three intravitreal injections of ranibizumab or aflibercept in combination with sozinibercept at various doses.
Results indicated that sozinibercept combination therapy was well tolerated, with no dose-limiting toxicities. In treatment-naive nAMD patients, the mean best-corrected visual acuity (BCVA) improved significantly from baseline at months 3 and 6. Previously treated nAMD patients also showed BCVA improvements, although to a lesser extent. For patients with persistent diabetic macular edema, switching to sozinibercept plus aflibercept resulted in notable BCVA gains. The mean time to requiring retreatment was longer in treatment-naive patients than in those previously treated, indicating a durable response.
“Combination therapy with sozinibercept is going to be really important,” said Dr. Lim, who was not involved in the study, “because it attacks with a dual mechanism of action.”
Oral agents promise a potentially easier alternative for patients compared with frequent injections. CU06-1004 is a novel orally administered endothelial dysfunction blocker that has shown promise in stabilizing damaged capillaries, reducing abnormal angiogenesis, and inhibiting inflammatory activation in preclinical studies. “CU06 is very interesting to me because by preventing endothelial loss, it gets to the pathophysiology of why the blood vessels break down,” Dr. Lim said.
In a proof-of-concept phase 2a, multicenter, open-label, parallel-group trial, investigators randomly assigned 67 patients with diabetic macular edema to receive 100 mg, 200 mg, or 300 mg of CU06-1004 once daily for 12 weeks, followed by a 4-week follow-up.
Results presented by Victor Gonzalez, MD, of Valley Retina Institute in Texas, indicated that the oral agent improved BCVA, stabilized central subfield thickness, and showed positive anatomical changes in optical coherence tomography images. CU06-1004 was well tolerated, with no drug-related serious adverse events.
“The number [of patients] was very small, and we will need a much longer, larger trial to see if [CU06-1004] has benefits long term,” said Dr. Boyer, who was not involved in the study. “But I think we’re all very excited if we can find an oral agent for treating diabetic retinopathy. It would be easier for the patient to take a pill than having to come in for injections.”
The sustained-release axitinib implant, OTX-TKI, is also generating significant interest, particularly for nonproliferative diabetic retinopathy. Axitinib, a tyrosine kinase inhibitor (TKI), targets signaling pathways crucial in cellular processes, providing a novel approach to managing diseases where traditional therapies might fall short. Unlike traditional anti-VEGF treatments that focus solely on cytokine levels, TKIs block the activation of signaling pathways, preventing downstream signaling regardless of cytokine levels. This mechanism is particularly important because it effectively inhibits disease progression even if levels of VEGF are high, Dr. Lim explained.
In the phase 1 HELIOS trial, OTX-TKI was assessed in patients with nonproliferative diabetic retinopathy. This multicenter, double-masked, parallel-group clinical study included 21 patients who had not received anti-VEGF treatment, dexamethasone intravitreal implants in the previous 12 months, or intraocular steroid injections in the prior 4 months. Patients were randomly assigned to receive either OTX-TKI or sham treatment.
Results presented by Dilsher S. Dhoot, MD, of California Retina Consultants, indicated that OTX-TKI was generally well tolerated, with no serious ocular adverse events. At 48 weeks, 46.2% of eyes treated with OTX-TKI showed a 1- or 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) compared with none in the sham arm. Additionally, no eyes treated with OTX-TKI experienced a worsening on the DRSS, whereas 25% of eyes in the sham arm did. Vision-threatening complications, such as proliferative diabetic retinopathy or diabetic macular edema, developed in 37.5% of the sham group but in none of the OTX-TKI treated eyes. A single injection of OTX-TKI provided durable DRSS improvement for up to 48 weeks, with no patients in either arm requiring rescue therapy.
“This is a really exciting add-on treatment,” Dr. Lim said, who was not involved in the study. She explained that it is initially necessary to control the disease with standard treatments, because TKIs may take longer to exhibit their effects. Once the disease is stabilized, TKIs can be used alongside other therapies, potentially reducing the reliance on frequent anti-VEGF injections. “These are preliminary results, but that’s the hope going forward.”
Dr. Lim and Dr. Boyer report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASRS 2024
New Drugs Could Reduce AMD Treatment Burden
STOCKHOLM — Current treatments for age-related macular degeneration (AMD) have proved effective and safe. However, these lifelong therapies involve frequent ocular injections. “It can be nerve-wracking for patients about to embark on this journey,” Lisa Olmos de Koo, MD, an ophthalmologist at the University of Washington Eye Institute at Harborview, Seattle, told this news organization.
At the American Society of Retina Specialists (ASRS) 2024 annual meeting, researchers from around the world presented results from clinical studies aiming at reducing the burden of AMD treatment by:
- Identifying patients at a higher risk for degeneration and vision loss who will be more likely to respond to treatment
- Developing gene therapies that promise to drastically reduce or eliminate the need for injections
- Testing novel drugs with mechanisms of action that use different pathways than currently available medications, offering patients more options and longer-lasting treatments
“It’s exciting to see the broad range of novel approaches in AMD treatments,” Dimitra Skondra, MD, PhD, a retina specialist at the University of Chicago, told this news organization.
Whom to Treat
Anti–vascular endothelial growth factor (anti-VEGF) therapies shook the AMD treatment scene when they were introduced in the early 2000s. “It was incredible,” Dr. Olmos de Koo said. Patients with wet AMD could finally see their vision improve with each injection. “It was a great motivator to begin therapy.”
However, patients with the advanced form of dry AMD involving geographic atrophy (GA) have had less luck. Pegcetacoplan and avacincaptad pegol, the only US Food and Drug Administration (FDA)–approved treatments for GA, slow the progression of the disease but do not restore vision. In fact, vision continues to decline. “Patients want to understand if their condition is worsening and whether treatment is necessary,” Dr. Olmos de Koo said.
Researchers are developing tools to help clinicians identify lesions that are more likely to grow and reach the fovea, causing vision loss.
For example, Cleveland Clinic’s Katherine Talcott, MD, presented an analysis of the GATHER1 and GATHER2 clinical trials that showed that spectral domain optical coherence tomography can be used to examine the integrity of the ellipsoid zone for predicting GA growth and treatment response. The retina’s ellipsoid zone contains densely packed mitochondria within the inner segments of the photoreceptor cells and plays a critical role in visual function.
Dr. Talcott and her team found that more severe baseline damage of the ellipsoid zone was associated with a faster growth rate of GA.
Another analysis of the same trials, presented by Dilraj Grewal, MD, associate professor of ophthalmology, vitreoretinal surgery, and uveitis at Duke Eye Center, Durham, North Carolina, showed that intravitreal administration of avacincaptad pegol efficiently reduced GA growth whether the treated eye developed macular neovascularization or not. Avacincaptad pegol is a complement factor inhibitor that aims to reduce complement-mediated inflammation and tissue damage in the retina.
Dr. Olmos de Koo explained that clinical trials have shown that more patients develop neovascularization when treated for dry GA than they would if left untreated. This has raised the question among clinicians whether the increased risk is a valid reason to avoid treatment. “This useful analysis tells us that there is still a rationale to continue treating GA, even while you’re concurrently treating the wet component with anti-VEGF therapies,” she said.
Another biomarker of GA growth is the position of the lesion at baseline. Daniel Muth, MD, an ophthalmology consultant at the Karolinska Institutet in Stockholm, Sweden, reported the results from a long-term, retrospective analysis of fundus autofluorescence in patients with GA. His semiautomated artificial intelligence–based analysis showed that patients affected bilaterally, but whose fovea was not yet affected, exhibited a faster GA growth rate than fovea-involving patients, with an approximate 15% risk for fovea involvement.
“Those patients whose atrophy has not yet affected the very center are the most likely to benefit from preventive therapy,” Dr. Olmos de Koo said. “Left untreated, a large proportion of them will develop atrophy that does affect their central vision — that’s their reading or facial recognition ability.”
“Potential predictors of rapid growth rates guide us clinically and allow patients to make more informed decisions about whether to pursue treatments that require frequent interventions,” Dr. Olmos de Koo said.
Forecasting the side to which the cost-benefit balance of treatment will tip for each patient is a complex decision-making process, she explained. “A patient is not a statistic, but these predictive studies are one important piece of the pie.”
The Promise of Gene Therapy
The one-and-done promise of gene therapy could rattle the field once again. Trials presented at the ASRS24 showed a drastic reduction (from 85% to 95%) in the number of anti-VEGF and complement treatments needed following gene therapy injection, improving patient vision while relieving them from the stress of monthly injections.
But researchers are still debating the optimal corticosteroid regimen that is required for reducing the inflammatory response associated with the administration of gene therapies, especially those that use viral vectors. The main controversy is whether systemic immunosuppression is necessary or if local therapies, such as topical and intravitreal administration, can suffice.
Results presented at the meeting suggest that local therapies alone can be effective, potentially reducing the need for systemic immunosuppression.
The LUNA trial evaluated the efficacy and tolerability of ixoberogene soroparvovec, a therapy that delivers an anti-VEGF gene into the eye. Investigators included various prophylactic regimens, including local corticosteroids with and without oral prednisone. They found that local corticosteroid therapy alone effectively reduced inflammation.
Biopharma company 4DMT conducted the PRISM study, which examined a dual transgene therapy for neovascular AMD. Patients in this trial received a 20-week topical steroid taper. Only one patient (of 39) required a 6-week extension of steroid therapy. No patients experienced clinically significant intraocular inflammation, indicating that local corticosteroid therapy was effective in managing immune responses.
Currently, gene therapy clinical trials are designed for patients who have failed standard therapy or require frequent injections. “Once we figure out possible long-term side effects and how to deal with inflammation, [gene therapy] could reach many more patients,” Dr. Olmos de Koo said.
New Approaches Enter Pipeline
While gene therapy brings excitement to the field, it might not be for everyone, experts agreed at the ASRS24. New agents are being evaluated to offer a broader range of treatment options with longer-lasting efficacy. Results from early-phase trials presented at the meeting show favorable safety and efficacy signals.
“Finally, after a long time, we have a lot of exciting drugs for geographic atrophy in the pipeline that seem to be safe, with many studies also showing a functional outcome in addition to anatomical outcome,” Dr. Skondra told this news organization.
Current FDA-approved treatments for GA focus on inhibiting the humoral arm of the immune system through C3 and C5 inhibitors. However, a new approach targets both the humoral and cellular arms of the immune response by inhibiting macrophages that release pro-inflammatory cytokines. The goal is to convert these macrophages to a “resolution state,” potentially reducing the release of inflammatory cytokines and offering a more comprehensive treatment for wet and dry AMD, said Rishi Singh, MD, a retina surgeon at the Cole Eye Institute, Cleveland Clinic.
AVD-104, a sialic acid–coated nanoparticle developed by Aviceda Therapeutics, is a promising candidate in this approach. This 100-nm-in-diameter particle, which is only as heavy as 20 hydrogen atoms, is designed for better tissue penetration and has a pharmacokinetic profile lasting 3-4 months after a single intravitreal dose.
AVD-104 aims to repolarize macrophages into a resolution phenotype and decreases complement factor overamplification through direct binding to complement factor H, which downregulates C3 production in immune cells. This dual-action approach could offer a more effective and long-lasting treatment option.
Dr. Singh, who presented the phase 2/3 SIGLEC clinical trial assessing AVD-104, said a single dose resulted in significantly slower rates of disease progression as early as 1 month post-treatment and a notable decrease in junctional zone hyper-autofluorescence.
In addition, about 40% of patients gained vision, which was unexpected but a pleasant surprise, Dr. Singh said. “This is a small study. I don’t want anyone to walk away with the conclusion that we’ve figured out how to improve visual acuity in GA. But it’s promising.”
Other researchers are tackling GA by focusing on therapies that aim to intervene before the complement system is activated.
ONL1204 is a novel agent designed to inhibit the activation of the tumor necrosis factor FAS receptor, which is activated and upregulated in a disease state and is implicated in multiple cell death and inflammatory pathways.
Multiple preclinical models of AMD have shown that ONL1204 preserves retinal cells and inhibits inflammation by inhibiting the FAS receptor. Phase 1 trial results presented at the meeting showed that ONL1204 was safe and showed strong efficacy signals as early as 6 months after treatment initiation.
“We need to be cautiously optimistic,” Dr. Skondra said. “Larger studies will tell us if these signals are real. But it’s a very exciting time. I’m happy to see different mechanisms of action besides the complement because we can attack the disease from multiple fronts.”
Dr. Grewal declared interests with Eyepoint, Iveric Bio, Regeneron, Alumis, Apellis, DORC, and Genentech. Dr. Muth declared interests with Bayer, Canon, and Roche. Dr. Olmos de Koo declared interests with Alcon and Pixium Vision. Dr. Singh declared interests with Gyroscope, 4DMT, Aviceda, Eyepoint, Alcon, Bausch and Lomb, Novartis, and Regeneron. Dr. Skondra declared interests with Biogen, Iveric Bio, Allergan, and Trinity Health Science. Dr. Talcott declared interests with Bausch and Lomb, Eyepoint, Regeneron, REGENXBIO, Zeiss, Apellis, Genentech, Alimera, Outlook, and Iveric Bio.
A version of this article first appeared on Medscape.com.
STOCKHOLM — Current treatments for age-related macular degeneration (AMD) have proved effective and safe. However, these lifelong therapies involve frequent ocular injections. “It can be nerve-wracking for patients about to embark on this journey,” Lisa Olmos de Koo, MD, an ophthalmologist at the University of Washington Eye Institute at Harborview, Seattle, told this news organization.
At the American Society of Retina Specialists (ASRS) 2024 annual meeting, researchers from around the world presented results from clinical studies aiming at reducing the burden of AMD treatment by:
- Identifying patients at a higher risk for degeneration and vision loss who will be more likely to respond to treatment
- Developing gene therapies that promise to drastically reduce or eliminate the need for injections
- Testing novel drugs with mechanisms of action that use different pathways than currently available medications, offering patients more options and longer-lasting treatments
“It’s exciting to see the broad range of novel approaches in AMD treatments,” Dimitra Skondra, MD, PhD, a retina specialist at the University of Chicago, told this news organization.
Whom to Treat
Anti–vascular endothelial growth factor (anti-VEGF) therapies shook the AMD treatment scene when they were introduced in the early 2000s. “It was incredible,” Dr. Olmos de Koo said. Patients with wet AMD could finally see their vision improve with each injection. “It was a great motivator to begin therapy.”
However, patients with the advanced form of dry AMD involving geographic atrophy (GA) have had less luck. Pegcetacoplan and avacincaptad pegol, the only US Food and Drug Administration (FDA)–approved treatments for GA, slow the progression of the disease but do not restore vision. In fact, vision continues to decline. “Patients want to understand if their condition is worsening and whether treatment is necessary,” Dr. Olmos de Koo said.
Researchers are developing tools to help clinicians identify lesions that are more likely to grow and reach the fovea, causing vision loss.
For example, Cleveland Clinic’s Katherine Talcott, MD, presented an analysis of the GATHER1 and GATHER2 clinical trials that showed that spectral domain optical coherence tomography can be used to examine the integrity of the ellipsoid zone for predicting GA growth and treatment response. The retina’s ellipsoid zone contains densely packed mitochondria within the inner segments of the photoreceptor cells and plays a critical role in visual function.
Dr. Talcott and her team found that more severe baseline damage of the ellipsoid zone was associated with a faster growth rate of GA.
Another analysis of the same trials, presented by Dilraj Grewal, MD, associate professor of ophthalmology, vitreoretinal surgery, and uveitis at Duke Eye Center, Durham, North Carolina, showed that intravitreal administration of avacincaptad pegol efficiently reduced GA growth whether the treated eye developed macular neovascularization or not. Avacincaptad pegol is a complement factor inhibitor that aims to reduce complement-mediated inflammation and tissue damage in the retina.
Dr. Olmos de Koo explained that clinical trials have shown that more patients develop neovascularization when treated for dry GA than they would if left untreated. This has raised the question among clinicians whether the increased risk is a valid reason to avoid treatment. “This useful analysis tells us that there is still a rationale to continue treating GA, even while you’re concurrently treating the wet component with anti-VEGF therapies,” she said.
Another biomarker of GA growth is the position of the lesion at baseline. Daniel Muth, MD, an ophthalmology consultant at the Karolinska Institutet in Stockholm, Sweden, reported the results from a long-term, retrospective analysis of fundus autofluorescence in patients with GA. His semiautomated artificial intelligence–based analysis showed that patients affected bilaterally, but whose fovea was not yet affected, exhibited a faster GA growth rate than fovea-involving patients, with an approximate 15% risk for fovea involvement.
“Those patients whose atrophy has not yet affected the very center are the most likely to benefit from preventive therapy,” Dr. Olmos de Koo said. “Left untreated, a large proportion of them will develop atrophy that does affect their central vision — that’s their reading or facial recognition ability.”
“Potential predictors of rapid growth rates guide us clinically and allow patients to make more informed decisions about whether to pursue treatments that require frequent interventions,” Dr. Olmos de Koo said.
Forecasting the side to which the cost-benefit balance of treatment will tip for each patient is a complex decision-making process, she explained. “A patient is not a statistic, but these predictive studies are one important piece of the pie.”
The Promise of Gene Therapy
The one-and-done promise of gene therapy could rattle the field once again. Trials presented at the ASRS24 showed a drastic reduction (from 85% to 95%) in the number of anti-VEGF and complement treatments needed following gene therapy injection, improving patient vision while relieving them from the stress of monthly injections.
But researchers are still debating the optimal corticosteroid regimen that is required for reducing the inflammatory response associated with the administration of gene therapies, especially those that use viral vectors. The main controversy is whether systemic immunosuppression is necessary or if local therapies, such as topical and intravitreal administration, can suffice.
Results presented at the meeting suggest that local therapies alone can be effective, potentially reducing the need for systemic immunosuppression.
The LUNA trial evaluated the efficacy and tolerability of ixoberogene soroparvovec, a therapy that delivers an anti-VEGF gene into the eye. Investigators included various prophylactic regimens, including local corticosteroids with and without oral prednisone. They found that local corticosteroid therapy alone effectively reduced inflammation.
Biopharma company 4DMT conducted the PRISM study, which examined a dual transgene therapy for neovascular AMD. Patients in this trial received a 20-week topical steroid taper. Only one patient (of 39) required a 6-week extension of steroid therapy. No patients experienced clinically significant intraocular inflammation, indicating that local corticosteroid therapy was effective in managing immune responses.
Currently, gene therapy clinical trials are designed for patients who have failed standard therapy or require frequent injections. “Once we figure out possible long-term side effects and how to deal with inflammation, [gene therapy] could reach many more patients,” Dr. Olmos de Koo said.
New Approaches Enter Pipeline
While gene therapy brings excitement to the field, it might not be for everyone, experts agreed at the ASRS24. New agents are being evaluated to offer a broader range of treatment options with longer-lasting efficacy. Results from early-phase trials presented at the meeting show favorable safety and efficacy signals.
“Finally, after a long time, we have a lot of exciting drugs for geographic atrophy in the pipeline that seem to be safe, with many studies also showing a functional outcome in addition to anatomical outcome,” Dr. Skondra told this news organization.
Current FDA-approved treatments for GA focus on inhibiting the humoral arm of the immune system through C3 and C5 inhibitors. However, a new approach targets both the humoral and cellular arms of the immune response by inhibiting macrophages that release pro-inflammatory cytokines. The goal is to convert these macrophages to a “resolution state,” potentially reducing the release of inflammatory cytokines and offering a more comprehensive treatment for wet and dry AMD, said Rishi Singh, MD, a retina surgeon at the Cole Eye Institute, Cleveland Clinic.
AVD-104, a sialic acid–coated nanoparticle developed by Aviceda Therapeutics, is a promising candidate in this approach. This 100-nm-in-diameter particle, which is only as heavy as 20 hydrogen atoms, is designed for better tissue penetration and has a pharmacokinetic profile lasting 3-4 months after a single intravitreal dose.
AVD-104 aims to repolarize macrophages into a resolution phenotype and decreases complement factor overamplification through direct binding to complement factor H, which downregulates C3 production in immune cells. This dual-action approach could offer a more effective and long-lasting treatment option.
Dr. Singh, who presented the phase 2/3 SIGLEC clinical trial assessing AVD-104, said a single dose resulted in significantly slower rates of disease progression as early as 1 month post-treatment and a notable decrease in junctional zone hyper-autofluorescence.
In addition, about 40% of patients gained vision, which was unexpected but a pleasant surprise, Dr. Singh said. “This is a small study. I don’t want anyone to walk away with the conclusion that we’ve figured out how to improve visual acuity in GA. But it’s promising.”
Other researchers are tackling GA by focusing on therapies that aim to intervene before the complement system is activated.
ONL1204 is a novel agent designed to inhibit the activation of the tumor necrosis factor FAS receptor, which is activated and upregulated in a disease state and is implicated in multiple cell death and inflammatory pathways.
Multiple preclinical models of AMD have shown that ONL1204 preserves retinal cells and inhibits inflammation by inhibiting the FAS receptor. Phase 1 trial results presented at the meeting showed that ONL1204 was safe and showed strong efficacy signals as early as 6 months after treatment initiation.
“We need to be cautiously optimistic,” Dr. Skondra said. “Larger studies will tell us if these signals are real. But it’s a very exciting time. I’m happy to see different mechanisms of action besides the complement because we can attack the disease from multiple fronts.”
Dr. Grewal declared interests with Eyepoint, Iveric Bio, Regeneron, Alumis, Apellis, DORC, and Genentech. Dr. Muth declared interests with Bayer, Canon, and Roche. Dr. Olmos de Koo declared interests with Alcon and Pixium Vision. Dr. Singh declared interests with Gyroscope, 4DMT, Aviceda, Eyepoint, Alcon, Bausch and Lomb, Novartis, and Regeneron. Dr. Skondra declared interests with Biogen, Iveric Bio, Allergan, and Trinity Health Science. Dr. Talcott declared interests with Bausch and Lomb, Eyepoint, Regeneron, REGENXBIO, Zeiss, Apellis, Genentech, Alimera, Outlook, and Iveric Bio.
A version of this article first appeared on Medscape.com.
STOCKHOLM — Current treatments for age-related macular degeneration (AMD) have proved effective and safe. However, these lifelong therapies involve frequent ocular injections. “It can be nerve-wracking for patients about to embark on this journey,” Lisa Olmos de Koo, MD, an ophthalmologist at the University of Washington Eye Institute at Harborview, Seattle, told this news organization.
At the American Society of Retina Specialists (ASRS) 2024 annual meeting, researchers from around the world presented results from clinical studies aiming at reducing the burden of AMD treatment by:
- Identifying patients at a higher risk for degeneration and vision loss who will be more likely to respond to treatment
- Developing gene therapies that promise to drastically reduce or eliminate the need for injections
- Testing novel drugs with mechanisms of action that use different pathways than currently available medications, offering patients more options and longer-lasting treatments
“It’s exciting to see the broad range of novel approaches in AMD treatments,” Dimitra Skondra, MD, PhD, a retina specialist at the University of Chicago, told this news organization.
Whom to Treat
Anti–vascular endothelial growth factor (anti-VEGF) therapies shook the AMD treatment scene when they were introduced in the early 2000s. “It was incredible,” Dr. Olmos de Koo said. Patients with wet AMD could finally see their vision improve with each injection. “It was a great motivator to begin therapy.”
However, patients with the advanced form of dry AMD involving geographic atrophy (GA) have had less luck. Pegcetacoplan and avacincaptad pegol, the only US Food and Drug Administration (FDA)–approved treatments for GA, slow the progression of the disease but do not restore vision. In fact, vision continues to decline. “Patients want to understand if their condition is worsening and whether treatment is necessary,” Dr. Olmos de Koo said.
Researchers are developing tools to help clinicians identify lesions that are more likely to grow and reach the fovea, causing vision loss.
For example, Cleveland Clinic’s Katherine Talcott, MD, presented an analysis of the GATHER1 and GATHER2 clinical trials that showed that spectral domain optical coherence tomography can be used to examine the integrity of the ellipsoid zone for predicting GA growth and treatment response. The retina’s ellipsoid zone contains densely packed mitochondria within the inner segments of the photoreceptor cells and plays a critical role in visual function.
Dr. Talcott and her team found that more severe baseline damage of the ellipsoid zone was associated with a faster growth rate of GA.
Another analysis of the same trials, presented by Dilraj Grewal, MD, associate professor of ophthalmology, vitreoretinal surgery, and uveitis at Duke Eye Center, Durham, North Carolina, showed that intravitreal administration of avacincaptad pegol efficiently reduced GA growth whether the treated eye developed macular neovascularization or not. Avacincaptad pegol is a complement factor inhibitor that aims to reduce complement-mediated inflammation and tissue damage in the retina.
Dr. Olmos de Koo explained that clinical trials have shown that more patients develop neovascularization when treated for dry GA than they would if left untreated. This has raised the question among clinicians whether the increased risk is a valid reason to avoid treatment. “This useful analysis tells us that there is still a rationale to continue treating GA, even while you’re concurrently treating the wet component with anti-VEGF therapies,” she said.
Another biomarker of GA growth is the position of the lesion at baseline. Daniel Muth, MD, an ophthalmology consultant at the Karolinska Institutet in Stockholm, Sweden, reported the results from a long-term, retrospective analysis of fundus autofluorescence in patients with GA. His semiautomated artificial intelligence–based analysis showed that patients affected bilaterally, but whose fovea was not yet affected, exhibited a faster GA growth rate than fovea-involving patients, with an approximate 15% risk for fovea involvement.
“Those patients whose atrophy has not yet affected the very center are the most likely to benefit from preventive therapy,” Dr. Olmos de Koo said. “Left untreated, a large proportion of them will develop atrophy that does affect their central vision — that’s their reading or facial recognition ability.”
“Potential predictors of rapid growth rates guide us clinically and allow patients to make more informed decisions about whether to pursue treatments that require frequent interventions,” Dr. Olmos de Koo said.
Forecasting the side to which the cost-benefit balance of treatment will tip for each patient is a complex decision-making process, she explained. “A patient is not a statistic, but these predictive studies are one important piece of the pie.”
The Promise of Gene Therapy
The one-and-done promise of gene therapy could rattle the field once again. Trials presented at the ASRS24 showed a drastic reduction (from 85% to 95%) in the number of anti-VEGF and complement treatments needed following gene therapy injection, improving patient vision while relieving them from the stress of monthly injections.
But researchers are still debating the optimal corticosteroid regimen that is required for reducing the inflammatory response associated with the administration of gene therapies, especially those that use viral vectors. The main controversy is whether systemic immunosuppression is necessary or if local therapies, such as topical and intravitreal administration, can suffice.
Results presented at the meeting suggest that local therapies alone can be effective, potentially reducing the need for systemic immunosuppression.
The LUNA trial evaluated the efficacy and tolerability of ixoberogene soroparvovec, a therapy that delivers an anti-VEGF gene into the eye. Investigators included various prophylactic regimens, including local corticosteroids with and without oral prednisone. They found that local corticosteroid therapy alone effectively reduced inflammation.
Biopharma company 4DMT conducted the PRISM study, which examined a dual transgene therapy for neovascular AMD. Patients in this trial received a 20-week topical steroid taper. Only one patient (of 39) required a 6-week extension of steroid therapy. No patients experienced clinically significant intraocular inflammation, indicating that local corticosteroid therapy was effective in managing immune responses.
Currently, gene therapy clinical trials are designed for patients who have failed standard therapy or require frequent injections. “Once we figure out possible long-term side effects and how to deal with inflammation, [gene therapy] could reach many more patients,” Dr. Olmos de Koo said.
New Approaches Enter Pipeline
While gene therapy brings excitement to the field, it might not be for everyone, experts agreed at the ASRS24. New agents are being evaluated to offer a broader range of treatment options with longer-lasting efficacy. Results from early-phase trials presented at the meeting show favorable safety and efficacy signals.
“Finally, after a long time, we have a lot of exciting drugs for geographic atrophy in the pipeline that seem to be safe, with many studies also showing a functional outcome in addition to anatomical outcome,” Dr. Skondra told this news organization.
Current FDA-approved treatments for GA focus on inhibiting the humoral arm of the immune system through C3 and C5 inhibitors. However, a new approach targets both the humoral and cellular arms of the immune response by inhibiting macrophages that release pro-inflammatory cytokines. The goal is to convert these macrophages to a “resolution state,” potentially reducing the release of inflammatory cytokines and offering a more comprehensive treatment for wet and dry AMD, said Rishi Singh, MD, a retina surgeon at the Cole Eye Institute, Cleveland Clinic.
AVD-104, a sialic acid–coated nanoparticle developed by Aviceda Therapeutics, is a promising candidate in this approach. This 100-nm-in-diameter particle, which is only as heavy as 20 hydrogen atoms, is designed for better tissue penetration and has a pharmacokinetic profile lasting 3-4 months after a single intravitreal dose.
AVD-104 aims to repolarize macrophages into a resolution phenotype and decreases complement factor overamplification through direct binding to complement factor H, which downregulates C3 production in immune cells. This dual-action approach could offer a more effective and long-lasting treatment option.
Dr. Singh, who presented the phase 2/3 SIGLEC clinical trial assessing AVD-104, said a single dose resulted in significantly slower rates of disease progression as early as 1 month post-treatment and a notable decrease in junctional zone hyper-autofluorescence.
In addition, about 40% of patients gained vision, which was unexpected but a pleasant surprise, Dr. Singh said. “This is a small study. I don’t want anyone to walk away with the conclusion that we’ve figured out how to improve visual acuity in GA. But it’s promising.”
Other researchers are tackling GA by focusing on therapies that aim to intervene before the complement system is activated.
ONL1204 is a novel agent designed to inhibit the activation of the tumor necrosis factor FAS receptor, which is activated and upregulated in a disease state and is implicated in multiple cell death and inflammatory pathways.
Multiple preclinical models of AMD have shown that ONL1204 preserves retinal cells and inhibits inflammation by inhibiting the FAS receptor. Phase 1 trial results presented at the meeting showed that ONL1204 was safe and showed strong efficacy signals as early as 6 months after treatment initiation.
“We need to be cautiously optimistic,” Dr. Skondra said. “Larger studies will tell us if these signals are real. But it’s a very exciting time. I’m happy to see different mechanisms of action besides the complement because we can attack the disease from multiple fronts.”
Dr. Grewal declared interests with Eyepoint, Iveric Bio, Regeneron, Alumis, Apellis, DORC, and Genentech. Dr. Muth declared interests with Bayer, Canon, and Roche. Dr. Olmos de Koo declared interests with Alcon and Pixium Vision. Dr. Singh declared interests with Gyroscope, 4DMT, Aviceda, Eyepoint, Alcon, Bausch and Lomb, Novartis, and Regeneron. Dr. Skondra declared interests with Biogen, Iveric Bio, Allergan, and Trinity Health Science. Dr. Talcott declared interests with Bausch and Lomb, Eyepoint, Regeneron, REGENXBIO, Zeiss, Apellis, Genentech, Alimera, Outlook, and Iveric Bio.
A version of this article first appeared on Medscape.com.
FROM ASRS 2024