Conference Coverage

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers have found a link between age of diagnosis and various clinical characteristics and outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The findings, presented at the annual meeting of the American College of Rheumatology, may have implications for research and treatment, especially in children.

AAV is a group of conditions characterized by the development of autoantibodies to the neutrophil proteins proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA).

The rare autoimmune condition can cause systemic inflammation and damage, sometimes permanent, to small- and medium-sized arteries. Clinical presentations vary and can include several organs, including skin, stomach, intestines, lung, and kidney, as well as airways in ear, nose, and throat.
 

Data limited on child vs. adult characteristics

AAV can be diagnosed in any decade of life, but clinical characteristics and outcomes often differ between children and adults, and data are limited. Studies often exclude children.

Lead author Jessica Bloom, MD, MSCS, a pediatric rheumatologist and assistant professor of pediatrics at Children’s Hospital Colorado, Aurora, and colleagues performed an analysis of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) who were enrolled in the Vasculitis Clinical Research Consortium Longitudinal Studies from 2013 to 2021.

Patients with eosinophilic GPA (EGPA) were analyzed separately. Children and young adults with EGPA were combined because of the small sample size (n = 87).

The groups were sorted by the age they were diagnosed: under 18 years old, 18-40, 40-65, and older than 65.
 

More than 1,000 patients included

Dr. Bloom’s team analyzed data from 1,020 patients: 61 diagnosed as children, 240 as young adults, 560 as middle-aged adults, and 159 diagnosed as older adults. At all ages, about nine out of 10 patients were White.

They found 852 (84%) had GPA and 165 (16%) had MPA. The analysis also showed 893 (92%) of patients with ANCA results were ANCA positive: 637 (65%) with PR3-ANCA, 247 (25%) with MPO-ANCA, and 9 (1%) with both.

Differences between age groups included:

• Children experienced more subglottic stenosis and alveolar hemorrhage than adults with the condition.
• About half of patients diagnosed in childhood received both cyclophosphamide and rituximab. That rate decreased with increasing age of diagnosis to as low as 14% for those diagnosed in older adulthood. 
• More females than males in all age groups were diagnosed with AAV, but the difference was most pronounced when diagnosed in childhood, and female predominance declined as age increased.
• Older adults experienced more neurologic disease and less musculoskeletal and sinus involvement.

Additionally, for those diagnosed after age 65, after adjusting for disease length and whether they were taking cyclophosphamide and/or rituximab, the Vasculitis Damage Index (VDI) and ANCA Vasculitis Index of Damage (AVID) scores were higher than for those diagnosed in childhood.

“However, these differences are no longer significant when medication toxicity and comorbidity-related items are excluded. Thus, differences in the VDI and AVID scores are driven by non–disease-specific damage,” Dr. Bloom said.
 

Bringing children into the clinical discussion

Dr. Bloom said in an interview that many pediatric rheumatologists believe kids with vasculitis are like small adults and should be treated similarly, but she said the picture may be more complex than that.

For example, the findings that children have more subglottic stenosis and alveolar hemorrhage than adults “may warrant more aggressive therapy,” she said. Children also have different growth and psychosocial risk factors during their disease course and may live longer with the disease than those in older age groups.

“Our study helps to point out these differences and bring children into the discussion,” Dr. Bloom said. “It also recognizes that damage scores used in studies and care may not adequately assess disease across the lifespan, as they are largely influenced by items not specific to the disease but rather medication toxicity and comorbidities, such as osteoporosis, cataracts, and malignancy.”

Robert Spiera, MD, director of the Scleroderma, Vasculitis, and Myositis Center at Hospital for Special Surgery, New York, said in an interview that the work highlights interesting information about the fact that disease features are skewed differently in children – “in particular the higher likelihood of upper airway [subglottic] disease, and potentially severe lower airway disease [alveolar hemorrhage].”

However, from a practical standpoint, Dr. Spiera said, “I am not sure that this will change our clinical approach to different patients, but the differences in disease features and even the sex differences in terms of who are afflicted with GPA [more often children and more likely to be female] may offer insights into disease pathogenesis.”

Dr. Bloom received funding from the Vasculitis Clinical Research Consortium and Vasculitis Foundation to conduct this work as a VCRC-VF fellow. Several coauthors reported various conflicts of interest with pharmaceutical companies. Dr. Spiera declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

AT ACR 2022

PHILADELPHIA – The first consensus screening guidelines for patients with idiopathic inflammatory myopathy (IIM) provide recommendations on risk stratification for individuals, basic and enhanced screening protocols, and screening frequency.

The recommendations, issued by the International Myositis Assessment and Clinical Studies Group (IMACS), stratify cancer risk for individual patients into low, intermediate, or high categories based on the IIM disease subtype, autoantibody status, and clinical features, reported Alexander Oldroyd, PhD, MSc, MBChB of the University of Manchester, England.

Neil Osterweil/MDedge News

“There’s a big unmet need for cancer screening. One in four adults with myositis has cancer, either 3 years before or after a diagnosis of myositis. It’s one of the leading causes of death in these patients, and they’re overwhelmingly diagnosed at a late stage, so we need standardized approaches to get early diagnosis,” he said in an interview at the annual meeting of the American College of Rheumatology.

Sharon Kolasinski, MD, of the University of Pennsylvania in Philadelphia, said in an interview that the guideline is a welcome development for rheumatologists. Dr. Kolasinski moderated the session where Dr. Oldroyd described the guideline, but she was not involved in its formulation.

“I think that we all have wondered for a very long time: What is the optimal cancer screening for myositis patients? We all worry that the onset of their diseases is associated with a coincident cancer, or that they will develop it soon,” she said.

Dr. Oldroyd emphasized that all patients with myositis have elevated risk for cancer compared with the general population and that the guideline categories of low, intermediate, and high are relative only to patients with IIM.
 

International consensus

The data on which the recommendations are based come from a systematic review and meta-analysis by Dr. Oldroyd and colleagues of 69 studies on cancer risk factors and 9 on IIM-specific cancer screening.

The authors of that paper found that the dermatomyositis subtype, older age, male sex, dysphagia, cutaneous ulceration and antitranscriptional intermediary factor-1 gamma (anti-TIF1-gamma) positivity were associated with significantly increased risk of cancer.

In contrast, polymyositis and clinically amyopathic dermatomyositis subtypes, Raynaud’s phenomenon, interstitial lung disease, very high serum creatine kinase or lactate dehydrogenase levels, and positivity for anti-Jo1 or anti-EJ antibodies were associated with significantly reduced risk of cancer.

The consensus recommendations were developed with anonymous contributions from 75 expert participants in 22 countries, with additional input from 3 patient partners.
 

Do this

The guideline lists 18 recommendations, of which 13 are strong and 5 are conditional.

An example of a strong recommendation is number 3, based on a moderate level of evidences:

“All adult IIM patients, irrespective of cancer risk, should continue to participate in country/region-specific age and sex appropriate cancer screening programs,” the guideline recommends.

Patients with verified inclusion body myositis or juvenile-onset IIM do not, however, require routine screening for myositis-associated cancer, the guideline says (recommendations 1 and 2).

There are also recommendations that all adults with new-onset IIM be tested for myositis-specific and myositis-associated autoantibodies to assist in stratifying patients by risk category.

The guideline divides screening recommendations into basic and enhanced. The basic screening should include a comprehensive history and physical exam, complete blood count, liver functions tests, erythrocyte sedimentation rates/plasma viscosity, serum protein electrophoresis, urinalysis, and chest x-ray.

Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening at the time of IIM diagnosis. Adults with intermediate risk should undergo both basic and enhanced screening at the time of IIM diagnosis, and those with high risk should undergo enhanced screening at the time of myositis diagnosis, with basic screening annually for 3 years, the recommendations say.
 

Consider doing this

Conditional recommendations (“clinicians should consider ...”) include the use of PET/CT for adults at high risk for cancer when an underlying cancer has not been detected at the time of IIM diagnosis. They also include a single screening test for anti-TIF1-gamma positive dermatomyositis patients whose disease onset was after age 40 and who have at least one additional risk factor.

Also conditionally recommended are upper and lower gastrointestinal endoscopy for patients at high risk when an underlying cancer is not found at the time of IIM diagnosis, nasoendoscopy in geographical regions with elevated risk for nasopharyngeal cancers, and screening for all IIM patients with red-flag symptoms or clinical features of cancer, including unexplained weight loss, family history of cancer, smoking, unexplained fever, or night sweats.
 

Guided steps

“I think clinicians have a lot of questions such as, ‘well, what should I do, when should I do it?’ These are important clinical questions, and we need guidance about this. We need to balance comprehensiveness with cost-effectiveness, and we need expert opinion about what steps we should take now and which should we take later,” Dr. Kolasinski said.

The guideline development process was supported by the University of Manchester, IMACS, National Institute for Health Research (United Kingdom), National Institutes of Health, National Health Service Northern Care Alliance, The Myositis Association, Myositis UK, University of Pittsburgh, Versus Arthritis, and the Center for Musculoskeletal Research. Dr. Oldroyd and Dr. Kolasinski reported having no relevant conflicts of interest.

AT ACR 2022

PHILADELPHIA – The first consensus screening guidelines for patients with idiopathic inflammatory myopathy (IIM) provide recommendations on risk stratification for individuals, basic and enhanced screening protocols, and screening frequency.

The recommendations, issued by the International Myositis Assessment and Clinical Studies Group (IMACS), stratify cancer risk for individual patients into low, intermediate, or high categories based on the IIM disease subtype, autoantibody status, and clinical features, reported Alexander Oldroyd, PhD, MSc, MBChB of the University of Manchester, England.

Neil Osterweil/MDedge News

“There’s a big unmet need for cancer screening. One in four adults with myositis has cancer, either 3 years before or after a diagnosis of myositis. It’s one of the leading causes of death in these patients, and they’re overwhelmingly diagnosed at a late stage, so we need standardized approaches to get early diagnosis,” he said in an interview at the annual meeting of the American College of Rheumatology.

Sharon Kolasinski, MD, of the University of Pennsylvania in Philadelphia, said in an interview that the guideline is a welcome development for rheumatologists. Dr. Kolasinski moderated the session where Dr. Oldroyd described the guideline, but she was not involved in its formulation.

“I think that we all have wondered for a very long time: What is the optimal cancer screening for myositis patients? We all worry that the onset of their diseases is associated with a coincident cancer, or that they will develop it soon,” she said.

Dr. Oldroyd emphasized that all patients with myositis have elevated risk for cancer compared with the general population and that the guideline categories of low, intermediate, and high are relative only to patients with IIM.
 

International consensus

The data on which the recommendations are based come from a systematic review and meta-analysis by Dr. Oldroyd and colleagues of 69 studies on cancer risk factors and 9 on IIM-specific cancer screening.

The authors of that paper found that the dermatomyositis subtype, older age, male sex, dysphagia, cutaneous ulceration and antitranscriptional intermediary factor-1 gamma (anti-TIF1-gamma) positivity were associated with significantly increased risk of cancer.

In contrast, polymyositis and clinically amyopathic dermatomyositis subtypes, Raynaud’s phenomenon, interstitial lung disease, very high serum creatine kinase or lactate dehydrogenase levels, and positivity for anti-Jo1 or anti-EJ antibodies were associated with significantly reduced risk of cancer.

The consensus recommendations were developed with anonymous contributions from 75 expert participants in 22 countries, with additional input from 3 patient partners.
 

Do this

The guideline lists 18 recommendations, of which 13 are strong and 5 are conditional.

An example of a strong recommendation is number 3, based on a moderate level of evidences:

“All adult IIM patients, irrespective of cancer risk, should continue to participate in country/region-specific age and sex appropriate cancer screening programs,” the guideline recommends.

Patients with verified inclusion body myositis or juvenile-onset IIM do not, however, require routine screening for myositis-associated cancer, the guideline says (recommendations 1 and 2).

There are also recommendations that all adults with new-onset IIM be tested for myositis-specific and myositis-associated autoantibodies to assist in stratifying patients by risk category.

The guideline divides screening recommendations into basic and enhanced. The basic screening should include a comprehensive history and physical exam, complete blood count, liver functions tests, erythrocyte sedimentation rates/plasma viscosity, serum protein electrophoresis, urinalysis, and chest x-ray.

Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening at the time of IIM diagnosis. Adults with intermediate risk should undergo both basic and enhanced screening at the time of IIM diagnosis, and those with high risk should undergo enhanced screening at the time of myositis diagnosis, with basic screening annually for 3 years, the recommendations say.
 

Consider doing this

Conditional recommendations (“clinicians should consider ...”) include the use of PET/CT for adults at high risk for cancer when an underlying cancer has not been detected at the time of IIM diagnosis. They also include a single screening test for anti-TIF1-gamma positive dermatomyositis patients whose disease onset was after age 40 and who have at least one additional risk factor.

Also conditionally recommended are upper and lower gastrointestinal endoscopy for patients at high risk when an underlying cancer is not found at the time of IIM diagnosis, nasoendoscopy in geographical regions with elevated risk for nasopharyngeal cancers, and screening for all IIM patients with red-flag symptoms or clinical features of cancer, including unexplained weight loss, family history of cancer, smoking, unexplained fever, or night sweats.
 

Guided steps

“I think clinicians have a lot of questions such as, ‘well, what should I do, when should I do it?’ These are important clinical questions, and we need guidance about this. We need to balance comprehensiveness with cost-effectiveness, and we need expert opinion about what steps we should take now and which should we take later,” Dr. Kolasinski said.

The guideline development process was supported by the University of Manchester, IMACS, National Institute for Health Research (United Kingdom), National Institutes of Health, National Health Service Northern Care Alliance, The Myositis Association, Myositis UK, University of Pittsburgh, Versus Arthritis, and the Center for Musculoskeletal Research. Dr. Oldroyd and Dr. Kolasinski reported having no relevant conflicts of interest.

AT ACR 2022

PHILADELPHIA – The first consensus screening guidelines for patients with idiopathic inflammatory myopathy (IIM) provide recommendations on risk stratification for individuals, basic and enhanced screening protocols, and screening frequency.

The recommendations, issued by the International Myositis Assessment and Clinical Studies Group (IMACS), stratify cancer risk for individual patients into low, intermediate, or high categories based on the IIM disease subtype, autoantibody status, and clinical features, reported Alexander Oldroyd, PhD, MSc, MBChB of the University of Manchester, England.

Neil Osterweil/MDedge News

“There’s a big unmet need for cancer screening. One in four adults with myositis has cancer, either 3 years before or after a diagnosis of myositis. It’s one of the leading causes of death in these patients, and they’re overwhelmingly diagnosed at a late stage, so we need standardized approaches to get early diagnosis,” he said in an interview at the annual meeting of the American College of Rheumatology.

Sharon Kolasinski, MD, of the University of Pennsylvania in Philadelphia, said in an interview that the guideline is a welcome development for rheumatologists. Dr. Kolasinski moderated the session where Dr. Oldroyd described the guideline, but she was not involved in its formulation.

“I think that we all have wondered for a very long time: What is the optimal cancer screening for myositis patients? We all worry that the onset of their diseases is associated with a coincident cancer, or that they will develop it soon,” she said.

Dr. Oldroyd emphasized that all patients with myositis have elevated risk for cancer compared with the general population and that the guideline categories of low, intermediate, and high are relative only to patients with IIM.
 

International consensus

The data on which the recommendations are based come from a systematic review and meta-analysis by Dr. Oldroyd and colleagues of 69 studies on cancer risk factors and 9 on IIM-specific cancer screening.

The authors of that paper found that the dermatomyositis subtype, older age, male sex, dysphagia, cutaneous ulceration and antitranscriptional intermediary factor-1 gamma (anti-TIF1-gamma) positivity were associated with significantly increased risk of cancer.

In contrast, polymyositis and clinically amyopathic dermatomyositis subtypes, Raynaud’s phenomenon, interstitial lung disease, very high serum creatine kinase or lactate dehydrogenase levels, and positivity for anti-Jo1 or anti-EJ antibodies were associated with significantly reduced risk of cancer.

The consensus recommendations were developed with anonymous contributions from 75 expert participants in 22 countries, with additional input from 3 patient partners.
 

Do this

The guideline lists 18 recommendations, of which 13 are strong and 5 are conditional.

An example of a strong recommendation is number 3, based on a moderate level of evidences:

“All adult IIM patients, irrespective of cancer risk, should continue to participate in country/region-specific age and sex appropriate cancer screening programs,” the guideline recommends.

Patients with verified inclusion body myositis or juvenile-onset IIM do not, however, require routine screening for myositis-associated cancer, the guideline says (recommendations 1 and 2).

There are also recommendations that all adults with new-onset IIM be tested for myositis-specific and myositis-associated autoantibodies to assist in stratifying patients by risk category.

The guideline divides screening recommendations into basic and enhanced. The basic screening should include a comprehensive history and physical exam, complete blood count, liver functions tests, erythrocyte sedimentation rates/plasma viscosity, serum protein electrophoresis, urinalysis, and chest x-ray.

Adults with IIM who are determined to be at low risk for IIM-related cancer should have basic cancer screening at the time of IIM diagnosis. Adults with intermediate risk should undergo both basic and enhanced screening at the time of IIM diagnosis, and those with high risk should undergo enhanced screening at the time of myositis diagnosis, with basic screening annually for 3 years, the recommendations say.
 

Consider doing this

Conditional recommendations (“clinicians should consider ...”) include the use of PET/CT for adults at high risk for cancer when an underlying cancer has not been detected at the time of IIM diagnosis. They also include a single screening test for anti-TIF1-gamma positive dermatomyositis patients whose disease onset was after age 40 and who have at least one additional risk factor.

Also conditionally recommended are upper and lower gastrointestinal endoscopy for patients at high risk when an underlying cancer is not found at the time of IIM diagnosis, nasoendoscopy in geographical regions with elevated risk for nasopharyngeal cancers, and screening for all IIM patients with red-flag symptoms or clinical features of cancer, including unexplained weight loss, family history of cancer, smoking, unexplained fever, or night sweats.
 

Guided steps

“I think clinicians have a lot of questions such as, ‘well, what should I do, when should I do it?’ These are important clinical questions, and we need guidance about this. We need to balance comprehensiveness with cost-effectiveness, and we need expert opinion about what steps we should take now and which should we take later,” Dr. Kolasinski said.

The guideline development process was supported by the University of Manchester, IMACS, National Institute for Health Research (United Kingdom), National Institutes of Health, National Health Service Northern Care Alliance, The Myositis Association, Myositis UK, University of Pittsburgh, Versus Arthritis, and the Center for Musculoskeletal Research. Dr. Oldroyd and Dr. Kolasinski reported having no relevant conflicts of interest.

From providing virtual therapy sessions to patients in the front seats of their cars, to sessions with patients who turn out to be in another state, the new paradigm of telepsychiatry is presenting clinicians with a host of situations with unwritten or constantly changing rules.

But key practice tips are emerging for the optimization of virtual sessions, said Sanjay Gupta, MD, chief medical officer of the BryLin Behavioral Health System in Buffalo, N.Y., during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists in Cincinnati, Ohio.

Dr. Gupta noted that while “many pitfalls [may] occur,” an overriding rule that should be emphasized with telepsychiatry is that “[virtual visits] are held to the same standard of care as an in-person visit.” This “rule” needs to be followed diligently, he said, as the key difference in virtual visits is a reduced sense of the formality of a psychotherapy session.

With virtual sessions, the therapeutic experience “can feel kind of trivialized,” said Dr. Gupta, who is also a clinical professor in the department of psychiatry, State University of New York at Buffalo. He noted that it is crucial that “the sacredness of a private setting should not be diluted.”

Challenges in finding that privacy for some, however, lead to the issue of the “patients in cars” scenario, Dr. Gupta said. Still, he added, while psychiatric sessions should never be conducted when a patient is driving, the front seat of a parked car may, for some, be the most private setting available.

“For many patients, their car may be the only private place from which they can take a video call,” Dr. Gupta noted. “Perhaps they are at work and the only way they could fit in the appointment is by going out to their car on their break. Or patients may even be at home, but they’re not alone and need to go out to their car for privacy.”

If the car isn’t being driven, sitting inside it should be fine for virtual therapy, but even there, clinicians should retain a focus on the consistency of care regardless of the setting.

Meanwhile, psychiatrists can take key measures to keep things professional, at least on their end of the session.

Before starting, for instance, keep in mind the patient’s viewing experience, Dr. Gupta suggested. Tips he offered include:

• Keep the background of your video image subtle, with no distractions, such as windows looking out to an ocean or other distracting background elements.
• The camera should be above eye level to suggest a face-to-face conversation more effectively.
• Try not to have other browser windows open and look directly into the camera lens so that the patient knows they have your full attention.
• Try not to take notes or document in the electronic health record during the session, which also can give the impression of being distracted and not listening to the patient.

Psychiatrists should remember that older patients – who may be uncomfortable with email, much less video conferencing – may still struggle with video-calling technology. In such cases, consider:

• Sending the patient instructions in advance of the appointment.
• Have your office hold a “tech check” prior to the appointment to ensure the patient is ready.
• Be prepared to provide troubleshooting.

Whether the patient is tech savvy or not, make sure communication is clear:

• Speak in short sentences on teleconferencing sessions.
• Speak slowly and use a lower frequency.
• Recognize that non-native English speakers may struggle with comprehension, and explore interpreter options.

Dr. Gupta noted that the first minute of the virtual therapy session is crucial in setting the tone.

“The patient wants to hear a professional, confident tone on the other end at the beginning of the session,” he said. “Be warm and respectful throughout the visit, and make sure to explain to the patient how the session will be reconnected if the call is interrupted.”

Clinicians should also make sure to identify the patient’s physical location during the session in case of an emergency, such as the patient becoming suicidal.
 

Impending ‘telehealth cliff’

Many laws and licensing requirements for telehealth are still relatively loose, falling under the COVID-19 public health emergency (PHE) policies. These policies allow practitioners who are eligible to bill Medicare for telehealth services regardless of where the patient or provider is located, and providers can also deliver telehealth services across state lines, depending on state and federal rules.

However, Dr. Gupta warns that practitioners should be prepared for the potential “telehealth cliff” that is anticipated when those PHE policies are lifted, as barriers in licensing, billing, and other factors, such as HIPAA, are reinstated.

“HIPAA is [flexible] now as long as the public emergency policies exist,” Dr. Gupta said. “However, in noncrisis times, technology will be required to be HIPAA compliant. If you are a solo provider, for instance, you really need to choose a telepsychiatry platform that is HIPAA compliant before that happens.”

While the timing of the “telehealth cliff” is still uncertain, providers have been promised a 60-day advance notice of the PHE end, and at that time, there will be an additional 151-day grace period before the waivers lift.

A key federal measure that could protect more favorable telemedicine policies across state lines, the Temporary Reciprocity to Ensure Access to Treatment Act, currently remains stalled in Congress.

Regardless of those developments, Dr. Gupta underscored that “telepsychiatry is here to stay because the patients and their families like it, and they will be the driving factors.”

He noted that “the future is likely going to be a hybrid model of in-person and virtual visits,” to accommodate the various scenarios in which in-person visits may be preferred or necessary, but many will still likely choose the convenience and greater flexibility of virtual sessions.

Dr. Gupta serves or has served as a speaker or member of a speaker’s bureau for AbbVie, Acadia, Alkermes, Intra-Cellular Therapies, Janssen, Neurocrine, and Otsuka, and serves as a consultant/on an advisory board for Intra-Cellular Therapies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

From providing virtual therapy sessions to patients in the front seats of their cars, to sessions with patients who turn out to be in another state, the new paradigm of telepsychiatry is presenting clinicians with a host of situations with unwritten or constantly changing rules.

But key practice tips are emerging for the optimization of virtual sessions, said Sanjay Gupta, MD, chief medical officer of the BryLin Behavioral Health System in Buffalo, N.Y., during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists in Cincinnati, Ohio.

Dr. Gupta noted that while “many pitfalls [may] occur,” an overriding rule that should be emphasized with telepsychiatry is that “[virtual visits] are held to the same standard of care as an in-person visit.” This “rule” needs to be followed diligently, he said, as the key difference in virtual visits is a reduced sense of the formality of a psychotherapy session.

With virtual sessions, the therapeutic experience “can feel kind of trivialized,” said Dr. Gupta, who is also a clinical professor in the department of psychiatry, State University of New York at Buffalo. He noted that it is crucial that “the sacredness of a private setting should not be diluted.”

Challenges in finding that privacy for some, however, lead to the issue of the “patients in cars” scenario, Dr. Gupta said. Still, he added, while psychiatric sessions should never be conducted when a patient is driving, the front seat of a parked car may, for some, be the most private setting available.

“For many patients, their car may be the only private place from which they can take a video call,” Dr. Gupta noted. “Perhaps they are at work and the only way they could fit in the appointment is by going out to their car on their break. Or patients may even be at home, but they’re not alone and need to go out to their car for privacy.”

If the car isn’t being driven, sitting inside it should be fine for virtual therapy, but even there, clinicians should retain a focus on the consistency of care regardless of the setting.

Meanwhile, psychiatrists can take key measures to keep things professional, at least on their end of the session.

Before starting, for instance, keep in mind the patient’s viewing experience, Dr. Gupta suggested. Tips he offered include:

• Keep the background of your video image subtle, with no distractions, such as windows looking out to an ocean or other distracting background elements.
• The camera should be above eye level to suggest a face-to-face conversation more effectively.
• Try not to have other browser windows open and look directly into the camera lens so that the patient knows they have your full attention.
• Try not to take notes or document in the electronic health record during the session, which also can give the impression of being distracted and not listening to the patient.

Psychiatrists should remember that older patients – who may be uncomfortable with email, much less video conferencing – may still struggle with video-calling technology. In such cases, consider:

• Sending the patient instructions in advance of the appointment.
• Have your office hold a “tech check” prior to the appointment to ensure the patient is ready.
• Be prepared to provide troubleshooting.

Whether the patient is tech savvy or not, make sure communication is clear:

• Speak in short sentences on teleconferencing sessions.
• Speak slowly and use a lower frequency.
• Recognize that non-native English speakers may struggle with comprehension, and explore interpreter options.

Dr. Gupta noted that the first minute of the virtual therapy session is crucial in setting the tone.

“The patient wants to hear a professional, confident tone on the other end at the beginning of the session,” he said. “Be warm and respectful throughout the visit, and make sure to explain to the patient how the session will be reconnected if the call is interrupted.”

Clinicians should also make sure to identify the patient’s physical location during the session in case of an emergency, such as the patient becoming suicidal.
 

Impending ‘telehealth cliff’

Many laws and licensing requirements for telehealth are still relatively loose, falling under the COVID-19 public health emergency (PHE) policies. These policies allow practitioners who are eligible to bill Medicare for telehealth services regardless of where the patient or provider is located, and providers can also deliver telehealth services across state lines, depending on state and federal rules.

However, Dr. Gupta warns that practitioners should be prepared for the potential “telehealth cliff” that is anticipated when those PHE policies are lifted, as barriers in licensing, billing, and other factors, such as HIPAA, are reinstated.

“HIPAA is [flexible] now as long as the public emergency policies exist,” Dr. Gupta said. “However, in noncrisis times, technology will be required to be HIPAA compliant. If you are a solo provider, for instance, you really need to choose a telepsychiatry platform that is HIPAA compliant before that happens.”

While the timing of the “telehealth cliff” is still uncertain, providers have been promised a 60-day advance notice of the PHE end, and at that time, there will be an additional 151-day grace period before the waivers lift.

A key federal measure that could protect more favorable telemedicine policies across state lines, the Temporary Reciprocity to Ensure Access to Treatment Act, currently remains stalled in Congress.

Regardless of those developments, Dr. Gupta underscored that “telepsychiatry is here to stay because the patients and their families like it, and they will be the driving factors.”

He noted that “the future is likely going to be a hybrid model of in-person and virtual visits,” to accommodate the various scenarios in which in-person visits may be preferred or necessary, but many will still likely choose the convenience and greater flexibility of virtual sessions.

Dr. Gupta serves or has served as a speaker or member of a speaker’s bureau for AbbVie, Acadia, Alkermes, Intra-Cellular Therapies, Janssen, Neurocrine, and Otsuka, and serves as a consultant/on an advisory board for Intra-Cellular Therapies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

From providing virtual therapy sessions to patients in the front seats of their cars, to sessions with patients who turn out to be in another state, the new paradigm of telepsychiatry is presenting clinicians with a host of situations with unwritten or constantly changing rules.

But key practice tips are emerging for the optimization of virtual sessions, said Sanjay Gupta, MD, chief medical officer of the BryLin Behavioral Health System in Buffalo, N.Y., during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists in Cincinnati, Ohio.

Dr. Gupta noted that while “many pitfalls [may] occur,” an overriding rule that should be emphasized with telepsychiatry is that “[virtual visits] are held to the same standard of care as an in-person visit.” This “rule” needs to be followed diligently, he said, as the key difference in virtual visits is a reduced sense of the formality of a psychotherapy session.

With virtual sessions, the therapeutic experience “can feel kind of trivialized,” said Dr. Gupta, who is also a clinical professor in the department of psychiatry, State University of New York at Buffalo. He noted that it is crucial that “the sacredness of a private setting should not be diluted.”

Challenges in finding that privacy for some, however, lead to the issue of the “patients in cars” scenario, Dr. Gupta said. Still, he added, while psychiatric sessions should never be conducted when a patient is driving, the front seat of a parked car may, for some, be the most private setting available.

“For many patients, their car may be the only private place from which they can take a video call,” Dr. Gupta noted. “Perhaps they are at work and the only way they could fit in the appointment is by going out to their car on their break. Or patients may even be at home, but they’re not alone and need to go out to their car for privacy.”

If the car isn’t being driven, sitting inside it should be fine for virtual therapy, but even there, clinicians should retain a focus on the consistency of care regardless of the setting.

Meanwhile, psychiatrists can take key measures to keep things professional, at least on their end of the session.

Before starting, for instance, keep in mind the patient’s viewing experience, Dr. Gupta suggested. Tips he offered include:

• Keep the background of your video image subtle, with no distractions, such as windows looking out to an ocean or other distracting background elements.
• The camera should be above eye level to suggest a face-to-face conversation more effectively.
• Try not to have other browser windows open and look directly into the camera lens so that the patient knows they have your full attention.
• Try not to take notes or document in the electronic health record during the session, which also can give the impression of being distracted and not listening to the patient.

Psychiatrists should remember that older patients – who may be uncomfortable with email, much less video conferencing – may still struggle with video-calling technology. In such cases, consider:

• Sending the patient instructions in advance of the appointment.
• Have your office hold a “tech check” prior to the appointment to ensure the patient is ready.
• Be prepared to provide troubleshooting.

Whether the patient is tech savvy or not, make sure communication is clear:

• Speak in short sentences on teleconferencing sessions.
• Speak slowly and use a lower frequency.
• Recognize that non-native English speakers may struggle with comprehension, and explore interpreter options.

Dr. Gupta noted that the first minute of the virtual therapy session is crucial in setting the tone.

“The patient wants to hear a professional, confident tone on the other end at the beginning of the session,” he said. “Be warm and respectful throughout the visit, and make sure to explain to the patient how the session will be reconnected if the call is interrupted.”

Clinicians should also make sure to identify the patient’s physical location during the session in case of an emergency, such as the patient becoming suicidal.
 

Impending ‘telehealth cliff’

Many laws and licensing requirements for telehealth are still relatively loose, falling under the COVID-19 public health emergency (PHE) policies. These policies allow practitioners who are eligible to bill Medicare for telehealth services regardless of where the patient or provider is located, and providers can also deliver telehealth services across state lines, depending on state and federal rules.

However, Dr. Gupta warns that practitioners should be prepared for the potential “telehealth cliff” that is anticipated when those PHE policies are lifted, as barriers in licensing, billing, and other factors, such as HIPAA, are reinstated.

“HIPAA is [flexible] now as long as the public emergency policies exist,” Dr. Gupta said. “However, in noncrisis times, technology will be required to be HIPAA compliant. If you are a solo provider, for instance, you really need to choose a telepsychiatry platform that is HIPAA compliant before that happens.”

While the timing of the “telehealth cliff” is still uncertain, providers have been promised a 60-day advance notice of the PHE end, and at that time, there will be an additional 151-day grace period before the waivers lift.

A key federal measure that could protect more favorable telemedicine policies across state lines, the Temporary Reciprocity to Ensure Access to Treatment Act, currently remains stalled in Congress.

Regardless of those developments, Dr. Gupta underscored that “telepsychiatry is here to stay because the patients and their families like it, and they will be the driving factors.”

He noted that “the future is likely going to be a hybrid model of in-person and virtual visits,” to accommodate the various scenarios in which in-person visits may be preferred or necessary, but many will still likely choose the convenience and greater flexibility of virtual sessions.

Dr. Gupta serves or has served as a speaker or member of a speaker’s bureau for AbbVie, Acadia, Alkermes, Intra-Cellular Therapies, Janssen, Neurocrine, and Otsuka, and serves as a consultant/on an advisory board for Intra-Cellular Therapies.

The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.

A new U.S. randomized trial has failed to show benefit of a 35-day course of oral anticoagulation with rivaroxaban for the prevention of thrombotic events in outpatients with symptomatic COVID-19.

The PREVENT-HD trial was presented at the American Heart Association scientific sessions by Gregory Piazza, MD, Brigham and Women’s Hospital, Boston.

“With the caveat that the trial was underpowered to provide a definitive conclusion, these data do not support routine antithrombotic prophylaxis in nonhospitalized patients with symptomatic COVID-19,” Dr. Piazza concluded.

PREVENT-HD is the largest randomized study to look at anticoagulation in nonhospitalized COVID-19 patients and joins a long list of smaller trials that have also shown no benefit with this approach.

However, anticoagulation is recommended in patients who are hospitalized with COVID-19.

Dr. Piazza noted that the issue of anticoagulation in COVID-19 has focused mainly on hospitalized patients, but most COVID-19 cases are treated as outpatients, who are also suspected to be at risk for venous and arterial thrombotic events, especially if they have additional risk factors. Histopathological evidence also suggests that at least part of the deterioration in lung function leading to hospitalization may be attributable to in situ pulmonary artery thrombosis.

The PREVENT-HD trial explored the question of whether early initiation of thromboprophylaxis dosing of rivaroxaban in higher-risk outpatients with COVID-19 may lower the incidence of venous and arterial thrombotic events, reduce in situ pulmonary thrombosis and the worsening of pulmonary function that may lead to hospitalization, and reduce all-cause mortality.

The trial included 1,284 outpatients with a positive test for COVID-19 and who were within 14 days of symptom onset. They also had to have at least one of the following additional risk factors: age over 60 years; prior history of venous thromboembolism (VTE), thrombophilia, coronary artery disease, peripheral artery disease, cardiovascular disease or ischemic stroke, cancer, diabetes, heart failure, obesity (body mass index ≥ 35 kg/m²) or D-dimer > upper limit of normal. Around 35% of the study population had two or more of these risk factors.

Patients were randomized to rivaroxaban 10 mg daily for 35 days or placebo.

The primary efficacy endpoint was time to first occurrence of a composite of symptomatic VTE, myocardial infarction, ischemic stroke, acute limb ischemia, non–central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality up to day 35.

The primary safety endpoint was time to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) critical-site and fatal bleeding.

A modified intention-to-treat analysis (all participants taking at least one dose of study intervention) was also planned.

The trial was stopped early in April this year because of a lower than expected event incidence (3.2%), compared with the planned rate (8.5%), giving a very low likelihood of being able to achieve the required number of events.

Dr. Piazza said reasons contributing to the low event rate included a falling COVID-19 death and hospitalization rate nationwide, and increased use of effective vaccines.

Results of the main intention-to-treat analysis (in 1,284 patients) showed no significant difference in the primary efficacy composite endpoint, which occurred in 3.4% of the rivaroxaban group versus 3.0% of the placebo group.

In the modified intention-to-treat analysis (which included 1,197 patients who actually took at least one dose of the study medication) there was shift in the directionality of the point estimate (rivaroxaban 2.0% vs. placebo 2.7%), which Dr. Piazza said was related to a higher number of patients hospitalized before receiving study drug in the rivaroxaban group. However, the difference was still nonsignificant. 

The first major secondary outcome of symptomatic VTE, arterial thrombotic events, and all-cause mortality occurred in 0.3% of rivaroxaban patients versus 1.1% of placebo patients, but this difference did not reach statistical significance.

However, a post hoc exploratory analysis did show a significant reduction in the outcome of symptomatic VTE and arterial thrombotic events. 

In terms of safety, there were no fatal critical-site bleeding events, and there was no difference in ISTH major bleeding, which occurred in one patient in the rivaroxaban group versus no patients in the placebo group.

There was, however, a significant increase in nonmajor clinically relevant bleeding with rivaroxaban, which occurred in nine patients (1.5%) versus one patient (0.2%) in the placebo group.

Trivial bleeding was also increased in the rivaroxaban group, occurring in 17 patients (2.8%) versus 5 patients (0.8%) in the placebo group.

Discussant for the study, Renato Lopes, MD, Duke University Medical Center, Durham, N.C., noted that the relationship between COVID-19 and thrombosis has been an important issue since the beginning of the pandemic, with many proposed mechanisms to explain the COVID-19–associated coagulopathy, which is a major cause of death and disability.

While observational data at the beginning of the pandemic suggested patients with COVID-19 might benefit from anticoagulation, looking at all the different randomized trials that have tested anticoagulation in COVID-19 outpatients, there is no treatment effect on the various different primary outcomes in those studies and also no effect on all-cause mortality, Dr. Lopes said. 

He pointed out that PREVENT-HD was stopped prematurely with only about one-third of the planned number of patients enrolled, “just like every other outpatient COVID-19 trial.”

He also drew attention to the low rates of vaccination in the trial population, which does not reflect the current vaccination rate in the United States, and said the different direction of the results between the main intention-to-treat and modified intention-to-treat analyses deserve further investigation.

However, Dr. Lopes concluded, “The results of this trial, in line with the body of evidence in this field, do not support the routine use of any antithrombotic therapy for outpatients with COVID-19.”

The PREVENT-HD trial was sponsored by Janssen. Dr. Piazza has reported receiving research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific, and consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific, Janssen, NAMSA, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen.

A version of this article first appeared on Medscape.com.

A new U.S. randomized trial has failed to show benefit of a 35-day course of oral anticoagulation with rivaroxaban for the prevention of thrombotic events in outpatients with symptomatic COVID-19.

The PREVENT-HD trial was presented at the American Heart Association scientific sessions by Gregory Piazza, MD, Brigham and Women’s Hospital, Boston.

“With the caveat that the trial was underpowered to provide a definitive conclusion, these data do not support routine antithrombotic prophylaxis in nonhospitalized patients with symptomatic COVID-19,” Dr. Piazza concluded.

PREVENT-HD is the largest randomized study to look at anticoagulation in nonhospitalized COVID-19 patients and joins a long list of smaller trials that have also shown no benefit with this approach.

However, anticoagulation is recommended in patients who are hospitalized with COVID-19.

Dr. Piazza noted that the issue of anticoagulation in COVID-19 has focused mainly on hospitalized patients, but most COVID-19 cases are treated as outpatients, who are also suspected to be at risk for venous and arterial thrombotic events, especially if they have additional risk factors. Histopathological evidence also suggests that at least part of the deterioration in lung function leading to hospitalization may be attributable to in situ pulmonary artery thrombosis.

The PREVENT-HD trial explored the question of whether early initiation of thromboprophylaxis dosing of rivaroxaban in higher-risk outpatients with COVID-19 may lower the incidence of venous and arterial thrombotic events, reduce in situ pulmonary thrombosis and the worsening of pulmonary function that may lead to hospitalization, and reduce all-cause mortality.

The trial included 1,284 outpatients with a positive test for COVID-19 and who were within 14 days of symptom onset. They also had to have at least one of the following additional risk factors: age over 60 years; prior history of venous thromboembolism (VTE), thrombophilia, coronary artery disease, peripheral artery disease, cardiovascular disease or ischemic stroke, cancer, diabetes, heart failure, obesity (body mass index ≥ 35 kg/m²) or D-dimer > upper limit of normal. Around 35% of the study population had two or more of these risk factors.

Patients were randomized to rivaroxaban 10 mg daily for 35 days or placebo.

The primary efficacy endpoint was time to first occurrence of a composite of symptomatic VTE, myocardial infarction, ischemic stroke, acute limb ischemia, non–central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality up to day 35.

The primary safety endpoint was time to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) critical-site and fatal bleeding.

A modified intention-to-treat analysis (all participants taking at least one dose of study intervention) was also planned.

The trial was stopped early in April this year because of a lower than expected event incidence (3.2%), compared with the planned rate (8.5%), giving a very low likelihood of being able to achieve the required number of events.

Dr. Piazza said reasons contributing to the low event rate included a falling COVID-19 death and hospitalization rate nationwide, and increased use of effective vaccines.

Results of the main intention-to-treat analysis (in 1,284 patients) showed no significant difference in the primary efficacy composite endpoint, which occurred in 3.4% of the rivaroxaban group versus 3.0% of the placebo group.

In the modified intention-to-treat analysis (which included 1,197 patients who actually took at least one dose of the study medication) there was shift in the directionality of the point estimate (rivaroxaban 2.0% vs. placebo 2.7%), which Dr. Piazza said was related to a higher number of patients hospitalized before receiving study drug in the rivaroxaban group. However, the difference was still nonsignificant. 

The first major secondary outcome of symptomatic VTE, arterial thrombotic events, and all-cause mortality occurred in 0.3% of rivaroxaban patients versus 1.1% of placebo patients, but this difference did not reach statistical significance.

However, a post hoc exploratory analysis did show a significant reduction in the outcome of symptomatic VTE and arterial thrombotic events. 

In terms of safety, there were no fatal critical-site bleeding events, and there was no difference in ISTH major bleeding, which occurred in one patient in the rivaroxaban group versus no patients in the placebo group.

There was, however, a significant increase in nonmajor clinically relevant bleeding with rivaroxaban, which occurred in nine patients (1.5%) versus one patient (0.2%) in the placebo group.

Trivial bleeding was also increased in the rivaroxaban group, occurring in 17 patients (2.8%) versus 5 patients (0.8%) in the placebo group.

Discussant for the study, Renato Lopes, MD, Duke University Medical Center, Durham, N.C., noted that the relationship between COVID-19 and thrombosis has been an important issue since the beginning of the pandemic, with many proposed mechanisms to explain the COVID-19–associated coagulopathy, which is a major cause of death and disability.

While observational data at the beginning of the pandemic suggested patients with COVID-19 might benefit from anticoagulation, looking at all the different randomized trials that have tested anticoagulation in COVID-19 outpatients, there is no treatment effect on the various different primary outcomes in those studies and also no effect on all-cause mortality, Dr. Lopes said. 

He pointed out that PREVENT-HD was stopped prematurely with only about one-third of the planned number of patients enrolled, “just like every other outpatient COVID-19 trial.”

He also drew attention to the low rates of vaccination in the trial population, which does not reflect the current vaccination rate in the United States, and said the different direction of the results between the main intention-to-treat and modified intention-to-treat analyses deserve further investigation.

However, Dr. Lopes concluded, “The results of this trial, in line with the body of evidence in this field, do not support the routine use of any antithrombotic therapy for outpatients with COVID-19.”

The PREVENT-HD trial was sponsored by Janssen. Dr. Piazza has reported receiving research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific, and consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific, Janssen, NAMSA, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen.

A version of this article first appeared on Medscape.com.

A new U.S. randomized trial has failed to show benefit of a 35-day course of oral anticoagulation with rivaroxaban for the prevention of thrombotic events in outpatients with symptomatic COVID-19.

The PREVENT-HD trial was presented at the American Heart Association scientific sessions by Gregory Piazza, MD, Brigham and Women’s Hospital, Boston.

“With the caveat that the trial was underpowered to provide a definitive conclusion, these data do not support routine antithrombotic prophylaxis in nonhospitalized patients with symptomatic COVID-19,” Dr. Piazza concluded.

PREVENT-HD is the largest randomized study to look at anticoagulation in nonhospitalized COVID-19 patients and joins a long list of smaller trials that have also shown no benefit with this approach.

However, anticoagulation is recommended in patients who are hospitalized with COVID-19.

Dr. Piazza noted that the issue of anticoagulation in COVID-19 has focused mainly on hospitalized patients, but most COVID-19 cases are treated as outpatients, who are also suspected to be at risk for venous and arterial thrombotic events, especially if they have additional risk factors. Histopathological evidence also suggests that at least part of the deterioration in lung function leading to hospitalization may be attributable to in situ pulmonary artery thrombosis.

The PREVENT-HD trial explored the question of whether early initiation of thromboprophylaxis dosing of rivaroxaban in higher-risk outpatients with COVID-19 may lower the incidence of venous and arterial thrombotic events, reduce in situ pulmonary thrombosis and the worsening of pulmonary function that may lead to hospitalization, and reduce all-cause mortality.

The trial included 1,284 outpatients with a positive test for COVID-19 and who were within 14 days of symptom onset. They also had to have at least one of the following additional risk factors: age over 60 years; prior history of venous thromboembolism (VTE), thrombophilia, coronary artery disease, peripheral artery disease, cardiovascular disease or ischemic stroke, cancer, diabetes, heart failure, obesity (body mass index ≥ 35 kg/m²) or D-dimer > upper limit of normal. Around 35% of the study population had two or more of these risk factors.

Patients were randomized to rivaroxaban 10 mg daily for 35 days or placebo.

The primary efficacy endpoint was time to first occurrence of a composite of symptomatic VTE, myocardial infarction, ischemic stroke, acute limb ischemia, non–central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality up to day 35.

The primary safety endpoint was time to first occurrence of International Society on Thrombosis and Hemostasis (ISTH) critical-site and fatal bleeding.

A modified intention-to-treat analysis (all participants taking at least one dose of study intervention) was also planned.

The trial was stopped early in April this year because of a lower than expected event incidence (3.2%), compared with the planned rate (8.5%), giving a very low likelihood of being able to achieve the required number of events.

Dr. Piazza said reasons contributing to the low event rate included a falling COVID-19 death and hospitalization rate nationwide, and increased use of effective vaccines.

Results of the main intention-to-treat analysis (in 1,284 patients) showed no significant difference in the primary efficacy composite endpoint, which occurred in 3.4% of the rivaroxaban group versus 3.0% of the placebo group.

In the modified intention-to-treat analysis (which included 1,197 patients who actually took at least one dose of the study medication) there was shift in the directionality of the point estimate (rivaroxaban 2.0% vs. placebo 2.7%), which Dr. Piazza said was related to a higher number of patients hospitalized before receiving study drug in the rivaroxaban group. However, the difference was still nonsignificant. 

The first major secondary outcome of symptomatic VTE, arterial thrombotic events, and all-cause mortality occurred in 0.3% of rivaroxaban patients versus 1.1% of placebo patients, but this difference did not reach statistical significance.

However, a post hoc exploratory analysis did show a significant reduction in the outcome of symptomatic VTE and arterial thrombotic events. 

In terms of safety, there were no fatal critical-site bleeding events, and there was no difference in ISTH major bleeding, which occurred in one patient in the rivaroxaban group versus no patients in the placebo group.

There was, however, a significant increase in nonmajor clinically relevant bleeding with rivaroxaban, which occurred in nine patients (1.5%) versus one patient (0.2%) in the placebo group.

Trivial bleeding was also increased in the rivaroxaban group, occurring in 17 patients (2.8%) versus 5 patients (0.8%) in the placebo group.

Discussant for the study, Renato Lopes, MD, Duke University Medical Center, Durham, N.C., noted that the relationship between COVID-19 and thrombosis has been an important issue since the beginning of the pandemic, with many proposed mechanisms to explain the COVID-19–associated coagulopathy, which is a major cause of death and disability.

While observational data at the beginning of the pandemic suggested patients with COVID-19 might benefit from anticoagulation, looking at all the different randomized trials that have tested anticoagulation in COVID-19 outpatients, there is no treatment effect on the various different primary outcomes in those studies and also no effect on all-cause mortality, Dr. Lopes said. 

He pointed out that PREVENT-HD was stopped prematurely with only about one-third of the planned number of patients enrolled, “just like every other outpatient COVID-19 trial.”

He also drew attention to the low rates of vaccination in the trial population, which does not reflect the current vaccination rate in the United States, and said the different direction of the results between the main intention-to-treat and modified intention-to-treat analyses deserve further investigation.

However, Dr. Lopes concluded, “The results of this trial, in line with the body of evidence in this field, do not support the routine use of any antithrombotic therapy for outpatients with COVID-19.”

The PREVENT-HD trial was sponsored by Janssen. Dr. Piazza has reported receiving research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific, and consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific, Janssen, NAMSA, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen.

A version of this article first appeared on Medscape.com.

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

Apple A. Bodemer, MD, a dermatologist at the University of Wisconsin, Madison, teaches patients how to breathe mindfully. So does Kathy Farah, MD, an integrative family physician who practices in Roberts, Wis.

Mindful breathing is the most basic mind-body skill and one that can help interrupt the itch-scratch cycle and relieve pain, stress, and distress often experienced by children, teens, and adults with dermatologic conditions, they said at the annual Integrative Dermatology Symposium.

“As with any integrative modality, if it’s safe and effective, then let’s use it,” Dr. Farah said in a presentation on the mind-body approach to pain and itch.

“A breathwork session can literally take 1 minute,” said Dr. Bodemer, associate professor of dermatology at the University of Wisconsin and director of an integrative dermatology clinic. Dr. Bodemer, who completed a fellowship in integrative medicine at the Andrew Weil Center for Integrative Medicine at the University of Arizona and sits on the American Board of Integrative Medicine, spoke on a mindfulness panel at the meeting.

Her favorite breathing practice is the “4-7-8” breath taught by Andrew Weil, MD, founder and director of the center. This involves inhaling through the nose for a count of 4, holding for 7, and exhaling through the mouth for a count of 8. “It doesn’t matter how slow or fast, it’s the tempo that matters ... On exhale, squeeze your abs in to engage your core and get air out of your lungs as much as you can,” she said, advising a cycle of three at a time.

A technique known as “square breathing” (breath in 4, hold for 4, breath out for 4, hold for 4) is another helpful technique to “reset the nervous system” said Dr. Farah, who worked for many years in a children’s hospital. With children, she said, “I often do five finger breathing.”

For five finger breathing, the children spread their fingers apart in front of them or on the ground and use the pointer finger of the opposite hand to trace each finger, inhaling while tracing upward, and exhaling while tracing down.

Dr. Farah, associate clinical director of The Center for Mind-Body Medicine in Washington, DC, said her commitment to mindfulness was influenced by a “seminal” study published over 20 years ago showing that patients with moderate to severe psoriasis who used a meditation-based, audiotape-guided stress reduction intervention during phototherapy sessions had more rapid resolution of psoriatic lesions than did patients who didn’t use the mindfulness exercise.

Among more recent findings: A cross-sectional study of 120 adult dermatology patients, published in the British Journal of Dermatology in 2016, assessed skin shame, social anxiety, anxiety, depression, dermatological quality of life, and levels of mindfulness, and found that higher levels of mindfulness were associated with lower levels of psychosocial distress.

Another cross-sectional questionnaire study looked at mindfulness and “itch catastrophizing” in 155 adult patients with atopic dermatitis. Higher levels of a specific facet of mindfulness termed “acting with awareness” were associated with lower levels of itch catastrophizing, the researchers found. “Catastrophizing is a negative way of thinking, this itching will never stop,” Dr. Farah explained. The study shows that “mindfulness can actually help reduce some of the automatic scratching and response to itch. So it’s a great adjunct to pharmaceuticals.”

Affirmations – phrases and statements that are repeated to oneself to help challenge negative thoughts – can also help reverse itch catastrophizing. Statements such as “I can breathe through this feeling of itching,” or “I can move to feel comfortable and relaxed” encourage positive change, she said.

“I teach [mindfulness skills like breathing] a lot, without any expectations. I’ll say ‘give it a try and see what you think.’ If patients feel even a micron better, then they’re invested” and can then find numerous tools online, Dr. Farah said. “Can I do this [in a busy schedule] with every patient? Absolutely not. But can I do it with every 10th patient? Maybe.”

Dr. Bodemer’s experience has shown her that “breathing with your patient builds rapport,” she said. “There’s something very powerful in that in terms of building trust. ... I’ll just do it [during a visit, to show them] and almost always, patients start breathing with me, with an invitation or without.”

For her own health, 4-7-8 breathing has “been a gateway to meditation and deeper practices,” she said. “But even without going very deep, it has a long history of being able to modulate the stress response. It’s the parasympathetic-sympathetic rebalancing I’m interested in.”

Mindful breathing and other mind-body practices also can be helpful for parents of children with eczema, she and Dr. Farah said.

Dr. Bodemer and Dr. Farah reported no financial relationships to disclose.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

CHICAGO – Early ablation of atrial fibrillation (AFib) reduces the risk of progression, compared with antiarrhythmic therapies, according to results of a multicenter, randomized trial called PROGRESSIVE-AF.

Over 36 months of follow-up, the trial linked early ablation with a reduced risk of persistent AFib (1.9% vs. 7.4%), and in addition, those in the ablation group were less likely to have recurrent atrial tachyarrhythmias of any kind (56.5% vs. 77.2%), reported Jason G. Andrade, MD, at the American Heart Association scientific sessions.

Ted Bosworth/MDedge

Serving as a long-term extension of the EARLY-AF trial published almost 2 years ago, this trial expands evidence that progressive AFib can be attenuated, a concept that has been debated.

“Can early AFib ablation stop progression?” asked Carina Blomström-Lindqvist, MD, PhD. The invited discussant for the PROGRESSION-AF trial, Dr. Blomström-Lundqvist concluded, “here is another set of data that suggests it can.”

By another set of data, Dr. Blomström-Lindqvist was referring to a previously published multinational study called ATTEST In this study, which involved 29 sites worldwide and compared radiofrequency ablation to antiarrhythmic drug therapy, early ablation also produced a lower risk of persistent AFib at the end of 3 years (2.4% vs. 17.5%; P = .0009).

In the previously published open-label EARLY-AF trial, 303 patients with paroxysmal, untreated AFib were randomized to cryoballoon ablation or antiarrhythmic drugs. The primary endpoint was the first documented recurrence of an atrial tachyarrhythmia between 91 and 365 days. The lower rate following ablation (42.9% vs. 67.8%) represented a more than 50% reduction in risk (hazard ratio, 0.48; P < .001) relative to antiarrhythmic therapy.

In PROGRESSIVE-AF, the same 303 patients were monitored continuously for an additional 24 months with an implanted cardiac monitor programmed with an AFib-detection algorithm. The data from the monitor were obtained daily. Over the final 2 years of the study, office visits were conducted every 6 months.
 

Tachyarrhythmias represent primary endpoint

In addition to persistent AFib, defined as lasting ≥ 7 days or lasting 48 hours to 7 days but requiring cardioversion for termination, patients in PROGRESSIVE-AF were also monitored for recurrent atrial tachyarrhythmias, AFib burden, quality of life (QOL), and health care utilization, and safety.

The average age was roughly 58 years. Although more than one-third had hypertension, most had no other comorbidities. The authors emphasized that the study population overall was relatively young and healthy.

Those randomized to antiarrhythmic therapy in EARLY-AF/PROGRESSIVE-AF received commonly prescribed therapies titrated to maximally tolerated doses using standardized protocols. At the start of EARLY-AF, flecainide, taken by 65% of patients, was the most commonly used agent, followed by sotalol, propafenone, dronedarone, and amiodarone.

At the end of PROGRESSIVE-AF, the order of the most common therapies did not change relative to EARLY-AF, but only 49% of patients were taking flecainide and 31% were no longer taking any antiarrhythmic therapy.

At the end of 3 years of follow-up in EARLY-AF/PROGRESSIVE-AF, the difference in persistent AFib represented a 75% reduction in favor of early ablation (HR, 0.25; 95% confidence interval, 0.09-0.70).

In those treated with ablation relative to those treated with antiarrhythmic therapy, the lower rate of atrial tachyarrhythmia lasting more than 7 days (1.9% vs. 6.0%) represented a 70% risk reduction (HR, 0.30; 95% CI 0.10-0.93). The protection from cardioversion for atrial tachyarrhythmia lasting between 2 and 7 days in duration (0.6% vs. 4.7%) translated into an 86% relative reduction (HR, 0.14; 95% CI, 0.02-0.85).

The impact on QOL for those randomized to ablation, which was measured with both AFib-specific and generic measures, was meaningful to patients, according to Dr. Andrade, director of the Cardiac Electrophysiology Laboratory, Vancouver General Hospital.

For example, the mean difference in the AF Quality of Life Survey (AFEQT), was 8.0 at 1 year and 7.4 at 3 years in favor of ablation. A change of 5 points in this score is considered to be a clinically meaningful difference, according to Dr. Andrade.

Numerically, the relative risk of emergency room visits and cardioversion were lower in the ablation group, but the differences did not reach statistical significance. However, the lower hazard ratio for hospitalization was significant (HR, 0.31; 95% CI, 0.15-0.66), supporting a reduction in consumption of health care resources.
 

Ablation found safer than drugs

The rate of adverse events of any kind (11.0% vs. 23.5%) and serious adverse events (4.5% vs. 10.1%) were lower in the ablation group.

There were no differences in major adverse cardiovascular events observed in this period of follow-up, but Dr. Andrade pointed out that follow-up was not long enough to expect differences in these events.

Impressed by the magnitude of the reduction in persistent AFib in a population of relatively young and healthy patients considered to be at a low risk of AFib progression, Dr. Blomström-Lindqvist, a professor of cardiology at the Institution of Medical Science, Uppsala, Sweden, indicated that the data support early ablation as a means to reduce risk of this outcome.

However, she did caution that progressive AFib was observed in a relatively small proportion of patients managed with antiarrhythmic therapy at 3 years, an outcome relevant when discussing treatment options with patients.

The results were published in New England Journal of Medicine simultaneously with Dr. Andrade’s presentation.

Dr. Andrade reports financial relationships with Bayer, Bayliss, Biosense, Bristol-Myers Squibb, Medtronic and Servier. The trial, funded largely by the Canadian government and Canadian professional societies, received additional funding from Bayliss and Medtronic. Dr. Blomström-Lundqvist reports financial relationships with Bayer, Boston Scientific, Cathprint, Medtronic, and Sanofi.

U.S. mortality for alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased at “alarming” rates during the COVID-19 pandemic, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Between 2019 and 2021, ALD-related deaths increased by 17.6% and NAFLD-related deaths increased by 14.5%, Yee Hui Yeo, MD, a resident physician and hepatology-focused investigator at Cedars-Sinai Medical Center in Los Angeles, said at a preconference press briefing.

“Even before the pandemic, the mortality rates for these two diseases have been increasing, with NAFLD having an even steeper increasing trend,” he said. “During the pandemic, these two diseases had a significant surge.”
 

Recent U.S. liver disease death rates

Dr. Yeo and colleagues analyzed data from the Center for Disease Control and Prevention’s National Vital Statistic System to estimate the age-standardized mortality rates (ASMR) of liver disease between 2010 and 2021, including ALD, NAFLD, hepatitis B, and hepatitis C. Using prediction modeling analyses based on trends from 2010 to 2019, they predicted mortality rates for 2020-2021 and compared them with the observed rates to quantify the differences related to the pandemic.

Between 2010 and 2021, there were about 626,000 chronic liver disease–related deaths, including about 343,000 ALD-related deaths, 204,000 hepatitis C–related deaths, 58,000 NAFLD-related deaths, and 21,000 hepatitis B–related deaths.

For ALD-related deaths, the annual percentage change was 3.5% for 2010-2019 and 17.6% for 2019-2021. The observed ASMR in 2020 was significantly higher than predicted, at 15.7 deaths per 100,000 people versus 13.0 predicted from the 2010-2019 rate. The trend continued in 2021, with 17.4 deaths per 100,000 people versus 13.4 in the previous decade.

The highest numbers of ALD-related deaths during the COVID-19 pandemic occurred in Alaska, Montana, Wyoming, Colorado, New Mexico, and South Dakota.

For NAFLD-related deaths, the annual percentage change was 7.6% for 2010-2014, 11.8% for 2014-2019, and 14.5% for 2019-2021. The observed ASMR was also higher than predicted, at 3.1 deaths per 100,000 people versus 2.6 in 2020, as well as 3.4 versus 2.8 in 2021.

The highest numbers of NAFLD-related deaths during the COVID-19 pandemic occurred in Oklahoma, Indiana, Kentucky, Tennessee, and West Virginia.
 

Hepatitis B and C gains lost in pandemic

In contrast, the annual percentage change in was –1.9% for hepatitis B and –2.8% for hepatitis C. After new treatment for hepatitis C emerged in 2013-2014, mortality rates were –7.8% for 2014-2019, Dr. Yeo noted.

“However, during the pandemic, we saw that this decrease has become a nonsignificant change,” he said. “That means our progress of the past 5 or 6 years has already stopped during the pandemic.”

By race and ethnicity, the increase in ALD-related mortality was most pronounced in non-Hispanic White, non-Hispanic Black, and Alaska Native/American Indian populations, Dr. Yeo said. Alaska Natives and American Indians had the highest annual percentage change, at 18%, followed by non-Hispanic Whites at 11.7% and non-Hispanic Blacks at 10.8%. There were no significant differences in race and ethnicity for NAFLD-related deaths, although all groups had major increases in recent years.
 

Biggest rise in young adults

By age, the increase in ALD-related mortality was particularly severe for ages 25-44, with an annual percentage change of 34.6% in 2019-2021, as compared with 13.7% for ages 45-64 and 12.6% for ages 65 and older.

For NAFLD-related deaths, another major increase was observed among ages 25-44, with an annual percentage change of 28.1% for 2019-2021, as compared with 12% for ages 65 and older and 7.4% for ages 45-64.

By sex, the ASMR increase in NAFLD-related mortality was steady throughout 2010-2021 for both men and women. In contrast, ALD-related death increased sharply between 2019 and 2021, with an annual percentage change of 19.1% for women and 16.7% for men.

“The increasing trend in mortality rates for ALD and NAFLD has been quite alarming, with disparities in age, race, and ethnicity,” Dr. Yeo said.

The study received no funding support. Some authors disclosed research funding, advisory board roles, and consulting fees with various pharmaceutical companies.

U.S. mortality for alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased at “alarming” rates during the COVID-19 pandemic, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Between 2019 and 2021, ALD-related deaths increased by 17.6% and NAFLD-related deaths increased by 14.5%, Yee Hui Yeo, MD, a resident physician and hepatology-focused investigator at Cedars-Sinai Medical Center in Los Angeles, said at a preconference press briefing.

“Even before the pandemic, the mortality rates for these two diseases have been increasing, with NAFLD having an even steeper increasing trend,” he said. “During the pandemic, these two diseases had a significant surge.”
 

Recent U.S. liver disease death rates

Dr. Yeo and colleagues analyzed data from the Center for Disease Control and Prevention’s National Vital Statistic System to estimate the age-standardized mortality rates (ASMR) of liver disease between 2010 and 2021, including ALD, NAFLD, hepatitis B, and hepatitis C. Using prediction modeling analyses based on trends from 2010 to 2019, they predicted mortality rates for 2020-2021 and compared them with the observed rates to quantify the differences related to the pandemic.

Between 2010 and 2021, there were about 626,000 chronic liver disease–related deaths, including about 343,000 ALD-related deaths, 204,000 hepatitis C–related deaths, 58,000 NAFLD-related deaths, and 21,000 hepatitis B–related deaths.

For ALD-related deaths, the annual percentage change was 3.5% for 2010-2019 and 17.6% for 2019-2021. The observed ASMR in 2020 was significantly higher than predicted, at 15.7 deaths per 100,000 people versus 13.0 predicted from the 2010-2019 rate. The trend continued in 2021, with 17.4 deaths per 100,000 people versus 13.4 in the previous decade.

The highest numbers of ALD-related deaths during the COVID-19 pandemic occurred in Alaska, Montana, Wyoming, Colorado, New Mexico, and South Dakota.

For NAFLD-related deaths, the annual percentage change was 7.6% for 2010-2014, 11.8% for 2014-2019, and 14.5% for 2019-2021. The observed ASMR was also higher than predicted, at 3.1 deaths per 100,000 people versus 2.6 in 2020, as well as 3.4 versus 2.8 in 2021.

The highest numbers of NAFLD-related deaths during the COVID-19 pandemic occurred in Oklahoma, Indiana, Kentucky, Tennessee, and West Virginia.
 

Hepatitis B and C gains lost in pandemic

In contrast, the annual percentage change in was –1.9% for hepatitis B and –2.8% for hepatitis C. After new treatment for hepatitis C emerged in 2013-2014, mortality rates were –7.8% for 2014-2019, Dr. Yeo noted.

“However, during the pandemic, we saw that this decrease has become a nonsignificant change,” he said. “That means our progress of the past 5 or 6 years has already stopped during the pandemic.”

By race and ethnicity, the increase in ALD-related mortality was most pronounced in non-Hispanic White, non-Hispanic Black, and Alaska Native/American Indian populations, Dr. Yeo said. Alaska Natives and American Indians had the highest annual percentage change, at 18%, followed by non-Hispanic Whites at 11.7% and non-Hispanic Blacks at 10.8%. There were no significant differences in race and ethnicity for NAFLD-related deaths, although all groups had major increases in recent years.
 

Biggest rise in young adults

By age, the increase in ALD-related mortality was particularly severe for ages 25-44, with an annual percentage change of 34.6% in 2019-2021, as compared with 13.7% for ages 45-64 and 12.6% for ages 65 and older.

For NAFLD-related deaths, another major increase was observed among ages 25-44, with an annual percentage change of 28.1% for 2019-2021, as compared with 12% for ages 65 and older and 7.4% for ages 45-64.

By sex, the ASMR increase in NAFLD-related mortality was steady throughout 2010-2021 for both men and women. In contrast, ALD-related death increased sharply between 2019 and 2021, with an annual percentage change of 19.1% for women and 16.7% for men.

“The increasing trend in mortality rates for ALD and NAFLD has been quite alarming, with disparities in age, race, and ethnicity,” Dr. Yeo said.

The study received no funding support. Some authors disclosed research funding, advisory board roles, and consulting fees with various pharmaceutical companies.

U.S. mortality for alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased at “alarming” rates during the COVID-19 pandemic, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Between 2019 and 2021, ALD-related deaths increased by 17.6% and NAFLD-related deaths increased by 14.5%, Yee Hui Yeo, MD, a resident physician and hepatology-focused investigator at Cedars-Sinai Medical Center in Los Angeles, said at a preconference press briefing.

“Even before the pandemic, the mortality rates for these two diseases have been increasing, with NAFLD having an even steeper increasing trend,” he said. “During the pandemic, these two diseases had a significant surge.”
 

Recent U.S. liver disease death rates

Dr. Yeo and colleagues analyzed data from the Center for Disease Control and Prevention’s National Vital Statistic System to estimate the age-standardized mortality rates (ASMR) of liver disease between 2010 and 2021, including ALD, NAFLD, hepatitis B, and hepatitis C. Using prediction modeling analyses based on trends from 2010 to 2019, they predicted mortality rates for 2020-2021 and compared them with the observed rates to quantify the differences related to the pandemic.

Between 2010 and 2021, there were about 626,000 chronic liver disease–related deaths, including about 343,000 ALD-related deaths, 204,000 hepatitis C–related deaths, 58,000 NAFLD-related deaths, and 21,000 hepatitis B–related deaths.

For ALD-related deaths, the annual percentage change was 3.5% for 2010-2019 and 17.6% for 2019-2021. The observed ASMR in 2020 was significantly higher than predicted, at 15.7 deaths per 100,000 people versus 13.0 predicted from the 2010-2019 rate. The trend continued in 2021, with 17.4 deaths per 100,000 people versus 13.4 in the previous decade.

The highest numbers of ALD-related deaths during the COVID-19 pandemic occurred in Alaska, Montana, Wyoming, Colorado, New Mexico, and South Dakota.

For NAFLD-related deaths, the annual percentage change was 7.6% for 2010-2014, 11.8% for 2014-2019, and 14.5% for 2019-2021. The observed ASMR was also higher than predicted, at 3.1 deaths per 100,000 people versus 2.6 in 2020, as well as 3.4 versus 2.8 in 2021.

The highest numbers of NAFLD-related deaths during the COVID-19 pandemic occurred in Oklahoma, Indiana, Kentucky, Tennessee, and West Virginia.
 

Hepatitis B and C gains lost in pandemic

In contrast, the annual percentage change in was –1.9% for hepatitis B and –2.8% for hepatitis C. After new treatment for hepatitis C emerged in 2013-2014, mortality rates were –7.8% for 2014-2019, Dr. Yeo noted.

“However, during the pandemic, we saw that this decrease has become a nonsignificant change,” he said. “That means our progress of the past 5 or 6 years has already stopped during the pandemic.”

By race and ethnicity, the increase in ALD-related mortality was most pronounced in non-Hispanic White, non-Hispanic Black, and Alaska Native/American Indian populations, Dr. Yeo said. Alaska Natives and American Indians had the highest annual percentage change, at 18%, followed by non-Hispanic Whites at 11.7% and non-Hispanic Blacks at 10.8%. There were no significant differences in race and ethnicity for NAFLD-related deaths, although all groups had major increases in recent years.
 

Biggest rise in young adults

By age, the increase in ALD-related mortality was particularly severe for ages 25-44, with an annual percentage change of 34.6% in 2019-2021, as compared with 13.7% for ages 45-64 and 12.6% for ages 65 and older.

For NAFLD-related deaths, another major increase was observed among ages 25-44, with an annual percentage change of 28.1% for 2019-2021, as compared with 12% for ages 65 and older and 7.4% for ages 45-64.

By sex, the ASMR increase in NAFLD-related mortality was steady throughout 2010-2021 for both men and women. In contrast, ALD-related death increased sharply between 2019 and 2021, with an annual percentage change of 19.1% for women and 16.7% for men.

“The increasing trend in mortality rates for ALD and NAFLD has been quite alarming, with disparities in age, race, and ethnicity,” Dr. Yeo said.

The study received no funding support. Some authors disclosed research funding, advisory board roles, and consulting fees with various pharmaceutical companies.

SAN DIEGO – A novel glucagonlike peptide-1 (GLP-1)/glucagon dual-receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma, led to “impressive” weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.

Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, at the annual meeting of the Obesity Society.

At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.

In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.

Sara Freeman/MDedge News

This is “very promising data as an anti-obesity compound,” said Dr. Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.

The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.

They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.

Patients had a mean initial weight of 97 kg (214 pounds).

After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).

Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight

The main adverse events were gastrointestinal.
 

‘Exciting data,’ but still early days

“This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety,” Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told this news organization in an email.

“The degree of weight loss is impressive for a 16-week study,” Dr. Bessesen, professor of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado at Denver, Aurora, added. “The longer-term weight loss will likely be more.”

The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.

However, he also noted a few caveats. This was only a phase 2 study, “so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow-up not long.”

In addition, “the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide.”

The next hurdle is the “need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time” before this drug potentially enters the marketplace.

The “bottom line” is that this potential new antiobesity/diabetes drug is “very promising, but [it is] still a little early to say where it ultimately will go.”
 

A1c results presented at EASD

To be included in this study, patients had to be 18-75 years old, have type 2 diabetes, a body mass index of 25-50 kg/m², and hemoglobin A1c of 7%-10%, and be stable on metformin therapy.

The patients had a mean age of 57 years, and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m², and a mean waist circumference of 110 cm (43 inches).

“We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering,” Dr. Rosenstock said.

“It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin.”

The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.

The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.

At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.

Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).

Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.

Most of the “gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related,” Dr. Rosenstock said, “and it’s highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events.”

BI 456906 was coinvented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A novel glucagonlike peptide-1 (GLP-1)/glucagon dual-receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma, led to “impressive” weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.

Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, at the annual meeting of the Obesity Society.

At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.

In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.

Sara Freeman/MDedge News

This is “very promising data as an anti-obesity compound,” said Dr. Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.

The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.

They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.

Patients had a mean initial weight of 97 kg (214 pounds).

After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).

Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight

The main adverse events were gastrointestinal.
 

‘Exciting data,’ but still early days

“This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety,” Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told this news organization in an email.

“The degree of weight loss is impressive for a 16-week study,” Dr. Bessesen, professor of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado at Denver, Aurora, added. “The longer-term weight loss will likely be more.”

The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.

However, he also noted a few caveats. This was only a phase 2 study, “so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow-up not long.”

In addition, “the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide.”

The next hurdle is the “need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time” before this drug potentially enters the marketplace.

The “bottom line” is that this potential new antiobesity/diabetes drug is “very promising, but [it is] still a little early to say where it ultimately will go.”
 

A1c results presented at EASD

To be included in this study, patients had to be 18-75 years old, have type 2 diabetes, a body mass index of 25-50 kg/m², and hemoglobin A1c of 7%-10%, and be stable on metformin therapy.

The patients had a mean age of 57 years, and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m², and a mean waist circumference of 110 cm (43 inches).

“We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering,” Dr. Rosenstock said.

“It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin.”

The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.

The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.

At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.

Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).

Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.

Most of the “gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related,” Dr. Rosenstock said, “and it’s highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events.”

BI 456906 was coinvented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A novel glucagonlike peptide-1 (GLP-1)/glucagon dual-receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma, led to “impressive” weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.

Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, at the annual meeting of the Obesity Society.

At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.

In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.

Sara Freeman/MDedge News

This is “very promising data as an anti-obesity compound,” said Dr. Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.

The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.

They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.

Patients had a mean initial weight of 97 kg (214 pounds).

After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).

Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight

The main adverse events were gastrointestinal.
 

‘Exciting data,’ but still early days

“This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety,” Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told this news organization in an email.

“The degree of weight loss is impressive for a 16-week study,” Dr. Bessesen, professor of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado at Denver, Aurora, added. “The longer-term weight loss will likely be more.”

The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.

However, he also noted a few caveats. This was only a phase 2 study, “so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow-up not long.”

In addition, “the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide.”

The next hurdle is the “need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time” before this drug potentially enters the marketplace.

The “bottom line” is that this potential new antiobesity/diabetes drug is “very promising, but [it is] still a little early to say where it ultimately will go.”
 

A1c results presented at EASD

To be included in this study, patients had to be 18-75 years old, have type 2 diabetes, a body mass index of 25-50 kg/m², and hemoglobin A1c of 7%-10%, and be stable on metformin therapy.

The patients had a mean age of 57 years, and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m², and a mean waist circumference of 110 cm (43 inches).

“We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering,” Dr. Rosenstock said.

“It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin.”

The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.

The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.

At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.

Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).

Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.

Most of the “gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related,” Dr. Rosenstock said, “and it’s highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events.”

BI 456906 was coinvented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

A version of this article first appeared on Medscape.com.


SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

A version of this article first appeared on Medscape.com.


SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

A version of this article first appeared on Medscape.com.


Living donor liver transplants (LDLT) for recipients with the most urgent need for a liver transplant in the next 3 months – a model for end-stage liver disease (MELD) score of 25 or higher – have become more frequent during the past decade, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Among LDLT recipients, researchers found comparable patient and graft survival at low and high MELD scores. But among patients with high MELD scores, researchers found lower adjusted graft survival and a higher transplant rate among those with living donors, compared with recipients of deceased donor liver transplantation (DDLT).

The findings suggest certain advantages of LDLT over DDLT may be lost in the high-MELD setting in terms of graft survival, said Benjamin Rosenthal, MD, an internal medicine resident focused on transplant hepatology at the Hospital of the University of Pennsylvania, Philadelphia.

“Historically, in the United States especially, living donor liver transplantation has been offered to patients with low or moderate MELD,” he said. “The outcomes of LDLT at high MELD are currently unknown.”

Previous data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) found that LDLT offered a survival benefit versus remaining on the wait list, independent of MELD score, he said. A recent study also has demonstrated a survival benefit across MELD scores of 11-26, but findings for MELD scores of 25 and higher have been mixed.

Trends and outcomes in LDLT at high MELD scores

Dr. Rosenthal and colleagues conducted a retrospective cohort study of adult LDLT recipients from 2010 to 2021 using data from the Organ Procurement and Transplantation Network (OPTN), the U.S. donation and transplantation system.

In baseline characteristics among LDLT transplant recipients, there weren’t significant differences in age, sex, race, and ethnicity for MELD scores below 25 or at 25 and higher. There also weren’t significant differences in donor age, relationship, use of nondirected grafts, or percentage of right and left lobe donors for LDLT recipients. However, recipients with high MELD scores had more nonalcoholic steatohepatitis (29.5% versus 24.6%) and alcohol-assisted cirrhosis (21.6% versus 14.3%).

The research team evaluated graft survival among LDLT recipients by MELD below 25 and at 25 or higher. They also compared posttransplant patient and graft survival between LDLT and DDLT recipients with a MELD of 25 or higher. They excluded transplant candidates on the wait list for Status 1/1A, redo transplant, or multiorgan transplant.

Among the 3,590 patients who had LDLT between 2010 and 2021, 342 patients (9.5%) had a MELD of 25 or higher at transplant. There was some progression during the waiting period, Dr. Rosenthal noted, with a median listing MELD score of 19 among those who had a MELD of 25 or higher at transplant and 21 among those who had a MELD of 30 or higher at transplant.

For LDLT recipients with MELD scores above or below 25, researchers found no significant differences in adjusted patient survival or adjusted graft survival.

Then the team compared outcomes of LDLT and DDLT in high-MELD recipients. Among the 67,279-patient DDLT comparator group, 27,552 patients (41%) had a MELD of 25 or higher at transplant.

In terms of LDLT versus DDLT, unadjusted and adjusted patient survival were no different for patients with MELD of 25 or higher. In addition, unadjusted graft survival was no different.

However, adjusted graft survival was worse for LDLT recipients with high MELD scores. In addition, the retransplant rate was higher in LDLT recipients, at 5.7% versus 2.4%.

The reason why graft survival may be worse remains unclear, Dr. Rosenthal said. One hypothesis is that a low graft-to-recipient weight ratio in LDLT can cause small-for-size syndrome. However, these ratios were not available from OPTN.

“Further studies should be done to see what the benefit is, with graft-to-recipient weight ratios included,” he said. “The differences between DDLT and LDLT in this setting should be further explored as well.”

The research team also described temporal and transplant center trends for LDLT by MELD group. For temporal trends, they expanded the study period from 2002-2021.

The found a marked U.S. increase in the percentage of LDLT with a MELD of 25 or higher, particularly in the last decade and especially in the last 5 years. But the percentage of LDLT with high MELD remains lower than 15%, even in recent years, Dr. Rosenthal noted.

Across transplant centers, there was a trend toward centers with increasing LDLT volume having a greater proportion of LDLT recipients with a MELD of 25 or higher. At the 19.6% of centers performing 10 or fewer LDLT during the study period, none of the LDLT recipients had a MELD of 25 or higher, Dr. Rosenthal said.

The authors didn’t report a funding source. The authors declared no relevant disclosures.

Living donor liver transplants (LDLT) for recipients with the most urgent need for a liver transplant in the next 3 months – a model for end-stage liver disease (MELD) score of 25 or higher – have become more frequent during the past decade, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Among LDLT recipients, researchers found comparable patient and graft survival at low and high MELD scores. But among patients with high MELD scores, researchers found lower adjusted graft survival and a higher transplant rate among those with living donors, compared with recipients of deceased donor liver transplantation (DDLT).

The findings suggest certain advantages of LDLT over DDLT may be lost in the high-MELD setting in terms of graft survival, said Benjamin Rosenthal, MD, an internal medicine resident focused on transplant hepatology at the Hospital of the University of Pennsylvania, Philadelphia.

“Historically, in the United States especially, living donor liver transplantation has been offered to patients with low or moderate MELD,” he said. “The outcomes of LDLT at high MELD are currently unknown.”

Previous data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) found that LDLT offered a survival benefit versus remaining on the wait list, independent of MELD score, he said. A recent study also has demonstrated a survival benefit across MELD scores of 11-26, but findings for MELD scores of 25 and higher have been mixed.

Trends and outcomes in LDLT at high MELD scores

Dr. Rosenthal and colleagues conducted a retrospective cohort study of adult LDLT recipients from 2010 to 2021 using data from the Organ Procurement and Transplantation Network (OPTN), the U.S. donation and transplantation system.

In baseline characteristics among LDLT transplant recipients, there weren’t significant differences in age, sex, race, and ethnicity for MELD scores below 25 or at 25 and higher. There also weren’t significant differences in donor age, relationship, use of nondirected grafts, or percentage of right and left lobe donors for LDLT recipients. However, recipients with high MELD scores had more nonalcoholic steatohepatitis (29.5% versus 24.6%) and alcohol-assisted cirrhosis (21.6% versus 14.3%).

The research team evaluated graft survival among LDLT recipients by MELD below 25 and at 25 or higher. They also compared posttransplant patient and graft survival between LDLT and DDLT recipients with a MELD of 25 or higher. They excluded transplant candidates on the wait list for Status 1/1A, redo transplant, or multiorgan transplant.

Among the 3,590 patients who had LDLT between 2010 and 2021, 342 patients (9.5%) had a MELD of 25 or higher at transplant. There was some progression during the waiting period, Dr. Rosenthal noted, with a median listing MELD score of 19 among those who had a MELD of 25 or higher at transplant and 21 among those who had a MELD of 30 or higher at transplant.

For LDLT recipients with MELD scores above or below 25, researchers found no significant differences in adjusted patient survival or adjusted graft survival.

Then the team compared outcomes of LDLT and DDLT in high-MELD recipients. Among the 67,279-patient DDLT comparator group, 27,552 patients (41%) had a MELD of 25 or higher at transplant.

In terms of LDLT versus DDLT, unadjusted and adjusted patient survival were no different for patients with MELD of 25 or higher. In addition, unadjusted graft survival was no different.

However, adjusted graft survival was worse for LDLT recipients with high MELD scores. In addition, the retransplant rate was higher in LDLT recipients, at 5.7% versus 2.4%.

The reason why graft survival may be worse remains unclear, Dr. Rosenthal said. One hypothesis is that a low graft-to-recipient weight ratio in LDLT can cause small-for-size syndrome. However, these ratios were not available from OPTN.

“Further studies should be done to see what the benefit is, with graft-to-recipient weight ratios included,” he said. “The differences between DDLT and LDLT in this setting should be further explored as well.”

The research team also described temporal and transplant center trends for LDLT by MELD group. For temporal trends, they expanded the study period from 2002-2021.

The found a marked U.S. increase in the percentage of LDLT with a MELD of 25 or higher, particularly in the last decade and especially in the last 5 years. But the percentage of LDLT with high MELD remains lower than 15%, even in recent years, Dr. Rosenthal noted.

Across transplant centers, there was a trend toward centers with increasing LDLT volume having a greater proportion of LDLT recipients with a MELD of 25 or higher. At the 19.6% of centers performing 10 or fewer LDLT during the study period, none of the LDLT recipients had a MELD of 25 or higher, Dr. Rosenthal said.

The authors didn’t report a funding source. The authors declared no relevant disclosures.

Living donor liver transplants (LDLT) for recipients with the most urgent need for a liver transplant in the next 3 months – a model for end-stage liver disease (MELD) score of 25 or higher – have become more frequent during the past decade, according to new findings presented at the annual meeting of the American Association for the Study of Liver Diseases.

Among LDLT recipients, researchers found comparable patient and graft survival at low and high MELD scores. But among patients with high MELD scores, researchers found lower adjusted graft survival and a higher transplant rate among those with living donors, compared with recipients of deceased donor liver transplantation (DDLT).

The findings suggest certain advantages of LDLT over DDLT may be lost in the high-MELD setting in terms of graft survival, said Benjamin Rosenthal, MD, an internal medicine resident focused on transplant hepatology at the Hospital of the University of Pennsylvania, Philadelphia.

“Historically, in the United States especially, living donor liver transplantation has been offered to patients with low or moderate MELD,” he said. “The outcomes of LDLT at high MELD are currently unknown.”

Previous data from the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) found that LDLT offered a survival benefit versus remaining on the wait list, independent of MELD score, he said. A recent study also has demonstrated a survival benefit across MELD scores of 11-26, but findings for MELD scores of 25 and higher have been mixed.

Trends and outcomes in LDLT at high MELD scores

Dr. Rosenthal and colleagues conducted a retrospective cohort study of adult LDLT recipients from 2010 to 2021 using data from the Organ Procurement and Transplantation Network (OPTN), the U.S. donation and transplantation system.

In baseline characteristics among LDLT transplant recipients, there weren’t significant differences in age, sex, race, and ethnicity for MELD scores below 25 or at 25 and higher. There also weren’t significant differences in donor age, relationship, use of nondirected grafts, or percentage of right and left lobe donors for LDLT recipients. However, recipients with high MELD scores had more nonalcoholic steatohepatitis (29.5% versus 24.6%) and alcohol-assisted cirrhosis (21.6% versus 14.3%).

The research team evaluated graft survival among LDLT recipients by MELD below 25 and at 25 or higher. They also compared posttransplant patient and graft survival between LDLT and DDLT recipients with a MELD of 25 or higher. They excluded transplant candidates on the wait list for Status 1/1A, redo transplant, or multiorgan transplant.

Among the 3,590 patients who had LDLT between 2010 and 2021, 342 patients (9.5%) had a MELD of 25 or higher at transplant. There was some progression during the waiting period, Dr. Rosenthal noted, with a median listing MELD score of 19 among those who had a MELD of 25 or higher at transplant and 21 among those who had a MELD of 30 or higher at transplant.

For LDLT recipients with MELD scores above or below 25, researchers found no significant differences in adjusted patient survival or adjusted graft survival.

Then the team compared outcomes of LDLT and DDLT in high-MELD recipients. Among the 67,279-patient DDLT comparator group, 27,552 patients (41%) had a MELD of 25 or higher at transplant.

In terms of LDLT versus DDLT, unadjusted and adjusted patient survival were no different for patients with MELD of 25 or higher. In addition, unadjusted graft survival was no different.

However, adjusted graft survival was worse for LDLT recipients with high MELD scores. In addition, the retransplant rate was higher in LDLT recipients, at 5.7% versus 2.4%.

The reason why graft survival may be worse remains unclear, Dr. Rosenthal said. One hypothesis is that a low graft-to-recipient weight ratio in LDLT can cause small-for-size syndrome. However, these ratios were not available from OPTN.

“Further studies should be done to see what the benefit is, with graft-to-recipient weight ratios included,” he said. “The differences between DDLT and LDLT in this setting should be further explored as well.”

The research team also described temporal and transplant center trends for LDLT by MELD group. For temporal trends, they expanded the study period from 2002-2021.

The found a marked U.S. increase in the percentage of LDLT with a MELD of 25 or higher, particularly in the last decade and especially in the last 5 years. But the percentage of LDLT with high MELD remains lower than 15%, even in recent years, Dr. Rosenthal noted.

Across transplant centers, there was a trend toward centers with increasing LDLT volume having a greater proportion of LDLT recipients with a MELD of 25 or higher. At the 19.6% of centers performing 10 or fewer LDLT during the study period, none of the LDLT recipients had a MELD of 25 or higher, Dr. Rosenthal said.

The authors didn’t report a funding source. The authors declared no relevant disclosures.