Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

Artificial intelligence (AI) is impacting many aspects of health care, and radiation oncology is no exception. It has the potential to cut costs and streamline work flows ranging from image analysis to treatment plan formulation, but its specific place in clinical practice is still being debated.

In a session at the annual meeting of the American Society for Radiation Oncology, researchers discussed some of the ways that AI is or will soon be relevant to the clinic. The general consensus was that AI provides a useful supplement but is no threat to replace the role of radiation oncologists.

In his talk, Sanjay Aneja, MD focused on practical applications of AI that are in the clinic or close to being ready. One example is image classification. “There has been recent evidence that suggests in a variety of different kind of scenarios, deep-learning models can be very good at image classification in automated ways,” said Dr. Aneja, who is a professor of radiology at Yale University, New Haven, Conn. He described one study that used AI to classify 14 different pathologies on chest x-ray images.

Dr. Aneja described the open-source nnU-net tool, which automatically configures itself and segments biomedical images for research or clinical purposes, including therapy planning support, intraoperative support, and tumor growth monitoring. The researchers who developed it also created a “recipe” to systematize configuration of nnU-net, making it useful as an out-of-the-box tool for image segmentation.

He predicted that AI will improve radiology oncology by assisting in the determination of disease extent, including microscopic areas of disease. It could also help plan treatment volume and monitor treatment response. “I think that these are the types of things that will be moving toward the clinic in the future; very specific applications and models trained on very specific scenarios that will help us answer a very important clinical question,” Dr. Aneja said.

He expects AI to contribute to auto-segmenting and clinical contouring, “but I will caution everyone that these algorithms have not been proven to be better than physician contours. They very frequently fail in the specific use cases when anatomy is distorted by, I don’t know, say a tumor. And so a lot of times, we don’t actually have the ability to just make it an automated process. I think it’ll be something that physicians will use to help them but not necessarily replace their contouring ability,” Dr. Aneja said.

Another, potentially more useful application, is in adaptive radiation planning. “I think that AI auto-contouring will be very helpful in establishing contours in a situation in which a physician doing them would not be feasible. We need to have nimble and computationally efficient auto segmentation algorithms that will be able to be easily deployed at the linear accelerator,” he said.
 

AI in pathology and treatment selection

In another talk, Osama Mohamad, MD talked about AI in pathology, and specifically treatment selection. He described research from his group that digitized pathology data from 5,500 patients drawn from five randomized, clinical trials. They used AI on data from four of the clinical trials to identify a prognostic biomarker for distant metastasis, then validated it on data from the remaining clinical trial, which compared radiation versus radiation plus short-term hormone therapy in prostate cancer.

The results suggested that most patients should receive hormone therapy, but the AI suggested a more nuanced answer. “Patients who had AI biomarker negative do not see any benefit from adding 4 months of hormone therapy ... whereas patients who have biomarker positive have significant difference and improvement in distant metastasis at 10 years and 15 years. This means that we can save a significant proportion of patients from getting [androgen deprivation therapy], which is hormonal therapy and has very well-known side effects, because they simply they will not benefit,” said Dr. Mohamad, who is an assistant professor of radiation oncology at University of California, San Francisco.

That study relied on the ArteraAI prostate cancer test, which is available through a Clinical Laboratory Improvement Amendment–certified laboratory in Florida.

Another example of AI used to plan treatment is On-line Real-time Benchmarking Informatics Technology for Radiotherapy (ORBIT-RT), developed at the University of California, San Diego. It focuses on radiotherapy treatment plan quality control, and has two main components: creating clinically validated plan routines and a free radiotherapy plan quality control system.

No matter how impressive the technical advances may be, AI contributions won’t impact clinical practice if radiation oncologists, physicians, and patients don’t accept AI. Dr. Aneja’s group surveyed patients about which health field they would feel more comfortable with AI having an important role. Most said they were extremely uncomfortable when it came to cancer. “Now, does that mean that we can’t use AI in oncology? No, I think it just means that we have to be a little bit more nuanced in our approach and how we develop AI solutions for cancer patients,” Dr. Aneja said.

Physicians also show reluctance, according to Alejandro Berlin, MD, who is an affiliate scientist at Princess Margaret Cancer Centre in Toronto. He discussed some research looking at physician acceptance of machine learning. His group looked at physician acceptance of treatment plans for prostate cancer that were generated by physicians and in parallel by machine learning. In a theoretical phase, physicians generally agreed that the machine learning plans were better, but when it came to a phase of the study in which physicians chose which plan to implement in a real patient, the acceptance of machine learning-generated plans dropped by 20%.

This tendency to trust humans over machines is what Dr. Berlin called “automation bias,” and he called for a more collaborative approach to implement AI. “In some cases, [machine learning] is going to be good and sufficient. And in some cases, you will need the expertise of a human.”

Dr. Aneja, who also moderated the session, expressed a similar sentiment when summing up the day’s talks: “I do feel like it’s a disruptive technology ... but I think there will still be a need for us to have people who are trained in order to evaluate and make sure that these algorithms are working correctly and efficiently.”

Dr. Aneja, Dr. Mohamad, and Dr. Berlin have no relevant financial disclosures.

* This article was updated on Nov. 15, 2022.

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.

The American folk hero John Henry pitted his hammer against a mechanical steam drill, only to die of exhaustion after winning the battle. In the legend, John Henry was African American, and it’s a fitting metaphor, according to Justin Xavier Moore, PhD.

It’s a metaphor for accumulated stress over a lifetime, also known as allostatic load. Though it affects everyone, Black, Indigenous, and people of color experience it in excess. “It serves as a symbolism for the plight of African Americans within the United States, that regardless of all the triumph and trying to overcompensate and work just as hard as your counterpart, it oftentimes leads to this overtaxing or exhaustion because your competitor has an unfair advantage. You have Jim Crow laws in the South. We have the history of slavery. We have individuals of racial subgroups that are exposed daily to microaggressions, racial discrimination, stereotypes, redlining, all of these different issues that basically reduce to systemic racism,” said Dr. Moore, who is an assistant professor of medicine at the Medical College of Georgia, Augusta.

Dr. Moore is also a coauthor of a new study published online in SSM–Population Health, which examined the association between increased allostatic load and cancer outcomes among participants in the National Health and Nutrition Examination Survey (NHANES) and the National Death Index. They found that both non-Hispanic Black and non-Hispanic White adults with high allostatic load had about a doubled risk of cancer death.

To determine allostatic load, the researchers looked at nine factors collected in NHANES: abnormal values of BMI, diastolic blood pressure, glycohemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, serum albumin, serum creatinine, and C-reactive protein. “The fact that we’re looking at cardiovascular, metabolic and immune function, all in one gives us a better risk assessment for morbidity and mortality. Allostatic load has actually been associated with cardiovascular disease. I think we are one of the first studies to actually look at whether allostatic load is associated with cancer mortality,” said Dr. Moore.

Previous research coauthored by Dr. Moore showed 20-year old African Americans have an allostatic load comparable with that seen in 30-year-old non-Hispanic Whites. That can lead to a proinflammatory state that might be causing increased cancer risk. But stress isn’t a simple concept to pin down, Dr. Moore said. “One of the founding fathers of public health research and epidemiology, Paracelsus, [said] ‘the dose makes the poison.’ ”

In this case, it means that not all stress is bad. Exercise is good stress. “Your heart rate goes up, you compete, and then it comes back down. That’s healthy. But then there’s those stressful situations like dealing with a horrible job, and a boss that may just be overdemanding. Deadlines, and not having a work-life balance. Too much stress, in this case, can cause cancer death,” Dr. Moore said.

In the study, both non-Hispanic Black adults and non-Hispanic White adults heightened risk of cancer death when dealing with high allostatic load, even though the cause of stress may be different. “It’s almost like the cause of the stress does not matter as much. There are millions of Americans that live in environments that are not conducive to their health. The fact of the matter is that because of racial discrimination, because all these different biases, African Americans may have higher allostatic load, which they did on an average, but high allostatic load for even White people is associated with dying from cancer,” Dr. Moore said.

After adjustment, the researchers found that a high allostatic load was linked to a 14% increased risk of cancer death overall (adjusted subdistributed hazard ratio, 1.14; 95% CI, 1.04-1.26). After stratification by age, high allostatic load was associated with an 80% increased risk of cancer death among adults (SHR, 1.80; 95% CI, 1.35-2.41). Non-Hispanic White adults had a 95% increased risk (SHR, 1.95; 95% CI, 1.22-3.12), non-Hispanic Black adults had a twofold increased risk (SHR, 1.06; 95% CI, 1.27-3.34), and Hispanic adults had a 36% increased risk.

Dr. Moore has no relevant financial disclosures.

The American folk hero John Henry pitted his hammer against a mechanical steam drill, only to die of exhaustion after winning the battle. In the legend, John Henry was African American, and it’s a fitting metaphor, according to Justin Xavier Moore, PhD.

It’s a metaphor for accumulated stress over a lifetime, also known as allostatic load. Though it affects everyone, Black, Indigenous, and people of color experience it in excess. “It serves as a symbolism for the plight of African Americans within the United States, that regardless of all the triumph and trying to overcompensate and work just as hard as your counterpart, it oftentimes leads to this overtaxing or exhaustion because your competitor has an unfair advantage. You have Jim Crow laws in the South. We have the history of slavery. We have individuals of racial subgroups that are exposed daily to microaggressions, racial discrimination, stereotypes, redlining, all of these different issues that basically reduce to systemic racism,” said Dr. Moore, who is an assistant professor of medicine at the Medical College of Georgia, Augusta.

Dr. Moore is also a coauthor of a new study published online in SSM–Population Health, which examined the association between increased allostatic load and cancer outcomes among participants in the National Health and Nutrition Examination Survey (NHANES) and the National Death Index. They found that both non-Hispanic Black and non-Hispanic White adults with high allostatic load had about a doubled risk of cancer death.

To determine allostatic load, the researchers looked at nine factors collected in NHANES: abnormal values of BMI, diastolic blood pressure, glycohemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, serum albumin, serum creatinine, and C-reactive protein. “The fact that we’re looking at cardiovascular, metabolic and immune function, all in one gives us a better risk assessment for morbidity and mortality. Allostatic load has actually been associated with cardiovascular disease. I think we are one of the first studies to actually look at whether allostatic load is associated with cancer mortality,” said Dr. Moore.

Previous research coauthored by Dr. Moore showed 20-year old African Americans have an allostatic load comparable with that seen in 30-year-old non-Hispanic Whites. That can lead to a proinflammatory state that might be causing increased cancer risk. But stress isn’t a simple concept to pin down, Dr. Moore said. “One of the founding fathers of public health research and epidemiology, Paracelsus, [said] ‘the dose makes the poison.’ ”

In this case, it means that not all stress is bad. Exercise is good stress. “Your heart rate goes up, you compete, and then it comes back down. That’s healthy. But then there’s those stressful situations like dealing with a horrible job, and a boss that may just be overdemanding. Deadlines, and not having a work-life balance. Too much stress, in this case, can cause cancer death,” Dr. Moore said.

In the study, both non-Hispanic Black adults and non-Hispanic White adults heightened risk of cancer death when dealing with high allostatic load, even though the cause of stress may be different. “It’s almost like the cause of the stress does not matter as much. There are millions of Americans that live in environments that are not conducive to their health. The fact of the matter is that because of racial discrimination, because all these different biases, African Americans may have higher allostatic load, which they did on an average, but high allostatic load for even White people is associated with dying from cancer,” Dr. Moore said.

After adjustment, the researchers found that a high allostatic load was linked to a 14% increased risk of cancer death overall (adjusted subdistributed hazard ratio, 1.14; 95% CI, 1.04-1.26). After stratification by age, high allostatic load was associated with an 80% increased risk of cancer death among adults (SHR, 1.80; 95% CI, 1.35-2.41). Non-Hispanic White adults had a 95% increased risk (SHR, 1.95; 95% CI, 1.22-3.12), non-Hispanic Black adults had a twofold increased risk (SHR, 1.06; 95% CI, 1.27-3.34), and Hispanic adults had a 36% increased risk.

Dr. Moore has no relevant financial disclosures.

The American folk hero John Henry pitted his hammer against a mechanical steam drill, only to die of exhaustion after winning the battle. In the legend, John Henry was African American, and it’s a fitting metaphor, according to Justin Xavier Moore, PhD.

It’s a metaphor for accumulated stress over a lifetime, also known as allostatic load. Though it affects everyone, Black, Indigenous, and people of color experience it in excess. “It serves as a symbolism for the plight of African Americans within the United States, that regardless of all the triumph and trying to overcompensate and work just as hard as your counterpart, it oftentimes leads to this overtaxing or exhaustion because your competitor has an unfair advantage. You have Jim Crow laws in the South. We have the history of slavery. We have individuals of racial subgroups that are exposed daily to microaggressions, racial discrimination, stereotypes, redlining, all of these different issues that basically reduce to systemic racism,” said Dr. Moore, who is an assistant professor of medicine at the Medical College of Georgia, Augusta.

Dr. Moore is also a coauthor of a new study published online in SSM–Population Health, which examined the association between increased allostatic load and cancer outcomes among participants in the National Health and Nutrition Examination Survey (NHANES) and the National Death Index. They found that both non-Hispanic Black and non-Hispanic White adults with high allostatic load had about a doubled risk of cancer death.

To determine allostatic load, the researchers looked at nine factors collected in NHANES: abnormal values of BMI, diastolic blood pressure, glycohemoglobin, systolic blood pressure, total cholesterol, serum triglycerides, serum albumin, serum creatinine, and C-reactive protein. “The fact that we’re looking at cardiovascular, metabolic and immune function, all in one gives us a better risk assessment for morbidity and mortality. Allostatic load has actually been associated with cardiovascular disease. I think we are one of the first studies to actually look at whether allostatic load is associated with cancer mortality,” said Dr. Moore.

Previous research coauthored by Dr. Moore showed 20-year old African Americans have an allostatic load comparable with that seen in 30-year-old non-Hispanic Whites. That can lead to a proinflammatory state that might be causing increased cancer risk. But stress isn’t a simple concept to pin down, Dr. Moore said. “One of the founding fathers of public health research and epidemiology, Paracelsus, [said] ‘the dose makes the poison.’ ”

In this case, it means that not all stress is bad. Exercise is good stress. “Your heart rate goes up, you compete, and then it comes back down. That’s healthy. But then there’s those stressful situations like dealing with a horrible job, and a boss that may just be overdemanding. Deadlines, and not having a work-life balance. Too much stress, in this case, can cause cancer death,” Dr. Moore said.

In the study, both non-Hispanic Black adults and non-Hispanic White adults heightened risk of cancer death when dealing with high allostatic load, even though the cause of stress may be different. “It’s almost like the cause of the stress does not matter as much. There are millions of Americans that live in environments that are not conducive to their health. The fact of the matter is that because of racial discrimination, because all these different biases, African Americans may have higher allostatic load, which they did on an average, but high allostatic load for even White people is associated with dying from cancer,” Dr. Moore said.

After adjustment, the researchers found that a high allostatic load was linked to a 14% increased risk of cancer death overall (adjusted subdistributed hazard ratio, 1.14; 95% CI, 1.04-1.26). After stratification by age, high allostatic load was associated with an 80% increased risk of cancer death among adults (SHR, 1.80; 95% CI, 1.35-2.41). Non-Hispanic White adults had a 95% increased risk (SHR, 1.95; 95% CI, 1.22-3.12), non-Hispanic Black adults had a twofold increased risk (SHR, 1.06; 95% CI, 1.27-3.34), and Hispanic adults had a 36% increased risk.

Dr. Moore has no relevant financial disclosures.

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.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

A third dose of coronavirus booster vaccine is effective in reducing death and hospitalization among people with cancer, though this population still suffers higher risks than those of the general population, according to a new large-scale observational study out of the United Kingdom.

People living with lymphoma and those who underwent recent systemic anti-cancer treatment or radiotherapy are at the highest risk, according to study author Lennard Y.W. Lee, PhD. “Our study is the largest evaluation of a coronavirus third dose vaccine booster effectiveness in people living with cancer in the world. For the first time we have quantified the benefits of boosters for COVID-19 in cancer patients,” said Dr. Lee, UK COVID Cancer program lead and a medical oncologist at the University of Oxford, England.

The research was published in the November issue of the European Journal of Cancer.

Despite the encouraging numbers, those with cancer continue to have a more than threefold increased risk of both hospitalization and death from coronavirus compared to the general population. “More needs to be done to reduce this excess risk, like prophylactic antibody therapies,” Dr. Lee said.

Third dose efficacy was lower among cancer patients who had been diagnosed within the past 12 months, as well as those with lymphoma, and those who had undergone systemic anti-cancer therapy or radiotherapy within the past 12 months.

The increased vulnerability among individuals with cancer is likely due to compromised immune systems. “Patients with cancer often have impaired B and T cell function and this study provides the largest global clinical study showing the definitive meaningful clinical impact of this,” Dr. Lee said. The greater risk among those with lymphoma likely traces to aberrant white cells or immunosuppressant regimens, he said.

“Vaccination probably should be used in combination with new forms of prevention and in Europe the strategy of using prophylactic antibodies is going to provide additional levels of protection,” Dr. Lee said.

Overall, the study reveals the challenges that cancer patients face in a pandemic that remains a critical health concern, one that can seriously affect quality of life. “Many are still shielding, unable to see family or hug loved ones. Furthermore, looking beyond the direct health risks, there is also the mental health impact. Shielding for nearly 3 years is very difficult. It is important to realize that behind this large-scale study, which is the biggest in the world, there are real people. The pandemic still goes on for them as they remain at higher risk from COVID-19 and we must be aware of the impact on them,” Dr. Lee said.

The study included data from the United Kingdom’s third dose booster vaccine program, representing 361,098 individuals who participated from December 2020 through December 2021. It also include results from all coronavirus tests conducted in the United Kingdom during that period. Among the participants, 97.8% got the Pfizer-BioNTech vaccine as a booster, while 1.5% received the Moderna vaccine. Overall, 8,371,139 individuals received a third dose booster, including 230,666 living with cancer. The researchers used a test-negative case-controlled analysis to estimate vaccine efficacy.

The booster shot had a 59.1% efficacy against breakthrough infections, 62.8% efficacy against symptomatic infections, 80.5% efficacy versus coronavirus hospitalization, and 94.5% efficacy against coronavirus death. Patients with solid tumors benefited from higher efficacy versus breakthrough infections 66.0% versus 53.2%) and symptomatic infections (69.6% versus 56.0%).

Patients with lymphoma experienced just a 10.5% efficacy of the primary dose vaccine versus breakthrough infections and 13.6% versus symptomatic infections, and this did not improve with a third dose. The benefit was greater for hospitalization (23.2%) and death (80.1%).

Despite the additional protection of a third dose, patients with cancer had a higher risk than the population control for coronavirus hospitalization (odds ratio, 3.38; P < .000001) and death (odds ratio, 3.01; P < .000001).

Dr. Lee has no relevant financial disclosures.

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.

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

The finding that serum dupilumab levels in patients with atopic dermatitis (AD) do not predict long-term response levels or adverse events (AEs) suggests that factors beyond interpatient variability of the interleukin-4 receptor subunit-alpha (IL-4R-alpha) may drive response levels, according to a study published in JAMA Dermatology.

The study results mean that researchers should continue exploring potential AD drugs with novel mechanisms to help patients who fail type 2 inflammatory inhibition, experts told this news organization. The search for accurate augurs of clinical performance also must continue.

Addressing inadequate response

Quantifying nonresponse and incomplete response levels with dupilumab is difficult, said Jonathan I. Silverberg, MD, PhD, MPH, offering perspective on the study. “True nonresponse is probably less than 20%, but many other patients are inadequate responders even if they are having partial response.” Dr. Silverberg, professor of dermatology and director of clinical research, at George Washington University, Washington, was not an investigator.

Robert Sidbury, MD, MPH, added, “When a patient doesn’t respond to a medication that you expect they should, we always ask ourselves why.” Dermatologists have long assumed that, as with biologics for psoriasis, low blood levels were to blame for dupilumab nonresponse, said Dr. Sidbury, who is division chief of dermatology at Seattle Children’s Hospital and was not involved with the study. “This study showed that there was no correlation between response and blood levels.”

In the study, Lotte S. Spekhorst, MD, of National Expertise Center for Atopic Dermatitis, department of dermatology and allergology, University Medical Center Utrecht (the Netherlands) and coinvestigators prospectively followed 295 consecutive adult patients with moderate AD who were treated with dupilumab for 1 year. All patients received the same loading (600 mg) and biweekly (300 mg) doses.

The median dupilumab level at 16 weeks was 86.6 mcg/mL, which is higher than serum levels observed with other monoclonal antibodies used for other indications, such as psoriasis and inflammatory bowel disease, the authors noted. More importantly, researchers found no significant relationship between median week 16 dupilumab levels and 1-year clinical responses measured either discretely (Eczema Area and Severity Index [EASI] < 50, 50, 75, or 90; P = .18) or as quartiles (P = .06).

“It may be that response is dependent on target availability of the IL-4R-alpha, with an interpatient variability producing heterogeneity in response,” the authors wrote. But because serum dupilumab levels were relatively high, they said, all patients’ IL-4R-alpha “was likely fully saturated” at 16 weeks.

“This would explain why serum dupilumab levels were not related to effectiveness,” they noted, “although we cannot rule out differential effects in the tissue associated with heterogeneity in serum dupilumab levels.”

The study helps explain why some patients do not fully respond to dupilumab, said Eric L. Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, who was not involved with the study.

“One hypothesis would be that drug serum levels differ due to metabolism or absorption reasons,” Dr. Simpson said in an interview. Results also suggest that heterogeneity in disease biology, such as other uninhibited cytokine pathways, might explain differences in clinical results. “Thus, more therapeutics that target different inflammatory pathways are needed to capture responses in patients not adequately responding to type 2 inflammatory blockade,” he said.
 

Assessing AEs

As with response levels, serum dupilumab levels at week 16 did not predict AEs including dupilumab-associated ocular surface disease (DAOSD), which impacted 46.4% of 216 patients who reported AEs. These findings also contradict what happens with biologics in other diseases such as psoriasis and inflammatory bowel disease, said Dr. Sidbury, wherein serum drug levels may predict both clinical response and side-effect risks.

A previous study showed that lowering dupilumab levels led to improvement in DAOSD. Authors of the current study therefore surmised that DAOSD development might be more associated with interpatient variability in IL-4R-alpha expression than with serum drug levels. “More research is necessary to confirm the hypothesis of interpatient variability of the IL-4Ra and the pharmacokinetics of dupilumab,” they concluded.

For now, said Dr. Sidbury, the study helps clinicians look beyond serum drug levels when patients respond inadequately to dupilumab. Moreover, added Dr. Silverberg, study results mean that physicians must find other ways to predict dupilumab response levels. “We need better predictors of clinical response – theranostic markers that we could test the patient to and understand how well they’re going to do,” he said.

Be it dupilumab or any other medication, he said, physicians lack even confirmatory biomarkers to reflect when a drug is working well. “Right now, we go with clinical assessments. But if it’s not drug levels, we have to figure out why some patients do markedly better than others.”

It was not unreasonable, Dr. Silverberg said, for the investigators to seek a biomarker in blood rather than tissue. “But in this disease, we believe that the more important place to look for biomarkers and drug levels would be in the skin itself. So we are still left with the issue” that drug levels in tissue might reflect response when serum levels do not.

The study was supported by grants from AbbVie, Eli Lilly, Leo Pharma, Pfizer, and Sanofi. Study patients participated in the BioDay Registry, which is sponsored by Sanofi, Regeneron, AbbVie, Eli Lilly, LEO Pharma, and Pfizer; the sponsors had no role in the study design and conduct. Dr. Spekhorst discloses receiving speaking fees from Abbvie outside the work; disclosures of other authors included receiving advisory, speaking consulting, and/or investigator fees from Sanofi Genzyme during the study. Several authors had no disclosures.

Dr. Simpson has been an investigator and consultant for Regeneron and Sanofi, makers of dupilumab. Dr. Silverberg has been an investigator, consultant, and speaker for Regeneron and Sanofi. Dr. Sidbury has been a clinical investigator for all dupilumab pediatric trials. (His institution has a contract with Regeneron and Sanofi, but he receives no money from the arrangement.)

Adjuvant immunotherapy with atezolizumab for patients with renal cell carcinoma who have had a nephrectomy with or without a metastasectomy, failed to improve clinical outcomes in a group of patients who are at high risk of recurrence, finds a new international study conducted across 28 countries.

The study, called IMmotion010 and published in The Lancet, was a randomized, double-blind, multicenter, phase 3 trial of 778 adult patients with renal cell carcinoma (RCC) with a clear cell or sarcomatoid component. The study failed to meet its primary endpoint which was defined as a statistically significant improvement in disease-free survival as compared with placebo.

“Our results add to an emerging body of literature around the role of adjuvant immunotherapy for renal cell carcinoma. With the longest duration of follow-up to date to our knowledge. We observed no evidence of clinical benefit in disease-free survival or overall survival with adjuvant atezolizumab in patients with high-risk localized or fully resected renal cell carcinoma,” wrote the authors who were led by Sumanta Kumar Pal, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif. “Given a growing list of trials that have not shown benefit with adjuvant immunotherapy, the results call for greater attention to patient selection with this approach.”

Dr. Pal and associates conducted the study to gain more insight into the potential role of adjuvant immunotherapy in patients with renal cell carcinoma who have undergone the standard treatment of nephrectomy with or without metastasectomy. Previous studies of anti-VEGF treatments have produced mixed results, including the large phase 3 ASSURE trial, the authors wrote. “Given these mixed results, use of adjuvant targeted therapy in renal cell carcinoma remains infrequent,” Dr. Pal and associates wrote.

However, pembrolizumab (Keytruda, Merck) a programmed death receptor-1–blocking antibody, is an immunotherapy which, in combination with axitinib, is approved as a first-line treatment for patients with advanced RCC.

Atezolizumab (Tecentriq, Genentech) is approved for treatment in urothelial carcinoma, non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), and melanoma. There are currently a number of ongoing studies that are exploring the use of atezolizumab as a treatment for renal cell carcinoma.

The study details

This new study was conducted between 2017 and 2019. It included 778 patients from 215 clinics in 28 countries who were assigned to the treatment arm (1,200 mg of IV atezolizumab (n = 390, 50%) once every 3 weeks for 16 cycles or 1 year, which ever came first – or, they were assigned to the placebo group (n = 388, 50%). The two groups were similar: average age 60-61, 72%-74% male, 78%-83% white, and 36%-37% based in North America. Most patients, (92%-93%) had clear cell cancer, and 64%-65% were at pathological disease stage T2 or T3a.

The 3-year disease-free survival rate at 36 months was 65.0% (95% confidence interval, 59.9-70.2) in the treatment group and 62.7% (95% CI, 57.5-67.9) in the placebo group. At follow-up at 44.7 months, there was no statistically significant difference in median disease-free survival between atezolizumab (57.2 months; 95% CI, 44.6 to not evaluable) and placebo (49.5 months; 95% CI, 47.4 to not evaluable).

While there were no deaths attributable to treatment, 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo experienced a serious adverse event.

“The results of IMmotion010 do not support the use of adjuvant atezolizumab for fully resected renal cell carcinoma. Future work will include exploration of clinical-based or biomarker-based subsets that might derive benefit from this approach,” the authors wrote.

The researchers acknowledge their findings contrast with those of the KEYNOTE-564 trial of adjuvant immunotherapy with pembrolizumab after nephrectomy in renal cell carcinoma. KEYNOTE-564 reported a disease-free survival benefit of over 24 months and in an analysis done at 30 months. But in KEYNOTE-564, the study comprised only 6% of patients with M1 no evidence of disease. And, it included only patients with synchronous metastases or metastases resected within 1 year of nephrectomy. In the new study, 14% of patients had M1 no evidence of disease, and it included both synchronous and metachronous disease with recurrence within 1year of surgery.

Adjuvant immunotherapy with pembrolizumab is considered optional for patients with intermediate-risk or high-risk operable clear cell renal cell carcinoma per European Society for Medical Oncology and European Association of Urology guidelines because of the lack of confirmed overall survival benefit and toxicity-related considerations associated with immunotherapy.

“These factors must be considered in the adjuvant setting as, following nephrectomy, patients are cancer free and might be cured by surgery alone. As such, additional trials are needed to clarify the role of adjuvant immunotherapy in this disease space,” the authors wrote.

What’s next? “Biomarker work is underway to determine whether tumor genomic characteristics or circulating biomarkers can identify patient populations who derive benefit from adjuvant atezolizumab,” Dr. Pal and associates wrote. “There is precedent for tissue-based adjuvant therapy selection in other diseases, such as HER2-based and endocrine receptor–based approaches in breast cancer and EGFR mutation–directed therapy in lung cancer.”

The study was funded by F Hoffmann-La Roche and Genentech. The academic authors of the study collaborated with F Hoffmann-La Roche and Genentech on all facets of the trial.

Adjuvant immunotherapy with atezolizumab for patients with renal cell carcinoma who have had a nephrectomy with or without a metastasectomy, failed to improve clinical outcomes in a group of patients who are at high risk of recurrence, finds a new international study conducted across 28 countries.

The study, called IMmotion010 and published in The Lancet, was a randomized, double-blind, multicenter, phase 3 trial of 778 adult patients with renal cell carcinoma (RCC) with a clear cell or sarcomatoid component. The study failed to meet its primary endpoint which was defined as a statistically significant improvement in disease-free survival as compared with placebo.

“Our results add to an emerging body of literature around the role of adjuvant immunotherapy for renal cell carcinoma. With the longest duration of follow-up to date to our knowledge. We observed no evidence of clinical benefit in disease-free survival or overall survival with adjuvant atezolizumab in patients with high-risk localized or fully resected renal cell carcinoma,” wrote the authors who were led by Sumanta Kumar Pal, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif. “Given a growing list of trials that have not shown benefit with adjuvant immunotherapy, the results call for greater attention to patient selection with this approach.”

Dr. Pal and associates conducted the study to gain more insight into the potential role of adjuvant immunotherapy in patients with renal cell carcinoma who have undergone the standard treatment of nephrectomy with or without metastasectomy. Previous studies of anti-VEGF treatments have produced mixed results, including the large phase 3 ASSURE trial, the authors wrote. “Given these mixed results, use of adjuvant targeted therapy in renal cell carcinoma remains infrequent,” Dr. Pal and associates wrote.

However, pembrolizumab (Keytruda, Merck) a programmed death receptor-1–blocking antibody, is an immunotherapy which, in combination with axitinib, is approved as a first-line treatment for patients with advanced RCC.

Atezolizumab (Tecentriq, Genentech) is approved for treatment in urothelial carcinoma, non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), and melanoma. There are currently a number of ongoing studies that are exploring the use of atezolizumab as a treatment for renal cell carcinoma.

The study details

This new study was conducted between 2017 and 2019. It included 778 patients from 215 clinics in 28 countries who were assigned to the treatment arm (1,200 mg of IV atezolizumab (n = 390, 50%) once every 3 weeks for 16 cycles or 1 year, which ever came first – or, they were assigned to the placebo group (n = 388, 50%). The two groups were similar: average age 60-61, 72%-74% male, 78%-83% white, and 36%-37% based in North America. Most patients, (92%-93%) had clear cell cancer, and 64%-65% were at pathological disease stage T2 or T3a.

The 3-year disease-free survival rate at 36 months was 65.0% (95% confidence interval, 59.9-70.2) in the treatment group and 62.7% (95% CI, 57.5-67.9) in the placebo group. At follow-up at 44.7 months, there was no statistically significant difference in median disease-free survival between atezolizumab (57.2 months; 95% CI, 44.6 to not evaluable) and placebo (49.5 months; 95% CI, 47.4 to not evaluable).

While there were no deaths attributable to treatment, 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo experienced a serious adverse event.

“The results of IMmotion010 do not support the use of adjuvant atezolizumab for fully resected renal cell carcinoma. Future work will include exploration of clinical-based or biomarker-based subsets that might derive benefit from this approach,” the authors wrote.

The researchers acknowledge their findings contrast with those of the KEYNOTE-564 trial of adjuvant immunotherapy with pembrolizumab after nephrectomy in renal cell carcinoma. KEYNOTE-564 reported a disease-free survival benefit of over 24 months and in an analysis done at 30 months. But in KEYNOTE-564, the study comprised only 6% of patients with M1 no evidence of disease. And, it included only patients with synchronous metastases or metastases resected within 1 year of nephrectomy. In the new study, 14% of patients had M1 no evidence of disease, and it included both synchronous and metachronous disease with recurrence within 1year of surgery.

Adjuvant immunotherapy with pembrolizumab is considered optional for patients with intermediate-risk or high-risk operable clear cell renal cell carcinoma per European Society for Medical Oncology and European Association of Urology guidelines because of the lack of confirmed overall survival benefit and toxicity-related considerations associated with immunotherapy.

“These factors must be considered in the adjuvant setting as, following nephrectomy, patients are cancer free and might be cured by surgery alone. As such, additional trials are needed to clarify the role of adjuvant immunotherapy in this disease space,” the authors wrote.

What’s next? “Biomarker work is underway to determine whether tumor genomic characteristics or circulating biomarkers can identify patient populations who derive benefit from adjuvant atezolizumab,” Dr. Pal and associates wrote. “There is precedent for tissue-based adjuvant therapy selection in other diseases, such as HER2-based and endocrine receptor–based approaches in breast cancer and EGFR mutation–directed therapy in lung cancer.”

The study was funded by F Hoffmann-La Roche and Genentech. The academic authors of the study collaborated with F Hoffmann-La Roche and Genentech on all facets of the trial.

Adjuvant immunotherapy with atezolizumab for patients with renal cell carcinoma who have had a nephrectomy with or without a metastasectomy, failed to improve clinical outcomes in a group of patients who are at high risk of recurrence, finds a new international study conducted across 28 countries.

The study, called IMmotion010 and published in The Lancet, was a randomized, double-blind, multicenter, phase 3 trial of 778 adult patients with renal cell carcinoma (RCC) with a clear cell or sarcomatoid component. The study failed to meet its primary endpoint which was defined as a statistically significant improvement in disease-free survival as compared with placebo.

“Our results add to an emerging body of literature around the role of adjuvant immunotherapy for renal cell carcinoma. With the longest duration of follow-up to date to our knowledge. We observed no evidence of clinical benefit in disease-free survival or overall survival with adjuvant atezolizumab in patients with high-risk localized or fully resected renal cell carcinoma,” wrote the authors who were led by Sumanta Kumar Pal, MD, of City of Hope Comprehensive Cancer Center, Duarte, Calif. “Given a growing list of trials that have not shown benefit with adjuvant immunotherapy, the results call for greater attention to patient selection with this approach.”

Dr. Pal and associates conducted the study to gain more insight into the potential role of adjuvant immunotherapy in patients with renal cell carcinoma who have undergone the standard treatment of nephrectomy with or without metastasectomy. Previous studies of anti-VEGF treatments have produced mixed results, including the large phase 3 ASSURE trial, the authors wrote. “Given these mixed results, use of adjuvant targeted therapy in renal cell carcinoma remains infrequent,” Dr. Pal and associates wrote.

However, pembrolizumab (Keytruda, Merck) a programmed death receptor-1–blocking antibody, is an immunotherapy which, in combination with axitinib, is approved as a first-line treatment for patients with advanced RCC.

Atezolizumab (Tecentriq, Genentech) is approved for treatment in urothelial carcinoma, non–small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma (HCC), and melanoma. There are currently a number of ongoing studies that are exploring the use of atezolizumab as a treatment for renal cell carcinoma.

The study details

This new study was conducted between 2017 and 2019. It included 778 patients from 215 clinics in 28 countries who were assigned to the treatment arm (1,200 mg of IV atezolizumab (n = 390, 50%) once every 3 weeks for 16 cycles or 1 year, which ever came first – or, they were assigned to the placebo group (n = 388, 50%). The two groups were similar: average age 60-61, 72%-74% male, 78%-83% white, and 36%-37% based in North America. Most patients, (92%-93%) had clear cell cancer, and 64%-65% were at pathological disease stage T2 or T3a.

The 3-year disease-free survival rate at 36 months was 65.0% (95% confidence interval, 59.9-70.2) in the treatment group and 62.7% (95% CI, 57.5-67.9) in the placebo group. At follow-up at 44.7 months, there was no statistically significant difference in median disease-free survival between atezolizumab (57.2 months; 95% CI, 44.6 to not evaluable) and placebo (49.5 months; 95% CI, 47.4 to not evaluable).

While there were no deaths attributable to treatment, 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo experienced a serious adverse event.

“The results of IMmotion010 do not support the use of adjuvant atezolizumab for fully resected renal cell carcinoma. Future work will include exploration of clinical-based or biomarker-based subsets that might derive benefit from this approach,” the authors wrote.

The researchers acknowledge their findings contrast with those of the KEYNOTE-564 trial of adjuvant immunotherapy with pembrolizumab after nephrectomy in renal cell carcinoma. KEYNOTE-564 reported a disease-free survival benefit of over 24 months and in an analysis done at 30 months. But in KEYNOTE-564, the study comprised only 6% of patients with M1 no evidence of disease. And, it included only patients with synchronous metastases or metastases resected within 1 year of nephrectomy. In the new study, 14% of patients had M1 no evidence of disease, and it included both synchronous and metachronous disease with recurrence within 1year of surgery.

Adjuvant immunotherapy with pembrolizumab is considered optional for patients with intermediate-risk or high-risk operable clear cell renal cell carcinoma per European Society for Medical Oncology and European Association of Urology guidelines because of the lack of confirmed overall survival benefit and toxicity-related considerations associated with immunotherapy.

“These factors must be considered in the adjuvant setting as, following nephrectomy, patients are cancer free and might be cured by surgery alone. As such, additional trials are needed to clarify the role of adjuvant immunotherapy in this disease space,” the authors wrote.

What’s next? “Biomarker work is underway to determine whether tumor genomic characteristics or circulating biomarkers can identify patient populations who derive benefit from adjuvant atezolizumab,” Dr. Pal and associates wrote. “There is precedent for tissue-based adjuvant therapy selection in other diseases, such as HER2-based and endocrine receptor–based approaches in breast cancer and EGFR mutation–directed therapy in lung cancer.”

The study was funded by F Hoffmann-La Roche and Genentech. The academic authors of the study collaborated with F Hoffmann-La Roche and Genentech on all facets of the trial.

Obsessive-compulsive disorder (OCD) affects 1-2% of the population. The disorder is characterized by recurrent intrusive unwanted thoughts (obsessions) that cause significant distress and anxiety, and behavioral or mental rituals (compulsions) that are performed to reduce distress stemming from obsessions. OCD may onset at any time in life, but most commonly begins in childhood or in early adulthood.

Cognitive behavioral therapy (CBT) with exposure and response prevention is an empirically based and highly effective treatment for OCD. However, most youth with OCD do not receive any treatment, which is related to a shortage of mental health care providers with expertise in assessment and treatment of the disorder, and misdiagnosis of the disorder is all too prevalent.

Aside from the subjective emotional toll associated with OCD, individuals living with this disorder frequently experience interpersonal, academic, and vocational impairments. Nevertheless, OCD is often overlooked or misdiagnosed. This may be more pronounced in youth with OCD, particularly in primary health care settings and large nonspecialized medical institutions. In fact, research indicates that pediatric OCD is often underrecognized even among mental health professionals. This situation is not new, and in fact the National Institute for Health and Care Excellence (NICE) in the United Kingdom stated that there is an urgent need to develop brief reliable screeners for OCD nearly 20 years ago.

Although there were several attempts to develop brief screening scales for adults and youth with OCD, none of them were found to be suitable for use as rapid screening tools in nonspecialized settings. One of the primary reasons is that OCD is associated with different “themes” or dimensions. For example, a child with OCD may engage in cleaning rituals because the context (or dimension) of their obsessions is contamination concerns. Another child with OCD, who may suffer from similar overall symptom severity, may primarily engage in checking rituals which are related with obsessions associated with fear of being responsible for harm. Therefore, one child with OCD may score very high on items assessing one dimension (e.g., contamination concerns), but very low on another dimension (e.g., harm obsessions).

This results in a known challenge in the assessment and psychometrics of self-report (as opposed to clinician administered) measures of OCD. Secondly, development of such measures requires very large carefully screened samples of individuals with OCD, with other disorders, and those without a known psychological disorder – which may be more challenging than requiring adult participants.

In order to address the urgent need for an ultrabrief measure for youth with OCD, we formed an international collaboration with the goal of developing a reliable ultrabrief self-report screening scale for this population. To accomplish this, we harmonized data from several sites that included three samples of carefully screened youths with OCD, with other disorders, and without known disorders who completed multiple self-report questionnaires, including the 21-item Obsessive-Compulsive Inventory – Child Version (OCI-CV).

Utilizing psychometric analyses including factor analyses, invariance analyses, and item response theory methodologies, we were able to develop an ultrabrief measure extracted from the OCI-CV: the 5-item Obsessive-Compulsive Inventory – Child Version (OCI-CV-5). This very brief self-report measure was found to have very good psychometric properties including a sensitive and specific clinical cutoff score. Youth who score at or above the cutoff score are nearly 21 times more likely to meet criteria for OCD.

This measure corresponds to a need to rapidly screen for OCD in children in nonspecialized settings, including community mental health clinics, primary care settings, and pediatric treatment facilities. However, it is important to note it is not a diagnostic measure. The measure is intended to identify youth who should be referred to a mental health care professional to conduct a diagnostic interview.

Dr. Abramovitch is a clinical psychologist and neuropsychologist based in Austin, Tex., and an associate professor at Texas State University. Dr. Abramowitz is professor and director of clinical training in the Anxiety and Stress Lab at University of North Carolina at Chapel Hill. Dr. McKay is professor of psychology at Fordham University, Bronx, N.Y.

Obsessive-compulsive disorder (OCD) affects 1-2% of the population. The disorder is characterized by recurrent intrusive unwanted thoughts (obsessions) that cause significant distress and anxiety, and behavioral or mental rituals (compulsions) that are performed to reduce distress stemming from obsessions. OCD may onset at any time in life, but most commonly begins in childhood or in early adulthood.

Cognitive behavioral therapy (CBT) with exposure and response prevention is an empirically based and highly effective treatment for OCD. However, most youth with OCD do not receive any treatment, which is related to a shortage of mental health care providers with expertise in assessment and treatment of the disorder, and misdiagnosis of the disorder is all too prevalent.

Aside from the subjective emotional toll associated with OCD, individuals living with this disorder frequently experience interpersonal, academic, and vocational impairments. Nevertheless, OCD is often overlooked or misdiagnosed. This may be more pronounced in youth with OCD, particularly in primary health care settings and large nonspecialized medical institutions. In fact, research indicates that pediatric OCD is often underrecognized even among mental health professionals. This situation is not new, and in fact the National Institute for Health and Care Excellence (NICE) in the United Kingdom stated that there is an urgent need to develop brief reliable screeners for OCD nearly 20 years ago.

Although there were several attempts to develop brief screening scales for adults and youth with OCD, none of them were found to be suitable for use as rapid screening tools in nonspecialized settings. One of the primary reasons is that OCD is associated with different “themes” or dimensions. For example, a child with OCD may engage in cleaning rituals because the context (or dimension) of their obsessions is contamination concerns. Another child with OCD, who may suffer from similar overall symptom severity, may primarily engage in checking rituals which are related with obsessions associated with fear of being responsible for harm. Therefore, one child with OCD may score very high on items assessing one dimension (e.g., contamination concerns), but very low on another dimension (e.g., harm obsessions).

This results in a known challenge in the assessment and psychometrics of self-report (as opposed to clinician administered) measures of OCD. Secondly, development of such measures requires very large carefully screened samples of individuals with OCD, with other disorders, and those without a known psychological disorder – which may be more challenging than requiring adult participants.

In order to address the urgent need for an ultrabrief measure for youth with OCD, we formed an international collaboration with the goal of developing a reliable ultrabrief self-report screening scale for this population. To accomplish this, we harmonized data from several sites that included three samples of carefully screened youths with OCD, with other disorders, and without known disorders who completed multiple self-report questionnaires, including the 21-item Obsessive-Compulsive Inventory – Child Version (OCI-CV).

Utilizing psychometric analyses including factor analyses, invariance analyses, and item response theory methodologies, we were able to develop an ultrabrief measure extracted from the OCI-CV: the 5-item Obsessive-Compulsive Inventory – Child Version (OCI-CV-5). This very brief self-report measure was found to have very good psychometric properties including a sensitive and specific clinical cutoff score. Youth who score at or above the cutoff score are nearly 21 times more likely to meet criteria for OCD.

This measure corresponds to a need to rapidly screen for OCD in children in nonspecialized settings, including community mental health clinics, primary care settings, and pediatric treatment facilities. However, it is important to note it is not a diagnostic measure. The measure is intended to identify youth who should be referred to a mental health care professional to conduct a diagnostic interview.

Dr. Abramovitch is a clinical psychologist and neuropsychologist based in Austin, Tex., and an associate professor at Texas State University. Dr. Abramowitz is professor and director of clinical training in the Anxiety and Stress Lab at University of North Carolina at Chapel Hill. Dr. McKay is professor of psychology at Fordham University, Bronx, N.Y.

Obsessive-compulsive disorder (OCD) affects 1-2% of the population. The disorder is characterized by recurrent intrusive unwanted thoughts (obsessions) that cause significant distress and anxiety, and behavioral or mental rituals (compulsions) that are performed to reduce distress stemming from obsessions. OCD may onset at any time in life, but most commonly begins in childhood or in early adulthood.

Cognitive behavioral therapy (CBT) with exposure and response prevention is an empirically based and highly effective treatment for OCD. However, most youth with OCD do not receive any treatment, which is related to a shortage of mental health care providers with expertise in assessment and treatment of the disorder, and misdiagnosis of the disorder is all too prevalent.

Aside from the subjective emotional toll associated with OCD, individuals living with this disorder frequently experience interpersonal, academic, and vocational impairments. Nevertheless, OCD is often overlooked or misdiagnosed. This may be more pronounced in youth with OCD, particularly in primary health care settings and large nonspecialized medical institutions. In fact, research indicates that pediatric OCD is often underrecognized even among mental health professionals. This situation is not new, and in fact the National Institute for Health and Care Excellence (NICE) in the United Kingdom stated that there is an urgent need to develop brief reliable screeners for OCD nearly 20 years ago.

Although there were several attempts to develop brief screening scales for adults and youth with OCD, none of them were found to be suitable for use as rapid screening tools in nonspecialized settings. One of the primary reasons is that OCD is associated with different “themes” or dimensions. For example, a child with OCD may engage in cleaning rituals because the context (or dimension) of their obsessions is contamination concerns. Another child with OCD, who may suffer from similar overall symptom severity, may primarily engage in checking rituals which are related with obsessions associated with fear of being responsible for harm. Therefore, one child with OCD may score very high on items assessing one dimension (e.g., contamination concerns), but very low on another dimension (e.g., harm obsessions).

This results in a known challenge in the assessment and psychometrics of self-report (as opposed to clinician administered) measures of OCD. Secondly, development of such measures requires very large carefully screened samples of individuals with OCD, with other disorders, and those without a known psychological disorder – which may be more challenging than requiring adult participants.

In order to address the urgent need for an ultrabrief measure for youth with OCD, we formed an international collaboration with the goal of developing a reliable ultrabrief self-report screening scale for this population. To accomplish this, we harmonized data from several sites that included three samples of carefully screened youths with OCD, with other disorders, and without known disorders who completed multiple self-report questionnaires, including the 21-item Obsessive-Compulsive Inventory – Child Version (OCI-CV).

Utilizing psychometric analyses including factor analyses, invariance analyses, and item response theory methodologies, we were able to develop an ultrabrief measure extracted from the OCI-CV: the 5-item Obsessive-Compulsive Inventory – Child Version (OCI-CV-5). This very brief self-report measure was found to have very good psychometric properties including a sensitive and specific clinical cutoff score. Youth who score at or above the cutoff score are nearly 21 times more likely to meet criteria for OCD.

This measure corresponds to a need to rapidly screen for OCD in children in nonspecialized settings, including community mental health clinics, primary care settings, and pediatric treatment facilities. However, it is important to note it is not a diagnostic measure. The measure is intended to identify youth who should be referred to a mental health care professional to conduct a diagnostic interview.

Dr. Abramovitch is a clinical psychologist and neuropsychologist based in Austin, Tex., and an associate professor at Texas State University. Dr. Abramowitz is professor and director of clinical training in the Anxiety and Stress Lab at University of North Carolina at Chapel Hill. Dr. McKay is professor of psychology at Fordham University, Bronx, N.Y.

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.