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FDA: No excess mortality risk from paclitaxel stents, balloons for peripheral intervention
, the agency July 11 in a statement to health care providers.
The FDA announcement comes about 4 years after it warned physicians of a “potentially concerning” signal of excess mortality linked to paclitaxel-coated balloons and paclitaxel-eluting stents in published analysis.
The agency’s concerns had been based on a December 2018 meta-analysis in the Journal of the American Heart Association that saw a 68% jump in mortality risk at 2 years and a 93% excess risk at 5 years associated with the paclitaxel devices in the periphery.
The findings, which led an FDA advisory committee to recommend device labeling changes and otherwise upended the practice of peripheral interventions, were followed by an FDA recommendation to limit the use of paclitaxel devices in the periphery to higher-risk cases.
In its July 11 update to providers, the FDA said it was satisfied the devices do not pose an excess mortality risk. It based its conclusion on extensive further evidence review and recently available “additional data” from the randomized controlled trials (RCTs) contributing to the meta-analysis that had ignited the controversy.
“FDA clinicians and statisticians reviewed the study data,” the agency said, “and concluded that the updated RCT meta-analysis does not indicate that the use of paclitaxel-coated devices is associated with a late mortality risk.”
A version of this article originally appeared on Medscape.com.
, the agency July 11 in a statement to health care providers.
The FDA announcement comes about 4 years after it warned physicians of a “potentially concerning” signal of excess mortality linked to paclitaxel-coated balloons and paclitaxel-eluting stents in published analysis.
The agency’s concerns had been based on a December 2018 meta-analysis in the Journal of the American Heart Association that saw a 68% jump in mortality risk at 2 years and a 93% excess risk at 5 years associated with the paclitaxel devices in the periphery.
The findings, which led an FDA advisory committee to recommend device labeling changes and otherwise upended the practice of peripheral interventions, were followed by an FDA recommendation to limit the use of paclitaxel devices in the periphery to higher-risk cases.
In its July 11 update to providers, the FDA said it was satisfied the devices do not pose an excess mortality risk. It based its conclusion on extensive further evidence review and recently available “additional data” from the randomized controlled trials (RCTs) contributing to the meta-analysis that had ignited the controversy.
“FDA clinicians and statisticians reviewed the study data,” the agency said, “and concluded that the updated RCT meta-analysis does not indicate that the use of paclitaxel-coated devices is associated with a late mortality risk.”
A version of this article originally appeared on Medscape.com.
, the agency July 11 in a statement to health care providers.
The FDA announcement comes about 4 years after it warned physicians of a “potentially concerning” signal of excess mortality linked to paclitaxel-coated balloons and paclitaxel-eluting stents in published analysis.
The agency’s concerns had been based on a December 2018 meta-analysis in the Journal of the American Heart Association that saw a 68% jump in mortality risk at 2 years and a 93% excess risk at 5 years associated with the paclitaxel devices in the periphery.
The findings, which led an FDA advisory committee to recommend device labeling changes and otherwise upended the practice of peripheral interventions, were followed by an FDA recommendation to limit the use of paclitaxel devices in the periphery to higher-risk cases.
In its July 11 update to providers, the FDA said it was satisfied the devices do not pose an excess mortality risk. It based its conclusion on extensive further evidence review and recently available “additional data” from the randomized controlled trials (RCTs) contributing to the meta-analysis that had ignited the controversy.
“FDA clinicians and statisticians reviewed the study data,” the agency said, “and concluded that the updated RCT meta-analysis does not indicate that the use of paclitaxel-coated devices is associated with a late mortality risk.”
A version of this article originally appeared on Medscape.com.
FDA approves cognitive-behavioral app for adults with type 2 diabetes
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
A smartphone-based app designed to deliver cognitive-behavioral therapy (CBT) to adults with type 2 diabetes received marketing approval as a class II medical device from the Food and Drug Administration on July 10, becoming the first digital behavioral therapeutic device for people with diabetes to receive this designation for U.S. patients.
Better Therapeutics representatives said that the app, formerly known as BT-001, will be called AspyreRX, with U.S. sales planned to launch in October-December 2023.
The app will be available to patients exclusively by prescription, with a planned 90-day use duration and an option for a second 90-day prescription. A company official said the price per prescription will be about $500-800, although this is not yet finalized. The app is intended for use in concert with the conventional pillars of glycemic control in people with type 2 diabetes: lifestyle modification and treatment with antidiabetes medications.
Senior staff members of Better Therapeutics acknowledged the critical need for an education program, which they will now launch for clinicians, payers, and patients to get across the message of the potential benefit and safety associated with using the CBT app. Their initial marketing will target patients with type 2 diabetes and poorly controlled hemoglobin A1c levels in five to six U.S. regions with high numbers of these patients. The company will also attempt to make the app available through the Department of Veterans Affairs health system and try to secure coverage by Medicare and commercial health-insurance providers.
Approval based on pivotal trial results
The FDA approval focused on data collected in the BT-001 randomized, controlled trial, which included 669 U.S. adults with poorly controlled type 2 diabetes. Results, published in 2022 in Diabetes Care, showed that after 90 days, people using the app had an average incremental reduction in A1c of 0.39 percentage points, compared with control patients who didn’t use the app, the primary endpoint. Use of the app also appeared safe.
Subsequent meeting presentations of study findings showed that A1c-lowering linked with app use was durable during continued use for a total of 180 days, that the effectiveness of the app in helping to lower A1c levels was “dose dependent” relative to the number of lessons a person completed, and that using the app significantly linked with a reduced need for intensified glycemic control through added medications.
Another finding of the extended-use phase of the study was that 81% of patients assigned to the app-using group continued to regularly use the app after 180 days, a level of durable engagement by patients that “exceeded our expectations,” said Diane Gomez-Thinnes, chief commercial officer of Better Therapeutics, during a press conference.
The company plans to tweak the app prior to its launch based on additional analyses of results from the pivotal study to further improve patient engagement and app ease of use. The company is also planning to expand the range of smartphones that can support the app, although about 90%-95% of U.S. smartphones have this capability.
Better Therapeutics is also actively developing and testing other modifications to the basic CBT app to make it usable by people with other cardiometabolic disorders such as hypertension, obesity, and fatty liver disease.
The BT-001 study was funded by Better Therapeutics.
A version of this article first appeared on Medscape.com.
Aging and type 1 diabetes: ‘Complete picture’ 40 years on
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SAN DIEGO –
New funding for 2022-2027 for the DCCT long-term observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) will go toward investigating aspects of type 1 diabetes that are associated with aging and are also common in type 2 diabetes, including cardiovascular disease, fatty liver disease, and sleep apnea.
The original randomized DCCT clinical trial results, published in 1993 in the New England Journal of Medicine, proved that early intensive glycemic control was the key to preventing or slowing the progression of long-term eye, kidney, and nerve complications of type 1 diabetes. Subsequently, EDIC has yielded many more major findings including that early tight glycemic control also reduces cardiovascular risk and prolongs survival in type 1 diabetes.
And although the phenomenon of metabolic memory initially seen in EDIC means that early glycemic control is important, subsequent EDIC data also have suggested that it is never too late to initiate intensive glycemic control, speakers emphasized during a special symposium commemorating 40 years since the start of DCCT, held during the annual scientific sessions of the American Diabetes Association. As with the 30-year DCCT/EDIC commemorative symposium held in 2013, local study participants were in the audience and were acknowledged with long applause.
Together, DCCT and EDIC – both funded by the National Institutes of Health at 27 sites in the United States and Canada – have changed the standard of care for people with type 1 diabetes and continue to inform clinical practice. Prior to the DCCT, between 1930 and 1970, about a third of people with type 1 diabetes developed vision loss and one in five experienced kidney failure and/or myocardial infarction. Stroke and amputation were also common, DCCT/EDIC chair David M. Nathan, MD, said while introducing the symposium.
“All of the advances in care of type 1 diabetes have developed because this study demonstrated that it was important – continuous glucose monitoring (CGM), new insulins, better [insulin] pumps. ... I think the most profound finding is that mortality in our intensively treated cohort is the same as in the general population. That says it all,” Dr. Nathan said in an interview.
And now, “what we still have yet to contribute is what happens to type 1 diabetes as people get older,” added Dr. Nathan, a professor of medicine at Harvard Medical School and director of the Diabetes Center at Massachusetts General Hospital, both in Boston.
‘Something that heretofore none of us could have imagined’
The 1,441 DCCT participants had a mean age of 27 years at baseline in 1983, when they were randomized to intensive insulin therapy or usual care. The 1,375 participants (96%) who continued into EDIC in 1994 were an average of 35 years old at that point, when the usual care group was taught intensive glycemic management and all participants returned to their personal health care teams. The 1,075 participants in EDIC today are an average age of 63 years.
Only 11 participants had died at the start of EDIC, and just 250 (17%) have died as of 2023, said study coordinator cochair Gayle Lorenzi, RN, who is a certified diabetes care and education specialist at the University of California, San Diego.
“DCCT/EDIC because of its longevity represents a unique opportunity to explore aging in long duration of type 1 diabetes, something that heretofore none of us could have imagined, especially for those of you in the audience who started your careers in the 70s and 80s,” Ms. Lorenzi commented.
About 36% of the cohort now has overweight and 40% have obesity, mirroring the general population. And they now have a mean hemoglobin A1c of 7.3%.
According to Barbara H. Braffett, PhD, co–principal investigator at the DCCT/EDIC data coordinating center: “The EDIC study is now shifting its focus during the next 5 years to understand the clinical course of type 1 diabetes in the setting of advancing duration and age, as well as increasing adiposity, which has progressively affected individuals with type 1 diabetes and has potential long-term adverse consequences.”
Dr. Braffett outlined the new study approaches added in 2022-2027. Cardiopulmonary exercise testing, two-dimensional Doppler echocardiography, and carotid-femoral pulse wave velocity will be used to quantify functional and structural changes central to heart failure.
Dr. Nathan commented that, although enough cardiovascular events were available in EDIC by 2006 to demonstrate a significant 58% reduction in the intensive therapy group, “now we can start looking at the aging heart. We have a bunch of great cardiologists working with us who will be guiding us on measuring everything.”
Fatty liver disease in the setting of increasing adiposity will also be investigated using transient elastography (FibroScan) and the Fibrosis-4 index, a quantification of liver enzymes and platelet count.
Dr. Nathan noted that the study participants have had “this kind of funny metabolic milieu in their liver for decades. They don’t make insulin in their pancreas, and therefore, the insulin they get is peripheral and then it goes to their liver. Well, what does that do to them?”
Participants will also complete three symptom questionnaires assessing obstructive sleep apnea, aimed at guiding future sleep studies in those found to be at high risk, Dr. Braffett said.
DCCT/EDIC over 40 years: ‘Incredibly complete picture’
As of 2023, the DCCT/EDIC participants have been studied for longer than 60% of their lifespans and for over 80% of their diabetes duration, Dr. Braffett noted.
During the EDIC 2017-2022 cycle, Dr. Braffett and other speakers summarized, prior EDIC efforts had focused on aspects of cognitive function, physical function, and cheiroarthropathy.
Other DCCT/EDIC studies examined the relationship of A1c and diabetes duration in cardiovascular disease risk, the association of microvascular complications with the risk of cardiovascular disease beyond traditional risk factors, and the risk of severe hypoglycemia over the first 30 years of DCCT/EDIC follow-up.
Moreover, the longitudinal eye and kidney assessments over the 40 years have informed screening guidelines for retinopathy and urinary albumin.
Dr. Nathan said: “Today, the number with horrible complications is very few, but we haven’t erased complications entirely. ... We have this incredibly complete picture of type 1 diabetes that allows us to explore everything. We welcome people to come to us with ideas. That’s the value of this research.”
Dr. Nathan, Ms. Lorenzi, and Dr. Braffett reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ADA 2023
Is there a link between body image concerns and polycystic ovary syndrome?
This transcript has been edited for clarity.
At ENDO 2023, I presented our systematic review and meta-analysis related to body image concerns in women and individuals with polycystic ovary syndrome (PCOS). PCOS is the most common endocrine condition affecting women worldwide. It’s as common as 10%-15%.
Previously thought to be a benign condition affecting a small proportion of women of reproductive age, it’s changed now. It affects women of all ages, all ethnicities, and throughout the world. Body image concern is an area where one feels uncomfortable with how they look and how they feel. Someone might wonder, why worry about body image concerns? When people have body image concerns, it leads to low self-esteem.
Low self-esteem can lead to depression and anxiety, eventually making you a not-so-productive member of society. Several studies have also shown that body image concerns can lead to eating disorders such as anorexia and bulimia, which can be life threatening. Several studies in the past have shown there is a link between PCOS and body image concerns, but what exactly is the link? We don’t know. How big is the problem? We didn’t know until now.
To answer this, we looked at everything published about PCOS and body image concerns together, be it a randomized study, a cluster study, or any kind of study. We put them all into one place and studied them for evidence. The second objective of our work was that we wanted to share any evidence with the international PCOS guidelines group, who are currently reviewing and revising the guidelines for 2023.
We looked at all the major scientific databases, such as PubMed, PubMed Central, and Medline, for any study that’s been published for polycystic ovary syndrome and body image concerns where they specifically used a validated questionnaire – that’s important, and I’ll come back to that later.
We found 6,221 articles on an initial search. After meticulously looking through all of them, we narrowed it down to 9 articles that were relevant to our work. That’s going from 6,221 articles to 9, which were reviewed by 2 independent researchers. If there was any conflict between them, a third independent researcher resolved the conflict.
We found some studies had used the same questionnaires and some had their own questionnaire. We combined the studies where they used the same questionnaire and we did what we call a meta-analysis. We used their data and combined them to find an additional analysis, which is a combination of the two.
The two most commonly used questionnaires were the Multidimensional Body-Self Relations Questionnaire (MBSRQ) survey and the Body-Esteem Scale for Adolescents and Adults (BESAA). I’m not going into detail, but in simplest terms, the MBSRQ has 69 questions, which breaks down into 5 subscales, and BESAA has 3 subscales, which has 23 questions.
When we combined the results in the MBSRQ questionnaire, women with PCOS fared worse in all the subscales, showing there is a concern about body image in women with PCOS when compared with their colleagues who are healthy and do not have PCOS.
With BESAA, we found a little bit of a mixed picture. There was still a significant difference about weight perception, but how they felt and how they attributed, there was no significant difference. Probably the main reason was that only two studies used it and there was a smaller number of people involved in the study.
Why is this important? We feel that by identifying or diagnosing body image concerns, we will be addressing patient concerns. That is important because we clinicians have our own thoughts of what we need to do to help women with PCOS to prevent long-term risk, but it’s also important to talk to the person sitting in front of you right now. What is their concern?
There’s also been a generational shift where women with PCOS used say, “Oh, I’m worried that I can’t have a kid,” to now say, “I’m worried that I don’t feel well about myself.” We need to address that.
When we shared these findings with the international PCOS guidelines, they said we should probably approach this on an individual case-by-case basis because it will mean that the length of consultation might increase if we spend time with body image concerns.
This is where questionnaires come into play. With a validated questionnaire, a person can complete that before they come into the consultation, thereby minimizing the amount of time spent. If they’re not scoring high on the questionnaire, we don’t need to address that. If they are scoring high, then it can be picked up as a topic to discuss.
As I mentioned, there are a couple of limitations, one being the fewer studies and lower numbers of people in the studies. We need to address this in the future.
Long story short, at the moment, there is evidence to say that body image concerns are quite significantly high in women and individuals with PCOS. This is something we need to address as soon as possible.
We are planning future work to understand how social media comes into play, how society influences body image, and how health care professionals across the world are addressing PCOS and body image concerns. Hopefully, we will be able to share these findings in the near future. Thank you.
Dr. Kempegowda is assistant professor in endocrinology, diabetes, and general medicine at the Institute of Applied Health Research, University of Birmingham, and a consultant in endocrinology, diabetes and acute medicine, Queen Elizabeth Hospital, Birmingham, England, and disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
At ENDO 2023, I presented our systematic review and meta-analysis related to body image concerns in women and individuals with polycystic ovary syndrome (PCOS). PCOS is the most common endocrine condition affecting women worldwide. It’s as common as 10%-15%.
Previously thought to be a benign condition affecting a small proportion of women of reproductive age, it’s changed now. It affects women of all ages, all ethnicities, and throughout the world. Body image concern is an area where one feels uncomfortable with how they look and how they feel. Someone might wonder, why worry about body image concerns? When people have body image concerns, it leads to low self-esteem.
Low self-esteem can lead to depression and anxiety, eventually making you a not-so-productive member of society. Several studies have also shown that body image concerns can lead to eating disorders such as anorexia and bulimia, which can be life threatening. Several studies in the past have shown there is a link between PCOS and body image concerns, but what exactly is the link? We don’t know. How big is the problem? We didn’t know until now.
To answer this, we looked at everything published about PCOS and body image concerns together, be it a randomized study, a cluster study, or any kind of study. We put them all into one place and studied them for evidence. The second objective of our work was that we wanted to share any evidence with the international PCOS guidelines group, who are currently reviewing and revising the guidelines for 2023.
We looked at all the major scientific databases, such as PubMed, PubMed Central, and Medline, for any study that’s been published for polycystic ovary syndrome and body image concerns where they specifically used a validated questionnaire – that’s important, and I’ll come back to that later.
We found 6,221 articles on an initial search. After meticulously looking through all of them, we narrowed it down to 9 articles that were relevant to our work. That’s going from 6,221 articles to 9, which were reviewed by 2 independent researchers. If there was any conflict between them, a third independent researcher resolved the conflict.
We found some studies had used the same questionnaires and some had their own questionnaire. We combined the studies where they used the same questionnaire and we did what we call a meta-analysis. We used their data and combined them to find an additional analysis, which is a combination of the two.
The two most commonly used questionnaires were the Multidimensional Body-Self Relations Questionnaire (MBSRQ) survey and the Body-Esteem Scale for Adolescents and Adults (BESAA). I’m not going into detail, but in simplest terms, the MBSRQ has 69 questions, which breaks down into 5 subscales, and BESAA has 3 subscales, which has 23 questions.
When we combined the results in the MBSRQ questionnaire, women with PCOS fared worse in all the subscales, showing there is a concern about body image in women with PCOS when compared with their colleagues who are healthy and do not have PCOS.
With BESAA, we found a little bit of a mixed picture. There was still a significant difference about weight perception, but how they felt and how they attributed, there was no significant difference. Probably the main reason was that only two studies used it and there was a smaller number of people involved in the study.
Why is this important? We feel that by identifying or diagnosing body image concerns, we will be addressing patient concerns. That is important because we clinicians have our own thoughts of what we need to do to help women with PCOS to prevent long-term risk, but it’s also important to talk to the person sitting in front of you right now. What is their concern?
There’s also been a generational shift where women with PCOS used say, “Oh, I’m worried that I can’t have a kid,” to now say, “I’m worried that I don’t feel well about myself.” We need to address that.
When we shared these findings with the international PCOS guidelines, they said we should probably approach this on an individual case-by-case basis because it will mean that the length of consultation might increase if we spend time with body image concerns.
This is where questionnaires come into play. With a validated questionnaire, a person can complete that before they come into the consultation, thereby minimizing the amount of time spent. If they’re not scoring high on the questionnaire, we don’t need to address that. If they are scoring high, then it can be picked up as a topic to discuss.
As I mentioned, there are a couple of limitations, one being the fewer studies and lower numbers of people in the studies. We need to address this in the future.
Long story short, at the moment, there is evidence to say that body image concerns are quite significantly high in women and individuals with PCOS. This is something we need to address as soon as possible.
We are planning future work to understand how social media comes into play, how society influences body image, and how health care professionals across the world are addressing PCOS and body image concerns. Hopefully, we will be able to share these findings in the near future. Thank you.
Dr. Kempegowda is assistant professor in endocrinology, diabetes, and general medicine at the Institute of Applied Health Research, University of Birmingham, and a consultant in endocrinology, diabetes and acute medicine, Queen Elizabeth Hospital, Birmingham, England, and disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
At ENDO 2023, I presented our systematic review and meta-analysis related to body image concerns in women and individuals with polycystic ovary syndrome (PCOS). PCOS is the most common endocrine condition affecting women worldwide. It’s as common as 10%-15%.
Previously thought to be a benign condition affecting a small proportion of women of reproductive age, it’s changed now. It affects women of all ages, all ethnicities, and throughout the world. Body image concern is an area where one feels uncomfortable with how they look and how they feel. Someone might wonder, why worry about body image concerns? When people have body image concerns, it leads to low self-esteem.
Low self-esteem can lead to depression and anxiety, eventually making you a not-so-productive member of society. Several studies have also shown that body image concerns can lead to eating disorders such as anorexia and bulimia, which can be life threatening. Several studies in the past have shown there is a link between PCOS and body image concerns, but what exactly is the link? We don’t know. How big is the problem? We didn’t know until now.
To answer this, we looked at everything published about PCOS and body image concerns together, be it a randomized study, a cluster study, or any kind of study. We put them all into one place and studied them for evidence. The second objective of our work was that we wanted to share any evidence with the international PCOS guidelines group, who are currently reviewing and revising the guidelines for 2023.
We looked at all the major scientific databases, such as PubMed, PubMed Central, and Medline, for any study that’s been published for polycystic ovary syndrome and body image concerns where they specifically used a validated questionnaire – that’s important, and I’ll come back to that later.
We found 6,221 articles on an initial search. After meticulously looking through all of them, we narrowed it down to 9 articles that were relevant to our work. That’s going from 6,221 articles to 9, which were reviewed by 2 independent researchers. If there was any conflict between them, a third independent researcher resolved the conflict.
We found some studies had used the same questionnaires and some had their own questionnaire. We combined the studies where they used the same questionnaire and we did what we call a meta-analysis. We used their data and combined them to find an additional analysis, which is a combination of the two.
The two most commonly used questionnaires were the Multidimensional Body-Self Relations Questionnaire (MBSRQ) survey and the Body-Esteem Scale for Adolescents and Adults (BESAA). I’m not going into detail, but in simplest terms, the MBSRQ has 69 questions, which breaks down into 5 subscales, and BESAA has 3 subscales, which has 23 questions.
When we combined the results in the MBSRQ questionnaire, women with PCOS fared worse in all the subscales, showing there is a concern about body image in women with PCOS when compared with their colleagues who are healthy and do not have PCOS.
With BESAA, we found a little bit of a mixed picture. There was still a significant difference about weight perception, but how they felt and how they attributed, there was no significant difference. Probably the main reason was that only two studies used it and there was a smaller number of people involved in the study.
Why is this important? We feel that by identifying or diagnosing body image concerns, we will be addressing patient concerns. That is important because we clinicians have our own thoughts of what we need to do to help women with PCOS to prevent long-term risk, but it’s also important to talk to the person sitting in front of you right now. What is their concern?
There’s also been a generational shift where women with PCOS used say, “Oh, I’m worried that I can’t have a kid,” to now say, “I’m worried that I don’t feel well about myself.” We need to address that.
When we shared these findings with the international PCOS guidelines, they said we should probably approach this on an individual case-by-case basis because it will mean that the length of consultation might increase if we spend time with body image concerns.
This is where questionnaires come into play. With a validated questionnaire, a person can complete that before they come into the consultation, thereby minimizing the amount of time spent. If they’re not scoring high on the questionnaire, we don’t need to address that. If they are scoring high, then it can be picked up as a topic to discuss.
As I mentioned, there are a couple of limitations, one being the fewer studies and lower numbers of people in the studies. We need to address this in the future.
Long story short, at the moment, there is evidence to say that body image concerns are quite significantly high in women and individuals with PCOS. This is something we need to address as soon as possible.
We are planning future work to understand how social media comes into play, how society influences body image, and how health care professionals across the world are addressing PCOS and body image concerns. Hopefully, we will be able to share these findings in the near future. Thank you.
Dr. Kempegowda is assistant professor in endocrinology, diabetes, and general medicine at the Institute of Applied Health Research, University of Birmingham, and a consultant in endocrinology, diabetes and acute medicine, Queen Elizabeth Hospital, Birmingham, England, and disclosed no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Was the fruquintinib trial for metastatic CRC a win?
The results of a phase 3 trial that assessed the use of a highly selective, potent oral vascular endothelial growth factor receptor (VEGFR) inhibitor for patients with refractory metastatic colorectal cancer (CRC) were recently published.
The trial, dubbed FRESCO-2, found that use of fruquintinib “resulted in a significant and clinically meaningful benefit in overall survival, compared with placebo in patients with refractory metastatic colorectal cancer.”
More specifically, the median overall survival benefit was 2.6 months – 7.4 months with fruquintinib versus 4.8 months with placebo – among 691 heavily pretreated adults with metastatic colorectal adenocarcinoma. The difference translated to a 34% reduction in the risk of death with fruquintinib at a median follow-up of about 11 months.
These patients had received “all current standard approved cytotoxic and targeted therapies and progressed on or were intolerant to trifluridine-tipiracil or regorafenib,” a less-selective VEGF inhibitor, according to investigators led by Arvind Dasari, MD, from the University of Texas MD Anderson Cancer Center, Houston.
Dr. Dasari and colleagues celebrated the results, stressing that “these data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer.”
The VEGF inhibitor has been approved in China for refractory metastatic CRC since 2018, and the recent phase 3 findings support the bid for Food and Drug Administration approval for this indication. The FDA granted fruquintinib priority review in May 2023.
However, in a tweet, Vinay Prasad, MD, an oncologist/epidemiologist at the University of California, San Francisco, who is an outspoken critic of the pharmaceutical industry, called the trial design “unethical.”
Fruquintinib, he explained, was compared with placebo, not investigators’ choice of treatment for patients dying of CRC.
Trial participants were considered to have refractory cases of CRC after previous lines of systemic treatment had failed. For almost three quarters of patients, more than three lines of therapy had failed, and patients still had options, including fluorouracil (5FU), oxaliplatin, or irinotecan, Dr. Prasad argued.
“Everyone who treats CRC would pull [their] mom off the trial and give 5FU and [bevacizumab] or IrOx [irinotecan plus oxaliplatin] or FOLFOX again, perhaps slightly differently,” Dr. Prasad said.
The “proof is they give [these drugs] post progression,” he continued. “After the control arm patients progressed, many doctors did try” these other options.
Hutchmed, the Hong Kong maker of fruquintinib, which sponsored the trial, did not respond to questions from this news organization about why the trial was designed with a placebo arm instead of investigators’ choice of treatment.
However, CRC specialist Alan Venook, MD, who was not involved in the trial, weighed in. He explained that he understands Dr. Prasad’s concerns but doesn’t necessarily think the trial was unethical.
For patients such as those in FRESCO-2, the impact of current treatment options is “so minimal” that forgoing active drug treatment is “not crazy,” said Dr. Venook, a medical oncologist at UCSF.
“If your chances of getting benefit are 1 in 20 and you are much more likely to get toxicity than benefit, you could argue” that having a placebo control arm in the trial is ethical, provided people understand what they are getting into, Dr. Venook said.
In the trial, almost two thirds of patients who received fruquintinib had grade 3 or worse toxicities, compared with half of placebo patients. The most common were hypertension (14% with fruquintinib vs. 1% with placebo), asthenia (8% vs. 4%), and hand-foot syndrome (6% vs. 0%).
Part of the risk-benefit assessment may also include weighing the estimated costs of fruquintinib against the 2.6-month median overall survival benefit.
“One could debate if 2.6 months of more time is worth the medication getting regulatory approval, or debate pricing when it’s approved, or delve closely into toxicity and quality of life data,” tweeted medical oncologist Temidayo Fadelu, MD, MPH, of Dana-Farber Cancer Center and Harvard Medical School, Boston, in response to Dr. Prasad’s thread. However, like Dr. Venook, Dr. Fadelu did not consider the trial design or the way the trial was conducted to be unethical.
Dr. Venook added that a treatment break is also not out of the question in this context. Some might even say that, given the risk-benefit ratio of current options, a temporary break from treatment “is the right thing to do.”
The study was funded by Hutchmed. The investigators reported ties to Hutchmed and other pharmaceutical companies. Dr. Dasari reported grants, contracts, speaker’s fees, and other payments from Hutchmed and other companies. Dr. Venook disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results of a phase 3 trial that assessed the use of a highly selective, potent oral vascular endothelial growth factor receptor (VEGFR) inhibitor for patients with refractory metastatic colorectal cancer (CRC) were recently published.
The trial, dubbed FRESCO-2, found that use of fruquintinib “resulted in a significant and clinically meaningful benefit in overall survival, compared with placebo in patients with refractory metastatic colorectal cancer.”
More specifically, the median overall survival benefit was 2.6 months – 7.4 months with fruquintinib versus 4.8 months with placebo – among 691 heavily pretreated adults with metastatic colorectal adenocarcinoma. The difference translated to a 34% reduction in the risk of death with fruquintinib at a median follow-up of about 11 months.
These patients had received “all current standard approved cytotoxic and targeted therapies and progressed on or were intolerant to trifluridine-tipiracil or regorafenib,” a less-selective VEGF inhibitor, according to investigators led by Arvind Dasari, MD, from the University of Texas MD Anderson Cancer Center, Houston.
Dr. Dasari and colleagues celebrated the results, stressing that “these data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer.”
The VEGF inhibitor has been approved in China for refractory metastatic CRC since 2018, and the recent phase 3 findings support the bid for Food and Drug Administration approval for this indication. The FDA granted fruquintinib priority review in May 2023.
However, in a tweet, Vinay Prasad, MD, an oncologist/epidemiologist at the University of California, San Francisco, who is an outspoken critic of the pharmaceutical industry, called the trial design “unethical.”
Fruquintinib, he explained, was compared with placebo, not investigators’ choice of treatment for patients dying of CRC.
Trial participants were considered to have refractory cases of CRC after previous lines of systemic treatment had failed. For almost three quarters of patients, more than three lines of therapy had failed, and patients still had options, including fluorouracil (5FU), oxaliplatin, or irinotecan, Dr. Prasad argued.
“Everyone who treats CRC would pull [their] mom off the trial and give 5FU and [bevacizumab] or IrOx [irinotecan plus oxaliplatin] or FOLFOX again, perhaps slightly differently,” Dr. Prasad said.
The “proof is they give [these drugs] post progression,” he continued. “After the control arm patients progressed, many doctors did try” these other options.
Hutchmed, the Hong Kong maker of fruquintinib, which sponsored the trial, did not respond to questions from this news organization about why the trial was designed with a placebo arm instead of investigators’ choice of treatment.
However, CRC specialist Alan Venook, MD, who was not involved in the trial, weighed in. He explained that he understands Dr. Prasad’s concerns but doesn’t necessarily think the trial was unethical.
For patients such as those in FRESCO-2, the impact of current treatment options is “so minimal” that forgoing active drug treatment is “not crazy,” said Dr. Venook, a medical oncologist at UCSF.
“If your chances of getting benefit are 1 in 20 and you are much more likely to get toxicity than benefit, you could argue” that having a placebo control arm in the trial is ethical, provided people understand what they are getting into, Dr. Venook said.
In the trial, almost two thirds of patients who received fruquintinib had grade 3 or worse toxicities, compared with half of placebo patients. The most common were hypertension (14% with fruquintinib vs. 1% with placebo), asthenia (8% vs. 4%), and hand-foot syndrome (6% vs. 0%).
Part of the risk-benefit assessment may also include weighing the estimated costs of fruquintinib against the 2.6-month median overall survival benefit.
“One could debate if 2.6 months of more time is worth the medication getting regulatory approval, or debate pricing when it’s approved, or delve closely into toxicity and quality of life data,” tweeted medical oncologist Temidayo Fadelu, MD, MPH, of Dana-Farber Cancer Center and Harvard Medical School, Boston, in response to Dr. Prasad’s thread. However, like Dr. Venook, Dr. Fadelu did not consider the trial design or the way the trial was conducted to be unethical.
Dr. Venook added that a treatment break is also not out of the question in this context. Some might even say that, given the risk-benefit ratio of current options, a temporary break from treatment “is the right thing to do.”
The study was funded by Hutchmed. The investigators reported ties to Hutchmed and other pharmaceutical companies. Dr. Dasari reported grants, contracts, speaker’s fees, and other payments from Hutchmed and other companies. Dr. Venook disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The results of a phase 3 trial that assessed the use of a highly selective, potent oral vascular endothelial growth factor receptor (VEGFR) inhibitor for patients with refractory metastatic colorectal cancer (CRC) were recently published.
The trial, dubbed FRESCO-2, found that use of fruquintinib “resulted in a significant and clinically meaningful benefit in overall survival, compared with placebo in patients with refractory metastatic colorectal cancer.”
More specifically, the median overall survival benefit was 2.6 months – 7.4 months with fruquintinib versus 4.8 months with placebo – among 691 heavily pretreated adults with metastatic colorectal adenocarcinoma. The difference translated to a 34% reduction in the risk of death with fruquintinib at a median follow-up of about 11 months.
These patients had received “all current standard approved cytotoxic and targeted therapies and progressed on or were intolerant to trifluridine-tipiracil or regorafenib,” a less-selective VEGF inhibitor, according to investigators led by Arvind Dasari, MD, from the University of Texas MD Anderson Cancer Center, Houston.
Dr. Dasari and colleagues celebrated the results, stressing that “these data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer.”
The VEGF inhibitor has been approved in China for refractory metastatic CRC since 2018, and the recent phase 3 findings support the bid for Food and Drug Administration approval for this indication. The FDA granted fruquintinib priority review in May 2023.
However, in a tweet, Vinay Prasad, MD, an oncologist/epidemiologist at the University of California, San Francisco, who is an outspoken critic of the pharmaceutical industry, called the trial design “unethical.”
Fruquintinib, he explained, was compared with placebo, not investigators’ choice of treatment for patients dying of CRC.
Trial participants were considered to have refractory cases of CRC after previous lines of systemic treatment had failed. For almost three quarters of patients, more than three lines of therapy had failed, and patients still had options, including fluorouracil (5FU), oxaliplatin, or irinotecan, Dr. Prasad argued.
“Everyone who treats CRC would pull [their] mom off the trial and give 5FU and [bevacizumab] or IrOx [irinotecan plus oxaliplatin] or FOLFOX again, perhaps slightly differently,” Dr. Prasad said.
The “proof is they give [these drugs] post progression,” he continued. “After the control arm patients progressed, many doctors did try” these other options.
Hutchmed, the Hong Kong maker of fruquintinib, which sponsored the trial, did not respond to questions from this news organization about why the trial was designed with a placebo arm instead of investigators’ choice of treatment.
However, CRC specialist Alan Venook, MD, who was not involved in the trial, weighed in. He explained that he understands Dr. Prasad’s concerns but doesn’t necessarily think the trial was unethical.
For patients such as those in FRESCO-2, the impact of current treatment options is “so minimal” that forgoing active drug treatment is “not crazy,” said Dr. Venook, a medical oncologist at UCSF.
“If your chances of getting benefit are 1 in 20 and you are much more likely to get toxicity than benefit, you could argue” that having a placebo control arm in the trial is ethical, provided people understand what they are getting into, Dr. Venook said.
In the trial, almost two thirds of patients who received fruquintinib had grade 3 or worse toxicities, compared with half of placebo patients. The most common were hypertension (14% with fruquintinib vs. 1% with placebo), asthenia (8% vs. 4%), and hand-foot syndrome (6% vs. 0%).
Part of the risk-benefit assessment may also include weighing the estimated costs of fruquintinib against the 2.6-month median overall survival benefit.
“One could debate if 2.6 months of more time is worth the medication getting regulatory approval, or debate pricing when it’s approved, or delve closely into toxicity and quality of life data,” tweeted medical oncologist Temidayo Fadelu, MD, MPH, of Dana-Farber Cancer Center and Harvard Medical School, Boston, in response to Dr. Prasad’s thread. However, like Dr. Venook, Dr. Fadelu did not consider the trial design or the way the trial was conducted to be unethical.
Dr. Venook added that a treatment break is also not out of the question in this context. Some might even say that, given the risk-benefit ratio of current options, a temporary break from treatment “is the right thing to do.”
The study was funded by Hutchmed. The investigators reported ties to Hutchmed and other pharmaceutical companies. Dr. Dasari reported grants, contracts, speaker’s fees, and other payments from Hutchmed and other companies. Dr. Venook disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE LANCET
Finding mild cognitive impairment quickly in primary care
Primary care is the ideal setting to screen for mild cognitive impairment. Screening can be performed in under 10 minutes using brief cognitive assessment tools. When it comes to treatment, deprescribing is a priority, as many drug interactions contribute to cognitive disorders. Drugs also influence the value of nondrug therapies.
At the XXIX National Congress of General and Family Medicine of the Spanish Society for General and Family Physicians, Granada, Spain, Alberto Freire, MD, a family doctor and head of the society’s neurology group, presented a way to detect cognitive impairment in a few minutes during a primary care office visit. He also presented a stepwise algorithm for diagnosing and treating the condition, which is highly prevalent and underdiagnosed.
The specialist dismissed the idea that “memory problems are associated with age,” though it is true that in normal aging, “cognitive frailty develops, and some processes will move a little slower. But there won’t be significant functional impairment.” Mild cognitive impairment falls between normal aging and dementia.
“Primary care is essential for screening for mild cognitive impairment due to its high level of accessibility, proximity, and continuity, but most of all due to its longitudinal perspective, which differentiates it from other specialties,” said Dr. Freire. He pointed out that screening is not the same as diagnosis because screening merely indicates probability or well-founded suspicion that can then be confirmed in secondary care.
He also highlighted the need for assessment of cognitive function using brief cognitive tests, as well as the need for functional assessment of activities of daily living. Many cognitive function tests are available, some of which are patient oriented and some caregiver oriented.
“The patient initially comes to see us due to memory loss that he or she, or that some reliable reporter, has detected,” said Dr. Freire. He indicated that 18.5% of consultations for cognitive impairment are prompted by subjective perceptions of memory complaints, which represent the most common subtype of the condition: mild amnestic cognitive impairment.
Quick cognitive tests
Dr. Freire was in favor of picture-based tests, which he strongly recommended. “These are the most-studied tests in Spain for detecting neurocognitive impairment, and they eliminate the reading factor. They’re quick, they’re easy to use and interpret, and are well-accepted by patients. Also, they assess executive function (verbal fluency) and memory.” Dr. Freire stressed the importance of referencing categories when showing the pictures, as well as the fact that the test is available for free online.
He also questioned whether the Mini-Mental State Examination is dead because “there’s an abbreviated version that the author rejects, and the author’s permission is required to use it. It’s very appropriate for Alzheimer’s disease, but not for cognitive impairment.”
Another notable test is the episodic test (a test that avoids interfering with working memory). It has been validated for amnestic mild cognitive impairment and Alzheimer’s disease, but a reliable caregiver is required to verify patient responses.
For caregiver-oriented tests, Dr. Freire pointed to AD8, which, when paired with any brief cognitive test, significantly increases detection of cognitive impairment.
He also recommended a useful website for everyday consultations created by several scientific societies, including the Spanish Society of General and Family Physicians. The site includes the AD8 and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) questionnaires that can be completed online. “It produces a score that indicates the likelihood that the patient has cognitive impairment, and it can be filled out by family members or caregivers to get the result during the consultation,” he said.
Functional assessment
“Functional assessment of the patient’s level of independence for their life in society is what conceptually differentiates mild cognitive impairment from dementia,” explained Dr. Freire. “There are several types of activities of daily living. The instrumental activities (cooking, laundry, talking on the phone, using transportation, managing finances, taking medications, etc.) are the activities that truly distinguish between mild cognitive impairment and dementia. They allow the person to adjust to their environment and retain their independence within the community.”
There are multiple tools for assessing activities of daily living, but Dr. Freire singled out the Mongil test (from Spain), which covers basic, instrumental, and advanced activities. The higher the score, the worse the patient’s condition, so the goal is to lower the score. On the other hand, grouping certain items together helps determine whether there is a risk of falling, sarcopenia, depression, or suicide, among other outcomes. “So, it’s not only useful for diagnosis and treatment but also detects geriatric problems and syndromes. That is, it’s useful for prevention and allows planning of preventive and therapeutic medical interventions,” he explained.
Reversible dementia
Dr. Freire presented a diagnostic and therapeutic algorithm for cognitive impairment to be used when brief cognitive tests are positive. “The first thing is to perform a clinical assessment because although many cases of cognitive impairment go undiagnosed, 10% of the cases of symptomatic dementia are potentially reversible. We shouldn’t overlook these.” These cases of dementia may be brought on by medication use, alcoholism, chronic meningoencephalitis, toxins, normal pressure hydrocephalus, certain brain tumors, hypothyroidism, and nutritional deficits, among other causes. Functional assessment follows, using the scales mentioned above.
Interactions and deprescribing
“As to polypharmacy, there is underuse of good, evidence-backed medications with no major contraindications. But care must also be taken with inappropriate or off-label medications, overtreatment, drug interactions, and adherence,” said Dr. Freire.
“We need to start deprescribing because the chemical basis of cognitive impairment traces back to reduced cholinergic activity, increased dopaminergic activity in the brain, or both. There are many commonly prescribed drugs with anticholinergic interactions that can cause cognitive disorders. These could be psychotropics, hypnotics, analgesics (nonsteroidal anti-inflammatory drugs), first-generation antihistamines, antihypertensives, antiarrhythmics, histamine2 blockers, and even antibiotics like penicillin and quinolones, among many others,” he emphasized.
The next step is to perform comprehensive laboratory testing to rule out vitamin and mineral deficiencies, diabetes, thyroid disorders, kidney failure, liver diseases, urinary infections, and infections of the central nervous system. After that, neuroimaging should be performed. MRI is the preferred method because it allows quantification of atrophy and volumetric measurements.
Strict cardiovascular control
“At this point, treatment can be started, and the patient can be referred to secondary care,” said Dr. Freire, as he proceeded through a therapeutic algorithm following diagnosis of the patient. Regular exercise increases coordination synapses, prevents disease onset, improves executive function, and delays the onset of dementia. “The problem lies in not knowing how much time should be spent daily and weekly on exercise to achieve these goals.
“It is known that a Mediterranean diet and omega-3 fatty acids improve cognitive impairment. However, care should be taken with omega-3s as they are no longer helpful in dementia that has already been established.” The importance of strictly controlling cardiovascular risk factors must also be kept in mind, as backed by validated studies; it has been shown that blood pressure levels below 128 mm Hg make mild cognitive impairment and dementia worse, atrial fibrillation increases the risk of dementia by a factor of 1.4-2.4, diabetes is a risk factor for developing amnestic mild cognitive impairment, tobacco use also leads to cognitive impairment – even in individuals exposed to second-hand smoke – and statins do not change the risk in cases of dyslipidemia.
Nondrug treatment
Dr. Freire also highlighted the importance of multiple nondrug therapies in this field, such as cognitive training and rehabilitation, reminiscence, music therapy, cognitive-behavioral psychotherapy, and sensory interventions, among others. He also recommended patient groups for these individuals.
He added: “In mild cognitive impairment, there is currently no drug that is an improvement over nondrug therapies.”
The drugs aim to improve memory loss, prevent or delay the onset of mild cognitive impairment, and treat initial symptoms of dementia if applicable. The most commonly prescribed drugs are citicoline alone in vascular disease and memory loss, EGb 761 (which is the only approved dose-dependent drug), and others such as phosphatidylserine, nimodipine, and memantine combined with galantamine or piracetam, Dr. Freire concluded.
Dr. Freire had declared receiving funding as a student in training and outreach activities for popular science sponsored by Ferrer, and on the topic of pain by Esteve, Grünenthal Pharma, and Menarini. He has also reported being a consultant for GSK, Lilly, and Pfizer.
A version of this article first appeared on Medscape.com.
Primary care is the ideal setting to screen for mild cognitive impairment. Screening can be performed in under 10 minutes using brief cognitive assessment tools. When it comes to treatment, deprescribing is a priority, as many drug interactions contribute to cognitive disorders. Drugs also influence the value of nondrug therapies.
At the XXIX National Congress of General and Family Medicine of the Spanish Society for General and Family Physicians, Granada, Spain, Alberto Freire, MD, a family doctor and head of the society’s neurology group, presented a way to detect cognitive impairment in a few minutes during a primary care office visit. He also presented a stepwise algorithm for diagnosing and treating the condition, which is highly prevalent and underdiagnosed.
The specialist dismissed the idea that “memory problems are associated with age,” though it is true that in normal aging, “cognitive frailty develops, and some processes will move a little slower. But there won’t be significant functional impairment.” Mild cognitive impairment falls between normal aging and dementia.
“Primary care is essential for screening for mild cognitive impairment due to its high level of accessibility, proximity, and continuity, but most of all due to its longitudinal perspective, which differentiates it from other specialties,” said Dr. Freire. He pointed out that screening is not the same as diagnosis because screening merely indicates probability or well-founded suspicion that can then be confirmed in secondary care.
He also highlighted the need for assessment of cognitive function using brief cognitive tests, as well as the need for functional assessment of activities of daily living. Many cognitive function tests are available, some of which are patient oriented and some caregiver oriented.
“The patient initially comes to see us due to memory loss that he or she, or that some reliable reporter, has detected,” said Dr. Freire. He indicated that 18.5% of consultations for cognitive impairment are prompted by subjective perceptions of memory complaints, which represent the most common subtype of the condition: mild amnestic cognitive impairment.
Quick cognitive tests
Dr. Freire was in favor of picture-based tests, which he strongly recommended. “These are the most-studied tests in Spain for detecting neurocognitive impairment, and they eliminate the reading factor. They’re quick, they’re easy to use and interpret, and are well-accepted by patients. Also, they assess executive function (verbal fluency) and memory.” Dr. Freire stressed the importance of referencing categories when showing the pictures, as well as the fact that the test is available for free online.
He also questioned whether the Mini-Mental State Examination is dead because “there’s an abbreviated version that the author rejects, and the author’s permission is required to use it. It’s very appropriate for Alzheimer’s disease, but not for cognitive impairment.”
Another notable test is the episodic test (a test that avoids interfering with working memory). It has been validated for amnestic mild cognitive impairment and Alzheimer’s disease, but a reliable caregiver is required to verify patient responses.
For caregiver-oriented tests, Dr. Freire pointed to AD8, which, when paired with any brief cognitive test, significantly increases detection of cognitive impairment.
He also recommended a useful website for everyday consultations created by several scientific societies, including the Spanish Society of General and Family Physicians. The site includes the AD8 and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) questionnaires that can be completed online. “It produces a score that indicates the likelihood that the patient has cognitive impairment, and it can be filled out by family members or caregivers to get the result during the consultation,” he said.
Functional assessment
“Functional assessment of the patient’s level of independence for their life in society is what conceptually differentiates mild cognitive impairment from dementia,” explained Dr. Freire. “There are several types of activities of daily living. The instrumental activities (cooking, laundry, talking on the phone, using transportation, managing finances, taking medications, etc.) are the activities that truly distinguish between mild cognitive impairment and dementia. They allow the person to adjust to their environment and retain their independence within the community.”
There are multiple tools for assessing activities of daily living, but Dr. Freire singled out the Mongil test (from Spain), which covers basic, instrumental, and advanced activities. The higher the score, the worse the patient’s condition, so the goal is to lower the score. On the other hand, grouping certain items together helps determine whether there is a risk of falling, sarcopenia, depression, or suicide, among other outcomes. “So, it’s not only useful for diagnosis and treatment but also detects geriatric problems and syndromes. That is, it’s useful for prevention and allows planning of preventive and therapeutic medical interventions,” he explained.
Reversible dementia
Dr. Freire presented a diagnostic and therapeutic algorithm for cognitive impairment to be used when brief cognitive tests are positive. “The first thing is to perform a clinical assessment because although many cases of cognitive impairment go undiagnosed, 10% of the cases of symptomatic dementia are potentially reversible. We shouldn’t overlook these.” These cases of dementia may be brought on by medication use, alcoholism, chronic meningoencephalitis, toxins, normal pressure hydrocephalus, certain brain tumors, hypothyroidism, and nutritional deficits, among other causes. Functional assessment follows, using the scales mentioned above.
Interactions and deprescribing
“As to polypharmacy, there is underuse of good, evidence-backed medications with no major contraindications. But care must also be taken with inappropriate or off-label medications, overtreatment, drug interactions, and adherence,” said Dr. Freire.
“We need to start deprescribing because the chemical basis of cognitive impairment traces back to reduced cholinergic activity, increased dopaminergic activity in the brain, or both. There are many commonly prescribed drugs with anticholinergic interactions that can cause cognitive disorders. These could be psychotropics, hypnotics, analgesics (nonsteroidal anti-inflammatory drugs), first-generation antihistamines, antihypertensives, antiarrhythmics, histamine2 blockers, and even antibiotics like penicillin and quinolones, among many others,” he emphasized.
The next step is to perform comprehensive laboratory testing to rule out vitamin and mineral deficiencies, diabetes, thyroid disorders, kidney failure, liver diseases, urinary infections, and infections of the central nervous system. After that, neuroimaging should be performed. MRI is the preferred method because it allows quantification of atrophy and volumetric measurements.
Strict cardiovascular control
“At this point, treatment can be started, and the patient can be referred to secondary care,” said Dr. Freire, as he proceeded through a therapeutic algorithm following diagnosis of the patient. Regular exercise increases coordination synapses, prevents disease onset, improves executive function, and delays the onset of dementia. “The problem lies in not knowing how much time should be spent daily and weekly on exercise to achieve these goals.
“It is known that a Mediterranean diet and omega-3 fatty acids improve cognitive impairment. However, care should be taken with omega-3s as they are no longer helpful in dementia that has already been established.” The importance of strictly controlling cardiovascular risk factors must also be kept in mind, as backed by validated studies; it has been shown that blood pressure levels below 128 mm Hg make mild cognitive impairment and dementia worse, atrial fibrillation increases the risk of dementia by a factor of 1.4-2.4, diabetes is a risk factor for developing amnestic mild cognitive impairment, tobacco use also leads to cognitive impairment – even in individuals exposed to second-hand smoke – and statins do not change the risk in cases of dyslipidemia.
Nondrug treatment
Dr. Freire also highlighted the importance of multiple nondrug therapies in this field, such as cognitive training and rehabilitation, reminiscence, music therapy, cognitive-behavioral psychotherapy, and sensory interventions, among others. He also recommended patient groups for these individuals.
He added: “In mild cognitive impairment, there is currently no drug that is an improvement over nondrug therapies.”
The drugs aim to improve memory loss, prevent or delay the onset of mild cognitive impairment, and treat initial symptoms of dementia if applicable. The most commonly prescribed drugs are citicoline alone in vascular disease and memory loss, EGb 761 (which is the only approved dose-dependent drug), and others such as phosphatidylserine, nimodipine, and memantine combined with galantamine or piracetam, Dr. Freire concluded.
Dr. Freire had declared receiving funding as a student in training and outreach activities for popular science sponsored by Ferrer, and on the topic of pain by Esteve, Grünenthal Pharma, and Menarini. He has also reported being a consultant for GSK, Lilly, and Pfizer.
A version of this article first appeared on Medscape.com.
Primary care is the ideal setting to screen for mild cognitive impairment. Screening can be performed in under 10 minutes using brief cognitive assessment tools. When it comes to treatment, deprescribing is a priority, as many drug interactions contribute to cognitive disorders. Drugs also influence the value of nondrug therapies.
At the XXIX National Congress of General and Family Medicine of the Spanish Society for General and Family Physicians, Granada, Spain, Alberto Freire, MD, a family doctor and head of the society’s neurology group, presented a way to detect cognitive impairment in a few minutes during a primary care office visit. He also presented a stepwise algorithm for diagnosing and treating the condition, which is highly prevalent and underdiagnosed.
The specialist dismissed the idea that “memory problems are associated with age,” though it is true that in normal aging, “cognitive frailty develops, and some processes will move a little slower. But there won’t be significant functional impairment.” Mild cognitive impairment falls between normal aging and dementia.
“Primary care is essential for screening for mild cognitive impairment due to its high level of accessibility, proximity, and continuity, but most of all due to its longitudinal perspective, which differentiates it from other specialties,” said Dr. Freire. He pointed out that screening is not the same as diagnosis because screening merely indicates probability or well-founded suspicion that can then be confirmed in secondary care.
He also highlighted the need for assessment of cognitive function using brief cognitive tests, as well as the need for functional assessment of activities of daily living. Many cognitive function tests are available, some of which are patient oriented and some caregiver oriented.
“The patient initially comes to see us due to memory loss that he or she, or that some reliable reporter, has detected,” said Dr. Freire. He indicated that 18.5% of consultations for cognitive impairment are prompted by subjective perceptions of memory complaints, which represent the most common subtype of the condition: mild amnestic cognitive impairment.
Quick cognitive tests
Dr. Freire was in favor of picture-based tests, which he strongly recommended. “These are the most-studied tests in Spain for detecting neurocognitive impairment, and they eliminate the reading factor. They’re quick, they’re easy to use and interpret, and are well-accepted by patients. Also, they assess executive function (verbal fluency) and memory.” Dr. Freire stressed the importance of referencing categories when showing the pictures, as well as the fact that the test is available for free online.
He also questioned whether the Mini-Mental State Examination is dead because “there’s an abbreviated version that the author rejects, and the author’s permission is required to use it. It’s very appropriate for Alzheimer’s disease, but not for cognitive impairment.”
Another notable test is the episodic test (a test that avoids interfering with working memory). It has been validated for amnestic mild cognitive impairment and Alzheimer’s disease, but a reliable caregiver is required to verify patient responses.
For caregiver-oriented tests, Dr. Freire pointed to AD8, which, when paired with any brief cognitive test, significantly increases detection of cognitive impairment.
He also recommended a useful website for everyday consultations created by several scientific societies, including the Spanish Society of General and Family Physicians. The site includes the AD8 and Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) questionnaires that can be completed online. “It produces a score that indicates the likelihood that the patient has cognitive impairment, and it can be filled out by family members or caregivers to get the result during the consultation,” he said.
Functional assessment
“Functional assessment of the patient’s level of independence for their life in society is what conceptually differentiates mild cognitive impairment from dementia,” explained Dr. Freire. “There are several types of activities of daily living. The instrumental activities (cooking, laundry, talking on the phone, using transportation, managing finances, taking medications, etc.) are the activities that truly distinguish between mild cognitive impairment and dementia. They allow the person to adjust to their environment and retain their independence within the community.”
There are multiple tools for assessing activities of daily living, but Dr. Freire singled out the Mongil test (from Spain), which covers basic, instrumental, and advanced activities. The higher the score, the worse the patient’s condition, so the goal is to lower the score. On the other hand, grouping certain items together helps determine whether there is a risk of falling, sarcopenia, depression, or suicide, among other outcomes. “So, it’s not only useful for diagnosis and treatment but also detects geriatric problems and syndromes. That is, it’s useful for prevention and allows planning of preventive and therapeutic medical interventions,” he explained.
Reversible dementia
Dr. Freire presented a diagnostic and therapeutic algorithm for cognitive impairment to be used when brief cognitive tests are positive. “The first thing is to perform a clinical assessment because although many cases of cognitive impairment go undiagnosed, 10% of the cases of symptomatic dementia are potentially reversible. We shouldn’t overlook these.” These cases of dementia may be brought on by medication use, alcoholism, chronic meningoencephalitis, toxins, normal pressure hydrocephalus, certain brain tumors, hypothyroidism, and nutritional deficits, among other causes. Functional assessment follows, using the scales mentioned above.
Interactions and deprescribing
“As to polypharmacy, there is underuse of good, evidence-backed medications with no major contraindications. But care must also be taken with inappropriate or off-label medications, overtreatment, drug interactions, and adherence,” said Dr. Freire.
“We need to start deprescribing because the chemical basis of cognitive impairment traces back to reduced cholinergic activity, increased dopaminergic activity in the brain, or both. There are many commonly prescribed drugs with anticholinergic interactions that can cause cognitive disorders. These could be psychotropics, hypnotics, analgesics (nonsteroidal anti-inflammatory drugs), first-generation antihistamines, antihypertensives, antiarrhythmics, histamine2 blockers, and even antibiotics like penicillin and quinolones, among many others,” he emphasized.
The next step is to perform comprehensive laboratory testing to rule out vitamin and mineral deficiencies, diabetes, thyroid disorders, kidney failure, liver diseases, urinary infections, and infections of the central nervous system. After that, neuroimaging should be performed. MRI is the preferred method because it allows quantification of atrophy and volumetric measurements.
Strict cardiovascular control
“At this point, treatment can be started, and the patient can be referred to secondary care,” said Dr. Freire, as he proceeded through a therapeutic algorithm following diagnosis of the patient. Regular exercise increases coordination synapses, prevents disease onset, improves executive function, and delays the onset of dementia. “The problem lies in not knowing how much time should be spent daily and weekly on exercise to achieve these goals.
“It is known that a Mediterranean diet and omega-3 fatty acids improve cognitive impairment. However, care should be taken with omega-3s as they are no longer helpful in dementia that has already been established.” The importance of strictly controlling cardiovascular risk factors must also be kept in mind, as backed by validated studies; it has been shown that blood pressure levels below 128 mm Hg make mild cognitive impairment and dementia worse, atrial fibrillation increases the risk of dementia by a factor of 1.4-2.4, diabetes is a risk factor for developing amnestic mild cognitive impairment, tobacco use also leads to cognitive impairment – even in individuals exposed to second-hand smoke – and statins do not change the risk in cases of dyslipidemia.
Nondrug treatment
Dr. Freire also highlighted the importance of multiple nondrug therapies in this field, such as cognitive training and rehabilitation, reminiscence, music therapy, cognitive-behavioral psychotherapy, and sensory interventions, among others. He also recommended patient groups for these individuals.
He added: “In mild cognitive impairment, there is currently no drug that is an improvement over nondrug therapies.”
The drugs aim to improve memory loss, prevent or delay the onset of mild cognitive impairment, and treat initial symptoms of dementia if applicable. The most commonly prescribed drugs are citicoline alone in vascular disease and memory loss, EGb 761 (which is the only approved dose-dependent drug), and others such as phosphatidylserine, nimodipine, and memantine combined with galantamine or piracetam, Dr. Freire concluded.
Dr. Freire had declared receiving funding as a student in training and outreach activities for popular science sponsored by Ferrer, and on the topic of pain by Esteve, Grünenthal Pharma, and Menarini. He has also reported being a consultant for GSK, Lilly, and Pfizer.
A version of this article first appeared on Medscape.com.
Oral IL-23 receptor antagonist for psoriasis promising: Phase 2b study
SINGAPORE – across all doses, compared with placebo, according to results of the FRONTIER 1 trial.
In the 16-week phase 2b study, 255 adults with moderate to severe plaque psoriasis were randomly assigned into six treatment groups: placebo (n = 43), JNJ-2113 25 mg daily (n = 43), 25 mg twice daily (n = 41), 50 mg daily (n = 43), 100 mg daily (n = 43), or 100 mg twice daily (n = 42).
Of those who took the placebo, only 9.3% achieved the study’s primary endpoint of a 75% or greater improvement in the Psoriasis Area and Severity Index (PASI-75) by week 16. This was compared with 78.6% in the group that took the highest dose.
“Additionally, the onset of action was fairly fast: at week 4, more than 20% of patients had achieved PASI 75,” said Robert Bissonnette, MD, CEO of Innovaderm Research in Montreal, who presented the findings during a late-breaker session at the World Congress of Dermatology.
Patients in the remaining groups demonstrated a response that corresponded to dosing level: with 37.2%, 51.2%, 58.1%, and 65.1% achieving PASI-75 in the 25 mg daily, 25 mg twice-daily, 50 mg daily, and 100 mg daily groups, respectively.
“These results are very interesting because in terms of psoriasis treatment, if this is confirmed in phase 3, it would give us an oral alternative that would be selective for IL-23,” said Dr. Bissonnette, referring to the signaling pathway that plays a critical role in the pathogenesis of several immune-mediated inflammatory diseases, including plaque psoriasis.
Although rarely life-threatening, the skin disorder is often intractable to treatment. In recent years, therapies that block IL-23 signaling and downstream inflammatory cytokine production have proven useful. “We have on the market a number of biological agents targeting IL-23 that we use on a regular basis,” said Dr. Bissonnette. “However, there are currently no orally delivered therapies.”
If successful, JNJ-2113 – a first-in-class oral IL-23 antagonist peptide developed by Janssen – could change the treatment paradigm for patients with moderate to severe plaque psoriasis. “When I was first introduced to the concept, I thought it wouldn’t work as it’s a peptide, that it would be digested by the stomach,” he told the audience. “But because of its GI stability and its potency, when you administer it orally, you can detect pharmacological activity.”
A well-tolerated alternative
Participants in the FRONTIER 1 trial were on average about 44 years old and weighed 88.9 kg (195 lb). Most had been living with psoriasis for about 18 years, with a total PASI score of 19.05. In addition, 43.1% had been treated with phototherapy in the past, 22% with biologics, and 78.4% with systemics.
PASI 90 and 100 were among some of the secondary outcomes measured. Similar to the primary outcome of PASI 75, all treatment groups demonstrated a statistically significant dose-response in PASI 90, compared with placebo. For those on the highest dose of JNJ-2113, 59.5% and 40.5% achieved PASI 90 and PASI 100, respectively, by week 16. The corresponding figures for those receiving placebo were 2.3% and 0%.
The safety profile for JNJ-2113 across all doses was similar to that of placebo, with no evidence of a dose-dependent increase in the occurrence of adverse events (AEs). The most frequently reported AEs were COVID-19 and nasopharyngitis. There were three serious AEs (COVID-19, infected cyst, suicide attempt) among those on the active drug, but the investigators assessed that they were not related to the study intervention. No deaths, major adverse cardiac events, or malignancies were reported during the study.
Approached for an independent comment, Marius-Anton Ionescu, MD, PhD, from the University Hospital Saint Louis, Paris, who specializes in psoriasis, told this news organization that the new development with JNJ-2113 “is really promising.”
Treatment for plaque psoriasis has improved to the point where some biologics, such as risankizumab (Skyrizi), only require patients to have “four shots a year,” he says. “This is the future of psoriasis treatment; it might go down to two shots a year” – a regimen that will be easier than taking an oral medication once or twice a day.
“But it’s good to have an oral option because you will always have some patients who say: ‘Shots are not for me, I’m afraid,’ ” he says.
However, Dr. Ionescu noted that if JNJ-2113 were to pass phase 3 trials, it might face stiff competition from the selective tyrosine kinase 2 (TYK2) inhibitor deucravacitinib (Sotyktu), which the U.S. Food and Drug Administration approved for use in adults with moderate to severe plaque psoriasis last September. “It has very good results and is the first oral therapy that is comparable with biologics for plaque psoriasis,” he says.
But Dr. Bissonnette remains hopeful for the future. “I think JNJ-2113 goes way beyond psoriasis because this type of strategy using oral peptide–blocking receptors could be used in other immune-mediated diseases, including atopic dermatitis and other diseases outside of dermatology.” In addition to running a phase 3 study for moderate to severe plaque psoriasis, Janssen is planning to initiate a phase 2b clinical trial of JNJ-2113 in adults with ulcerative colitis.
The study was funded by Janssen. Dr. Bissonnette reports consulting and investigating for Janssen, and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Dr. Ionescu is an investigator for Psoriasis National Register France Psobioteq (no honoraria), and an investigator and speaker for Uriage cosmetics (honoraria).
A version of this article first appeared on Medscape.com.
SINGAPORE – across all doses, compared with placebo, according to results of the FRONTIER 1 trial.
In the 16-week phase 2b study, 255 adults with moderate to severe plaque psoriasis were randomly assigned into six treatment groups: placebo (n = 43), JNJ-2113 25 mg daily (n = 43), 25 mg twice daily (n = 41), 50 mg daily (n = 43), 100 mg daily (n = 43), or 100 mg twice daily (n = 42).
Of those who took the placebo, only 9.3% achieved the study’s primary endpoint of a 75% or greater improvement in the Psoriasis Area and Severity Index (PASI-75) by week 16. This was compared with 78.6% in the group that took the highest dose.
“Additionally, the onset of action was fairly fast: at week 4, more than 20% of patients had achieved PASI 75,” said Robert Bissonnette, MD, CEO of Innovaderm Research in Montreal, who presented the findings during a late-breaker session at the World Congress of Dermatology.
Patients in the remaining groups demonstrated a response that corresponded to dosing level: with 37.2%, 51.2%, 58.1%, and 65.1% achieving PASI-75 in the 25 mg daily, 25 mg twice-daily, 50 mg daily, and 100 mg daily groups, respectively.
“These results are very interesting because in terms of psoriasis treatment, if this is confirmed in phase 3, it would give us an oral alternative that would be selective for IL-23,” said Dr. Bissonnette, referring to the signaling pathway that plays a critical role in the pathogenesis of several immune-mediated inflammatory diseases, including plaque psoriasis.
Although rarely life-threatening, the skin disorder is often intractable to treatment. In recent years, therapies that block IL-23 signaling and downstream inflammatory cytokine production have proven useful. “We have on the market a number of biological agents targeting IL-23 that we use on a regular basis,” said Dr. Bissonnette. “However, there are currently no orally delivered therapies.”
If successful, JNJ-2113 – a first-in-class oral IL-23 antagonist peptide developed by Janssen – could change the treatment paradigm for patients with moderate to severe plaque psoriasis. “When I was first introduced to the concept, I thought it wouldn’t work as it’s a peptide, that it would be digested by the stomach,” he told the audience. “But because of its GI stability and its potency, when you administer it orally, you can detect pharmacological activity.”
A well-tolerated alternative
Participants in the FRONTIER 1 trial were on average about 44 years old and weighed 88.9 kg (195 lb). Most had been living with psoriasis for about 18 years, with a total PASI score of 19.05. In addition, 43.1% had been treated with phototherapy in the past, 22% with biologics, and 78.4% with systemics.
PASI 90 and 100 were among some of the secondary outcomes measured. Similar to the primary outcome of PASI 75, all treatment groups demonstrated a statistically significant dose-response in PASI 90, compared with placebo. For those on the highest dose of JNJ-2113, 59.5% and 40.5% achieved PASI 90 and PASI 100, respectively, by week 16. The corresponding figures for those receiving placebo were 2.3% and 0%.
The safety profile for JNJ-2113 across all doses was similar to that of placebo, with no evidence of a dose-dependent increase in the occurrence of adverse events (AEs). The most frequently reported AEs were COVID-19 and nasopharyngitis. There were three serious AEs (COVID-19, infected cyst, suicide attempt) among those on the active drug, but the investigators assessed that they were not related to the study intervention. No deaths, major adverse cardiac events, or malignancies were reported during the study.
Approached for an independent comment, Marius-Anton Ionescu, MD, PhD, from the University Hospital Saint Louis, Paris, who specializes in psoriasis, told this news organization that the new development with JNJ-2113 “is really promising.”
Treatment for plaque psoriasis has improved to the point where some biologics, such as risankizumab (Skyrizi), only require patients to have “four shots a year,” he says. “This is the future of psoriasis treatment; it might go down to two shots a year” – a regimen that will be easier than taking an oral medication once or twice a day.
“But it’s good to have an oral option because you will always have some patients who say: ‘Shots are not for me, I’m afraid,’ ” he says.
However, Dr. Ionescu noted that if JNJ-2113 were to pass phase 3 trials, it might face stiff competition from the selective tyrosine kinase 2 (TYK2) inhibitor deucravacitinib (Sotyktu), which the U.S. Food and Drug Administration approved for use in adults with moderate to severe plaque psoriasis last September. “It has very good results and is the first oral therapy that is comparable with biologics for plaque psoriasis,” he says.
But Dr. Bissonnette remains hopeful for the future. “I think JNJ-2113 goes way beyond psoriasis because this type of strategy using oral peptide–blocking receptors could be used in other immune-mediated diseases, including atopic dermatitis and other diseases outside of dermatology.” In addition to running a phase 3 study for moderate to severe plaque psoriasis, Janssen is planning to initiate a phase 2b clinical trial of JNJ-2113 in adults with ulcerative colitis.
The study was funded by Janssen. Dr. Bissonnette reports consulting and investigating for Janssen, and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Dr. Ionescu is an investigator for Psoriasis National Register France Psobioteq (no honoraria), and an investigator and speaker for Uriage cosmetics (honoraria).
A version of this article first appeared on Medscape.com.
SINGAPORE – across all doses, compared with placebo, according to results of the FRONTIER 1 trial.
In the 16-week phase 2b study, 255 adults with moderate to severe plaque psoriasis were randomly assigned into six treatment groups: placebo (n = 43), JNJ-2113 25 mg daily (n = 43), 25 mg twice daily (n = 41), 50 mg daily (n = 43), 100 mg daily (n = 43), or 100 mg twice daily (n = 42).
Of those who took the placebo, only 9.3% achieved the study’s primary endpoint of a 75% or greater improvement in the Psoriasis Area and Severity Index (PASI-75) by week 16. This was compared with 78.6% in the group that took the highest dose.
“Additionally, the onset of action was fairly fast: at week 4, more than 20% of patients had achieved PASI 75,” said Robert Bissonnette, MD, CEO of Innovaderm Research in Montreal, who presented the findings during a late-breaker session at the World Congress of Dermatology.
Patients in the remaining groups demonstrated a response that corresponded to dosing level: with 37.2%, 51.2%, 58.1%, and 65.1% achieving PASI-75 in the 25 mg daily, 25 mg twice-daily, 50 mg daily, and 100 mg daily groups, respectively.
“These results are very interesting because in terms of psoriasis treatment, if this is confirmed in phase 3, it would give us an oral alternative that would be selective for IL-23,” said Dr. Bissonnette, referring to the signaling pathway that plays a critical role in the pathogenesis of several immune-mediated inflammatory diseases, including plaque psoriasis.
Although rarely life-threatening, the skin disorder is often intractable to treatment. In recent years, therapies that block IL-23 signaling and downstream inflammatory cytokine production have proven useful. “We have on the market a number of biological agents targeting IL-23 that we use on a regular basis,” said Dr. Bissonnette. “However, there are currently no orally delivered therapies.”
If successful, JNJ-2113 – a first-in-class oral IL-23 antagonist peptide developed by Janssen – could change the treatment paradigm for patients with moderate to severe plaque psoriasis. “When I was first introduced to the concept, I thought it wouldn’t work as it’s a peptide, that it would be digested by the stomach,” he told the audience. “But because of its GI stability and its potency, when you administer it orally, you can detect pharmacological activity.”
A well-tolerated alternative
Participants in the FRONTIER 1 trial were on average about 44 years old and weighed 88.9 kg (195 lb). Most had been living with psoriasis for about 18 years, with a total PASI score of 19.05. In addition, 43.1% had been treated with phototherapy in the past, 22% with biologics, and 78.4% with systemics.
PASI 90 and 100 were among some of the secondary outcomes measured. Similar to the primary outcome of PASI 75, all treatment groups demonstrated a statistically significant dose-response in PASI 90, compared with placebo. For those on the highest dose of JNJ-2113, 59.5% and 40.5% achieved PASI 90 and PASI 100, respectively, by week 16. The corresponding figures for those receiving placebo were 2.3% and 0%.
The safety profile for JNJ-2113 across all doses was similar to that of placebo, with no evidence of a dose-dependent increase in the occurrence of adverse events (AEs). The most frequently reported AEs were COVID-19 and nasopharyngitis. There were three serious AEs (COVID-19, infected cyst, suicide attempt) among those on the active drug, but the investigators assessed that they were not related to the study intervention. No deaths, major adverse cardiac events, or malignancies were reported during the study.
Approached for an independent comment, Marius-Anton Ionescu, MD, PhD, from the University Hospital Saint Louis, Paris, who specializes in psoriasis, told this news organization that the new development with JNJ-2113 “is really promising.”
Treatment for plaque psoriasis has improved to the point where some biologics, such as risankizumab (Skyrizi), only require patients to have “four shots a year,” he says. “This is the future of psoriasis treatment; it might go down to two shots a year” – a regimen that will be easier than taking an oral medication once or twice a day.
“But it’s good to have an oral option because you will always have some patients who say: ‘Shots are not for me, I’m afraid,’ ” he says.
However, Dr. Ionescu noted that if JNJ-2113 were to pass phase 3 trials, it might face stiff competition from the selective tyrosine kinase 2 (TYK2) inhibitor deucravacitinib (Sotyktu), which the U.S. Food and Drug Administration approved for use in adults with moderate to severe plaque psoriasis last September. “It has very good results and is the first oral therapy that is comparable with biologics for plaque psoriasis,” he says.
But Dr. Bissonnette remains hopeful for the future. “I think JNJ-2113 goes way beyond psoriasis because this type of strategy using oral peptide–blocking receptors could be used in other immune-mediated diseases, including atopic dermatitis and other diseases outside of dermatology.” In addition to running a phase 3 study for moderate to severe plaque psoriasis, Janssen is planning to initiate a phase 2b clinical trial of JNJ-2113 in adults with ulcerative colitis.
The study was funded by Janssen. Dr. Bissonnette reports consulting and investigating for Janssen, and being on advisory panels and receiving research funding from multiple other pharmaceutical companies. Dr. Ionescu is an investigator for Psoriasis National Register France Psobioteq (no honoraria), and an investigator and speaker for Uriage cosmetics (honoraria).
A version of this article first appeared on Medscape.com.
AT WCD 2023
JAK inhibitors efficacious for atopic dermatitis in Asian patients, study finds
SINGAPORE – conducted in Singapore has found.
“Abrocitinib and upadacitinib surprisingly appeared to have better treatment efficacy compared to baricitinib,” said study lead Yik Weng Yew, MD, PhD, MPH, deputy head of research at Singapore’s National Skin Centre (NSC), who presented the results at the 25th World Congress of Dermatology. “But overall, as a group, I think they show a very good treatment response, as well as a good effect on itch response.”
JAK inhibitors are used to treat a variety of inflammatory diseases including alopecia areata, rheumatoid arthritis, and inflammatory bowel disease. Although treatment for severe eczema was previously limited to topical steroids and oral immunosuppressants, there are now two oral JAK inhibitors – abrocitinib and upadacitinib – approved in 2022 by the Food and Drug Administration for treating AD, which affects up to 2.4% of the global population. (A topical formulation of ruxolitinib, a JAK inhibitor, was approved for AD in 2021.)
The Singapore study is one of the few that have examined the safety and efficacy of JAK inhibitors for treatment of AD in a non-White population.
Chinese population
For the 12-week trial, conducted in 2022, Dr. Yew and associates recruited 35 patients from the NSC. More than half of participants (64%) were men and most (96%) were of Chinese ethnicity. Four of every five patients had previously received systemic agents: 17% had been treated with one systemic agent, 18.9% with two, 15.1% with three, 22.6% with four, and 3.8% with five. The most commonly used agents were cyclosporine (62.3%), methotrexate (47.2%), azathioprine (39.6%), and dupilumab (35.8%).
“The switch in therapy could have been a result of inadequate efficacy or cost reasons because in Singapore patients pay out of pocket for AD treatments,” said Dr. Yew.
Additionally, he offered a caveat on the profile of participants: “Perhaps they were more difficult atopic eczema patients, and therefore, the efficacy [of JAK inhibitors] might be a bit different.”
Clearer skin, less itch
Patients received one of the three study drugs: baricitinib (66%), abrocitinib (21%), and upadacitinib (13%). The distribution was “affected by reimbursement patterns and availability of the drug,” explained Dr. Yew.
They were assessed at weeks 4 and 12. By study end, the proportion of patients who self-reported an improvement in their condition was 100% for upadacitinib, 90% for abrocitinib, and 69% for baricitinib.
Scores on the Investigator Global Assessment (IGA) also improved with treatment. Patients in the baricitinib group saw their mean score fall from 4.0 to 3.0 by week 4, then to 2.0 by week 12. With upadacitinib and abrocitinib, “you can see that there is a nice decrease in IGA responses,” said Dr. Yew, referring to the larger improvement in scores experienced by patients on those two treatments. For patients on upadacitinib, IGA decreased from 3.5 to 2 at 4 weeks, then to 0.5 at 12 weeks, while those taking abrocitinib had their scores drop from 4.0 to 2.0 at 4 weeks, then to 1.0 at 12 weeks.
When it came to itch reduction, the abrocitinib group experienced the biggest reduction, with a median reduction of 5.5 points in itch score. Median reduction in itch score was 4 points for the other two groups. “Oral JAK inhibitors appear to have a good effect on itch response,” said Dr. Yew.
However, the researchers observed no significant reduction in percentage of body surface area affected, the last outcome assessed.
The most commonly reported adverse events were increased creatine kinase levels (11.3% of patients), increased LDL cholesterol levels (9.4%), and herpes zoster (9.4%). Those in the abrocitinib reported a higher number of these adverse events, compared with the other two treatment groups. (There were no herpes zoster cases among those taking baricitinib.)
For herpes zoster, Dr. Yew said “the common recommendation” is to give the inactivated shingles vaccine. “But the problem is that, number one, these patients would have probably failed multiple agents so they probably can’t wait for you to vaccinate before you initiate treatment.”
In addition, people in Singapore have to pay out-of-pocket for the two vaccine doses, “which is probably a month’s worth of medication,” he noted. “So we have a lot of resistance from patients.”
Additionally, Dr. Yew noted that contrary to what has previously been reported in the literature, there were few complaints of acne as a side effect in the Singaporean study population.
Toward greater representation
Dr. Yew pointed out that the study was limited by a few factors: neither the Eczema Area and Severity Index or Scoring of Atopic Dermatitis index data was used, and the study population was small and not representative of the real world.
Still, the new findings contribute to the overall safety and efficacy profile of JAK inhibitors in AD, which has so far been scarce in non-White populations.
“In Western studies, unfortunately, the representation of the population of skin of color or different ethnicities is underrepresented,” said Yousef Binamer, MD, chair of the dermatology department at King Faisal Specialist Hospital, Riyadh, Saudi Arabia, when approached for an independent comment on the results.
“This is now why researchers are looking into specific groups to study them,” which he pointed out, is crucial because “the immunophenotyping of AD is different for each background.”
The incidence and severity of AD tend to be higher in Asian and Middle Eastern populations, for instance, he noted. “It’s very common in Asia, and not so common in very white skin. I did my training in Canada so I see the difference,” said Dr. Binamer. “Asian people tend to be more itchy and have a tendency to scar on pigmentation.” Whereas White people “usually do not have this issue.”
“So I think real-world evidence of JAK inhibitors in the other populations is important,” he said. Studies such as the one conducted in Singapore, as well as the recently reported QUARTZ3 study, which examined the use of the JAK inhibitor ivarmacitinib in 256 Chinese patients with AD, are helping to pave the way.
The study was independently supported. Dr. Yew and Dr. Binamer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SINGAPORE – conducted in Singapore has found.
“Abrocitinib and upadacitinib surprisingly appeared to have better treatment efficacy compared to baricitinib,” said study lead Yik Weng Yew, MD, PhD, MPH, deputy head of research at Singapore’s National Skin Centre (NSC), who presented the results at the 25th World Congress of Dermatology. “But overall, as a group, I think they show a very good treatment response, as well as a good effect on itch response.”
JAK inhibitors are used to treat a variety of inflammatory diseases including alopecia areata, rheumatoid arthritis, and inflammatory bowel disease. Although treatment for severe eczema was previously limited to topical steroids and oral immunosuppressants, there are now two oral JAK inhibitors – abrocitinib and upadacitinib – approved in 2022 by the Food and Drug Administration for treating AD, which affects up to 2.4% of the global population. (A topical formulation of ruxolitinib, a JAK inhibitor, was approved for AD in 2021.)
The Singapore study is one of the few that have examined the safety and efficacy of JAK inhibitors for treatment of AD in a non-White population.
Chinese population
For the 12-week trial, conducted in 2022, Dr. Yew and associates recruited 35 patients from the NSC. More than half of participants (64%) were men and most (96%) were of Chinese ethnicity. Four of every five patients had previously received systemic agents: 17% had been treated with one systemic agent, 18.9% with two, 15.1% with three, 22.6% with four, and 3.8% with five. The most commonly used agents were cyclosporine (62.3%), methotrexate (47.2%), azathioprine (39.6%), and dupilumab (35.8%).
“The switch in therapy could have been a result of inadequate efficacy or cost reasons because in Singapore patients pay out of pocket for AD treatments,” said Dr. Yew.
Additionally, he offered a caveat on the profile of participants: “Perhaps they were more difficult atopic eczema patients, and therefore, the efficacy [of JAK inhibitors] might be a bit different.”
Clearer skin, less itch
Patients received one of the three study drugs: baricitinib (66%), abrocitinib (21%), and upadacitinib (13%). The distribution was “affected by reimbursement patterns and availability of the drug,” explained Dr. Yew.
They were assessed at weeks 4 and 12. By study end, the proportion of patients who self-reported an improvement in their condition was 100% for upadacitinib, 90% for abrocitinib, and 69% for baricitinib.
Scores on the Investigator Global Assessment (IGA) also improved with treatment. Patients in the baricitinib group saw their mean score fall from 4.0 to 3.0 by week 4, then to 2.0 by week 12. With upadacitinib and abrocitinib, “you can see that there is a nice decrease in IGA responses,” said Dr. Yew, referring to the larger improvement in scores experienced by patients on those two treatments. For patients on upadacitinib, IGA decreased from 3.5 to 2 at 4 weeks, then to 0.5 at 12 weeks, while those taking abrocitinib had their scores drop from 4.0 to 2.0 at 4 weeks, then to 1.0 at 12 weeks.
When it came to itch reduction, the abrocitinib group experienced the biggest reduction, with a median reduction of 5.5 points in itch score. Median reduction in itch score was 4 points for the other two groups. “Oral JAK inhibitors appear to have a good effect on itch response,” said Dr. Yew.
However, the researchers observed no significant reduction in percentage of body surface area affected, the last outcome assessed.
The most commonly reported adverse events were increased creatine kinase levels (11.3% of patients), increased LDL cholesterol levels (9.4%), and herpes zoster (9.4%). Those in the abrocitinib reported a higher number of these adverse events, compared with the other two treatment groups. (There were no herpes zoster cases among those taking baricitinib.)
For herpes zoster, Dr. Yew said “the common recommendation” is to give the inactivated shingles vaccine. “But the problem is that, number one, these patients would have probably failed multiple agents so they probably can’t wait for you to vaccinate before you initiate treatment.”
In addition, people in Singapore have to pay out-of-pocket for the two vaccine doses, “which is probably a month’s worth of medication,” he noted. “So we have a lot of resistance from patients.”
Additionally, Dr. Yew noted that contrary to what has previously been reported in the literature, there were few complaints of acne as a side effect in the Singaporean study population.
Toward greater representation
Dr. Yew pointed out that the study was limited by a few factors: neither the Eczema Area and Severity Index or Scoring of Atopic Dermatitis index data was used, and the study population was small and not representative of the real world.
Still, the new findings contribute to the overall safety and efficacy profile of JAK inhibitors in AD, which has so far been scarce in non-White populations.
“In Western studies, unfortunately, the representation of the population of skin of color or different ethnicities is underrepresented,” said Yousef Binamer, MD, chair of the dermatology department at King Faisal Specialist Hospital, Riyadh, Saudi Arabia, when approached for an independent comment on the results.
“This is now why researchers are looking into specific groups to study them,” which he pointed out, is crucial because “the immunophenotyping of AD is different for each background.”
The incidence and severity of AD tend to be higher in Asian and Middle Eastern populations, for instance, he noted. “It’s very common in Asia, and not so common in very white skin. I did my training in Canada so I see the difference,” said Dr. Binamer. “Asian people tend to be more itchy and have a tendency to scar on pigmentation.” Whereas White people “usually do not have this issue.”
“So I think real-world evidence of JAK inhibitors in the other populations is important,” he said. Studies such as the one conducted in Singapore, as well as the recently reported QUARTZ3 study, which examined the use of the JAK inhibitor ivarmacitinib in 256 Chinese patients with AD, are helping to pave the way.
The study was independently supported. Dr. Yew and Dr. Binamer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
SINGAPORE – conducted in Singapore has found.
“Abrocitinib and upadacitinib surprisingly appeared to have better treatment efficacy compared to baricitinib,” said study lead Yik Weng Yew, MD, PhD, MPH, deputy head of research at Singapore’s National Skin Centre (NSC), who presented the results at the 25th World Congress of Dermatology. “But overall, as a group, I think they show a very good treatment response, as well as a good effect on itch response.”
JAK inhibitors are used to treat a variety of inflammatory diseases including alopecia areata, rheumatoid arthritis, and inflammatory bowel disease. Although treatment for severe eczema was previously limited to topical steroids and oral immunosuppressants, there are now two oral JAK inhibitors – abrocitinib and upadacitinib – approved in 2022 by the Food and Drug Administration for treating AD, which affects up to 2.4% of the global population. (A topical formulation of ruxolitinib, a JAK inhibitor, was approved for AD in 2021.)
The Singapore study is one of the few that have examined the safety and efficacy of JAK inhibitors for treatment of AD in a non-White population.
Chinese population
For the 12-week trial, conducted in 2022, Dr. Yew and associates recruited 35 patients from the NSC. More than half of participants (64%) were men and most (96%) were of Chinese ethnicity. Four of every five patients had previously received systemic agents: 17% had been treated with one systemic agent, 18.9% with two, 15.1% with three, 22.6% with four, and 3.8% with five. The most commonly used agents were cyclosporine (62.3%), methotrexate (47.2%), azathioprine (39.6%), and dupilumab (35.8%).
“The switch in therapy could have been a result of inadequate efficacy or cost reasons because in Singapore patients pay out of pocket for AD treatments,” said Dr. Yew.
Additionally, he offered a caveat on the profile of participants: “Perhaps they were more difficult atopic eczema patients, and therefore, the efficacy [of JAK inhibitors] might be a bit different.”
Clearer skin, less itch
Patients received one of the three study drugs: baricitinib (66%), abrocitinib (21%), and upadacitinib (13%). The distribution was “affected by reimbursement patterns and availability of the drug,” explained Dr. Yew.
They were assessed at weeks 4 and 12. By study end, the proportion of patients who self-reported an improvement in their condition was 100% for upadacitinib, 90% for abrocitinib, and 69% for baricitinib.
Scores on the Investigator Global Assessment (IGA) also improved with treatment. Patients in the baricitinib group saw their mean score fall from 4.0 to 3.0 by week 4, then to 2.0 by week 12. With upadacitinib and abrocitinib, “you can see that there is a nice decrease in IGA responses,” said Dr. Yew, referring to the larger improvement in scores experienced by patients on those two treatments. For patients on upadacitinib, IGA decreased from 3.5 to 2 at 4 weeks, then to 0.5 at 12 weeks, while those taking abrocitinib had their scores drop from 4.0 to 2.0 at 4 weeks, then to 1.0 at 12 weeks.
When it came to itch reduction, the abrocitinib group experienced the biggest reduction, with a median reduction of 5.5 points in itch score. Median reduction in itch score was 4 points for the other two groups. “Oral JAK inhibitors appear to have a good effect on itch response,” said Dr. Yew.
However, the researchers observed no significant reduction in percentage of body surface area affected, the last outcome assessed.
The most commonly reported adverse events were increased creatine kinase levels (11.3% of patients), increased LDL cholesterol levels (9.4%), and herpes zoster (9.4%). Those in the abrocitinib reported a higher number of these adverse events, compared with the other two treatment groups. (There were no herpes zoster cases among those taking baricitinib.)
For herpes zoster, Dr. Yew said “the common recommendation” is to give the inactivated shingles vaccine. “But the problem is that, number one, these patients would have probably failed multiple agents so they probably can’t wait for you to vaccinate before you initiate treatment.”
In addition, people in Singapore have to pay out-of-pocket for the two vaccine doses, “which is probably a month’s worth of medication,” he noted. “So we have a lot of resistance from patients.”
Additionally, Dr. Yew noted that contrary to what has previously been reported in the literature, there were few complaints of acne as a side effect in the Singaporean study population.
Toward greater representation
Dr. Yew pointed out that the study was limited by a few factors: neither the Eczema Area and Severity Index or Scoring of Atopic Dermatitis index data was used, and the study population was small and not representative of the real world.
Still, the new findings contribute to the overall safety and efficacy profile of JAK inhibitors in AD, which has so far been scarce in non-White populations.
“In Western studies, unfortunately, the representation of the population of skin of color or different ethnicities is underrepresented,” said Yousef Binamer, MD, chair of the dermatology department at King Faisal Specialist Hospital, Riyadh, Saudi Arabia, when approached for an independent comment on the results.
“This is now why researchers are looking into specific groups to study them,” which he pointed out, is crucial because “the immunophenotyping of AD is different for each background.”
The incidence and severity of AD tend to be higher in Asian and Middle Eastern populations, for instance, he noted. “It’s very common in Asia, and not so common in very white skin. I did my training in Canada so I see the difference,” said Dr. Binamer. “Asian people tend to be more itchy and have a tendency to scar on pigmentation.” Whereas White people “usually do not have this issue.”
“So I think real-world evidence of JAK inhibitors in the other populations is important,” he said. Studies such as the one conducted in Singapore, as well as the recently reported QUARTZ3 study, which examined the use of the JAK inhibitor ivarmacitinib in 256 Chinese patients with AD, are helping to pave the way.
The study was independently supported. Dr. Yew and Dr. Binamer have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT WCD 2023
No benefit to adding limited radiation in advanced cancer
TOPLINE:
METHODOLOGY:
- In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
- Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
- Most patients had more than three lesions.
- Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.
TAKEAWAY:
- Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
- Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
- However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
- The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.
IN PRACTICE:
Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
SOURCE:
The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.
LIMITATIONS:
- There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
- More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.
DISCLOSURES:
The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.
Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
- Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
- Most patients had more than three lesions.
- Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.
TAKEAWAY:
- Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
- Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
- However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
- The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.
IN PRACTICE:
Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
SOURCE:
The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.
LIMITATIONS:
- There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
- More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.
DISCLOSURES:
The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.
Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- In the phase 2 CHEERS trial, 52 patients with advanced solid tumors were randomized to anti-PD-1/PD-L1 monotherapy and 47 patients to the same treatment plus stereotactic body radiotherapy (3 x 8 Gy) to a maximum of three lesions before the second or third cycle of an immune checkpoint inhibitor.
- Patients had locally advanced or metastatic melanoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung carcinoma, or head and neck squamous cell carcinoma and were treated at five Belgian hospitals.
- Most patients had more than three lesions.
- Seven patients in the experimental group did not complete radiotherapy because of early progression or intercurrent illness.
TAKEAWAY:
- Over a median follow-up of 12.5 months, median progression-free survival was 4.4 months in the radiotherapy group versus 2.8 months in the control group (hazard ratio, 0.95; P = .82).
- Median overall survival was not significantly better with radiotherapy, compared with the control group (14.3 vs. 11 months; HR, 0.82; P = .47), nor was the objective response rate (27% vs. 22%; P = .56).
- However, a post hoc analysis demonstrated a significant association between the number of irradiated lesions and overall survival among patients receiving radiotherapy (HR, 0.31; P = .002).
- The incidence of grade 3 or worse treatment-related adverse events was 18% in both groups.
IN PRACTICE:
Although the study was negative overall, the post hoc analysis coupled with “recent evidence suggests that treating all active disease sites with higher radiation doses ... may be a more promising strategy to optimize systemic disease control,” the authors concluded.
SOURCE:
The study was led by Mathieu Spaas, MD, department of radiation oncology, Ghent (Bellgium) University, and published online in JAMA Oncology.
LIMITATIONS:
- There was insufficient power to detect if certain cancers benefited more from add-on radiation because of the small sample size.
- More than half of patients in the control group had already received some form of radiotherapy before study inclusion, which may mean the study underestimated the benefit of radiotherapy.
DISCLOSURES:
The work was funded by Kom Op Tegen Kanker and Varian Medical Systems.
Investigators disclosed numerous industry ties, including Merck, Novartis, and Bristol Myers Squibb.
A version of this article first appeared on Medscape.com.