PHILADELPHIA – A proprietary formula showed good performance stratifying the risk of adults with early-stage chronic kidney disease (CKD) advancing to more severe kidney dysfunction and increased health care needs. The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.

The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.

Mitchel L. Zoler/MDedge News

In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
 

‘Ready to implement’

“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.

For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).

He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.

Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.

“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”

Simplified data collection

“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.

Mitchel L. Zoler/MDedge News

The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”

Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”

Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.

Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.

The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.

PHILADELPHIA – A proprietary formula showed good performance stratifying the risk of adults with early-stage chronic kidney disease (CKD) advancing to more severe kidney dysfunction and increased health care needs. The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.

The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.

Mitchel L. Zoler/MDedge News

In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
 

‘Ready to implement’

“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.

For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).

He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.

Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.

“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”

Simplified data collection

“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.

Mitchel L. Zoler/MDedge News

The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”

Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”

Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.

Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.

The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.

PHILADELPHIA – A proprietary formula showed good performance stratifying the risk of adults with early-stage chronic kidney disease (CKD) advancing to more severe kidney dysfunction and increased health care needs. The analyses offer the possibility of focusing intensified medical management of early-stage CKD on those patients who could potentially receive the most benefit.

The Klinrisk model predicts the risk of an adult with early-stage CKD developing either a 40% or greater drop in estimated glomerular filtration rate or kidney failure. It calculates risk based on 20 lab-measured variables that include serum creatinine, urine albumin-to-creatinine ratio, and other values taken from routinely ordered tests such as complete blood cell counts, chemistry panels, comprehensive metabolic panels, and urinalysis.

Mitchel L. Zoler/MDedge News

In the most recent and largest external validation study using data from 4.6 million American adults enrolled in commercial and Medicare insurance plans, the results showed Klinrisk correctly predicted CKD progression in 80%-83% of individuals over 2 years and in 78%-83% of individuals over 5 years, depending on the insurance provider, Navdeep Tangri, MD, PhD, reported at the annual meeting of the American Society of Nephrology. When urinalysis data were available, the model correctly predicted CKD progression in 81%-87% of individuals over 2 years and in 80%-87% of individuals over 5 years. These results follow prior reports of several other successful validations of Klinrisk.
 

‘Ready to implement’

“The Klinrisk model is ready to implement by any payer, health system, or clinic where the needed lab data are available,” said Dr. Tangri, a nephrologist and professor at the University of Manitoba, Winnipeg, and founder of Klinrisk Inc., the company developing and commercializing the Klinrisk assessment tool.

For the time being, Dr. Tangri sees Klinrisk as a population health device that can allow insurers and health systems to track management quality and quality improvement and to target patients who stand to benefit most from relatively expensive resources. This includes prescriptions for finerenone (Kerendia, Bayer) for people who also have type 2 diabetes, and agents from the class of sodium-glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim and Lilly).

He has also begun discussions with the Food and Drug Administration about the data the agency will need to consider Klinrisk for potential approval as a new medical device, perhaps in 2025. That’s how he envisions getting a Klinrisk assessment into the hands of caregivers that they could use with individual patients to create an appropriate treatment plan.

Results from his new analysis showed that “all the kidney disease action is in the 10%-20% of people with the highest risk on Klinrisk, while not much happens in those in the bottom half,” Dr. Tangri said during his presentation.

“We’re trying to find the patients who get the largest [absolute] benefit from intensified treatment,” he added in an interview. “Klinrisk finds people with high-risk kidney disease early on, when kidney function is still normal or near normal. High-risk patients are often completely unrecognized. Risk-based management” that identifies the early-stage CKD patients who would benefit most from treatment with an SGLT2 inhibitor, finerenone, and other foundational treatments to slow CKD progression “is better than the free-for-all that occurs today.”

Simplified data collection

“Klinrisk is very effective,” but requires follow-up by clinicians and health systems to implement its findings, commented Josef Coresh, MD, a professor of clinical epidemiology at Johns Hopkins Bloomberg, Baltimore. Dr. Coresh compared it with a free equation that estimates a person’s risk for a 40% drop in kidney function over the next 3 years developed by Dr. Tangri, Dr. Coresh, and many collaborators led by Morgan C. Grams, MD, PhD, of New York University that they published in 2022, and posted on a website of the CKD Prognosis Consortium.

Mitchel L. Zoler/MDedge News

The CKD Prognosis Consortium formula “takes a different approach” from Klinrisk. The commercial formula “is simpler, only using lab measures, and avoids inputs taken from physical examination such as systolic blood pressure and body mass index and health history data such as smoking, noted Dr. Coresh. He also speculated that “a commercial formula that must be paid for may counterintuitively result in better follow-up for making management changes if it uses some of the resources for education and system changes.”

Using data from multiple sources, like the CKD Prognosis Consortium equation, can create implementation challenges, said Dr. Tangri. “Lab results don’t vary much,” which makes Klinrisk “quite an improvement for implementation. It’s easier to implement.”

Other findings from the newest validation study that Dr. Tangri presented were that the people studied with Klinrisk scores in the top 10% had, over the next 2 years of follow-up and compared with people in the bottom half for Klinrisk staging, a 3- to 5-fold higher rate of all-cause medical costs, a 13-30-fold increase in CKD-related costs, and a 5- to 10-fold increase in hospitalizations and ED visits.

Early identification of CKD and early initiation of intensified treatment for high-risk patients can reduce the rate of progression to dialysis, reduce hospitalizations for heart failure, and lower the cost of care, Dr. Tangri said.

The validation study in 4.6 million Americans was sponsored by Boehringer Ingelheim. Dr. Tangri founded and has an ownership interest in Klinrisk. He has also received honoraria from, has ownership interests in, and has been a consultant to multiple pharmaceutical companies. Dr. Coresh had no disclosures.

BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.

That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.

Cleveland Clinic

“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.

The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.

Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
 

Validated model

They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.

As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.

The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.

In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.

The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
 

A “tsunami” of liver disease

In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.

“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.

“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.

Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.

The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.


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

BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.

That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.

Cleveland Clinic

“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.

The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.

Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
 

Validated model

They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.

As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.

The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.

In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.

The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
 

A “tsunami” of liver disease

In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.

“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.

“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.

Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.

The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.


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

BOSTON – The nomenclature may have changed, but the steady rise in the most common form of liver disease – metabolic dysfunction–associated steatotic liver disease (MASLD, formerly known as NAFLD) – is predicted to continue into the middle of this century.

That’s according to Phuc Le, PhD, MPH, and colleagues at the Cleveland Clinic. They created a mathematical model incorporating data on the growth of the U.S. population and the natural history of MASLD/NAFLD. The model projected a relative 23% increase in MASLD among U.S. adults from 2020 to 2050.

Cleveland Clinic

“Our model forecasts a substantial clinical burden of NAFLD over the next 3 decades. In the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant,” Dr. Le said in a media briefing held on Nov. 7 prior to her presentation of the data at the annual meeting of the American Association for the Study of Liver Diseases.

The estimated worldwide prevalence of MASLD is 38%. In the United States, an estimated 27.8% of adults had MASLD as of 2020.

Dr. Le and colleagues wanted to get a clearer picture of the expected increase in the clinical burden of MASLD in the coming decades. The researchers used data from the medical literature to create an individual-level state transition model. They took into account projections of the growth of the U.S. population and the progression of MASLD and metabolic dysfunction–associated steatohepatitis (MASH, formerly NASH) through stages of fibrosis to decompensation, hepatocellular carcinoma (HCC), transplant, and liver-related death as a proportion of all-cause mortality.
 

Validated model

They validated the model by testing it against liver outcomes from 2000 through 2018 and published data on the U.S. population. The model closely matched trends in MASLD prevalence, MASH proportion, HCC and liver transplant incidences, and overall survival rates for patients with MASLD.

As noted, the model predicted a steady increase in MASLD prevalence, from 27.8% in 2020 to 34.3% by 2050, a relative increase of about 23%. The model also predicted a slight uptick in the proportion of MASH among patients with MASLD, from 20% to 21.8%.

The investigators said that the prevalence of MASLD/MASH would likely remain relatively stable among people aged 18-29 years but would increase significantly for all other age groups.

In addition, the model predicted an increase in the proportion of cirrhosis in patients with MASLD from 1.9% to 3.1%, as well as a rise in liver-related deaths from 0.4% of all deaths in 2020 to 1% by 2050.

The investigators also foresaw a rise in HCC cases, from 10,400 annually to 19,300 by 2050 and a more than twofold increase in liver transplants, from 1,700 in 2020 to 4,200 in 2050.
 

A “tsunami” of liver disease

In the question-and-answer portion of the briefing, Norah Terrault, MD, AASLD president and chief of gastroenterology and hepatology at the University of Southern California, Los Angeles, commented on the study findings and “the frightening trajectory in terms of disease burden.

“I’m thinking to myself there’s no way we’re going to be able to transplant our way out of this tsunami of disease that’s coming our way,” she said, and asked Dr. Le what policy or societal approaches might be implemented to help stem the tide.

“This is a really huge question,” Dr. Le acknowledged. The study only provides estimates of what the future burden of disease might be if there are no changes in clinical care for patients with MASLD or if the trajectory of contributing factors, such as obesity, diabetes, and other metabolic diseases, continued to increase, she cautioned.

Raising awareness of MASLD/MASH and working to improve collaboration among liver specialists and general practitioners could help to flatten the curve, she suggested.

The study was supported by a grant from the Agency for Healthcare Research and Quality. Dr. Le and Dr. Terrault have disclosed no relevant financial relations.


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

Angiosarcomas are uncommon, high-grade malignant tumors of endothelial cell origin that can arise via the lymphatics or vasculature. They typically occur spontaneously; however, there have been cases reported of benign vascular transformation. These tumors are more commonly found in elderly men on the head and neck in sun-damaged skin. Radiation-induced angiosarcoma occurs in an estimated 0.05%-0.3% of patients with breast cancer who underwent surgery and radiation therapy. This is a late complication, typically occurring about 5-10 years after radiation. Stewart-Treves syndrome, chronic lymphedema occurring after breast cancer treatment with axillary node dissection, increases the risk of angiosarcoma. As a vascular tumor, angiosarcoma spreads hematogenously and carries a poor prognosis if not caught early. Differential diagnoses include other vascular tumors such as retiform hemangioendothelioma. In this specific patient, the differential diagnosis includes Paget’s disease, chronic radiation skin changes, and eczema.

Histopathologically, angiosarcomas exhibit abnormal, pleomorphic, malignant endothelial cells. As the tumor progresses, the cell architecture becomes more distorted and cells form layers with papillary projections into the vascular lumen. Malignant cells may stain positive for CD31, CD34, the oncogene ERG and the proto-oncogene FLI-1. Histology in this patient revealed radiation changes in the dermis, as well as few vascular channels lined by large endothelial cells with marked nuclear atypia, in the form of large nucleoli and variably coarse chromatin. The cells were positive for MYC.

Treatment of angiosarcoma involves a multidisciplinary approach. Resection with wide margins is generally the treatment of choice. However, recurrence is relatively common, which may be a result of microsatellite deposits of the tumor. Perioperative radiation is recommended, and adjuvant chemotherapy often is recommended for metastatic disease. Specifically, paclitaxel has been found to promote survival in some cases of cutaneous angiosarcoma. Metastatic disease may be treated with cytotoxic drugs such as anthracyclines and taxanes. Additionally, targeted therapy including anti-VEGF drugs and tyrosine kinase inhibitors have been tested.

The case and photo were submitted by Mr. Shapiro of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Dr. Bilu Martin. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cohen-Hallaleh RB et al. Clin Sarcoma Res. 2017 Aug 7:7:15.

Cozzi S et al. Rep Pract Oncol Radiother. 2021 Sep 30;26(5):827-32.

Spiker AM, Mangla A, Ramsey ML. Angiosarcoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing; 2023 Jan-. Available from: www.ncbi.nlm.nih.gov/books/NBK441983/

Angiosarcomas are uncommon, high-grade malignant tumors of endothelial cell origin that can arise via the lymphatics or vasculature. They typically occur spontaneously; however, there have been cases reported of benign vascular transformation. These tumors are more commonly found in elderly men on the head and neck in sun-damaged skin. Radiation-induced angiosarcoma occurs in an estimated 0.05%-0.3% of patients with breast cancer who underwent surgery and radiation therapy. This is a late complication, typically occurring about 5-10 years after radiation. Stewart-Treves syndrome, chronic lymphedema occurring after breast cancer treatment with axillary node dissection, increases the risk of angiosarcoma. As a vascular tumor, angiosarcoma spreads hematogenously and carries a poor prognosis if not caught early. Differential diagnoses include other vascular tumors such as retiform hemangioendothelioma. In this specific patient, the differential diagnosis includes Paget’s disease, chronic radiation skin changes, and eczema.

Histopathologically, angiosarcomas exhibit abnormal, pleomorphic, malignant endothelial cells. As the tumor progresses, the cell architecture becomes more distorted and cells form layers with papillary projections into the vascular lumen. Malignant cells may stain positive for CD31, CD34, the oncogene ERG and the proto-oncogene FLI-1. Histology in this patient revealed radiation changes in the dermis, as well as few vascular channels lined by large endothelial cells with marked nuclear atypia, in the form of large nucleoli and variably coarse chromatin. The cells were positive for MYC.

Treatment of angiosarcoma involves a multidisciplinary approach. Resection with wide margins is generally the treatment of choice. However, recurrence is relatively common, which may be a result of microsatellite deposits of the tumor. Perioperative radiation is recommended, and adjuvant chemotherapy often is recommended for metastatic disease. Specifically, paclitaxel has been found to promote survival in some cases of cutaneous angiosarcoma. Metastatic disease may be treated with cytotoxic drugs such as anthracyclines and taxanes. Additionally, targeted therapy including anti-VEGF drugs and tyrosine kinase inhibitors have been tested.

The case and photo were submitted by Mr. Shapiro of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Dr. Bilu Martin. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cohen-Hallaleh RB et al. Clin Sarcoma Res. 2017 Aug 7:7:15.

Cozzi S et al. Rep Pract Oncol Radiother. 2021 Sep 30;26(5):827-32.

Spiker AM, Mangla A, Ramsey ML. Angiosarcoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing; 2023 Jan-. Available from: www.ncbi.nlm.nih.gov/books/NBK441983/

Angiosarcomas are uncommon, high-grade malignant tumors of endothelial cell origin that can arise via the lymphatics or vasculature. They typically occur spontaneously; however, there have been cases reported of benign vascular transformation. These tumors are more commonly found in elderly men on the head and neck in sun-damaged skin. Radiation-induced angiosarcoma occurs in an estimated 0.05%-0.3% of patients with breast cancer who underwent surgery and radiation therapy. This is a late complication, typically occurring about 5-10 years after radiation. Stewart-Treves syndrome, chronic lymphedema occurring after breast cancer treatment with axillary node dissection, increases the risk of angiosarcoma. As a vascular tumor, angiosarcoma spreads hematogenously and carries a poor prognosis if not caught early. Differential diagnoses include other vascular tumors such as retiform hemangioendothelioma. In this specific patient, the differential diagnosis includes Paget’s disease, chronic radiation skin changes, and eczema.

Histopathologically, angiosarcomas exhibit abnormal, pleomorphic, malignant endothelial cells. As the tumor progresses, the cell architecture becomes more distorted and cells form layers with papillary projections into the vascular lumen. Malignant cells may stain positive for CD31, CD34, the oncogene ERG and the proto-oncogene FLI-1. Histology in this patient revealed radiation changes in the dermis, as well as few vascular channels lined by large endothelial cells with marked nuclear atypia, in the form of large nucleoli and variably coarse chromatin. The cells were positive for MYC.

Treatment of angiosarcoma involves a multidisciplinary approach. Resection with wide margins is generally the treatment of choice. However, recurrence is relatively common, which may be a result of microsatellite deposits of the tumor. Perioperative radiation is recommended, and adjuvant chemotherapy often is recommended for metastatic disease. Specifically, paclitaxel has been found to promote survival in some cases of cutaneous angiosarcoma. Metastatic disease may be treated with cytotoxic drugs such as anthracyclines and taxanes. Additionally, targeted therapy including anti-VEGF drugs and tyrosine kinase inhibitors have been tested.

The case and photo were submitted by Mr. Shapiro of Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, Fla., and Dr. Bilu Martin. The column was edited by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Cohen-Hallaleh RB et al. Clin Sarcoma Res. 2017 Aug 7:7:15.

Cozzi S et al. Rep Pract Oncol Radiother. 2021 Sep 30;26(5):827-32.

Spiker AM, Mangla A, Ramsey ML. Angiosarcoma. [Updated 2023 Jul 17]. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing; 2023 Jan-. Available from: www.ncbi.nlm.nih.gov/books/NBK441983/

The Food and Drug Administration has approved the Paradise Ultrasound Renal Denervation system for the treatment of hypertension, Recor Medical and parent company Otsuka Medical Devices have announced.
 

Approval follows a positive review by the FDA’s Circulatory Systems Device panel in August that deemed the system both safe and effective in lowering blood pressure for adults with uncontrolled hypertension who may be inadequately responsive to, or who are intolerant of, antihypertensive medications. 

Olivier Le Moal/Getty Images

Data supporting approval were provided by the RADIANCE program, the pivotal RADIANCE II trial, as well as RADIANCE-HTN SOLO and RADIANCE-HTN TRIO. RADIANCE II and RADIANCE-HTN SOLO studied patients with mild to moderate hypertension in an “off-meds” setting, and RADIANCE-HTN TRIO enrolled patients with resistant hypertension on standardized triple antihypertensive therapy.  

Renal denervation is intended as an adjunctive treatment option when lifestyle changes and medication have not resulted in adequate blood pressure control, the statement notes. It works by denervating the sympathetic nerves surrounding the renal arteries, reducing the overactivity that can lead to hypertension.

The system delivers two to three doses of 360-degree ultrasound energy, lasting 7 seconds each, through each of the main renal arteries to the surrounding nerves. This particular system is water-cooled to protect the renal artery wall, the statement adds.

“Given the significant blood pressure reductions seen in the ultrasound renal denervation trials, the Paradise Ultrasound Renal Denervation system offers a much-needed advancement in our currently available options to control hypertension,” site principal investigator Naomi Fisher, MD, associate professor of medicine, Harvard Medical School, and director of hypertension service and hypertension innovation, division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, said in the statement.

Ultrasound renal denervation “has proven efficacy in patients with truly resistant hypertension, a population for whom medication therapy often fails. It is also effective in patients with mild to moderate hypertension who cannot tolerate enough medication to control their blood pressure,” Dr. Fisher added.

The Paradise ultrasound renal denervation system previously received CE mark and has been successfully introduced in Europe and is an investigational device in Japan, the companies note.

A second renal denervation system, the Symplicity Spyral Renal Denervation System (Medtronic) underwent FDA panel review the day after the Paradise system review in August, and although the panel voted unanimously that the Symplicity system is safe, they were split on whether or not it was efficacious. A final decision on approval by the FDA of that system is still pending.

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

The Food and Drug Administration has approved the Paradise Ultrasound Renal Denervation system for the treatment of hypertension, Recor Medical and parent company Otsuka Medical Devices have announced.
 

Approval follows a positive review by the FDA’s Circulatory Systems Device panel in August that deemed the system both safe and effective in lowering blood pressure for adults with uncontrolled hypertension who may be inadequately responsive to, or who are intolerant of, antihypertensive medications. 

Olivier Le Moal/Getty Images

Data supporting approval were provided by the RADIANCE program, the pivotal RADIANCE II trial, as well as RADIANCE-HTN SOLO and RADIANCE-HTN TRIO. RADIANCE II and RADIANCE-HTN SOLO studied patients with mild to moderate hypertension in an “off-meds” setting, and RADIANCE-HTN TRIO enrolled patients with resistant hypertension on standardized triple antihypertensive therapy.  

Renal denervation is intended as an adjunctive treatment option when lifestyle changes and medication have not resulted in adequate blood pressure control, the statement notes. It works by denervating the sympathetic nerves surrounding the renal arteries, reducing the overactivity that can lead to hypertension.

The system delivers two to three doses of 360-degree ultrasound energy, lasting 7 seconds each, through each of the main renal arteries to the surrounding nerves. This particular system is water-cooled to protect the renal artery wall, the statement adds.

“Given the significant blood pressure reductions seen in the ultrasound renal denervation trials, the Paradise Ultrasound Renal Denervation system offers a much-needed advancement in our currently available options to control hypertension,” site principal investigator Naomi Fisher, MD, associate professor of medicine, Harvard Medical School, and director of hypertension service and hypertension innovation, division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, said in the statement.

Ultrasound renal denervation “has proven efficacy in patients with truly resistant hypertension, a population for whom medication therapy often fails. It is also effective in patients with mild to moderate hypertension who cannot tolerate enough medication to control their blood pressure,” Dr. Fisher added.

The Paradise ultrasound renal denervation system previously received CE mark and has been successfully introduced in Europe and is an investigational device in Japan, the companies note.

A second renal denervation system, the Symplicity Spyral Renal Denervation System (Medtronic) underwent FDA panel review the day after the Paradise system review in August, and although the panel voted unanimously that the Symplicity system is safe, they were split on whether or not it was efficacious. A final decision on approval by the FDA of that system is still pending.

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

The Food and Drug Administration has approved the Paradise Ultrasound Renal Denervation system for the treatment of hypertension, Recor Medical and parent company Otsuka Medical Devices have announced.
 

Approval follows a positive review by the FDA’s Circulatory Systems Device panel in August that deemed the system both safe and effective in lowering blood pressure for adults with uncontrolled hypertension who may be inadequately responsive to, or who are intolerant of, antihypertensive medications. 

Olivier Le Moal/Getty Images

Data supporting approval were provided by the RADIANCE program, the pivotal RADIANCE II trial, as well as RADIANCE-HTN SOLO and RADIANCE-HTN TRIO. RADIANCE II and RADIANCE-HTN SOLO studied patients with mild to moderate hypertension in an “off-meds” setting, and RADIANCE-HTN TRIO enrolled patients with resistant hypertension on standardized triple antihypertensive therapy.  

Renal denervation is intended as an adjunctive treatment option when lifestyle changes and medication have not resulted in adequate blood pressure control, the statement notes. It works by denervating the sympathetic nerves surrounding the renal arteries, reducing the overactivity that can lead to hypertension.

The system delivers two to three doses of 360-degree ultrasound energy, lasting 7 seconds each, through each of the main renal arteries to the surrounding nerves. This particular system is water-cooled to protect the renal artery wall, the statement adds.

“Given the significant blood pressure reductions seen in the ultrasound renal denervation trials, the Paradise Ultrasound Renal Denervation system offers a much-needed advancement in our currently available options to control hypertension,” site principal investigator Naomi Fisher, MD, associate professor of medicine, Harvard Medical School, and director of hypertension service and hypertension innovation, division of endocrinology, diabetes, and hypertension at Brigham and Women’s Hospital, Boston, said in the statement.

Ultrasound renal denervation “has proven efficacy in patients with truly resistant hypertension, a population for whom medication therapy often fails. It is also effective in patients with mild to moderate hypertension who cannot tolerate enough medication to control their blood pressure,” Dr. Fisher added.

The Paradise ultrasound renal denervation system previously received CE mark and has been successfully introduced in Europe and is an investigational device in Japan, the companies note.

A second renal denervation system, the Symplicity Spyral Renal Denervation System (Medtronic) underwent FDA panel review the day after the Paradise system review in August, and although the panel voted unanimously that the Symplicity system is safe, they were split on whether or not it was efficacious. A final decision on approval by the FDA of that system is still pending.

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

Short- or long-term use of opioids may increase risk of poor outcomes in patients with inflammatory bowel disease (IBD), according to investigators.

These findings amplify the safety signal from previous inpatient studies by showing that even a short course of opioids in an outpatient setting may increase risks of corticosteroid use and emergency department utilization, prompting caution among prescribers, reported Laura Telfer, MS, of Penn State College of Medicine, Hershey, Pa., and colleagues.

“Opioids are frequently prescribed to treat pain associated with IBD,” the investigators wrote in Gastro Hep Advances. “Unfortunately, they are associated with many problems in IBD, including increased risk of emergency room visits, hospitalization, surgery, and mortality. Chronic opioid use may also exacerbate symptoms and induce IBD flares, prompting discontinuation, thus increasing the risk of opioid withdrawal syndrome. Ironically, there is no published evidence that opioids even help to improve abdominal pain in IBD, particularly in the long term. Notably, most studies investigating opioid use in IBD have been limited to hospitalized patients, and few have directly evaluated the impact of opioid prescription length.”

Penn State College of Medicine

To address this knowledge gap, Ms. Telfer and colleagues conducted a retrospective, population-based cohort study involving patients with IBD who were classified as either long-term opioid users, short-term opioid users, or nonusers. Drawing data from more than 80,000 patients in the TriNetX Diamond Network, the investigators evaluated relative, intergroup risks for corticosteroid use, emergency department utilization, mortality, and IBD-related surgery.

Comparing short-term opioid users and nonusers revealed that short-term use more than doubled the risk of corticosteroid prescription (relative risk [RR], 2.517; P less than .001), and increased the risk of an emergency department visit by approximately 32% (RR, 1.315; P less than .001). Long-term use was associated with a similar doubling in risk of corticosteroid prescription (RR, 2.383; P less than .001), and an even greater risk of emergency department utilization (RR, 2.083; P less than .001). Risks of death or IBD-related surgery did not differ for either of these comparisons.

Next, the investigators compared long-term opioid use versus short-term opioid use. This suggested a duration-related effect, as long-term users were 57% more likely than were short-term users to utilize emergency department services (RR, 1.572; P less than .001). No significant differences for the other outcomes were detected in this comparison.

“Unlike previous studies, we did not find an association between opioid use and IBD-related surgery or death,” the investigators wrote. “Notably, these [previously reported] associations utilized opioid dosage (e.g., morphine equivalent or number of prescriptions), rather than length of opioid prescription (as we did). We also focused on IBD outpatients, while prior studies evaluated (in part or completely) inpatient populations, who typically present with more severe illness.”

Still, they added, the present findings should serve as a warning to prescribers considering even a short course of opioids for patients with IBD.

“This study demonstrates that prescribing opioids to IBD outpatients carries significant, specific risks, regardless of prescription length,” Ms. Telfer and colleagues wrote. “Healthcare professionals should exercise caution before prescribing these agents.”

The study was supported by the Peter and Marshia Carlino Early Career Professorship in Inflammatory Bowel Disease, the Margot E. Walrath Career Development Professorship in Gastroenterology, and the National Institutes of Health. The investigators disclosed no conflicts of interest.

Short- or long-term use of opioids may increase risk of poor outcomes in patients with inflammatory bowel disease (IBD), according to investigators.

These findings amplify the safety signal from previous inpatient studies by showing that even a short course of opioids in an outpatient setting may increase risks of corticosteroid use and emergency department utilization, prompting caution among prescribers, reported Laura Telfer, MS, of Penn State College of Medicine, Hershey, Pa., and colleagues.

“Opioids are frequently prescribed to treat pain associated with IBD,” the investigators wrote in Gastro Hep Advances. “Unfortunately, they are associated with many problems in IBD, including increased risk of emergency room visits, hospitalization, surgery, and mortality. Chronic opioid use may also exacerbate symptoms and induce IBD flares, prompting discontinuation, thus increasing the risk of opioid withdrawal syndrome. Ironically, there is no published evidence that opioids even help to improve abdominal pain in IBD, particularly in the long term. Notably, most studies investigating opioid use in IBD have been limited to hospitalized patients, and few have directly evaluated the impact of opioid prescription length.”

Penn State College of Medicine

To address this knowledge gap, Ms. Telfer and colleagues conducted a retrospective, population-based cohort study involving patients with IBD who were classified as either long-term opioid users, short-term opioid users, or nonusers. Drawing data from more than 80,000 patients in the TriNetX Diamond Network, the investigators evaluated relative, intergroup risks for corticosteroid use, emergency department utilization, mortality, and IBD-related surgery.

Comparing short-term opioid users and nonusers revealed that short-term use more than doubled the risk of corticosteroid prescription (relative risk [RR], 2.517; P less than .001), and increased the risk of an emergency department visit by approximately 32% (RR, 1.315; P less than .001). Long-term use was associated with a similar doubling in risk of corticosteroid prescription (RR, 2.383; P less than .001), and an even greater risk of emergency department utilization (RR, 2.083; P less than .001). Risks of death or IBD-related surgery did not differ for either of these comparisons.

Next, the investigators compared long-term opioid use versus short-term opioid use. This suggested a duration-related effect, as long-term users were 57% more likely than were short-term users to utilize emergency department services (RR, 1.572; P less than .001). No significant differences for the other outcomes were detected in this comparison.

“Unlike previous studies, we did not find an association between opioid use and IBD-related surgery or death,” the investigators wrote. “Notably, these [previously reported] associations utilized opioid dosage (e.g., morphine equivalent or number of prescriptions), rather than length of opioid prescription (as we did). We also focused on IBD outpatients, while prior studies evaluated (in part or completely) inpatient populations, who typically present with more severe illness.”

Still, they added, the present findings should serve as a warning to prescribers considering even a short course of opioids for patients with IBD.

“This study demonstrates that prescribing opioids to IBD outpatients carries significant, specific risks, regardless of prescription length,” Ms. Telfer and colleagues wrote. “Healthcare professionals should exercise caution before prescribing these agents.”

The study was supported by the Peter and Marshia Carlino Early Career Professorship in Inflammatory Bowel Disease, the Margot E. Walrath Career Development Professorship in Gastroenterology, and the National Institutes of Health. The investigators disclosed no conflicts of interest.

Short- or long-term use of opioids may increase risk of poor outcomes in patients with inflammatory bowel disease (IBD), according to investigators.

These findings amplify the safety signal from previous inpatient studies by showing that even a short course of opioids in an outpatient setting may increase risks of corticosteroid use and emergency department utilization, prompting caution among prescribers, reported Laura Telfer, MS, of Penn State College of Medicine, Hershey, Pa., and colleagues.

“Opioids are frequently prescribed to treat pain associated with IBD,” the investigators wrote in Gastro Hep Advances. “Unfortunately, they are associated with many problems in IBD, including increased risk of emergency room visits, hospitalization, surgery, and mortality. Chronic opioid use may also exacerbate symptoms and induce IBD flares, prompting discontinuation, thus increasing the risk of opioid withdrawal syndrome. Ironically, there is no published evidence that opioids even help to improve abdominal pain in IBD, particularly in the long term. Notably, most studies investigating opioid use in IBD have been limited to hospitalized patients, and few have directly evaluated the impact of opioid prescription length.”

Penn State College of Medicine

To address this knowledge gap, Ms. Telfer and colleagues conducted a retrospective, population-based cohort study involving patients with IBD who were classified as either long-term opioid users, short-term opioid users, or nonusers. Drawing data from more than 80,000 patients in the TriNetX Diamond Network, the investigators evaluated relative, intergroup risks for corticosteroid use, emergency department utilization, mortality, and IBD-related surgery.

Comparing short-term opioid users and nonusers revealed that short-term use more than doubled the risk of corticosteroid prescription (relative risk [RR], 2.517; P less than .001), and increased the risk of an emergency department visit by approximately 32% (RR, 1.315; P less than .001). Long-term use was associated with a similar doubling in risk of corticosteroid prescription (RR, 2.383; P less than .001), and an even greater risk of emergency department utilization (RR, 2.083; P less than .001). Risks of death or IBD-related surgery did not differ for either of these comparisons.

Next, the investigators compared long-term opioid use versus short-term opioid use. This suggested a duration-related effect, as long-term users were 57% more likely than were short-term users to utilize emergency department services (RR, 1.572; P less than .001). No significant differences for the other outcomes were detected in this comparison.

“Unlike previous studies, we did not find an association between opioid use and IBD-related surgery or death,” the investigators wrote. “Notably, these [previously reported] associations utilized opioid dosage (e.g., morphine equivalent or number of prescriptions), rather than length of opioid prescription (as we did). We also focused on IBD outpatients, while prior studies evaluated (in part or completely) inpatient populations, who typically present with more severe illness.”

Still, they added, the present findings should serve as a warning to prescribers considering even a short course of opioids for patients with IBD.

“This study demonstrates that prescribing opioids to IBD outpatients carries significant, specific risks, regardless of prescription length,” Ms. Telfer and colleagues wrote. “Healthcare professionals should exercise caution before prescribing these agents.”

The study was supported by the Peter and Marshia Carlino Early Career Professorship in Inflammatory Bowel Disease, the Margot E. Walrath Career Development Professorship in Gastroenterology, and the National Institutes of Health. The investigators disclosed no conflicts of interest.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent private organization, recognized as being in the public interest. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent private organization, recognized as being in the public interest. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

MADRID – Fine particulate matter pollution in the atmosphere around homes and workplaces increases the risk for breast cancer, according to a new analysis of the XENAIR study presented at the European Society of Medical Oncology (ESMO) Congress 2023. Béatrice Fervers, MD, PhD, head of the environmental cancer prevention department at the Léon Bérard Center, Lyon, France, presented her findings.

“To our knowledge, this study is the first to examine the risk of breast cancer associated with long-term exposure of subjects to atmospheric pollution both at home and in the workplace, estimated using a very small spatial resolution [statistical] model,” said the researchers.

“Our data showed a statistically significant association between long-term exposure to fine particulate matter air pollution, at home and at work, and risk of breast cancer. This [finding] contrasts with previous research that looked only at fine particulate exposure where women were living and showed small or no effects on breast cancer risk,” said Dr. Fervers in a press release issued before the Congress.

The XENAIR study carried out on the prospective, longitudinal E3N cohort a year ago showed an increased risk for breast cancer after exposure to five atmospheric pollutants. Notably, it showed an increased risk in women exposed to BaP and PCB153, two pollutants classed as endocrine-disrupting chemicals, during perimenopause.
 

Increased linear risk

In this new analysis, exposure to PM2.5, PM10, and NO2 pollution at home and in the workplace of 2,419 women with breast cancer was compared with that of 2,984 women without breast cancer during the period from 1990 to 2011.

This was a case-control study in which participants were matched by department of residence in France, age (± 1 year), date (± 3 months), and menopausal status at the time of the blood draw.

Breast cancer risk increased by 28% when exposure to fine particulate (PM2.5) air pollution increased by 10 mcg/m3. The increment is approximately equivalent to the difference in PM2.5 particulate concentration typically seen in rural versus urban areas of Europe.

Smaller increases in breast cancer risk were also recorded in women exposed to high levels of larger particulate air pollution (PM10 and NO2).

No change in effect was seen according to menopausal status. Analyses that examined hormone receptor status showed a positive but not significant association for PM2.5 in cases of estrogen receptor positive breast cancer.

Dr. Fervers and colleagues plan to investigate the effects of pollution exposure during the commute to get a complete picture of effects on breast cancer risk.
 

Regulators respond

Charles Swanton, PhD, a clinician scientist at the Francis Crick Institute, London, emphasized the importance of these new results for breast cancer. At last year’s ESMO Congress, he explained how particulate matter air pollution caused tumor proliferation in patients with a certain type of genetic mutation.

“Fine particle pollutants can penetrate deep into the lungs, enter the bloodstream, and be absorbed into breast and other tissue. There is already evidence that air pollutants can change the architecture of the breast. It will be important to test if pollutants allow cells in breast tissue with pre-existing mutations to expand and drive tumor promotion, possibly through inflammatory processes, similar to our observations in nonsmokers with lung cancer,” said Dr. Swanton in the ESMO press release.

“It is very concerning that small pollutant particles in the air and indeed microplastic particles of similar size are getting into the environment when we don’t yet understand their potential to promote cancer. There is an urgent need to set up laboratory studies to investigate the effects of these small air pollutant particles on the latency, grade, aggression, and progression of breast tumors,” he added.

“There is now strong epidemiological and biological evidence for the link between PM2.5 particulate exposure and cancer, and there are good clinical and economic reasons for reducing pollution to prevent cancers,” said Jean-Yves Blay, MD, PhD, director of public policy for ESMO.

Following a proposal from the European Commission in October 2022 to reduce the limit for PM2.5 particulates in the air from the current 25 mcg/m3 to 10 mcg/m3 by 2030, ESMO urged a further reduction in the PM2.5 limit to 5 mcg/m3, in line with the World Health Organization’s air quality guidance, according to the press release.

“Reducing PM2.5 particles in the air to the WHO recommended level is critical because of their association with a variety of tumor types, including breast cancer,” Dr. Blay added.

In September 2023, the European Parliament adopted in a plenary session its report on the ongoing revision of the EU Ambient Air Quality Directives, which reflects ESMO’s recommendations to set the annual limit value for PM2.5 at 5 mcg/m³. This adoption opens interinstitutional negotiations between the legislators (the European Parliament, European Commission, and EU Council) to agree on the final text of the directive.

“By supporting our requests with solid scientific evidence, we are offering a new dimension to health public policy. The work is not over, and change will not happen overnight, but we are moving in the right direction,” concluded Dr. Blay.

The new analysis of the XENAIR study was funded by ARC Foundation for cancer research; the French Agency for Food, Environmental, and Occupational Health and Safety; French National League against Cancer; and Fondation de France, an independent private organization, recognized as being in the public interest. The authors report no relevant financial relationships.

This article was translated from the Medscape French edition and a version appeared on Medscape.com.

TOPLINE:

Obtaining standing office blood pressure measurements improves detection of hypertension, either alone or when added to a seated BP reading, results of a new study suggest.

METHODOLOGY:

• The study included 125 adults, mean age 49 years and 62% female, who were free of cardiovascular disease and had no previous history of hypertension.
• Researchers collected data on 24-hour ambulatory blood pressure monitoring (ABPM), and three BP measurements in the seated position, then three in the standing position.
• They assessed overall diagnostic accuracy of seated and standing BP using the area under the receiver operating characteristic (AUROC) curve and considered a Bayes factor (BF) of 3 or greater as significant.
• They defined the presence of hypertension (HTN) by the 2017 American College of Cardiology/American Heart Association and 2023 European Society of Hypertension HTN guidelines based on ABPM.
• Sensitivity and specificity of standing BP was determined using cutoffs derived from Youden index, while sensitivity and specificity of seated BP was determined using the cutoff of 130/80 mm Hg and by 140/90 mm Hg.

TAKEAWAY:

• The AUROC for standing office systolic blood pressure (SBP; 0.81; 0.71-0.92) was significantly higher than for seated office SBP (0.70; 0.49-0.91) in diagnosing HTN when defined as an average 24-hour SBP ≥ 125 mm Hg (BF = 11.8), and significantly higher for seated versus standing office diastolic blood pressure (DBP; 0.65; 0.49-0.82) in diagnosing HTN when defined as an average 24-hour DBP ≥ 75 mm Hg (BF = 4.9).
• The AUROCs for adding standing office BP to seated office BP improved the accuracy of detecting HTN, compared with seated office BP alone when HTN was defined as an average 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg, or when defined as an average 24-hour SBP/DBP ≥ 130/80 mm Hg or daytime SBP/DBP ≥ 135/85 mm Hg (all BFs > 3).
• Sensitivity of standing SBP was 71%, compared with 43% for seated SBP.

IN PRACTICE:

The “excellent diagnostic performance” for standing BP measures revealed by the study “highlights that standing office BP has acceptable discriminative capabilities in identifying the presence of hypertension in adults,” the authors write.

SOURCE:

The study was conducted by John M. Giacona, Hypertension Section, department of internal medicine, University of Texas Southwestern Medical Center, Dallas, and colleagues. It was published online in Scientific Reports.

LIMITATIONS:

As the study enrolled only adults free of comorbidities who were not taking antihypertensive medications, the results may not be applicable to other patients. The study design was retrospective, and the order of BP measurements was not randomized (standing BP measurements were obtained only after seated BP).

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Obtaining standing office blood pressure measurements improves detection of hypertension, either alone or when added to a seated BP reading, results of a new study suggest.

METHODOLOGY:

• The study included 125 adults, mean age 49 years and 62% female, who were free of cardiovascular disease and had no previous history of hypertension.
• Researchers collected data on 24-hour ambulatory blood pressure monitoring (ABPM), and three BP measurements in the seated position, then three in the standing position.
• They assessed overall diagnostic accuracy of seated and standing BP using the area under the receiver operating characteristic (AUROC) curve and considered a Bayes factor (BF) of 3 or greater as significant.
• They defined the presence of hypertension (HTN) by the 2017 American College of Cardiology/American Heart Association and 2023 European Society of Hypertension HTN guidelines based on ABPM.
• Sensitivity and specificity of standing BP was determined using cutoffs derived from Youden index, while sensitivity and specificity of seated BP was determined using the cutoff of 130/80 mm Hg and by 140/90 mm Hg.

TAKEAWAY:

• The AUROC for standing office systolic blood pressure (SBP; 0.81; 0.71-0.92) was significantly higher than for seated office SBP (0.70; 0.49-0.91) in diagnosing HTN when defined as an average 24-hour SBP ≥ 125 mm Hg (BF = 11.8), and significantly higher for seated versus standing office diastolic blood pressure (DBP; 0.65; 0.49-0.82) in diagnosing HTN when defined as an average 24-hour DBP ≥ 75 mm Hg (BF = 4.9).
• The AUROCs for adding standing office BP to seated office BP improved the accuracy of detecting HTN, compared with seated office BP alone when HTN was defined as an average 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg, or when defined as an average 24-hour SBP/DBP ≥ 130/80 mm Hg or daytime SBP/DBP ≥ 135/85 mm Hg (all BFs > 3).
• Sensitivity of standing SBP was 71%, compared with 43% for seated SBP.

IN PRACTICE:

The “excellent diagnostic performance” for standing BP measures revealed by the study “highlights that standing office BP has acceptable discriminative capabilities in identifying the presence of hypertension in adults,” the authors write.

SOURCE:

The study was conducted by John M. Giacona, Hypertension Section, department of internal medicine, University of Texas Southwestern Medical Center, Dallas, and colleagues. It was published online in Scientific Reports.

LIMITATIONS:

As the study enrolled only adults free of comorbidities who were not taking antihypertensive medications, the results may not be applicable to other patients. The study design was retrospective, and the order of BP measurements was not randomized (standing BP measurements were obtained only after seated BP).

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Obtaining standing office blood pressure measurements improves detection of hypertension, either alone or when added to a seated BP reading, results of a new study suggest.

METHODOLOGY:

• The study included 125 adults, mean age 49 years and 62% female, who were free of cardiovascular disease and had no previous history of hypertension.
• Researchers collected data on 24-hour ambulatory blood pressure monitoring (ABPM), and three BP measurements in the seated position, then three in the standing position.
• They assessed overall diagnostic accuracy of seated and standing BP using the area under the receiver operating characteristic (AUROC) curve and considered a Bayes factor (BF) of 3 or greater as significant.
• They defined the presence of hypertension (HTN) by the 2017 American College of Cardiology/American Heart Association and 2023 European Society of Hypertension HTN guidelines based on ABPM.
• Sensitivity and specificity of standing BP was determined using cutoffs derived from Youden index, while sensitivity and specificity of seated BP was determined using the cutoff of 130/80 mm Hg and by 140/90 mm Hg.

TAKEAWAY:

• The AUROC for standing office systolic blood pressure (SBP; 0.81; 0.71-0.92) was significantly higher than for seated office SBP (0.70; 0.49-0.91) in diagnosing HTN when defined as an average 24-hour SBP ≥ 125 mm Hg (BF = 11.8), and significantly higher for seated versus standing office diastolic blood pressure (DBP; 0.65; 0.49-0.82) in diagnosing HTN when defined as an average 24-hour DBP ≥ 75 mm Hg (BF = 4.9).
• The AUROCs for adding standing office BP to seated office BP improved the accuracy of detecting HTN, compared with seated office BP alone when HTN was defined as an average 24-hour SBP/DBP ≥ 125/75 mm Hg or daytime SBP/DBP ≥ 130/80 mm Hg, or when defined as an average 24-hour SBP/DBP ≥ 130/80 mm Hg or daytime SBP/DBP ≥ 135/85 mm Hg (all BFs > 3).
• Sensitivity of standing SBP was 71%, compared with 43% for seated SBP.

IN PRACTICE:

The “excellent diagnostic performance” for standing BP measures revealed by the study “highlights that standing office BP has acceptable discriminative capabilities in identifying the presence of hypertension in adults,” the authors write.

SOURCE:

The study was conducted by John M. Giacona, Hypertension Section, department of internal medicine, University of Texas Southwestern Medical Center, Dallas, and colleagues. It was published online in Scientific Reports.

LIMITATIONS:

As the study enrolled only adults free of comorbidities who were not taking antihypertensive medications, the results may not be applicable to other patients. The study design was retrospective, and the order of BP measurements was not randomized (standing BP measurements were obtained only after seated BP).

DISCLOSURES:

The study was supported by the National Institutes of Health. The authors have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved tirzepatide for chronic weight management in adults with obesity or overweight.

Eli Lilly will market tirzepatide injections for weight management under the trade name Zepbound. It was approved in May 2022 for treating type 2 diabetes. The new indication is for adults with either obesity, defined as a body mass index of 30 kg/m² or greater, or overweight, with a BMI of 27 or greater with at least one weight-related comorbidity, including hypertension, type 2 diabetes, or dyslipidemia.

“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death, such as heart disease, stroke, and diabetes,” said John Sharretts, MD, director of the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research. “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”

A once-weekly injection, tirzepatide reduces appetite by activating two gut hormones, glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The dosage is increased over 4-20 weeks to achieve a weekly dose target of 5 mg, 10 mg, or 15 mg maximum.

Efficacy was established in two pivotal randomized, double-blind, placebo-controlled trials of adults with obesity or overweight plus another condition. One trial measured weight reduction after 72 weeks in a total of 2,519 patients without diabetes who received either 5 mg, 10 mg or 15 mg of tirzepatide once weekly. Those who received the 15-mg dose achieved on average 18% of their initial body weight, compared with placebo.

The other pivotal trial enrolled a total of 938 patients with type 2 diabetes. These patients achieved an average weight loss of 12% with once-weekly tirzepatide compared to placebo.

Another trial, which was presented at the 2023 Obesity Week meeting and was published in Nature Medicine, showed clinically meaningful added weight loss for adults with obesity who did not have diabetes and who had already experienced weight loss of at least 5% after a 12-week intensive lifestyle intervention.

Another trial, which was reported at the 2023 annual meeting of the European Association for the Study of Diabetes, found that tirzepatide continued to produce “highly significant weight loss” when the drug was continued in a 1-year follow-up trial. Those who discontinued taking the drug regained some weight but not all.

Tirzepatide can cause gastrointestinal side effects, such as nausea, diarrhea, vomiting, constipation, and abdominal pain or discomfort. Site reactions, hypersensitivity, hair loss, burping, and gastrointestinal reflux disease have also been reported.

The medication should not be used by patients with a personal or family history of medullary thyroid cancer or by patients with multiple endocrine neoplasia syndrome type 2. It should also not be used in combination with Mounjaro or another GLP-1 receptor agonist. The safety and effectiveness of the coadministration of tirzepatide with other medications for weight management have not been established.

Zepbound should go to market in the United States by the end of 2023, with an anticipated monthly list price of $1,060, according to a news release from Eli Lilly.

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

The Food and Drug Administration has approved tirzepatide for chronic weight management in adults with obesity or overweight.

Eli Lilly will market tirzepatide injections for weight management under the trade name Zepbound. It was approved in May 2022 for treating type 2 diabetes. The new indication is for adults with either obesity, defined as a body mass index of 30 kg/m² or greater, or overweight, with a BMI of 27 or greater with at least one weight-related comorbidity, including hypertension, type 2 diabetes, or dyslipidemia.

“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death, such as heart disease, stroke, and diabetes,” said John Sharretts, MD, director of the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research. “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”

A once-weekly injection, tirzepatide reduces appetite by activating two gut hormones, glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The dosage is increased over 4-20 weeks to achieve a weekly dose target of 5 mg, 10 mg, or 15 mg maximum.

Efficacy was established in two pivotal randomized, double-blind, placebo-controlled trials of adults with obesity or overweight plus another condition. One trial measured weight reduction after 72 weeks in a total of 2,519 patients without diabetes who received either 5 mg, 10 mg or 15 mg of tirzepatide once weekly. Those who received the 15-mg dose achieved on average 18% of their initial body weight, compared with placebo.

The other pivotal trial enrolled a total of 938 patients with type 2 diabetes. These patients achieved an average weight loss of 12% with once-weekly tirzepatide compared to placebo.

Another trial, which was presented at the 2023 Obesity Week meeting and was published in Nature Medicine, showed clinically meaningful added weight loss for adults with obesity who did not have diabetes and who had already experienced weight loss of at least 5% after a 12-week intensive lifestyle intervention.

Another trial, which was reported at the 2023 annual meeting of the European Association for the Study of Diabetes, found that tirzepatide continued to produce “highly significant weight loss” when the drug was continued in a 1-year follow-up trial. Those who discontinued taking the drug regained some weight but not all.

Tirzepatide can cause gastrointestinal side effects, such as nausea, diarrhea, vomiting, constipation, and abdominal pain or discomfort. Site reactions, hypersensitivity, hair loss, burping, and gastrointestinal reflux disease have also been reported.

The medication should not be used by patients with a personal or family history of medullary thyroid cancer or by patients with multiple endocrine neoplasia syndrome type 2. It should also not be used in combination with Mounjaro or another GLP-1 receptor agonist. The safety and effectiveness of the coadministration of tirzepatide with other medications for weight management have not been established.

Zepbound should go to market in the United States by the end of 2023, with an anticipated monthly list price of $1,060, according to a news release from Eli Lilly.

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

The Food and Drug Administration has approved tirzepatide for chronic weight management in adults with obesity or overweight.

Eli Lilly will market tirzepatide injections for weight management under the trade name Zepbound. It was approved in May 2022 for treating type 2 diabetes. The new indication is for adults with either obesity, defined as a body mass index of 30 kg/m² or greater, or overweight, with a BMI of 27 or greater with at least one weight-related comorbidity, including hypertension, type 2 diabetes, or dyslipidemia.

“Obesity and overweight are serious conditions that can be associated with some of the leading causes of death, such as heart disease, stroke, and diabetes,” said John Sharretts, MD, director of the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research. “In light of increasing rates of both obesity and overweight in the United States, today’s approval addresses an unmet medical need.”

A once-weekly injection, tirzepatide reduces appetite by activating two gut hormones, glucagonlike peptide–1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The dosage is increased over 4-20 weeks to achieve a weekly dose target of 5 mg, 10 mg, or 15 mg maximum.

Efficacy was established in two pivotal randomized, double-blind, placebo-controlled trials of adults with obesity or overweight plus another condition. One trial measured weight reduction after 72 weeks in a total of 2,519 patients without diabetes who received either 5 mg, 10 mg or 15 mg of tirzepatide once weekly. Those who received the 15-mg dose achieved on average 18% of their initial body weight, compared with placebo.

The other pivotal trial enrolled a total of 938 patients with type 2 diabetes. These patients achieved an average weight loss of 12% with once-weekly tirzepatide compared to placebo.

Another trial, which was presented at the 2023 Obesity Week meeting and was published in Nature Medicine, showed clinically meaningful added weight loss for adults with obesity who did not have diabetes and who had already experienced weight loss of at least 5% after a 12-week intensive lifestyle intervention.

Another trial, which was reported at the 2023 annual meeting of the European Association for the Study of Diabetes, found that tirzepatide continued to produce “highly significant weight loss” when the drug was continued in a 1-year follow-up trial. Those who discontinued taking the drug regained some weight but not all.

Tirzepatide can cause gastrointestinal side effects, such as nausea, diarrhea, vomiting, constipation, and abdominal pain or discomfort. Site reactions, hypersensitivity, hair loss, burping, and gastrointestinal reflux disease have also been reported.

The medication should not be used by patients with a personal or family history of medullary thyroid cancer or by patients with multiple endocrine neoplasia syndrome type 2. It should also not be used in combination with Mounjaro or another GLP-1 receptor agonist. The safety and effectiveness of the coadministration of tirzepatide with other medications for weight management have not been established.

Zepbound should go to market in the United States by the end of 2023, with an anticipated monthly list price of $1,060, according to a news release from Eli Lilly.

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

It takes an average of 4 years for a pancreatic lesion to progress from high-grade dysplasia (HGD) to cancer, suggesting a window of opportunity for screening, based on a microsimulation model.

To seize this opportunity, however, a greater understanding of natural disease course is needed, along with more sensitive screening tools, reported Brechtje D. M. Koopmann, MD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues.

Previous studies have suggested that the window of opportunity for pancreatic cancer screening may span decades, with estimates ranging from 12 to 50 years, the investigators wrote. Their report was published in Gastroenterology.

“Unfortunately, the poor results of pancreatic cancer screening do not align with this assumption, leaving unanswered whether this large window of opportunity truly exists,” they noted. “Microsimulation modeling, combined with available, if limited data, can provide new information on the natural disease course.”

For the present study, the investigators used the Microsimulation Screening Analysis (MISCAN) model, which has guided development of screening programs around the world for cervical, breast, and colorectal cancer. The model incorporates natural disease course, screening, and demographic data, then uses observable inputs such as precursor lesion prevalence and cancer incidence to estimate unobservable outcomes like stage durations and precursor lesion onset.

Dr. Koopmann and colleagues programmed this model with Dutch pancreatic cancer incidence data and findings from Japanese autopsy cases without pancreatic cancer.

First, the model offered insights into precursor lesion prevalence.

The estimated prevalence of any cystic lesion in the pancreas was 6.1% for individuals 50 years of age and 29.6% for those 80 years of age. Solid precursor lesions (PanINs) were estimated to be mainly multifocal (three or more lesions) in individuals older than 80 years. By this age, almost 12% had at least two PanINs. For those lesions that eventually became cancerous, the mean time since cyst onset was estimated to be 8.8 years, and mean time since PanIN onset was 9.0 years.

However, less than 10% of cystic and PanIN lesions progress to become cancers. PanIN lesions are not visible on imaging, and therefore current screening focuses on finding cystic precursor lesions, although these represent only about 10% of pancreatic cancers.

“Given the low pancreatic cancer progression risk of cysts, evaluation of the efficiency of current surveillance guidelines is necessary,” the investigators noted.

Screening should instead focus on identifying high-grade dysplastic lesions, they suggested. While these lesions may have a very low estimated prevalence, at just 0.3% among individuals 90 years of age, they present the greatest risk of pancreatic cancer.

For precursor cysts exhibiting HGD that progressed to pancreatic cancer, the mean interval between dysplasia and cancer was just 4 years. Among 13.7% of individuals, the interval was less than 1 year, suggesting an even shorter window of opportunity for screening.

Beyond this brief timeframe, low test sensitivity explains why screening efforts to date have fallen short, the investigators wrote.

Better tests are “urgently needed,” they added, while acknowledging the challenges inherent to this endeavor. Previous research has shown that precursor lesions in the pancreas are often less than 5 mm in diameter, making them extremely challenging to detect. An effective tool would need to identify solid precursor lesions (PanINs), and also need to simultaneously determine grade of dysplasia.

“Biomarkers could be the future in this matter,” the investigators suggested.

Dr. Koopmann and colleagues concluded by noting that more research is needed to characterize the pathophysiology of pancreatic cancer. On their part, “the current model will be validated, adjusted, and improved whenever new data from autopsy or prospective surveillance studies become available.”

The study was funded in part by Maag Lever Darm Stichting. The investigators disclosed no conflicts of interest.

It takes an average of 4 years for a pancreatic lesion to progress from high-grade dysplasia (HGD) to cancer, suggesting a window of opportunity for screening, based on a microsimulation model.

To seize this opportunity, however, a greater understanding of natural disease course is needed, along with more sensitive screening tools, reported Brechtje D. M. Koopmann, MD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues.

Previous studies have suggested that the window of opportunity for pancreatic cancer screening may span decades, with estimates ranging from 12 to 50 years, the investigators wrote. Their report was published in Gastroenterology.

“Unfortunately, the poor results of pancreatic cancer screening do not align with this assumption, leaving unanswered whether this large window of opportunity truly exists,” they noted. “Microsimulation modeling, combined with available, if limited data, can provide new information on the natural disease course.”

For the present study, the investigators used the Microsimulation Screening Analysis (MISCAN) model, which has guided development of screening programs around the world for cervical, breast, and colorectal cancer. The model incorporates natural disease course, screening, and demographic data, then uses observable inputs such as precursor lesion prevalence and cancer incidence to estimate unobservable outcomes like stage durations and precursor lesion onset.

Dr. Koopmann and colleagues programmed this model with Dutch pancreatic cancer incidence data and findings from Japanese autopsy cases without pancreatic cancer.

First, the model offered insights into precursor lesion prevalence.

The estimated prevalence of any cystic lesion in the pancreas was 6.1% for individuals 50 years of age and 29.6% for those 80 years of age. Solid precursor lesions (PanINs) were estimated to be mainly multifocal (three or more lesions) in individuals older than 80 years. By this age, almost 12% had at least two PanINs. For those lesions that eventually became cancerous, the mean time since cyst onset was estimated to be 8.8 years, and mean time since PanIN onset was 9.0 years.

However, less than 10% of cystic and PanIN lesions progress to become cancers. PanIN lesions are not visible on imaging, and therefore current screening focuses on finding cystic precursor lesions, although these represent only about 10% of pancreatic cancers.

“Given the low pancreatic cancer progression risk of cysts, evaluation of the efficiency of current surveillance guidelines is necessary,” the investigators noted.

Screening should instead focus on identifying high-grade dysplastic lesions, they suggested. While these lesions may have a very low estimated prevalence, at just 0.3% among individuals 90 years of age, they present the greatest risk of pancreatic cancer.

For precursor cysts exhibiting HGD that progressed to pancreatic cancer, the mean interval between dysplasia and cancer was just 4 years. Among 13.7% of individuals, the interval was less than 1 year, suggesting an even shorter window of opportunity for screening.

Beyond this brief timeframe, low test sensitivity explains why screening efforts to date have fallen short, the investigators wrote.

Better tests are “urgently needed,” they added, while acknowledging the challenges inherent to this endeavor. Previous research has shown that precursor lesions in the pancreas are often less than 5 mm in diameter, making them extremely challenging to detect. An effective tool would need to identify solid precursor lesions (PanINs), and also need to simultaneously determine grade of dysplasia.

“Biomarkers could be the future in this matter,” the investigators suggested.

Dr. Koopmann and colleagues concluded by noting that more research is needed to characterize the pathophysiology of pancreatic cancer. On their part, “the current model will be validated, adjusted, and improved whenever new data from autopsy or prospective surveillance studies become available.”

The study was funded in part by Maag Lever Darm Stichting. The investigators disclosed no conflicts of interest.

It takes an average of 4 years for a pancreatic lesion to progress from high-grade dysplasia (HGD) to cancer, suggesting a window of opportunity for screening, based on a microsimulation model.

To seize this opportunity, however, a greater understanding of natural disease course is needed, along with more sensitive screening tools, reported Brechtje D. M. Koopmann, MD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues.

Previous studies have suggested that the window of opportunity for pancreatic cancer screening may span decades, with estimates ranging from 12 to 50 years, the investigators wrote. Their report was published in Gastroenterology.

“Unfortunately, the poor results of pancreatic cancer screening do not align with this assumption, leaving unanswered whether this large window of opportunity truly exists,” they noted. “Microsimulation modeling, combined with available, if limited data, can provide new information on the natural disease course.”

For the present study, the investigators used the Microsimulation Screening Analysis (MISCAN) model, which has guided development of screening programs around the world for cervical, breast, and colorectal cancer. The model incorporates natural disease course, screening, and demographic data, then uses observable inputs such as precursor lesion prevalence and cancer incidence to estimate unobservable outcomes like stage durations and precursor lesion onset.

Dr. Koopmann and colleagues programmed this model with Dutch pancreatic cancer incidence data and findings from Japanese autopsy cases without pancreatic cancer.

First, the model offered insights into precursor lesion prevalence.

The estimated prevalence of any cystic lesion in the pancreas was 6.1% for individuals 50 years of age and 29.6% for those 80 years of age. Solid precursor lesions (PanINs) were estimated to be mainly multifocal (three or more lesions) in individuals older than 80 years. By this age, almost 12% had at least two PanINs. For those lesions that eventually became cancerous, the mean time since cyst onset was estimated to be 8.8 years, and mean time since PanIN onset was 9.0 years.

However, less than 10% of cystic and PanIN lesions progress to become cancers. PanIN lesions are not visible on imaging, and therefore current screening focuses on finding cystic precursor lesions, although these represent only about 10% of pancreatic cancers.

“Given the low pancreatic cancer progression risk of cysts, evaluation of the efficiency of current surveillance guidelines is necessary,” the investigators noted.

Screening should instead focus on identifying high-grade dysplastic lesions, they suggested. While these lesions may have a very low estimated prevalence, at just 0.3% among individuals 90 years of age, they present the greatest risk of pancreatic cancer.

For precursor cysts exhibiting HGD that progressed to pancreatic cancer, the mean interval between dysplasia and cancer was just 4 years. Among 13.7% of individuals, the interval was less than 1 year, suggesting an even shorter window of opportunity for screening.

Beyond this brief timeframe, low test sensitivity explains why screening efforts to date have fallen short, the investigators wrote.

Better tests are “urgently needed,” they added, while acknowledging the challenges inherent to this endeavor. Previous research has shown that precursor lesions in the pancreas are often less than 5 mm in diameter, making them extremely challenging to detect. An effective tool would need to identify solid precursor lesions (PanINs), and also need to simultaneously determine grade of dysplasia.

“Biomarkers could be the future in this matter,” the investigators suggested.

Dr. Koopmann and colleagues concluded by noting that more research is needed to characterize the pathophysiology of pancreatic cancer. On their part, “the current model will be validated, adjusted, and improved whenever new data from autopsy or prospective surveillance studies become available.”

The study was funded in part by Maag Lever Darm Stichting. The investigators disclosed no conflicts of interest.