Federal Practitioner

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.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

SAN DIEGO – Scientists are seeing positive early results from treating relapsed/refractory T-cell blood cancers with un–gene-edited chimeric antigen receptor (CAR) T-cell therapy, a translational immunologist told colleagues at the annual meeting of the Society for Immunotherapy of Cancer. Some patients have had durable complete remission.

As Baylor College of Medicine’s Max Mamonkin, PhD, noted in a presentation, patients with conditions such as T-cell lymphoma and T-cell acute lymphoblastic leukemia (ALL) have limited treatment options and grim prognoses. “This is an area with huge unmet need,” he said. “They don’t have options that patients with B-cell malignancies have, like [CAR T-cell therapy] and bispecifics.”

One big challenge is that CAR-targeted antigens in T-cell blood cancers are shared by both normal and malignant T-cells, he said. That poses a risk during therapy that the engineered cells will target each other with “disastrous consequences.”

Research by his team and others have shown that gene editing can help the cells to stop engaging in “fratricide,” Dr. Mamonkin said.

The problem is “it’s much easier to do gene editing on the bench and much harder to translate it into the clinic,” especially in light of limitations posed by the Food and Drug administration, he said. “We started to think about alternative methods to get this approach to the clinic.”

One strategy is to use pharmacologic inhibition via the Bruton’s tyrosine kinase inhibitors ibrutinib and dasatinib to mute the tendency of CAR T toward self-destruction. When tested in mice, “the unedited cells not just persisted, they expanded with sustained anti-leukemic activity and significantly prolonged their lives even more than the knock-out [gene-edited] cells.”

The research has now moved to human subjects. In 2021, researchers at Texas Children’s Hospital and Houston Methodist Hospital launched a clinical trial to test CD7 CAR T-cell therapy with CD28 in 21 patients with CD7-positive T-cell lymphoma. The initial part of the transplant-enabling CRIMSON-NE study is expected to be completed by mid-2024, and patients will be followed for 15 years.

Early results show that CD7 CAR T-cells have persisted in the blood of patients over weeks and months, Dr. Mamonkin said. In eight patients, “we’re seeing good evidence of activity,” with two patients reaching complete remissions.

The findings suggest that CD7 can be targeted in T-cell malignancies, he said. What about CD5? A similar study known as MAGENTA is testing CD5 CAR T-cell therapy with CD28 in T-cell leukemia and lymphoma in 42 patients. The phase 1 trial began in 2017. It’s expected to be completed by 2024 and to track patients for 15 years.

Results so far have been positive with complete remission achieved in three of nine patients with T-cell lymphoma; two remained in remission for more than 4 years.

Results in T-cell ALL improved after researchers adjusted the manufacturing of the cells. As for durability in these patients, “we try to bridge them to transplantation as soon as possible.”

As for side effects overall, there wasn’t much immune effector cell-associated neurotoxicity syndrome, and the CD7 approach seems to be more inflammatory, he said.

The presentation didn’t address the potential cost of the therapies. CAR T-cell therapy can cost between $500,000 and $1 million. Medicare covers it, but Medicaid may not depending on the state, and insurers may refuse to pay for it.

Dr. Mamonkin disclosed ties with Allogene, Amgen, Fate, Galapagos, March Bio, and NKILT.

The American Heart Association (AHA) has now formally voted to join several other cardiovascular societies to form a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM).  

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists along with 20 other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.”

The AHA will be joining the American College of Cardiology (ACC), Heart Failure Society of America (HFSA), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography & Interventions (SCAI) in forming the ABCVM. 

These four other societies issued a joint statement in September saying that they will apply to the American Board of Medical Specialties (ABMS) to request an independent cardiology board that follows a “new competency-based approach to continuous certification — one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

The new board requirements will “de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills,” the statement noted.

At the time the September statement was issued, the AHA was said to be supportive of the move but was waiting for formal endorsement to join the effort by its board of directors.

That has now happened, with the AHA’s national board of directors voting to provide “full support” for the creation of the proposed ABCVM.

“We enthusiastically join with our colleagues in proposing a new professional certification body to accredit cardiovascular professionals called the American Board of Cardiovascular Medicine,” said the association’s volunteer president Joseph C. Wu, MD. “The new ABCVM will be independent of the ABIM and focus on the specific competency-based trainings and appropriate ongoing certifications that align with and strengthen skills for cardiovascular physicians and enhance quality of care for people with cardiovascular disease,” Wu said.

“The AHA joins the consortium to submit the application to the American Board of Medical Specialties (ABMS) requesting an independent medical board for cardiovascular medicine. The consortium’s robust proposal harnesses the knowledge, skills, and benchmarks appropriate for professional excellence and delivery of effective, high-quality cardiovascular care,” Wu added.

The leaders of the ABCVM will include professional representatives from the consortium of member organizations, with a specific focus on relevant education, trainings, and supports that recognize the increasing specialization in cardiology and the latest advances in the various subspecialties of cardiovascular medicine, the AHA notes in a statement.

Professional certification by ABIM is a condition of employment for physicians practicing in large hospitals or health systems. A dedicated certification board separate from ABIM will help to ensure that cardiovascular professionals are maintaining the expertise appropriate to high-quality care and improved outcomes for their patients, the AHA said.

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

The American Heart Association (AHA) has now formally voted to join several other cardiovascular societies to form a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM).  

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists along with 20 other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.”

The AHA will be joining the American College of Cardiology (ACC), Heart Failure Society of America (HFSA), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography & Interventions (SCAI) in forming the ABCVM. 

These four other societies issued a joint statement in September saying that they will apply to the American Board of Medical Specialties (ABMS) to request an independent cardiology board that follows a “new competency-based approach to continuous certification — one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

The new board requirements will “de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills,” the statement noted.

At the time the September statement was issued, the AHA was said to be supportive of the move but was waiting for formal endorsement to join the effort by its board of directors.

That has now happened, with the AHA’s national board of directors voting to provide “full support” for the creation of the proposed ABCVM.

“We enthusiastically join with our colleagues in proposing a new professional certification body to accredit cardiovascular professionals called the American Board of Cardiovascular Medicine,” said the association’s volunteer president Joseph C. Wu, MD. “The new ABCVM will be independent of the ABIM and focus on the specific competency-based trainings and appropriate ongoing certifications that align with and strengthen skills for cardiovascular physicians and enhance quality of care for people with cardiovascular disease,” Wu said.

“The AHA joins the consortium to submit the application to the American Board of Medical Specialties (ABMS) requesting an independent medical board for cardiovascular medicine. The consortium’s robust proposal harnesses the knowledge, skills, and benchmarks appropriate for professional excellence and delivery of effective, high-quality cardiovascular care,” Wu added.

The leaders of the ABCVM will include professional representatives from the consortium of member organizations, with a specific focus on relevant education, trainings, and supports that recognize the increasing specialization in cardiology and the latest advances in the various subspecialties of cardiovascular medicine, the AHA notes in a statement.

Professional certification by ABIM is a condition of employment for physicians practicing in large hospitals or health systems. A dedicated certification board separate from ABIM will help to ensure that cardiovascular professionals are maintaining the expertise appropriate to high-quality care and improved outcomes for their patients, the AHA said.

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

The American Heart Association (AHA) has now formally voted to join several other cardiovascular societies to form a new professional certification board for cardiovascular medicine, to be known as the American Board of Cardiovascular Medicine (ABCVM).  

The ABCVM would be independent of the American Board of Internal Medicine (ABIM), the current organization providing maintenance of certification for cardiologists along with 20 other internal medicine subspecialties. The ABIM’s maintenance of certification process has been widely criticized for many years and has been described as “needlessly burdensome and expensive.”

The AHA will be joining the American College of Cardiology (ACC), Heart Failure Society of America (HFSA), Heart Rhythm Society (HRS), and Society for Cardiovascular Angiography & Interventions (SCAI) in forming the ABCVM. 

These four other societies issued a joint statement in September saying that they will apply to the American Board of Medical Specialties (ABMS) to request an independent cardiology board that follows a “new competency-based approach to continuous certification — one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

The new board requirements will “de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills,” the statement noted.

At the time the September statement was issued, the AHA was said to be supportive of the move but was waiting for formal endorsement to join the effort by its board of directors.

That has now happened, with the AHA’s national board of directors voting to provide “full support” for the creation of the proposed ABCVM.

“We enthusiastically join with our colleagues in proposing a new professional certification body to accredit cardiovascular professionals called the American Board of Cardiovascular Medicine,” said the association’s volunteer president Joseph C. Wu, MD. “The new ABCVM will be independent of the ABIM and focus on the specific competency-based trainings and appropriate ongoing certifications that align with and strengthen skills for cardiovascular physicians and enhance quality of care for people with cardiovascular disease,” Wu said.

“The AHA joins the consortium to submit the application to the American Board of Medical Specialties (ABMS) requesting an independent medical board for cardiovascular medicine. The consortium’s robust proposal harnesses the knowledge, skills, and benchmarks appropriate for professional excellence and delivery of effective, high-quality cardiovascular care,” Wu added.

The leaders of the ABCVM will include professional representatives from the consortium of member organizations, with a specific focus on relevant education, trainings, and supports that recognize the increasing specialization in cardiology and the latest advances in the various subspecialties of cardiovascular medicine, the AHA notes in a statement.

Professional certification by ABIM is a condition of employment for physicians practicing in large hospitals or health systems. A dedicated certification board separate from ABIM will help to ensure that cardiovascular professionals are maintaining the expertise appropriate to high-quality care and improved outcomes for their patients, the AHA said.

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

TOPLINE:

Patients with breast cancer who have low levels of vitamin D when they begin treatment with paclitaxel are more likely to develop peripheral neuropathy, suggesting that correcting levels before treatment might help prevent the condition.

METHODOLOGY:

• Past studies have suggested an association between vitamin D insufficiency and paclitaxel-induced peripheral neuropathy, a largely untreatable and sometimes permanent side effect of chemotherapy.
• To confirm the association, investigators reviewed data and samples from 1,191 women in the phase 3 SWOG S0221 trial, which compared weekly and biweekly paclitaxel regimens for early-stage breast cancer.
• Using serum samples collected at baseline, the team evaluated the relationship between insufficient vitamin D levels (20 ng/mL or less) before treatment and grade 3 or higher sensory chemotherapy-induced peripheral neuropathy.

TAKEAWAY:

• Overall, 33.3% of the women had insufficient vitamin D levels at baseline, and 16.4% developed grade 3 or worse sensory chemotherapy-induced peripheral neuropathy.
• The incidence of peripheral neuropathy of grade 3 or greater was higher among patients with pretreatment vitamin D insufficiency (20.7% vs. 14.2%; odds ratio, 1.57; P = .005).
• The association grew stronger after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; P = .003), but not after adjusting for race (adjusted OR, 1.39; P = .066).

IN PRACTICE:

The study “confirms that patients with pretreatment vitamin D insufficiency have a higher incidence of [chemotherapy-induced peripheral neuropathy],” the authors concluded. These results also “suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” senior researcher Daniel L. Hertz, PharmD, PhD, University of Michigan College of Pharmacy, Ann Arbor, said in a press release.

SOURCE:

The study, led by Ciao-Sin Chen, PharmD, of the University of Michigan, Ann Arbor, was published in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The trial did not collect data on other peripheral neuropathy risk factors, including preexisting peripheral neuropathy and diabetes. The study included a limited number of non-White participants (16%); larger numbers are needed to elucidate a potential interplay between race, vitamin D, and chemotherapy-induced peripheral neuropathy. The researchers also did not collect data on grade 1 and 2 chemotherapy-induced peripheral neuropathy.

DISCLOSURES:

The study was funded by Amgen, the American Cancer Society, and others. The investigators disclosed no relevant financial relationships.

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

TOPLINE:

Patients with breast cancer who have low levels of vitamin D when they begin treatment with paclitaxel are more likely to develop peripheral neuropathy, suggesting that correcting levels before treatment might help prevent the condition.

METHODOLOGY:

• Past studies have suggested an association between vitamin D insufficiency and paclitaxel-induced peripheral neuropathy, a largely untreatable and sometimes permanent side effect of chemotherapy.
• To confirm the association, investigators reviewed data and samples from 1,191 women in the phase 3 SWOG S0221 trial, which compared weekly and biweekly paclitaxel regimens for early-stage breast cancer.
• Using serum samples collected at baseline, the team evaluated the relationship between insufficient vitamin D levels (20 ng/mL or less) before treatment and grade 3 or higher sensory chemotherapy-induced peripheral neuropathy.

TAKEAWAY:

• Overall, 33.3% of the women had insufficient vitamin D levels at baseline, and 16.4% developed grade 3 or worse sensory chemotherapy-induced peripheral neuropathy.
• The incidence of peripheral neuropathy of grade 3 or greater was higher among patients with pretreatment vitamin D insufficiency (20.7% vs. 14.2%; odds ratio, 1.57; P = .005).
• The association grew stronger after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; P = .003), but not after adjusting for race (adjusted OR, 1.39; P = .066).

IN PRACTICE:

The study “confirms that patients with pretreatment vitamin D insufficiency have a higher incidence of [chemotherapy-induced peripheral neuropathy],” the authors concluded. These results also “suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” senior researcher Daniel L. Hertz, PharmD, PhD, University of Michigan College of Pharmacy, Ann Arbor, said in a press release.

SOURCE:

The study, led by Ciao-Sin Chen, PharmD, of the University of Michigan, Ann Arbor, was published in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The trial did not collect data on other peripheral neuropathy risk factors, including preexisting peripheral neuropathy and diabetes. The study included a limited number of non-White participants (16%); larger numbers are needed to elucidate a potential interplay between race, vitamin D, and chemotherapy-induced peripheral neuropathy. The researchers also did not collect data on grade 1 and 2 chemotherapy-induced peripheral neuropathy.

DISCLOSURES:

The study was funded by Amgen, the American Cancer Society, and others. The investigators disclosed no relevant financial relationships.

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

TOPLINE:

Patients with breast cancer who have low levels of vitamin D when they begin treatment with paclitaxel are more likely to develop peripheral neuropathy, suggesting that correcting levels before treatment might help prevent the condition.

METHODOLOGY:

• Past studies have suggested an association between vitamin D insufficiency and paclitaxel-induced peripheral neuropathy, a largely untreatable and sometimes permanent side effect of chemotherapy.
• To confirm the association, investigators reviewed data and samples from 1,191 women in the phase 3 SWOG S0221 trial, which compared weekly and biweekly paclitaxel regimens for early-stage breast cancer.
• Using serum samples collected at baseline, the team evaluated the relationship between insufficient vitamin D levels (20 ng/mL or less) before treatment and grade 3 or higher sensory chemotherapy-induced peripheral neuropathy.

TAKEAWAY:

• Overall, 33.3% of the women had insufficient vitamin D levels at baseline, and 16.4% developed grade 3 or worse sensory chemotherapy-induced peripheral neuropathy.
• The incidence of peripheral neuropathy of grade 3 or greater was higher among patients with pretreatment vitamin D insufficiency (20.7% vs. 14.2%; odds ratio, 1.57; P = .005).
• The association grew stronger after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; P = .003), but not after adjusting for race (adjusted OR, 1.39; P = .066).

IN PRACTICE:

The study “confirms that patients with pretreatment vitamin D insufficiency have a higher incidence of [chemotherapy-induced peripheral neuropathy],” the authors concluded. These results also “suggest that vitamin D supplementation in patients with lower levels of vitamin D may reduce peripheral neuropathy, and particularly high-grade peripheral neuropathy, which would improve these patients’ long-term quality of life,” senior researcher Daniel L. Hertz, PharmD, PhD, University of Michigan College of Pharmacy, Ann Arbor, said in a press release.

SOURCE:

The study, led by Ciao-Sin Chen, PharmD, of the University of Michigan, Ann Arbor, was published in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The trial did not collect data on other peripheral neuropathy risk factors, including preexisting peripheral neuropathy and diabetes. The study included a limited number of non-White participants (16%); larger numbers are needed to elucidate a potential interplay between race, vitamin D, and chemotherapy-induced peripheral neuropathy. The researchers also did not collect data on grade 1 and 2 chemotherapy-induced peripheral neuropathy.

DISCLOSURES:

The study was funded by Amgen, the American Cancer Society, and others. The investigators disclosed no relevant financial relationships.

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

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

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

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

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

Epilepsy affects over 50 million people worldwide, making it one of the most common neurologic disorders. Though current antiseizure medications can control seizures in two-thirds of patients, drug-resistant epilepsy remains a major challenge for the remaining one-third, as does the lack of disease-modifying therapies.

But RNA-based therapeutics offer new hope, and experts predict they could fill these gaps and revolutionize epilepsy treatment.

“Current medicines for epilepsy are barely scraping the surface of what could be targeted. RNA therapeutics is going to change everything. It opens up entirely new targets – virtually anything in our genome becomes ‘druggable,’ ” said David Henshall, PhD, Royal College of Surgeons Ireland, Dublin.

Edward Kaye, MD, a pediatric neurologist and CEO of Stoke Therapeutics, agrees. “RNA therapeutics open up possibilities that could not have been imagined when I started my career,” he said in an interview.

“We now have the potential to change the way genetic epilepsies are treated by addressing the underlying genetic cause of the disease instead of just the seizures,” Dr. Kaye said.
 

Thank COVID?

Henrik Klitgaard, PhD, and Sakari Kauppinen, PhD, scientific co-founders of NEUmiRNA Therapeutics, noted that the success of messenger RNA (mRNA) vaccines to counter the COVID-19 pandemic has fueled interest in exploring the potential of RNA-based therapies as a new modality in epilepsy with improved therapeutic properties.

Dr. Klitgaard and Dr. Kauppinen recently co-authored a “critical review” on RNA therapies for epilepsy published online in Epilepsia.

Unlike current antiseizure medications, which only target ion channels and receptors, RNA therapeutics can directly intervene at the genetic level.

RNA drugs can be targeted toward noncoding RNAs, such as microRNAs, or toward mRNA. Targeting noncoding RNAs shows promise in sporadic, nongenetic epilepsies, and targeting of mRNAs shows promise in childhood monogenic epilepsies.

Preclinical studies have highlighted the potential of RNA therapies for treatment of epilepsy.

“At NEUmiRNA Therapeutics, we have successfully designed potent and selective RNA drugs for a novel disease target that enable unprecedented elimination of the drug resistance and chronic epilepsy in a preclinical model mimicking temporal lobe epilepsy,” said Dr. Klitgaard.

“Interestingly,” he said, “these experiments also showed a disappearance of symptoms for epilepsy that outlasted drug exposure, suggesting significant disease-modifying properties with a curative potential for epilepsy.”
 

Hope for Dravet syndrome

Currently, there is significant interest in development of antisense oligonucleotides (ASOs), particularly for Dravet syndrome, a rare genetic epileptic encephalopathy that begins in infancy and gives rise to seizures that don’t respond well to seizure medications.

Stoke Therapeutics is developing antisense therapies aimed at correcting mutations in sodium channel genes, which cause up to 80% of cases of Dravet syndrome.

The company recently reported positive safety and efficacy data from patients treated with STK-001, a proprietary ASO, in the two ongoing phase 1/2a studies (MONARCH and ADMIRAL) and the SWALLOWTAIL open-label extension study.

“These new data suggest clinical benefit for patients 2-18 years of age treated with multiple doses of STK-001. The observed reductions in convulsive seizure frequency as well as substantial improvements in cognition and behavior support the potential for disease modification in a highly refractory patient population,” the company said in a news release.

Dr. Kaye noted that the company anticipates reporting additional data in the first quarter of 2024 and expects to provide an update on phase 3 planning in the first half of 2024.

“Twenty-five years ago, when I was caring for patients in my clinic, half of epilepsy was considered idiopathic because we didn’t know the cause,” Dr. Kaye commented.

“Since then, thanks to an understanding of the genetics and more widely available access to genetic testing, we can determine the root cause of most of them. Today, I believe we are on the verge of a fundamental shift in how we approach the treatment of Dravet syndrome and, hopefully, other genetic epilepsies,” said Dr. Kaye.

“We are now finally getting to the point that we not only know the causes, but we are in a position to develop medicines that target those causes. We have seen this happen in other diseases like cystic fibrosis, and the time has come for genetic epilepsies,” he added.
 

A promising future

Dr. Henshall said that the ability to target the cause rather than just the symptoms of epilepsy “offers the promise of disease-modifying and potentially curative medicines in the future.”

And what’s exciting is that the time frame of developing RNA medicines may be “radically” different than it is for traditional small-drug development, he noted.

Take, for example, a case reported recently in the New England Journal of Medicine.

Researchers identified a novel mutation in a child with neuronal ceroid lipofuscinosis 7 (a form of Batten’s disease), a rare and fatal neurodegenerative disease. Identification of the mutation was followed by the development and use (within 1 year) of a tailored RNA drug to treat the patient.

One downside perhaps is that current RNA drugs for epilepsy are delivered intrathecally, which is different from oral administration of small-molecule drugs.

However, Dr. Kauppinen from NEUmiRNA Therapeutics noted that “advances in intrathecal delivery technologies [and] the frequent use of this route of administration in other diseases and IT administration only being required two to three times per year will certainly facilitate use of RNA medicines.”

“This will also eliminate the issue of drug adherence by ensuring full patient compliance to treatment,” Dr. Kauppinen said.

The review article on RNA therapies in epilepsy had no commercial funding. Dr. Henshall holds a patent and has filed intellectual property related to microRNA targeting therapies for epilepsy and has received funding for microRNA research from NEUmiRNA Therapeutics. Dr. Klitgaard and Dr. Kauppinen are cofounders of NEUmiRNA Therapeutics. Dr. Kaye is CEO of Stoke Therapeutics.

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

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Today we are going to talk about the American Geriatrics Society 2023 updated Beers Criteria guidance for medication use in older adults. These criteria have been updated and revised approximately every 5 years since 1991 and serve to alert us to medications for which the risk-benefit ratio is not as good in older adults as in the rest of the population.

These are important criteria because medications are metabolized differently in older adults and have different effects compared with younger patients. For the sake of these criteria, older adults are 65 years of age or older. That said, we know that everyone from 65 to 100 is not the same. As people age, they develop more comorbidities, they become more frail, and they are more sensitive to the effects and side effects of drugs.

The guidance covers potentially inappropriate medications for older adults. The word “potentially” is important because this is guidance. As clinicians, we make decisions involving individuals. This guidance should be used with judgment, integrating the clinical context of the individual patient.

There is a lot in this guidance. I am going to try to cover what I feel are the most important points.

Aspirin. Since the risk for major bleeding increases with age, for primary prevention of atherosclerotic cardiovascular disease, the harm can be greater than the benefit in older adults, so aspirin should not be used for primary prevention. Aspirin remains indicated for secondary prevention in individuals with established cardiovascular disease.

Warfarin. For treatment of atrial fibrillation or venous thromboembolism (deep vein thrombosis or pulmonary embolism), warfarin should be avoided if possible. Warfarin has a higher risk for major bleeding, particularly intracranial bleeding, than direct oral anticoagulants (DOACs); therefore the latter are preferred. Rivaroxaban should be avoided, as it has a higher risk for major bleeding in older adults than the other DOACs. Apixaban is preferred over dabigatran. If a patient is well controlled on warfarin, you can consider continuing that treatment.

Antipsychotics. These include first- and second-generation antipsychotics such as aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and others. The guidance says to avoid these agents except for FDA-approved indications such as schizophrenia, bipolar disorder, and adjuvant treatment of depression. Use of these antipsychotics can increase risk for stroke, heart attack, and mortality. Essentially, the guidance says do not use these medications lightly for the treatment of agitated dementia. For those of us with older patients, this can get tricky because agitated dementia is a difficult issue for which there are no good effective medications. The Beers guidance recognizes this in saying that these medications should be avoided unless behavioral interventions have failed. So, there are times where you may need to use these medicines, but use them judiciously.

For patients with dementia, anticholinergics, antipsychotics, and benzodiazepines should be avoided if possible.

Benzodiazepines. Benzodiazepines should also be avoided because older adults have increased sensitivity to their effects due to slower metabolism and clearance of these medications, which can lead to a much longer half-life and higher serum level. In older adults, benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and even motor accidents. The same concerns affect the group of non-benzodiazepine sleeping medicines known as “Z-drugs.”

Nonsteroidal anti-inflammatory drugs (NSAIDs). Used frequently in our practices, NSAIDs are nevertheless on the list. As we think through the risk-benefit ratio of using NSAIDs in older adults, we often underappreciate the risks of these agents. Upper gastrointestinal ulcers with bleeding occur in approximately 1% of patients treated for 3-6 months with an NSAID and in 2%-4% of patients treated for a year. NSAIDs also increase the risk for renal impairment and cardiovascular disease.

Other medications to avoid (if possible). These include:

Sulfonylureas, due to a high risk for hypoglycemia. A short-acting sulfonylurea, such as glipizide, should be used if one is needed.

Proton pump inhibitors should not be used long-term if it can be avoided.

Digoxin should not be first-line treatment for atrial fibrillation or heart failure. Decreased renal clearance in older adults can lead to toxic levels of digoxin, particularly during acute illnesses. Avoid doses > 0.125 mg/day.

Nitrofurantoin should be avoided when the patient’s creatinine clearance is < 30 or for long-term suppressive therapy.

Avoid combining medications that have high anticholinergic side effects, such as scopolamine, diphenhydramine, oxybutynin, cyclobenzaprine, and others.

It is always important to understand the benefits and the risks of the drugs we prescribe. It is also important to remember that older adults are a particularly vulnerable population. The Beers criteria provide important guidance, which we can then use to make decisions about medicines for individual patients.

Dr. Skolnik is a professor in the department of family medicine at Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director in the department of family medicine at Abington (Pa.) Jefferson Health. He disclosed ties with AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Merck, Sanofi, Sanofi Pasteur, and Teva.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I am far from the only doctor, and certainly far from the only oncologist, to recently comment on the topic of Maintenance of Certification. Of course, this is happening in a wider debate about our relationship as subspecialists to the American Board of Internal Medicine, and what they deem acceptable for the recertification of doctors in practice.

My take is that every oncologist is already engaged in lifelong learning. One of the things I tell my patients is that if I practiced exactly the way I was trained to practice — and I had a very good fellowship program with superb faculty – if I practiced the way they taught me, it would now be malpractice. I finished my fellowship in 2012, just over a decade ago. The rate of progress in the interim is simply staggering. It looks so different now than it did then.

For instance, 2011 was my first experience ever using a form of immunotherapy. It was an anti-CTLA4 agent, ipilimumab, and I was treating metastatic melanoma. I learned in that instance just how effective these drugs can be, but also how toxic they can be. Ever since then, I’ve been refining my use of immunotherapy. We do that iteratively. We do that as we encounter patients and as we try to meet their needs.

I do understand that the ABIM is saying they want an independent governing body to legislate that process. I think the reason this is stuck in the craw of so many oncologists is that we demonstrate our commitment to continuing medical education all the time.

I’m recording this in my office, which is separate from the space where I see patients. I see patients in a different group of exam rooms for their privacy and it’s a better setup for aspects of the physical encounter. Not a single patient has ever asked to come into my office and see my diplomas, and I sometimes wonder if I keep them here mostly as a visual cue to myself, sort of an antidote to ward off imposter syndrome and remind myself, Oh yeah – I earned these. I earned these through formal training.

Then something happens once you finish your training, whether it’s residency or fellowship, and you become an attending. I think you feel a weight of responsibility, the responsibility of independent learning. All of us are doing this. We have to do this. The field is moving along at such a rapid clip that it’s essentially built into what we do that we are going to keep up. In fact, channels such as the various aspects of social media are a way I curate my own information feed so I can stay up to speed and not feel like I’m drowning in a deluge of new data.

But what’s hard to demonstrate to the ABIM is that [this learning] is already happening. I think we can do it if we submit our records of CME credits that we formally accrue. The reason this is such an almost insult to oncologists in practice is because it is a necessary part of our day-to-day existence to keep apprised of developments so we can apply them to patient care.

One litmus test of attending a medical conference like the annual meeting of the American Society of Clinical Oncology is to ask oneself, When I go back to clinic, is this meeting going to change the way that I take care of patients? The answer almost invariably these days is yes. I go to multiple meetings per year, and I think it’s the exception, not the rule, that I return home and nothing changes in my management patterns. Again, this process is happening whether the ABIM recognizes it or not.

Lastly, I sat down in the fall of 2022 and I did my recertification. I looked at the span of all the things that had happened between 2012, when I first sat for my board examination in medical oncology, and 2022. It was staggering. I think the reason that it wasn’t such an overwhelming amount of information to review is that I had actually been accreting it slowly and gradually, month by month, year by year throughout that decade.

Again, it’s necessary that the ABIM hear us, hear oncologists, and know that of all the medical subspecialties they govern, it is basically already an essential task of our day-to-day professional existence that we engage in lifelong learning. To suggest otherwise really paints us as outdated. The reason that matters so much is that if we’re not up-to-date, then we are underserving our patients.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City. He reported no relevant conflicts of interest.

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

This transcript has been edited for clarity.

I am far from the only doctor, and certainly far from the only oncologist, to recently comment on the topic of Maintenance of Certification. Of course, this is happening in a wider debate about our relationship as subspecialists to the American Board of Internal Medicine, and what they deem acceptable for the recertification of doctors in practice.

My take is that every oncologist is already engaged in lifelong learning. One of the things I tell my patients is that if I practiced exactly the way I was trained to practice — and I had a very good fellowship program with superb faculty – if I practiced the way they taught me, it would now be malpractice. I finished my fellowship in 2012, just over a decade ago. The rate of progress in the interim is simply staggering. It looks so different now than it did then.

For instance, 2011 was my first experience ever using a form of immunotherapy. It was an anti-CTLA4 agent, ipilimumab, and I was treating metastatic melanoma. I learned in that instance just how effective these drugs can be, but also how toxic they can be. Ever since then, I’ve been refining my use of immunotherapy. We do that iteratively. We do that as we encounter patients and as we try to meet their needs.

I do understand that the ABIM is saying they want an independent governing body to legislate that process. I think the reason this is stuck in the craw of so many oncologists is that we demonstrate our commitment to continuing medical education all the time.

I’m recording this in my office, which is separate from the space where I see patients. I see patients in a different group of exam rooms for their privacy and it’s a better setup for aspects of the physical encounter. Not a single patient has ever asked to come into my office and see my diplomas, and I sometimes wonder if I keep them here mostly as a visual cue to myself, sort of an antidote to ward off imposter syndrome and remind myself, Oh yeah – I earned these. I earned these through formal training.

Then something happens once you finish your training, whether it’s residency or fellowship, and you become an attending. I think you feel a weight of responsibility, the responsibility of independent learning. All of us are doing this. We have to do this. The field is moving along at such a rapid clip that it’s essentially built into what we do that we are going to keep up. In fact, channels such as the various aspects of social media are a way I curate my own information feed so I can stay up to speed and not feel like I’m drowning in a deluge of new data.

But what’s hard to demonstrate to the ABIM is that [this learning] is already happening. I think we can do it if we submit our records of CME credits that we formally accrue. The reason this is such an almost insult to oncologists in practice is because it is a necessary part of our day-to-day existence to keep apprised of developments so we can apply them to patient care.

One litmus test of attending a medical conference like the annual meeting of the American Society of Clinical Oncology is to ask oneself, When I go back to clinic, is this meeting going to change the way that I take care of patients? The answer almost invariably these days is yes. I go to multiple meetings per year, and I think it’s the exception, not the rule, that I return home and nothing changes in my management patterns. Again, this process is happening whether the ABIM recognizes it or not.

Lastly, I sat down in the fall of 2022 and I did my recertification. I looked at the span of all the things that had happened between 2012, when I first sat for my board examination in medical oncology, and 2022. It was staggering. I think the reason that it wasn’t such an overwhelming amount of information to review is that I had actually been accreting it slowly and gradually, month by month, year by year throughout that decade.

Again, it’s necessary that the ABIM hear us, hear oncologists, and know that of all the medical subspecialties they govern, it is basically already an essential task of our day-to-day professional existence that we engage in lifelong learning. To suggest otherwise really paints us as outdated. The reason that matters so much is that if we’re not up-to-date, then we are underserving our patients.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City. He reported no relevant conflicts of interest.

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

This transcript has been edited for clarity.

I am far from the only doctor, and certainly far from the only oncologist, to recently comment on the topic of Maintenance of Certification. Of course, this is happening in a wider debate about our relationship as subspecialists to the American Board of Internal Medicine, and what they deem acceptable for the recertification of doctors in practice.

My take is that every oncologist is already engaged in lifelong learning. One of the things I tell my patients is that if I practiced exactly the way I was trained to practice — and I had a very good fellowship program with superb faculty – if I practiced the way they taught me, it would now be malpractice. I finished my fellowship in 2012, just over a decade ago. The rate of progress in the interim is simply staggering. It looks so different now than it did then.

For instance, 2011 was my first experience ever using a form of immunotherapy. It was an anti-CTLA4 agent, ipilimumab, and I was treating metastatic melanoma. I learned in that instance just how effective these drugs can be, but also how toxic they can be. Ever since then, I’ve been refining my use of immunotherapy. We do that iteratively. We do that as we encounter patients and as we try to meet their needs.

I do understand that the ABIM is saying they want an independent governing body to legislate that process. I think the reason this is stuck in the craw of so many oncologists is that we demonstrate our commitment to continuing medical education all the time.

I’m recording this in my office, which is separate from the space where I see patients. I see patients in a different group of exam rooms for their privacy and it’s a better setup for aspects of the physical encounter. Not a single patient has ever asked to come into my office and see my diplomas, and I sometimes wonder if I keep them here mostly as a visual cue to myself, sort of an antidote to ward off imposter syndrome and remind myself, Oh yeah – I earned these. I earned these through formal training.

Then something happens once you finish your training, whether it’s residency or fellowship, and you become an attending. I think you feel a weight of responsibility, the responsibility of independent learning. All of us are doing this. We have to do this. The field is moving along at such a rapid clip that it’s essentially built into what we do that we are going to keep up. In fact, channels such as the various aspects of social media are a way I curate my own information feed so I can stay up to speed and not feel like I’m drowning in a deluge of new data.

But what’s hard to demonstrate to the ABIM is that [this learning] is already happening. I think we can do it if we submit our records of CME credits that we formally accrue. The reason this is such an almost insult to oncologists in practice is because it is a necessary part of our day-to-day existence to keep apprised of developments so we can apply them to patient care.

One litmus test of attending a medical conference like the annual meeting of the American Society of Clinical Oncology is to ask oneself, When I go back to clinic, is this meeting going to change the way that I take care of patients? The answer almost invariably these days is yes. I go to multiple meetings per year, and I think it’s the exception, not the rule, that I return home and nothing changes in my management patterns. Again, this process is happening whether the ABIM recognizes it or not.

Lastly, I sat down in the fall of 2022 and I did my recertification. I looked at the span of all the things that had happened between 2012, when I first sat for my board examination in medical oncology, and 2022. It was staggering. I think the reason that it wasn’t such an overwhelming amount of information to review is that I had actually been accreting it slowly and gradually, month by month, year by year throughout that decade.

Again, it’s necessary that the ABIM hear us, hear oncologists, and know that of all the medical subspecialties they govern, it is basically already an essential task of our day-to-day professional existence that we engage in lifelong learning. To suggest otherwise really paints us as outdated. The reason that matters so much is that if we’re not up-to-date, then we are underserving our patients.

Mark A. Lewis, MD, is director of gastrointestinal oncology at Intermountain Healthcare in Salt Lake City. He reported no relevant conflicts of interest.

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