Heidi Splete

Socioeconomic factors were associated with greater disease severity at the time of initial presentation in adults with sarcoidosis, based on a new study of more than 700 individuals presented at the American Thoracic Society’s International Conference 2024.

“We know socioeconomic status plays an important role in health outcomes; however, there is little research into the impact of socioeconomic status on patients with sarcoidosis, particularly with disease severity,” said lead author Joshua Boron, MD, of Virginia Commonwealth University, Richmond, Virginia, in an interview. Identification of patients at higher risk of developing severe lung disease can help clinicians stratify these patients, he said.

Overall, the risk for severe lung disease at initial presentation was nearly three times higher in patients with no insurance than in those with private insurance and nearly three times higher in Black patients than in White patients (odds ratio [OR], 2.97 and 2.83, respectively). In addition, older age was associated with increased risk of fibrosis, with an OR of 1.03 per year increase in age.

No differences in fibrosis at presentation occurred based on sex or median income, and no difference in the likelihood of fibrosis at presentation appeared between patients with Medicaid vs private insurance.

“We were surprised at the degree of risk associated with no insurance,” said Dr. Boron. The researchers also were surprised at the lack of association between higher risk of severe stage lung disease in sarcoidosis patients and zip code estimates of household income as an indicator of socioeconomic status, he said.

For clinical practice, the study findings highlight the potentially increased risk for fibrotic lung disease among patients who are older, uninsured, and African American, said Dr. Boron.

“A limitation of our study was the utilization of zip code based on the US Census Bureau to get an estimation of average household income — a particular limitation in our city because of gentrification over the past few decades,” Dr. Boron said in an interview. “Utilizing area deprivation indices could be a better marker for identifying household income and give a more accurate representation of the true impact of socioeconomic disparities and severity of sarcoidosis at presentation,” he said.
 

Pinpointing Persistent Disparities

“We know there are multiple sources of disparities in the sarcoidosis population,” said Rohit Gupta, MD, director of the sarcoidosis program at Temple University Hospital, Philadelphia, in an interview.

The current study identified the relationship between several socioeconomic factors and sarcoidosis severity, showing greater disease severity in people experiencing socioeconomic inequalities, said Dr. Gupta, who was not involved in the study.

“I have personally seen this [disparity] in clinic,” said Dr. Gupta. However, supporting data are limited, aside from recent studies published in the last few years by researchers at the Cleveland Clinic and Johns Hopkins University, Baltimore, he said. The current study reflects those previous findings that people suffering from inequality have worse medical care, he added.

Overall, the findings were not surprising, “as we know this cohort of patients have chronic disease and worse morbidity and, in some cases, higher mortality,” but the results reinforce the need to pay closer attention to socioeconomic factors, said Dr. Gupta.

In practice, “we might use these findings as a reminder that when we see these patients for the first time, we should pay closer attention because they might need higher care,” he said. “The study also suggests these patients are coming late to a center of excellence,” he noted. When patients with socioeconomic disparities are seen for sarcoidosis at community hospitals and small centers, providers should keep in mind that their disease might progress faster and, therefore, send them to advanced centers earlier, he said.

The study was limited to the use of data from a single center and by the retrospective design, Dr. Gupta said. “Additional research should focus on building better platforms to understand these disparities,” he emphasized, so clinicians can develop plans not only to identify inequalities but also to address them.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gupta had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Socioeconomic factors were associated with greater disease severity at the time of initial presentation in adults with sarcoidosis, based on a new study of more than 700 individuals presented at the American Thoracic Society’s International Conference 2024.

“We know socioeconomic status plays an important role in health outcomes; however, there is little research into the impact of socioeconomic status on patients with sarcoidosis, particularly with disease severity,” said lead author Joshua Boron, MD, of Virginia Commonwealth University, Richmond, Virginia, in an interview. Identification of patients at higher risk of developing severe lung disease can help clinicians stratify these patients, he said.

Overall, the risk for severe lung disease at initial presentation was nearly three times higher in patients with no insurance than in those with private insurance and nearly three times higher in Black patients than in White patients (odds ratio [OR], 2.97 and 2.83, respectively). In addition, older age was associated with increased risk of fibrosis, with an OR of 1.03 per year increase in age.

No differences in fibrosis at presentation occurred based on sex or median income, and no difference in the likelihood of fibrosis at presentation appeared between patients with Medicaid vs private insurance.

“We were surprised at the degree of risk associated with no insurance,” said Dr. Boron. The researchers also were surprised at the lack of association between higher risk of severe stage lung disease in sarcoidosis patients and zip code estimates of household income as an indicator of socioeconomic status, he said.

For clinical practice, the study findings highlight the potentially increased risk for fibrotic lung disease among patients who are older, uninsured, and African American, said Dr. Boron.

“A limitation of our study was the utilization of zip code based on the US Census Bureau to get an estimation of average household income — a particular limitation in our city because of gentrification over the past few decades,” Dr. Boron said in an interview. “Utilizing area deprivation indices could be a better marker for identifying household income and give a more accurate representation of the true impact of socioeconomic disparities and severity of sarcoidosis at presentation,” he said.
 

Pinpointing Persistent Disparities

“We know there are multiple sources of disparities in the sarcoidosis population,” said Rohit Gupta, MD, director of the sarcoidosis program at Temple University Hospital, Philadelphia, in an interview.

The current study identified the relationship between several socioeconomic factors and sarcoidosis severity, showing greater disease severity in people experiencing socioeconomic inequalities, said Dr. Gupta, who was not involved in the study.

“I have personally seen this [disparity] in clinic,” said Dr. Gupta. However, supporting data are limited, aside from recent studies published in the last few years by researchers at the Cleveland Clinic and Johns Hopkins University, Baltimore, he said. The current study reflects those previous findings that people suffering from inequality have worse medical care, he added.

Overall, the findings were not surprising, “as we know this cohort of patients have chronic disease and worse morbidity and, in some cases, higher mortality,” but the results reinforce the need to pay closer attention to socioeconomic factors, said Dr. Gupta.

In practice, “we might use these findings as a reminder that when we see these patients for the first time, we should pay closer attention because they might need higher care,” he said. “The study also suggests these patients are coming late to a center of excellence,” he noted. When patients with socioeconomic disparities are seen for sarcoidosis at community hospitals and small centers, providers should keep in mind that their disease might progress faster and, therefore, send them to advanced centers earlier, he said.

The study was limited to the use of data from a single center and by the retrospective design, Dr. Gupta said. “Additional research should focus on building better platforms to understand these disparities,” he emphasized, so clinicians can develop plans not only to identify inequalities but also to address them.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gupta had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Socioeconomic factors were associated with greater disease severity at the time of initial presentation in adults with sarcoidosis, based on a new study of more than 700 individuals presented at the American Thoracic Society’s International Conference 2024.

“We know socioeconomic status plays an important role in health outcomes; however, there is little research into the impact of socioeconomic status on patients with sarcoidosis, particularly with disease severity,” said lead author Joshua Boron, MD, of Virginia Commonwealth University, Richmond, Virginia, in an interview. Identification of patients at higher risk of developing severe lung disease can help clinicians stratify these patients, he said.

Overall, the risk for severe lung disease at initial presentation was nearly three times higher in patients with no insurance than in those with private insurance and nearly three times higher in Black patients than in White patients (odds ratio [OR], 2.97 and 2.83, respectively). In addition, older age was associated with increased risk of fibrosis, with an OR of 1.03 per year increase in age.

No differences in fibrosis at presentation occurred based on sex or median income, and no difference in the likelihood of fibrosis at presentation appeared between patients with Medicaid vs private insurance.

“We were surprised at the degree of risk associated with no insurance,” said Dr. Boron. The researchers also were surprised at the lack of association between higher risk of severe stage lung disease in sarcoidosis patients and zip code estimates of household income as an indicator of socioeconomic status, he said.

For clinical practice, the study findings highlight the potentially increased risk for fibrotic lung disease among patients who are older, uninsured, and African American, said Dr. Boron.

“A limitation of our study was the utilization of zip code based on the US Census Bureau to get an estimation of average household income — a particular limitation in our city because of gentrification over the past few decades,” Dr. Boron said in an interview. “Utilizing area deprivation indices could be a better marker for identifying household income and give a more accurate representation of the true impact of socioeconomic disparities and severity of sarcoidosis at presentation,” he said.
 

Pinpointing Persistent Disparities

“We know there are multiple sources of disparities in the sarcoidosis population,” said Rohit Gupta, MD, director of the sarcoidosis program at Temple University Hospital, Philadelphia, in an interview.

The current study identified the relationship between several socioeconomic factors and sarcoidosis severity, showing greater disease severity in people experiencing socioeconomic inequalities, said Dr. Gupta, who was not involved in the study.

“I have personally seen this [disparity] in clinic,” said Dr. Gupta. However, supporting data are limited, aside from recent studies published in the last few years by researchers at the Cleveland Clinic and Johns Hopkins University, Baltimore, he said. The current study reflects those previous findings that people suffering from inequality have worse medical care, he added.

Overall, the findings were not surprising, “as we know this cohort of patients have chronic disease and worse morbidity and, in some cases, higher mortality,” but the results reinforce the need to pay closer attention to socioeconomic factors, said Dr. Gupta.

In practice, “we might use these findings as a reminder that when we see these patients for the first time, we should pay closer attention because they might need higher care,” he said. “The study also suggests these patients are coming late to a center of excellence,” he noted. When patients with socioeconomic disparities are seen for sarcoidosis at community hospitals and small centers, providers should keep in mind that their disease might progress faster and, therefore, send them to advanced centers earlier, he said.

The study was limited to the use of data from a single center and by the retrospective design, Dr. Gupta said. “Additional research should focus on building better platforms to understand these disparities,” he emphasized, so clinicians can develop plans not only to identify inequalities but also to address them.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gupta had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

A majority of internal medicine physicians report feeling underpaid, but approximately half say that potential pay was not a factor in their decision to choose the specialty, based on data from Medscape’s annual Internist Compensation Report.

Data from the Mercer consulting firm cited in the Medscape report showed an increase of 3% in 2023 over 2022 earnings for physicians in the United States overall. However, on a list of 29 specialties included in the report, internal medicine ranked near the bottom for annual compensation.

The report, based on data from 7000 physicians across the United States, showed that 58% of internal medicine physicians think physicians in general are underpaid, while 33% said that “most physicians are paid about right,” and 8% said that physicians are overpaid. Similarly, when asked about their personal compensation, 55% said that internists are not fairly paid, given their work demands.

Despite concerns about pay, 65% of the internists surveyed said that they were not taking on extra work to boost their incomes. Although less than half (45%) reported being happy with their current pay, 49% said that pay was not a factor in their choice of internal medicine.

Among internists, 60% reported opportunities for bonuses, but the average primary care provider bonus in 2023 was $27,000, compared with an average of $51,000 for bonus pay among specialists.

Money was relatively low on the list as being the most rewarding part of the job for an internist, according to the report. While 34% of respondents cited being good at their jobs and finding answers and diagnoses as the most rewarding part of their jobs, only 9% said “making good money at a job I like” was the most rewarding. The most commonly cited most challenging part of the job was “having so many rules and regulations (22%).”

In addition, approximately two thirds of respondents said other medical businesses (such as telemedicine, retailer clinics, and nonphysician healthcare providers) had no impact on their income, nor did competing physician practices.

More than half (58%) of the respondents were women and the most common age group (based on 5-year increments) was 50-54 years (15%).
 

Regular Pay Assessment Increases Awareness

Assessing physician compensation annually or at regular intervals allows organizations and physicians to know their financial situation and compensation/benefits compared with other professionals, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview. “During the COVID-19 pandemic, many individual practices and employed physicians saw a decline in their revenue due to decrease in routine patient visits to the clinician offices, and decrease in routine and preventative procedures,” he noted.

“The findings from the current report were not unexpected, as certain specialties are more lucrative than primary care,” Dr. Deep said. “Specialties such as orthopedics, plastic surgery, and cardiology have the potential not only to generate more income for those specialist physicians, but also for the healthcare organizations that employ them,” he said.
 

Job Satisfaction Remains Important

As a practicing internist, Dr. Deep agreed that many internal medicine physicians would state that the satisfaction that their job and caring for patients brings to them is more important than the financial aspect of their practice.

“I am asked on occasion if I had an opportunity to go back to medical school and make a choice, whether I would have picked a different specialty. My answer is no,” Dr. Deep said.

“I would have picked internal medicine because of the satisfaction that it brings me,” he said.

Dr. Deep shared some potential strategies for employers to recruit and retain internal medicine physicians. If employers could incentivize internal medicine and other primary care specialties with higher signing bonuses and try to make their annual bonuses comparable to surgical specialties, that would help ensure that internal medicine specialists feel they are being paid fairly for their work, he said. “Decreasing the bureaucratic burden and involving physicians in decision-making and determination of compensation would also help,” he said.

Dr. Deep had no financial conflicts to disclose, and serves on the Editorial Advisory Board of Internal Medicine News.

A majority of internal medicine physicians report feeling underpaid, but approximately half say that potential pay was not a factor in their decision to choose the specialty, based on data from Medscape’s annual Internist Compensation Report.

Data from the Mercer consulting firm cited in the Medscape report showed an increase of 3% in 2023 over 2022 earnings for physicians in the United States overall. However, on a list of 29 specialties included in the report, internal medicine ranked near the bottom for annual compensation.

The report, based on data from 7000 physicians across the United States, showed that 58% of internal medicine physicians think physicians in general are underpaid, while 33% said that “most physicians are paid about right,” and 8% said that physicians are overpaid. Similarly, when asked about their personal compensation, 55% said that internists are not fairly paid, given their work demands.

Despite concerns about pay, 65% of the internists surveyed said that they were not taking on extra work to boost their incomes. Although less than half (45%) reported being happy with their current pay, 49% said that pay was not a factor in their choice of internal medicine.

Among internists, 60% reported opportunities for bonuses, but the average primary care provider bonus in 2023 was $27,000, compared with an average of $51,000 for bonus pay among specialists.

Money was relatively low on the list as being the most rewarding part of the job for an internist, according to the report. While 34% of respondents cited being good at their jobs and finding answers and diagnoses as the most rewarding part of their jobs, only 9% said “making good money at a job I like” was the most rewarding. The most commonly cited most challenging part of the job was “having so many rules and regulations (22%).”

In addition, approximately two thirds of respondents said other medical businesses (such as telemedicine, retailer clinics, and nonphysician healthcare providers) had no impact on their income, nor did competing physician practices.

More than half (58%) of the respondents were women and the most common age group (based on 5-year increments) was 50-54 years (15%).
 

Regular Pay Assessment Increases Awareness

Assessing physician compensation annually or at regular intervals allows organizations and physicians to know their financial situation and compensation/benefits compared with other professionals, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview. “During the COVID-19 pandemic, many individual practices and employed physicians saw a decline in their revenue due to decrease in routine patient visits to the clinician offices, and decrease in routine and preventative procedures,” he noted.

“The findings from the current report were not unexpected, as certain specialties are more lucrative than primary care,” Dr. Deep said. “Specialties such as orthopedics, plastic surgery, and cardiology have the potential not only to generate more income for those specialist physicians, but also for the healthcare organizations that employ them,” he said.
 

Job Satisfaction Remains Important

As a practicing internist, Dr. Deep agreed that many internal medicine physicians would state that the satisfaction that their job and caring for patients brings to them is more important than the financial aspect of their practice.

“I am asked on occasion if I had an opportunity to go back to medical school and make a choice, whether I would have picked a different specialty. My answer is no,” Dr. Deep said.

“I would have picked internal medicine because of the satisfaction that it brings me,” he said.

Dr. Deep shared some potential strategies for employers to recruit and retain internal medicine physicians. If employers could incentivize internal medicine and other primary care specialties with higher signing bonuses and try to make their annual bonuses comparable to surgical specialties, that would help ensure that internal medicine specialists feel they are being paid fairly for their work, he said. “Decreasing the bureaucratic burden and involving physicians in decision-making and determination of compensation would also help,” he said.

Dr. Deep had no financial conflicts to disclose, and serves on the Editorial Advisory Board of Internal Medicine News.

A majority of internal medicine physicians report feeling underpaid, but approximately half say that potential pay was not a factor in their decision to choose the specialty, based on data from Medscape’s annual Internist Compensation Report.

Data from the Mercer consulting firm cited in the Medscape report showed an increase of 3% in 2023 over 2022 earnings for physicians in the United States overall. However, on a list of 29 specialties included in the report, internal medicine ranked near the bottom for annual compensation.

The report, based on data from 7000 physicians across the United States, showed that 58% of internal medicine physicians think physicians in general are underpaid, while 33% said that “most physicians are paid about right,” and 8% said that physicians are overpaid. Similarly, when asked about their personal compensation, 55% said that internists are not fairly paid, given their work demands.

Despite concerns about pay, 65% of the internists surveyed said that they were not taking on extra work to boost their incomes. Although less than half (45%) reported being happy with their current pay, 49% said that pay was not a factor in their choice of internal medicine.

Among internists, 60% reported opportunities for bonuses, but the average primary care provider bonus in 2023 was $27,000, compared with an average of $51,000 for bonus pay among specialists.

Money was relatively low on the list as being the most rewarding part of the job for an internist, according to the report. While 34% of respondents cited being good at their jobs and finding answers and diagnoses as the most rewarding part of their jobs, only 9% said “making good money at a job I like” was the most rewarding. The most commonly cited most challenging part of the job was “having so many rules and regulations (22%).”

In addition, approximately two thirds of respondents said other medical businesses (such as telemedicine, retailer clinics, and nonphysician healthcare providers) had no impact on their income, nor did competing physician practices.

More than half (58%) of the respondents were women and the most common age group (based on 5-year increments) was 50-54 years (15%).
 

Regular Pay Assessment Increases Awareness

Assessing physician compensation annually or at regular intervals allows organizations and physicians to know their financial situation and compensation/benefits compared with other professionals, said Noel Deep, MD, an internal medicine physician in group practice in Antigo, Wisconsin, in an interview. “During the COVID-19 pandemic, many individual practices and employed physicians saw a decline in their revenue due to decrease in routine patient visits to the clinician offices, and decrease in routine and preventative procedures,” he noted.

“The findings from the current report were not unexpected, as certain specialties are more lucrative than primary care,” Dr. Deep said. “Specialties such as orthopedics, plastic surgery, and cardiology have the potential not only to generate more income for those specialist physicians, but also for the healthcare organizations that employ them,” he said.
 

Job Satisfaction Remains Important

As a practicing internist, Dr. Deep agreed that many internal medicine physicians would state that the satisfaction that their job and caring for patients brings to them is more important than the financial aspect of their practice.

“I am asked on occasion if I had an opportunity to go back to medical school and make a choice, whether I would have picked a different specialty. My answer is no,” Dr. Deep said.

“I would have picked internal medicine because of the satisfaction that it brings me,” he said.

Dr. Deep shared some potential strategies for employers to recruit and retain internal medicine physicians. If employers could incentivize internal medicine and other primary care specialties with higher signing bonuses and try to make their annual bonuses comparable to surgical specialties, that would help ensure that internal medicine specialists feel they are being paid fairly for their work, he said. “Decreasing the bureaucratic burden and involving physicians in decision-making and determination of compensation would also help,” he said.

Dr. Deep had no financial conflicts to disclose, and serves on the Editorial Advisory Board of Internal Medicine News.

Use of combined contraceptive vaginal rings was associated with an increased risk for several types of sexually transmitted infections (STIs), based on data from a pair of studies presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Previous research has shown that the use of a combined contraceptive vaginal ring (CCVR) may promote changes in immunity in the female genital tract by upregulating immune-related genes in the endocervix and immune mediators within the cervicovaginal fluid, wrote Amy Arceneaux, BS, a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, and colleagues.

The infection rates in the female genital tract can vary according to hormones in the local environment and continued safety analysis is needed as the use of CCVR continues to rise, the researchers noted.

In a retrospective chart review, the researchers assessed de-identified data from TriNetX, a patient database, including 30,796 women who received etonogestrel and ethinyl estradiol CCVRs without segesterone and an equal number who were using oral contraceptive pills (OCP) without vaginal hormones. Patients were matched for age, race, and ethnicity.

Overall use of CCVRs was significantly associated with an increased risk for Herpes simplex virus 2 (HSV-2; relative risk [RR], 1.790), acute vaginitis (RR, 1.722), subacute/chronic vaginitis (RR, 1.904), subacute/chronic vulvitis (RR, 1.969), acute vulvitis (RR, 1.894), candidiasis (RR, 1.464), trichomoniasis (RR, 2.162), and pelvic inflammatory disease (RR, 2.984; P < .0005 for all).

By contrast, use of CCVRs was significantly associated with a decreased risk for chlamydia (RR, 0.760; P = .047). No differences in risk appeared for gonorrhea, syphilis, HIV, or anogenital warts between the CCVR and OCP groups.

Another study presented at the meeting, led by Kathleen Karam, BS, also a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, focused on outcomes on vaginal health and infection risk in women who used CCVRs compared with women who did not use hormones.

The study by Ms. Karam and colleagues included de-identified TriNetX data for two cohorts of 274,743 women.

Overall, the researchers found a significantly increased risk for gonorrhea, HSV-2, vaginitis, vulvitis, pelvic inflammatory disease, anogenital warts, and candidiasis in women using CCVR compared with those using no hormonal contraception, while the risk for chlamydia, syphilis, and HIV was decreased in women using CCVR compared with those using no hormonal contraception.

“I was pleasantly surprised by the finding that the group of women using the hormonal contraception vaginal ring had decreased risk for HIV and syphilis infections,” said Kathleen L. Vincent, MD, of the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, and senior author on both studies, in an interview. She hypothesized that the estrogen released from the ring might have contributed to the decreased risk for those infections.

The findings of both studies were limited primarily by the retrospective design, but the results suggest a need for further study of the effect of local hormone delivery on the vaginal mucosa, the researchers wrote.

Although the study population was large, the lack of randomization can allow for differences in the behaviors or risk-taking of the groups, Dr. Vincent said in an interview.

“The fact that there were STIs that were increased and some that were decreased with use of the vaginal ring tells us that there were women with similar behaviors in both groups, or we might have seen STIs only in one group,” she said. “Additional research could be done to look at varying time courses of outcomes after initiation of the vaginal ring or to go more in-depth with matching the groups at baseline based on a history of risky behaviors,” she noted.
 

Data Inform Multipurpose Prevention Technology

Dr. Vincent and her colleague, Richard Pyles, PhD, have a 15-year history of studying vaginal drug and hormone effects on the vaginal mucosa in women and preclinical and cell models. “Based on that work, it was plausible for estrogen to be protective for several types of infections,” she said. The availability of TriNetX allowed the researchers to explore these relationships in a large database of women in the studies presented at the meeting. “We began with a basic science observation in an animal model and grew it into this clinical study because of the available TriNetX system that supported extensive medical record review,” Dr. Pyles noted.

The take-home messages from the current research remain that vaginal rings delivering hormones are indicated only for contraception or birth control, not for protection against STIs or HIV, and women at an increased risk for these infections should protect themselves by using condoms, Dr. Vincent said.

However, “the real clinical implication is for the future for the drugs that we call MPTs or multi-purpose prevention technologies,” Dr. Vincent said.

“This could be a vaginal ring that releases medications for birth control and prevention of HIV or an STI,” she explained.

The findings from the studies presented at the meeting have great potential for an MPT on which Dr. Vincent and Dr. Pyles are working that would provide protection against both HIV and pregnancy. “For HIV prevention, the hormonal vaginal ring components have potential to work synergistically with the HIV prevention drug rather than working against each other, and this could be realized as a need for less HIV prevention drug, and subsequently fewer potential side effects from that drug,” said Dr. Vincent.

The studies received no outside funding. The researchers had no financial conflicts to disclose.

Use of combined contraceptive vaginal rings was associated with an increased risk for several types of sexually transmitted infections (STIs), based on data from a pair of studies presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Previous research has shown that the use of a combined contraceptive vaginal ring (CCVR) may promote changes in immunity in the female genital tract by upregulating immune-related genes in the endocervix and immune mediators within the cervicovaginal fluid, wrote Amy Arceneaux, BS, a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, and colleagues.

The infection rates in the female genital tract can vary according to hormones in the local environment and continued safety analysis is needed as the use of CCVR continues to rise, the researchers noted.

In a retrospective chart review, the researchers assessed de-identified data from TriNetX, a patient database, including 30,796 women who received etonogestrel and ethinyl estradiol CCVRs without segesterone and an equal number who were using oral contraceptive pills (OCP) without vaginal hormones. Patients were matched for age, race, and ethnicity.

Overall use of CCVRs was significantly associated with an increased risk for Herpes simplex virus 2 (HSV-2; relative risk [RR], 1.790), acute vaginitis (RR, 1.722), subacute/chronic vaginitis (RR, 1.904), subacute/chronic vulvitis (RR, 1.969), acute vulvitis (RR, 1.894), candidiasis (RR, 1.464), trichomoniasis (RR, 2.162), and pelvic inflammatory disease (RR, 2.984; P < .0005 for all).

By contrast, use of CCVRs was significantly associated with a decreased risk for chlamydia (RR, 0.760; P = .047). No differences in risk appeared for gonorrhea, syphilis, HIV, or anogenital warts between the CCVR and OCP groups.

Another study presented at the meeting, led by Kathleen Karam, BS, also a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, focused on outcomes on vaginal health and infection risk in women who used CCVRs compared with women who did not use hormones.

The study by Ms. Karam and colleagues included de-identified TriNetX data for two cohorts of 274,743 women.

Overall, the researchers found a significantly increased risk for gonorrhea, HSV-2, vaginitis, vulvitis, pelvic inflammatory disease, anogenital warts, and candidiasis in women using CCVR compared with those using no hormonal contraception, while the risk for chlamydia, syphilis, and HIV was decreased in women using CCVR compared with those using no hormonal contraception.

“I was pleasantly surprised by the finding that the group of women using the hormonal contraception vaginal ring had decreased risk for HIV and syphilis infections,” said Kathleen L. Vincent, MD, of the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, and senior author on both studies, in an interview. She hypothesized that the estrogen released from the ring might have contributed to the decreased risk for those infections.

The findings of both studies were limited primarily by the retrospective design, but the results suggest a need for further study of the effect of local hormone delivery on the vaginal mucosa, the researchers wrote.

Although the study population was large, the lack of randomization can allow for differences in the behaviors or risk-taking of the groups, Dr. Vincent said in an interview.

“The fact that there were STIs that were increased and some that were decreased with use of the vaginal ring tells us that there were women with similar behaviors in both groups, or we might have seen STIs only in one group,” she said. “Additional research could be done to look at varying time courses of outcomes after initiation of the vaginal ring or to go more in-depth with matching the groups at baseline based on a history of risky behaviors,” she noted.
 

Data Inform Multipurpose Prevention Technology

Dr. Vincent and her colleague, Richard Pyles, PhD, have a 15-year history of studying vaginal drug and hormone effects on the vaginal mucosa in women and preclinical and cell models. “Based on that work, it was plausible for estrogen to be protective for several types of infections,” she said. The availability of TriNetX allowed the researchers to explore these relationships in a large database of women in the studies presented at the meeting. “We began with a basic science observation in an animal model and grew it into this clinical study because of the available TriNetX system that supported extensive medical record review,” Dr. Pyles noted.

The take-home messages from the current research remain that vaginal rings delivering hormones are indicated only for contraception or birth control, not for protection against STIs or HIV, and women at an increased risk for these infections should protect themselves by using condoms, Dr. Vincent said.

However, “the real clinical implication is for the future for the drugs that we call MPTs or multi-purpose prevention technologies,” Dr. Vincent said.

“This could be a vaginal ring that releases medications for birth control and prevention of HIV or an STI,” she explained.

The findings from the studies presented at the meeting have great potential for an MPT on which Dr. Vincent and Dr. Pyles are working that would provide protection against both HIV and pregnancy. “For HIV prevention, the hormonal vaginal ring components have potential to work synergistically with the HIV prevention drug rather than working against each other, and this could be realized as a need for less HIV prevention drug, and subsequently fewer potential side effects from that drug,” said Dr. Vincent.

The studies received no outside funding. The researchers had no financial conflicts to disclose.

Use of combined contraceptive vaginal rings was associated with an increased risk for several types of sexually transmitted infections (STIs), based on data from a pair of studies presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Previous research has shown that the use of a combined contraceptive vaginal ring (CCVR) may promote changes in immunity in the female genital tract by upregulating immune-related genes in the endocervix and immune mediators within the cervicovaginal fluid, wrote Amy Arceneaux, BS, a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, and colleagues.

The infection rates in the female genital tract can vary according to hormones in the local environment and continued safety analysis is needed as the use of CCVR continues to rise, the researchers noted.

In a retrospective chart review, the researchers assessed de-identified data from TriNetX, a patient database, including 30,796 women who received etonogestrel and ethinyl estradiol CCVRs without segesterone and an equal number who were using oral contraceptive pills (OCP) without vaginal hormones. Patients were matched for age, race, and ethnicity.

Overall use of CCVRs was significantly associated with an increased risk for Herpes simplex virus 2 (HSV-2; relative risk [RR], 1.790), acute vaginitis (RR, 1.722), subacute/chronic vaginitis (RR, 1.904), subacute/chronic vulvitis (RR, 1.969), acute vulvitis (RR, 1.894), candidiasis (RR, 1.464), trichomoniasis (RR, 2.162), and pelvic inflammatory disease (RR, 2.984; P < .0005 for all).

By contrast, use of CCVRs was significantly associated with a decreased risk for chlamydia (RR, 0.760; P = .047). No differences in risk appeared for gonorrhea, syphilis, HIV, or anogenital warts between the CCVR and OCP groups.

Another study presented at the meeting, led by Kathleen Karam, BS, also a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, focused on outcomes on vaginal health and infection risk in women who used CCVRs compared with women who did not use hormones.

The study by Ms. Karam and colleagues included de-identified TriNetX data for two cohorts of 274,743 women.

Overall, the researchers found a significantly increased risk for gonorrhea, HSV-2, vaginitis, vulvitis, pelvic inflammatory disease, anogenital warts, and candidiasis in women using CCVR compared with those using no hormonal contraception, while the risk for chlamydia, syphilis, and HIV was decreased in women using CCVR compared with those using no hormonal contraception.

“I was pleasantly surprised by the finding that the group of women using the hormonal contraception vaginal ring had decreased risk for HIV and syphilis infections,” said Kathleen L. Vincent, MD, of the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, and senior author on both studies, in an interview. She hypothesized that the estrogen released from the ring might have contributed to the decreased risk for those infections.

The findings of both studies were limited primarily by the retrospective design, but the results suggest a need for further study of the effect of local hormone delivery on the vaginal mucosa, the researchers wrote.

Although the study population was large, the lack of randomization can allow for differences in the behaviors or risk-taking of the groups, Dr. Vincent said in an interview.

“The fact that there were STIs that were increased and some that were decreased with use of the vaginal ring tells us that there were women with similar behaviors in both groups, or we might have seen STIs only in one group,” she said. “Additional research could be done to look at varying time courses of outcomes after initiation of the vaginal ring or to go more in-depth with matching the groups at baseline based on a history of risky behaviors,” she noted.
 

Data Inform Multipurpose Prevention Technology

Dr. Vincent and her colleague, Richard Pyles, PhD, have a 15-year history of studying vaginal drug and hormone effects on the vaginal mucosa in women and preclinical and cell models. “Based on that work, it was plausible for estrogen to be protective for several types of infections,” she said. The availability of TriNetX allowed the researchers to explore these relationships in a large database of women in the studies presented at the meeting. “We began with a basic science observation in an animal model and grew it into this clinical study because of the available TriNetX system that supported extensive medical record review,” Dr. Pyles noted.

The take-home messages from the current research remain that vaginal rings delivering hormones are indicated only for contraception or birth control, not for protection against STIs or HIV, and women at an increased risk for these infections should protect themselves by using condoms, Dr. Vincent said.

However, “the real clinical implication is for the future for the drugs that we call MPTs or multi-purpose prevention technologies,” Dr. Vincent said.

“This could be a vaginal ring that releases medications for birth control and prevention of HIV or an STI,” she explained.

The findings from the studies presented at the meeting have great potential for an MPT on which Dr. Vincent and Dr. Pyles are working that would provide protection against both HIV and pregnancy. “For HIV prevention, the hormonal vaginal ring components have potential to work synergistically with the HIV prevention drug rather than working against each other, and this could be realized as a need for less HIV prevention drug, and subsequently fewer potential side effects from that drug,” said Dr. Vincent.

The studies received no outside funding. The researchers had no financial conflicts to disclose.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of biologics significantly reduced exacerbations and hospitalizations in adults with chronic obstructive pulmonary disease (COPD) and overlapping type 2 asthma inflammation, based on data from a new study presented at the American Thoracic Society’s international conference.

Patients diagnosed with COPD on maximum medical therapy may continue to have disease exacerbations that are highly morbid and are associated with worsening lung function, increased hospitalizations, and worsened mortality, said lead author Stephen Dachert, MD, Temple University Hospital, Philadelphia, in an interview.

“Biologic therapy has been shown to reduce exacerbations in type 2 airway inflammation in patients with asthma and may be a potential target in patients with COPD and type 2 inflammation,” he said. In type 2 inflammation, a systematic allergic response activates immune cells, including eosinophils, mast cells, and T cells.

Previous research has examined the association between use of individual biologics and reduction in acute exacerbations of COPD, but real-world data on the use of biologics for COPD and asthma-COPD overlap syndrome (ACOS) are lacking, Dr. Dachert and colleagues wrote in their abstract.

In the current study, the researchers reviewed data from 53 adults with COPD who were seen at a single center; 30 had ACOS, and 23 had COPD only. The mean age of the participants was 68.2 years, approximately half were White/Caucasian individuals, 26% were Black/African American individuals, 17% were Hispanic individuals, 4% were Asian individuals/Pacific Islanders, and 2% were from other races/ethnicities; 62% were women. The study population included patients with prior diagnosis codes for COPD and dupilumab, mepolizumab, benralizumab, or tezepelumab; the mean eosinophil count before biologics initiation was 471.
 

Reduction in Exacerbations and Hospitalizations

The researchers assessed change in exacerbations, hospitalizations, and spirometry from 1 year before to 1 year after initiation of treatment with biologics. Overall, after the use of biologics, patients experienced a significant mean reduction in exacerbations and hospitalizations of 1.780 and 0.944, respectively (both P < .001, using a paired T-test). 

In addition, the researchers found a mean reduction of forced expiratory volume per second percent predicted of 0.57% and a mean increase in forced vital capacity percent predicted of 1.3% after the initiation of biologics.

Increases also occurred in total lung capacity percent predicted, residual volume percent predicted, and diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted (3.37%, 9.90%, and 4.58%, respectively). Of these, only DLCO percent predicted approached statistical significance, the researchers wrote.

The study findings make sense physiologically, Dr. Dachert said in an interview. “If large, randomized trials have shown a reduction in exacerbations in patients with type 2 inflammation asthma, it makes sense that we would see similar results in patients with COPD and type 2 inflammation,” he said. However, as yet only one of several large randomized trials has shown reductions in exacerbations and COPD with type 2 inflammation, he added.

“In our real-world cohort, we saw both a reduction in exacerbations and hospitalizations in the year following initiation of biologic therapy,” Dr. Dachert said. A reduction in hospitalizations, in particular, had not previously been shown in this population, he noted.

The findings were limited by the retrospective design and use of data from a single center; moreover, larger real-world studies are needed to confirm the results, said Dr. Dachert. “As we add patients to our cohort, we may be able to identify which clinical characteristics/risk factors may be associated with an even more robust reduction in exacerbations or hospitalizations,” he said.

“Our cohort of patients was more diverse than those included in prior randomized clinical trials and also has high rates of emphysema and airflow obstruction, populations typically excluded in large randomized trials,” he said.
 

Data Support the Potential of Biologics for COPD

Biologic agents have been effective in reducing asthma exacerbations, and understanding their effectiveness in reducing COPD exacerbations in a real-world setting is important, said Arianne K. Baldomero, MD, assistant professor of medicine at Minneapolis VA Health Care System, Minneapolis, in an interview.

Dr, Baldomero said she was not surprised by the current study results “as clinical trials are showing similar findings among this group of patients with elevated eosinophil counts.”

The current study adds to the growing evidence supporting the use of biologics to reduce COPD exacerbations, Dr. Baldomero told this news organization. “I anticipate that we will soon begin using biologics to manage frequent exacerbations in patients with COPD,” she said.

“For both asthma and COPD, more research is needed to guide clinicians in tapering or weaning down biologic treatment and determining whether patients still need to use inhalers,” Dr. Baldomero added.

The study received no outside funding. The researchers and Dr. Baldomero had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

The addition of abemaciclib to fulvestrant significantly improved progression-free survival for patients with hormone receptor positive, HER2 negative advanced breast cancer who had been previously treated with cyclin-dependent kinase 4 and 6 inhibitor plus endocrine therapy, in a new study.

Disease progression is common in these patients, for whom first-line treatment is cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors plus endocrine therapy, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the American Society of Clinical Oncology (ASCO) annual meeting.

A need exists for additional targeted therapies for patients with advanced hormone receptor (HR)+, HER2- breast cancer whose tumors have progressed on endocrine therapy plus a CDK4/6 inhibitor, he said.

Data on the benefits of continuing CDK4/6 inhibitor therapy after progression have been mixed in phase 2 trials, Dr. Kalinsky noted in his presentation. Abemaciclib, an oral CDK4/6 inhibitor, has shown more selectivity for CDK 4 than CDK 6, and is approved in combination with fulvestrant or an aromatase inhibitor for advanced breast cancer, he said.

In a phase 3 study known as postMONARCH, the researchers randomized 182 patients to abemaciclib plus fulvestrant and 186 to placebo plus fulvestrant. The primary endpoint was progression-free survival (PFS) based on investigator assessment; secondary endpoints included PFS based on blinded independent central review (BICR), objective response rate (ORR), and safety.

The PFS rates at 6 months were 50% and 37% for the abemaciclib and placebo arms, respectively.

In the primary analysis, abemaciclib led to a 27% reduction in risk of investigator-assessed progression-free survival events compared with the placebo (117 vs. 141 events, hazard ratio 0.73, P = 0.02).

The study population included men and pre- and postmenopausal women with advanced HR+, HER2- breast cancer and progression after initial CDK4/6 plus endocrine therapy from 96 centers in 16 countries, enrolled between March 2022 and June 2023. The median age of the patients in the abemaciclib and placebo groups was 58 years and 61 years, respectively. Patients underwent scans every 8 weeks for the first 12 months, then every 12 weeks. Most of the patients were enrolled immediately after CDK4/6i + ET as initial therapy for advanced breast cancer. The most common previous CDK4/6 inhibitor therapy was palbociclib (59%), followed by ribociclib (33%) and abemaciclib (8%).
 

Secondary Endpoints Also Favor Abemaciclib

The effects in favor of abemaciclib were consistent across subgroups, regardless of the presence or absence of baseline genetic mutations (ESR1 or PIK3CA), Dr. Kalinsky said in his presentation.

Overall response rate was significantly improved in the abemaciclib group compared with the placebo group in patients with measurable disease (17% vs. 7%) and PFS according to BICR also significantly improved (HR 0.55).

The magnitude of benefit was less in the subgroup of patients with visceral metastases, Dr. Kalinsky noted.

“Safety was consistent with what is known about the abemaciclib profile,” he added. Six percent of abemaciclib patients discontinued treatment because of adverse events.

The study is the first phase 3 trial to show improvement with CDK4/6 inhibition therapy with a combination of abemaciclib and fulvestrant and offers a new option for patients with HR+, HER2- advanced breast cancer not selected for biomarker status, Dr. Kalinsky concluded.
 

Data Support Switching CDK Inhibitors in Absence of Mutations

Switching CDK inhibitors to abemaciclib plus endocrine therapy significantly prolonged progression-free survival compared with endocrine therapy alone, with especially pronounced improvement in those without visceral metastases and those with longer durations of first-line CKD4/6 inhibitor therapy, said Ruth O’Regan, MD, of the University of Rochester, New York, who served as the discussant for the new research.

Dr. Regan referenced the improvement with abemaciclib in the BICR, a technique used to identify potential bias introduced by the assessment of local investigators. This can result in more favorable PFS on a treatment arm as seen in this study, but its use generally does not impact overall trial results, she said.

In the context of other studies involving switching CDK 4/6 inhibitors post-progression, the difference of 0.7 months in PFS between the abemaciclib and placebo groups was less than the 2.5 months difference seen in the MAINTAIN trial and the 1.3 months difference seen in the PALMIRA trial, Dr. O’Regan said in her presentation. Conversely, in the PACE trial, the intervention group did worse (4.6 months) than the control group in terms of the PFS (4.8 months), she said. Overall, the results of the postMONARCH trial support the use abemaciclib in patients with no actionable genetic mutation, she said.

In a question-and-answer session, Dr. Kalinsky was asked whether clinicians should still bother with genetic testing, since patients in the current study showed benefits regardless of the presence or absence of a mutation.

“I would still recommend that we check for mutations,” he emphasized. The current study “is one chapter in a much larger book,” and the field continues to evolve, he said.
 

A Clinician’s Take

“Currently, no standard second-line treatment after progression on first line CDK4/6 inhibitor plus endocrine therapy exists,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. “Using a different CDK4/6 inhibitor after progression on a first CDK4/6 inhibitor has mixed data,” she said.

“If benefit with a second CDK4/6 inhibitor is confirmed, it may represent an additional low toxicity, chemotherapy-sparing regimen,” she noted.

Earlier data from the MAINTAIN trial had shown benefit with using ribociclib after progression on a primarily first line palbociclib, though other trials looking at use of palbociclib after progression on CDK 4/6 inhibitor [including the PACE and PALMIRA trials] had not, she said.

Overall, the results from postMONARCH support that switching the CDK4/6 inhibitor at progression to ribociclib or abemaciclib may be another treatment option, and reasonable for patients who don’t have other actionable mutations, Dr. West told this news organization.

The study was supported by Eli Lilly. Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma; AstraZeneca; Cullinan Oncology; Daiichi Sankyo/AstraZeneca; eFFECTOR Therapeutics; Genentech/Roche; Immunomedics; Lilly; Menarini Silicon Biosystems; Merck; Mersana; Myovant Sciences; Novartis; Oncosec; Prelude Therapeutics; Puma Biotechnology; RayzeBio; Seagen; and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma; AstraZeneca; Daiichi Sankyo; Genentech/Roche; Lilly; Novartis; and Seagen, and relationships with Genentech and Immunomedics.

Dr. O’Regan disclosed honoraria from AstraZeneca/MedImmune; bioTheranostics; Gilead Sciences; Novartis; Pfizer; Puma Biotechnology; and Seagen, serving as a consultant or adviser for AstraZeneca/MedImmune; bioTheranostics; Lilly; Novartis; Puma Biotechnology; and Seagen, and funding to her institution from Novartis and Puma Biotechnology.

Dr. West, who was not involved in the new research or other studies mentioned in this article, had no financial conflicts to disclose.

Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.

Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.

Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.

“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.

12 Months of COPD, Triple Inhaler Therapy

In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.

The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.

The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.

At 52 weeks, the annualized rate of moderate or severe exacerbations was significantly lower (34%) in the dupilumab group than in the placebo group (0.86 vs 1.30, P < .001).

Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).

Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).

Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.

The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.

Data May Drive US Food and Drug Administration (FDA) Approval

In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.

With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.

Potential Change in Patient Management

Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.

The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.

If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.

“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.

In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.

Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.

A version of this article appeared on Medscape.com.

Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.

Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.

Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.

“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.

12 Months of COPD, Triple Inhaler Therapy

In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.

The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.

The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.

At 52 weeks, the annualized rate of moderate or severe exacerbations was significantly lower (34%) in the dupilumab group than in the placebo group (0.86 vs 1.30, P < .001).

Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).

Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).

Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.

The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.

Data May Drive US Food and Drug Administration (FDA) Approval

In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.

With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.

Potential Change in Patient Management

Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.

The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.

If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.

“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.

In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.

Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.

A version of this article appeared on Medscape.com.

Dupilumab significantly reduced exacerbations and improved lung function in adults with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation, based on data from more than 900 individuals.

Data from a phase 3 trial known as NOTUS were presented at the American Thoracic Society’s international conference and published simultaneously in The New England Journal of Medicine.

Dupilumab, a fully human monoclonal antibody, works by inhibiting the signaling of the interleukin 4 (IL-4) and IL-13 pathways and is approved for many conditions characterized by type 2 inflammation, wrote Surya P. Bhatt, MD, of The University of Alabama at Birmingham, and colleagues in the NEJM study.

“Last year, we showed in the BOREAS trial that dupilumab was very effective in lowering exacerbation frequency in patients with COPD who continued to have frequent exacerbations despite being on maximal inhaled therapy,” Dr. Bhatt said in an interview.

12 Months of COPD, Triple Inhaler Therapy

In the NOTUS study, the researchers randomized 470 adults with uncontrolled COPD and type 2 inflammation (defined as a blood eosinophil count of ≥ 300 cells/µL) to 300-mg subcutaneous dupilumab and 465 to a placebo every 2 weeks. Patients were enrolled between July 2020 and May 2023.

The study population included adults aged 40-85 years with physician-diagnosed COPD for at least 12 months who had received background triple inhaler therapy (an inhaled glucocorticoid agent plus long-acting muscarinic antagonist [LAMA]–long-acting beta-agonist [LABA] or LAMA-LABA alone) for at least 3 months and at a stable dose for at least 1 month. All participants were current or former smokers with a smoking history of at least 10 pack-years.

The primary endpoint was a reduction in the annualized rate of moderate or severe COPD exacerbations at 52 weeks.

At 52 weeks, the annualized rate of moderate or severe exacerbations was significantly lower (34%) in the dupilumab group than in the placebo group (0.86 vs 1.30, P < .001).

Patients in the dupilumab group also saw a significantly greater improvement in lung function compared with individuals in the placebo group based on prebronchodilator forced expiratory volume in 1 second from baseline to 12 weeks (least squares mean change of 139 mL vs 57 mL). This improvement was sustained at 52 weeks (least squares mean change of 115 mL vs 54 mL).

Improvement in respiratory symptom severity based on the St. George’s Respiratory Questionnaire was another secondary endpoint, and changes in total score were greater in the dupilumab group than in the placebo group (least squares mean change of 9.8 vs 6.4).

Safety outcomes were similar between the dupilumab and placebo groups, with approximately 66% of patients in each group reporting adverse events during the 52-week study period. Serious adverse events occurred in 13% and 15.9% of dupilumab and placebo patients, respectively, and adverse events resulting in death occurred in 2.6% and 1.5%, respectively. The most common adverse events were COVID-19, which occurred in 9.4% and 8.2% of the dupilumab and placebo patients, respectively, followed by headache, COPD, and nasopharyngitis. Major adverse cardiovascular events occurred in three patients in the dupilumab group and seven patients in the placebo group.

The findings were limited by several factors including the reduced sample size for 52-week endpoints because of the earlier analysis and the primarily White study population, the researchers noted. The study was conducted in part during the COVID-19 pandemic period, which contributed to healthcare disruptions and behavior changes that decreased exposure to viral respiratory infections, they wrote in their discussion. However, the results were strengthened by the large numbers and international population without other major pulmonary diseases, such as asthma, and the 34% reduction in exacerbations with dupilumab vs placebo is clinically significant, they said.

Data May Drive US Food and Drug Administration (FDA) Approval

In the BOREAS trial, dupilumab also improved lung function and quality of life, with no notable safety concerns. “As with any trial evaluating the efficacy and safety of a medication, it is important to confirm the findings in a replicative study,” said Dr. Bhatt. “With NOTUS, we confirmed the findings of BOREAS,” and the researchers were reassured by the substantial reduction in exacerbation frequency and the replication of key secondary outcomes, he said.

With the NOTUS study, “two randomized trials have now shown near identical reductions in exacerbation frequency in a difficult-to-treat population of patients with COPD with type 2 inflammation and frequent exacerbations,” as well as a significant and meaningful improvement in lung function, Dr. Bhatt said in an interview. “We hope these trials pave for the way for regulatory body approval of dupilumab for clinical use,” he said. Looking ahead, more studies are needed to test the potential disease modification effects of dupilumab in patients with COPD, he added.

Potential Change in Patient Management

Approximately 20%-40% of patients with COPD have type 2 inflammation with elevated blood eosinophil count, and this subset of patients has an increased risk for exacerbations, with worsening lung function and quality of life, Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, said in an interview.

Prior phase 3 studies have shown that dupilumab, a blocker of IL-4 and IL-13 pathways, could effectively reduce exacerbations and improve lung function in these patients, and the NOTUS study aimed to confirm the findings in a larger, more diverse population, said Dr. Narendra, who was not involved in the study.

The NOTUS study represents a paradigm shift in the management of COPD patients with type 2 inflammation, said Narendra. “This study validates the previous BOREAS trial and has shown that dupilumab reduces exacerbations, improves lung function and quality of life, and potentially slows disease progression,” she said.

If approved, potential barriers to the use of dupilumab in practice include cost and insurance coverage, education and dissemination of study findings, and limited data on side effects, said Dr. Narendra.

“While the NOTUS study provides valuable insights into the efficacy and safety of dupilumab over 52 weeks, longer-term studies are needed to understand the sustained benefits and risks of continued treatment,” Dr. Narendra told this news organization. “Studies comparing dupilumab with other biological agents and newer COPD treatments could provide insights into its relative efficacy and position in treatment protocols,” she said.

In addition, further research into dupilumab’s underlying mechanisms could provide deeper insights into the pathophysiology of type 2 inflammation in COPD and inform the development of new treatments, Dr. Narendra said. “These steps will help integrate dupilumab more effectively into clinical practice and optimize its use for COPD patients with type 2 inflammation,” she noted.

Dupilumab is undergoing Priority Review by the FDA as an add-on maintenance therapy for adults with uncontrolled COPD and type 2 inflammation, with a target action date of June 27, 2024, according to a company press release.

The study was funded by Sanofi and Regeneron Pharmaceuticals. Dr. Narendra had no financial conflicts to disclose but serves on the Editorial Advisory Board of CHEST Physician.

A version of this article appeared on Medscape.com.

Bronchoscopic lung volume reduction (BLVR) significantly improved lung function in a subset of patients with chronic obstructive pulmonary disease (COPD) with alpha-1 antitrypsin deficiency (AATD), based on data from more than 200 individuals.

BLVR has shown promising results in previous studies for carefully selected patients with COPD, said Michael J. Nicholson, DO, of Temple University Hospital, Philadelphia. However, those with AATD have often been excluded from large BLVR trials, so data on its effectiveness in this population are limited, he said.

“The distinct pathophysiology of AATD poses challenges in extrapolating findings from trials involving COPD patients without AATD,” Dr. Nicholson noted. “Variations in affected lung lobes and disease progression are major differences between the AATD and non-AATD populations; we sought to examine if BLVR could provide significant, sustained benefit to AATD patients despite their differences from the typical COPD cohort,” he said.

Patients With COPD and AATD

In a study presented at the American Thoracic Society (ATS) 2024 International Conference, Dr. Nicholson and colleagues reviewed data from 238 adults with COPD including 14 with AATD who underwent BLVR at a single center between August 2018 and December 2022. Pulmonary function test data were collected at baseline and at a median of 7 months post-BLVR. The mean age of patients with AATD was 61.5 years, and 79% were men.

The primary outcome was the percentage of patients with forced expiratory volume per second (FEV1) improvement greater than 15%. Half of the patients with AATD achieved this outcome, with a median improvement in FEV1 of 110 mL and a significant difference in pre- and post-BLVR FEV1 volume based on a Wilcoxon signed rank test (W = 11.5; P < .05).

Patients with AATD also showed significant improvement in several secondary outcomes including BODE index, residual volume (RV), total lung capacity (TLC), RV/TLC ratio, and inspiratory capacity/RV ratio between pre- and post-BLVR.

“The sustained improvements seen at 7 months post-BLVR in patients with lower lobe disease were unexpected and promising,” Dr. Nicholson said in an interview. “In contrast to the National Emphysema Treatment Trial (NETT), which found lung volume reduction surgery ineffective for lower lobe disease, our study revealed significant improvements in lower lobe disease following BLVR,” he said. The sustained improvements up to 7 months post-BLVR are encouraging, given clinical concerns that the ongoing destruction of lung tissue in AATD could cause initial BLVR improvements to regress, he added.

Overall, the results suggest that BLVR is an effective therapy for appropriately selected patients with AATD and COPD, and that significant improvement in lung function can be achieved regardless of the affected lobe, Dr. Nicholson said.

“The primary obstacles to widespread BLVR implementation include the scarcity of equipment, as well as insufficient education and training for pulmonologists outside of major academic institutions,” Dr. Nicholson told this news organization. “Successful outcomes in BLVR require clinicians to have a deep understanding of patient selection criteria, extensive training in BLVR techniques, and access to the necessary technology within their facilities,” he said. However, BLVR has been integrated into pulmonary and interventional pulmonary fellowships nationwide, which paves the way for a new generation of pulmonologists to expand the use of the procedure, he said.

Looking ahead, prospective examination of BLVR vs the current standard of care in patients with AATD would provide invaluable data, Dr. Nicholson said. Since the presentation of the study at the meeting, additional patient data have been added to the analysis and increased the power of the findings, he said. “We intend to extend our assessment of pulmonary function testing beyond 7 months post-BLVR to evaluate the persistence of improvements in the long term,” he added.

Study Confirms Benefits for Wider Patient Population

“Lung volume reduction is an important intervention in patients with severe emphysema,” said David M. Mannino, MD, of the University of Kentucky, Lexington, Kentucky, in an interview. Most emphysema is in the upper lobes, but it tends to occur more in the lower lobes in patients with AATD, said Dr. Mannino, who was not involved in the study.

The findings were not especially surprising, but they were reassuring, Dr. Mannino told this news organization. “We know this intervention works in those with severe emphysema,” and it was helpful to confirm similar success in patients with AATD, he said.

The implications for practice are that BLVR is both a safe and an effective intervention for patients with lower or upper lobe emphysema, although longer-term follow-up studies are needed, he said.

The study received no outside funding. Dr. Nicholson and Dr. Mannino had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Bronchoscopic lung volume reduction (BLVR) significantly improved lung function in a subset of patients with chronic obstructive pulmonary disease (COPD) with alpha-1 antitrypsin deficiency (AATD), based on data from more than 200 individuals.

BLVR has shown promising results in previous studies for carefully selected patients with COPD, said Michael J. Nicholson, DO, of Temple University Hospital, Philadelphia. However, those with AATD have often been excluded from large BLVR trials, so data on its effectiveness in this population are limited, he said.

“The distinct pathophysiology of AATD poses challenges in extrapolating findings from trials involving COPD patients without AATD,” Dr. Nicholson noted. “Variations in affected lung lobes and disease progression are major differences between the AATD and non-AATD populations; we sought to examine if BLVR could provide significant, sustained benefit to AATD patients despite their differences from the typical COPD cohort,” he said.

Patients With COPD and AATD

In a study presented at the American Thoracic Society (ATS) 2024 International Conference, Dr. Nicholson and colleagues reviewed data from 238 adults with COPD including 14 with AATD who underwent BLVR at a single center between August 2018 and December 2022. Pulmonary function test data were collected at baseline and at a median of 7 months post-BLVR. The mean age of patients with AATD was 61.5 years, and 79% were men.

The primary outcome was the percentage of patients with forced expiratory volume per second (FEV1) improvement greater than 15%. Half of the patients with AATD achieved this outcome, with a median improvement in FEV1 of 110 mL and a significant difference in pre- and post-BLVR FEV1 volume based on a Wilcoxon signed rank test (W = 11.5; P < .05).

Patients with AATD also showed significant improvement in several secondary outcomes including BODE index, residual volume (RV), total lung capacity (TLC), RV/TLC ratio, and inspiratory capacity/RV ratio between pre- and post-BLVR.

“The sustained improvements seen at 7 months post-BLVR in patients with lower lobe disease were unexpected and promising,” Dr. Nicholson said in an interview. “In contrast to the National Emphysema Treatment Trial (NETT), which found lung volume reduction surgery ineffective for lower lobe disease, our study revealed significant improvements in lower lobe disease following BLVR,” he said. The sustained improvements up to 7 months post-BLVR are encouraging, given clinical concerns that the ongoing destruction of lung tissue in AATD could cause initial BLVR improvements to regress, he added.

Overall, the results suggest that BLVR is an effective therapy for appropriately selected patients with AATD and COPD, and that significant improvement in lung function can be achieved regardless of the affected lobe, Dr. Nicholson said.

“The primary obstacles to widespread BLVR implementation include the scarcity of equipment, as well as insufficient education and training for pulmonologists outside of major academic institutions,” Dr. Nicholson told this news organization. “Successful outcomes in BLVR require clinicians to have a deep understanding of patient selection criteria, extensive training in BLVR techniques, and access to the necessary technology within their facilities,” he said. However, BLVR has been integrated into pulmonary and interventional pulmonary fellowships nationwide, which paves the way for a new generation of pulmonologists to expand the use of the procedure, he said.

Looking ahead, prospective examination of BLVR vs the current standard of care in patients with AATD would provide invaluable data, Dr. Nicholson said. Since the presentation of the study at the meeting, additional patient data have been added to the analysis and increased the power of the findings, he said. “We intend to extend our assessment of pulmonary function testing beyond 7 months post-BLVR to evaluate the persistence of improvements in the long term,” he added.

Study Confirms Benefits for Wider Patient Population

“Lung volume reduction is an important intervention in patients with severe emphysema,” said David M. Mannino, MD, of the University of Kentucky, Lexington, Kentucky, in an interview. Most emphysema is in the upper lobes, but it tends to occur more in the lower lobes in patients with AATD, said Dr. Mannino, who was not involved in the study.

The findings were not especially surprising, but they were reassuring, Dr. Mannino told this news organization. “We know this intervention works in those with severe emphysema,” and it was helpful to confirm similar success in patients with AATD, he said.

The implications for practice are that BLVR is both a safe and an effective intervention for patients with lower or upper lobe emphysema, although longer-term follow-up studies are needed, he said.

The study received no outside funding. Dr. Nicholson and Dr. Mannino had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Bronchoscopic lung volume reduction (BLVR) significantly improved lung function in a subset of patients with chronic obstructive pulmonary disease (COPD) with alpha-1 antitrypsin deficiency (AATD), based on data from more than 200 individuals.

BLVR has shown promising results in previous studies for carefully selected patients with COPD, said Michael J. Nicholson, DO, of Temple University Hospital, Philadelphia. However, those with AATD have often been excluded from large BLVR trials, so data on its effectiveness in this population are limited, he said.

“The distinct pathophysiology of AATD poses challenges in extrapolating findings from trials involving COPD patients without AATD,” Dr. Nicholson noted. “Variations in affected lung lobes and disease progression are major differences between the AATD and non-AATD populations; we sought to examine if BLVR could provide significant, sustained benefit to AATD patients despite their differences from the typical COPD cohort,” he said.

Patients With COPD and AATD

In a study presented at the American Thoracic Society (ATS) 2024 International Conference, Dr. Nicholson and colleagues reviewed data from 238 adults with COPD including 14 with AATD who underwent BLVR at a single center between August 2018 and December 2022. Pulmonary function test data were collected at baseline and at a median of 7 months post-BLVR. The mean age of patients with AATD was 61.5 years, and 79% were men.

The primary outcome was the percentage of patients with forced expiratory volume per second (FEV1) improvement greater than 15%. Half of the patients with AATD achieved this outcome, with a median improvement in FEV1 of 110 mL and a significant difference in pre- and post-BLVR FEV1 volume based on a Wilcoxon signed rank test (W = 11.5; P < .05).

Patients with AATD also showed significant improvement in several secondary outcomes including BODE index, residual volume (RV), total lung capacity (TLC), RV/TLC ratio, and inspiratory capacity/RV ratio between pre- and post-BLVR.

“The sustained improvements seen at 7 months post-BLVR in patients with lower lobe disease were unexpected and promising,” Dr. Nicholson said in an interview. “In contrast to the National Emphysema Treatment Trial (NETT), which found lung volume reduction surgery ineffective for lower lobe disease, our study revealed significant improvements in lower lobe disease following BLVR,” he said. The sustained improvements up to 7 months post-BLVR are encouraging, given clinical concerns that the ongoing destruction of lung tissue in AATD could cause initial BLVR improvements to regress, he added.

Overall, the results suggest that BLVR is an effective therapy for appropriately selected patients with AATD and COPD, and that significant improvement in lung function can be achieved regardless of the affected lobe, Dr. Nicholson said.

“The primary obstacles to widespread BLVR implementation include the scarcity of equipment, as well as insufficient education and training for pulmonologists outside of major academic institutions,” Dr. Nicholson told this news organization. “Successful outcomes in BLVR require clinicians to have a deep understanding of patient selection criteria, extensive training in BLVR techniques, and access to the necessary technology within their facilities,” he said. However, BLVR has been integrated into pulmonary and interventional pulmonary fellowships nationwide, which paves the way for a new generation of pulmonologists to expand the use of the procedure, he said.

Looking ahead, prospective examination of BLVR vs the current standard of care in patients with AATD would provide invaluable data, Dr. Nicholson said. Since the presentation of the study at the meeting, additional patient data have been added to the analysis and increased the power of the findings, he said. “We intend to extend our assessment of pulmonary function testing beyond 7 months post-BLVR to evaluate the persistence of improvements in the long term,” he added.

Study Confirms Benefits for Wider Patient Population

“Lung volume reduction is an important intervention in patients with severe emphysema,” said David M. Mannino, MD, of the University of Kentucky, Lexington, Kentucky, in an interview. Most emphysema is in the upper lobes, but it tends to occur more in the lower lobes in patients with AATD, said Dr. Mannino, who was not involved in the study.

The findings were not especially surprising, but they were reassuring, Dr. Mannino told this news organization. “We know this intervention works in those with severe emphysema,” and it was helpful to confirm similar success in patients with AATD, he said.

The implications for practice are that BLVR is both a safe and an effective intervention for patients with lower or upper lobe emphysema, although longer-term follow-up studies are needed, he said.

The study received no outside funding. Dr. Nicholson and Dr. Mannino had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of an electronic tool contributed to the deprescribing of unnecessary inhalers in patients with interstitial lung disease (ILD), based on data from nearly 200 individuals.

Patients with ILD often have symptoms that overlap with those of obstructive airways diseases, Stephanie Nevison, MD, of the University of Toronto, and colleagues wrote in a study presented at the American Thoracic Society’s international conference.

These patients may be started on inhalers to improve their symptoms but with no expected physiologic benefit, and inappropriate use of inhalers may lead to not only unnecessary side effects but also increased health care costs and environmental impact, they noted.

“Our aim was twofold: To quantify the extent of inappropriate inhaler use in patients with ILD and to discontinue them where appropriate,” the researchers wrote.

“We hypothesized that inappropriate inhaler use in ILD is common and that an electronic initiative would improve deprescribing rates,” they said.

The researchers conducted a quality improvement project in an ILD clinic at a single center. They reviewed 5 months of baseline data for 191 patients with ILD to assess baseline frequency of inappropriate inhaler use, defined as one or more of the following criteria: Reported asthma history, smoking history of > 15 pack/years, emphysema on chest CT, patient-reported benefits from therapy, airflow obstruction, or bronchodilator response on spirometry.

A total of 48 patients (25.1%) were on inhalers, and 15 (7.8%) had no indication for them (9% of new referrals and 7% of follow-up patients). The most-prescribed inhalers for patients with no indication were corticosteroids (10 patients), short-acting beta-agonists (8 patients), and long-acting beta-agonists (7 patients).

None of the patients on inhalers received counseling about discontinuing their use. The results of the baseline assessment were shared with clinicians along with education about reducing unnecessary inhaler use in the form of a prompt linked to electronic medical records to discuss deprescription of unnecessary inhalers.

The electronic intervention was applied in 400 of 518 patient encounters, and the researchers reviewed data over another 5-month period. A total of 99 patients were on inhalers, and 3.3% had no indication (5.3% of new referrals and 3.0% of follow-up patients). In the wake of the intervention, “all patients on unnecessary inhalers were counseled on deprescribing, representing a significant increase compared to the preintervention period,” the researchers wrote.
 

Intervention Shows Potential to Curb Unnecessary Inhaler Use

More research is needed as the findings were limited by the relatively small sample size and use of data from a single center, the researchers noted.

However, the results suggest that electronic reminders are effective for prompting a review of inhaler use, and deprescribing inappropriate inhalers for patients with ILD could reduce the potential for adverse events associated with their use, they concluded.

The current study is important because some patients with ILD may not benefit from inhaler use, David Mannino, MD, of the University of Kentucky, Lexington, said in an interview. In the study, “I was a bit surprised that only 3.3% of patients had no indication for them; this seems rather low,” said Dr. Mannino, who was not involved in the study.

Use of an electronic system that evaluates patients and flags inappropriate therapy is an effective way to decrease overprescribing of medications, Dr. Mannino told this news organization.

As for additional research, application of the tool used in this study to other pulmonary populations could be interesting and potentially useful, he said.

The study received no outside funding. The researchers and Dr. Mannino had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of an electronic tool contributed to the deprescribing of unnecessary inhalers in patients with interstitial lung disease (ILD), based on data from nearly 200 individuals.

Patients with ILD often have symptoms that overlap with those of obstructive airways diseases, Stephanie Nevison, MD, of the University of Toronto, and colleagues wrote in a study presented at the American Thoracic Society’s international conference.

These patients may be started on inhalers to improve their symptoms but with no expected physiologic benefit, and inappropriate use of inhalers may lead to not only unnecessary side effects but also increased health care costs and environmental impact, they noted.

“Our aim was twofold: To quantify the extent of inappropriate inhaler use in patients with ILD and to discontinue them where appropriate,” the researchers wrote.

“We hypothesized that inappropriate inhaler use in ILD is common and that an electronic initiative would improve deprescribing rates,” they said.

The researchers conducted a quality improvement project in an ILD clinic at a single center. They reviewed 5 months of baseline data for 191 patients with ILD to assess baseline frequency of inappropriate inhaler use, defined as one or more of the following criteria: Reported asthma history, smoking history of > 15 pack/years, emphysema on chest CT, patient-reported benefits from therapy, airflow obstruction, or bronchodilator response on spirometry.

A total of 48 patients (25.1%) were on inhalers, and 15 (7.8%) had no indication for them (9% of new referrals and 7% of follow-up patients). The most-prescribed inhalers for patients with no indication were corticosteroids (10 patients), short-acting beta-agonists (8 patients), and long-acting beta-agonists (7 patients).

None of the patients on inhalers received counseling about discontinuing their use. The results of the baseline assessment were shared with clinicians along with education about reducing unnecessary inhaler use in the form of a prompt linked to electronic medical records to discuss deprescription of unnecessary inhalers.

The electronic intervention was applied in 400 of 518 patient encounters, and the researchers reviewed data over another 5-month period. A total of 99 patients were on inhalers, and 3.3% had no indication (5.3% of new referrals and 3.0% of follow-up patients). In the wake of the intervention, “all patients on unnecessary inhalers were counseled on deprescribing, representing a significant increase compared to the preintervention period,” the researchers wrote.
 

Intervention Shows Potential to Curb Unnecessary Inhaler Use

More research is needed as the findings were limited by the relatively small sample size and use of data from a single center, the researchers noted.

However, the results suggest that electronic reminders are effective for prompting a review of inhaler use, and deprescribing inappropriate inhalers for patients with ILD could reduce the potential for adverse events associated with their use, they concluded.

The current study is important because some patients with ILD may not benefit from inhaler use, David Mannino, MD, of the University of Kentucky, Lexington, said in an interview. In the study, “I was a bit surprised that only 3.3% of patients had no indication for them; this seems rather low,” said Dr. Mannino, who was not involved in the study.

Use of an electronic system that evaluates patients and flags inappropriate therapy is an effective way to decrease overprescribing of medications, Dr. Mannino told this news organization.

As for additional research, application of the tool used in this study to other pulmonary populations could be interesting and potentially useful, he said.

The study received no outside funding. The researchers and Dr. Mannino had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Use of an electronic tool contributed to the deprescribing of unnecessary inhalers in patients with interstitial lung disease (ILD), based on data from nearly 200 individuals.

Patients with ILD often have symptoms that overlap with those of obstructive airways diseases, Stephanie Nevison, MD, of the University of Toronto, and colleagues wrote in a study presented at the American Thoracic Society’s international conference.

These patients may be started on inhalers to improve their symptoms but with no expected physiologic benefit, and inappropriate use of inhalers may lead to not only unnecessary side effects but also increased health care costs and environmental impact, they noted.

“Our aim was twofold: To quantify the extent of inappropriate inhaler use in patients with ILD and to discontinue them where appropriate,” the researchers wrote.

“We hypothesized that inappropriate inhaler use in ILD is common and that an electronic initiative would improve deprescribing rates,” they said.

The researchers conducted a quality improvement project in an ILD clinic at a single center. They reviewed 5 months of baseline data for 191 patients with ILD to assess baseline frequency of inappropriate inhaler use, defined as one or more of the following criteria: Reported asthma history, smoking history of > 15 pack/years, emphysema on chest CT, patient-reported benefits from therapy, airflow obstruction, or bronchodilator response on spirometry.

A total of 48 patients (25.1%) were on inhalers, and 15 (7.8%) had no indication for them (9% of new referrals and 7% of follow-up patients). The most-prescribed inhalers for patients with no indication were corticosteroids (10 patients), short-acting beta-agonists (8 patients), and long-acting beta-agonists (7 patients).

None of the patients on inhalers received counseling about discontinuing their use. The results of the baseline assessment were shared with clinicians along with education about reducing unnecessary inhaler use in the form of a prompt linked to electronic medical records to discuss deprescription of unnecessary inhalers.

The electronic intervention was applied in 400 of 518 patient encounters, and the researchers reviewed data over another 5-month period. A total of 99 patients were on inhalers, and 3.3% had no indication (5.3% of new referrals and 3.0% of follow-up patients). In the wake of the intervention, “all patients on unnecessary inhalers were counseled on deprescribing, representing a significant increase compared to the preintervention period,” the researchers wrote.
 

Intervention Shows Potential to Curb Unnecessary Inhaler Use

More research is needed as the findings were limited by the relatively small sample size and use of data from a single center, the researchers noted.

However, the results suggest that electronic reminders are effective for prompting a review of inhaler use, and deprescribing inappropriate inhalers for patients with ILD could reduce the potential for adverse events associated with their use, they concluded.

The current study is important because some patients with ILD may not benefit from inhaler use, David Mannino, MD, of the University of Kentucky, Lexington, said in an interview. In the study, “I was a bit surprised that only 3.3% of patients had no indication for them; this seems rather low,” said Dr. Mannino, who was not involved in the study.

Use of an electronic system that evaluates patients and flags inappropriate therapy is an effective way to decrease overprescribing of medications, Dr. Mannino told this news organization.

As for additional research, application of the tool used in this study to other pulmonary populations could be interesting and potentially useful, he said.

The study received no outside funding. The researchers and Dr. Mannino had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.

Exercise interventions are recommended to help prevent falls and fall-related morbidity in community-dwelling adults aged 65 years and older who are at increased risk of falls, according to a new recommendation statement from the U.S. Preventive Services Task Force (USPSTF) (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.8481).

Falls remain the leading cause of injury-related morbidity and mortality among older adults in the United States, with approximately 27% of community-dwelling individuals aged 65 years and older reporting at least one fall in the past year, wrote lead author Wanda K. Nicholson, MD, of George Washington University, Washington, and colleagues.

The task force concluded with moderate certainty that exercise interventions yielded a moderate benefit in fall reduction among older adults at risk (grade B recommendation).

The decision to offer multifactorial fall prevention interventions to older adults at risk for falls should be individualized based on assessment of potential risks and benefits of these interventions, including circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences (grade C recommendation), the authors wrote.

The exercise intervention could include individual or group activity, although most of the studies in the systematic review involved group exercise, the authors noted.

The recommendation was based on data from a systematic evidence review published in JAMA (2024 Jun 4. doi: 10.1001/jama.2024.4166). The task force reviewed data from 83 randomized trials published between January 1, 2016, and May 8, 2023, deemed fair to good quality that examined six types of fall prevention interventions in a total of 48,839 individuals. Of these, 28 studies involved multifactorial interventions and 27 involved exercise interventions.

Overall, multifactorial interventions and exercise interventions were associated with a significant reduction in falls (incidence rate ratio 0.84 and 0.85, respectively).

Exercise interventions were significantly associated with reduced individual risk of one or more falls and injurious falls, but not with reduced individual risk of injurious falls. However, multifactorial interventions were not significantly associated with reductions in risk of one or more falls, injurious falls, fall-related fractures, individual risk of injurious falls, or individual risk of fall-related fractures.

Although teasing out the specific exercise components that are most effective for fall prevention is challenging, the most commonly studied components associated with reduced risk of falls included gait training, balance training, and functional training, followed by strength and resistance training, the task force noted.

Duration of exercise interventions in the reviewed studies ranged from 2 to 30 months and the most common frequency of sessions was 2 to 3 per week.

Based on these findings, the task force found that exercise had the most consistent benefits for reduced risk across several fall-related outcomes. Although individuals in the studies of multifactorial interventions were at increased risk for falls, the multistep process of interventions to address an individual’s multiple risk factors limited their effectiveness, in part because of logistical challenges and inconsistent adherence, the authors wrote.

The results of the review were limited by several factors, including the focus on studies with a primary or secondary aim of fall prevention, the fact that the recommendation does not apply to many subgroups of older adults, and the lack of data on health outcomes unrelated to falls that were associated with the interventions, the authors noted.

The new recommendation is consistent with and replaces the 2018 USPSTF recommendation on interventions for fall prevention in community-dwelling older adults, but without the recommendation against vitamin D supplementation as a fall prevention intervention. The new recommendation does not address vitamin D use; evidence will be examined in a separate recommendation, the task force wrote.
 

How to Get Older Adults Moving

“The biggest obstacle to exercise is patient inertia and choice to engage in other sedentary activities,” David B. Reuben, MD, and David A. Ganz, MD, both of the University of California, Los Angeles, wrote in an accompanying editorial (JAMA. 2024 Jun 4. doi: 10.1001/jama.2024.9063).

“Given the demonstrated benefits of exercise for cardiovascular disease, cognitive function, and favorable associations with all-cause, cardiovascular, and cancer mortality, specific fall prevention exercise recommendations need to be considered in the context of universal exercise recommendations, including aerobic and muscle strengthening exercise,” the authors wrote. However, maintaining regular exercise is a challenge for many older adults, and more research is needed on factors that drive exercise initiation and adherence in this population, they said.

Multifactorial fall assessments in particular take time, and more fall prevention programs are needed that include multifactorial assessments and interventions, the editorialists said. “Even if primary care clinicians faithfully implement the USPSTF recommendations, a significant reduction in falls and their resulting injuries is still far off,” in part, because of the need for more programs and policies, and the need to improve access to exercise programs and provide insurance coverage for them, they noted.

“Above all, older persons need to be active participants in exercise and reduction of risk factors for falls,” the editorialists concluded.

The research for the recommendation was funded by the Agency for Healthcare Research and Quality (AHRQ). The authors had no financial conflicts to disclose. Dr. Ganz disclosed serving as an author of the 2022 World Guidelines for Falls Prevention and Management for Older Adults.