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Metformin Gets a Reproductive Reprieve — For Diabetic Moms and Dads Alike
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
For decades it’s been thought that preconception use of the oral antidiabetic metformin by mothers and fathers might result in adverse fetal outcomes, including congenital malformations and stillbirths.
Women with type 2 diabetes (T2D) are often advised to switch to insulin before or during early pregnancy out of concern for fetal safety. But two studies from the Harvard T.H. Chan School of Public Health in Boston, Massachusetts — one in mothers, the other in fathers — report that metformin, a common and cost-effective antidiabetic agent, is not associated with a significant increased risk of teratogenicity and negative perinatal outcomes. The studies appear in Annals of Internal Medicine.
The studies may make it easier for physicians to reassure diabetic parents-to-be about the safety of metformin use before conception and in early pregnancy,
In the context of sparse existing safety data, the maternal analysis looked at Medicaid data on 12,489 mothers (mean age, about 30) receiving metformin for pregestational T2D during the period 2000-2018. “Many women become pregnant while still taking noninsulin oral antidiabetics, mostly metformin, and one safety concern is whether metformin could cause birth defects,” lead author Yu-Han Chiu, MD, ScD, an epidemiologist, said in an interview, commenting on the impetus for the study.
“On the one hand, metformin can cross the placenta and might directly affect the fetus. On the other hand, poor blood sugar control is a risk factor for birth defects,” she continued. “Insulin in combination with metformin might control blood sugar better than using insulin alone, which may lower the risk of birth defects.”
Switched to insulin monotherapy or prescribed additional insulin within 90 days of their last menstrual period, mothers were assessed for nonchromosomal fetal malformations and nonlive births, spontaneous abortion, and termination. Continuing metformin or adding insulin to metformin in early pregnancy resulted in little to no increased risk for major malformations in infants.
The estimated risk for nonlive birth was 32.7% with insulin monotherapy and 34.3% with insulin plus metformin polytherapy, for a risk ratio (RR) of 1.02 (95% confidence interval (CI), 1.01-1.04).
In addition, the estimated risk for live birth with congenital malformations was 8.0% (5.70-10.2) under insulin monotherapy and 5.7% under insulin plus metformin (95% CI, 4.5-7.3), amounting to a risk ratio of 0.72 (0.51-1.09).
While the results may involve residual confounding by participants’ glycemic control and body mass index, Dr. Chiu said, “Our findings suggest that the current clinical recommendations to switch from metformin to insulin before pregnancy, due to concerns about birth defects, may require reconsideration.”
She noted that previous trials showed adding metformin to insulin in mid-late pregnancy also improved blood sugar control with no increase in risk of birth defects. “However, most of these studies started treatment too late — between 10 and 34 weeks of pregnancy — to determine if metformin could cause birth defects.”
Observational studies found that women with pregestational diabetes who used noninsulin antidiabetics (mainly metformin) in the first trimester had a lower risk of birth defects, compared with those who used insulin, Dr. Chiu added. “However, comparing metformin with insulin may have some biases because women who used metformin generally have less severe diabetes than those who used insulin.”
Aligning with these reassuring findings, a randomized, placebo-controlled trial reported that adding metformin to insulin did not lead to a higher incidence of neonatal morbidity and mortality and was associated with better maternal glycemic control and reduced maternal weight gain. Metformin-exposed offspring, however, had lower birth weights and a higher incidence of being small for gestational age.
Similarly, a recent Nordic register study of more than 3.7 million infants also found no evidence of an increased risk of major defects with the use of metformin vs insulin in the first trimester.
Despite such reassuring findings, however, Dr. Chiu stressed the need to study other pregnancy and infant outcomes as well as the safety of other oral antidiabetics during pregnancy.
Metformin in Fathers
Turning to fathers, a much larger cohort study by Harvard T.H. Chan investigators looked at the effect of paternal metformin use and also found it to be safe.
The Harvard investigators analyzed diabetic men in 383,851 live births from 1999 to 2020 in an Israeli health fund cohort, excluding those with diabetic spouses. Across different T2D medication groups, paternal age ranged from about 35 to about 43 years. The data revealed that paternal use of metformin monotherapy in the preconception sperm production period was, after adjustment of crude numbers, not associated with major congenital malformations (MCMs) in newborns.
“While metformin has an overall good safety profile, it can lower androgen levels, and there had been some concerns that its use in fathers could alter the sperm, causing adverse effects to the fetus,” lead author and neuroepidemiologist Ran S. Rotem, MD, ScD, of the Harvard School of Public Health, Boston, Massachusetts, said in interview. “Given the increasing prevalence of diabetes in young individuals, more fathers are conceiving a child while using the medication, which could lead to a substantial population effect even if the individual risk is low. But our study suggests that the medication is safe to use by fathers before conception.”
The prevalence of MCMs in the cohort was 4.7% in children of fathers unexposed to diabetes medications (n = 381,041), compared with 6.2% in children of fathers exposed during preconception spermatogenesis to metformin (n = 1730).
By these crude numbers, children with preconception paternal metformin exposure had a nearly 30% increased odds of MCMs. But whereas the crude odds ratio (OR) for MCMs with paternal metformin exposure in all formulations was 1.28 (95% CI, 1.01-1.64), the adjusted OR was 1.00 (95% CI, 0.76 -1.31). Within specific regimens, the adjusted OR was 0.86 (95% CI, 0.60-1.23) for metformin in monotherapy and 1.36 (95% CI, 1.00-1.85) for metformin in polytherapy.
At the outset, Dr. Rotem’s group hypothesized that any crude associations between metformin in polytherapy and birth defects could potentially be explained by poorer underlying parental cardiometabolic risk profiles in those taking multiple diabetes medications. Compared with that of unexposed fathers, the prevalence of cardiometabolic morbidity was indeed substantially higher among both fathers who used metformin during spermatogenesis and their spouses.
In addition, these fathers were more likely to be older, to be smokers, and to have fertility problems. Similarly, mothers were more likely to have cardiovascular comorbidity and to have had fertility problems when the father used metformin.
Moreover, children born to men who used diabetes medications before conception were much more likely to have mothers who also had diabetes and other metabolic conditions, Dr. Rotem noted. “This makes sense since we know that many of these conditions are affected by diet and lifestyle factors that are probably shared across individuals living in the same household.”
Recent research has shown that paternal health and behavior before conception can affect offspring development and long-term health. Characteristics including obesity, diabetes, and metabolic syndrome are seen to affect offspring via complex indirect and direct mechanisms, both genetic and nongenetic.
Doing little to dispel safety concerns, a recent Danish national study reported a link between preconception paternal metformin and major birth defects, particularly genital birth defects in boys. That study, however, lacked data on medication adherence and glycemic control.
“These are well-conducted studies, but it would be useful to see them replicated in different populations, as the sample sizes eligible for analysis are relatively small and some of the confidence intervals are wide,” said Robert W. Platt, PhD, a professor in the departments of Pediatrics and of Epidemiology, Biostatistics, and Occupational Health at McGill University in Montreal, Canada. “However, the results suggest that type 2 diabetics can focus on the most effective treatment pathway for their condition. Metformin does not appear to confer an increased risk of congenital malformations.”
According to an accompanying editorial by Sarah Martins da Silva. MBChB, MD, a reproductive medicine specialist at the University of Dundee in Scotland, the Israeli findings highlight the importance of factoring the sometimes overlooked issue of paternal health into reproductive planning and prenatal care. She stressed that individual risks and benefits should always be carefully considered and results interpreted with caution since such studies lack information on glycemic control. “Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for T2D for men and women trying to conceive as well as for managing hyperglycemia in pregnant women in the first trimester,” she wrote and agreed that it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy.
The studies by Dr. Chiu and Dr. Rotem were funded by the National Institutes of Health. Dr. Chiu and Dr. Rotem had no competing interests to declare. Dr. Hernandez Diaz, a coauthor on both studies, reported funding from Takeda and consulting for Moderna, Johnson & Johnson, and UCB. Several authors reported support from government and not-for-profit research funding agencies. Dr. Platt disclosed no competing interests. Editorial commentator Dr. Martins da Silva disclosed consulting, speaking, travel, and advisory fees from, variously, Dyneval, Ferring Pharmaceutical, Merck, IBSA, and Gedeon Richer.
Metabolic Health Tied to Lower Prediabetes Risk
TOPLINE:
Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.
METHODOLOGY:
- The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
- This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
- Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
- The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
- In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
- In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
- Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.
TAKEAWAY:
- eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
- The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
- The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
- Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.
IN PRACTICE:
The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”
SOURCE:
The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.
LIMITATIONS:
There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.
DISCLOSURES:
The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.
METHODOLOGY:
- The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
- This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
- Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
- The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
- In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
- In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
- Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.
TAKEAWAY:
- eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
- The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
- The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
- Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.
IN PRACTICE:
The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”
SOURCE:
The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.
LIMITATIONS:
There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.
DISCLOSURES:
The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
Whether they have normal weight, overweight, or obesity, individuals with metabolically healthy (MH) phenotypes show a lower frequency of impaired glucose metabolism than their unhealthy counterparts across all weight categories.
METHODOLOGY:
- The concepts of MH overweight and MH obesity refer to a subset of people who exhibit an absence of cardiometabolic risk factors despite excess body fat, but the prevalence of prediabetes has not been investigated by metabolic phenotype and body mass index (BMI).
- This study first validated the use of estimated glucose disposal rate (eGDR), an index of insulin sensitivity calculated from clinical variables, in 350 individuals without diabetes (mean age, 37 years; 219 women; mean BMI, 30.3) from the EUGENE2 project who had varying glucose tolerance values originally assessed by insulin-stimulated glucose disposal.
- Researchers then stratified 2201 participants without diabetes (mean age, 46 years; White; 1290 women; mean BMI, 31.2) from the CATAMERI study according to BMI into three groups — individuals with normal weight (BMI, 18-24.9), overweight (BMI, 25-29.9), and obesity (BMI, ≥ 30).
- The men and women in each BMI group were separated into quartiles of insulin sensitivity based on eGDR index:
- In the normal weight group, men and women were defined as MH in the top three eGDR quartiles and metabolically unhealthy (MU) in the lowest quartile.
- In the overweight and obesity groups, people were defined as MH in the top eGDR quartile and MU in the lower three quartiles.
- Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG+IGT conditions (from an oral glucose tolerance test) were compared in individuals without diabetes based on MH or unhealthy phenotypes across normal weight, overweight, and obese categories.
TAKEAWAY:
- eGDR demonstrated good accuracy in detecting individuals with higher insulin sensitivity in the EUGENE2 cohort.
- The MH overweight and MH obesity groups showed comparable glycemic parameters as the MH normal weight group, whereas the MU overweight and MU obesity groups exhibited higher A1c levels and fasting and 2-hour post-load glucose than the MH normal weight group.
- The frequencies of IFG, IGT, and IFG+IGT conditions were similar among the MH normal weight, MH overweight, and MH obesity groups but were higher in the MU overweight and MU obesity groups than in the MU normal weight group.
- Furthermore, compared with those in the MH normal weight group, the odds of prediabetes were at least two times higher in the MU obesity (odds ratio [OR], 2.54; P < .001) and MU overweight (OR, 2.06; P < .001) groups but not significantly different in the MU normal weight, MH obesity, and MH overweight groups.
IN PRACTICE:
The authors wrote, “Overall, the results of this cross-sectional study support the notion that metabolically healthy individuals with overweight or obesity have a more favorable metabolic risk profile in comparison to metabolically unhealthy subjects with overweight or obesity.”
SOURCE:
The study was conducted by Chiara M.A. Cefalo, MD, department of clinical and molecular medicine, Sapienza University of Rome, Rome, Italy, and was published online in Diabetes, Obesity and Metabolism.
LIMITATIONS:
There was no consensus on the parameters and cutoff values for defining metabolic health status, allowing for potential variations in results. The study design suggested an association with prevalent IFG and IGT conditions but not with incident IFG and IGT conditions. All participants in this study were White, limiting the generalizability of its findings.
DISCLOSURES:
The study was supported by Sapienza University of Rome and the Italian Ministry of University. The authors declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
More and More Are Living With Type 1 Diabetes Into Old Age
TOPLINE:
Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.
METHODOLOGY:
- A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.
TAKEAWAY:
- Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
- The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
- Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
- Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
- Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
- No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
- Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.
IN PRACTICE:
“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”
SOURCE:
The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.
LIMITATIONS:
Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.
DISCLOSURES:
The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.
METHODOLOGY:
- A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.
TAKEAWAY:
- Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
- The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
- Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
- Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
- Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
- No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
- Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.
IN PRACTICE:
“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”
SOURCE:
The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.
LIMITATIONS:
Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.
DISCLOSURES:
The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.
A version of this article first appeared on Medscape.com.
TOPLINE:
Mortality and disability-adjusted life years (DALYs) among people with type 1 diabetes (T1D) aged ≥ 65 years dropped significantly from 1990 to 2019. Both were lower among women and those living in higher sociodemographic areas.
METHODOLOGY:
- A population-based study of adults aged ≥ 65 years from 21 regions and 204 countries and territories, 1990-2019, was conducted.
TAKEAWAY:
- Globally, the prevalence of T1D among people aged ≥ 65 years increased by 180% between 1990 and 2019, from 1.3 million to 3.7 million.
- The proportion of older people with T1D has consistently trended upward, from 12% of all people with T1D in 1990 to 17% in 2019.
- Age-standardized mortality from T1D among this age group significantly decreased by 25%, from 4.7/100,000 population in 1990 to 3.5/100,000 in 2019.
- Age-standardized increases in T1D prevalence have occurred in both men and women worldwide, while the increase was more rapid among men (average annual percent change, 1.00% vs 0.74%).
- Globally, T1D prevalence at least tripled in every age subgroup of those aged ≥ 65 years, and even fivefold to sixfold for those ≥ 90-95 years (0.02-0.11 million for ages 90-94 years; 0.005-0.03 million for ages ≥ 95 years).
- No decreases occurred in T1D prevalence among those aged ≥ 65 years in any of the 21 global regions.
- Three primary risk factors associated with DALYs for T1D among people aged ≥ 65 years were high fasting plasma glucose levels, low temperature, and high temperature, accounting for 103 DALYs per 100,000 people, 3/100,000 people, and 1/100,000 people, respectively, in 2019.
IN PRACTICE:
“The results suggest that T1DM is no longer a contributory factor in decreased life expectancy owing to improvements in medical care over the three decades,” the authors wrote. “Management of high fasting plasma glucose levels remains a major challenge for older people with T1D, and targeted clinical guidelines are needed.”
SOURCE:
The study was conducted by Kaijie Yang, the Department of Endocrinology and Metabolism, the Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, First Hospital of China Medical University, Shenyang, China, and colleagues. The study was published online in the BMJ.
LIMITATIONS:
Data were extrapolated from countries that have epidemiologic data. Health information systems and reporting mechanisms vary across countries and regions. Disease burden data include a time lag. Diagnosing T1D in older people can be challenging.
DISCLOSURES:
The study was supported by the National Natural Science Foundation of China and the China Postdoctoral Science Foundation. The authors reported no additional financial relationships.
A version of this article first appeared on Medscape.com.
Bariatric Surgery Beats GLP-1 RAs in Reducing Mortality Risk
TOPLINE:
Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.
METHODOLOGY:
- There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
- This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
- Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
- The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.
TAKEAWAY:
- Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
- Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
- The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
- Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
- The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.
IN PRACTICE:
“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.
SOURCE:
The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.
LIMITATIONS:
The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.
DISCLOSURES:
The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
TOPLINE:
Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.
METHODOLOGY:
- There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
- This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
- Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
- The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.
TAKEAWAY:
- Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
- Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
- The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
- Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
- The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.
IN PRACTICE:
“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.
SOURCE:
The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.
LIMITATIONS:
The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.
DISCLOSURES:
The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
TOPLINE:
Bariatric metabolic surgery (BMS) offers a survival advantage over glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in adults with obesity and diabetes for 10 years or less, which may be explained by greater weight loss with surgery, new research shows.
METHODOLOGY:
- There is limited evidence regarding the relative effectiveness of BMS and GLP-1 RAs in reducing mortality and major adverse cardiovascular events (MACE).
- This observational, retrospective cohort study analyzed the electronic medical records of Clalit Health Services, Israel’s largest healthcare organization.
- Researchers included patients aged 24 years or older who had diabetes and obesity but no prior cardiovascular disease and who either underwent BMS or received a GLP-1 RA.
- The primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACE, assessed by multivariate competing risk models.
TAKEAWAY:
- Researchers included 3035 matched pairs of patients (total, 6070; mean age, 51 years; 65% women), who were followed for a median of 6.8 years.
- Among patients with diabetes for 10 years or less, those who underwent BMS had a 62% lower risk for mortality than those treated with a GLP-1 RA (hazard ratio [HR], 0.38).
- The survival advantage associated with BMS vs GLP-1 RA may be explained by the greater relative decrease in body mass index in the surgery group (–31.4% vs –12.8%, respectively).
- Among patients with diabetes for more than 10 years, no survival advantage was observed for BMS over GLP-1 RA (HR, 0.65), which may be explained by the adverse effects of prolonged diabetes duration masking the benefit associated with weight loss.
- The risk for nonfatal MACE did not differ significantly between the treatment groups in both diabetes duration categories.
IN PRACTICE:
“This study suggests that BMS was associated with greater reduced mortality compared with GLP-1 RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss,” the authors wrote.
SOURCE:
The study, with first author Dror Dicker, MD, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, was published online in JAMA Network Open.
LIMITATIONS:
The observational design may have introduced residual confounding despite matching and multivariable adjustment. The analyses did not account for the types of BMS or GLP-1 RAs or the level of adherence to GLP-1 RA treatment. Information regarding cause of death was unavailable.
DISCLOSURES:
The study was funded by the Israel Science Foundation. Dicker reported financial relationships with Novo Nordisk, Eli Lilly, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
Psychiatric Comorbidity Tied to Early Mortality in Anorexia
TOPLINE:
Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.
METHODOLOGY:
- Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
- Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
- Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.
TAKEAWAY:
- AN is associated with a 4.5-fold increased mortality risk vs the general population.
- About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
- Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
- Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.
IN PRACTICE:
“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.
SOURCE:
The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.
LIMITATIONS:
The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.
DISCLOSURES:
The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.
METHODOLOGY:
- Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
- Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
- Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.
TAKEAWAY:
- AN is associated with a 4.5-fold increased mortality risk vs the general population.
- About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
- Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
- Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.
IN PRACTICE:
“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.
SOURCE:
The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.
LIMITATIONS:
The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.
DISCLOSURES:
The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
TOPLINE:
Anorexia nervosa (AN) is associated with a 4.5-fold increased risk for mortality — a rate that nearly doubles when AN patients have psychiatric comorbidities.
METHODOLOGY:
- Researchers analyzed data from 14,774 patients diagnosed with AN at age ≥ 6 years from 1977 to 2018.
- Patients were followed-up for a median time of 9.1 years, with some followed-up for ≤ 40 years and matched 1:10 with age- and sex-matched controls.
- Investigators calculated adjusted hazard ratios for mortality, considering psychiatric comorbidity, sex, and age at diagnosis.
TAKEAWAY:
- AN is associated with a 4.5-fold increased mortality risk vs the general population.
- About half of the sample with AN (47%) had a psychiatric comorbidity, which is associated with a 7.7% mortality risk at 10 years.
- Psychiatric comorbidity in anorexia nervosa patients nearly doubles the 10-year mortality risk.
- Suicide was the primary cause of unnatural death (9% died by suicide), and the rate was higher among patients with a psychiatric comorbidity.
IN PRACTICE:
“These findings highlight the crucial need for clinicians to recognize additional mental health disorders in adolescents and adults with anorexia,” author Mette Søeby, MD, Aarhus University/Aarhus University Hospital, in Aarhus, Denmark, said in a press release.
SOURCE:
The study was led by Dr. Søeby and was published online on June 12, 2024, in the International Journal of Eating Disorders.
LIMITATIONS:
The transition from International Classification of Diseases, 8th edition (ICD-8) to ICD-10 and inclusion of outpatient visits may have influenced the study’s results by including more patients with less severe illness. The ICD-10 diagnosis code for anorexia nervosa in Danish registers has not been validated, potentially affecting the accuracy of the study’s findings.
DISCLOSURES:
The study was supported by grants from the Novo Nordic Foundation and The Danish Foundation for Research in Mental Disorders. The authors declared no conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article appeared on Medscape.com.
Walking and Education Plan Improves Low Back Pain in Older Adults
An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.
Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.
In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.
The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.
The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.
The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).
Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.
The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.
More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
Preventive Interventions Need More Real-World Research
“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.
Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.
“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.
They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.
However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.
The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.
An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.
Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.
In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.
The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.
The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.
The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).
Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.
The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.
More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
Preventive Interventions Need More Real-World Research
“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.
Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.
“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.
They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.
However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.
The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.
An intervention combining an individualized walking program and education and significantly reduced low back pain recurrence in adults, compared with controls, based on data from approximately 700 individuals.
Exercise, including walking, is recommended to prevent recurrence of low back pain, but data on the effectiveness and cost-effectiveness of walking as an intervention are lacking, wrote Natasha C. Pocovi, PhD, of Macquarie University, Sydney, Australia, and colleagues.
In a study known as WalkBack, published in the Lancet, the researchers randomized 351 adults aged 18 years and older with a history of more than two prior episodes of low back pain to an intervention and 350 to no intervention.
The intervention consisted of six sessions of education and progressive walking with a physiotherapist over 6 months; both intervention and control groups were followed for a minimum of 12 months and a maximum of 36 months. The mean age of the participants was 54 years, and 81% were female. The primary outcome was the number of days to recurrence of low back pain severe enough to limit activity, based on monthly self-reports.
The intervention was significantly more effective at preventing activity-limiting low back pain recurrence, compared with no intervention (hazard ratio, 0.72; P = .0002), with a median of 208 days and 112 days to recurrence in the intervention and control groups, respectively.
The risk of any low back pain recurrence also was significantly reduced in the intervention group, compared with the controls (HR, 0.80; P = .0066); as was the risk of care-seeking recurrence of low back pain (HR, 0.57; P < .0001).
Overall, the experience of at least one adverse event over 12 months was similar between the intervention and control groups (52% and 54%, respectively), but significantly more adverse events related to lower extremities occurred in the intervention group, compared with the control group (100 vs 54). The intervention also was more likely to be cost effective, compared with a no-treatment control, the researchers wrote.
The findings were limited by several factors including the relatively homogeneous population and that neither the therapists nor participants were masked to group allocation. In addition, the study was conducted during the COVID-19 pandemic, so a telehealth model of video consultations was used instead of in-person meetings, but this protocol change allowed for inclusion of participants from diverse locations including rural and remote areas, the researchers said.
More research is needed to assess the implementation of a walking and exercise intervention as part of a discharge plan after an episode of low back pain and to examine the effectiveness of an intervention involving fewer sessions and a range of healthcare providers, they added. However, the results support the value of the intervention, which has a strong potential for successful implementation because of accessibility and low cost.
Preventive Interventions Need More Real-World Research
“Preventive interventions for back pain are an important yet neglected consideration,” Diarmuid Denneny, a doctoral candidate at Brunel University London, and Jackie Walumbe, PhD, of the University of Oxford (England), wrote in an accompanying editorial.
Although recurrence of low back pain is common, guidance on prevention and management is lacking, they said. Strengths of the current study include attention to patient and public preferences in the study design; however, the majority of the participants were of relatively high socioeconomic status and 89% reported post-secondary education.
“Given that pain is known to have a higher impact on marginalized and minoritized groups and those experiencing socioeconomic deprivation, we recommend caution in extrapolating these findings to different contexts,” the editorialists wrote.
They also cautioned that the complex nature of the intervention, which included not only walking but education and physiotherapist appointments, might make it difficult to isolate walking as the key factor in the patients’ improvement. The editorialists also emphasized the need for studies of similar interventions conducted by alternative providers including exercise professionals and digital platforms.
However, the WalkBack trial represents progress toward greater support for individuals with recurrent back pain and may be a foundation for other research involving how other forms of physical activity compare in improving back pain, with attention to the role of publish health in delivering physical activity interventions, they said.
The study was supported by the National Health and Medical Research Council, Australia. Dr. Pocovi disclosed scholarships funded by the National Health and Medical Research Council Low Back Pain Centre of Research Excellence (ANZBACK) and Macquarie University. Mr. Denneny disclosed support from an Economic and Social Research Council fellowship, and disclosed consulting fees from Live Well with Pain and Leva clinic; a grant from the Chartered Society of Physiotherapy. Dr. Walumbe disclosed travel support from the Chartered Society of Physiotherapy Charitable Trust.
FROM THE LANCET
FDA Approves Skyrizi for Ulcerative Colitis
This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease.
The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.
The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND).
The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.
“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”
For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.
After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release.
Full prescribing information is available online.
A version of this article appeared on Medscape.com.
This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease.
The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.
The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND).
The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.
“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”
For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.
After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release.
Full prescribing information is available online.
A version of this article appeared on Medscape.com.
This approval makes it the first specific anti-interleukin 23 monoclonal antibody indicated for both ulcerative colitis and moderate to severe Crohn’s disease.
The drug is also approved in the United States for the treatment of adults with active psoriatic arthritis and moderate to severe plaque psoriasis.
The safety and efficacy of Skyrizi for ulcerative colitis is supported by data from two phase 3 clinical trials: a 12-week induction study (INSPIRE) and a 52-week maintenance study (COMMAND).
The data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, which was a key secondary endpoint.
“When treating patients with ulcerative colitis, it’s important to prioritize both early and sustained clinical remission as well as endoscopic improvement,” Edward V. Loftus Jr., MD, AGAF, gastroenterologist at Mayo Clinic in Rochester, Minnesota, said in a news release. “This approval for Skyrizi is an important step toward addressing these treatment goals.”
For the treatment of ulcerative colitis, dosing includes a 12-week induction period with three 1200-mg doses delivered every 4 weeks followed by maintenance therapy of either 180 mg or 360 mg delivered every 8 weeks.
After the induction period, Skyrizi treatment can be maintained at home using an on-body injector (OBI). “The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about 5 minutes to deliver the medication following preparation steps,” according to the news release.
Full prescribing information is available online.
A version of this article appeared on Medscape.com.
DLBCL: Glofitamab Plus Chemo Boosts Survival
“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.
“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.
The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).
At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).
“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.
Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
Unmet Need for Accessible Therapies
Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.
“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.
While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.
That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.
To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).
Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).
In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).
The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.
Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.
The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).
Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).
CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.
Other AEs were consistent with the known risks associated with the therapy regimens.
“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.
He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”
Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
Improved Accessibility Vs CAR-T Therapy
Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.
Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.
“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”
However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.
“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”
He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
Long-Term Durability?
Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.
“The major ongoing question with this trial is the long-term durability of remissions,” he said.
“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.
“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.”
Is Chemo Necessary?
Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”
Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.
“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said.
With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”
Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.
“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”
The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.
“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.
“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.
The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).
At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).
“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.
Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
Unmet Need for Accessible Therapies
Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.
“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.
While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.
That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.
To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).
Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).
In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).
The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.
Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.
The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).
Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).
CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.
Other AEs were consistent with the known risks associated with the therapy regimens.
“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.
He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”
Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
Improved Accessibility Vs CAR-T Therapy
Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.
Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.
“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”
However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.
“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”
He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
Long-Term Durability?
Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.
“The major ongoing question with this trial is the long-term durability of remissions,” he said.
“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.
“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.”
Is Chemo Necessary?
Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”
Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.
“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said.
With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”
Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.
“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”
The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.
“Glofitamab is the first CD20xCD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase 3 trial,” said first author Jeremy Abramson, MD, of the Massachusetts General Hospital Cancer Center, Boston, Massachusetts, in a press briefing at the annual meeting of the European Hematology Association (EHA) in Madrid.
“These results support the use of glofitamab GemOx as new, off-the-shelf treatment for relapsed/refractory DLBCL in patients who are transplant ineligible in the second-line or later setting,” he said.
The findings are from the phase 3 STARGLO study involving 274 patients with R/R DLBCL who had previously been treated either with at least two prior lines of therapy, or—if only one prior line of therapy—were determined to be ineligible for autologous stem cell transplant (ASCT).
At a median follow-up of 21 months, those treated with glofitamab combined with GemOx had a significantly higher median overall survival of 25.5 months, compared with those treated with the standard of care of rituximab and GemOx (12.9 months; hazard ratio [HR], 0.62; P = .006).
“The results show a 38% lower risk of death with the glofitamab plus GemOx, compared with [the rituximab regimen],” Dr. Abramson said.
Secondary endpoints showed consistent benefits with the glofitamab regimen, with significant improvements in progression-free survival and complete remission.
Unmet Need for Accessible Therapies
Relapsed/refractory DLBCL, the most common form of non-Hodgkin lymphoma (NHL) in the United States, is an aggressive blood cancer. The standard second-line therapy is high-dose chemotherapy followed by ASCT. However, factors including older age or coexisting medical conditions can compromise response, and those who relapse or are refractory to subsequent therapies have poor outcomes.
“Relapsed DLBCL in the second-line setting or later continues to represent an area of medical need,” Dr. Abramson said.
While several CD20xCD3 bispecific antibody drugs are under development to address the need, glofitamab was the first off-the-shelf, fixed-duration bispecific antibody to receive accelerated approval from the US Food and Drug Administration (FDA) for the treatment of R/R DLBCL, specifically as monotherapy after two or more lines of systemic therapy.
That approval was based on results from a pivotal phase 1/2 study, which showed high rates of deep and durable complete remission with the monotherapy.
To further evaluate glofitamab in combination with GemOx, the authors conducted the multicenter, open-label STARGLO trial, which extended enrollment to patients with just one prior therapy if they were determined to be stem cell transplant ineligible. Patients were also required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Patients were randomized 2:1 either to treatment with glofitamab combined with GemOx, involving 8 cycles, in addition to 4 cycles of glofitamab monotherapy (n = 183), or to the rituximab plus GemOx regimen in 8 cycles (n = 91).
Overall, 153 (55.8%) of patients had primary refractory disease and 166 (60.6%) were refractory to their last therapy. The median age was 68, and 37% had two or more lines of therapy, including some who had received chimeric antigen receptor T-cell (CAR T) therapy (8.8% in the glofitamab group and 7.1% in the rituximab group).
In addition to the significant overall survival benefit, the glofitamab regimen also showed significantly improved progression-free survival at a median follow-up of 16.1 months, as observed by IRC-assessed PFS, with a median progression-free survival rate of 13.8 months vs 3.6 months (HR, 0.40; P < .0001).
The complete remission rate was doubled with glofitamab-GemOx, with a rate of 58.5% vs 25.3%, respectively; P < .0001.
Similar results were observed in subgroups, including relapsed vs refractory patients and those treated as a second or third line of care.
The median number of cycles received was higher among those receiving glofitamab (11 vs four cycles).
Adverse event (AE) rates were higher with glofitamab vs rituximab, including grade 3-4 AEs (69.4 vs 36.4%), grade 5 AEs (8.3 vs 4.5%; primarily driven by an imbalance of COVID-19 AEs), and serious AEs (54.4 vs 17.0%; primarily cytokine release syndrome [CRS]).
CRS was the most frequently reported AE in the glofitamab group (grade 1: 31.4%; grade 2: 10.5%; and grade 3: 2.3%), and events consistent with immune effector cell–associated neurotoxicity syndrome were reported in four patients (2.3%), all of which were concurrent with CRS.
Other AEs were consistent with the known risks associated with the therapy regimens.
“We found that with glofitamab GemOx, the toxicities were manageable, and the most common toxicity of CRS was predominantly low-grade and occurred with step-up dosing in cycle one and was completely reversible,” Dr. Abramson said.
He noted that the higher rate of grade 5 AEs with glofitamab GemOx “was far outweighed by the survival benefit for disease control.”
Overall, “these findings represent the best outcomes observed in a phase 3 trial for relapsed/refractory diffuse large B-cell lymphoma patients who are considered transplant ineligible,” Dr. Abramson said in an interview.
Improved Accessibility Vs CAR-T Therapy
Among key developments in the treatment of R/R DLBCL has been the advent and approval of potentially highly effective CAR T-cell therapy, with the anti-CD19 CAR T cell isiocabtagene maraleucel also FDA approved in the non–transplant eligible DLBCL second-line setting.
Asked in the press briefing about the role of glofitamab GemOx in relation to CAR T cell’s significant benefits, Dr. Abramson underscored the important limitations in CAR T-cell accessibility.
“What I would say is a rising tide lifts all boats,” he responded. “It’s great to have multiple effective immunotherapy strategies.”
However, “CAR T cells of course are not available to most people in the US or worldwide,” he explained.
“They are more difficult to access, they require lymphodepleting chemotherapy, and so ultimately, the majority of patients who could potentially benefit from a CAR T cell probably don’t have access to them in the first place.”
He noted that “the appeal of a regimen like [glofitamab] is that it is an off-the-shelf, targeted immunotherapy combined with a well-tolerated chemotherapy backbone and should be more broadly accessible outside of just tertiary care centers in major cities.”
Long-Term Durability?
Looking ahead, Dr. Abramson noted that a key issue of focus is how long the encouraging results actually last.
“The major ongoing question with this trial is the long-term durability of remissions,” he said.
“Thus far, with a median of 21 months of follow-up for overall survival, the results are encouraging but longer follow-up is needed,” he added.
“Further trials are needed in a broader large B-cell lymphoma population as this trial was limited to DLBCL not otherwise specified, so did not include patients with transformed lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, etc.”
Is Chemo Necessary?
Commenting on the findings, Jonathan W. Friedberg, MD, director of the Wilmot Cancer Institute, University of Rochester School of Medicine, in Rochester, New York, underscored that, “given the overall survival benefit, these findings are clearly clinically significant.”
Noting that “these results add to evidence of high activity of bispecific antibodies in this disease,” Dr. Friedberg speculated on the role of chemotherapy with the therapy.
“Indeed, an important question in this study is whether the addition of chemotherapy to glofitamab is necessary, as high response rates with durable responses in patients who achieve complete remission have been demonstrated with single agent bispecific antibody therapy,” he said.
With the durability of CAR T therapy shown in long-term follow-up of trials to exceed 5 years, Dr. Friedberg added that “it is not known how bispecific antibody therapy, with or without chemotherapy, compares to CAR T-cell therapy and how to sequence CAR T and bispecific antibody therapy.”
Dr. Friedberg agreed that longer-term results are needed get a clearer, fuller picture of the therapy’s effects.
“I have no doubt that the overall survival benefit will endure, but in DLBCL our goal should be cure, and whether glofitamab cures as many patients as CAR T-cell therapy is not currently known and will require further follow-up of this and other trials.”
The study was sponsored by F. Hoffman-La Roche Ltd. Dr. Abramson reported ties with AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar, Caribou Biosciences, Celgene, Genentech, Gilead, Incyte, Interius, Janssen, Lilly, Novartis, F. Hoffmann-La Roche Ltd, Seagen, and Takeda. Dr. Friedberg had no disclosures.
FROM EHA 2024
Should You Offer Medical Credit Cards?
Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.
Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.
Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.
Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.
The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.
The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.
According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.
Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.
Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.
Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.
Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.
Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.
Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.
Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.
Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.
Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.
The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.
The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.
According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.
Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.
Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.
Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.
Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.
Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.
Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Editor’s note: This is Dr. Eastern’s last “Managing Your Practice” column for Dermatology News. After his first column was published in 1986, Dr. Eastern continued writing his column monthly until the mid-1990s, resuming in 2005. In total, he has written over 300 columns on topics relevant to medical practice, ranging from hiring employees, selling and merging practices, complying with OSHA, and avoiding embezzlement, to electronic health records, burnout, medical assistants, negative online reviews, artificial intelligence in the office, and more. In the future, he will continue to provide commentary on practice issues with an occasional guest editorial.
Medicare reimbursement cuts, increasing overhead and staff salaries, and inflation have made running a profitable private practice increasingly challenging, particularly for rural and smaller offices. Medical credit cards are an increasingly popular choice to fill this gap.
Traditionally, these cards were used to help cover procedures insurance didn’t cover — such as cosmetic procedures — but over the years, they have been expanded to cover other healthcare charges, mostly for patients who are paying out of pocket due to inadequate insurance or other reasons.
Advantages for physicians include immediate payment from the credit card company and reduced billing and collection costs. Patients are also less likely to delay or defer treatment if they can charge the payment and pay it back in installments.
The first step in offering medical credit cards is signing up with one or more third-party card companies. CareCredit is the most common provider in the medical credit card market. Other vendors include Wells Fargo, AccessOne, Alphaeon Credit, and iCare Financial. (As always, I have no financial interest in any product or service mentioned in this column.) A member of your staff signs patients up, and the credit card company checks their credit. If approved, the card company pays you your fee and assumes responsibility for collecting from the patient.
The interest charge on medical credit cards is often deferred for a period of time, typically between 6 and 24 months. If patients pay off the debt within this time, they can avoid paying interest. But, like other credit cards, if they make late payments or have an unpaid balance once the promotional period ends, they may end up with interest and fees totaling 25%-30% or more. It is important to make it very clear to your patients that payments are interest-free only if they are all made on time and within the promotional period.
According to a Consumer Financial Protection Bureau report released earlier this year, deferred interest medical credit cards or loans were used to pay nearly $23 billion in healthcare expenses from 2018 to 2020. Individuals unable to complete payment during the promotional period paid $1 billion in deferred interest payments during that period.
Despite the growing popularity of medical credit cards among physicians, it is worth noting that some consumer groups view them as predatory financial products, marketed toward people in tough financial situations. A coalition of 60 health advocacy groups has urged the Biden Administration to ban deferred interest medical credit cards. So there is that much more reason to choose candidates for medical credit cards carefully, and to make them fully aware of what obligations they are assuming.
Patients who do not think they can pay off the balance within the interest-free time frame should probably be advised to pursue an alternative payment method, such as using a conventional credit card, taking out a personal or home-equity loan, or borrowing from a retirement savings account. Some physicians are willing to negotiate a reduced fee for patients who agree to pay cash at the time of service.
Those who do choose to apply for a medical credit card should be informed of their options, which can vary considerably depending on the product and the third-party vendor. Some medical credit products can be used only for elective procedures, but some can be used more broadly for various medical expenses. Check to make sure that each patient’s financing option can be used for his or her desired medical service.
Some payment products can only be used at specific practices or groups, while others can be used at a variety of medical offices and hospitals. If a patient arrives with a medical credit card already in hand, confirm that it is one that your office accepts.
Interest rates generally vary with each card and vendor. Make patients aware of when interest rates start accruing and if the plan offers a fixed or variable APR, or if it charges compounding interest. Confirm if there is a deferred interest option, and if so, for how long.
Different medical credit products also have varying fees and payment schedules. See that each patient reads the terms of the agreement to understand when interest may start to accrue or change, as well as when certain fees may apply. Understanding when the payments are due will help them avoid additional fees, including late fees. Some medical payment plans may also have administrative or processing fees. If so, patients should be made aware of them.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, New Jersey. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Lung Cancer Expert at ASCO: From Fatal to ‘Chronic Disease’
After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.
That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.
Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?
Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.
Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?
Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.
I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.
Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.
That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.
Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.
Question: And you went from being a community oncologist to academic research?
Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.
Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.
In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.
Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.
Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.
Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.
And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.
But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.
And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.
And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.
Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.
This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.
After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.
That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.
Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?
Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.
Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?
Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.
I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.
Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.
That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.
Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.
Question: And you went from being a community oncologist to academic research?
Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.
Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.
In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.
Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.
Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.
Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.
And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.
But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.
And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.
And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.
Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.
This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.
After 20 years in Canada — 7 spent practicing community oncology near Toronto — Dr. Mok was visiting family in his native Hong Kong back in 1996 when a job offer there enabled him to revive his early dream of doing academic research. Dr. Mok and his family moved back home just before the former British colony was returned to China in 1997.
That leap of faith helped Dr. Mok play a role in the global paradigm shift on treating lung cancer. He chairs the department of clinical oncology at the Chinese University of Hong Kong. A leader in ushering in targeted therapies and personalized medicine in China and globally, he has helped advance the goal of transforming lung cancer from a death sentence to a chronic disease.
Among Dr. Mok’s other accomplishments, he has published eight books and more than 200 journal articles. Since 2006, he has been writing a twice-weekly column in the Hong Kong Economic Times. At the annual meeting of the American Society of Clinical Oncology (ASCO), Dr. Mok sat down with this news organization to discuss his latest findings, his career path, and China’s ever-growing presence in multinational clinical trials, pharmaceuticals, and cancer research in general.
Question: At ASCO 2024 in Chicago, you presented as first author of the KRYSTAL-12 study. Can you give a short “elevator speech” summarizing those findings?
Dr. Mok: KRYSTAL-12 is a randomized phase 3 study comparing adagrasib with docetaxel in patients with previously treated advanced/metastatic non–small cell lung cancer harboring a KRAS G12C-mutation. And the findings are positive, with a median progression free survival of 5.5 months vs 3.8 months, with a significant hazard ratio [of 0.58]. And then there are also differences in their response rates of 32% versus 9%, and that gives you an [odds] ratio of 4.86. So yes, it’s significant.
Question: Now that you’ve given this presentation and perhaps taken some good, meaningful questions about it, are there any further points you’d like to make — anything you’d like to add?
Dr. Mok: You have to understand that whatever I said has been scrutinized by the pharmaceutical company, but now I can say whatever I like. I think the key point is that we actually have made the first so-called achievement in the KRAS G12C space. But this is only the beginning.
I want to note that the median progression-free survival is different, but not the best. The median 5.5 months result is good, but not good enough. So, we still have to work hard to answer the question: How can we best deliver care to patients with KRAS G12C?
Question: Speaking more generally about the challenges of targeting KRAS, what issues arise in terms of biomarker testing for KRAS mutations in the clinic? Dr. Mok: In colorectal cancer, there has been testing for KRAS [mutations] for a long, long time. So, most of the laboratories, as long as they are well equipped, will be able to test for KRAS. Usually, the cheaper way is to buy PCR [polymerase chain reaction]. However, these days it’s getting trendier to use NGS [next-generation sequencing]. So, one way or another, specificity is very high. I don’t think we have too much of a problem. The only difference between colorectal cancer and lung cancer is that the tissue sample may not be as good for lung cancer with a small biopsy, but otherwise testing is not an issue.
Question: What clinical trials should oncologist be watching to come into this space?Dr. Mok: There are a lot. Right now, there is the so-called first-line study that’s coming up. So, I can cite you some examples for the KRYSTAL-7 trial, which is the combination of pembrolizumab together with adagrasib in the PD-L1 Tumor Proportion Score ≥ 50%.
That’s one example. And then there is the CodeBreaK 202 trial, which is actually the combination of chemotherapy with sotorasib versus chemotherapy and I-O [immune-oncology]. That is also an ongoing study.
Question: I also want to ask you some background questions about yourself. Back in the day, you lived in Canada and were a community oncologist. Then you made a very big change in your life and moved back home to Hong Kong in 1996, on the eve of its return to China the following year.
Dr. Mok: Well, I was born and raised in Hong Kong, but I left for Canada for education when I was 16 and kind of stayed there and got medical school oncology training and then started my practice. At that time, I never imagined myself going back. But 1996 was a big year. Incidentally, I went back to Hong Kong then to visit my friends and was offered a job at the Chinese University of Hong Kong. Then 1997 was coming. I found it very exciting that we could work with China. So that’s why I decided to return. And this was probably one of my best decisions I ever made in my life.
Question: And you went from being a community oncologist to academic research?
Dr. Mok: Here’s a personal thing that I can share with you: When I finished my oncology training at Princess Margaret Hospital in Toronto, I thought of going into research and becoming an academic. However, my son was born. Household costs went up, and I didn’t want to be a low-income, poor PhD student, so I decided that I may as well go into private practice. Returning to Hong Kong [in 1996] gave me a second chance. I went from being a community oncologist for seven years in Canada to a totally new environment in Hong Kong, where I started my academic work at age 36. It has been a good journey.
Question: Why do you say that was the best decision you ever made?Dr. Mok: At that time, it took me about 2 weeks to make this important decision. Basically: I had to give up my big house and my big car in Canada and move back to a small apartment in Hong Kong. That was a tough decision to make. However, it was a matter of certainty versus uncertainty.
In Canada, I actually had a very stable situation. I had a big practice in the Scarborough area [of Toronto], with a lot of Chinese patients, so I had a better, more comfortable life. It was predictable. But then I asked myself what I would be like in 10 years if I stayed in Canada versus Hong Kong. My answer is that I had no idea what would happen to me 10 years later in Hong Kong. In certain parts of life, you have to decide between certainty and uncertainty. And this time, uncertainty brought me great adventure. I definitely would not have done the things I’ve done if I’d stayed in Canada.
Question: At this ASCO, you’ve spoken primarily about your latest research on non–small cell lung cancer with KRAS G12C mutation.Dr. Mok: Actually, my research has been mostly on targeted therapy. My first break was on the EGFR [epidermal growth factor receptor] mutation. I was one of the first to help define personalized medicine according to the EGFR mutation in the IPASS study [2009]. That’s how I started my academic career.
Question: I read some quotes from your writing some years back about “living with imperfection,” and where you wrote about the whole continuum of cancer research. Years ago, you noted that lung cancer was moving from being a death sentence to becoming a chronic condition.
Dr. Mok: The objective is this: A lot of cancer patients, especially lung cancer patients, had a very short survival, but now we are able to identify a subgroup of patients with a driver oncogene.
And with that, we can use a tyrosine kinase inhibitor — which although it has toxicity, it’s manageable toxicity — such that you can take one pill a day and continue to live a normal life. So that would be not so different from diabetes or hypertension: You live with the disease. So that’s what we like to see: the conversion of a fatal disease into a chronic disease.
Question: So many countries now, including the United States and many others, are facing the challenges of cancer care in rural versus urban areas. Is this a topic you’d be willing to address? Dr. Mok: Well, in Hong Kong we don’t have rural areas! But in China, this is a major problem. There most of the cancer care is focused on the so-called three major cities [Shanghai, Beijing, Guangzhou]. And after that, there are second-tier cities that also have reasonably good care. But when you filter down to the third and fourth layer, the oncology care actually deteriorates. So that’s why we end up with a lot of people from the more rural areas moving and going to the city looking for care and consultation. So yes, the disparity is significant.
But China is a growing country. It takes time to change. Right now, we can see at ASCO this year, there are a lot of investigators from China sharing their new findings, which is a major development, compared to 10 years ago. Therefore, I think that when you have this type of proliferative development, eventually the good care, the high-quality care will filter down to more rural areas. So, at this moment, I think there is still a lot of work to do.
Question: You’ve talked about how oncologists from China are coming up in the field, and this year they have an even greater presence at ASCO, as well as oncologists from elsewhere in Asia, including South Korea, Japan, and Vietnam. You’ve been coming to ASCO for many years. Can you talk about the factors behind China’s increasing presence? Dr. Mok: I think it’s a combination of factors. First of all, I had the honor of working with lung cancer researchers from China from way back, 25 years ago. At that time, we all had nothing. Then with the development of multitargeted therapies, they managed to build up a very good infrastructure for clinical trials. And then, based on that good infrastructure, they were able to do international collaborative studies and provide a supply of patient resources and high-quality data. So, they’ve learned the trick, done a good job, but they cannot have so-called independence until there is a development of pharmaceuticals in China.
And then over the past 10 years, there’s been a proliferation — actually an explosion I would even say — of high-quality pharmaceutical companies in China. First, they’ve got the resources to build the companies. Second, they’ve got the talent resources returning from the United States. So, putting all that together, these were able to go from start-ups to full-fledged functional companies in a very short time.
And with that, they actually sponsored a lot of trials within China. And you can see that putting all the components together: you’ve got high-quality researchers, you’ve got the infrastructure, and now you’ve got your drugs and the money to do the trials. As a result, you’ve got a lot of good data coming from China.
Question: There’s also a population with these mutations.Dr. Mok: That for one, but most have multitargeted therapies, but they also have immunotherapies that have nothing to do with the high incidence. But I think in a sense, in the beginning, they were doing `me-too’ compounds, but now I think they are starting to do ‘me-better’ compounds.
Question: Is there anything you want to say about some of the other presentations that have your name on them at ASCO this year?Dr. Mok: I think the most important one I was engaged in is the CROWN study. The CROWN study is actually a phase 3 study that compares lorlatinib versus crizotinib in patients with advanced, ALK-positive non–small cell lung cancer.
This is a 5-year follow-up, and we were actually able to report an outrageously encouraging 5-year progression-free rate at 60%, meaning that the patient is walking in the door 5 years later when they are on the drug, and 60% of them actually do not have progression, not death, just not progression, just staying on the same pill—which is quite outrageously good for lung cancer.
FROM ASCO 2024