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Mutations missed in early-onset colorectal cancer
As many as one in six patients with early-onset colorectal cancer (CRC) have a pathogenic genetic mutation, but around one-third of these patients may not have met the criteria for genetic testing for at least one of their mutations under current guidelines, researchers say.
Rachel Pearlman, MS, CGC, of The Ohio State University Comprehensive Cancer Center, and her coauthors reported the results of multigene panel testing of 450 patients aged under 50 years, from 51 institutions, who had been diagnosed with CRC (JAMA Oncol 2016 Dec 15. doi: 10.1001/jamaoncol.2016.5194).
Overall, 16% of patients were found to have a pathogenic or likely pathogenic cancer susceptibility gene mutations, with 83.3% having at least one gene mutation.
Thirty-seven patients had Lynch syndrome; 13 were MLH1, 16 were LSH2, 1 patient was MSH2/monoallelic MUTYH; 2 were MSH6, and 5 were PMS2.
“While the prevalence of Lynch syndrome reported herein (8.4%) is consistent with previous publications, this is the first study to our knowledge to determine the prevalence and spectrum of other hereditary cancer syndromes (8%) found in an unselected series of patients with early-onset CRC,” the authors wrote. 
Forty-eight patients (10.7%) had mismatch repair–deficient tumors, nine of which were in high-penetrance genes linked to CRC risk.
But for 145 patients, their genetic variants were of uncertain significance. Thirteen patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC, including ATM, ATM/ CHEK2, BRCA1, BRCA2, CDKN2A, and PALB2.
The authors pointed out that the multigene panel testing approach enables identification of hereditary cancer syndromes in patients who might not have otherwise met the criteria for testing.
“Importantly, 24 of 72 patients (33.3%) with pathogenic mutations did not meet NCCN Guidelines for at least 1 of the gene(s) in which they were found to have a mutation,” the researchers noted. These included three patients with MMR-deficient tumors who had additional mutations in genes that would not have been assessed, one patient with an MMR-proficient tumor who was also found to have Lynch syndrome, and six patients with BRCA1/2 mutations.
“Previous studies have reported early-onset CRC in women with BRCA1 mutations and BRCA2 mutations in families with familial colorectal cancer type X,” they noted.
The Ohio Colorectal Cancer Prevention Initiative (OCCPI) is supported by a grant from Pelotonia, and by the National Cancer Institute. Myriad Genetics Inc. donated next-generation sequencing testing. Nine authors disclosed ties with private industry, including Myriad Genetics.
This study illustrates the shortcomings of current algorithms for diagnosing and managing younger patients with CRC. First, although family history is one of the main components used to stratify an individual’s risk for CRC, it is imperfect because only one in five younger patients with CRC reported having a first-degree relative with CRC. Second, although clinical criteria define the phenotypes typically associated with specific gene mutations, variability in penetrance and expressivity can result in overlap among the different hereditary cancer syndromes (e.g., BRCA germline mutations in younger patients with CRC).
The findings of this large population-based study demonstrate that the incorporation of multigene panel genetic testing in the evaluation of patients with CRC will increase the diagnosis of individuals with genetic predisposition to cancer and will expand current knowledge regarding the associated phenotypes, further supporting the cost-effectiveness of testing that can guide management for patients with cancer and their at-risk relatives. The study found germline mutations in one in six patients with CRC and has argued for comprehensive germline genetic testing of patients diagnosed at younger than 50 years.
Eduardo Vilar-Sanchez, MD, PhD, is in the department of clinical cancer prevention and clinical cancer genetics program at The University of Texas MD Anderson Cancer Center, Houston. Elena M. Stoffel, MD, is in the department of internal medicine at the University of Michigan, Ann Arbor. These comments are adapted from an editorial (JAMA Oncology 2016 Dec 15. doi: 10.1001/jamaoncol.2016.5193). No conflicts of interest were declared.
This study illustrates the shortcomings of current algorithms for diagnosing and managing younger patients with CRC. First, although family history is one of the main components used to stratify an individual’s risk for CRC, it is imperfect because only one in five younger patients with CRC reported having a first-degree relative with CRC. Second, although clinical criteria define the phenotypes typically associated with specific gene mutations, variability in penetrance and expressivity can result in overlap among the different hereditary cancer syndromes (e.g., BRCA germline mutations in younger patients with CRC).
The findings of this large population-based study demonstrate that the incorporation of multigene panel genetic testing in the evaluation of patients with CRC will increase the diagnosis of individuals with genetic predisposition to cancer and will expand current knowledge regarding the associated phenotypes, further supporting the cost-effectiveness of testing that can guide management for patients with cancer and their at-risk relatives. The study found germline mutations in one in six patients with CRC and has argued for comprehensive germline genetic testing of patients diagnosed at younger than 50 years.
Eduardo Vilar-Sanchez, MD, PhD, is in the department of clinical cancer prevention and clinical cancer genetics program at The University of Texas MD Anderson Cancer Center, Houston. Elena M. Stoffel, MD, is in the department of internal medicine at the University of Michigan, Ann Arbor. These comments are adapted from an editorial (JAMA Oncology 2016 Dec 15. doi: 10.1001/jamaoncol.2016.5193). No conflicts of interest were declared.
This study illustrates the shortcomings of current algorithms for diagnosing and managing younger patients with CRC. First, although family history is one of the main components used to stratify an individual’s risk for CRC, it is imperfect because only one in five younger patients with CRC reported having a first-degree relative with CRC. Second, although clinical criteria define the phenotypes typically associated with specific gene mutations, variability in penetrance and expressivity can result in overlap among the different hereditary cancer syndromes (e.g., BRCA germline mutations in younger patients with CRC).
The findings of this large population-based study demonstrate that the incorporation of multigene panel genetic testing in the evaluation of patients with CRC will increase the diagnosis of individuals with genetic predisposition to cancer and will expand current knowledge regarding the associated phenotypes, further supporting the cost-effectiveness of testing that can guide management for patients with cancer and their at-risk relatives. The study found germline mutations in one in six patients with CRC and has argued for comprehensive germline genetic testing of patients diagnosed at younger than 50 years.
Eduardo Vilar-Sanchez, MD, PhD, is in the department of clinical cancer prevention and clinical cancer genetics program at The University of Texas MD Anderson Cancer Center, Houston. Elena M. Stoffel, MD, is in the department of internal medicine at the University of Michigan, Ann Arbor. These comments are adapted from an editorial (JAMA Oncology 2016 Dec 15. doi: 10.1001/jamaoncol.2016.5193). No conflicts of interest were declared.
As many as one in six patients with early-onset colorectal cancer (CRC) have a pathogenic genetic mutation, but around one-third of these patients may not have met the criteria for genetic testing for at least one of their mutations under current guidelines, researchers say.
Rachel Pearlman, MS, CGC, of The Ohio State University Comprehensive Cancer Center, and her coauthors reported the results of multigene panel testing of 450 patients aged under 50 years, from 51 institutions, who had been diagnosed with CRC (JAMA Oncol 2016 Dec 15. doi: 10.1001/jamaoncol.2016.5194).
Overall, 16% of patients were found to have a pathogenic or likely pathogenic cancer susceptibility gene mutations, with 83.3% having at least one gene mutation.
Thirty-seven patients had Lynch syndrome; 13 were MLH1, 16 were LSH2, 1 patient was MSH2/monoallelic MUTYH; 2 were MSH6, and 5 were PMS2.
“While the prevalence of Lynch syndrome reported herein (8.4%) is consistent with previous publications, this is the first study to our knowledge to determine the prevalence and spectrum of other hereditary cancer syndromes (8%) found in an unselected series of patients with early-onset CRC,” the authors wrote.
Forty-eight patients (10.7%) had mismatch repair–deficient tumors, nine of which were in high-penetrance genes linked to CRC risk.
But for 145 patients, their genetic variants were of uncertain significance. Thirteen patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC, including ATM, ATM/ CHEK2, BRCA1, BRCA2, CDKN2A, and PALB2.
The authors pointed out that the multigene panel testing approach enables identification of hereditary cancer syndromes in patients who might not have otherwise met the criteria for testing.
“Importantly, 24 of 72 patients (33.3%) with pathogenic mutations did not meet NCCN Guidelines for at least 1 of the gene(s) in which they were found to have a mutation,” the researchers noted. These included three patients with MMR-deficient tumors who had additional mutations in genes that would not have been assessed, one patient with an MMR-proficient tumor who was also found to have Lynch syndrome, and six patients with BRCA1/2 mutations.
“Previous studies have reported early-onset CRC in women with BRCA1 mutations and BRCA2 mutations in families with familial colorectal cancer type X,” they noted.
The Ohio Colorectal Cancer Prevention Initiative (OCCPI) is supported by a grant from Pelotonia, and by the National Cancer Institute. Myriad Genetics Inc. donated next-generation sequencing testing. Nine authors disclosed ties with private industry, including Myriad Genetics.
As many as one in six patients with early-onset colorectal cancer (CRC) have a pathogenic genetic mutation, but around one-third of these patients may not have met the criteria for genetic testing for at least one of their mutations under current guidelines, researchers say.
Rachel Pearlman, MS, CGC, of The Ohio State University Comprehensive Cancer Center, and her coauthors reported the results of multigene panel testing of 450 patients aged under 50 years, from 51 institutions, who had been diagnosed with CRC (JAMA Oncol 2016 Dec 15. doi: 10.1001/jamaoncol.2016.5194).
Overall, 16% of patients were found to have a pathogenic or likely pathogenic cancer susceptibility gene mutations, with 83.3% having at least one gene mutation.
Thirty-seven patients had Lynch syndrome; 13 were MLH1, 16 were LSH2, 1 patient was MSH2/monoallelic MUTYH; 2 were MSH6, and 5 were PMS2.
“While the prevalence of Lynch syndrome reported herein (8.4%) is consistent with previous publications, this is the first study to our knowledge to determine the prevalence and spectrum of other hereditary cancer syndromes (8%) found in an unselected series of patients with early-onset CRC,” the authors wrote.
Forty-eight patients (10.7%) had mismatch repair–deficient tumors, nine of which were in high-penetrance genes linked to CRC risk.
But for 145 patients, their genetic variants were of uncertain significance. Thirteen patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC, including ATM, ATM/ CHEK2, BRCA1, BRCA2, CDKN2A, and PALB2.
The authors pointed out that the multigene panel testing approach enables identification of hereditary cancer syndromes in patients who might not have otherwise met the criteria for testing.
“Importantly, 24 of 72 patients (33.3%) with pathogenic mutations did not meet NCCN Guidelines for at least 1 of the gene(s) in which they were found to have a mutation,” the researchers noted. These included three patients with MMR-deficient tumors who had additional mutations in genes that would not have been assessed, one patient with an MMR-proficient tumor who was also found to have Lynch syndrome, and six patients with BRCA1/2 mutations.
“Previous studies have reported early-onset CRC in women with BRCA1 mutations and BRCA2 mutations in families with familial colorectal cancer type X,” they noted.
The Ohio Colorectal Cancer Prevention Initiative (OCCPI) is supported by a grant from Pelotonia, and by the National Cancer Institute. Myriad Genetics Inc. donated next-generation sequencing testing. Nine authors disclosed ties with private industry, including Myriad Genetics.
FROM JAMA ONCOLOGY
Key clinical point: As many as one in six patients with early-onset colorectal cancer have a pathogenic genetic mutation but around one-third of these patients may not have met the criteria for genetic testing for at least one of their mutations, under current guidelines.
Major finding: 16% of patients with early-onset colorectal cancer were found to have a pathogenic or likely pathogenic cancer susceptibility gene mutation.
Data source: Cohort study of 450 patients aged under 50 years diagnosed with colorectal cancer.
Disclosures: The Ohio Colorectal Cancer Prevention Initiative (OCCPI) is supported by a grant from Pelotonia, and by the National Cancer Institute. Myriad Genetics Inc. donated next-generation sequencing testing. Nine authors disclosed ties with private industry, including Myriad Genetics.
Anxiety, poverty contribute to depression in at-risk children
Fear and anxiety, economic disadvantage, and recent psychosocial adversity contribute significantly to the onset of major depressive disorder in children and adolescents with a strong family history of the condition.
A 4-year longitudinal study followed the offspring of 279 families in which one parent had experienced at least two episodes of major depressive disorder (MDD) and in which there was a biologically related child living with that index parent.
Fear and anxiety showed a strong and significant association with new-onset major depressive disorder, as did irritability. Furthermore, the association between the two symptoms was low but significant, suggesting that they do not often co-occur (JAMA Psychiatry. 2016 Dec 7. doi: 10.1001/jamapsychiatry.2016.3140).
“The results suggested that generalized anxiety symptoms were driving the predictive effect of fear/anxiety on new-onset MDD and that fear/anxiety (and not irritability) predicted an especially early MDD onset,” wrote Frances Rice, PhD, of the division of psychological medicine and clinical neurosciences at Cardiff University, Wales, and coauthors.
Recent psychosocial adversity – stressful events such as the death of a friend, illness, bullying, or parents fighting – also showed a strong association with new-onset major depressive disorder, while economic disadvantage had a lesser but still significant contribution. Both of these also were associated with fear and anxiety, and irritability.
Greater family history and more severe parental depression also contributed significantly to the emergence of depression in the offspring, although those factors were not associated with the clinical antecedents such as fear and anxiety.
“Therefore, the indicators of social risk predicted MDD independent of correlated familial risk, parental depression severity, and clinical antecedents in the child,” the authors wrote. “This result has important implications for treatment and prevention and highlights the need to resolve not only clinical phenomena in the child but also wider contextual difficulties.”
The study also suggested that neither disruptive behavior nor low mood were significantly associated with new-onset MDD in children and adolescents.
The children and adolescents in the study had a mean of 1.85 DSM-IV major depressive disorder symptoms at follow-up, and 20 of them – six males and 14 females – had new-onset MDD, with a mean age of onset of 14.4 years.
“Our findings suggest that primary prevention methods for depression in groups with high familial risk will need to include effective treatment of parental depression, irritability, and fear/anxiety in the child and consider social risk factors,” Dr. Rice and her coauthors wrote.
The research and researchers were supported by the Sir Jules Thorn Charitable Trust, the Medical Research Council, the Economic and Social Research Council, the British Academy, and the British Medical Association. No conflicts of interest were declared.
Fear and anxiety, economic disadvantage, and recent psychosocial adversity contribute significantly to the onset of major depressive disorder in children and adolescents with a strong family history of the condition.
A 4-year longitudinal study followed the offspring of 279 families in which one parent had experienced at least two episodes of major depressive disorder (MDD) and in which there was a biologically related child living with that index parent.
Fear and anxiety showed a strong and significant association with new-onset major depressive disorder, as did irritability. Furthermore, the association between the two symptoms was low but significant, suggesting that they do not often co-occur (JAMA Psychiatry. 2016 Dec 7. doi: 10.1001/jamapsychiatry.2016.3140).
“The results suggested that generalized anxiety symptoms were driving the predictive effect of fear/anxiety on new-onset MDD and that fear/anxiety (and not irritability) predicted an especially early MDD onset,” wrote Frances Rice, PhD, of the division of psychological medicine and clinical neurosciences at Cardiff University, Wales, and coauthors.
Recent psychosocial adversity – stressful events such as the death of a friend, illness, bullying, or parents fighting – also showed a strong association with new-onset major depressive disorder, while economic disadvantage had a lesser but still significant contribution. Both of these also were associated with fear and anxiety, and irritability.
Greater family history and more severe parental depression also contributed significantly to the emergence of depression in the offspring, although those factors were not associated with the clinical antecedents such as fear and anxiety.
“Therefore, the indicators of social risk predicted MDD independent of correlated familial risk, parental depression severity, and clinical antecedents in the child,” the authors wrote. “This result has important implications for treatment and prevention and highlights the need to resolve not only clinical phenomena in the child but also wider contextual difficulties.”
The study also suggested that neither disruptive behavior nor low mood were significantly associated with new-onset MDD in children and adolescents.
The children and adolescents in the study had a mean of 1.85 DSM-IV major depressive disorder symptoms at follow-up, and 20 of them – six males and 14 females – had new-onset MDD, with a mean age of onset of 14.4 years.
“Our findings suggest that primary prevention methods for depression in groups with high familial risk will need to include effective treatment of parental depression, irritability, and fear/anxiety in the child and consider social risk factors,” Dr. Rice and her coauthors wrote.
The research and researchers were supported by the Sir Jules Thorn Charitable Trust, the Medical Research Council, the Economic and Social Research Council, the British Academy, and the British Medical Association. No conflicts of interest were declared.
Fear and anxiety, economic disadvantage, and recent psychosocial adversity contribute significantly to the onset of major depressive disorder in children and adolescents with a strong family history of the condition.
A 4-year longitudinal study followed the offspring of 279 families in which one parent had experienced at least two episodes of major depressive disorder (MDD) and in which there was a biologically related child living with that index parent.
Fear and anxiety showed a strong and significant association with new-onset major depressive disorder, as did irritability. Furthermore, the association between the two symptoms was low but significant, suggesting that they do not often co-occur (JAMA Psychiatry. 2016 Dec 7. doi: 10.1001/jamapsychiatry.2016.3140).
“The results suggested that generalized anxiety symptoms were driving the predictive effect of fear/anxiety on new-onset MDD and that fear/anxiety (and not irritability) predicted an especially early MDD onset,” wrote Frances Rice, PhD, of the division of psychological medicine and clinical neurosciences at Cardiff University, Wales, and coauthors.
Recent psychosocial adversity – stressful events such as the death of a friend, illness, bullying, or parents fighting – also showed a strong association with new-onset major depressive disorder, while economic disadvantage had a lesser but still significant contribution. Both of these also were associated with fear and anxiety, and irritability.
Greater family history and more severe parental depression also contributed significantly to the emergence of depression in the offspring, although those factors were not associated with the clinical antecedents such as fear and anxiety.
“Therefore, the indicators of social risk predicted MDD independent of correlated familial risk, parental depression severity, and clinical antecedents in the child,” the authors wrote. “This result has important implications for treatment and prevention and highlights the need to resolve not only clinical phenomena in the child but also wider contextual difficulties.”
The study also suggested that neither disruptive behavior nor low mood were significantly associated with new-onset MDD in children and adolescents.
The children and adolescents in the study had a mean of 1.85 DSM-IV major depressive disorder symptoms at follow-up, and 20 of them – six males and 14 females – had new-onset MDD, with a mean age of onset of 14.4 years.
“Our findings suggest that primary prevention methods for depression in groups with high familial risk will need to include effective treatment of parental depression, irritability, and fear/anxiety in the child and consider social risk factors,” Dr. Rice and her coauthors wrote.
The research and researchers were supported by the Sir Jules Thorn Charitable Trust, the Medical Research Council, the Economic and Social Research Council, the British Academy, and the British Medical Association. No conflicts of interest were declared.
FROM JAMA PSYCHIATRY
Key clinical point:
Major finding: Fear and anxiety, psychosocial adversity, economic disadvantage, and stronger family history showed a strong and significant association with new-onset major depressive disorder..
Data source: Longitudinal cohort study of the offspring of 279 families in which one parent had experienced at least two episodes of major depressive disorder.
Disclosures: The research and researchers were supported by the Sir Jules Thorn Charitable Trust, the Medical Research Council, the Economic and Social Research Council, the British Academy, and the British Medical Association. No conflicts of interest were declared.
Abortion denial increases short-term anxiety, depression
Women denied an abortion appear to experience more psychological problems in the short term, compared with women who are able to access the procedure, according to findings published in JAMA Psychiatry.
The prospective, longitudinal Turnaway Study involved regular follow-up telephone interviews of 956 women recruited from 30 abortion facilities in 21 states. Of these women, 273 received abortions in the first trimester, 452 received abortions just under the facility’s gestational limit, 161 sought an abortion but were turned away because they were just past the limit and later gave birth (turnaway-births), and 70 were turned away but either miscarried or obtained an abortion elsewhere (turnaway-no-births).
At 1 week after seeking an abortion, women denied an abortion reported significantly more anxiety symptoms (turnaway-births, coefficient 0.57; 95% CI, 0.01 to 1.13; turnaway-no-births, 2.29; 95% CI, 1.39 to 3.18) and lower self-esteem (turnaway-births, –0.33; 95% CI, –0.56 to –0.09; turnaway-no-births, –0.40; 95% CI, –0.78 to –0.02), compared with women who received abortions near the gestational limit.
Similarly, women denied abortions experienced lower life satisfaction at 1 week (turnaway-births, –0.16; 95% CI, –0.38 to 0.06; turnaway-no-births, –0.41; 95% CI, –0.77 to –0.06).
The study found that levels of depression were similar between the abortion and no-abortion groups in the first week, and depression levels also declined significantly over time in all groups except among women who were turned away for an abortion and later gave birth (JAMA Psychiatry. 2016 Dec 14. doi: 10.1001/jamapsychiatry.2016.3478).
“Our findings add to the body of evidence rejecting the notion that abortion increases women’s risk of experiencing adverse psychological outcomes,” wrote M. Antonia Biggs, PhD, of the Bixby Center for Global Reproductive Health at the University of California, San Francisco, and her coauthors. “Women who had an abortion demonstrated more positive outcomes initially compared with women who were denied an abortion.”
At the last follow-up, 5-6 years after the seeking of an abortion, the differences in mental well-being between women who had received an abortion and those who had not had all but disappeared.
“These initial elevated levels of distress experienced by both turnaway groups may be a response to being denied an abortion, as well as other social and emotional challenges faced on discovery of unwanted pregnancy and abortion seeking,” the researchers wrote.
Of all the groups, women who were initially denied an abortion but later miscarried or received an abortion elsewhere showed the most elevated levels of anxiety and lowest self-esteem and life satisfaction 1 week after being denied an abortion. Women in the turnaway-no-birth group may have had higher levels of stress because they were trying to find and travel to another abortion facility, or to raise extra money to pay for the procedure, the researchers noted.
Given these study findings, there is no evidence to justify laws requiring women seeking abortion to be warned about negative psychological responses, according to the researchers. “Women considering abortion are best served by being provided with the most accurate, scientific information available to help them make their pregnancy decisions,” they wrote.
The study was supported by grants from the Wallace Alexander Gerbode Foundation, the David and Lucile Packard Foundation, the William and Flora Hewlett Foundation, and an anonymous foundation. The researchers reported having no relevant financial disclosures.
Women denied an abortion appear to experience more psychological problems in the short term, compared with women who are able to access the procedure, according to findings published in JAMA Psychiatry.
The prospective, longitudinal Turnaway Study involved regular follow-up telephone interviews of 956 women recruited from 30 abortion facilities in 21 states. Of these women, 273 received abortions in the first trimester, 452 received abortions just under the facility’s gestational limit, 161 sought an abortion but were turned away because they were just past the limit and later gave birth (turnaway-births), and 70 were turned away but either miscarried or obtained an abortion elsewhere (turnaway-no-births).
At 1 week after seeking an abortion, women denied an abortion reported significantly more anxiety symptoms (turnaway-births, coefficient 0.57; 95% CI, 0.01 to 1.13; turnaway-no-births, 2.29; 95% CI, 1.39 to 3.18) and lower self-esteem (turnaway-births, –0.33; 95% CI, –0.56 to –0.09; turnaway-no-births, –0.40; 95% CI, –0.78 to –0.02), compared with women who received abortions near the gestational limit.
Similarly, women denied abortions experienced lower life satisfaction at 1 week (turnaway-births, –0.16; 95% CI, –0.38 to 0.06; turnaway-no-births, –0.41; 95% CI, –0.77 to –0.06).
The study found that levels of depression were similar between the abortion and no-abortion groups in the first week, and depression levels also declined significantly over time in all groups except among women who were turned away for an abortion and later gave birth (JAMA Psychiatry. 2016 Dec 14. doi: 10.1001/jamapsychiatry.2016.3478).
“Our findings add to the body of evidence rejecting the notion that abortion increases women’s risk of experiencing adverse psychological outcomes,” wrote M. Antonia Biggs, PhD, of the Bixby Center for Global Reproductive Health at the University of California, San Francisco, and her coauthors. “Women who had an abortion demonstrated more positive outcomes initially compared with women who were denied an abortion.”
At the last follow-up, 5-6 years after the seeking of an abortion, the differences in mental well-being between women who had received an abortion and those who had not had all but disappeared.
“These initial elevated levels of distress experienced by both turnaway groups may be a response to being denied an abortion, as well as other social and emotional challenges faced on discovery of unwanted pregnancy and abortion seeking,” the researchers wrote.
Of all the groups, women who were initially denied an abortion but later miscarried or received an abortion elsewhere showed the most elevated levels of anxiety and lowest self-esteem and life satisfaction 1 week after being denied an abortion. Women in the turnaway-no-birth group may have had higher levels of stress because they were trying to find and travel to another abortion facility, or to raise extra money to pay for the procedure, the researchers noted.
Given these study findings, there is no evidence to justify laws requiring women seeking abortion to be warned about negative psychological responses, according to the researchers. “Women considering abortion are best served by being provided with the most accurate, scientific information available to help them make their pregnancy decisions,” they wrote.
The study was supported by grants from the Wallace Alexander Gerbode Foundation, the David and Lucile Packard Foundation, the William and Flora Hewlett Foundation, and an anonymous foundation. The researchers reported having no relevant financial disclosures.
Women denied an abortion appear to experience more psychological problems in the short term, compared with women who are able to access the procedure, according to findings published in JAMA Psychiatry.
The prospective, longitudinal Turnaway Study involved regular follow-up telephone interviews of 956 women recruited from 30 abortion facilities in 21 states. Of these women, 273 received abortions in the first trimester, 452 received abortions just under the facility’s gestational limit, 161 sought an abortion but were turned away because they were just past the limit and later gave birth (turnaway-births), and 70 were turned away but either miscarried or obtained an abortion elsewhere (turnaway-no-births).
At 1 week after seeking an abortion, women denied an abortion reported significantly more anxiety symptoms (turnaway-births, coefficient 0.57; 95% CI, 0.01 to 1.13; turnaway-no-births, 2.29; 95% CI, 1.39 to 3.18) and lower self-esteem (turnaway-births, –0.33; 95% CI, –0.56 to –0.09; turnaway-no-births, –0.40; 95% CI, –0.78 to –0.02), compared with women who received abortions near the gestational limit.
Similarly, women denied abortions experienced lower life satisfaction at 1 week (turnaway-births, –0.16; 95% CI, –0.38 to 0.06; turnaway-no-births, –0.41; 95% CI, –0.77 to –0.06).
The study found that levels of depression were similar between the abortion and no-abortion groups in the first week, and depression levels also declined significantly over time in all groups except among women who were turned away for an abortion and later gave birth (JAMA Psychiatry. 2016 Dec 14. doi: 10.1001/jamapsychiatry.2016.3478).
“Our findings add to the body of evidence rejecting the notion that abortion increases women’s risk of experiencing adverse psychological outcomes,” wrote M. Antonia Biggs, PhD, of the Bixby Center for Global Reproductive Health at the University of California, San Francisco, and her coauthors. “Women who had an abortion demonstrated more positive outcomes initially compared with women who were denied an abortion.”
At the last follow-up, 5-6 years after the seeking of an abortion, the differences in mental well-being between women who had received an abortion and those who had not had all but disappeared.
“These initial elevated levels of distress experienced by both turnaway groups may be a response to being denied an abortion, as well as other social and emotional challenges faced on discovery of unwanted pregnancy and abortion seeking,” the researchers wrote.
Of all the groups, women who were initially denied an abortion but later miscarried or received an abortion elsewhere showed the most elevated levels of anxiety and lowest self-esteem and life satisfaction 1 week after being denied an abortion. Women in the turnaway-no-birth group may have had higher levels of stress because they were trying to find and travel to another abortion facility, or to raise extra money to pay for the procedure, the researchers noted.
Given these study findings, there is no evidence to justify laws requiring women seeking abortion to be warned about negative psychological responses, according to the researchers. “Women considering abortion are best served by being provided with the most accurate, scientific information available to help them make their pregnancy decisions,” they wrote.
The study was supported by grants from the Wallace Alexander Gerbode Foundation, the David and Lucile Packard Foundation, the William and Flora Hewlett Foundation, and an anonymous foundation. The researchers reported having no relevant financial disclosures.
FROM JAMA PSYCHIATRY
Key clinical point:
Major finding: After 1 week, women denied an abortion reported significantly more anxiety symptoms, lower self-esteem, and lower life satisfaction than did women who received abortions.
Data source: Prospective longitudinal study in 956 women requesting abortions at 30 facilities across the United States.
Disclosures: The study was supported by grants from the Wallace Alexander Gerbode Foundation, the David and Lucile Packard Foundation, the William and Flora Hewlett Foundation, and an anonymous foundation. The researchers reported having no relevant financial disclosures.
Telephone calls improve long-term follow-up after hernia repair
Follow-up telephone calls can significantly improve the collection of long-term patient-reported outcomes following ventral hernia repair, according to a study published online in the Oct. 20 edition of the Journal of the American College of Surgeons.
Nishant Ganesh Kumar, a medical student, and his colleagues at Vanderbilt University, Nashville, Tenn., wrote that while ventral hernia repair is one of the most common surgical procedures in the world, reliable long-term, prospective data on outcomes has been extremely difficult to collect.
In this Plan-Do-Study-Act (PDSA) prospective study, 99 patients who had undergone ventral hernia repair were followed up by telephone, in addition to the usual email communication, 1 year after their procedure. The calls were initially made between 1:00 p.m. and 3:00 p.m. in the first phase of the study, then changed to after 3:00 p.m. in the second phase.
Compared to the long-term completion rate of 16.3% prior to the intervention – where follow-up was largely through physical clinical visits – researchers saw a completion rate of 35.7% with the telephone calls between 1:00 p.m. and 3:00 p.m., and a 55.1% completion rate after changing the call time to after 3:00 p.m. The mean participation rate was 45.4%.
Once contact was made, all the patients completed the full patient-reported outcomes assessment, although the researchers did note that some seem to experience fatigue during questioning that required the interviewers to gently steer them back to the questions.
“The advantage of making phone calls was severalfold, including clarification of survey questions to help patients with providing more insightful responses, allaying concerns of patients, and personalizing long-term follow-up, a crucial aspect missing through automated surveys,” the authors wrote.
In addition to changing the time in which the calls were made, the researchers also changed how the survey was introduced to the patients, such as referring to the survey as “follow-up,” which seemed to improve patient participation.
“Further, it was observed that during conversations with the patient, highlighting relevant features of their medical and surgical history, such as the date of the surgery, the surgeon who operated on them, and their disease progression since surgery helped in developing a rapport with the patient and increased the chances of their participation,” they reported. “With these approaches, the participation rate after the second PDSA cycle increased to 55.1%.”
The data analyses in the study were supported by the Americas Hernia Society Quality Collaborative. There were no disclosures relevant to the study.
Follow-up telephone calls can significantly improve the collection of long-term patient-reported outcomes following ventral hernia repair, according to a study published online in the Oct. 20 edition of the Journal of the American College of Surgeons.
Nishant Ganesh Kumar, a medical student, and his colleagues at Vanderbilt University, Nashville, Tenn., wrote that while ventral hernia repair is one of the most common surgical procedures in the world, reliable long-term, prospective data on outcomes has been extremely difficult to collect.
In this Plan-Do-Study-Act (PDSA) prospective study, 99 patients who had undergone ventral hernia repair were followed up by telephone, in addition to the usual email communication, 1 year after their procedure. The calls were initially made between 1:00 p.m. and 3:00 p.m. in the first phase of the study, then changed to after 3:00 p.m. in the second phase.
Compared to the long-term completion rate of 16.3% prior to the intervention – where follow-up was largely through physical clinical visits – researchers saw a completion rate of 35.7% with the telephone calls between 1:00 p.m. and 3:00 p.m., and a 55.1% completion rate after changing the call time to after 3:00 p.m. The mean participation rate was 45.4%.
Once contact was made, all the patients completed the full patient-reported outcomes assessment, although the researchers did note that some seem to experience fatigue during questioning that required the interviewers to gently steer them back to the questions.
“The advantage of making phone calls was severalfold, including clarification of survey questions to help patients with providing more insightful responses, allaying concerns of patients, and personalizing long-term follow-up, a crucial aspect missing through automated surveys,” the authors wrote.
In addition to changing the time in which the calls were made, the researchers also changed how the survey was introduced to the patients, such as referring to the survey as “follow-up,” which seemed to improve patient participation.
“Further, it was observed that during conversations with the patient, highlighting relevant features of their medical and surgical history, such as the date of the surgery, the surgeon who operated on them, and their disease progression since surgery helped in developing a rapport with the patient and increased the chances of their participation,” they reported. “With these approaches, the participation rate after the second PDSA cycle increased to 55.1%.”
The data analyses in the study were supported by the Americas Hernia Society Quality Collaborative. There were no disclosures relevant to the study.
Follow-up telephone calls can significantly improve the collection of long-term patient-reported outcomes following ventral hernia repair, according to a study published online in the Oct. 20 edition of the Journal of the American College of Surgeons.
Nishant Ganesh Kumar, a medical student, and his colleagues at Vanderbilt University, Nashville, Tenn., wrote that while ventral hernia repair is one of the most common surgical procedures in the world, reliable long-term, prospective data on outcomes has been extremely difficult to collect.
In this Plan-Do-Study-Act (PDSA) prospective study, 99 patients who had undergone ventral hernia repair were followed up by telephone, in addition to the usual email communication, 1 year after their procedure. The calls were initially made between 1:00 p.m. and 3:00 p.m. in the first phase of the study, then changed to after 3:00 p.m. in the second phase.
Compared to the long-term completion rate of 16.3% prior to the intervention – where follow-up was largely through physical clinical visits – researchers saw a completion rate of 35.7% with the telephone calls between 1:00 p.m. and 3:00 p.m., and a 55.1% completion rate after changing the call time to after 3:00 p.m. The mean participation rate was 45.4%.
Once contact was made, all the patients completed the full patient-reported outcomes assessment, although the researchers did note that some seem to experience fatigue during questioning that required the interviewers to gently steer them back to the questions.
“The advantage of making phone calls was severalfold, including clarification of survey questions to help patients with providing more insightful responses, allaying concerns of patients, and personalizing long-term follow-up, a crucial aspect missing through automated surveys,” the authors wrote.
In addition to changing the time in which the calls were made, the researchers also changed how the survey was introduced to the patients, such as referring to the survey as “follow-up,” which seemed to improve patient participation.
“Further, it was observed that during conversations with the patient, highlighting relevant features of their medical and surgical history, such as the date of the surgery, the surgeon who operated on them, and their disease progression since surgery helped in developing a rapport with the patient and increased the chances of their participation,” they reported. “With these approaches, the participation rate after the second PDSA cycle increased to 55.1%.”
The data analyses in the study were supported by the Americas Hernia Society Quality Collaborative. There were no disclosures relevant to the study.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Key clinical point: Follow-up telephone calls can significantly improve the collection of long-term patient-reported outcomes following ventral hernia repair.
Major finding: Compared to the long-term completion rate of 16.3% prior to the intervention, a telephone call follow-up increased the mean participation rate to 45.4%.
Data source: Prospective cohort study of 99 patients who underwent ventral hernia repair.
Disclosures: The data analyses in the study were supported by the Americas Hernia Society Quality Collaborative. There were no disclosures relevant to the study.
Azathioprine linked to increased risk of SCC in transplant recipients
Immunosuppressive treatment with azathioprine may be associated with an increased risk of squamous cell carcinoma in organ transplant recipients, but does not appear to increase the risk of basal cell carcinoma or keratinocyte cancers overall, according to a systematic review and meta-analysis of 27 studies.
While immunosuppressive agents generally are known to contribute to an increased risk of skin carcinogenesis, azathioprine – a purine antimetabolite immunosuppressant – is thought to add to this increase through its photosensitizing effects and the accumulation of mutagenic reactive oxygen species when exposed to UVA.
To address conflicting data on whether azathioprine increases the risk of skin cancer, the authors conducted the analysis of 27 studies (23 cohort studies, 1 randomized study, and 3 case control studies) published between 1996 and 2011, which evaluated skin cancer risk associated with azathioprine in people who received an organ transplant from 1963 to 2011, at a median age of 38-54 years.
In the studies that evaluated the risk of squamous cell carcinoma, risk was elevated by 56% among patients treated with azathioprine (95% CI 1.11-2.18, P less than .001), but estimates ranged from 0.64 to 8.64. The risk was sevenfold higher in two case-control studies combined, but was not significant in eight cohort studies, reported Zainab Jiyad, MD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia, and St. George’s University of London, and coauthors. They noted that there was significant heterogeneity between the studies, probably because of differences in study design, organ transplant type, and period of transplantation (Am J Transplant. 2016 Dec;16[12]:3490-503).
“Despite the substantial heterogeneity, which would tend to dilute the observed summary risk estimate, a significant effect of azathioprine was detected,” they added. “Thus, we acknowledge that our summary estimate may be a conservative estimate of the risk associated with azathioprine.”
The subgroup analysis comparing the risk among kidney and heart transplant recipients showed the increased risk of squamous cell carcinoma was significant among kidney transplant recipients but not among heart transplant recipients.
Among the six cohort studies that evaluated the risk of basal cell carcinoma, the risk was increased in four studies, while two suggested that azathioprine was actually protective against it. When the studies were pooled, the estimated risk was 0.96.
Similarly, when researchers looked at studies of keratinocyte cancers (the combined risk of squamous cell and basal cell cancers), there was no significant association with overall risk of KC.
Older age and transplantation, fair skin type, high sun exposure, childhood sunburn, a history of skin cancer, and rejection episodes in the first year of transplantation were all risk factors for developing squamous cell carcinoma. Therefore, avoiding azathioprine in organ transplant recipients “with one or more of these risk factors may help reduce the future risk” of squamous cell cancer, they wrote.
The authors added that more high quality studies were needed and that studies should evaluate the risk of squamous cell and basal cell cancer separately, because of the apparent difference in risk.
No conflicts of interest were declared.
Immunosuppressive treatment with azathioprine may be associated with an increased risk of squamous cell carcinoma in organ transplant recipients, but does not appear to increase the risk of basal cell carcinoma or keratinocyte cancers overall, according to a systematic review and meta-analysis of 27 studies.
While immunosuppressive agents generally are known to contribute to an increased risk of skin carcinogenesis, azathioprine – a purine antimetabolite immunosuppressant – is thought to add to this increase through its photosensitizing effects and the accumulation of mutagenic reactive oxygen species when exposed to UVA.
To address conflicting data on whether azathioprine increases the risk of skin cancer, the authors conducted the analysis of 27 studies (23 cohort studies, 1 randomized study, and 3 case control studies) published between 1996 and 2011, which evaluated skin cancer risk associated with azathioprine in people who received an organ transplant from 1963 to 2011, at a median age of 38-54 years.
In the studies that evaluated the risk of squamous cell carcinoma, risk was elevated by 56% among patients treated with azathioprine (95% CI 1.11-2.18, P less than .001), but estimates ranged from 0.64 to 8.64. The risk was sevenfold higher in two case-control studies combined, but was not significant in eight cohort studies, reported Zainab Jiyad, MD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia, and St. George’s University of London, and coauthors. They noted that there was significant heterogeneity between the studies, probably because of differences in study design, organ transplant type, and period of transplantation (Am J Transplant. 2016 Dec;16[12]:3490-503).
“Despite the substantial heterogeneity, which would tend to dilute the observed summary risk estimate, a significant effect of azathioprine was detected,” they added. “Thus, we acknowledge that our summary estimate may be a conservative estimate of the risk associated with azathioprine.”
The subgroup analysis comparing the risk among kidney and heart transplant recipients showed the increased risk of squamous cell carcinoma was significant among kidney transplant recipients but not among heart transplant recipients.
Among the six cohort studies that evaluated the risk of basal cell carcinoma, the risk was increased in four studies, while two suggested that azathioprine was actually protective against it. When the studies were pooled, the estimated risk was 0.96.
Similarly, when researchers looked at studies of keratinocyte cancers (the combined risk of squamous cell and basal cell cancers), there was no significant association with overall risk of KC.
Older age and transplantation, fair skin type, high sun exposure, childhood sunburn, a history of skin cancer, and rejection episodes in the first year of transplantation were all risk factors for developing squamous cell carcinoma. Therefore, avoiding azathioprine in organ transplant recipients “with one or more of these risk factors may help reduce the future risk” of squamous cell cancer, they wrote.
The authors added that more high quality studies were needed and that studies should evaluate the risk of squamous cell and basal cell cancer separately, because of the apparent difference in risk.
No conflicts of interest were declared.
Immunosuppressive treatment with azathioprine may be associated with an increased risk of squamous cell carcinoma in organ transplant recipients, but does not appear to increase the risk of basal cell carcinoma or keratinocyte cancers overall, according to a systematic review and meta-analysis of 27 studies.
While immunosuppressive agents generally are known to contribute to an increased risk of skin carcinogenesis, azathioprine – a purine antimetabolite immunosuppressant – is thought to add to this increase through its photosensitizing effects and the accumulation of mutagenic reactive oxygen species when exposed to UVA.
To address conflicting data on whether azathioprine increases the risk of skin cancer, the authors conducted the analysis of 27 studies (23 cohort studies, 1 randomized study, and 3 case control studies) published between 1996 and 2011, which evaluated skin cancer risk associated with azathioprine in people who received an organ transplant from 1963 to 2011, at a median age of 38-54 years.
In the studies that evaluated the risk of squamous cell carcinoma, risk was elevated by 56% among patients treated with azathioprine (95% CI 1.11-2.18, P less than .001), but estimates ranged from 0.64 to 8.64. The risk was sevenfold higher in two case-control studies combined, but was not significant in eight cohort studies, reported Zainab Jiyad, MD, of QIMR Berghofer Medical Research Institute in Brisbane, Australia, and St. George’s University of London, and coauthors. They noted that there was significant heterogeneity between the studies, probably because of differences in study design, organ transplant type, and period of transplantation (Am J Transplant. 2016 Dec;16[12]:3490-503).
“Despite the substantial heterogeneity, which would tend to dilute the observed summary risk estimate, a significant effect of azathioprine was detected,” they added. “Thus, we acknowledge that our summary estimate may be a conservative estimate of the risk associated with azathioprine.”
The subgroup analysis comparing the risk among kidney and heart transplant recipients showed the increased risk of squamous cell carcinoma was significant among kidney transplant recipients but not among heart transplant recipients.
Among the six cohort studies that evaluated the risk of basal cell carcinoma, the risk was increased in four studies, while two suggested that azathioprine was actually protective against it. When the studies were pooled, the estimated risk was 0.96.
Similarly, when researchers looked at studies of keratinocyte cancers (the combined risk of squamous cell and basal cell cancers), there was no significant association with overall risk of KC.
Older age and transplantation, fair skin type, high sun exposure, childhood sunburn, a history of skin cancer, and rejection episodes in the first year of transplantation were all risk factors for developing squamous cell carcinoma. Therefore, avoiding azathioprine in organ transplant recipients “with one or more of these risk factors may help reduce the future risk” of squamous cell cancer, they wrote.
The authors added that more high quality studies were needed and that studies should evaluate the risk of squamous cell and basal cell cancer separately, because of the apparent difference in risk.
No conflicts of interest were declared.
FROM THE AMERICAN JOURNAL OF TRANSPLANTATION
Key clinical point: Immunosuppressive treatment with azathioprine may be associated with an increased risk of squamous cell carcinoma but not basal cell carcinoma.
Major finding: Patients treated with azathioprine after an organ transplant had a 56% increased risk of squamous cell carcinoma.
Data source: A systematic review and meta-analysis of 27 studies that evaluated the risk of skin cancer in organ transplant recipients treated with azathioprine.
Disclosures: The authors had no conflicts of interest to disclose.
Rosacea improved with fractional microneedling radiofrequency therapy
Fractional microneedling radiofrequency (FMR) therapy resulted in modest but clinically significant improvements in the appearance and inflammation of rosacea in a small study of patients with mild to moderate rosacea.
The treatment delivers bipolar radiofrequency energy to the dermis via an array of microneedles, without damaging the epidermis, noted Seon Yong Park, MD, and colleagues from the department of dermatology at Seoul (South Korea) National University. It has previously been associated with clinical and histological improvements in acne-associated postinflammatory erythema and is used in the treatment of cutaneous wrinkles. The authors said that, as far as they know, this is the first study to evaluate the use of FMR in patients with rosacea.
In the prospective, single-blind, randomized, split-face clinical study, 21 patients (20 females, 1 male) with mild to moderate rosacea were treated with two FMR sessions, 4 weeks apart, then assessed 4, 8, and 12 weeks after the second session. The mean age of the patients was 43 years; they had Fitzpatrick skin type III (13 patients) or IV (8 patients), and rosacea was considered mild in 12 patients and moderate in 9 patients at baseline.
Researchers saw clinical improvements in 17 (81%) of the patients on the treated side; these patients had a mean improvement in the Investigator’s Global Assessment (IGA) score of 2.47 by week 12, representing about a 20% improvement (Dermatol Surg. 2016 Dec;42[12]:1362-9).
In the group overall, mean IGA scores at weeks 4, 8, and 12 were 1.05, 1.57, and 2.00 for the treated side, compared with 0.29, 0.38, and 0.38, respectively, for the untreated side, which, the authors wrote, indicated that “there was modest but statistically significant improvements in the treated side.”
Photometric measurements of redness showed significant reductions on the treated side, compared with the untreated side and baseline, with reductions in the erythema index of 11.9%, 10.7%, and 13.6% at week 4, 8, and 12, respectively.
Histological assessment showed reduced dermal inflammation, significant reductions in average mast cell count, and an overall decrease in immunohistochemical intensity in the treated skin 8 weeks after treatment. Similarly, there were significant decreases in markers of angiogenesis, inflammation, innate immunity, and neuroimmunity on the treated side, compared with baseline.
“Fractional microneedling radiofrequency was slightly more effective in reducing erythema in patients with PPR [papulopustular rosacea] than in those with ETR [erythematotelangiectatic rosacea], suggesting that inflammatory lesions, such as papules and pustules, could be more effectively treated with this device,” the authors wrote. “This result agreed with reports showing that FMR is effective in treating inflammatory acne.”
No serious adverse effects were reported, although 19 patients (90.5%) experienced mild pain during the procedure and 17 (81%) had mild erythema that lasted for up to 5 days. Patients also reported less itching, heat, burning, or pricking on the treated side, which showed that the treatment was effective in controlling the symptoms of rosacea, Dr. Park and associates said.
The study was supported by the SNUH Research Fund and National Research Foundation of Korea. The authors, who are also in the acne and rosacea research laboratory, Seoul National University Hospital, had no conflicts to disclose.
Fractional microneedling radiofrequency (FMR) therapy resulted in modest but clinically significant improvements in the appearance and inflammation of rosacea in a small study of patients with mild to moderate rosacea.
The treatment delivers bipolar radiofrequency energy to the dermis via an array of microneedles, without damaging the epidermis, noted Seon Yong Park, MD, and colleagues from the department of dermatology at Seoul (South Korea) National University. It has previously been associated with clinical and histological improvements in acne-associated postinflammatory erythema and is used in the treatment of cutaneous wrinkles. The authors said that, as far as they know, this is the first study to evaluate the use of FMR in patients with rosacea.
In the prospective, single-blind, randomized, split-face clinical study, 21 patients (20 females, 1 male) with mild to moderate rosacea were treated with two FMR sessions, 4 weeks apart, then assessed 4, 8, and 12 weeks after the second session. The mean age of the patients was 43 years; they had Fitzpatrick skin type III (13 patients) or IV (8 patients), and rosacea was considered mild in 12 patients and moderate in 9 patients at baseline.
Researchers saw clinical improvements in 17 (81%) of the patients on the treated side; these patients had a mean improvement in the Investigator’s Global Assessment (IGA) score of 2.47 by week 12, representing about a 20% improvement (Dermatol Surg. 2016 Dec;42[12]:1362-9).
In the group overall, mean IGA scores at weeks 4, 8, and 12 were 1.05, 1.57, and 2.00 for the treated side, compared with 0.29, 0.38, and 0.38, respectively, for the untreated side, which, the authors wrote, indicated that “there was modest but statistically significant improvements in the treated side.”
Photometric measurements of redness showed significant reductions on the treated side, compared with the untreated side and baseline, with reductions in the erythema index of 11.9%, 10.7%, and 13.6% at week 4, 8, and 12, respectively.
Histological assessment showed reduced dermal inflammation, significant reductions in average mast cell count, and an overall decrease in immunohistochemical intensity in the treated skin 8 weeks after treatment. Similarly, there were significant decreases in markers of angiogenesis, inflammation, innate immunity, and neuroimmunity on the treated side, compared with baseline.
“Fractional microneedling radiofrequency was slightly more effective in reducing erythema in patients with PPR [papulopustular rosacea] than in those with ETR [erythematotelangiectatic rosacea], suggesting that inflammatory lesions, such as papules and pustules, could be more effectively treated with this device,” the authors wrote. “This result agreed with reports showing that FMR is effective in treating inflammatory acne.”
No serious adverse effects were reported, although 19 patients (90.5%) experienced mild pain during the procedure and 17 (81%) had mild erythema that lasted for up to 5 days. Patients also reported less itching, heat, burning, or pricking on the treated side, which showed that the treatment was effective in controlling the symptoms of rosacea, Dr. Park and associates said.
The study was supported by the SNUH Research Fund and National Research Foundation of Korea. The authors, who are also in the acne and rosacea research laboratory, Seoul National University Hospital, had no conflicts to disclose.
Fractional microneedling radiofrequency (FMR) therapy resulted in modest but clinically significant improvements in the appearance and inflammation of rosacea in a small study of patients with mild to moderate rosacea.
The treatment delivers bipolar radiofrequency energy to the dermis via an array of microneedles, without damaging the epidermis, noted Seon Yong Park, MD, and colleagues from the department of dermatology at Seoul (South Korea) National University. It has previously been associated with clinical and histological improvements in acne-associated postinflammatory erythema and is used in the treatment of cutaneous wrinkles. The authors said that, as far as they know, this is the first study to evaluate the use of FMR in patients with rosacea.
In the prospective, single-blind, randomized, split-face clinical study, 21 patients (20 females, 1 male) with mild to moderate rosacea were treated with two FMR sessions, 4 weeks apart, then assessed 4, 8, and 12 weeks after the second session. The mean age of the patients was 43 years; they had Fitzpatrick skin type III (13 patients) or IV (8 patients), and rosacea was considered mild in 12 patients and moderate in 9 patients at baseline.
Researchers saw clinical improvements in 17 (81%) of the patients on the treated side; these patients had a mean improvement in the Investigator’s Global Assessment (IGA) score of 2.47 by week 12, representing about a 20% improvement (Dermatol Surg. 2016 Dec;42[12]:1362-9).
In the group overall, mean IGA scores at weeks 4, 8, and 12 were 1.05, 1.57, and 2.00 for the treated side, compared with 0.29, 0.38, and 0.38, respectively, for the untreated side, which, the authors wrote, indicated that “there was modest but statistically significant improvements in the treated side.”
Photometric measurements of redness showed significant reductions on the treated side, compared with the untreated side and baseline, with reductions in the erythema index of 11.9%, 10.7%, and 13.6% at week 4, 8, and 12, respectively.
Histological assessment showed reduced dermal inflammation, significant reductions in average mast cell count, and an overall decrease in immunohistochemical intensity in the treated skin 8 weeks after treatment. Similarly, there were significant decreases in markers of angiogenesis, inflammation, innate immunity, and neuroimmunity on the treated side, compared with baseline.
“Fractional microneedling radiofrequency was slightly more effective in reducing erythema in patients with PPR [papulopustular rosacea] than in those with ETR [erythematotelangiectatic rosacea], suggesting that inflammatory lesions, such as papules and pustules, could be more effectively treated with this device,” the authors wrote. “This result agreed with reports showing that FMR is effective in treating inflammatory acne.”
No serious adverse effects were reported, although 19 patients (90.5%) experienced mild pain during the procedure and 17 (81%) had mild erythema that lasted for up to 5 days. Patients also reported less itching, heat, burning, or pricking on the treated side, which showed that the treatment was effective in controlling the symptoms of rosacea, Dr. Park and associates said.
The study was supported by the SNUH Research Fund and National Research Foundation of Korea. The authors, who are also in the acne and rosacea research laboratory, Seoul National University Hospital, had no conflicts to disclose.
FROM DERMATOLOGIC SURGERY
Key clinical point: Fractional microneedling radiofrequency therapy may achieve modest but clinically significant improvements in the appearance and inflammation of rosacea.
Major finding: Fractional microneedling radiofrequency therapy was associated with clinical improvements in 81% of treated patients.
Data source: A prospective, single-blind, randomized, split-face clinical trial in 21 patients with mild to moderate rosacea.
Disclosures: The study was supported by the SNUH Research Fund and National Research Foundation of Korea. No conflicts of interest were declared.
Halogenated anesthetic linked to less chronic postop mastectomy pain
The use of halogenated agents for anesthetic during a mastectomy operation may be associated with a lower incidence of long-term chronic postmastectomy pain (CPMP), according to a paper published in the the Journal of Clinical Anesthesia.
The retrospective cross-sectional survey of 128 women who underwent mastectomy with axillary lymph node dissection set out to determine whether the anesthetic or analgesic regimen used perioperatively had any impact on the risk of long-term chronic postoperative pain.
Overall, 43.8% of the women reported chronic pain, and nearly half of these showed neuropathic characteristics with an ID Pain score greater than or equal to 2 (J Clin Anesthesia. 2016;33:20-25. doi: 10.1016/j.jclinane.2015.07.010).
Those who were given a halogenated agent for anesthesia during the operation – 64% of patients in the survey - had a significant 19% lower incidence of chronic long-term postoperative mastectomy pain (95% CI, 0.70-0.95; P = .012).
Arnaud Steyaert, MD, and colleagues at the Catholic University of Louvain (Belgium) described this result as surprising, noting that sevoflurane use was recently found to be a risk factor for chronic pain after breast cancer surgery.
“An explanation for this discrepancy could be that the influence of sevoflurane on the development of CPMP depends on the other components of the anesthetic regimen,” the authors wrote, pointing out that the aforementioned study included the use of remifentanil in all patients, which can trigger acute opioid-induced hyperalgesia and chronic pain after surgery.
Apart from this effect, the authors said they did not see any impact from other analgesics – which included sufentanil, ketamine, clonidine, NSAIDs, and/or magnesium sulfate – on the risk of long-term chronic pain. However, patients treated with piritramide in the recovery room did have a significant 30% greater risk of chronic postoperative pain.
The study also found that patients who needed strong opioids in the postanesthesia care unit had a 30% higher risk of chronic long-term pain (95% CI, 1.11-1.53). “This was expected, as more intense acute postoperative pain is a known risk factor for developing chronic postsurgical pain, including CPMP,” the authors wrote.
Patients who had received adjuvant chemotherapy had a 32% higher incidence of chronic long-term pain, but there was no increase in risk associated with adjuvant radiotherapy. Both are known to cause neurotoxicity and therefore neuropathic pain, the authors commented.
No conflicts of interest were declared.
The use of halogenated agents for anesthetic during a mastectomy operation may be associated with a lower incidence of long-term chronic postmastectomy pain (CPMP), according to a paper published in the the Journal of Clinical Anesthesia.
The retrospective cross-sectional survey of 128 women who underwent mastectomy with axillary lymph node dissection set out to determine whether the anesthetic or analgesic regimen used perioperatively had any impact on the risk of long-term chronic postoperative pain.
Overall, 43.8% of the women reported chronic pain, and nearly half of these showed neuropathic characteristics with an ID Pain score greater than or equal to 2 (J Clin Anesthesia. 2016;33:20-25. doi: 10.1016/j.jclinane.2015.07.010).
Those who were given a halogenated agent for anesthesia during the operation – 64% of patients in the survey - had a significant 19% lower incidence of chronic long-term postoperative mastectomy pain (95% CI, 0.70-0.95; P = .012).
Arnaud Steyaert, MD, and colleagues at the Catholic University of Louvain (Belgium) described this result as surprising, noting that sevoflurane use was recently found to be a risk factor for chronic pain after breast cancer surgery.
“An explanation for this discrepancy could be that the influence of sevoflurane on the development of CPMP depends on the other components of the anesthetic regimen,” the authors wrote, pointing out that the aforementioned study included the use of remifentanil in all patients, which can trigger acute opioid-induced hyperalgesia and chronic pain after surgery.
Apart from this effect, the authors said they did not see any impact from other analgesics – which included sufentanil, ketamine, clonidine, NSAIDs, and/or magnesium sulfate – on the risk of long-term chronic pain. However, patients treated with piritramide in the recovery room did have a significant 30% greater risk of chronic postoperative pain.
The study also found that patients who needed strong opioids in the postanesthesia care unit had a 30% higher risk of chronic long-term pain (95% CI, 1.11-1.53). “This was expected, as more intense acute postoperative pain is a known risk factor for developing chronic postsurgical pain, including CPMP,” the authors wrote.
Patients who had received adjuvant chemotherapy had a 32% higher incidence of chronic long-term pain, but there was no increase in risk associated with adjuvant radiotherapy. Both are known to cause neurotoxicity and therefore neuropathic pain, the authors commented.
No conflicts of interest were declared.
The use of halogenated agents for anesthetic during a mastectomy operation may be associated with a lower incidence of long-term chronic postmastectomy pain (CPMP), according to a paper published in the the Journal of Clinical Anesthesia.
The retrospective cross-sectional survey of 128 women who underwent mastectomy with axillary lymph node dissection set out to determine whether the anesthetic or analgesic regimen used perioperatively had any impact on the risk of long-term chronic postoperative pain.
Overall, 43.8% of the women reported chronic pain, and nearly half of these showed neuropathic characteristics with an ID Pain score greater than or equal to 2 (J Clin Anesthesia. 2016;33:20-25. doi: 10.1016/j.jclinane.2015.07.010).
Those who were given a halogenated agent for anesthesia during the operation – 64% of patients in the survey - had a significant 19% lower incidence of chronic long-term postoperative mastectomy pain (95% CI, 0.70-0.95; P = .012).
Arnaud Steyaert, MD, and colleagues at the Catholic University of Louvain (Belgium) described this result as surprising, noting that sevoflurane use was recently found to be a risk factor for chronic pain after breast cancer surgery.
“An explanation for this discrepancy could be that the influence of sevoflurane on the development of CPMP depends on the other components of the anesthetic regimen,” the authors wrote, pointing out that the aforementioned study included the use of remifentanil in all patients, which can trigger acute opioid-induced hyperalgesia and chronic pain after surgery.
Apart from this effect, the authors said they did not see any impact from other analgesics – which included sufentanil, ketamine, clonidine, NSAIDs, and/or magnesium sulfate – on the risk of long-term chronic pain. However, patients treated with piritramide in the recovery room did have a significant 30% greater risk of chronic postoperative pain.
The study also found that patients who needed strong opioids in the postanesthesia care unit had a 30% higher risk of chronic long-term pain (95% CI, 1.11-1.53). “This was expected, as more intense acute postoperative pain is a known risk factor for developing chronic postsurgical pain, including CPMP,” the authors wrote.
Patients who had received adjuvant chemotherapy had a 32% higher incidence of chronic long-term pain, but there was no increase in risk associated with adjuvant radiotherapy. Both are known to cause neurotoxicity and therefore neuropathic pain, the authors commented.
No conflicts of interest were declared.
FROM THE JOURNAL OF CLINICAL ANESTHESIA
Key clinical point: The use of halogenated agents for anesthetic during a mastectomy operation may be associated with a lower incidence of long-term chronic postmastectomy pain.
Major finding: Patients given a halogenated agent for anesthesia during a mastectomy had a significant 19% lower incidence of chronic long-term postoperative mastectomy pain.
Data source: A retrospective cross-sectional survey.
Disclosures: No conflicts of interest were declared.
RSV is top cause of severe respiratory disease in preterm infants
Respiratory syncytial virus is the number one virus causing severe lower respiratory disease in preterm infants, while those of younger age and those exposed to young children are at greatest risk, Eric A. F. Simões, MD, of the University of Colorado at Denver, Aurora, and his coauthors reported in the Nov. 29 edition of PLOS ONE.
“These data demonstrate that higher risk for 32 to 35 wGA [weeks gestational age] infants can be easily identified by age or birth month and significant exposure to other young children,” they wrote. “These infants would benefit from targeted efforts to prevent severe RSV disease.”
The overall rates of lower respiratory infections per 100 infant-seasons – a season being 5 months of observation from November 1 to March 31 in 2009-2010 or 2010-2011 – were 13.7 for respiratory syncytial virus (RSV), 2.9 for adenovirus, 1.7 for parainfluenza virus type 2, 1.3 for human metapneumovirus, and 0.3 for parainfluenza virus type 2 (PLoS One. 2016 Nov 29. doi: 10.1371/journal.pone.0166226).
Infants who had been exposed to young children, either through attending day care or living with non–multiple birth preschool-age siblings, had a twofold higher risk of RSV and human metapneumovirus, and a 3.3-fold greater risk of adenovirus.
The youngest infants showed the highest rate of hospitalizations with RSV: the incidence ranged from 8.2 per 100 infant season in those aged less than 1 month to 2.3 per 100 infant seasons in those aged 10 months of age. Similarly, the incidence of admission to ICU was significantly higher among younger infants.
Infants born in May, before the RSV season, had a much lower incidence of hospitalization, compared with those born in the height of RSV season in February. ICU admission rates also were higher among those born in February, compared with those born in May.
The highest overall rates of hospitalization with RSV – 19 per 100 infant-seasons – were among those born in February, and also those who were exposed to other young children.
“The current results are unique in that they provide continuous age-based risk models for outpatient and inpatient disease for infants with and without young child exposure,” wrote Dr. Simões and his coauthors.
They argued that their findings refute earlier suggestions that the rate of RSV infection in preterm infants is similar to the rate in term infants, and suggested that the limitations of their study may have even underestimated the incidence in preterm babies.
The study was supported by AstraZeneca, parent company of MedImmune. Two authors declared grant support and research funding from AstraZeneca, one author was a former employee of AstraZeneca, one author was a former employee of MedImmune and now contractor to AstraZeneca. One author was a current employee of AstraZeneca and holds stock options. Two authors also declared funding and consultancies with AbbVie.
Respiratory syncytial virus is the number one virus causing severe lower respiratory disease in preterm infants, while those of younger age and those exposed to young children are at greatest risk, Eric A. F. Simões, MD, of the University of Colorado at Denver, Aurora, and his coauthors reported in the Nov. 29 edition of PLOS ONE.
“These data demonstrate that higher risk for 32 to 35 wGA [weeks gestational age] infants can be easily identified by age or birth month and significant exposure to other young children,” they wrote. “These infants would benefit from targeted efforts to prevent severe RSV disease.”
The overall rates of lower respiratory infections per 100 infant-seasons – a season being 5 months of observation from November 1 to March 31 in 2009-2010 or 2010-2011 – were 13.7 for respiratory syncytial virus (RSV), 2.9 for adenovirus, 1.7 for parainfluenza virus type 2, 1.3 for human metapneumovirus, and 0.3 for parainfluenza virus type 2 (PLoS One. 2016 Nov 29. doi: 10.1371/journal.pone.0166226).
Infants who had been exposed to young children, either through attending day care or living with non–multiple birth preschool-age siblings, had a twofold higher risk of RSV and human metapneumovirus, and a 3.3-fold greater risk of adenovirus.
The youngest infants showed the highest rate of hospitalizations with RSV: the incidence ranged from 8.2 per 100 infant season in those aged less than 1 month to 2.3 per 100 infant seasons in those aged 10 months of age. Similarly, the incidence of admission to ICU was significantly higher among younger infants.
Infants born in May, before the RSV season, had a much lower incidence of hospitalization, compared with those born in the height of RSV season in February. ICU admission rates also were higher among those born in February, compared with those born in May.
The highest overall rates of hospitalization with RSV – 19 per 100 infant-seasons – were among those born in February, and also those who were exposed to other young children.
“The current results are unique in that they provide continuous age-based risk models for outpatient and inpatient disease for infants with and without young child exposure,” wrote Dr. Simões and his coauthors.
They argued that their findings refute earlier suggestions that the rate of RSV infection in preterm infants is similar to the rate in term infants, and suggested that the limitations of their study may have even underestimated the incidence in preterm babies.
The study was supported by AstraZeneca, parent company of MedImmune. Two authors declared grant support and research funding from AstraZeneca, one author was a former employee of AstraZeneca, one author was a former employee of MedImmune and now contractor to AstraZeneca. One author was a current employee of AstraZeneca and holds stock options. Two authors also declared funding and consultancies with AbbVie.
Respiratory syncytial virus is the number one virus causing severe lower respiratory disease in preterm infants, while those of younger age and those exposed to young children are at greatest risk, Eric A. F. Simões, MD, of the University of Colorado at Denver, Aurora, and his coauthors reported in the Nov. 29 edition of PLOS ONE.
“These data demonstrate that higher risk for 32 to 35 wGA [weeks gestational age] infants can be easily identified by age or birth month and significant exposure to other young children,” they wrote. “These infants would benefit from targeted efforts to prevent severe RSV disease.”
The overall rates of lower respiratory infections per 100 infant-seasons – a season being 5 months of observation from November 1 to March 31 in 2009-2010 or 2010-2011 – were 13.7 for respiratory syncytial virus (RSV), 2.9 for adenovirus, 1.7 for parainfluenza virus type 2, 1.3 for human metapneumovirus, and 0.3 for parainfluenza virus type 2 (PLoS One. 2016 Nov 29. doi: 10.1371/journal.pone.0166226).
Infants who had been exposed to young children, either through attending day care or living with non–multiple birth preschool-age siblings, had a twofold higher risk of RSV and human metapneumovirus, and a 3.3-fold greater risk of adenovirus.
The youngest infants showed the highest rate of hospitalizations with RSV: the incidence ranged from 8.2 per 100 infant season in those aged less than 1 month to 2.3 per 100 infant seasons in those aged 10 months of age. Similarly, the incidence of admission to ICU was significantly higher among younger infants.
Infants born in May, before the RSV season, had a much lower incidence of hospitalization, compared with those born in the height of RSV season in February. ICU admission rates also were higher among those born in February, compared with those born in May.
The highest overall rates of hospitalization with RSV – 19 per 100 infant-seasons – were among those born in February, and also those who were exposed to other young children.
“The current results are unique in that they provide continuous age-based risk models for outpatient and inpatient disease for infants with and without young child exposure,” wrote Dr. Simões and his coauthors.
They argued that their findings refute earlier suggestions that the rate of RSV infection in preterm infants is similar to the rate in term infants, and suggested that the limitations of their study may have even underestimated the incidence in preterm babies.
The study was supported by AstraZeneca, parent company of MedImmune. Two authors declared grant support and research funding from AstraZeneca, one author was a former employee of AstraZeneca, one author was a former employee of MedImmune and now contractor to AstraZeneca. One author was a current employee of AstraZeneca and holds stock options. Two authors also declared funding and consultancies with AbbVie.
FROM PLOS ONE
Key clinical point: Respiratory syncytial virus is the leading viral cause of severe lower respiratory disease in preterm infants, with those of younger age and those exposed to young children at greatest risk.
Major finding: The rates of lower respiratory infections per 100 infant-seasons were 13.7 for RSV, 2.9 for adenovirus, 1.7 for parainfluenza virus type 2, and 1.3 for human metapneumovirus.
Data source: The prospective RSV Respiratory Events Among Preterm Infants Outcomes and Risk Tracking (REPORT) study, in 1,642 preterm infants with medically attended acute respiratory illness.
Disclosures: The study was supported by AstraZeneca, parent company of MedImmune. Two authors declared grant support and research funding from AstraZeneca, one author was a former employee of AstraZeneca, and one author was a former employee of MedImmune and now contractor to AstraZeneca. One author was a current employee of AstraZeneca and holds stock options. Two authors also declared funding and consultancies with AbbVie.
Biosimilar trastuzumab shows similar efficacy
A trastuzumab biosimilar drug has shown an equivalent response, compared with trastuzumab, in the treatment of ERBB2 (HER2)-positive metastatic breast cancer, according to the results of a randomized double-blind controlled trial.
The anti-ERBB2 humanized monoclonal antibody trastuzumab in combination with chemotherapy has been found in numerous trials to significantly improve progression-free survival and overall survival in women with ERBB2-positive metastatic breast, compared with chemotherapy alone.
“With impending patent expiration of some biological agents, development of biosimilars has become a high priority for drug developers and health authorities throughout the world to provide access to high-quality alternatives,” the authors wrote. “A biosimilar drug is a biological product that is highly similar to a licensed biological product, with no clinically meaningful differences in terms of safety, purity, or potency.”
In a phase III multicenter trial, 500 women with ERBB2 (HER2)-positive metastatic breast cancer, recruited from 95 sites in Europe, Africa, South America, and Asia, were randomized 1:1 to intravenous infusions of trastuzumab or a biosimilar labeled MYL-1401O, with both arms also receiving taxane therapy.
At 24 weeks, the overall response rate (ORR) was not significantly different between the biosimilar and trastuzumab groups (69.6% vs. 64.0%; ORR ratio, 1.09; 90% confidence interval, 0.974-1.211) and within the predefined equivalence boundaries, the investigators report (JAMA. 2016 Dec 1. doi: 10.1001/jama.2016.18305).
By week 48, both groups also showed no significant differences in time to tumor progression, progression-free survival (44.3% vs. 44.7%), or overall survival (89.1% vs. 85.1%).
Pharmacokinetic analysis showed the mean concentrations of trastuzumab were similar for the two treatments, and minimum drug concentrations were also comparable at week 16 of treatment.
“This confirmatory efficacy and safety study was the last step in the multistep process to demonstrate similarity of a trastuzumab biosimilar and was adequately powered to demonstrate equivalence with trastuzumab,” the authors wrote. “The results of this study are consistent with the physicochemical and functional similarity shown in vitro and in vivo and with the similar pharmacokinetics shown in healthy participants between the candidate biosimilar and trastuzumab.”
This consistency also extended to adverse events. Almost all participants in both the biosimilar and the trastuzumab groups reported at least one adverse event, which included neutropenia (57.5% vs. 53.3%), peripheral neuropathy (23.1% vs. 24.8%), and diarrhea (20.6% vs. 20.7%).
“A biosimilar treatment option may increase global access to biological cancer therapies, provided, among other issues, that the price of the biosimilar is sufficiently inexpensive to enable women in non–high-income countries to access this therapy,” the authors wrote.
However, they pointed out that the stepwise development program for biosimilar drugs tended to use shorter end-points – 24 weeks for the primary endpoint and 48 weeks for secondary endpoints in this particular study. By 48 weeks, more than 50% of patients had not shown progression, suggesting that the medians for efficacy parameters may have been longer with a longer data cut-off.
“The choice of the 24-week evaluation period for part 1 of this study was related to the ability to analyze the ORR as a short-term measure of clinical activity and safety directly related to the combination of taxanes with trastuzumab and the proposed biosimilar as first-line treatment.”
The study was funded and sponsored by Mylan, which manufactured the biosimilar drug, and Biocon Research Limited. Four authors declared stock in Mylan, two declared consulting fees from Mylan and one also declared stock in Biocon Research Limited. One author declared research and travel support from other pharmaceutical companies.
The availability of a biosimilar agent that achieves equivalent clinical outcomes at lower cost could enable many patients with breast cancer to have access to a therapy that may improve survival. Moreover, given the large number of patients with breast cancer, widespread use of this trastuzumab biosimilar evaluated by Rugo et al. (if approved for use by the U.S. FDA, the European Medicines Agency, and other regulatory agencies) also could have financial implications for the manufacturer of this product.
In announcing their FDA submission for the proposed trastuzumab biosimilar, the sponsors of the trial by Rugo et al. have expressed their “shared commitment to increasing access to these critical medicines worldwide” and indicated that “this advancement in the U.S. will enable us to enhance access to this affordable therapy to larger patient pools.” Ultimately, to fulfill these pledges, the manufacturers must ensure that the pricing of this biosimilar product is responsible and fair and provides access to this important therapy at an affordable price.
Howard Bauchner, MD, is editor in chief of JAMA, Phil B. Fontanarosa, MD, MBA, is executive editor of JAMA, and Robert M. Golub, MD, is deputy editor of JAMA. These comments are taken from an accompanying editorial (JAMA. 2016 Dec 1. doi: 10.1001/jama.2016.18743). No conflicts of interest were declared.
The availability of a biosimilar agent that achieves equivalent clinical outcomes at lower cost could enable many patients with breast cancer to have access to a therapy that may improve survival. Moreover, given the large number of patients with breast cancer, widespread use of this trastuzumab biosimilar evaluated by Rugo et al. (if approved for use by the U.S. FDA, the European Medicines Agency, and other regulatory agencies) also could have financial implications for the manufacturer of this product.
In announcing their FDA submission for the proposed trastuzumab biosimilar, the sponsors of the trial by Rugo et al. have expressed their “shared commitment to increasing access to these critical medicines worldwide” and indicated that “this advancement in the U.S. will enable us to enhance access to this affordable therapy to larger patient pools.” Ultimately, to fulfill these pledges, the manufacturers must ensure that the pricing of this biosimilar product is responsible and fair and provides access to this important therapy at an affordable price.
Howard Bauchner, MD, is editor in chief of JAMA, Phil B. Fontanarosa, MD, MBA, is executive editor of JAMA, and Robert M. Golub, MD, is deputy editor of JAMA. These comments are taken from an accompanying editorial (JAMA. 2016 Dec 1. doi: 10.1001/jama.2016.18743). No conflicts of interest were declared.
The availability of a biosimilar agent that achieves equivalent clinical outcomes at lower cost could enable many patients with breast cancer to have access to a therapy that may improve survival. Moreover, given the large number of patients with breast cancer, widespread use of this trastuzumab biosimilar evaluated by Rugo et al. (if approved for use by the U.S. FDA, the European Medicines Agency, and other regulatory agencies) also could have financial implications for the manufacturer of this product.
In announcing their FDA submission for the proposed trastuzumab biosimilar, the sponsors of the trial by Rugo et al. have expressed their “shared commitment to increasing access to these critical medicines worldwide” and indicated that “this advancement in the U.S. will enable us to enhance access to this affordable therapy to larger patient pools.” Ultimately, to fulfill these pledges, the manufacturers must ensure that the pricing of this biosimilar product is responsible and fair and provides access to this important therapy at an affordable price.
Howard Bauchner, MD, is editor in chief of JAMA, Phil B. Fontanarosa, MD, MBA, is executive editor of JAMA, and Robert M. Golub, MD, is deputy editor of JAMA. These comments are taken from an accompanying editorial (JAMA. 2016 Dec 1. doi: 10.1001/jama.2016.18743). No conflicts of interest were declared.
A trastuzumab biosimilar drug has shown an equivalent response, compared with trastuzumab, in the treatment of ERBB2 (HER2)-positive metastatic breast cancer, according to the results of a randomized double-blind controlled trial.
The anti-ERBB2 humanized monoclonal antibody trastuzumab in combination with chemotherapy has been found in numerous trials to significantly improve progression-free survival and overall survival in women with ERBB2-positive metastatic breast, compared with chemotherapy alone.
“With impending patent expiration of some biological agents, development of biosimilars has become a high priority for drug developers and health authorities throughout the world to provide access to high-quality alternatives,” the authors wrote. “A biosimilar drug is a biological product that is highly similar to a licensed biological product, with no clinically meaningful differences in terms of safety, purity, or potency.”
In a phase III multicenter trial, 500 women with ERBB2 (HER2)-positive metastatic breast cancer, recruited from 95 sites in Europe, Africa, South America, and Asia, were randomized 1:1 to intravenous infusions of trastuzumab or a biosimilar labeled MYL-1401O, with both arms also receiving taxane therapy.
At 24 weeks, the overall response rate (ORR) was not significantly different between the biosimilar and trastuzumab groups (69.6% vs. 64.0%; ORR ratio, 1.09; 90% confidence interval, 0.974-1.211) and within the predefined equivalence boundaries, the investigators report (JAMA. 2016 Dec 1. doi: 10.1001/jama.2016.18305).
By week 48, both groups also showed no significant differences in time to tumor progression, progression-free survival (44.3% vs. 44.7%), or overall survival (89.1% vs. 85.1%).
Pharmacokinetic analysis showed the mean concentrations of trastuzumab were similar for the two treatments, and minimum drug concentrations were also comparable at week 16 of treatment.
“This confirmatory efficacy and safety study was the last step in the multistep process to demonstrate similarity of a trastuzumab biosimilar and was adequately powered to demonstrate equivalence with trastuzumab,” the authors wrote. “The results of this study are consistent with the physicochemical and functional similarity shown in vitro and in vivo and with the similar pharmacokinetics shown in healthy participants between the candidate biosimilar and trastuzumab.”
This consistency also extended to adverse events. Almost all participants in both the biosimilar and the trastuzumab groups reported at least one adverse event, which included neutropenia (57.5% vs. 53.3%), peripheral neuropathy (23.1% vs. 24.8%), and diarrhea (20.6% vs. 20.7%).
“A biosimilar treatment option may increase global access to biological cancer therapies, provided, among other issues, that the price of the biosimilar is sufficiently inexpensive to enable women in non–high-income countries to access this therapy,” the authors wrote.
However, they pointed out that the stepwise development program for biosimilar drugs tended to use shorter end-points – 24 weeks for the primary endpoint and 48 weeks for secondary endpoints in this particular study. By 48 weeks, more than 50% of patients had not shown progression, suggesting that the medians for efficacy parameters may have been longer with a longer data cut-off.
“The choice of the 24-week evaluation period for part 1 of this study was related to the ability to analyze the ORR as a short-term measure of clinical activity and safety directly related to the combination of taxanes with trastuzumab and the proposed biosimilar as first-line treatment.”
The study was funded and sponsored by Mylan, which manufactured the biosimilar drug, and Biocon Research Limited. Four authors declared stock in Mylan, two declared consulting fees from Mylan and one also declared stock in Biocon Research Limited. One author declared research and travel support from other pharmaceutical companies.
A trastuzumab biosimilar drug has shown an equivalent response, compared with trastuzumab, in the treatment of ERBB2 (HER2)-positive metastatic breast cancer, according to the results of a randomized double-blind controlled trial.
The anti-ERBB2 humanized monoclonal antibody trastuzumab in combination with chemotherapy has been found in numerous trials to significantly improve progression-free survival and overall survival in women with ERBB2-positive metastatic breast, compared with chemotherapy alone.
“With impending patent expiration of some biological agents, development of biosimilars has become a high priority for drug developers and health authorities throughout the world to provide access to high-quality alternatives,” the authors wrote. “A biosimilar drug is a biological product that is highly similar to a licensed biological product, with no clinically meaningful differences in terms of safety, purity, or potency.”
In a phase III multicenter trial, 500 women with ERBB2 (HER2)-positive metastatic breast cancer, recruited from 95 sites in Europe, Africa, South America, and Asia, were randomized 1:1 to intravenous infusions of trastuzumab or a biosimilar labeled MYL-1401O, with both arms also receiving taxane therapy.
At 24 weeks, the overall response rate (ORR) was not significantly different between the biosimilar and trastuzumab groups (69.6% vs. 64.0%; ORR ratio, 1.09; 90% confidence interval, 0.974-1.211) and within the predefined equivalence boundaries, the investigators report (JAMA. 2016 Dec 1. doi: 10.1001/jama.2016.18305).
By week 48, both groups also showed no significant differences in time to tumor progression, progression-free survival (44.3% vs. 44.7%), or overall survival (89.1% vs. 85.1%).
Pharmacokinetic analysis showed the mean concentrations of trastuzumab were similar for the two treatments, and minimum drug concentrations were also comparable at week 16 of treatment.
“This confirmatory efficacy and safety study was the last step in the multistep process to demonstrate similarity of a trastuzumab biosimilar and was adequately powered to demonstrate equivalence with trastuzumab,” the authors wrote. “The results of this study are consistent with the physicochemical and functional similarity shown in vitro and in vivo and with the similar pharmacokinetics shown in healthy participants between the candidate biosimilar and trastuzumab.”
This consistency also extended to adverse events. Almost all participants in both the biosimilar and the trastuzumab groups reported at least one adverse event, which included neutropenia (57.5% vs. 53.3%), peripheral neuropathy (23.1% vs. 24.8%), and diarrhea (20.6% vs. 20.7%).
“A biosimilar treatment option may increase global access to biological cancer therapies, provided, among other issues, that the price of the biosimilar is sufficiently inexpensive to enable women in non–high-income countries to access this therapy,” the authors wrote.
However, they pointed out that the stepwise development program for biosimilar drugs tended to use shorter end-points – 24 weeks for the primary endpoint and 48 weeks for secondary endpoints in this particular study. By 48 weeks, more than 50% of patients had not shown progression, suggesting that the medians for efficacy parameters may have been longer with a longer data cut-off.
“The choice of the 24-week evaluation period for part 1 of this study was related to the ability to analyze the ORR as a short-term measure of clinical activity and safety directly related to the combination of taxanes with trastuzumab and the proposed biosimilar as first-line treatment.”
The study was funded and sponsored by Mylan, which manufactured the biosimilar drug, and Biocon Research Limited. Four authors declared stock in Mylan, two declared consulting fees from Mylan and one also declared stock in Biocon Research Limited. One author declared research and travel support from other pharmaceutical companies.
FROM JAMA
Key clinical point: A trastuzumab biosimilar drug has shown an equivalent response, compared with trastuzumab, in the treatment of ERBB2 (HER2)-positive metastatic breast cancer.
Major finding: Patients treated with biosimilar trastuzumab showed no significant differences in response rate, progression, and survival, compared with those treated with trastuzumab.
Data source: Randomized, double-blind phase III controlled trial in 500 women with ERBB2 (HER2)-positive metastatic breast cancer.
Disclosures: The study was funded and sponsored by Mylan, which manufactured the biosimilar drug, and Biocon Research Limited. Four authors declared stock in Mylan, two declared consulting fees from Mylan, and one also declared stock in Biocon Research Limited. One author declared research and travel support from other pharmaceutical companies.
Targeted therapies predicted to blow out costs for CLL
The lifetime cost of treating chronic lymphocytic leukemia is forecast to rise precipitously for patients diagnosed today, as oral targeted therapies take over as the first-line treatment option, according to a study published November 21 in the Journal of Clinical Oncology.
The conclusion is based on economic models that also indicated the annual cost in the United States of managing chronic lymphocytic leukemia (CLL) will increase from its current level of $0.74 billion to $5.13 billion by 2025 (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.68.2856).
While the majority of patients with CLL are covered by Medicare in the United States, they still currently pay $9,200 in out-of-pocket costs for oral agents. This figure is forecast to increase to $57,000 for those who start treatment in 2016 due to the increased costs of oral targeted therapeutics.
“Such an economic impact could result in financial toxicity, limited access, and lower adherence to the oral therapies, which may undermine their clinical effectiveness,” Qiushi Chen, from the Georgia Institute of Technology, Atlanta, and his coauthors wrote. They called for a more sustainable pricing strategy for oral targeted therapies, rather than have clinicians be forced to choose less effective but more affordable management strategies.
The researchers developed a microsimulation model of CLL, simulating the dynamics of the patient population under given management strategies from 2011-2025.
Around 130,000 patients live with CLL in the United States and around 15,000 new cases are diagnosed each year. By 2025, the authors forecast that 199,000 people will be living with the disease; a 55% increase that is both the result of new diagnoses and of improved survival with new oral targeted therapies.
Chemoimmunotherapy regimens – such as fludarabine, cyclophosphamide, and rituximab – have long been the standard first-line approach to CLL. But in recent years, new oral targeted agents such as ibrutinib and idelalisib have significantly improved progression-free survival and overall survival in CLL.
Ibrutinib is approved for first-line management of CLL, idelalisib is approved in combination with rituximab for patients with relapsed/refractory chronic lymphocytic leukemia, and venetoclax is approved for patients with relapsed chronic lymphocytic leukemia with del(17p).
“Both ibrutinib and idelalisib are priced at approximately $130,000 per [CLL patient per] year and are recommended until patients have progressive disease or significant toxicities,” the authors wrote. “In contrast, the costs for chemoimmunotherapy-based treatments range from $60,000 to $100,000 for a finite duration, that is, a typical six-cycle course that lasts for approximately 6 months.”
The higher costs will add up to additional annual spending of $29 billion to 2025, compared with around $1.12 billion annually for chemoimmunotherapy alone.
“Compared with the CIT scenario, the oral targeted therapy scenario resulted in an increase of 107,000 person–quality-adjusted life-years (149,000 person–life years), with additional discounted costs of $20.2 billion,” the authors reported.
The annual cost of cancer care in the United States is increasing across the board, from $143 billion in 2010 to $180 billion in 2020, but the cost of care for CLL is increasing more significantly than for other cancers. For example, breast and prostate cancers are forecast to have a 24%-38% increase in annual cost by 2020, while CLL is predicted to increase by 500%.
Seven authors declared research funding, honoraria and consultancy funding from a range of pharmaceutical companies including those involved in the manufacture of therapies for chronic lymphocytic leukemia. Two authors had no conflicts to declare.
The lifetime cost of treating chronic lymphocytic leukemia is forecast to rise precipitously for patients diagnosed today, as oral targeted therapies take over as the first-line treatment option, according to a study published November 21 in the Journal of Clinical Oncology.
The conclusion is based on economic models that also indicated the annual cost in the United States of managing chronic lymphocytic leukemia (CLL) will increase from its current level of $0.74 billion to $5.13 billion by 2025 (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.68.2856).
While the majority of patients with CLL are covered by Medicare in the United States, they still currently pay $9,200 in out-of-pocket costs for oral agents. This figure is forecast to increase to $57,000 for those who start treatment in 2016 due to the increased costs of oral targeted therapeutics.
“Such an economic impact could result in financial toxicity, limited access, and lower adherence to the oral therapies, which may undermine their clinical effectiveness,” Qiushi Chen, from the Georgia Institute of Technology, Atlanta, and his coauthors wrote. They called for a more sustainable pricing strategy for oral targeted therapies, rather than have clinicians be forced to choose less effective but more affordable management strategies.
The researchers developed a microsimulation model of CLL, simulating the dynamics of the patient population under given management strategies from 2011-2025.
Around 130,000 patients live with CLL in the United States and around 15,000 new cases are diagnosed each year. By 2025, the authors forecast that 199,000 people will be living with the disease; a 55% increase that is both the result of new diagnoses and of improved survival with new oral targeted therapies.
Chemoimmunotherapy regimens – such as fludarabine, cyclophosphamide, and rituximab – have long been the standard first-line approach to CLL. But in recent years, new oral targeted agents such as ibrutinib and idelalisib have significantly improved progression-free survival and overall survival in CLL.
Ibrutinib is approved for first-line management of CLL, idelalisib is approved in combination with rituximab for patients with relapsed/refractory chronic lymphocytic leukemia, and venetoclax is approved for patients with relapsed chronic lymphocytic leukemia with del(17p).
“Both ibrutinib and idelalisib are priced at approximately $130,000 per [CLL patient per] year and are recommended until patients have progressive disease or significant toxicities,” the authors wrote. “In contrast, the costs for chemoimmunotherapy-based treatments range from $60,000 to $100,000 for a finite duration, that is, a typical six-cycle course that lasts for approximately 6 months.”
The higher costs will add up to additional annual spending of $29 billion to 2025, compared with around $1.12 billion annually for chemoimmunotherapy alone.
“Compared with the CIT scenario, the oral targeted therapy scenario resulted in an increase of 107,000 person–quality-adjusted life-years (149,000 person–life years), with additional discounted costs of $20.2 billion,” the authors reported.
The annual cost of cancer care in the United States is increasing across the board, from $143 billion in 2010 to $180 billion in 2020, but the cost of care for CLL is increasing more significantly than for other cancers. For example, breast and prostate cancers are forecast to have a 24%-38% increase in annual cost by 2020, while CLL is predicted to increase by 500%.
Seven authors declared research funding, honoraria and consultancy funding from a range of pharmaceutical companies including those involved in the manufacture of therapies for chronic lymphocytic leukemia. Two authors had no conflicts to declare.
The lifetime cost of treating chronic lymphocytic leukemia is forecast to rise precipitously for patients diagnosed today, as oral targeted therapies take over as the first-line treatment option, according to a study published November 21 in the Journal of Clinical Oncology.
The conclusion is based on economic models that also indicated the annual cost in the United States of managing chronic lymphocytic leukemia (CLL) will increase from its current level of $0.74 billion to $5.13 billion by 2025 (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.68.2856).
While the majority of patients with CLL are covered by Medicare in the United States, they still currently pay $9,200 in out-of-pocket costs for oral agents. This figure is forecast to increase to $57,000 for those who start treatment in 2016 due to the increased costs of oral targeted therapeutics.
“Such an economic impact could result in financial toxicity, limited access, and lower adherence to the oral therapies, which may undermine their clinical effectiveness,” Qiushi Chen, from the Georgia Institute of Technology, Atlanta, and his coauthors wrote. They called for a more sustainable pricing strategy for oral targeted therapies, rather than have clinicians be forced to choose less effective but more affordable management strategies.
The researchers developed a microsimulation model of CLL, simulating the dynamics of the patient population under given management strategies from 2011-2025.
Around 130,000 patients live with CLL in the United States and around 15,000 new cases are diagnosed each year. By 2025, the authors forecast that 199,000 people will be living with the disease; a 55% increase that is both the result of new diagnoses and of improved survival with new oral targeted therapies.
Chemoimmunotherapy regimens – such as fludarabine, cyclophosphamide, and rituximab – have long been the standard first-line approach to CLL. But in recent years, new oral targeted agents such as ibrutinib and idelalisib have significantly improved progression-free survival and overall survival in CLL.
Ibrutinib is approved for first-line management of CLL, idelalisib is approved in combination with rituximab for patients with relapsed/refractory chronic lymphocytic leukemia, and venetoclax is approved for patients with relapsed chronic lymphocytic leukemia with del(17p).
“Both ibrutinib and idelalisib are priced at approximately $130,000 per [CLL patient per] year and are recommended until patients have progressive disease or significant toxicities,” the authors wrote. “In contrast, the costs for chemoimmunotherapy-based treatments range from $60,000 to $100,000 for a finite duration, that is, a typical six-cycle course that lasts for approximately 6 months.”
The higher costs will add up to additional annual spending of $29 billion to 2025, compared with around $1.12 billion annually for chemoimmunotherapy alone.
“Compared with the CIT scenario, the oral targeted therapy scenario resulted in an increase of 107,000 person–quality-adjusted life-years (149,000 person–life years), with additional discounted costs of $20.2 billion,” the authors reported.
The annual cost of cancer care in the United States is increasing across the board, from $143 billion in 2010 to $180 billion in 2020, but the cost of care for CLL is increasing more significantly than for other cancers. For example, breast and prostate cancers are forecast to have a 24%-38% increase in annual cost by 2020, while CLL is predicted to increase by 500%.
Seven authors declared research funding, honoraria and consultancy funding from a range of pharmaceutical companies including those involved in the manufacture of therapies for chronic lymphocytic leukemia. Two authors had no conflicts to declare.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The high cost of oral therapies for chronic lymphocytic leukemia could result in financial toxicity, limited access, and lower adherence, which may undermine their clinical effectiveness.
Major finding: The cost of treating chronic lymphocytic leukemia is forecast to increase from its current level of $0.74 billion to $5.13 billion by 2025.
Data source: Microsimulation model of chronic lymphocytic leukemia treatment from 2010-2025.
Disclosures: Seven authors declared research funding, honoraria, and consultancy funding from a range of pharmaceutical companies including those involved in the manufacture of therapies for chronic lymphocytic leukemia. Two authors had no conflicts to declare.