User login
Why Do Minority Women Have a Higher Risk of Postpartum Depression?
About 10% to 15% of women in the US have postpartum depression (PPD)—but that estimate is based mostly on women of European ancestry. In black women the rates are doubled, and among Latinas the prevalence is 30% to 43%. But those 2 groups have been inadequately studied, say researchers from University of North Carolina. To help remedy the lack of information, they conducted a study with the largest and “most robustly phenotyped” cohort of minority women with PPD. Their study also is the first to examine genetic ancestry as it contributes to PPD risk.
The researchers recruited 549 women with PPD and 968 without PPD who were within 6 weeks of having given birth. Of those, 67.4% were black, 14.4% were Latina, and 18.2% were white. The median age was 26.7; nearly half of the participants were married. Only 3.6% had given birth for the first time.
The women completed a battery of tests, including the Abuse and Trauma Inventory, Everyday Stressors Index (ESI), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Bonding Questionnaire. The researchers also assessed estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanolone.
The women with PPD had significantly higher rates of previous psychiatric diagnoses, significantly higher EPDS total scores, and higher rates of family history of PPD. They also had significantly higher rates of previous diagnoses of major depressive disorder (MDD) (53% vs 15%), although 47% were experiencing their first episode of MDD. Dramatically higher numbers of women with PPD vs without PPD had suicidal thoughts in the month prior to assessment: 36% vs 2%, respectively.
Genetic ancestry was not predictive of case status, nor were hormonal influences any different between the 2 groups. Instead, psychiatric history and exposure to adverse life events were significant predictors. Nearly half of all the women with PPD had a lifetime anxiety disorder diagnosis compared with 7% of the controls. And although 67% of all participants reported a history of ≥ 1 traumatic event, women with PPD had double the proportion of multiple events of abuse and trauma. Women who had experienced multiple adverse life events were 3 times more likely to have PPD. Childhood and adult sexual abuse and life-threatening attack were among the most predictive.
The women with PPD had an ESI score > 3 times higher than that of the controls (19% vs 6%, respectively). The researchers note that cumulative lifetime stress may lead to epigenetic modification, and thus to PPD. Women with PPD also had a significantly higher proportion of dysfunctional mother-infant relationships, although the numbers were low in both groups (7% vs 0.35%, respectively).
The researchers say that although genetic ancestry did not play a role in determining case status, there are important ethnic and cultural differences that do play a role in treatment. For instance, Latinas and black women may be less likely to accept antidepressants as therapy. And because socioeconomic status is a determinant of health care access, they also face major barriers to mental health care. However, neither insurance nor education status (markers of socioeconomic status) distinguished cases from controls, even when the researchers controlled for genetic ancestry.
Their data provide a set of risk factors that can be used in screening new mothers, the researchers say. A brief, single assessment for previous psychiatric and abuse/trauma history during the perinatal period, along with regular mood monitoring, could increase a clinician’s ability to predict the onset of PPD.
Source:
Guintivano J, Sullivan PF, Stuebe AM. Psychol Med. 2018;48(7):1190-1200.
doi: 10.1017/S0033291717002641.
About 10% to 15% of women in the US have postpartum depression (PPD)—but that estimate is based mostly on women of European ancestry. In black women the rates are doubled, and among Latinas the prevalence is 30% to 43%. But those 2 groups have been inadequately studied, say researchers from University of North Carolina. To help remedy the lack of information, they conducted a study with the largest and “most robustly phenotyped” cohort of minority women with PPD. Their study also is the first to examine genetic ancestry as it contributes to PPD risk.
The researchers recruited 549 women with PPD and 968 without PPD who were within 6 weeks of having given birth. Of those, 67.4% were black, 14.4% were Latina, and 18.2% were white. The median age was 26.7; nearly half of the participants were married. Only 3.6% had given birth for the first time.
The women completed a battery of tests, including the Abuse and Trauma Inventory, Everyday Stressors Index (ESI), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Bonding Questionnaire. The researchers also assessed estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanolone.
The women with PPD had significantly higher rates of previous psychiatric diagnoses, significantly higher EPDS total scores, and higher rates of family history of PPD. They also had significantly higher rates of previous diagnoses of major depressive disorder (MDD) (53% vs 15%), although 47% were experiencing their first episode of MDD. Dramatically higher numbers of women with PPD vs without PPD had suicidal thoughts in the month prior to assessment: 36% vs 2%, respectively.
Genetic ancestry was not predictive of case status, nor were hormonal influences any different between the 2 groups. Instead, psychiatric history and exposure to adverse life events were significant predictors. Nearly half of all the women with PPD had a lifetime anxiety disorder diagnosis compared with 7% of the controls. And although 67% of all participants reported a history of ≥ 1 traumatic event, women with PPD had double the proportion of multiple events of abuse and trauma. Women who had experienced multiple adverse life events were 3 times more likely to have PPD. Childhood and adult sexual abuse and life-threatening attack were among the most predictive.
The women with PPD had an ESI score > 3 times higher than that of the controls (19% vs 6%, respectively). The researchers note that cumulative lifetime stress may lead to epigenetic modification, and thus to PPD. Women with PPD also had a significantly higher proportion of dysfunctional mother-infant relationships, although the numbers were low in both groups (7% vs 0.35%, respectively).
The researchers say that although genetic ancestry did not play a role in determining case status, there are important ethnic and cultural differences that do play a role in treatment. For instance, Latinas and black women may be less likely to accept antidepressants as therapy. And because socioeconomic status is a determinant of health care access, they also face major barriers to mental health care. However, neither insurance nor education status (markers of socioeconomic status) distinguished cases from controls, even when the researchers controlled for genetic ancestry.
Their data provide a set of risk factors that can be used in screening new mothers, the researchers say. A brief, single assessment for previous psychiatric and abuse/trauma history during the perinatal period, along with regular mood monitoring, could increase a clinician’s ability to predict the onset of PPD.
Source:
Guintivano J, Sullivan PF, Stuebe AM. Psychol Med. 2018;48(7):1190-1200.
doi: 10.1017/S0033291717002641.
About 10% to 15% of women in the US have postpartum depression (PPD)—but that estimate is based mostly on women of European ancestry. In black women the rates are doubled, and among Latinas the prevalence is 30% to 43%. But those 2 groups have been inadequately studied, say researchers from University of North Carolina. To help remedy the lack of information, they conducted a study with the largest and “most robustly phenotyped” cohort of minority women with PPD. Their study also is the first to examine genetic ancestry as it contributes to PPD risk.
The researchers recruited 549 women with PPD and 968 without PPD who were within 6 weeks of having given birth. Of those, 67.4% were black, 14.4% were Latina, and 18.2% were white. The median age was 26.7; nearly half of the participants were married. Only 3.6% had given birth for the first time.
The women completed a battery of tests, including the Abuse and Trauma Inventory, Everyday Stressors Index (ESI), Edinburgh Postnatal Depression Scale (EPDS), and Postpartum Bonding Questionnaire. The researchers also assessed estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanolone.
The women with PPD had significantly higher rates of previous psychiatric diagnoses, significantly higher EPDS total scores, and higher rates of family history of PPD. They also had significantly higher rates of previous diagnoses of major depressive disorder (MDD) (53% vs 15%), although 47% were experiencing their first episode of MDD. Dramatically higher numbers of women with PPD vs without PPD had suicidal thoughts in the month prior to assessment: 36% vs 2%, respectively.
Genetic ancestry was not predictive of case status, nor were hormonal influences any different between the 2 groups. Instead, psychiatric history and exposure to adverse life events were significant predictors. Nearly half of all the women with PPD had a lifetime anxiety disorder diagnosis compared with 7% of the controls. And although 67% of all participants reported a history of ≥ 1 traumatic event, women with PPD had double the proportion of multiple events of abuse and trauma. Women who had experienced multiple adverse life events were 3 times more likely to have PPD. Childhood and adult sexual abuse and life-threatening attack were among the most predictive.
The women with PPD had an ESI score > 3 times higher than that of the controls (19% vs 6%, respectively). The researchers note that cumulative lifetime stress may lead to epigenetic modification, and thus to PPD. Women with PPD also had a significantly higher proportion of dysfunctional mother-infant relationships, although the numbers were low in both groups (7% vs 0.35%, respectively).
The researchers say that although genetic ancestry did not play a role in determining case status, there are important ethnic and cultural differences that do play a role in treatment. For instance, Latinas and black women may be less likely to accept antidepressants as therapy. And because socioeconomic status is a determinant of health care access, they also face major barriers to mental health care. However, neither insurance nor education status (markers of socioeconomic status) distinguished cases from controls, even when the researchers controlled for genetic ancestry.
Their data provide a set of risk factors that can be used in screening new mothers, the researchers say. A brief, single assessment for previous psychiatric and abuse/trauma history during the perinatal period, along with regular mood monitoring, could increase a clinician’s ability to predict the onset of PPD.
Source:
Guintivano J, Sullivan PF, Stuebe AM. Psychol Med. 2018;48(7):1190-1200.
doi: 10.1017/S0033291717002641.
Ivacaftor reduced hospitalizations in CF
with a variety of mutations, according to results published May 7 in Health Affairs.
The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.
Ms. Feng, who is senior director for policy and advocacy at the Cystic Fibrosis Foundation and her colleagues analyzed administrative claims data from the Truven Health Analytics Market Scan Commercial Research Database. All of the claims were for patients from the United States with employer-sponsored insurance plans. Eligibility criteria included an ICD-9 CM diagnosis of cystic fibrosis on one or more inpatient claims or two or more outpatient claims at least 30 days apart, a prescription claim for ivacaftor monotherapy, being at least 6 years of age at the time of the first filled prescription, and 12 months of continuous enrollment before and after the first filled prescription.
The “pre-ivacaftor” period was defined as the 12 months before the first filled prescription. The “post-ivacaftor” period was defined as the 12 months after the first filled prescription. For each period, the numbers and percentages of patients hospitalized were calculated, for any reason and for cystic fibrosis–related reasons. Hospitalization rates also were calculated as numbers of admissions per person-year, the authors said.
Data also were analyzed for two subcohorts: the 86 patients who started using ivacaftor between Feb. 6, 2012, and Feb. 21, 2014, under the initial Food and Drug Administration label; and the 57 patients who initiated use between Feb. 22, 2014, and Dec. 31, 2015, under the expanded FDA label, which included nine additional genetic mutations.
Of the 143 patients who had filled prescriptions for ivacaftor, 63% were aged 18 years or older. The rate of overall inpatient admissions decreased 55%, from 0.57 admissions per person-year in the pre-ivacaftor period to 0.26 admissions per person-year in the post-ivacaftor period, the investigators reported.
The declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admissions of 59% and 57%, respectively.
Hospital admissions related to cystic fibrosis also decreased significantly, by 78%. Admissions with principal diagnosis codes for cystic fibrosis decreased from 42 in the preprescription period, to 8 after filling the prescription. Rates per person per year decreased by 82% in patients aged 6-17 years and 80% among adults aged 18 years and older. Additionally, patients who filled at least 10 prescriptions during the study period experienced a 68% reduction in inpatient admissions, compared with 45% for those with three to nine prescriptions filled.
Ivacaftor also was associated with 60% lower per-person inpatient spending overall, with a greater proportional reduction in hospital costs for adults (68%) than for children (45%), and an absolute per-person reduction of $10,567, the authors reported.
“Treatments that target the protein defect that causes cystic fibrosis illustrate the promise of precision medicine,” the authors wrote. “To deliver the right care to the right patient, cystic fibrosis care must continue to account for other aspects unique to individuals such as environment, physiology, patients’ preferences, and lifestyle,” they concluded.
Ivacaftor (Kalydeco) is manufactured for Vertex Pharmaceuticals. No disclosures or conflicts of interest were reported.
SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554
with a variety of mutations, according to results published May 7 in Health Affairs.
The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.
Ms. Feng, who is senior director for policy and advocacy at the Cystic Fibrosis Foundation and her colleagues analyzed administrative claims data from the Truven Health Analytics Market Scan Commercial Research Database. All of the claims were for patients from the United States with employer-sponsored insurance plans. Eligibility criteria included an ICD-9 CM diagnosis of cystic fibrosis on one or more inpatient claims or two or more outpatient claims at least 30 days apart, a prescription claim for ivacaftor monotherapy, being at least 6 years of age at the time of the first filled prescription, and 12 months of continuous enrollment before and after the first filled prescription.
The “pre-ivacaftor” period was defined as the 12 months before the first filled prescription. The “post-ivacaftor” period was defined as the 12 months after the first filled prescription. For each period, the numbers and percentages of patients hospitalized were calculated, for any reason and for cystic fibrosis–related reasons. Hospitalization rates also were calculated as numbers of admissions per person-year, the authors said.
Data also were analyzed for two subcohorts: the 86 patients who started using ivacaftor between Feb. 6, 2012, and Feb. 21, 2014, under the initial Food and Drug Administration label; and the 57 patients who initiated use between Feb. 22, 2014, and Dec. 31, 2015, under the expanded FDA label, which included nine additional genetic mutations.
Of the 143 patients who had filled prescriptions for ivacaftor, 63% were aged 18 years or older. The rate of overall inpatient admissions decreased 55%, from 0.57 admissions per person-year in the pre-ivacaftor period to 0.26 admissions per person-year in the post-ivacaftor period, the investigators reported.
The declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admissions of 59% and 57%, respectively.
Hospital admissions related to cystic fibrosis also decreased significantly, by 78%. Admissions with principal diagnosis codes for cystic fibrosis decreased from 42 in the preprescription period, to 8 after filling the prescription. Rates per person per year decreased by 82% in patients aged 6-17 years and 80% among adults aged 18 years and older. Additionally, patients who filled at least 10 prescriptions during the study period experienced a 68% reduction in inpatient admissions, compared with 45% for those with three to nine prescriptions filled.
Ivacaftor also was associated with 60% lower per-person inpatient spending overall, with a greater proportional reduction in hospital costs for adults (68%) than for children (45%), and an absolute per-person reduction of $10,567, the authors reported.
“Treatments that target the protein defect that causes cystic fibrosis illustrate the promise of precision medicine,” the authors wrote. “To deliver the right care to the right patient, cystic fibrosis care must continue to account for other aspects unique to individuals such as environment, physiology, patients’ preferences, and lifestyle,” they concluded.
Ivacaftor (Kalydeco) is manufactured for Vertex Pharmaceuticals. No disclosures or conflicts of interest were reported.
SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554
with a variety of mutations, according to results published May 7 in Health Affairs.
The study involved 143 patients being treated with ivacaftor between February 2012 and February 2015. In 2014, the FDA expanded its approval for the use of ivacaftor by cystic fibrosis patients to include nine additional mutations, and patients with these mutations were included in this study.
Ms. Feng, who is senior director for policy and advocacy at the Cystic Fibrosis Foundation and her colleagues analyzed administrative claims data from the Truven Health Analytics Market Scan Commercial Research Database. All of the claims were for patients from the United States with employer-sponsored insurance plans. Eligibility criteria included an ICD-9 CM diagnosis of cystic fibrosis on one or more inpatient claims or two or more outpatient claims at least 30 days apart, a prescription claim for ivacaftor monotherapy, being at least 6 years of age at the time of the first filled prescription, and 12 months of continuous enrollment before and after the first filled prescription.
The “pre-ivacaftor” period was defined as the 12 months before the first filled prescription. The “post-ivacaftor” period was defined as the 12 months after the first filled prescription. For each period, the numbers and percentages of patients hospitalized were calculated, for any reason and for cystic fibrosis–related reasons. Hospitalization rates also were calculated as numbers of admissions per person-year, the authors said.
Data also were analyzed for two subcohorts: the 86 patients who started using ivacaftor between Feb. 6, 2012, and Feb. 21, 2014, under the initial Food and Drug Administration label; and the 57 patients who initiated use between Feb. 22, 2014, and Dec. 31, 2015, under the expanded FDA label, which included nine additional genetic mutations.
Of the 143 patients who had filled prescriptions for ivacaftor, 63% were aged 18 years or older. The rate of overall inpatient admissions decreased 55%, from 0.57 admissions per person-year in the pre-ivacaftor period to 0.26 admissions per person-year in the post-ivacaftor period, the investigators reported.
The declines in hospital admissions also were similar between the initial label and the expanded FDA label groups, with declines in overall admissions of 59% and 57%, respectively.
Hospital admissions related to cystic fibrosis also decreased significantly, by 78%. Admissions with principal diagnosis codes for cystic fibrosis decreased from 42 in the preprescription period, to 8 after filling the prescription. Rates per person per year decreased by 82% in patients aged 6-17 years and 80% among adults aged 18 years and older. Additionally, patients who filled at least 10 prescriptions during the study period experienced a 68% reduction in inpatient admissions, compared with 45% for those with three to nine prescriptions filled.
Ivacaftor also was associated with 60% lower per-person inpatient spending overall, with a greater proportional reduction in hospital costs for adults (68%) than for children (45%), and an absolute per-person reduction of $10,567, the authors reported.
“Treatments that target the protein defect that causes cystic fibrosis illustrate the promise of precision medicine,” the authors wrote. “To deliver the right care to the right patient, cystic fibrosis care must continue to account for other aspects unique to individuals such as environment, physiology, patients’ preferences, and lifestyle,” they concluded.
Ivacaftor (Kalydeco) is manufactured for Vertex Pharmaceuticals. No disclosures or conflicts of interest were reported.
SOURCE: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554
FROM HEALTH AFFAIRS
Key clinical point: Ivacaftor significantly reduced hospital admission rates in patients with cystic fibrosis.
Major finding: Overall rate of inpatient admissions dropped by 55% and cystic fibrosis related admissions rates by 78% (P less than .0001).
Study details: A study of 143 patients treated with ivacaftor between February 2012 and February 2015.
Disclosures: No disclosures or conflicts of interest were reported.
Source: Feng LB et al. Health Aff. 2018 May 8. doi: 10.1377/hlthaff.2017.1554.
In PAH trials, clinical worsening risk rose with time
Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.
, according to results of the study published in the May issue of the journal Chest®.
The meta-analysis by Dr. Lajoie and her colleagues included 3,801 patients enrolled in one of 15 previously published randomized clinical trials. Of those trials, four were long-term, event driven studies, with a mean duration of 87 weeks, while the remainder were shorter studies with a mean duration of 15 weeks.
For the long-term, event-driven trials, the mean number needed to treat (NNT) was 17.4 at week 16, gradually decreasing to 8.8 at 52 weeks of follow-up, remaining stable after that, according to investigators.
Consistent with that finding, the mean relative risk of clinical worsening was 0.38 at 16 weeks, and similarly, 0.41 at 26 weeks, investigators reported. After that, the relative risk progressively increased to 0.54 at 52 weeks and 0.68 at 104 weeks.
Looking at all trials combined, Dr. Lajoie and her colleagues observed that longer trial duration had a positive correlation with relative risk of clinical worsening (P = .0002).
Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.
“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.
They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.
Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.
“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.
Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.
SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Key clinical point: A meta-analysis calls into question the need to perform pulmonary arterial hypertension (PAH) trials beyond 6 to 12 months of treatment in the future.
Major finding: The mean number needed to treat was stable at 52 weeks of follow-up and thereafter, while the mean relative risk of clinical worsening progressively increased from approximately 0.38 at week 16 to 0.68 at week 104.
Study details: A systematic review of 3,801 patients enrolled in 15 randomized clinical trials.
Disclosures: The authors reported disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among other entities.
Source: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Key clinical point: A meta-analysis calls into question the need to perform pulmonary arterial hypertension (PAH) trials beyond 6 to 12 months of treatment in the future.
Major finding: The mean number needed to treat was stable at 52 weeks of follow-up and thereafter, while the mean relative risk of clinical worsening progressively increased from approximately 0.38 at week 16 to 0.68 at week 104.
Study details: A systematic review of 3,801 patients enrolled in 15 randomized clinical trials.
Disclosures: The authors reported disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among other entities.
Source: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Key clinical point: A meta-analysis calls into question the need to perform pulmonary arterial hypertension (PAH) trials beyond 6 to 12 months of treatment in the future.
Major finding: The mean number needed to treat was stable at 52 weeks of follow-up and thereafter, while the mean relative risk of clinical worsening progressively increased from approximately 0.38 at week 16 to 0.68 at week 104.
Study details: A systematic review of 3,801 patients enrolled in 15 randomized clinical trials.
Disclosures: The authors reported disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among other entities.
Source: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.
, according to results of the study published in the May issue of the journal Chest®.
The meta-analysis by Dr. Lajoie and her colleagues included 3,801 patients enrolled in one of 15 previously published randomized clinical trials. Of those trials, four were long-term, event driven studies, with a mean duration of 87 weeks, while the remainder were shorter studies with a mean duration of 15 weeks.
For the long-term, event-driven trials, the mean number needed to treat (NNT) was 17.4 at week 16, gradually decreasing to 8.8 at 52 weeks of follow-up, remaining stable after that, according to investigators.
Consistent with that finding, the mean relative risk of clinical worsening was 0.38 at 16 weeks, and similarly, 0.41 at 26 weeks, investigators reported. After that, the relative risk progressively increased to 0.54 at 52 weeks and 0.68 at 104 weeks.
Looking at all trials combined, Dr. Lajoie and her colleagues observed that longer trial duration had a positive correlation with relative risk of clinical worsening (P = .0002).
Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.
“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.
They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.
Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.
“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.
Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.
SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
Current clinical trials evaluating combination therapy for pulmonary artery hypertension (PAH) may be longer than what is needed to demonstrate treatment benefit, results of a recent meta-analysis suggest.
, according to results of the study published in the May issue of the journal Chest®.
The meta-analysis by Dr. Lajoie and her colleagues included 3,801 patients enrolled in one of 15 previously published randomized clinical trials. Of those trials, four were long-term, event driven studies, with a mean duration of 87 weeks, while the remainder were shorter studies with a mean duration of 15 weeks.
For the long-term, event-driven trials, the mean number needed to treat (NNT) was 17.4 at week 16, gradually decreasing to 8.8 at 52 weeks of follow-up, remaining stable after that, according to investigators.
Consistent with that finding, the mean relative risk of clinical worsening was 0.38 at 16 weeks, and similarly, 0.41 at 26 weeks, investigators reported. After that, the relative risk progressively increased to 0.54 at 52 weeks and 0.68 at 104 weeks.
Looking at all trials combined, Dr. Lajoie and her colleagues observed that longer trial duration had a positive correlation with relative risk of clinical worsening (P = .0002).
Pragmatically, these results raise the possibility that PAH combination therapy trials could be shorter in duration. Some recent event-driven studies have lasted up to 6 years, with patients on treatment for about 2 of those years, investigators noted.
“In the context of an orphan disease with limited and competing recruitment for trials and the rapidly changing treatment paradigm in PAH, the optimal duration of future trials should be revisited,” Dr. Lajoie and her colleagues wrote in a discussion of their findings.
They also cautioned that NNT, a measure of how many patient treatments are needed to prevent one additional adverse event, could be “misleading” despite its value as a simple measure of treatment impact.
Likewise, relative risk can be misleading; for example, a treatment reducing event risk from 30% to 20% represents a relative risk reduction of approximately 35%, but so does a treatment reducing event risk from 3% to 2%, the researchers noted.
“Multiple factors, in addition to the efficacy of the therapy and the comparator, may directly influence the NNT and relative risk and should be taken into account in their interpretation,” they said in their report.
Dr. Lajoie had no disclosures related to the study. Her coauthors had disclosures related to Actelion Pharmaceuticals, Bayer, and GlaxoSmithKline, among others.
SOURCE: Lajoie AC et al. Chest. 2017 May;153(5):1142-52.
FROM CHEST®
When and how to suspect asthma misdiagnosis
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
NEW ORLEANS – Kyle I. Happel, MD, said at the annual meeting of the American College of Physicians.
“Asthma is a disease whose symptoms are caused by variable airflow obstruction. It varies throughout the day, usually, and certainly by the week or by the month. I want you to think about the variability of a patient’s disease symptoms in forming your index of suspicion for this disease,” urged Dr. Happel, of the section of pulmonary, critical care, and allergy/immunology at Louisiana State University Medical Center in New Orleans.
These phenomena occur often. In a Canadian multicenter study of more than 700 patients with a history of physician-diagnosed asthma within the past 5 years, current asthma was ruled out in fully 33% of them on the basis of no deterioration of asthma symptoms, no evidence of reversible airway obstruction, and no bronchial hyperresponsiveness after all asthma drugs were tapered off (JAMA. 2017 Jan 17;317[3]:269-79).
Wheezing is the most specific symptom of asthma, although it is not, in fact, terribly specific. In descending order, the next most specific symptoms are breathlessness, chest tightness, and cough.
The top seven diseases that mimic asthma symptoms are chronic obstructive pulmonary disease, rhinosinusitis, heart failure with preserved or reduced ejection fraction, gastroesophageal reflux disease, angina, anxiety, and vocal cord dysfunction syndrome.
Strike two for an asthma diagnosis is a patient’s report that albuterol doesn’t improve the symptoms. That definitely raises questions about the diagnosis.
“Most asthmatics get symptomatic relief from their disease,” Dr. Happel observed.
And, if there is no indication in the patient’s chart that the asthma diagnosis was based upon demonstration of airflow obstruction on spirometry, the diagnosis is thrown further into doubt. In the recent Canadian study, patients who didn’t undergo pulmonary function testing (PFT) to establish airflow limitation at their time of diagnosis were significantly less likely to have current asthma.
“I would strongly suggest everyone with the diagnosis of asthma get spirometry with bronchodilator testing,” Dr. Happel said. “Good-quality PFTs are critical in forming a solid diagnosis of asthma.”
In a patient who has symptoms consistent with asthma, a 200-cc and 12% or more improvement in forced expiratory volume in 1 second (FEV1) in response to bronchodilator challenge is supportive of the diagnosis. However, absence of reversible airway obstruction doesn’t exclude the possibility of asthma.
In the setting of low to-moderate clinical suspicion of asthma plus no demonstrable obstruction on spirometry, Dr. Happel recommends moving on to bronchial hyperreactivity testing via a methacholine challenge.
“The beauty of a methacholine challenge is that is has a high negative predictive value to help exclude the diagnosis of asthma, particularly in people who are having symptoms suggestive of asthma,” Dr. Happel explained. “If it takes more than 8 mg/mL of methacholine to elicit a 20% or greater decrease in FEV1, it’s probably something else. It’s not a particularly specific test, though; you can get false positives from a methacholine challenge.”
REPORTING FROM ACP INTERNAL MEDICINE
ED visits higher among pediatric asthma patients with comorbid depression, anxiety
TORONTO – Children with asthma who have a comorbid diagnosis of anxiety or depression are significantly more likely to make asthma-related visits to the emergency department, compared with their peers who do not have a mental health condition, results from a large administrative data analysis showed.
“There has been a fair bit of research on how comorbid mental health conditions can affect health care utilization for asthma in adults, but few studies have examined how comorbid mental health conditions like anxiety or depression can affect children with asthma,” one of the study authors, Caroline Neel, said in an interview in advance of the Pediatric Academic Societies meeting.
In all, the researchers identified 71,326 patients with asthma, with an overall rate of 16.3 ED visits per 100 child-years. Among these, children with a diagnosis of depression had significantly higher rates of ED visits (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01). Being enrolled in a Medicaid managed care plan or Medicaid fee-for-service plan also increased the rates of asthma-related ED visits (20.3 and 21.5 ED visits per 100 child-years, respectively; P less than .01 for both associations.)
“We were surprised to see that anxiety and depression seemed to increase asthma emergency department visits as much as other medical chronic illnesses like cystic fibrosis or sickle cell disease, and that kids on Medicaid, who tend to be our poorer kids, also had an independent risk of going to the emergency department,” Ms. Neel said. “Having Medicaid as well as anxiety or depression were independently related to going to the emergency room for asthma, so the study suggests that some of our highest-risk kids for asthma have multiple different contributors to getting sick and needing to go to the emergency room for an asthma attack.”
She acknowledged certain limitations of the analysis, including its reliance on administrative claims data to identify whether or not children had a diagnosis of anxiety or depression. “This doesn’t necessarily identify all the kids who may have these mental health conditions, since sometimes providers are less likely to document a diagnosis of a mental health conditions for children,” she said. “However, we still saw a significant association between a comorbid mental health condition and emergency department use for asthma, despite the potential that mental health conditions may have been under reported.”
The study’s senior author was Naomi Bardach, MD. The researchers reported having no financial disclosures.
TORONTO – Children with asthma who have a comorbid diagnosis of anxiety or depression are significantly more likely to make asthma-related visits to the emergency department, compared with their peers who do not have a mental health condition, results from a large administrative data analysis showed.
“There has been a fair bit of research on how comorbid mental health conditions can affect health care utilization for asthma in adults, but few studies have examined how comorbid mental health conditions like anxiety or depression can affect children with asthma,” one of the study authors, Caroline Neel, said in an interview in advance of the Pediatric Academic Societies meeting.
In all, the researchers identified 71,326 patients with asthma, with an overall rate of 16.3 ED visits per 100 child-years. Among these, children with a diagnosis of depression had significantly higher rates of ED visits (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01). Being enrolled in a Medicaid managed care plan or Medicaid fee-for-service plan also increased the rates of asthma-related ED visits (20.3 and 21.5 ED visits per 100 child-years, respectively; P less than .01 for both associations.)
“We were surprised to see that anxiety and depression seemed to increase asthma emergency department visits as much as other medical chronic illnesses like cystic fibrosis or sickle cell disease, and that kids on Medicaid, who tend to be our poorer kids, also had an independent risk of going to the emergency department,” Ms. Neel said. “Having Medicaid as well as anxiety or depression were independently related to going to the emergency room for asthma, so the study suggests that some of our highest-risk kids for asthma have multiple different contributors to getting sick and needing to go to the emergency room for an asthma attack.”
She acknowledged certain limitations of the analysis, including its reliance on administrative claims data to identify whether or not children had a diagnosis of anxiety or depression. “This doesn’t necessarily identify all the kids who may have these mental health conditions, since sometimes providers are less likely to document a diagnosis of a mental health conditions for children,” she said. “However, we still saw a significant association between a comorbid mental health condition and emergency department use for asthma, despite the potential that mental health conditions may have been under reported.”
The study’s senior author was Naomi Bardach, MD. The researchers reported having no financial disclosures.
TORONTO – Children with asthma who have a comorbid diagnosis of anxiety or depression are significantly more likely to make asthma-related visits to the emergency department, compared with their peers who do not have a mental health condition, results from a large administrative data analysis showed.
“There has been a fair bit of research on how comorbid mental health conditions can affect health care utilization for asthma in adults, but few studies have examined how comorbid mental health conditions like anxiety or depression can affect children with asthma,” one of the study authors, Caroline Neel, said in an interview in advance of the Pediatric Academic Societies meeting.
In all, the researchers identified 71,326 patients with asthma, with an overall rate of 16.3 ED visits per 100 child-years. Among these, children with a diagnosis of depression had significantly higher rates of ED visits (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01). Being enrolled in a Medicaid managed care plan or Medicaid fee-for-service plan also increased the rates of asthma-related ED visits (20.3 and 21.5 ED visits per 100 child-years, respectively; P less than .01 for both associations.)
“We were surprised to see that anxiety and depression seemed to increase asthma emergency department visits as much as other medical chronic illnesses like cystic fibrosis or sickle cell disease, and that kids on Medicaid, who tend to be our poorer kids, also had an independent risk of going to the emergency department,” Ms. Neel said. “Having Medicaid as well as anxiety or depression were independently related to going to the emergency room for asthma, so the study suggests that some of our highest-risk kids for asthma have multiple different contributors to getting sick and needing to go to the emergency room for an asthma attack.”
She acknowledged certain limitations of the analysis, including its reliance on administrative claims data to identify whether or not children had a diagnosis of anxiety or depression. “This doesn’t necessarily identify all the kids who may have these mental health conditions, since sometimes providers are less likely to document a diagnosis of a mental health conditions for children,” she said. “However, we still saw a significant association between a comorbid mental health condition and emergency department use for asthma, despite the potential that mental health conditions may have been under reported.”
The study’s senior author was Naomi Bardach, MD. The researchers reported having no financial disclosures.
Key clinical point: Anxiety and depression are associated with higher rates of ED use in children with asthma.
Major finding: (21.5 visits per 100 child-years; P less than .01), as did those with a diagnosis of anxiety (19.5 ED visits per 100 child-years; P less than .01).
Study details: An analysis of 71,326 patients with asthma from the Massachusetts All Payer Claims Database for 2014-2015.
Disclosures: The researchers reported having no financial disclosures.
In young MCL patients, optimal treatment may vary
, according to a recent review published in Best Practice & Research Clinical Haematology.
Use of high-dose cytarabine plus rituximab as frontline treatment is well established, with median overall survival now exceeding 10 years, said Rory McCulloch, MD, and Simon Rule, MD, of the department of Haematology, Derriford Hospital, Plymouth, England. However, there is no proven benefit to conventional therapy in patients with asymptomatic, non-bulky disease, making a watch-and-wait strategy appropriate for these patients, the authors said.
On the opposite end of the spectrum there is a subgroup of patients characterized by TP53 mutations and poor prognostic index scores that have poor outcomes in spite of conventional therapy.
These patients might have improved outcomes either with early allogeneic haematopoietic cell transplantation (allo-HCT), or, especially, clinical trials of novel agents in the upfront setting, the authors noted.
“There are a host of exciting novel agents, most prominently the BTK inhibitors, that are game changing with respect to their activity,” wrote Dr. McCulloch and Dr. Rule. “Based on the long-term results seen with conventional therapy, it is premature to be considering such new drugs in the frontline setting outside the context of a clinical trial, but it is hard to believe they will not become incorporated into treatment protocols in the future.”
Watch-and-wait treatment strategies for lower-risk patients are supported by the results of two single-center, retrospective studies published in 2009 that suggest the practice has no adverse impact on overall survival. More recent registry studies, published in 2016 and 2017, have shown that a significant proportion of patients can be managed according to the watch-and-wait strategy.
Although it’s been challenging to precisely define the group of patients for whom watch-and-wait is appropriate, enrollment criteria for studies have generally specified that patients be asymptomatic with non-bulky disease and non-blastoid morphology, they said.
For the minority of patients presenting with high-risk disease, allo-HCT may improve outcomes, according to Dr. McCulloch and Dr. Rule. One prospective study evaluating allogeneic transplants in frontline therapy showed favorable outcomes in younger patients, although few high-risk patients were enrolled.
However, a second prospective study of allo-HCT, involving 25 patients with untreated MCL in the United Kingdom, demonstrated a 2-year overall survival of 80%. “Although immature, the results are encouraging and provide data to support frontline allogeneic transplant for some patients,” Dr. McCulloch and Dr. Rule said in a comment on that study.
Novel agent studies have produced mixed results in treatment settings relevant to younger, high-risk MCL patients, though key trials are ongoing that could change practice.
One phase 2 study is evaluating obinituzumab, the fully humanized anti-CD20, as part of MCL induction and maintenance. Results of that study could challenge the role of rituximab in maintenance, the review authors noted. Likewise, the immune modulator lenalidomide has been evaluated as maintenance in an Italian phase 3 trial that recently closed to recruitment.
BTK inhibitors represent a “step change” in the management of MCL, according to the authors of this review.
“It has become clear that earlier use of ibrutinib leads to an improved outcome [in MCL] and it is logical to extend this into frontline treatment,” they wrote.
A randomized phase 3, multinational trial known as TRIANGLE, now open to recruitment, is designed to evaluate use of ibrutinib in both induction and maintenance. Investigators plan to enroll 870 patients into the three-arm study, which will also evaluate the use of ibrutinib as part of induction, but with no autologous stem cell transplant.
“The trial is the first to randomize to a non-ASCT arm since the introduction of rituximab and cytarabine to the induction regimen and the results have the potential to significantly reduce chemotherapy intensity and toxicity,” the authors said.
Dr. Rule reported consulting for Pharmacyclics, Napp, Sunesis, Acerta Pharma, Kite, AstraZeneca, Roche, Janssen, and Celgene, and research funding from Janssen, Celgene, and GSK. Dr. McCulloch reported having no financial disclosures.
SOURCE: McCulloch R et al. Best Pract Res Clin Haematol. 2018 Mar;31(1):90-8.
, according to a recent review published in Best Practice & Research Clinical Haematology.
Use of high-dose cytarabine plus rituximab as frontline treatment is well established, with median overall survival now exceeding 10 years, said Rory McCulloch, MD, and Simon Rule, MD, of the department of Haematology, Derriford Hospital, Plymouth, England. However, there is no proven benefit to conventional therapy in patients with asymptomatic, non-bulky disease, making a watch-and-wait strategy appropriate for these patients, the authors said.
On the opposite end of the spectrum there is a subgroup of patients characterized by TP53 mutations and poor prognostic index scores that have poor outcomes in spite of conventional therapy.
These patients might have improved outcomes either with early allogeneic haematopoietic cell transplantation (allo-HCT), or, especially, clinical trials of novel agents in the upfront setting, the authors noted.
“There are a host of exciting novel agents, most prominently the BTK inhibitors, that are game changing with respect to their activity,” wrote Dr. McCulloch and Dr. Rule. “Based on the long-term results seen with conventional therapy, it is premature to be considering such new drugs in the frontline setting outside the context of a clinical trial, but it is hard to believe they will not become incorporated into treatment protocols in the future.”
Watch-and-wait treatment strategies for lower-risk patients are supported by the results of two single-center, retrospective studies published in 2009 that suggest the practice has no adverse impact on overall survival. More recent registry studies, published in 2016 and 2017, have shown that a significant proportion of patients can be managed according to the watch-and-wait strategy.
Although it’s been challenging to precisely define the group of patients for whom watch-and-wait is appropriate, enrollment criteria for studies have generally specified that patients be asymptomatic with non-bulky disease and non-blastoid morphology, they said.
For the minority of patients presenting with high-risk disease, allo-HCT may improve outcomes, according to Dr. McCulloch and Dr. Rule. One prospective study evaluating allogeneic transplants in frontline therapy showed favorable outcomes in younger patients, although few high-risk patients were enrolled.
However, a second prospective study of allo-HCT, involving 25 patients with untreated MCL in the United Kingdom, demonstrated a 2-year overall survival of 80%. “Although immature, the results are encouraging and provide data to support frontline allogeneic transplant for some patients,” Dr. McCulloch and Dr. Rule said in a comment on that study.
Novel agent studies have produced mixed results in treatment settings relevant to younger, high-risk MCL patients, though key trials are ongoing that could change practice.
One phase 2 study is evaluating obinituzumab, the fully humanized anti-CD20, as part of MCL induction and maintenance. Results of that study could challenge the role of rituximab in maintenance, the review authors noted. Likewise, the immune modulator lenalidomide has been evaluated as maintenance in an Italian phase 3 trial that recently closed to recruitment.
BTK inhibitors represent a “step change” in the management of MCL, according to the authors of this review.
“It has become clear that earlier use of ibrutinib leads to an improved outcome [in MCL] and it is logical to extend this into frontline treatment,” they wrote.
A randomized phase 3, multinational trial known as TRIANGLE, now open to recruitment, is designed to evaluate use of ibrutinib in both induction and maintenance. Investigators plan to enroll 870 patients into the three-arm study, which will also evaluate the use of ibrutinib as part of induction, but with no autologous stem cell transplant.
“The trial is the first to randomize to a non-ASCT arm since the introduction of rituximab and cytarabine to the induction regimen and the results have the potential to significantly reduce chemotherapy intensity and toxicity,” the authors said.
Dr. Rule reported consulting for Pharmacyclics, Napp, Sunesis, Acerta Pharma, Kite, AstraZeneca, Roche, Janssen, and Celgene, and research funding from Janssen, Celgene, and GSK. Dr. McCulloch reported having no financial disclosures.
SOURCE: McCulloch R et al. Best Pract Res Clin Haematol. 2018 Mar;31(1):90-8.
, according to a recent review published in Best Practice & Research Clinical Haematology.
Use of high-dose cytarabine plus rituximab as frontline treatment is well established, with median overall survival now exceeding 10 years, said Rory McCulloch, MD, and Simon Rule, MD, of the department of Haematology, Derriford Hospital, Plymouth, England. However, there is no proven benefit to conventional therapy in patients with asymptomatic, non-bulky disease, making a watch-and-wait strategy appropriate for these patients, the authors said.
On the opposite end of the spectrum there is a subgroup of patients characterized by TP53 mutations and poor prognostic index scores that have poor outcomes in spite of conventional therapy.
These patients might have improved outcomes either with early allogeneic haematopoietic cell transplantation (allo-HCT), or, especially, clinical trials of novel agents in the upfront setting, the authors noted.
“There are a host of exciting novel agents, most prominently the BTK inhibitors, that are game changing with respect to their activity,” wrote Dr. McCulloch and Dr. Rule. “Based on the long-term results seen with conventional therapy, it is premature to be considering such new drugs in the frontline setting outside the context of a clinical trial, but it is hard to believe they will not become incorporated into treatment protocols in the future.”
Watch-and-wait treatment strategies for lower-risk patients are supported by the results of two single-center, retrospective studies published in 2009 that suggest the practice has no adverse impact on overall survival. More recent registry studies, published in 2016 and 2017, have shown that a significant proportion of patients can be managed according to the watch-and-wait strategy.
Although it’s been challenging to precisely define the group of patients for whom watch-and-wait is appropriate, enrollment criteria for studies have generally specified that patients be asymptomatic with non-bulky disease and non-blastoid morphology, they said.
For the minority of patients presenting with high-risk disease, allo-HCT may improve outcomes, according to Dr. McCulloch and Dr. Rule. One prospective study evaluating allogeneic transplants in frontline therapy showed favorable outcomes in younger patients, although few high-risk patients were enrolled.
However, a second prospective study of allo-HCT, involving 25 patients with untreated MCL in the United Kingdom, demonstrated a 2-year overall survival of 80%. “Although immature, the results are encouraging and provide data to support frontline allogeneic transplant for some patients,” Dr. McCulloch and Dr. Rule said in a comment on that study.
Novel agent studies have produced mixed results in treatment settings relevant to younger, high-risk MCL patients, though key trials are ongoing that could change practice.
One phase 2 study is evaluating obinituzumab, the fully humanized anti-CD20, as part of MCL induction and maintenance. Results of that study could challenge the role of rituximab in maintenance, the review authors noted. Likewise, the immune modulator lenalidomide has been evaluated as maintenance in an Italian phase 3 trial that recently closed to recruitment.
BTK inhibitors represent a “step change” in the management of MCL, according to the authors of this review.
“It has become clear that earlier use of ibrutinib leads to an improved outcome [in MCL] and it is logical to extend this into frontline treatment,” they wrote.
A randomized phase 3, multinational trial known as TRIANGLE, now open to recruitment, is designed to evaluate use of ibrutinib in both induction and maintenance. Investigators plan to enroll 870 patients into the three-arm study, which will also evaluate the use of ibrutinib as part of induction, but with no autologous stem cell transplant.
“The trial is the first to randomize to a non-ASCT arm since the introduction of rituximab and cytarabine to the induction regimen and the results have the potential to significantly reduce chemotherapy intensity and toxicity,” the authors said.
Dr. Rule reported consulting for Pharmacyclics, Napp, Sunesis, Acerta Pharma, Kite, AstraZeneca, Roche, Janssen, and Celgene, and research funding from Janssen, Celgene, and GSK. Dr. McCulloch reported having no financial disclosures.
SOURCE: McCulloch R et al. Best Pract Res Clin Haematol. 2018 Mar;31(1):90-8.
FROM BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
SAMHSA Helps Translate Science Into Real-Life Practice
The Substance Abuse and Mental Health Services Administration (SAMHSA) has launched a new Resource Center, aiming to give communities, clinicians, policy makers, and others the tools they need to put evidence-based information into practice.
The Evidence-Based Resource Center (www.samhsa.gov/ebp-resource-center) provides new or updated Treatment Improvement Protocols, tool kits, resource guides, clinical practice guidelines , and other science-based resources. The website has an easy-to-use point-and-click system. Users can search by topic, resource, target population, and target audience. The site also includes an opioid-specific resources section.
The center is part of a new comprehensive approach that allows rapid development and dissemination of the latest expert consensus on prevention, treatment, and recovery, SAMHSA says. It also provides communities and practitioners with tools to facilitate comprehensive needs assessment, match interventions to those needs, support implementation, and evaluate and incorporate continuous quality improvement as they translate science into action.
The Substance Abuse and Mental Health Services Administration (SAMHSA) has launched a new Resource Center, aiming to give communities, clinicians, policy makers, and others the tools they need to put evidence-based information into practice.
The Evidence-Based Resource Center (www.samhsa.gov/ebp-resource-center) provides new or updated Treatment Improvement Protocols, tool kits, resource guides, clinical practice guidelines , and other science-based resources. The website has an easy-to-use point-and-click system. Users can search by topic, resource, target population, and target audience. The site also includes an opioid-specific resources section.
The center is part of a new comprehensive approach that allows rapid development and dissemination of the latest expert consensus on prevention, treatment, and recovery, SAMHSA says. It also provides communities and practitioners with tools to facilitate comprehensive needs assessment, match interventions to those needs, support implementation, and evaluate and incorporate continuous quality improvement as they translate science into action.
The Substance Abuse and Mental Health Services Administration (SAMHSA) has launched a new Resource Center, aiming to give communities, clinicians, policy makers, and others the tools they need to put evidence-based information into practice.
The Evidence-Based Resource Center (www.samhsa.gov/ebp-resource-center) provides new or updated Treatment Improvement Protocols, tool kits, resource guides, clinical practice guidelines , and other science-based resources. The website has an easy-to-use point-and-click system. Users can search by topic, resource, target population, and target audience. The site also includes an opioid-specific resources section.
The center is part of a new comprehensive approach that allows rapid development and dissemination of the latest expert consensus on prevention, treatment, and recovery, SAMHSA says. It also provides communities and practitioners with tools to facilitate comprehensive needs assessment, match interventions to those needs, support implementation, and evaluate and incorporate continuous quality improvement as they translate science into action.
Interferon-gamma release assay trumps tuberculin skin test in school-aged children
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
The interferon-gamma release assay (IGRA) was significantly more sensitive than a tuberculin skin test as an adjunct tuberculosis diagnosis of children aged 5 years and older, according to data from a population-based study of 778 cases.
IGRAs have shown greater specificity than tuberculin skin tests (TSTs), but data on their sensitivity to TB in children are limited, wrote Alexander W. Kay, MD, of the California Department of Public Health and his colleagues in a study published in Pediatrics.
Children younger than 1 year of age and those with CNS disease were significantly more likely to have indeterminate IGRA results, the researchers noted.
The study results were limited by the use of mainly enzyme-linked immunosorbent assay–based IGRA, which limited the data on enzyme-linked immunospot tests, the researchers said. The findings also were limited by the small number of children younger than 5 years.
However, the study is the largest North American analysis of IGRA in children, and based on the findings, “we argue that an IGRA should be considered the test of choice when evaluating children 5-18 years old for TB disease in high-resource, low-TB burden settings,” Dr. Kay and his associates wrote.
The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test. Dr. Kay and the other investigators had no financial conflicts to disclose.
SOURCE: Kay A et al. Pediatrics. 2018 May 4. doi: 10.1542/peds.2017-3918.
FROM PEDIATRICS
Key clinical point:
Major finding: Sensitivity was 96% for IGRA versus 83% for TST among children aged 5-18 years.
Study details: The data come from TB patients aged 18 years and younger enrolled in the California TB registry during 2010-2015.
Disclosures: The study was funded by the Centers for Disease Control and Prevention. Coauthor Shamim Islam, MD, disclosed financial support from Qiagen, maker of the QuantiFERON test; Dr. Kay and the other investigators had no financial conflicts to disclose.
Source: Kay A et al. Pediatrics. 2018 May 4. doi: 10. 1542/ peds. 2017- 3918.
In COPD, tai chi confers long-term benefit
and seems to confer better long-term improvement, suggests a study published online in the journal CHEST®.
Following 12 weeks of participation in tai chi or pulmonary rehabilitation, patients improved in most of the measurements taken, although no significant between-group differences were observed at that time. However, further improvements were observed in the tai chi group 12 weeks after the intervention had ended. These improvements manifested as a statistically significant 4.5 between-group difference in St. George’s Respiratory Questionnaire points in favor of tai chi (P less than .001)
“This observation, supported also by improvements in dyspnea and exercise performance, suggests that tai chi could be substituted for PR [pulmonary rehabilitation] in the treatment of COPD with greater convenience for patients,” the researchers concluded.
SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.
and seems to confer better long-term improvement, suggests a study published online in the journal CHEST®.
Following 12 weeks of participation in tai chi or pulmonary rehabilitation, patients improved in most of the measurements taken, although no significant between-group differences were observed at that time. However, further improvements were observed in the tai chi group 12 weeks after the intervention had ended. These improvements manifested as a statistically significant 4.5 between-group difference in St. George’s Respiratory Questionnaire points in favor of tai chi (P less than .001)
“This observation, supported also by improvements in dyspnea and exercise performance, suggests that tai chi could be substituted for PR [pulmonary rehabilitation] in the treatment of COPD with greater convenience for patients,” the researchers concluded.
SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.
and seems to confer better long-term improvement, suggests a study published online in the journal CHEST®.
Following 12 weeks of participation in tai chi or pulmonary rehabilitation, patients improved in most of the measurements taken, although no significant between-group differences were observed at that time. However, further improvements were observed in the tai chi group 12 weeks after the intervention had ended. These improvements manifested as a statistically significant 4.5 between-group difference in St. George’s Respiratory Questionnaire points in favor of tai chi (P less than .001)
“This observation, supported also by improvements in dyspnea and exercise performance, suggests that tai chi could be substituted for PR [pulmonary rehabilitation] in the treatment of COPD with greater convenience for patients,” the researchers concluded.
SOURCE: Polkey MI et al. CHEST. 2018 May;153[5]:1116-24.
FROM THE JOURNAL CHEST®
Novartis CAR T-cell therapy adds a lymphoma indication
Novartis’s after failure of two or more lines of systemic therapy.
The Food and Drug Administration approved the expanded indication on May 1. The chimeric antigen receptor (CAR) T-cell therapy was initially approved in Aug. 2017 for refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old. The new approval brings tisagenlecleucel into direct competition with Gilead Science’s CAR T-cell therapy axicabtagene ciloleucel (Yescarta), which was approved in Oct. 2017 for B-cell lymphoma.
Besides matching the competition, she said the lower price is because tisagenlecleucel takes longer to work for lymphoma, and the response isn’t as potent as for childhood ALL. Novartis is looking into chronic lymphocytic leukemia, multiple myeloma, and solid tumor indications for tisagenlecleucel and other CAR T-cell agents, she added.
The Centers for Medicare & Medicaid Services recently committed to covering outpatient administration of both agents for their initial indications; Novartis is working with CMS for coverage of the new lymphoma indication.
With both products, T cells are collected then shipped off to a company facility where a CAR gene is spliced into their DNA, essentially programming the T cells to attack the targeted cancer. The cells are then infused back into the patient.
In the phase 2 JULIET trial, tisagenlecleucel showed an overall response rate of 50% among 68 B-cell lymphoma patients, with 32% achieving complete response (CR) and 18% achieving partial response (PR). The median duration of response was not reached.
Axicabtagene ciloleucel’s label reports an objective response rate of 72% among 101 patients, with CR in 51% and PR in 21%. Median duration of response was 9.2 months but was also not reached among complete responders.
“Different trials. Different CARTs. Different levels of disease. Our drug is cryopreserved and theirs is not. No way to compare them,” the Novartis spokeswoman said when asked about the response differences.
T-cell reprogramming isn’t clean at this point in medical history; both agents carry black box warnings of potentially fatal cytokine release syndrome and neurologic toxicity, and both are subject to Risk Evaluation and Mitigation Strategy programs.
The B-cell lymphoma indication for both therapies includes diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The Gilead product carries an additional indication for primary mediastinal large B-cell lymphoma. Neither agent is indicated for primary central nervous system lymphoma. Both labels say that patients should not donate blood, organs, or tissues after treatment. Tisagenlecleucel labeling also notes that some commercial HIV nucleic acid tests may yield false positives after treatment.
Novartis said in a press release that T cells are treated at the company’s Morris Plains, N.J., facility with a turnaround time of about 22 days. Cryopreservation of the harvested cells gives providers some flexibility in treatment timing.
Novartis’s after failure of two or more lines of systemic therapy.
The Food and Drug Administration approved the expanded indication on May 1. The chimeric antigen receptor (CAR) T-cell therapy was initially approved in Aug. 2017 for refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old. The new approval brings tisagenlecleucel into direct competition with Gilead Science’s CAR T-cell therapy axicabtagene ciloleucel (Yescarta), which was approved in Oct. 2017 for B-cell lymphoma.
Besides matching the competition, she said the lower price is because tisagenlecleucel takes longer to work for lymphoma, and the response isn’t as potent as for childhood ALL. Novartis is looking into chronic lymphocytic leukemia, multiple myeloma, and solid tumor indications for tisagenlecleucel and other CAR T-cell agents, she added.
The Centers for Medicare & Medicaid Services recently committed to covering outpatient administration of both agents for their initial indications; Novartis is working with CMS for coverage of the new lymphoma indication.
With both products, T cells are collected then shipped off to a company facility where a CAR gene is spliced into their DNA, essentially programming the T cells to attack the targeted cancer. The cells are then infused back into the patient.
In the phase 2 JULIET trial, tisagenlecleucel showed an overall response rate of 50% among 68 B-cell lymphoma patients, with 32% achieving complete response (CR) and 18% achieving partial response (PR). The median duration of response was not reached.
Axicabtagene ciloleucel’s label reports an objective response rate of 72% among 101 patients, with CR in 51% and PR in 21%. Median duration of response was 9.2 months but was also not reached among complete responders.
“Different trials. Different CARTs. Different levels of disease. Our drug is cryopreserved and theirs is not. No way to compare them,” the Novartis spokeswoman said when asked about the response differences.
T-cell reprogramming isn’t clean at this point in medical history; both agents carry black box warnings of potentially fatal cytokine release syndrome and neurologic toxicity, and both are subject to Risk Evaluation and Mitigation Strategy programs.
The B-cell lymphoma indication for both therapies includes diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The Gilead product carries an additional indication for primary mediastinal large B-cell lymphoma. Neither agent is indicated for primary central nervous system lymphoma. Both labels say that patients should not donate blood, organs, or tissues after treatment. Tisagenlecleucel labeling also notes that some commercial HIV nucleic acid tests may yield false positives after treatment.
Novartis said in a press release that T cells are treated at the company’s Morris Plains, N.J., facility with a turnaround time of about 22 days. Cryopreservation of the harvested cells gives providers some flexibility in treatment timing.
Novartis’s after failure of two or more lines of systemic therapy.
The Food and Drug Administration approved the expanded indication on May 1. The chimeric antigen receptor (CAR) T-cell therapy was initially approved in Aug. 2017 for refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL) in patients up to 25 years old. The new approval brings tisagenlecleucel into direct competition with Gilead Science’s CAR T-cell therapy axicabtagene ciloleucel (Yescarta), which was approved in Oct. 2017 for B-cell lymphoma.
Besides matching the competition, she said the lower price is because tisagenlecleucel takes longer to work for lymphoma, and the response isn’t as potent as for childhood ALL. Novartis is looking into chronic lymphocytic leukemia, multiple myeloma, and solid tumor indications for tisagenlecleucel and other CAR T-cell agents, she added.
The Centers for Medicare & Medicaid Services recently committed to covering outpatient administration of both agents for their initial indications; Novartis is working with CMS for coverage of the new lymphoma indication.
With both products, T cells are collected then shipped off to a company facility where a CAR gene is spliced into their DNA, essentially programming the T cells to attack the targeted cancer. The cells are then infused back into the patient.
In the phase 2 JULIET trial, tisagenlecleucel showed an overall response rate of 50% among 68 B-cell lymphoma patients, with 32% achieving complete response (CR) and 18% achieving partial response (PR). The median duration of response was not reached.
Axicabtagene ciloleucel’s label reports an objective response rate of 72% among 101 patients, with CR in 51% and PR in 21%. Median duration of response was 9.2 months but was also not reached among complete responders.
“Different trials. Different CARTs. Different levels of disease. Our drug is cryopreserved and theirs is not. No way to compare them,” the Novartis spokeswoman said when asked about the response differences.
T-cell reprogramming isn’t clean at this point in medical history; both agents carry black box warnings of potentially fatal cytokine release syndrome and neurologic toxicity, and both are subject to Risk Evaluation and Mitigation Strategy programs.
The B-cell lymphoma indication for both therapies includes diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The Gilead product carries an additional indication for primary mediastinal large B-cell lymphoma. Neither agent is indicated for primary central nervous system lymphoma. Both labels say that patients should not donate blood, organs, or tissues after treatment. Tisagenlecleucel labeling also notes that some commercial HIV nucleic acid tests may yield false positives after treatment.
Novartis said in a press release that T cells are treated at the company’s Morris Plains, N.J., facility with a turnaround time of about 22 days. Cryopreservation of the harvested cells gives providers some flexibility in treatment timing.