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FDA clears test to monitor residual disease in CML
The Food and Drug Administration has cleared Bio-Rad’s digital polymerase chain reaction (PCR) testing solution to monitor patients’ molecular response to treatment for chronic myeloid leukemia.
The QXDx AutoDG ddPCR System combines Bio-Rad’s Droplet Digital PCR technology and the QXDx BCR-ABL %IS Kit, according to the company.
This so-called liquid biopsy test can “precisely and reproducibly” monitor the molecular response to tyrosine kinase inhibitor therapy. The current standard – reverse transcription quantitative PCR – can have variable results, especially at low levels of disease, according to Bio-Rad.
FDA clearance means that the product is “substantially equivalent” to an already-approved product and can be sold in the United States, according to the agency.
The Food and Drug Administration has cleared Bio-Rad’s digital polymerase chain reaction (PCR) testing solution to monitor patients’ molecular response to treatment for chronic myeloid leukemia.
The QXDx AutoDG ddPCR System combines Bio-Rad’s Droplet Digital PCR technology and the QXDx BCR-ABL %IS Kit, according to the company.
This so-called liquid biopsy test can “precisely and reproducibly” monitor the molecular response to tyrosine kinase inhibitor therapy. The current standard – reverse transcription quantitative PCR – can have variable results, especially at low levels of disease, according to Bio-Rad.
FDA clearance means that the product is “substantially equivalent” to an already-approved product and can be sold in the United States, according to the agency.
The Food and Drug Administration has cleared Bio-Rad’s digital polymerase chain reaction (PCR) testing solution to monitor patients’ molecular response to treatment for chronic myeloid leukemia.
The QXDx AutoDG ddPCR System combines Bio-Rad’s Droplet Digital PCR technology and the QXDx BCR-ABL %IS Kit, according to the company.
This so-called liquid biopsy test can “precisely and reproducibly” monitor the molecular response to tyrosine kinase inhibitor therapy. The current standard – reverse transcription quantitative PCR – can have variable results, especially at low levels of disease, according to Bio-Rad.
FDA clearance means that the product is “substantially equivalent” to an already-approved product and can be sold in the United States, according to the agency.
Death data spur black-box warning for gout drug Uloric
, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.
“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.
The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”
Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).
However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).
“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”
, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.
“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.
The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”
Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).
However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).
“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”
, the Food and Drug Administration declared on Feb. 21. The agency is now mandating a black-box warning.
“Health care professionals should reserve Uloric for use only in patients who have failed or do not tolerate allopurinol,” the FDA announced. “Counsel patients about the cardiovascular risk with Uloric,” the agency suggested, and advise them to seek medical attention at once if they have cardiac symptoms such as chest pain, shortness of breath, rapid or irregular heartbeat, or dizziness.
The FDA’s move comes a decade after it approved febuxostat as a gout treatment. As the FDA noted in its announcement, “the number of medicines to treat gout is limited, and there is an unmet need for treatments for this disease.”
Research has suggested that both febuxostat and allopurinol have similar efficacy. Some experts have recommended febuxostat as an alternative for patients who shouldn’t take allopurinol (Semin Arthritis Rheum. 2013 Dec;43[3]:367-75).
However, research has raised concerns about febuxostat’s cardiac risk. In its Feb. 21 statement, the FDA pointed to the findings of a 2010-2017 postmarket clinical trial of 6,190 patients with gout who were treated with febuxostat or allopurinol (N Engl J Med. 2018;378:1200-10).
“In patients treated with Uloric, 15 deaths from heart-related causes were observed for every 1,000 patients treated for a year compared to 11 deaths from heart-related causes per 1,000 patients treated with allopurinol for a year,” the FDA said. “In addition, there were 26 deaths from any cause per 1,000 patients treated for a year with Uloric compared to 22 deaths per 1,000 patients treated for a year with allopurinol.”
SABR response rate falls short in early NSCLC
For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.
SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.
“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”
The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).
Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.
“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.
The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.
SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.
For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.
SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.
“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”
The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).
Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.
“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.
The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.
SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.
For patients with resectable stage I non–small cell lung cancer (NSCLC), stereotactic ablative radiotherapy (SABR) may lack the efficacy needed to replace surgical intervention, according to a recent phase II trial.
SABR provided a pathologic complete response rate (pCR) of 60%, which was “lower than hypothesized,” reported lead author David A. Palma, MD, PhD, of London (Ont.) Health Sciences Centre, and his colleagues.
“In patients with cancer who are fit for resection ... the role of SABR is controversial,” the investigators wrote in JAMA Oncology. “Although some recent studies suggest that SABR may achieve outcomes similar to surgery, others do not, and randomized clinical trials are currently under way to compare these 2 modalities.”
The present trial involved 40 adult patients with stage I NSCLC, good pulmonary function, and good performance status. Of these, 35 were evaluable for the primary endpoint, which was tumor pCR rate after SABR. Secondary endpoints were toxic effects, quality of life, distant control, regional control, and local control. Patients with tumors no larger than 3 cm in diameter were given 54 Gy in 3 fractions, while bigger tumors received 55 Gy in 5 fractions. Patients with tumors 2 cm or closer to the brachial plexus or mediastinum were given 60 Gy in 8 fractions. Ten weeks after SABR, sublobar resection or lobectomy was performed, via an open approach or with video-assisted thoracoscopic surgery (VATS).
Analysis revealed a pCR rate of 60%, which was lower than anticipated. One-month and 3-month survival rates were both 100%. After a median follow-up of 19 months, local control rate was 100%, but only three out of four patients (76%) had distant control, and half (53%) had regional control. After 2 years, three out of four patients were still alive (77%). Eighteen percent of patients experienced grade 3 or higher toxic effects.
“[T]he pCR rate of 60% at 10 weeks suggests that practitioners should be cautious in the use of SABR in patients with cancers who are fit for resection,” the investigators concluded.
The Ontario Institute for Cancer Research funded the study. Dr. Palma and Dr. Ward are patent holders for a computed tomography technology that assesses responses after radiotherapy. Dr. Louie reported honoraria from AstraZeneca and Varian Medical Systems Inc.
SOURCE: Palma et al. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.6993.
FROM JAMA ONCOLOGY
Good news on antipsychotics and birth defects
Boomers will spike U.S. health costs, but growing uninsured will soften their impact. Don’t miss early joint involvement in psoriasis. And an algorithm provides practical clinical guidance on managing diabetes.
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Boomers will spike U.S. health costs, but growing uninsured will soften their impact. Don’t miss early joint involvement in psoriasis. And an algorithm provides practical clinical guidance on managing diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Boomers will spike U.S. health costs, but growing uninsured will soften their impact. Don’t miss early joint involvement in psoriasis. And an algorithm provides practical clinical guidance on managing diabetes.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
Parental leave inequities: Kirti Magudia and Thomas Ng, Part I
The research was published in JAMA. Dr. Magudia talks about their experience doing this research, what they learned, and what the next steps are.
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The research was published in JAMA. Dr. Magudia talks about their experience doing this research, what they learned, and what the next steps are.
Apple Podcasts
Google Podcasts
Spotify
The research was published in JAMA. Dr. Magudia talks about their experience doing this research, what they learned, and what the next steps are.
Apple Podcasts
Google Podcasts
Spotify
A New Way to Measure How HIV Drugs Are Working
One of the tricky parts of HIV drug therapy is determining how well the drugs have worked. The HIV DNA (provirus) in resting cells is usually too defective to replicate itself the way intact provirus can. But most current tests cannot tell the difference between the two. However, researchers from Johns Hopkins University School of Medicine in Baltimore have developed an accurate and scalable assay to easily count the cells in the HIV reservoir.
A stable, latent reservoir for HIV-1 in resting CD4+ T cells is “the principle barrier to a cure,” the researchers say. Quantitative outgrowth assays and assays for cells that produce viral RNA after T-cell activation may underestimate the reservoir size because 1 round of activation does not induce all proviruses. Many studies, the researchers say, rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of those assays is unclear since the vast majority of proviruses are defective.
In their study, supported by the National Institute of Allergy and Infectious Diseases, the researchers analyzed DNA sequences from > 400 HIV proviruses from 28 people with HIV. They mapped 2 types of flaws: deletions and lethal mutations. They then developed strategically placed “genetic probes” that could distinguish between deleted or highly mutated proviruses and intact ones. Finally, they developed a nanotechnology-based method to analyze 1 provirus at a time to determine how many in a sample are intact.
The researchers say their findings show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. Their hope is that their method will speed HIV research by allowing scientists to easily quantify the number of proviruses in an individual, which must be eliminated to achieve a cure.
One of the tricky parts of HIV drug therapy is determining how well the drugs have worked. The HIV DNA (provirus) in resting cells is usually too defective to replicate itself the way intact provirus can. But most current tests cannot tell the difference between the two. However, researchers from Johns Hopkins University School of Medicine in Baltimore have developed an accurate and scalable assay to easily count the cells in the HIV reservoir.
A stable, latent reservoir for HIV-1 in resting CD4+ T cells is “the principle barrier to a cure,” the researchers say. Quantitative outgrowth assays and assays for cells that produce viral RNA after T-cell activation may underestimate the reservoir size because 1 round of activation does not induce all proviruses. Many studies, the researchers say, rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of those assays is unclear since the vast majority of proviruses are defective.
In their study, supported by the National Institute of Allergy and Infectious Diseases, the researchers analyzed DNA sequences from > 400 HIV proviruses from 28 people with HIV. They mapped 2 types of flaws: deletions and lethal mutations. They then developed strategically placed “genetic probes” that could distinguish between deleted or highly mutated proviruses and intact ones. Finally, they developed a nanotechnology-based method to analyze 1 provirus at a time to determine how many in a sample are intact.
The researchers say their findings show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. Their hope is that their method will speed HIV research by allowing scientists to easily quantify the number of proviruses in an individual, which must be eliminated to achieve a cure.
One of the tricky parts of HIV drug therapy is determining how well the drugs have worked. The HIV DNA (provirus) in resting cells is usually too defective to replicate itself the way intact provirus can. But most current tests cannot tell the difference between the two. However, researchers from Johns Hopkins University School of Medicine in Baltimore have developed an accurate and scalable assay to easily count the cells in the HIV reservoir.
A stable, latent reservoir for HIV-1 in resting CD4+ T cells is “the principle barrier to a cure,” the researchers say. Quantitative outgrowth assays and assays for cells that produce viral RNA after T-cell activation may underestimate the reservoir size because 1 round of activation does not induce all proviruses. Many studies, the researchers say, rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of those assays is unclear since the vast majority of proviruses are defective.
In their study, supported by the National Institute of Allergy and Infectious Diseases, the researchers analyzed DNA sequences from > 400 HIV proviruses from 28 people with HIV. They mapped 2 types of flaws: deletions and lethal mutations. They then developed strategically placed “genetic probes” that could distinguish between deleted or highly mutated proviruses and intact ones. Finally, they developed a nanotechnology-based method to analyze 1 provirus at a time to determine how many in a sample are intact.
The researchers say their findings show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. Their hope is that their method will speed HIV research by allowing scientists to easily quantify the number of proviruses in an individual, which must be eliminated to achieve a cure.
Combination model predicts imminent preeclampsia
A triple test was a significantly more effective predictor of preeclampsia than was either angiogenic placental growth factor (PlGF) alone or the antiangiogenic factor soluble fms-like tyrosine kinase-1(sFLT)/PlGF ratio, based on data from more than 15,000 pregnancies.
The use of either PlGF or sFLT/PlGF alone to predict preeclampsia fails to account for individual maternal risk factors or the measurement of blood pressure at presentation, wrote Anca Ciobanu, MD, of King’s College London, and her colleagues.
In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 15,247 singleton pregnancies with live births of healthy babies and compared the preeclampsia detection rates of PlGF, sFLT/PlGF and a competing risks model that included a combination of maternal factors and median values of PlGF, sFLT, and mean arterial pressure (triple test). Preeclampsia developed in 2.1% of pregnancies.
Overall, the triple-test detection rate for delivery with preeclampsia was 10% higher than the sFLT/PlGF ratio and 20% higher than PlGF alone based on assessment at 2 weeks or less or 4 weeks or less before delivery. The negative predictive value was similar for the three tests.
At 2 weeks or less before delivery, the area under the receiver operating characteristic curves (AUROC) for preeclampsia was significantly higher for the combination model (0.975), compared with PlGF (0.900) or the sFLT/PlGF ratio (0.932), with P less than .0001 in each case. Similarly, at 4 weeks or less before delivery, the AUROC for preeclampsia was 0.907 for the triple test, 0.827 for PlGF alone, and 0.857 for the sFLT/PlGF ratio, with P less than .0001 in each case.
The competing risks model allows clinicians more flexibility to identify patients at increased risk by considering factors including maternal characteristics and variations from normal blood pressure, Dr. Ciobanu and her associates noted. Also, the combination model, “can form the basis of future research that would quantify and incorporate into the model, symptoms such as headache and epigastric pain, as well as proteinuria, creatinine, liver enzymes and platelets.”
The study findings were limited by several factors including the potential predictive value of screening for women with hypertensive symptoms attending specialist clinics, and whether mean arterial pressure would be an effective measure in patients seen at these clinics, the researchers noted. However, the results support the value of the competing risks model, which “provides a personalized risk for delivery with preeclampsia that could lead to personalized stratification of the intensity of monitoring and timing of delivery.”
The study was supported by a grant from the Fetal Medicine Foundation; Thermo Fisher Scientific provided the reagents and equipment. The researchers had no financial conflicts of interest.
SOURCE: Ciobanu A et al. Am J Obstet Gynecol. 2019 Feb 7. doi. org/10.1016/j.ajog.2019.01.235.
A triple test was a significantly more effective predictor of preeclampsia than was either angiogenic placental growth factor (PlGF) alone or the antiangiogenic factor soluble fms-like tyrosine kinase-1(sFLT)/PlGF ratio, based on data from more than 15,000 pregnancies.
The use of either PlGF or sFLT/PlGF alone to predict preeclampsia fails to account for individual maternal risk factors or the measurement of blood pressure at presentation, wrote Anca Ciobanu, MD, of King’s College London, and her colleagues.
In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 15,247 singleton pregnancies with live births of healthy babies and compared the preeclampsia detection rates of PlGF, sFLT/PlGF and a competing risks model that included a combination of maternal factors and median values of PlGF, sFLT, and mean arterial pressure (triple test). Preeclampsia developed in 2.1% of pregnancies.
Overall, the triple-test detection rate for delivery with preeclampsia was 10% higher than the sFLT/PlGF ratio and 20% higher than PlGF alone based on assessment at 2 weeks or less or 4 weeks or less before delivery. The negative predictive value was similar for the three tests.
At 2 weeks or less before delivery, the area under the receiver operating characteristic curves (AUROC) for preeclampsia was significantly higher for the combination model (0.975), compared with PlGF (0.900) or the sFLT/PlGF ratio (0.932), with P less than .0001 in each case. Similarly, at 4 weeks or less before delivery, the AUROC for preeclampsia was 0.907 for the triple test, 0.827 for PlGF alone, and 0.857 for the sFLT/PlGF ratio, with P less than .0001 in each case.
The competing risks model allows clinicians more flexibility to identify patients at increased risk by considering factors including maternal characteristics and variations from normal blood pressure, Dr. Ciobanu and her associates noted. Also, the combination model, “can form the basis of future research that would quantify and incorporate into the model, symptoms such as headache and epigastric pain, as well as proteinuria, creatinine, liver enzymes and platelets.”
The study findings were limited by several factors including the potential predictive value of screening for women with hypertensive symptoms attending specialist clinics, and whether mean arterial pressure would be an effective measure in patients seen at these clinics, the researchers noted. However, the results support the value of the competing risks model, which “provides a personalized risk for delivery with preeclampsia that could lead to personalized stratification of the intensity of monitoring and timing of delivery.”
The study was supported by a grant from the Fetal Medicine Foundation; Thermo Fisher Scientific provided the reagents and equipment. The researchers had no financial conflicts of interest.
SOURCE: Ciobanu A et al. Am J Obstet Gynecol. 2019 Feb 7. doi. org/10.1016/j.ajog.2019.01.235.
A triple test was a significantly more effective predictor of preeclampsia than was either angiogenic placental growth factor (PlGF) alone or the antiangiogenic factor soluble fms-like tyrosine kinase-1(sFLT)/PlGF ratio, based on data from more than 15,000 pregnancies.
The use of either PlGF or sFLT/PlGF alone to predict preeclampsia fails to account for individual maternal risk factors or the measurement of blood pressure at presentation, wrote Anca Ciobanu, MD, of King’s College London, and her colleagues.
In a study published in the American Journal of Obstetrics & Gynecology, the researchers reviewed data from 15,247 singleton pregnancies with live births of healthy babies and compared the preeclampsia detection rates of PlGF, sFLT/PlGF and a competing risks model that included a combination of maternal factors and median values of PlGF, sFLT, and mean arterial pressure (triple test). Preeclampsia developed in 2.1% of pregnancies.
Overall, the triple-test detection rate for delivery with preeclampsia was 10% higher than the sFLT/PlGF ratio and 20% higher than PlGF alone based on assessment at 2 weeks or less or 4 weeks or less before delivery. The negative predictive value was similar for the three tests.
At 2 weeks or less before delivery, the area under the receiver operating characteristic curves (AUROC) for preeclampsia was significantly higher for the combination model (0.975), compared with PlGF (0.900) or the sFLT/PlGF ratio (0.932), with P less than .0001 in each case. Similarly, at 4 weeks or less before delivery, the AUROC for preeclampsia was 0.907 for the triple test, 0.827 for PlGF alone, and 0.857 for the sFLT/PlGF ratio, with P less than .0001 in each case.
The competing risks model allows clinicians more flexibility to identify patients at increased risk by considering factors including maternal characteristics and variations from normal blood pressure, Dr. Ciobanu and her associates noted. Also, the combination model, “can form the basis of future research that would quantify and incorporate into the model, symptoms such as headache and epigastric pain, as well as proteinuria, creatinine, liver enzymes and platelets.”
The study findings were limited by several factors including the potential predictive value of screening for women with hypertensive symptoms attending specialist clinics, and whether mean arterial pressure would be an effective measure in patients seen at these clinics, the researchers noted. However, the results support the value of the competing risks model, which “provides a personalized risk for delivery with preeclampsia that could lead to personalized stratification of the intensity of monitoring and timing of delivery.”
The study was supported by a grant from the Fetal Medicine Foundation; Thermo Fisher Scientific provided the reagents and equipment. The researchers had no financial conflicts of interest.
SOURCE: Ciobanu A et al. Am J Obstet Gynecol. 2019 Feb 7. doi. org/10.1016/j.ajog.2019.01.235.
FROM THE AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY
Aripiprazole/clozapine combo more effective than monotherapies
Certain antipsychotic polytherapies, including aripiprazole and clozapine, are associated with a lower risk of psychiatric rehospitalization in patients with schizophrenia, according to Jari Tiihonen, MD, PhD, of the Karolinska Institute in Stockholm, and his associates.
The study population included a total of 62,250 patients from the Finnish Hospital Discharge register who were treated for schizophrenia in the inpatient setting from 1972 to 2014. The median patient age was 45.6 years and the median length of follow-up was 14.1 years. Over the study period, 58.8% of this cohort were readmitted for psychiatric inpatient care, 67.2% used antipsychotic polypharmacy during the follow-up, and 57.5% were exposed to antipsychotic polypharmacy for at least 90 days, Dr. Tiihonen and his associates wrote in JAMA Psychiatry.
The combination of aripiprazole and clozapine was associated with the lowest risk of psychiatric rehospitalization, compared with those who received no therapy (hazard ratio, 0.42, 95% confidence interval, 0.39-0.46). Clozapine alone was the most effective antipsychotic monotherapy (HR, 0.49; 95% CI, 0.47-0.51), and when aripiprazole/clozapine was compared with clozapine alone, the polytherapy was significantly more effective (HR, 0.86; 95% CI, 0.79-0.94).
The difference between aripiprazole/clozapine and clozapine alone was even greater in patients who initially were hospitalized for their first episode of schizophrenia (HR, 0.78; 95% CI, 0.63-0.96). Overall, any antipsychotic polypharmacy was associated with a 7%-13% lower risk of hospitalization, compared with any monotherapy; , the authors noted.
“It should be acknowledged that statements about a preferential use of antipsychotic monotherapy for maintenance treatment of schizophrenia lack evidence, and that currently available evidence – although gathered with few nonrandomized cohort studies that have their own limitations – indicates the opposite,” they concluded.
Dr. Tiihonen and several of his associates reported numerous conflicts of interest.
SOURCE: Tiihonen J et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4320.
Certain antipsychotic polytherapies, including aripiprazole and clozapine, are associated with a lower risk of psychiatric rehospitalization in patients with schizophrenia, according to Jari Tiihonen, MD, PhD, of the Karolinska Institute in Stockholm, and his associates.
The study population included a total of 62,250 patients from the Finnish Hospital Discharge register who were treated for schizophrenia in the inpatient setting from 1972 to 2014. The median patient age was 45.6 years and the median length of follow-up was 14.1 years. Over the study period, 58.8% of this cohort were readmitted for psychiatric inpatient care, 67.2% used antipsychotic polypharmacy during the follow-up, and 57.5% were exposed to antipsychotic polypharmacy for at least 90 days, Dr. Tiihonen and his associates wrote in JAMA Psychiatry.
The combination of aripiprazole and clozapine was associated with the lowest risk of psychiatric rehospitalization, compared with those who received no therapy (hazard ratio, 0.42, 95% confidence interval, 0.39-0.46). Clozapine alone was the most effective antipsychotic monotherapy (HR, 0.49; 95% CI, 0.47-0.51), and when aripiprazole/clozapine was compared with clozapine alone, the polytherapy was significantly more effective (HR, 0.86; 95% CI, 0.79-0.94).
The difference between aripiprazole/clozapine and clozapine alone was even greater in patients who initially were hospitalized for their first episode of schizophrenia (HR, 0.78; 95% CI, 0.63-0.96). Overall, any antipsychotic polypharmacy was associated with a 7%-13% lower risk of hospitalization, compared with any monotherapy; , the authors noted.
“It should be acknowledged that statements about a preferential use of antipsychotic monotherapy for maintenance treatment of schizophrenia lack evidence, and that currently available evidence – although gathered with few nonrandomized cohort studies that have their own limitations – indicates the opposite,” they concluded.
Dr. Tiihonen and several of his associates reported numerous conflicts of interest.
SOURCE: Tiihonen J et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4320.
Certain antipsychotic polytherapies, including aripiprazole and clozapine, are associated with a lower risk of psychiatric rehospitalization in patients with schizophrenia, according to Jari Tiihonen, MD, PhD, of the Karolinska Institute in Stockholm, and his associates.
The study population included a total of 62,250 patients from the Finnish Hospital Discharge register who were treated for schizophrenia in the inpatient setting from 1972 to 2014. The median patient age was 45.6 years and the median length of follow-up was 14.1 years. Over the study period, 58.8% of this cohort were readmitted for psychiatric inpatient care, 67.2% used antipsychotic polypharmacy during the follow-up, and 57.5% were exposed to antipsychotic polypharmacy for at least 90 days, Dr. Tiihonen and his associates wrote in JAMA Psychiatry.
The combination of aripiprazole and clozapine was associated with the lowest risk of psychiatric rehospitalization, compared with those who received no therapy (hazard ratio, 0.42, 95% confidence interval, 0.39-0.46). Clozapine alone was the most effective antipsychotic monotherapy (HR, 0.49; 95% CI, 0.47-0.51), and when aripiprazole/clozapine was compared with clozapine alone, the polytherapy was significantly more effective (HR, 0.86; 95% CI, 0.79-0.94).
The difference between aripiprazole/clozapine and clozapine alone was even greater in patients who initially were hospitalized for their first episode of schizophrenia (HR, 0.78; 95% CI, 0.63-0.96). Overall, any antipsychotic polypharmacy was associated with a 7%-13% lower risk of hospitalization, compared with any monotherapy; , the authors noted.
“It should be acknowledged that statements about a preferential use of antipsychotic monotherapy for maintenance treatment of schizophrenia lack evidence, and that currently available evidence – although gathered with few nonrandomized cohort studies that have their own limitations – indicates the opposite,” they concluded.
Dr. Tiihonen and several of his associates reported numerous conflicts of interest.
SOURCE: Tiihonen J et al. JAMA Psychiatry. 2019 Feb 20. doi: 10.1001/jamapsychiatry.2018.4320.
FROM JAMA PSYCHIATRY
Delayed cord clamping didn’t drop maternal hemoglobin in term cesarean deliveries
LAS VEGAS – according to a recent study.
The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.
For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)
However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).
Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.
Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.
Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.
Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.
In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.
Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.
Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m2.
Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.
Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).
“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”
The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.
SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.
LAS VEGAS – according to a recent study.
The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.
For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)
However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).
Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.
Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.
Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.
Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.
In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.
Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.
Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m2.
Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.
Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).
“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”
The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.
SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.
LAS VEGAS – according to a recent study.
The change in maternal hemoglobin from preoperative level to postoperative day 1, the study’s primary outcome measure, was not significantly different whether the umbilical cord was clamped within 15 seconds of delivery or clamping was delayed for 1 minute.
For the 56 women who received immediate cord clamping, hemoglobin dropped a mean 1.78 g/dL; for the 57 women who received delayed cord clamping, the drop was 1.85 g/dL (P = .69). Mean estimated blood loss for the delayed clamping group was numerically higher at 884 mL, compared with 830 mL for the immediate clamping group, but this was not a statistically significant difference (P = .13)
However, the practice did result in significantly greater neonatal hemoglobin measured at 24-72 hours post delivery. Hemoglobin data were available for 90 infants, or about 80% of participants. For the 44 infants in the immediate clamping group, mean hemoglobin was 16.4 g/dL; for the delayed clamping group, the figure was 18.1 g/dL (P less than .01).
Although delayed cord clamping has clear benefits to the neonate, whether the practice adversely affects women undergoing cesarean was not clear, said Stephanie Purisch, MD, who discussed the findings of the two-site, randomized, clinical trial during a fellows research session at the meeting sponsored by the Society for Maternal-Fetal Medicine.
“Maternal outcomes have not been a focus of research” in the cord clamping literature, said Dr. Purisch, from Columbia University, New York. A 2013 Cochrane review found that delayed cord clamping did not change postpartum hemoglobin levels or increase blood loss or the need for transfusion. However, she said, the review included only healthy women who expected a vaginal delivery, so cesarean deliveries were undersampled in the data.
Of the 3,911 deliveries included in all prior randomized, controlled trials of delayed cord clamping, just 87, or 2.2%, were cesarean deliveries, she said. In cesarean deliveries, mean blood loss is double that of vaginal deliveries. Delayed clamping could further increase bleeding because the hysterotomy closure is delayed, said Dr. Purisch, so the question of safety in cesarean deliveries is clinically important.
Faced with this knowledge gap, Dr. Purisch and her colleagues constructed a prospective, randomized, controlled trial of delayed cord clamping in cesarean delivery at term, with the hypothesis that maternal blood loss would be increased by the practice.
Patients were eligible if they had singleton gestations with cesarean deliveries scheduled at 37 weeks’ gestation or more. Patients with known placentation problems, significant maternal or known fetal anemia, maternal bleeding disorders, and preeclampsia were excluded. The study also did not include pregnancies with known fetal anomalies or intrauterine growth retardation, or those in which cord blood banking was planned or the mother would refuse blood products.
In an intention-to-treat analysis, Dr. Purisch and her colleagues randomly assigned participants 1:1 to immediate cord clamping, defined as clamping the cord by 15 seconds after delivery, or delayed cord clamping, in which the umbilical cord was clamped 1 minute after delivery.
Oxytocin was routinely administered to each group on delivery, and there was no umbilical cord milking in either group. For the delayed-clamping group, the infant was kept at the level of the placenta and tended by the pediatric team during the minute before clamping. Dr. Purisch explained that cord clamping was performed before 60 seconds in the intervention group if needed for neonatal resuscitation.
Participants were similar in the two study arms, with a median gestational age of 39.1 weeks at delivery. Most women (60%-64%) had one prior cesarean delivery, with about a quarter having two or more prior cesarean deliveries. Preoperative maternal hemoglobin was 11.6-12.0 g/dL. About 41% of participants were Hispanic, and the median prepregnancy body mass index for participants was about 27 kg/m2.
Looking at secondary outcome measures, there was no difference in rates of postpartum hemorrhage or uterotonic administration between the two groups (P = .99 for both). Hemoglobin levels at postoperative day 1 were numerically higher for the delayed cord clamping group, but the difference wasn’t significant (10.2 vs. 9.8 g/dL; P = .18). Just two women, both in the immediate cord clamping group, required blood transfusions.
Additional neonatal secondary outcome measures included birth weight, Apgar scores at 1 and 5 minutes, the need for phototherapy for jaundice, and umbilical cord artery pH. There were no between-group differences except that umbilical cord artery pH was slightly lower in the delayed group (7.2 vs. 7.3; P = .04).
“Delayed cord clamping is not associated with increased maternal blood loss … but it does achieve higher neonatal hemoglobin levels at 24-72 hours of life,” said Dr. Purisch. “These results provide support for the application of current [American College of Obstetricians and Gynecologists] recommendations to women planned for cesarean delivery.”
The study was funded by the Columbia Maternal-Fetal Medicine Fellow Research Fund. Dr. Purisch reported no conflicts of interest.
SOURCE: Purisch, S. et al. Am J Obstet Gynecol. 2019 Jan;220(1):S37-38, Abstract 47.
REPORTING FROM THE PREGNANCY MEETING
Alcohol abstinence questioned as addiction treatment goal
BONITA SPRINGS, FLA. – Reductions in alcohol use bring about significant improvement in adverse consequences, mental health status, and quality of life, even if the reductions do not reach the level of abstinence, according to recent research presented at the annual meeting of the American Academy of Addiction Psychiatry.
The findings, experts say, demonstrate how a fixation on abstinence or elimination of all heavy drinking – the endpoints the Food and Drug Administration now require in pivotal clinical trials on alcohol use disorder (AUD) treatments – is shortsighted and can unnecessarily discourage people with alcohol use disorder from pursuing treatment.
“We need to think a little differently, or a little out of the box, from the way we’ve been thinking in the past,” said Raymond F. Anton, MD, professor of psychiatry at the Medical University of South Carolina in Charleston and chair of the Alcohol Clinical Trials Initiative (ACTIVE), a group advocating for a new endpoint that recognizes the benefits of lesser reductions in alcohol intake.
In a new analysis using data from the COMBINE study, researchers looked at the associations between reduction in World Health Organization drinking risk levels of alcohol consumption and clinically meaningful outcomes among people in treatment.
There are four levels: very high (more than 7.1 14-g drinks a day for men and more than 4.3 for women); high (4.3-7.1 or 2.9-4.3, respectively); moderate (2.9-4.3 or 1.4-2.9); and low (less than 2.9 or less than 1.4).
Researchers assessed responses to treatment with acamprosate, naltrexone, and psychological intervention in patients an average of 44 years old with 71% of their days being heavy drinking days. They found significant improvement in consequences tied to drinking, according to the Drinker Inventory of Consequences, and in mental health according to the Short Form Health Survey and the WHO Quality of Life assessment – even when the improvement was only by one WHO risk level – or just a few drinks a day – and did not involve abstaining (P less than .001 for all improvement categories).
“Reductions in WHO drinking risk levels are predictive of clinical benefit” or how the patient feels and functions, said Daniel Falk, PhD, health scientist administrator at the National Institute on Alcohol Abuse and Alcoholism.
The ACTIVE group he chairs, Dr. Anton said, is proposing that the FDA add a new endpoint for phase 3 trials: percentage of subjects who attain a 1- or 2-level reduction in WHO drinking risk levels.
Stephanie O’Malley, PhD, professor of psychiatry at Yale University in New Haven, Conn., said a 30-year-old with a moderate drinking problem – occasionally missing a family function, but never letting it interfere with work, say – might be turned off by a treatment plan that preaches abstinence, she said. Varenicline, for example, results in abstinence just 7% of the time, with some risk of suicidality and nausea. That person might not want to stop drinking entirely for the rest of his or her life, but could benefit by reducing the drinking, she said.
But 55% of the time, varenicline produces a reduction of one level of risk, which is associated with clinically meaningful results. That will sound much more appealing to a prospective patient, she said.
“From a clinical perspective, these WHO outcomes have some advantages,” she said. “I think you’re going to, one, encourage more people to accept treatment, and … be more optimistic about the outcomes.”
Dr. Anton reported consulting and/or funding from Alkermes, Allergan, Indivior, Insys Life Epigenetics, and Laboratori Farmaceutico CT. Dr. O’Malley reported consulting and/or funding from Alkermes, Amygdala, Indivior, Mistubishi Tanabe, Opiant, and other sources. Dr. Falk reported no disclosures.
BONITA SPRINGS, FLA. – Reductions in alcohol use bring about significant improvement in adverse consequences, mental health status, and quality of life, even if the reductions do not reach the level of abstinence, according to recent research presented at the annual meeting of the American Academy of Addiction Psychiatry.
The findings, experts say, demonstrate how a fixation on abstinence or elimination of all heavy drinking – the endpoints the Food and Drug Administration now require in pivotal clinical trials on alcohol use disorder (AUD) treatments – is shortsighted and can unnecessarily discourage people with alcohol use disorder from pursuing treatment.
“We need to think a little differently, or a little out of the box, from the way we’ve been thinking in the past,” said Raymond F. Anton, MD, professor of psychiatry at the Medical University of South Carolina in Charleston and chair of the Alcohol Clinical Trials Initiative (ACTIVE), a group advocating for a new endpoint that recognizes the benefits of lesser reductions in alcohol intake.
In a new analysis using data from the COMBINE study, researchers looked at the associations between reduction in World Health Organization drinking risk levels of alcohol consumption and clinically meaningful outcomes among people in treatment.
There are four levels: very high (more than 7.1 14-g drinks a day for men and more than 4.3 for women); high (4.3-7.1 or 2.9-4.3, respectively); moderate (2.9-4.3 or 1.4-2.9); and low (less than 2.9 or less than 1.4).
Researchers assessed responses to treatment with acamprosate, naltrexone, and psychological intervention in patients an average of 44 years old with 71% of their days being heavy drinking days. They found significant improvement in consequences tied to drinking, according to the Drinker Inventory of Consequences, and in mental health according to the Short Form Health Survey and the WHO Quality of Life assessment – even when the improvement was only by one WHO risk level – or just a few drinks a day – and did not involve abstaining (P less than .001 for all improvement categories).
“Reductions in WHO drinking risk levels are predictive of clinical benefit” or how the patient feels and functions, said Daniel Falk, PhD, health scientist administrator at the National Institute on Alcohol Abuse and Alcoholism.
The ACTIVE group he chairs, Dr. Anton said, is proposing that the FDA add a new endpoint for phase 3 trials: percentage of subjects who attain a 1- or 2-level reduction in WHO drinking risk levels.
Stephanie O’Malley, PhD, professor of psychiatry at Yale University in New Haven, Conn., said a 30-year-old with a moderate drinking problem – occasionally missing a family function, but never letting it interfere with work, say – might be turned off by a treatment plan that preaches abstinence, she said. Varenicline, for example, results in abstinence just 7% of the time, with some risk of suicidality and nausea. That person might not want to stop drinking entirely for the rest of his or her life, but could benefit by reducing the drinking, she said.
But 55% of the time, varenicline produces a reduction of one level of risk, which is associated with clinically meaningful results. That will sound much more appealing to a prospective patient, she said.
“From a clinical perspective, these WHO outcomes have some advantages,” she said. “I think you’re going to, one, encourage more people to accept treatment, and … be more optimistic about the outcomes.”
Dr. Anton reported consulting and/or funding from Alkermes, Allergan, Indivior, Insys Life Epigenetics, and Laboratori Farmaceutico CT. Dr. O’Malley reported consulting and/or funding from Alkermes, Amygdala, Indivior, Mistubishi Tanabe, Opiant, and other sources. Dr. Falk reported no disclosures.
BONITA SPRINGS, FLA. – Reductions in alcohol use bring about significant improvement in adverse consequences, mental health status, and quality of life, even if the reductions do not reach the level of abstinence, according to recent research presented at the annual meeting of the American Academy of Addiction Psychiatry.
The findings, experts say, demonstrate how a fixation on abstinence or elimination of all heavy drinking – the endpoints the Food and Drug Administration now require in pivotal clinical trials on alcohol use disorder (AUD) treatments – is shortsighted and can unnecessarily discourage people with alcohol use disorder from pursuing treatment.
“We need to think a little differently, or a little out of the box, from the way we’ve been thinking in the past,” said Raymond F. Anton, MD, professor of psychiatry at the Medical University of South Carolina in Charleston and chair of the Alcohol Clinical Trials Initiative (ACTIVE), a group advocating for a new endpoint that recognizes the benefits of lesser reductions in alcohol intake.
In a new analysis using data from the COMBINE study, researchers looked at the associations between reduction in World Health Organization drinking risk levels of alcohol consumption and clinically meaningful outcomes among people in treatment.
There are four levels: very high (more than 7.1 14-g drinks a day for men and more than 4.3 for women); high (4.3-7.1 or 2.9-4.3, respectively); moderate (2.9-4.3 or 1.4-2.9); and low (less than 2.9 or less than 1.4).
Researchers assessed responses to treatment with acamprosate, naltrexone, and psychological intervention in patients an average of 44 years old with 71% of their days being heavy drinking days. They found significant improvement in consequences tied to drinking, according to the Drinker Inventory of Consequences, and in mental health according to the Short Form Health Survey and the WHO Quality of Life assessment – even when the improvement was only by one WHO risk level – or just a few drinks a day – and did not involve abstaining (P less than .001 for all improvement categories).
“Reductions in WHO drinking risk levels are predictive of clinical benefit” or how the patient feels and functions, said Daniel Falk, PhD, health scientist administrator at the National Institute on Alcohol Abuse and Alcoholism.
The ACTIVE group he chairs, Dr. Anton said, is proposing that the FDA add a new endpoint for phase 3 trials: percentage of subjects who attain a 1- or 2-level reduction in WHO drinking risk levels.
Stephanie O’Malley, PhD, professor of psychiatry at Yale University in New Haven, Conn., said a 30-year-old with a moderate drinking problem – occasionally missing a family function, but never letting it interfere with work, say – might be turned off by a treatment plan that preaches abstinence, she said. Varenicline, for example, results in abstinence just 7% of the time, with some risk of suicidality and nausea. That person might not want to stop drinking entirely for the rest of his or her life, but could benefit by reducing the drinking, she said.
But 55% of the time, varenicline produces a reduction of one level of risk, which is associated with clinically meaningful results. That will sound much more appealing to a prospective patient, she said.
“From a clinical perspective, these WHO outcomes have some advantages,” she said. “I think you’re going to, one, encourage more people to accept treatment, and … be more optimistic about the outcomes.”
Dr. Anton reported consulting and/or funding from Alkermes, Allergan, Indivior, Insys Life Epigenetics, and Laboratori Farmaceutico CT. Dr. O’Malley reported consulting and/or funding from Alkermes, Amygdala, Indivior, Mistubishi Tanabe, Opiant, and other sources. Dr. Falk reported no disclosures.
REPORTING FROM AAAP 2018