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Getting hematologic cancer drugs on the fast track
LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.
“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
Hematologic drug bonanza
In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.
Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.
Who minds the store
Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.
“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.
Getting the nod
To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.
For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.
FDA accelerated approval programs include:
- Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
- Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
- Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
- Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”
Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.
“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
Hematologic drug bonanza
In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.
Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.
Who minds the store
Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.
“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.
Getting the nod
To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.
For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.
FDA accelerated approval programs include:
- Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
- Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
- Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
- Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”
Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – The words “rapid approval” and “Food and Drug Administration” rarely appear in the same sentence. But despite that perception, the pace of hematologic drug development has been accelerating over the last several years, according to an agency staffer.
“FDA is committed toward the expedited development of safe and effective therapies for serious and life-threatening diseases,” R. Angelo de Claro, MD, of the FDA’s Office of Hematology and Oncology Products said at the annual T-cell Lymphoma Forum. Dr. de Claro outlined his agency’s efforts to accelerate approval of drugs for treatment of T-cell malignancies.
Hematologic drug bonanza
In 2017 alone, the FDA approved 17 agents for new or expanded indications for hematologic malignancies, including brentuximab vedotin (Adcetris) for anaplastic large cell lymphoma (ALCL) and CD30-positive mycosis fungoides (MF).
Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or primary cutaneous ALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.
Dr. de Claro noted that in the ALCANZA trial, patients were required to have one or more biopsy samples with at least 10% CD30 expression, but among 184 patients with MF screened for the trial, 32% were ineligible because of less than 10% CD30 expression. The FDA therefore requested additional efficacy data for patients with MF with less than 10% CD30 expression and accepted data from two investigator-sponsored trials showing that 35 patients with MF expressing CD30 on 1%-9% of cells had a 31% overall response rate, whereas two patients with no CD30 expression did not have responses.
Who minds the store
Hematology products are under the aegis of the FDA’s Oncology Center of Excellence. Oversight includes benign hematology products, as well as products for hematologic cancers and hematologic support. Hematology and oncology toxicology is monitored by pharmacologists and toxicologists in a separate division, he explained.
“The Oncology Center of Excellence was formally launched in 2017 as part of the 21st century CURES Act. The mission of the Oncology Center of Excellence is to achieve patient-centered regulatory decision making through innovation and collaboration,” he said.
Getting the nod
To get approved, a new therapy requires “substantial” evidence of efficacy and safety. Regular approvals are based on either direct measures of clinical benefits – how a patient “feels, functions, or survives” – or a measure of the effect of a drug on an established surrogate endpoint.
For an accelerated approval, developers must be able to show evidence on either a surrogate or intermediate clinical endpoint that the agent is reasonably likely to offer a benefit and be a meaningful improvement over available therapies. Postapproval trials may be needed to verify the proposed benefits.
FDA accelerated approval programs include:
- Fast track. The pathway requires nonclinical or clinical data demonstrating the potential for addressing an unmet need.
- Breakthrough therapy. This pathway requires preliminary clinical evidence demonstrating substantial improvement over existing available therapies.
- Priority review. These are agents that, if approved, would provide significant improvements in safety or effectiveness.
- Accelerated approval. The drug must demonstrate an effect on an “endpoint reasonably likely to predict clinical benefit over available therapies.”
Dr. de Claro is employed by the FDA. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
EXPERT ANALYSIS FROM TCLF 2018
Hospitalist empathy associated with reduced patient anxiety
Clinical question: What effect does hospitalist empathy have on patient anxiety, ratings of physician communication, and duration of encounter?
Background: Physician empathy is associated with better patient-reported and medical outcomes in a number of settings. The effects of hospitalist empathy have been less well studied.
Study design: Observational study of audio recordings of hospitalist admission encounters.
Setting: General medical service at two urban hospitals within an academic medical center from August 2008 to March 2009. 
Synopsis: Admission encounters (76 patients, 27 hospitalists) were recorded. Researchers detected negative emotional expressions from patients and characterized resultant physician replies as either empathic (“focuses toward further expression of emotion”), neutral (“focuses neither toward nor away from emotion”), or nonempathic (“focuses away from emotion”). Through use of regression models, response frequency was compared with change in pre/post-encounter patient anxiety, patient ratings of physician communication, and duration of encounter. Every additional empathic response was associated with a small decrease in anxiety, better ratings of physician communication, and no change in encounter duration. Nonempathic responses were associated with worse communication ratings. Limitations of the study include its observational nature, small sample size, exclusion of non–English-speaking patients, absence of data on nonverbal communication, and exclusively urban academic setting.
Bottom line: Empathic hospitalist responses during admission encounters are associated with reductions in patient anxiety and better ratings of physician communication without increases in encounter duration.
Citation: Weiss R et al. Associations of physician empathy with patient anxiety and ratings of communication in hospital admission encounters. J Hosp Med. 2017;12(10):805-10.
Dr. Kanjee is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.
Clinical question: What effect does hospitalist empathy have on patient anxiety, ratings of physician communication, and duration of encounter?
Background: Physician empathy is associated with better patient-reported and medical outcomes in a number of settings. The effects of hospitalist empathy have been less well studied.
Study design: Observational study of audio recordings of hospitalist admission encounters.
Setting: General medical service at two urban hospitals within an academic medical center from August 2008 to March 2009.
Synopsis: Admission encounters (76 patients, 27 hospitalists) were recorded. Researchers detected negative emotional expressions from patients and characterized resultant physician replies as either empathic (“focuses toward further expression of emotion”), neutral (“focuses neither toward nor away from emotion”), or nonempathic (“focuses away from emotion”). Through use of regression models, response frequency was compared with change in pre/post-encounter patient anxiety, patient ratings of physician communication, and duration of encounter. Every additional empathic response was associated with a small decrease in anxiety, better ratings of physician communication, and no change in encounter duration. Nonempathic responses were associated with worse communication ratings. Limitations of the study include its observational nature, small sample size, exclusion of non–English-speaking patients, absence of data on nonverbal communication, and exclusively urban academic setting.
Bottom line: Empathic hospitalist responses during admission encounters are associated with reductions in patient anxiety and better ratings of physician communication without increases in encounter duration.
Citation: Weiss R et al. Associations of physician empathy with patient anxiety and ratings of communication in hospital admission encounters. J Hosp Med. 2017;12(10):805-10.
Dr. Kanjee is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.
Clinical question: What effect does hospitalist empathy have on patient anxiety, ratings of physician communication, and duration of encounter?
Background: Physician empathy is associated with better patient-reported and medical outcomes in a number of settings. The effects of hospitalist empathy have been less well studied.
Study design: Observational study of audio recordings of hospitalist admission encounters.
Setting: General medical service at two urban hospitals within an academic medical center from August 2008 to March 2009.
Synopsis: Admission encounters (76 patients, 27 hospitalists) were recorded. Researchers detected negative emotional expressions from patients and characterized resultant physician replies as either empathic (“focuses toward further expression of emotion”), neutral (“focuses neither toward nor away from emotion”), or nonempathic (“focuses away from emotion”). Through use of regression models, response frequency was compared with change in pre/post-encounter patient anxiety, patient ratings of physician communication, and duration of encounter. Every additional empathic response was associated with a small decrease in anxiety, better ratings of physician communication, and no change in encounter duration. Nonempathic responses were associated with worse communication ratings. Limitations of the study include its observational nature, small sample size, exclusion of non–English-speaking patients, absence of data on nonverbal communication, and exclusively urban academic setting.
Bottom line: Empathic hospitalist responses during admission encounters are associated with reductions in patient anxiety and better ratings of physician communication without increases in encounter duration.
Citation: Weiss R et al. Associations of physician empathy with patient anxiety and ratings of communication in hospital admission encounters. J Hosp Med. 2017;12(10):805-10.
Dr. Kanjee is a hospitalist, Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, Boston.
Cerclage plus progesterone for preventing preterm births
DALLAS – Placing a cerclage conferred additional benefit over vaginal progesterone alone for women with extreme short cervixes and singleton pregnancies, in a recent study. Those who received rescue cerclage in addition to vaginal progesterone had a 92% overall reduction in spontaneous preterm birth rates, and infants had fewer neonatal ICU admissions and neonatal complications.
The single-center retrospective cohort study of 75 women with cervical length less than 10 cm who were receiving vaginal progesterone was presented by Christopher Enakpene, MD, at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Women who received rescue cerclage in addition to progesterone delivered at a mean 34.3 weeks gestational age, compared with 27.5 weeks for those receiving progesterone alone (P less than .001).
There were 13 neonatal ICU admissions for infants born to the 36 patients in the cerclage group, compared with 23 for the 39 women receiving progesterone alone (P = .009). And there were seven perinatal or neonatal deaths among the group who did not receive cerclage; no deaths occurred in the cerclage group.
“Premature cervical ripening plays a significant role in spontaneous preterm birth,” said Dr. Enakpene. “And studies have shown that, the shorter the cervix, the higher the risk of spontaneous preterm birth.”
Preterm birth, said Dr. Enakpene, is the top cause of neonatal morbidity and mortality both in the United States and worldwide; it is associated with 70% of neonatal deaths and half of all neurodevelopmental delay, he said.
At the University of Illinois at Chicago, where Dr. Enakpene is a maternal-fetal medicine fellow in the department of obstetrics and gynecology, all pregnant women are screened for cervical length by transvaginal ultrasound during their second trimester.
If screening reveals cervical length of less than 20 mm, the patient receives vaginal progesterone, “the current standard of care in singleton pregnancy with incidental short cervix,” said Dr. Enakpene. Vaginal progesterone can reduce the risk of spontaneous preterm birth by about half, he said.
At his facility, women with a short cervix then receive serial cervical length assessments every week or 2 until 24 weeks’ gestation, to identify women whose cervixes continue to shorten. For these women, it’s usually physician preference that determines whether cerclage is placed to reinforce the progressively shortening cervix, said Dr. Enakpene.
There had been previous retrospective work showing that cerclage was more effective at preventing spontaneous preterm birth than was doing nothing when a woman with a singleton pregnancy had a short cervix. However, Dr. Enakpene said that vaginal progesterone alone had not been compared with continuing progesterone and adding a cerclage.
During the study period, 310 women with cervical length of less than 20 mm were placed on progesterone. These women were included in the study cohort if, over the course of at least two cervical length measurements, their cervix shortened to less than 10 mm while they were on vaginal progesterone. They could not have indications that delivery was imminent when the 10 mm threshold was met, said Dr. Enakpene.
Women with known intrauterine fetal death, an undesired pregnancy, or any sign of intra-amniotic infection or fetal anomalies were excluded from the study.
A total of 75 women met final inclusion criteria, and received cerclage (n = 36), or not (n = 39) according to physician judgment. Demographic and pregnancy-specific characteristics were generally similar between the two groups.
In their statistical analysis, Dr. Enakpene and his colleagues used Kaplan-Meier survival analysis to look at pregnancy latency over time for women who did – or didn’t – receive a cerclage. There were significantly fewer spontaneous preterm births before 24, 28, and 34 weeks gestational age in the cerclage group (P less than .001 for all).
Dr. Enakpene acknowledged the study’s limitations, including its retrospective nature, the small sample size, and the fact that cerclage placement was done by the preference of the attending physician. However, this study was the first to examine rescue cerclage as add-on to vaginal progesterone, he said, adding, “Following this study, we are designing a prospective randomized interventional study to address this important topic.”
Dr. Enakpene reported that he had no conflicts of interest, and reported no outside sources of funding.
SOURCE: Enakpene C et al. Am J Obstet Gynecol. 2018 Jan;218:S72-S73.
DALLAS – Placing a cerclage conferred additional benefit over vaginal progesterone alone for women with extreme short cervixes and singleton pregnancies, in a recent study. Those who received rescue cerclage in addition to vaginal progesterone had a 92% overall reduction in spontaneous preterm birth rates, and infants had fewer neonatal ICU admissions and neonatal complications.
The single-center retrospective cohort study of 75 women with cervical length less than 10 cm who were receiving vaginal progesterone was presented by Christopher Enakpene, MD, at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Women who received rescue cerclage in addition to progesterone delivered at a mean 34.3 weeks gestational age, compared with 27.5 weeks for those receiving progesterone alone (P less than .001).
There were 13 neonatal ICU admissions for infants born to the 36 patients in the cerclage group, compared with 23 for the 39 women receiving progesterone alone (P = .009). And there were seven perinatal or neonatal deaths among the group who did not receive cerclage; no deaths occurred in the cerclage group.
“Premature cervical ripening plays a significant role in spontaneous preterm birth,” said Dr. Enakpene. “And studies have shown that, the shorter the cervix, the higher the risk of spontaneous preterm birth.”
Preterm birth, said Dr. Enakpene, is the top cause of neonatal morbidity and mortality both in the United States and worldwide; it is associated with 70% of neonatal deaths and half of all neurodevelopmental delay, he said.
At the University of Illinois at Chicago, where Dr. Enakpene is a maternal-fetal medicine fellow in the department of obstetrics and gynecology, all pregnant women are screened for cervical length by transvaginal ultrasound during their second trimester.
If screening reveals cervical length of less than 20 mm, the patient receives vaginal progesterone, “the current standard of care in singleton pregnancy with incidental short cervix,” said Dr. Enakpene. Vaginal progesterone can reduce the risk of spontaneous preterm birth by about half, he said.
At his facility, women with a short cervix then receive serial cervical length assessments every week or 2 until 24 weeks’ gestation, to identify women whose cervixes continue to shorten. For these women, it’s usually physician preference that determines whether cerclage is placed to reinforce the progressively shortening cervix, said Dr. Enakpene.
There had been previous retrospective work showing that cerclage was more effective at preventing spontaneous preterm birth than was doing nothing when a woman with a singleton pregnancy had a short cervix. However, Dr. Enakpene said that vaginal progesterone alone had not been compared with continuing progesterone and adding a cerclage.
During the study period, 310 women with cervical length of less than 20 mm were placed on progesterone. These women were included in the study cohort if, over the course of at least two cervical length measurements, their cervix shortened to less than 10 mm while they were on vaginal progesterone. They could not have indications that delivery was imminent when the 10 mm threshold was met, said Dr. Enakpene.
Women with known intrauterine fetal death, an undesired pregnancy, or any sign of intra-amniotic infection or fetal anomalies were excluded from the study.
A total of 75 women met final inclusion criteria, and received cerclage (n = 36), or not (n = 39) according to physician judgment. Demographic and pregnancy-specific characteristics were generally similar between the two groups.
In their statistical analysis, Dr. Enakpene and his colleagues used Kaplan-Meier survival analysis to look at pregnancy latency over time for women who did – or didn’t – receive a cerclage. There were significantly fewer spontaneous preterm births before 24, 28, and 34 weeks gestational age in the cerclage group (P less than .001 for all).
Dr. Enakpene acknowledged the study’s limitations, including its retrospective nature, the small sample size, and the fact that cerclage placement was done by the preference of the attending physician. However, this study was the first to examine rescue cerclage as add-on to vaginal progesterone, he said, adding, “Following this study, we are designing a prospective randomized interventional study to address this important topic.”
Dr. Enakpene reported that he had no conflicts of interest, and reported no outside sources of funding.
SOURCE: Enakpene C et al. Am J Obstet Gynecol. 2018 Jan;218:S72-S73.
DALLAS – Placing a cerclage conferred additional benefit over vaginal progesterone alone for women with extreme short cervixes and singleton pregnancies, in a recent study. Those who received rescue cerclage in addition to vaginal progesterone had a 92% overall reduction in spontaneous preterm birth rates, and infants had fewer neonatal ICU admissions and neonatal complications.
The single-center retrospective cohort study of 75 women with cervical length less than 10 cm who were receiving vaginal progesterone was presented by Christopher Enakpene, MD, at the meeting sponsored by the Society for Maternal-Fetal Medicine.
Women who received rescue cerclage in addition to progesterone delivered at a mean 34.3 weeks gestational age, compared with 27.5 weeks for those receiving progesterone alone (P less than .001).
There were 13 neonatal ICU admissions for infants born to the 36 patients in the cerclage group, compared with 23 for the 39 women receiving progesterone alone (P = .009). And there were seven perinatal or neonatal deaths among the group who did not receive cerclage; no deaths occurred in the cerclage group.
“Premature cervical ripening plays a significant role in spontaneous preterm birth,” said Dr. Enakpene. “And studies have shown that, the shorter the cervix, the higher the risk of spontaneous preterm birth.”
Preterm birth, said Dr. Enakpene, is the top cause of neonatal morbidity and mortality both in the United States and worldwide; it is associated with 70% of neonatal deaths and half of all neurodevelopmental delay, he said.
At the University of Illinois at Chicago, where Dr. Enakpene is a maternal-fetal medicine fellow in the department of obstetrics and gynecology, all pregnant women are screened for cervical length by transvaginal ultrasound during their second trimester.
If screening reveals cervical length of less than 20 mm, the patient receives vaginal progesterone, “the current standard of care in singleton pregnancy with incidental short cervix,” said Dr. Enakpene. Vaginal progesterone can reduce the risk of spontaneous preterm birth by about half, he said.
At his facility, women with a short cervix then receive serial cervical length assessments every week or 2 until 24 weeks’ gestation, to identify women whose cervixes continue to shorten. For these women, it’s usually physician preference that determines whether cerclage is placed to reinforce the progressively shortening cervix, said Dr. Enakpene.
There had been previous retrospective work showing that cerclage was more effective at preventing spontaneous preterm birth than was doing nothing when a woman with a singleton pregnancy had a short cervix. However, Dr. Enakpene said that vaginal progesterone alone had not been compared with continuing progesterone and adding a cerclage.
During the study period, 310 women with cervical length of less than 20 mm were placed on progesterone. These women were included in the study cohort if, over the course of at least two cervical length measurements, their cervix shortened to less than 10 mm while they were on vaginal progesterone. They could not have indications that delivery was imminent when the 10 mm threshold was met, said Dr. Enakpene.
Women with known intrauterine fetal death, an undesired pregnancy, or any sign of intra-amniotic infection or fetal anomalies were excluded from the study.
A total of 75 women met final inclusion criteria, and received cerclage (n = 36), or not (n = 39) according to physician judgment. Demographic and pregnancy-specific characteristics were generally similar between the two groups.
In their statistical analysis, Dr. Enakpene and his colleagues used Kaplan-Meier survival analysis to look at pregnancy latency over time for women who did – or didn’t – receive a cerclage. There were significantly fewer spontaneous preterm births before 24, 28, and 34 weeks gestational age in the cerclage group (P less than .001 for all).
Dr. Enakpene acknowledged the study’s limitations, including its retrospective nature, the small sample size, and the fact that cerclage placement was done by the preference of the attending physician. However, this study was the first to examine rescue cerclage as add-on to vaginal progesterone, he said, adding, “Following this study, we are designing a prospective randomized interventional study to address this important topic.”
Dr. Enakpene reported that he had no conflicts of interest, and reported no outside sources of funding.
SOURCE: Enakpene C et al. Am J Obstet Gynecol. 2018 Jan;218:S72-S73.
REPORTING FROM THE PREGNANCY MEETING
Key clinical point: Women receiving rescue cerclage plus progesterone had fewer spontaneous preterm births.
Major finding: Those who also received cerclage delivered at 34.3 weeks gestational age, compared with 27.5 weeks for those on progesterone alone (P less than .001).
Study details: Retrospective cohort study of 75 women with singleton pregnancies and very short cervixes.
Disclosures: Dr. Enakpene reported no outside sources of funding and had no conflicts of interest.
Source: Enakpene C et al. Am J Obstet Gynecol. 2018 Jan;218:S72-S73.
Adil Harroud, MD
Katharina Eikermann-Haerter, MD
Jes Olesen, MD
States show large disparities in lung cancer mortality
, with the highest rate in West Virginia and the lowest in Utah.
Approximately 154,050 deaths from lung cancer – three times as many as any other cancer – are predicted for the year in the United States by the American Cancer Society in its Cancer Facts & Figures 2018, based on analysis of 2001-2015 data from the National Center for Health Statistics. That figure is down from the 155,870 predicted for 2017, as the most recent trend (2011-2015) in the death rate has been a decline of about 2.3% per year for women and 3.8% per year for men, the ACS noted.
The expected number of deaths for 2018, coupled with a current population estimate of nearly 326 million, works out to an expected death rate of 47.3 per a population of 100,000. The Census Bureau estimates for the state populations and the deaths projected by the ACS produce expected death rates of 80.8 per 100,000 for West Virginia and 15.2 for Utah. Kentucky’s rate of 79.3 is just behind West Virginia, but Colorado, the next-lowest state after Utah, has an estimated rate that’s almost twice as high at 28.5.
Nationally, death rates for lung cancer were 53.8 per 100,000 for males and 35.4 for females for 2011-2015, and incidence rates were 73 per 100,000 for males and 52.8 for females for 2010-2014, the ACS reported.
Among racial and ethnic groups, in men, the mortality was highest for those who were both non-Hispanic and black (66.9 per 100,00) during 2011-2015. Of the racial and ethnic groups of women for the same period, white women had the highest death rate (39). Hispanic/Latino men (26.4) and Hispanic/Latino women (13.3) had the lowest deaths rates, according to the report.
, with the highest rate in West Virginia and the lowest in Utah.
Approximately 154,050 deaths from lung cancer – three times as many as any other cancer – are predicted for the year in the United States by the American Cancer Society in its Cancer Facts & Figures 2018, based on analysis of 2001-2015 data from the National Center for Health Statistics. That figure is down from the 155,870 predicted for 2017, as the most recent trend (2011-2015) in the death rate has been a decline of about 2.3% per year for women and 3.8% per year for men, the ACS noted.
The expected number of deaths for 2018, coupled with a current population estimate of nearly 326 million, works out to an expected death rate of 47.3 per a population of 100,000. The Census Bureau estimates for the state populations and the deaths projected by the ACS produce expected death rates of 80.8 per 100,000 for West Virginia and 15.2 for Utah. Kentucky’s rate of 79.3 is just behind West Virginia, but Colorado, the next-lowest state after Utah, has an estimated rate that’s almost twice as high at 28.5.
Nationally, death rates for lung cancer were 53.8 per 100,000 for males and 35.4 for females for 2011-2015, and incidence rates were 73 per 100,000 for males and 52.8 for females for 2010-2014, the ACS reported.
Among racial and ethnic groups, in men, the mortality was highest for those who were both non-Hispanic and black (66.9 per 100,00) during 2011-2015. Of the racial and ethnic groups of women for the same period, white women had the highest death rate (39). Hispanic/Latino men (26.4) and Hispanic/Latino women (13.3) had the lowest deaths rates, according to the report.
, with the highest rate in West Virginia and the lowest in Utah.
Approximately 154,050 deaths from lung cancer – three times as many as any other cancer – are predicted for the year in the United States by the American Cancer Society in its Cancer Facts & Figures 2018, based on analysis of 2001-2015 data from the National Center for Health Statistics. That figure is down from the 155,870 predicted for 2017, as the most recent trend (2011-2015) in the death rate has been a decline of about 2.3% per year for women and 3.8% per year for men, the ACS noted.
The expected number of deaths for 2018, coupled with a current population estimate of nearly 326 million, works out to an expected death rate of 47.3 per a population of 100,000. The Census Bureau estimates for the state populations and the deaths projected by the ACS produce expected death rates of 80.8 per 100,000 for West Virginia and 15.2 for Utah. Kentucky’s rate of 79.3 is just behind West Virginia, but Colorado, the next-lowest state after Utah, has an estimated rate that’s almost twice as high at 28.5.
Nationally, death rates for lung cancer were 53.8 per 100,000 for males and 35.4 for females for 2011-2015, and incidence rates were 73 per 100,000 for males and 52.8 for females for 2010-2014, the ACS reported.
Among racial and ethnic groups, in men, the mortality was highest for those who were both non-Hispanic and black (66.9 per 100,00) during 2011-2015. Of the racial and ethnic groups of women for the same period, white women had the highest death rate (39). Hispanic/Latino men (26.4) and Hispanic/Latino women (13.3) had the lowest deaths rates, according to the report.
Jeffrey S. Mogil, PhD
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
T-cell lymphoma therapies on the horizon
LA JOLLA, CALIF. – There are several biologic compounds in early clinical development for treatment of patients with T-cell lymphomas, including an antibody-drug conjugate, novel immune checkpoint inhibitor, and bi-specific antibody.
These investigational agents show promising single-agent activity and have the potential to improve clinical responses when combined with combination chemotherapy regimens or other treatments, Ahmed Sawas, MD, of the Center for Lymphoid Malignancies at Columbia University, New York, said at the annual T-cell Lymphoma Forum.
AGS67E: Antibody-drug conjugate
AGS67E is an antibody-drug conjugate targeted against CD37, a transmembrane protein preferentially expressed on malignant B cells, T cells, and acute myeloid leukemia cells. In a study published in 2015 in Molecular Cancer Therapeutics, investigators from Agensys (an affiliate of Astellas Pharma) reported that this compound bound to more than 80% of patient-derived T cells in vitro (Mol Cancer Ther. 2015;14[7]:1650-60).
In a phase 1 dose-escalation study reported at the 2017 International Conference on Malignant Lymphoma in Lugano, Switzerland, Dr. Sawas and his colleagues found that patients with B-cell and T-cell malignancies, including cutaneous T-cell lymphoma and peripheral T-cell lymphoma, tolerated the drug well when it was delivered both with or without growth factor. Neutropenia was the most frequent adverse event and dose-limiting toxicity.
The drug showed single-agent activity in 16 of 53 patients with heavily pretreated non-Hodgkin lymphoma, including a partial response in one of two patients with cutaneous T-cell lymphoma, and partial responses in two of four patients with peripheral T-cell lymphoma. There were no complete responses at any of three dose levels of the drug, with or without growth factor.
One patient, a 75-year-old man with stage IVB mycosis fungoides who had disease progression on prior therapy with methotrexate, romidepsin, bendamustine, whole-body irradiation, liposomal doxorubicin, pralatrexate, and pembrolizumab experienced significant reduction in tumor burden and resolution of lymph node involvement after three 3-week cycles of therapy with AGS67E. The patient had a deepening of the response with additional cycles, and remained on therapy for 30 cycles until he experienced disease progression.
TTI-621: Tuck in, macrophages
TT1-621 is a molecule with two functions: It acts as an immune checkpoint inhibitor by blocking CD47, which binds to signal-regulatory protein alpha to produce an antiphagocytic or “do not eat” signal. TTI-621 does not, however, bind to CD47-positive erythrocytes.
In addition to blocking CD47 and the do-not-eat signal, TTI-621 delivers an activating signal to macrophages through Fc gamma receptors, telling them, in effect, “bon appétit.”
In a study presented at the 2017 annual meeting of the American Society of Hematology (Abstract 4076), investigators from City of Hope in Duarte, Calif., and other centers reported that a single direct intratumoral injection of TTI-621 was associated with significant antitumor activity in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, with one of nine patients having a complete response in the injected lesion, and five having decreases in tumor size and/or circulating Sézary cells.
Patients appeared to tolerate this agent very well, with 1 of 18 having a grade 3 increase in white blood cell count. The most commonly reported side effects were fatigue, chills, decreased appetite, headache, injection site pain, and generalized pruritus, each occurring in 3 of the 18 patients.
TTI-621 injection was associated with rapid declines in Composite Assessment of Index Lesion Severity scores in dose-finding studies in patients with heavily pretreated cutaneous T-cell lymphoma, Dr. Sawas said.
AFM13: Two for the price of one
AFM13 is a bi-specific antibody that binds to CD30, which is expressed on anaplastic large cell lymphoma cells, as well as Reed-Sternberg cells of classical Hodgkin lymphoma. This antibody also engages CD16A-positive cells, resulting in lysis of CD30-positive tumor cells. It is a specific recruiter of natural killer cells, and does not bind to neutrophils.
In an early biologic effects study of this agent in CD30-positive lymphoid malignancies with cutaneous presentation, Dr. Sawas and his colleagues observed an early response and regression of cutaneous anaplastic large cell lymphoma lesions in a heavily pretreated patient, with progression occurring when the patient went off therapy, and tumors that diminished on reinitiation of therapy that sustained beyond a second discontinuation of therapy. This patient had measurable reductions in lymphoma burden on PET CT scans and improvements in cutaneous lesions. Dr. Sawas did not present safety data for this agent.
AGS67E studies are supported by Agensys. TTI-621 studies are supported by Trillium Therapeutics. The AFM13 study is supported by Columbia University, with Dr. Sawas listed as the sponsor. He did not report potential conflicts of interests. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – There are several biologic compounds in early clinical development for treatment of patients with T-cell lymphomas, including an antibody-drug conjugate, novel immune checkpoint inhibitor, and bi-specific antibody.
These investigational agents show promising single-agent activity and have the potential to improve clinical responses when combined with combination chemotherapy regimens or other treatments, Ahmed Sawas, MD, of the Center for Lymphoid Malignancies at Columbia University, New York, said at the annual T-cell Lymphoma Forum.
AGS67E: Antibody-drug conjugate
AGS67E is an antibody-drug conjugate targeted against CD37, a transmembrane protein preferentially expressed on malignant B cells, T cells, and acute myeloid leukemia cells. In a study published in 2015 in Molecular Cancer Therapeutics, investigators from Agensys (an affiliate of Astellas Pharma) reported that this compound bound to more than 80% of patient-derived T cells in vitro (Mol Cancer Ther. 2015;14[7]:1650-60).
In a phase 1 dose-escalation study reported at the 2017 International Conference on Malignant Lymphoma in Lugano, Switzerland, Dr. Sawas and his colleagues found that patients with B-cell and T-cell malignancies, including cutaneous T-cell lymphoma and peripheral T-cell lymphoma, tolerated the drug well when it was delivered both with or without growth factor. Neutropenia was the most frequent adverse event and dose-limiting toxicity.
The drug showed single-agent activity in 16 of 53 patients with heavily pretreated non-Hodgkin lymphoma, including a partial response in one of two patients with cutaneous T-cell lymphoma, and partial responses in two of four patients with peripheral T-cell lymphoma. There were no complete responses at any of three dose levels of the drug, with or without growth factor.
One patient, a 75-year-old man with stage IVB mycosis fungoides who had disease progression on prior therapy with methotrexate, romidepsin, bendamustine, whole-body irradiation, liposomal doxorubicin, pralatrexate, and pembrolizumab experienced significant reduction in tumor burden and resolution of lymph node involvement after three 3-week cycles of therapy with AGS67E. The patient had a deepening of the response with additional cycles, and remained on therapy for 30 cycles until he experienced disease progression.
TTI-621: Tuck in, macrophages
TT1-621 is a molecule with two functions: It acts as an immune checkpoint inhibitor by blocking CD47, which binds to signal-regulatory protein alpha to produce an antiphagocytic or “do not eat” signal. TTI-621 does not, however, bind to CD47-positive erythrocytes.
In addition to blocking CD47 and the do-not-eat signal, TTI-621 delivers an activating signal to macrophages through Fc gamma receptors, telling them, in effect, “bon appétit.”
In a study presented at the 2017 annual meeting of the American Society of Hematology (Abstract 4076), investigators from City of Hope in Duarte, Calif., and other centers reported that a single direct intratumoral injection of TTI-621 was associated with significant antitumor activity in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, with one of nine patients having a complete response in the injected lesion, and five having decreases in tumor size and/or circulating Sézary cells.
Patients appeared to tolerate this agent very well, with 1 of 18 having a grade 3 increase in white blood cell count. The most commonly reported side effects were fatigue, chills, decreased appetite, headache, injection site pain, and generalized pruritus, each occurring in 3 of the 18 patients.
TTI-621 injection was associated with rapid declines in Composite Assessment of Index Lesion Severity scores in dose-finding studies in patients with heavily pretreated cutaneous T-cell lymphoma, Dr. Sawas said.
AFM13: Two for the price of one
AFM13 is a bi-specific antibody that binds to CD30, which is expressed on anaplastic large cell lymphoma cells, as well as Reed-Sternberg cells of classical Hodgkin lymphoma. This antibody also engages CD16A-positive cells, resulting in lysis of CD30-positive tumor cells. It is a specific recruiter of natural killer cells, and does not bind to neutrophils.
In an early biologic effects study of this agent in CD30-positive lymphoid malignancies with cutaneous presentation, Dr. Sawas and his colleagues observed an early response and regression of cutaneous anaplastic large cell lymphoma lesions in a heavily pretreated patient, with progression occurring when the patient went off therapy, and tumors that diminished on reinitiation of therapy that sustained beyond a second discontinuation of therapy. This patient had measurable reductions in lymphoma burden on PET CT scans and improvements in cutaneous lesions. Dr. Sawas did not present safety data for this agent.
AGS67E studies are supported by Agensys. TTI-621 studies are supported by Trillium Therapeutics. The AFM13 study is supported by Columbia University, with Dr. Sawas listed as the sponsor. He did not report potential conflicts of interests. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – There are several biologic compounds in early clinical development for treatment of patients with T-cell lymphomas, including an antibody-drug conjugate, novel immune checkpoint inhibitor, and bi-specific antibody.
These investigational agents show promising single-agent activity and have the potential to improve clinical responses when combined with combination chemotherapy regimens or other treatments, Ahmed Sawas, MD, of the Center for Lymphoid Malignancies at Columbia University, New York, said at the annual T-cell Lymphoma Forum.
AGS67E: Antibody-drug conjugate
AGS67E is an antibody-drug conjugate targeted against CD37, a transmembrane protein preferentially expressed on malignant B cells, T cells, and acute myeloid leukemia cells. In a study published in 2015 in Molecular Cancer Therapeutics, investigators from Agensys (an affiliate of Astellas Pharma) reported that this compound bound to more than 80% of patient-derived T cells in vitro (Mol Cancer Ther. 2015;14[7]:1650-60).
In a phase 1 dose-escalation study reported at the 2017 International Conference on Malignant Lymphoma in Lugano, Switzerland, Dr. Sawas and his colleagues found that patients with B-cell and T-cell malignancies, including cutaneous T-cell lymphoma and peripheral T-cell lymphoma, tolerated the drug well when it was delivered both with or without growth factor. Neutropenia was the most frequent adverse event and dose-limiting toxicity.
The drug showed single-agent activity in 16 of 53 patients with heavily pretreated non-Hodgkin lymphoma, including a partial response in one of two patients with cutaneous T-cell lymphoma, and partial responses in two of four patients with peripheral T-cell lymphoma. There were no complete responses at any of three dose levels of the drug, with or without growth factor.
One patient, a 75-year-old man with stage IVB mycosis fungoides who had disease progression on prior therapy with methotrexate, romidepsin, bendamustine, whole-body irradiation, liposomal doxorubicin, pralatrexate, and pembrolizumab experienced significant reduction in tumor burden and resolution of lymph node involvement after three 3-week cycles of therapy with AGS67E. The patient had a deepening of the response with additional cycles, and remained on therapy for 30 cycles until he experienced disease progression.
TTI-621: Tuck in, macrophages
TT1-621 is a molecule with two functions: It acts as an immune checkpoint inhibitor by blocking CD47, which binds to signal-regulatory protein alpha to produce an antiphagocytic or “do not eat” signal. TTI-621 does not, however, bind to CD47-positive erythrocytes.
In addition to blocking CD47 and the do-not-eat signal, TTI-621 delivers an activating signal to macrophages through Fc gamma receptors, telling them, in effect, “bon appétit.”
In a study presented at the 2017 annual meeting of the American Society of Hematology (Abstract 4076), investigators from City of Hope in Duarte, Calif., and other centers reported that a single direct intratumoral injection of TTI-621 was associated with significant antitumor activity in patients with relapsed or refractory mycosis fungoides and Sézary syndrome, with one of nine patients having a complete response in the injected lesion, and five having decreases in tumor size and/or circulating Sézary cells.
Patients appeared to tolerate this agent very well, with 1 of 18 having a grade 3 increase in white blood cell count. The most commonly reported side effects were fatigue, chills, decreased appetite, headache, injection site pain, and generalized pruritus, each occurring in 3 of the 18 patients.
TTI-621 injection was associated with rapid declines in Composite Assessment of Index Lesion Severity scores in dose-finding studies in patients with heavily pretreated cutaneous T-cell lymphoma, Dr. Sawas said.
AFM13: Two for the price of one
AFM13 is a bi-specific antibody that binds to CD30, which is expressed on anaplastic large cell lymphoma cells, as well as Reed-Sternberg cells of classical Hodgkin lymphoma. This antibody also engages CD16A-positive cells, resulting in lysis of CD30-positive tumor cells. It is a specific recruiter of natural killer cells, and does not bind to neutrophils.
In an early biologic effects study of this agent in CD30-positive lymphoid malignancies with cutaneous presentation, Dr. Sawas and his colleagues observed an early response and regression of cutaneous anaplastic large cell lymphoma lesions in a heavily pretreated patient, with progression occurring when the patient went off therapy, and tumors that diminished on reinitiation of therapy that sustained beyond a second discontinuation of therapy. This patient had measurable reductions in lymphoma burden on PET CT scans and improvements in cutaneous lesions. Dr. Sawas did not present safety data for this agent.
AGS67E studies are supported by Agensys. TTI-621 studies are supported by Trillium Therapeutics. The AFM13 study is supported by Columbia University, with Dr. Sawas listed as the sponsor. He did not report potential conflicts of interests. The T-Cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
EXPERT ANALYSIS FROM TCLF 2018
Prazosin falls short for veterans’ PTSD-related sleep problems
The alpha-1 adrenergic receptor prazosin failed to improve recurring nightmares or sleep quality compared with placebo in veterans with PTSD in a 26-week randomized trial of 304 adult veterans.
In several previous randomized trials lasting fewer than 15 weeks, veterans with PTSD and recurring nightmares who received prazosin showed benefits, including improved sleep quality and PTSD symptoms, compared with placebo patients, wrote Murray A. Raskind, MD, of the Department of Veterans Affairs Puget Sound Health Care System, Seattle, and his colleagues.
In a study published in the New England Journal of Medicine, the researchers randomized 152 veterans with sleep problems and PTSD to prazosin and 152 to a placebo. The participants were recruited from 12 VA medical centers. The average age of the participants was 52 years, more than 96% were male, and about two-thirds were white. Demographics were similar between the two groups.
After 10 weeks and after 26 weeks, there were no significant differences between the two groups in changes from baseline measures of recurring nightmares, using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). Similarly, no significant differences appeared between the two groups based on Pittsburgh Sleep Quality Index scores.
“A possible explanation for these negative results is selection bias resulting from recruitment of patients who were mainly in clinically stable condition, since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” reported Dr. Raskind and his colleagues.
The average maintenance dose of prazosin was 14.8 mg, compared with 16.4 mg in the placebo group; 187 male study participants reached the maximum dose of 20 mg/day (54% of the prazosin group and 70% of the placebo group).
After 10 weeks, no significant differences were found between the two groups in changes from baseline measures of “recurring distressing dreams,” using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). The between group difference was 0.2. In addition, no significant differences were found at 10 weeks in the average change from baseline Pittsburgh Sleep Quality Index scores.
Similarly, no significant differences appeared between the two groups at 26 weeks. “ since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” the researchers said.
On average, patients in the prazosin group had significantly greater decreases in blood pressure, compared with the placebo group. In addition, they had fewer reports of new or worsening suicidal ideation, compared with the placebo group (8% vs.15%).
“Given the concern about suicide among veterans, it is noteworthy that the specifically solicited adverse event of new or worsening suicidal ideation was less common in the prazosin group than in the placebo group, but the absolute number of events was small; this issue warrants further study,” the researchers said.
The study was limited by several factors, including the absence of screening for sleep apnea or sleep-disordered breathing, Dr. Raskind and his colleagues noted. However, the results suggest that “further studies with more refined characterization of autonomic nervous system activity and nocturnal behaviors are needed to determine whether there might be subgroups of veterans with PTSD who can benefit from prazosin.”
Dr. Raskind had no financial conflicts to disclose. The study was supported by the Department of Veterans Affairs Cooperative Studies Program.
SOURCE: Raskind MA et al. N Engl J Med. 2018 Feb 8;378:507-17. doi: 10.1056/NEJMoa1507598.
The alpha-1 adrenergic receptor prazosin failed to improve recurring nightmares or sleep quality compared with placebo in veterans with PTSD in a 26-week randomized trial of 304 adult veterans.
In several previous randomized trials lasting fewer than 15 weeks, veterans with PTSD and recurring nightmares who received prazosin showed benefits, including improved sleep quality and PTSD symptoms, compared with placebo patients, wrote Murray A. Raskind, MD, of the Department of Veterans Affairs Puget Sound Health Care System, Seattle, and his colleagues.
In a study published in the New England Journal of Medicine, the researchers randomized 152 veterans with sleep problems and PTSD to prazosin and 152 to a placebo. The participants were recruited from 12 VA medical centers. The average age of the participants was 52 years, more than 96% were male, and about two-thirds were white. Demographics were similar between the two groups.
After 10 weeks and after 26 weeks, there were no significant differences between the two groups in changes from baseline measures of recurring nightmares, using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). Similarly, no significant differences appeared between the two groups based on Pittsburgh Sleep Quality Index scores.
“A possible explanation for these negative results is selection bias resulting from recruitment of patients who were mainly in clinically stable condition, since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” reported Dr. Raskind and his colleagues.
The average maintenance dose of prazosin was 14.8 mg, compared with 16.4 mg in the placebo group; 187 male study participants reached the maximum dose of 20 mg/day (54% of the prazosin group and 70% of the placebo group).
After 10 weeks, no significant differences were found between the two groups in changes from baseline measures of “recurring distressing dreams,” using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). The between group difference was 0.2. In addition, no significant differences were found at 10 weeks in the average change from baseline Pittsburgh Sleep Quality Index scores.
Similarly, no significant differences appeared between the two groups at 26 weeks. “ since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” the researchers said.
On average, patients in the prazosin group had significantly greater decreases in blood pressure, compared with the placebo group. In addition, they had fewer reports of new or worsening suicidal ideation, compared with the placebo group (8% vs.15%).
“Given the concern about suicide among veterans, it is noteworthy that the specifically solicited adverse event of new or worsening suicidal ideation was less common in the prazosin group than in the placebo group, but the absolute number of events was small; this issue warrants further study,” the researchers said.
The study was limited by several factors, including the absence of screening for sleep apnea or sleep-disordered breathing, Dr. Raskind and his colleagues noted. However, the results suggest that “further studies with more refined characterization of autonomic nervous system activity and nocturnal behaviors are needed to determine whether there might be subgroups of veterans with PTSD who can benefit from prazosin.”
Dr. Raskind had no financial conflicts to disclose. The study was supported by the Department of Veterans Affairs Cooperative Studies Program.
SOURCE: Raskind MA et al. N Engl J Med. 2018 Feb 8;378:507-17. doi: 10.1056/NEJMoa1507598.
The alpha-1 adrenergic receptor prazosin failed to improve recurring nightmares or sleep quality compared with placebo in veterans with PTSD in a 26-week randomized trial of 304 adult veterans.
In several previous randomized trials lasting fewer than 15 weeks, veterans with PTSD and recurring nightmares who received prazosin showed benefits, including improved sleep quality and PTSD symptoms, compared with placebo patients, wrote Murray A. Raskind, MD, of the Department of Veterans Affairs Puget Sound Health Care System, Seattle, and his colleagues.
In a study published in the New England Journal of Medicine, the researchers randomized 152 veterans with sleep problems and PTSD to prazosin and 152 to a placebo. The participants were recruited from 12 VA medical centers. The average age of the participants was 52 years, more than 96% were male, and about two-thirds were white. Demographics were similar between the two groups.
After 10 weeks and after 26 weeks, there were no significant differences between the two groups in changes from baseline measures of recurring nightmares, using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). Similarly, no significant differences appeared between the two groups based on Pittsburgh Sleep Quality Index scores.
“A possible explanation for these negative results is selection bias resulting from recruitment of patients who were mainly in clinically stable condition, since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” reported Dr. Raskind and his colleagues.
The average maintenance dose of prazosin was 14.8 mg, compared with 16.4 mg in the placebo group; 187 male study participants reached the maximum dose of 20 mg/day (54% of the prazosin group and 70% of the placebo group).
After 10 weeks, no significant differences were found between the two groups in changes from baseline measures of “recurring distressing dreams,” using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). The between group difference was 0.2. In addition, no significant differences were found at 10 weeks in the average change from baseline Pittsburgh Sleep Quality Index scores.
Similarly, no significant differences appeared between the two groups at 26 weeks. “ since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” the researchers said.
On average, patients in the prazosin group had significantly greater decreases in blood pressure, compared with the placebo group. In addition, they had fewer reports of new or worsening suicidal ideation, compared with the placebo group (8% vs.15%).
“Given the concern about suicide among veterans, it is noteworthy that the specifically solicited adverse event of new or worsening suicidal ideation was less common in the prazosin group than in the placebo group, but the absolute number of events was small; this issue warrants further study,” the researchers said.
The study was limited by several factors, including the absence of screening for sleep apnea or sleep-disordered breathing, Dr. Raskind and his colleagues noted. However, the results suggest that “further studies with more refined characterization of autonomic nervous system activity and nocturnal behaviors are needed to determine whether there might be subgroups of veterans with PTSD who can benefit from prazosin.”
Dr. Raskind had no financial conflicts to disclose. The study was supported by the Department of Veterans Affairs Cooperative Studies Program.
SOURCE: Raskind MA et al. N Engl J Med. 2018 Feb 8;378:507-17. doi: 10.1056/NEJMoa1507598.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Prazosin had no apparent effect on recurrent distressing dreams or sleep quality in veterans with PTSD.
Major finding: The between-group difference in scores on a measure of “recurrent distressing dreams” between the prazosin and placebo groups was a nonsignificant 0.2.
Study details: The data come from a randomized trial of 304 military veterans with PTSD who reported frequent nightmares.
Disclosures: Dr. Raskind had no financial conflicts to disclose. The study was supported by the Department of Veterans Affairs Cooperative Studies Program.
Source: Raskind MA et al. N Engl J Med. 2018;378:507-17.