Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.

The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.

Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.

However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.

The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.

Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.

Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.

Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.

“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.

Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.

Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.

SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.

Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.

The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.

Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.

However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.

The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.

Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.

Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.

Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.

“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.

Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.

Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.

SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.

Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.

The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.

Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.

However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.

The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.

Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.

Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.

Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.

“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.

Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.

Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.

SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.

Patients with self-reported mild bleeding symptoms may have impaired clot lysis, according to investigators. This finding is remarkable because it contrasts with known bleeding disorders, such as hemophilia, which are associated with enhanced clot lysis, reported lead author Minka J.A. Vries, MD, of the Cardiovascular Research Institute Maastricht (CARIM) at Maastricht (the Netherlands) University and her colleagues.

Svisio/Thinkstock

The observational study, which included 335 patients undergoing elective surgery at Maastricht University Medical Center, was conducted to better understand lysis capacity, which is challenging to assess in a clinical setting. Although the Euglobulin Lysis Time (ELT) is often used in the clinic, it cannot determine the influence of hemostatic proteins or formation of a fibrin clot under physiological conditions.

“In the more recently developed lysis assays,” the investigators wrote in Thrombosis Research, “the turbidity lysis assay and the tissue plasminogen activator–rotational thromboelastometry (tPA-ROTEM) [assay], all plasma proteins are present and fibrin is formed under more physiological conditions for the measurement of fibrinolysis.” These two tests were used in the present study.

Of the 335 adult patients, 240 had self-reported mild bleeding symptoms, and 95 did not. Patients with bleeding disorders, thrombocytopenia, or anemia were excluded, as were pregnant women and those taking blood thinners or NSAIDs. Along with assessing time parameters of fibrinolysis, clot-associated proteins were measured for possible imbalances.

“We hypothesized that clot lysis capacity is enhanced in patients with mild bleeding symptoms,” the investigators wrote, based on other bleeding disorders. Surprisingly, the results told a different story.

After adjusting for sex, BMI, and age, patients with bleeding symptoms had lower tPA-ROTEM lysis speed (beta −0.35; P = .007) and longer tPA-ROTEM lysis time (beta 0.29; P = .022) than did patients without bleeding symptoms. The investigators found that tPA-ROTEM measurements depended on factor II, factor XII, alpha2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor–1 (PAI-1) level. In contrast, turbidity lysis assay measurements were not significantly different between groups. This latter assay was influenced by alpha2-antiplasmin, TAFI, and PAI-1.

“We did not find evidence for systemic hyperfibrinolytic capacity in patients reporting mild bleeding symptoms in comparison to patients not reporting bleeding symptoms,” the investigators concluded. “tPA-ROTEM even suggested a slower clot lysis in these patients. Though this may appear counterintuitive, our results are in line with two papers assessing systemic clot lysis in mild bleeders.”

While this phenomenon gains supporting evidence, it remains poorly understood.

“We have no good explanation for these findings,” the investigators noted.

This study was funded by the Sint Annadal Foundation Maastricht, Maastricht University Medical Centre, CTMM INCOAG Maastricht, Cardiovascular Research Institute Maastricht, and the British Heart Foundation. No conflicts of interest were reported.

SOURCE: Vries MJA et al. Thromb Res. 2018 Dec 4. doi: 10.1016/j.thromres.2018.12.004.

Patients with self-reported mild bleeding symptoms may have impaired clot lysis, according to investigators. This finding is remarkable because it contrasts with known bleeding disorders, such as hemophilia, which are associated with enhanced clot lysis, reported lead author Minka J.A. Vries, MD, of the Cardiovascular Research Institute Maastricht (CARIM) at Maastricht (the Netherlands) University and her colleagues.

Svisio/Thinkstock

The observational study, which included 335 patients undergoing elective surgery at Maastricht University Medical Center, was conducted to better understand lysis capacity, which is challenging to assess in a clinical setting. Although the Euglobulin Lysis Time (ELT) is often used in the clinic, it cannot determine the influence of hemostatic proteins or formation of a fibrin clot under physiological conditions.

“In the more recently developed lysis assays,” the investigators wrote in Thrombosis Research, “the turbidity lysis assay and the tissue plasminogen activator–rotational thromboelastometry (tPA-ROTEM) [assay], all plasma proteins are present and fibrin is formed under more physiological conditions for the measurement of fibrinolysis.” These two tests were used in the present study.

Of the 335 adult patients, 240 had self-reported mild bleeding symptoms, and 95 did not. Patients with bleeding disorders, thrombocytopenia, or anemia were excluded, as were pregnant women and those taking blood thinners or NSAIDs. Along with assessing time parameters of fibrinolysis, clot-associated proteins were measured for possible imbalances.

“We hypothesized that clot lysis capacity is enhanced in patients with mild bleeding symptoms,” the investigators wrote, based on other bleeding disorders. Surprisingly, the results told a different story.

After adjusting for sex, BMI, and age, patients with bleeding symptoms had lower tPA-ROTEM lysis speed (beta −0.35; P = .007) and longer tPA-ROTEM lysis time (beta 0.29; P = .022) than did patients without bleeding symptoms. The investigators found that tPA-ROTEM measurements depended on factor II, factor XII, alpha2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor–1 (PAI-1) level. In contrast, turbidity lysis assay measurements were not significantly different between groups. This latter assay was influenced by alpha2-antiplasmin, TAFI, and PAI-1.

“We did not find evidence for systemic hyperfibrinolytic capacity in patients reporting mild bleeding symptoms in comparison to patients not reporting bleeding symptoms,” the investigators concluded. “tPA-ROTEM even suggested a slower clot lysis in these patients. Though this may appear counterintuitive, our results are in line with two papers assessing systemic clot lysis in mild bleeders.”

While this phenomenon gains supporting evidence, it remains poorly understood.

“We have no good explanation for these findings,” the investigators noted.

This study was funded by the Sint Annadal Foundation Maastricht, Maastricht University Medical Centre, CTMM INCOAG Maastricht, Cardiovascular Research Institute Maastricht, and the British Heart Foundation. No conflicts of interest were reported.

SOURCE: Vries MJA et al. Thromb Res. 2018 Dec 4. doi: 10.1016/j.thromres.2018.12.004.

Patients with self-reported mild bleeding symptoms may have impaired clot lysis, according to investigators. This finding is remarkable because it contrasts with known bleeding disorders, such as hemophilia, which are associated with enhanced clot lysis, reported lead author Minka J.A. Vries, MD, of the Cardiovascular Research Institute Maastricht (CARIM) at Maastricht (the Netherlands) University and her colleagues.

Svisio/Thinkstock

The observational study, which included 335 patients undergoing elective surgery at Maastricht University Medical Center, was conducted to better understand lysis capacity, which is challenging to assess in a clinical setting. Although the Euglobulin Lysis Time (ELT) is often used in the clinic, it cannot determine the influence of hemostatic proteins or formation of a fibrin clot under physiological conditions.

“In the more recently developed lysis assays,” the investigators wrote in Thrombosis Research, “the turbidity lysis assay and the tissue plasminogen activator–rotational thromboelastometry (tPA-ROTEM) [assay], all plasma proteins are present and fibrin is formed under more physiological conditions for the measurement of fibrinolysis.” These two tests were used in the present study.

Of the 335 adult patients, 240 had self-reported mild bleeding symptoms, and 95 did not. Patients with bleeding disorders, thrombocytopenia, or anemia were excluded, as were pregnant women and those taking blood thinners or NSAIDs. Along with assessing time parameters of fibrinolysis, clot-associated proteins were measured for possible imbalances.

“We hypothesized that clot lysis capacity is enhanced in patients with mild bleeding symptoms,” the investigators wrote, based on other bleeding disorders. Surprisingly, the results told a different story.

After adjusting for sex, BMI, and age, patients with bleeding symptoms had lower tPA-ROTEM lysis speed (beta −0.35; P = .007) and longer tPA-ROTEM lysis time (beta 0.29; P = .022) than did patients without bleeding symptoms. The investigators found that tPA-ROTEM measurements depended on factor II, factor XII, alpha2-antiplasmin, plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor–1 (PAI-1) level. In contrast, turbidity lysis assay measurements were not significantly different between groups. This latter assay was influenced by alpha2-antiplasmin, TAFI, and PAI-1.

“We did not find evidence for systemic hyperfibrinolytic capacity in patients reporting mild bleeding symptoms in comparison to patients not reporting bleeding symptoms,” the investigators concluded. “tPA-ROTEM even suggested a slower clot lysis in these patients. Though this may appear counterintuitive, our results are in line with two papers assessing systemic clot lysis in mild bleeders.”

While this phenomenon gains supporting evidence, it remains poorly understood.

“We have no good explanation for these findings,” the investigators noted.

This study was funded by the Sint Annadal Foundation Maastricht, Maastricht University Medical Centre, CTMM INCOAG Maastricht, Cardiovascular Research Institute Maastricht, and the British Heart Foundation. No conflicts of interest were reported.

SOURCE: Vries MJA et al. Thromb Res. 2018 Dec 4. doi: 10.1016/j.thromres.2018.12.004.

Transitioning toward retirement or looking for postgrad training opportunities? Or maybe you need some advice on good “power meals” to have during your busy days? These are only a few of the many threads attracting comments on SVSConnect, your online community. Members can discuss, collaborate, network and even share documents with one another. Log in with your SVS credentials and add your thoughts. If you’re not signed up, do so today.

Transitioning toward retirement or looking for postgrad training opportunities? Or maybe you need some advice on good “power meals” to have during your busy days? These are only a few of the many threads attracting comments on SVSConnect, your online community. Members can discuss, collaborate, network and even share documents with one another. Log in with your SVS credentials and add your thoughts. If you’re not signed up, do so today.

Transitioning toward retirement or looking for postgrad training opportunities? Or maybe you need some advice on good “power meals” to have during your busy days? These are only a few of the many threads attracting comments on SVSConnect, your online community. Members can discuss, collaborate, network and even share documents with one another. Log in with your SVS credentials and add your thoughts. If you’re not signed up, do so today.

CORONADO, CALIF. – Eosinophilic chronic rhinosinusitis with nasal polyposis decreases quality of life improvement after sinus surgery in patients with concurrent asthma, results from a retrospective study demonstrated.

They also have significantly higher Lund-Kennedy endoscopy and Lund-McKay CT scores, compared with control groups.

“Patients with concurrent asthma and chronic sinusitis require more aggressive management than nonasthmatics,” one of the study authors, Aykut A. Unsal, DO, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Additionally, the degree of improvement of not only their sinusitis but possibly their asthma following medical/surgical treatment will also be limited if that patient also suffers from nasal polyps and/or eosinophilia. These patients will ultimately become more difficult to manage.”

In order to examine the relationship of eosinophilia and nasal polyps on quality of life (QOL) in patients with asthma who have chronic rhinosinusitis (CRS) who were treated with surgery, Dr. Unsal and his associates reviewed the records of 457 patients with a diagnosis of CRS who underwent sinus surgery in the department of otolaryngology at the Medical College of Georgia, Augusta. The researchers subdivided patients based on the presence or absence of an asthma diagnosis and further subdivided them based on tissue eosinophilia and nasal polyposis. Next, they compared the Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopy scores, and Lund-McKay CT scores preoperatively and postoperatively at 6 months – 1 year and at 2, 3, 4, and 5 years. They performed a T-test analysis to determine statistical significance.

Of the 457 patients included in the analysis, 92 had asthma and eosinophilic CRS with nasal polyps (eCRScNP), 20 had asthma and eosinophilic CRS without nasal polyps (eCRSsNP), 8 had asthma and noneosinophilic CRS with nasal polyps (neCRScNP), and 16 had asthma and noneosinophilic CRS without nasal polyps (neCRSsNP). The researchers observed that patients in the eCRScNP group showed no difference in QOL preoperatively, but their QOL declined significantly at the 1- and 2-year analysis (P less than .03). No significant QOL improvement appeared in the eCRSsNP group until 4 years (P less than .008), and there was no significant QOL difference among the neCRS groups regardless of nasal polyposis. A statistical difference in endoscopy scores was seen among patients in the preoperative neCRScNP group (P less than .001) and in the eCRScNP group from preoperatively until 5 years postoperatively (P less than .03). Finally, statistical significance appeared in preoperative CT scores analysis among patients in the eCRScNP group (P less than .001).

Dragana991/Getty Images

dbrunk@mdedge.com

CORONADO, CALIF. – Eosinophilic chronic rhinosinusitis with nasal polyposis decreases quality of life improvement after sinus surgery in patients with concurrent asthma, results from a retrospective study demonstrated.

They also have significantly higher Lund-Kennedy endoscopy and Lund-McKay CT scores, compared with control groups.

“Patients with concurrent asthma and chronic sinusitis require more aggressive management than nonasthmatics,” one of the study authors, Aykut A. Unsal, DO, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Additionally, the degree of improvement of not only their sinusitis but possibly their asthma following medical/surgical treatment will also be limited if that patient also suffers from nasal polyps and/or eosinophilia. These patients will ultimately become more difficult to manage.”

In order to examine the relationship of eosinophilia and nasal polyps on quality of life (QOL) in patients with asthma who have chronic rhinosinusitis (CRS) who were treated with surgery, Dr. Unsal and his associates reviewed the records of 457 patients with a diagnosis of CRS who underwent sinus surgery in the department of otolaryngology at the Medical College of Georgia, Augusta. The researchers subdivided patients based on the presence or absence of an asthma diagnosis and further subdivided them based on tissue eosinophilia and nasal polyposis. Next, they compared the Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopy scores, and Lund-McKay CT scores preoperatively and postoperatively at 6 months – 1 year and at 2, 3, 4, and 5 years. They performed a T-test analysis to determine statistical significance.

Of the 457 patients included in the analysis, 92 had asthma and eosinophilic CRS with nasal polyps (eCRScNP), 20 had asthma and eosinophilic CRS without nasal polyps (eCRSsNP), 8 had asthma and noneosinophilic CRS with nasal polyps (neCRScNP), and 16 had asthma and noneosinophilic CRS without nasal polyps (neCRSsNP). The researchers observed that patients in the eCRScNP group showed no difference in QOL preoperatively, but their QOL declined significantly at the 1- and 2-year analysis (P less than .03). No significant QOL improvement appeared in the eCRSsNP group until 4 years (P less than .008), and there was no significant QOL difference among the neCRS groups regardless of nasal polyposis. A statistical difference in endoscopy scores was seen among patients in the preoperative neCRScNP group (P less than .001) and in the eCRScNP group from preoperatively until 5 years postoperatively (P less than .03). Finally, statistical significance appeared in preoperative CT scores analysis among patients in the eCRScNP group (P less than .001).

Dragana991/Getty Images

dbrunk@mdedge.com

CORONADO, CALIF. – Eosinophilic chronic rhinosinusitis with nasal polyposis decreases quality of life improvement after sinus surgery in patients with concurrent asthma, results from a retrospective study demonstrated.

They also have significantly higher Lund-Kennedy endoscopy and Lund-McKay CT scores, compared with control groups.

“Patients with concurrent asthma and chronic sinusitis require more aggressive management than nonasthmatics,” one of the study authors, Aykut A. Unsal, DO, said in an interview in advance of the Triological Society’s Combined Sections Meeting. “Additionally, the degree of improvement of not only their sinusitis but possibly their asthma following medical/surgical treatment will also be limited if that patient also suffers from nasal polyps and/or eosinophilia. These patients will ultimately become more difficult to manage.”

In order to examine the relationship of eosinophilia and nasal polyps on quality of life (QOL) in patients with asthma who have chronic rhinosinusitis (CRS) who were treated with surgery, Dr. Unsal and his associates reviewed the records of 457 patients with a diagnosis of CRS who underwent sinus surgery in the department of otolaryngology at the Medical College of Georgia, Augusta. The researchers subdivided patients based on the presence or absence of an asthma diagnosis and further subdivided them based on tissue eosinophilia and nasal polyposis. Next, they compared the Sinonasal Outcome Test (SNOT-22), Lund-Kennedy endoscopy scores, and Lund-McKay CT scores preoperatively and postoperatively at 6 months – 1 year and at 2, 3, 4, and 5 years. They performed a T-test analysis to determine statistical significance.

Of the 457 patients included in the analysis, 92 had asthma and eosinophilic CRS with nasal polyps (eCRScNP), 20 had asthma and eosinophilic CRS without nasal polyps (eCRSsNP), 8 had asthma and noneosinophilic CRS with nasal polyps (neCRScNP), and 16 had asthma and noneosinophilic CRS without nasal polyps (neCRSsNP). The researchers observed that patients in the eCRScNP group showed no difference in QOL preoperatively, but their QOL declined significantly at the 1- and 2-year analysis (P less than .03). No significant QOL improvement appeared in the eCRSsNP group until 4 years (P less than .008), and there was no significant QOL difference among the neCRS groups regardless of nasal polyposis. A statistical difference in endoscopy scores was seen among patients in the preoperative neCRScNP group (P less than .001) and in the eCRScNP group from preoperatively until 5 years postoperatively (P less than .03). Finally, statistical significance appeared in preoperative CT scores analysis among patients in the eCRScNP group (P less than .001).

Dragana991/Getty Images

dbrunk@mdedge.com

BROOKLYN, N.Y. – There are studies demonstrating depression is more likely to resolve if depressed parents are also treated dating back more than 10 years, but new evidence suggests this effect may extend to children as young as 3 years of age, according to an update on current strategies for early intervention presented at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

Of multiple triggers that can be caught and treated early to prevent children from progressing to chronic depression, addressing parental depression is an important target, according to Karen Dineen Wagner, MD, Director of the Division of Child and Adolescent Psychiatry at the University of Texas Medical Branch in Galveston.

In an overview of strategies for intervening early in children who have or are at risk for depression, Dr. Wagner looked at several targets. The purpose of recognizing and addressing such targets as parental depression is to get children well faster and avoid disease chronicity.

“If we want to intervene and potentially prevent the occurrence of depression, we need to look at disorders or triggers that may precede the depression and that, had they been treated, might have eliminated the stressors that tip the child into depression,” Dr. Wagner said.

Parental depression was just one of these factors, but along with others, such as child abuse of any kind and bullying, each poses a threat for chronic mood disorders, according to Dr. Wagner.

In the case of parental depression, Dr. Wagner cited numerous studies demonstrating a close correlation between remission in the parent and remission in the child. These trajectories interact, so children are less likely to get well if an affected parent does not get well.

“Make sure you consider depression in the parent when you are doing an evaluation, and it is not just depression in the parent who is there. Ask about the other partner who is not there,” Dr. Wagner advised. Parents reluctant to address their own depression should be informed that the mental health of their child is at risk.

The most recent evidence to show benefit from treating both child and parent was drawn from a controlled study that enrolled young children (Luby JL et al. Am J Psychiatry. 2018 Jun 20. doi: 10.1176/appi.ajp.2018.18030321).

In this study, 229 parent-child dyads were randomized to receive parent-child psychotherapy for early childhood depression or to a wait-list. The age range for the children was 3-6.2 years. The therapy was specifically designed to improve the parents’ ability to help young children cope with their feelings.

The parent-child interaction therapy “focused on emotional development which was designed to train parents to work with the child on developing emotional competence in which the child understands their emotions, understands how events affect how they are feeling, and controls emotional reactivity,” Dr. Wagner explained.

For the primary outcome of depression at the end of 18 weeks, the rates were significantly lower in those who participated in the interaction therapy than they were in those on the wait-list. Measures of parent depression and stress were also lower in the therapy group.

Currently, the U. S. Preventive Task Force recommends screening all children at age 12 for depression with the adolescent version of the Patient Health Questionnaire (PHQ-A), according to Dr. Wagner. Given the rising prevalence of depression in adolescents, which climbed 46% from 2005 (8.7%) to 2015 (12.7%) according to a published national survey, this screening is prudent, Dr. Wagner indicated. However, she further suggested that it is reasonable to screen children with risk factors, such as learning disorders or anxiety disorders, even earlier.

The reason is that there are effective therapies. Early treatment may prevent chronic and more severe forms of depression, according to Dr. Wagner. She suggested that there is a growing emphasis on not just treating depression at its early stages but also in recognizing the child at risk, identifying subsyndromal symptoms leading toward depression, and preventing children from ever reaching diagnostic criteria.

Indeed, an initiative for better and earlier detection and treatment of depression in children was begun by the AACAP when Dr. Wagner served recently as its president. Several parts of that program have now been launched. Dr. Wagner encouraged those with an interest to visit the AACAP website, where more information about this initiative can be accessed.

Dr. Wagner reported no potential conflicts of interest.

BROOKLYN, N.Y. – There are studies demonstrating depression is more likely to resolve if depressed parents are also treated dating back more than 10 years, but new evidence suggests this effect may extend to children as young as 3 years of age, according to an update on current strategies for early intervention presented at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

Of multiple triggers that can be caught and treated early to prevent children from progressing to chronic depression, addressing parental depression is an important target, according to Karen Dineen Wagner, MD, Director of the Division of Child and Adolescent Psychiatry at the University of Texas Medical Branch in Galveston.

In an overview of strategies for intervening early in children who have or are at risk for depression, Dr. Wagner looked at several targets. The purpose of recognizing and addressing such targets as parental depression is to get children well faster and avoid disease chronicity.

“If we want to intervene and potentially prevent the occurrence of depression, we need to look at disorders or triggers that may precede the depression and that, had they been treated, might have eliminated the stressors that tip the child into depression,” Dr. Wagner said.

Parental depression was just one of these factors, but along with others, such as child abuse of any kind and bullying, each poses a threat for chronic mood disorders, according to Dr. Wagner.

In the case of parental depression, Dr. Wagner cited numerous studies demonstrating a close correlation between remission in the parent and remission in the child. These trajectories interact, so children are less likely to get well if an affected parent does not get well.

“Make sure you consider depression in the parent when you are doing an evaluation, and it is not just depression in the parent who is there. Ask about the other partner who is not there,” Dr. Wagner advised. Parents reluctant to address their own depression should be informed that the mental health of their child is at risk.

The most recent evidence to show benefit from treating both child and parent was drawn from a controlled study that enrolled young children (Luby JL et al. Am J Psychiatry. 2018 Jun 20. doi: 10.1176/appi.ajp.2018.18030321).

In this study, 229 parent-child dyads were randomized to receive parent-child psychotherapy for early childhood depression or to a wait-list. The age range for the children was 3-6.2 years. The therapy was specifically designed to improve the parents’ ability to help young children cope with their feelings.

The parent-child interaction therapy “focused on emotional development which was designed to train parents to work with the child on developing emotional competence in which the child understands their emotions, understands how events affect how they are feeling, and controls emotional reactivity,” Dr. Wagner explained.

For the primary outcome of depression at the end of 18 weeks, the rates were significantly lower in those who participated in the interaction therapy than they were in those on the wait-list. Measures of parent depression and stress were also lower in the therapy group.

Currently, the U. S. Preventive Task Force recommends screening all children at age 12 for depression with the adolescent version of the Patient Health Questionnaire (PHQ-A), according to Dr. Wagner. Given the rising prevalence of depression in adolescents, which climbed 46% from 2005 (8.7%) to 2015 (12.7%) according to a published national survey, this screening is prudent, Dr. Wagner indicated. However, she further suggested that it is reasonable to screen children with risk factors, such as learning disorders or anxiety disorders, even earlier.

The reason is that there are effective therapies. Early treatment may prevent chronic and more severe forms of depression, according to Dr. Wagner. She suggested that there is a growing emphasis on not just treating depression at its early stages but also in recognizing the child at risk, identifying subsyndromal symptoms leading toward depression, and preventing children from ever reaching diagnostic criteria.

Indeed, an initiative for better and earlier detection and treatment of depression in children was begun by the AACAP when Dr. Wagner served recently as its president. Several parts of that program have now been launched. Dr. Wagner encouraged those with an interest to visit the AACAP website, where more information about this initiative can be accessed.

Dr. Wagner reported no potential conflicts of interest.

BROOKLYN, N.Y. – There are studies demonstrating depression is more likely to resolve if depressed parents are also treated dating back more than 10 years, but new evidence suggests this effect may extend to children as young as 3 years of age, according to an update on current strategies for early intervention presented at a pediatric psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.

Of multiple triggers that can be caught and treated early to prevent children from progressing to chronic depression, addressing parental depression is an important target, according to Karen Dineen Wagner, MD, Director of the Division of Child and Adolescent Psychiatry at the University of Texas Medical Branch in Galveston.

In an overview of strategies for intervening early in children who have or are at risk for depression, Dr. Wagner looked at several targets. The purpose of recognizing and addressing such targets as parental depression is to get children well faster and avoid disease chronicity.

“If we want to intervene and potentially prevent the occurrence of depression, we need to look at disorders or triggers that may precede the depression and that, had they been treated, might have eliminated the stressors that tip the child into depression,” Dr. Wagner said.

Parental depression was just one of these factors, but along with others, such as child abuse of any kind and bullying, each poses a threat for chronic mood disorders, according to Dr. Wagner.

In the case of parental depression, Dr. Wagner cited numerous studies demonstrating a close correlation between remission in the parent and remission in the child. These trajectories interact, so children are less likely to get well if an affected parent does not get well.

“Make sure you consider depression in the parent when you are doing an evaluation, and it is not just depression in the parent who is there. Ask about the other partner who is not there,” Dr. Wagner advised. Parents reluctant to address their own depression should be informed that the mental health of their child is at risk.

The most recent evidence to show benefit from treating both child and parent was drawn from a controlled study that enrolled young children (Luby JL et al. Am J Psychiatry. 2018 Jun 20. doi: 10.1176/appi.ajp.2018.18030321).

In this study, 229 parent-child dyads were randomized to receive parent-child psychotherapy for early childhood depression or to a wait-list. The age range for the children was 3-6.2 years. The therapy was specifically designed to improve the parents’ ability to help young children cope with their feelings.

The parent-child interaction therapy “focused on emotional development which was designed to train parents to work with the child on developing emotional competence in which the child understands their emotions, understands how events affect how they are feeling, and controls emotional reactivity,” Dr. Wagner explained.

For the primary outcome of depression at the end of 18 weeks, the rates were significantly lower in those who participated in the interaction therapy than they were in those on the wait-list. Measures of parent depression and stress were also lower in the therapy group.

Currently, the U. S. Preventive Task Force recommends screening all children at age 12 for depression with the adolescent version of the Patient Health Questionnaire (PHQ-A), according to Dr. Wagner. Given the rising prevalence of depression in adolescents, which climbed 46% from 2005 (8.7%) to 2015 (12.7%) according to a published national survey, this screening is prudent, Dr. Wagner indicated. However, she further suggested that it is reasonable to screen children with risk factors, such as learning disorders or anxiety disorders, even earlier.

The reason is that there are effective therapies. Early treatment may prevent chronic and more severe forms of depression, according to Dr. Wagner. She suggested that there is a growing emphasis on not just treating depression at its early stages but also in recognizing the child at risk, identifying subsyndromal symptoms leading toward depression, and preventing children from ever reaching diagnostic criteria.

Indeed, an initiative for better and earlier detection and treatment of depression in children was begun by the AACAP when Dr. Wagner served recently as its president. Several parts of that program have now been launched. Dr. Wagner encouraged those with an interest to visit the AACAP website, where more information about this initiative can be accessed.

Dr. Wagner reported no potential conflicts of interest.

BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.

Mitchel L. Zoler/MDedge News

“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.

Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.

Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.

The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.

Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.

During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.

At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.

A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).

mzoler@mdedge.com

BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.

Mitchel L. Zoler/MDedge News

“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.

Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.

Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.

The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.

Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.

During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.

At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.

A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).

mzoler@mdedge.com

BOSTON – Sixty-three patients with atrial fibrillation (AF) and a history of intracranial hemorrhage have safely received a Watchman device for left atrial appendage (LAA) closure followed by 6 months of treatment with an individualized drug regimen to prevent thrombus formation at three U.S. centers. The 6-month outcomes of these patients were as good as the outcomes of 95 similar patients who did not have a history of intracranial hemorrhage, Moussa C. Mansour, MD, said at the annual International AF Symposium.

Mitchel L. Zoler/MDedge News

“Individualized, postprocedural antithrombotic management ranging from dual antiplatelet therapy to oral anticoagulation plus aspirin can be used short term,” said Dr. Mansour, director of the atrial AF program at Massachusetts General Hospital. He and his associates devised this approach “out of necessity,” he said. The findings “show that you can get these patients through the initial postprocedural period” by individualizing their antiplatelet or anticoagulant treatment.

Not many U.S. operators are currently placing LAA closure devices in patients with a history of intracranial hemorrhage (ICH). “No one knows what to do with them. There is no standard approach; it’s an evolving field,” he said in an interview.

Dr. Mansour reviewed his group’s experience at Massachusetts General with LAA closure using the Watchman device combined with the experience of teams at the Texas Cardiac Arrhythmia Institute in Austin and the HCA Midwest Health in Overland Park, Kan. This included 63 AF patients with an ICH history and 95 similar AF patients with no hemorrhagic history. Nearly half of the patients with a prior ICH also had a history of at least one ischemic stroke or transient ischemic attack, compared with just over a third of the patients without a prior ICH. The two groups had nearly identical CHA2DS2-VASc scores, 4.9 and 4.7, and also very similar HAS-BLED scores.

The patients with a prior ICH included 57% with a prior intracerebral hemorrhage, 29% with a prior subdural hemorrhage, 10% with a subarachnoid hemorrhage, and the remainder unspecified.

Thirty-two of the 63 patients with an ICH history received postprocedural anticoagulation with a direct-acting oral anticoagulant, 18 received warfarin, and 13 received dual antiplatelet therapy but no anticoagulant. Among the 45 patients treated with an oral anticoagulant, 27 also received aspirin. Among the 95 patients reviewed without an ICH history, 93 received an oral anticoagulant, and 2 received dual antiplatelet therapy.

During 180 days of follow-up, the combined incidence of death, stroke, or a major bleed was about 5% among the patients with an ICH history and about 10% among those without this history, a difference that was not statistically significant, Dr. Mansour said.

At Massachusetts General, the decision on how to treat AF patients with an ICH history after they undergo LAA closure is made by a multidisciplinary team of clinicians from the arrhythmia, neurology, radiology, anesthesia, and cardiovascular surgery services. A key factor when determining the drug regimen these patients will receive is the location and size of the ICH when imaged with CT or MRI, Dr. Mansour said. The team also assessed the current likelihood that the patient will bleed. “One size does not fit all” patients, he explained.

A randomized trial, ASAP-TOO (Assessment of the Watchman Device in Patients Unsuitable for Oral Anticoagulation) is now in progress and was designed to compare the safety and efficacy of LAA closure using Watchman with medical management in 888 patients deemed ineligible for anticoagulation, but enrollment into the trial has been slow. As of early 2019, the study’s organizers posted an estimated completion date of late 2023. Until that study finishes, the field will have no definitive data on how to manage these patients, Dr. Mansour said. He noted that a handful of other reports have presented evidence for the safety of LAA closure in these patients, including a review from the Cleveland Clinic on 38 AF patients who received the Watchman device after an ICH (Heart Rhythm. 2018 Dec 2. doi: 10.1016/j.hrthm.2018.11.022); a review of the Amplatzer Cardiac Plug registry, which included 198 patients with an ICH history (Int J Cardiol. 2017 June 1;236[1]:232-6); and a single-center review of 46 French patients who underwent LAA closure after intracerebral hemorrhage (J Stroke Cerebrovasc Dis. 2017 March;26[3]:545-51).

mzoler@mdedge.com

Although first detected in summer 2018, angiotensin II receptor blockers (ARBs) contaminated with nitrosamines have been on the market in the United States for 4 years, according to the Food and Drug Administration.

“FDA scientists estimate that, if 8,000 people took the highest daily valsartan dose (320 mg) that contained NDMA [N-Nitrosodimethylamine] for 4 years (the time we think the affected products had been on the U.S. market), there may be one additional case of cancer beyond the average cancer rate among those 8,000 Americans,” the agency said in a Jan. 25 update from Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research.

“The vast majority of patients exposed to NDMA through ARBs received much smaller amounts of the impurity than this worst-case scenario. Since not all ARBs are affected, it’s very likely that a patient taking an ARB for 4 years would not have always received one of the affected products. We’re still seeking to similarly quantify the risk from NDEA [N-Nitrosodiethylamine] and plan to communicate our findings as soon as possible,” they said.

“While the total exposure to these impurities for most patients was small, we are deeply concerned that patients were exposed to this impurity in the first place and that the presence of nitrosamines went undetected for a period of time,” Dr. Gottlieb and Dr. Woodcock said in the statement. Through ongoing and “exhaustive” efforts, they pledged the agency will resolve the problem and ensure it never happens again.

Meanwhile, the ongoing recalls have led to a shortage of valsartan, and other ARBs may soon follow suit. The agency hoped the one case of cancer per 8,000 patients analysis would help providers “balance the risk of patients ingesting low levels of the impurities ... for a short period of time” during shortages until a suitable replacement or alternative is found.

The problem surfaced last year when FDA was alerted to nitrosamine contamination in valsartan manufactured in China and marketed in the U.S. by generic pharmaceutical companies. Contamination has since been detected in generic irbesartan and losartan.

The impurities are generated “when specific chemicals and reaction conditions are present in the manufacturing process ... and may also result from the reuse of materials, such as solvents,” something “neither regulators nor industry fully understood” before. The agency has developed and shared new tests to detect nitrosamines. “Manufacturers using processes at risk for these impurities are expected to test for them to ensure that active ingredients and finished products are free of detectable levels,” it said.

Meanwhile, the recalls keep coming, the latest for losartan and hydrochlorothiazide combination tablets from Torrent Pharmaceuticals. The recalls are listed on FDA’s website.

aotto@mdedge.com

Although first detected in summer 2018, angiotensin II receptor blockers (ARBs) contaminated with nitrosamines have been on the market in the United States for 4 years, according to the Food and Drug Administration.

“FDA scientists estimate that, if 8,000 people took the highest daily valsartan dose (320 mg) that contained NDMA [N-Nitrosodimethylamine] for 4 years (the time we think the affected products had been on the U.S. market), there may be one additional case of cancer beyond the average cancer rate among those 8,000 Americans,” the agency said in a Jan. 25 update from Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research.

“The vast majority of patients exposed to NDMA through ARBs received much smaller amounts of the impurity than this worst-case scenario. Since not all ARBs are affected, it’s very likely that a patient taking an ARB for 4 years would not have always received one of the affected products. We’re still seeking to similarly quantify the risk from NDEA [N-Nitrosodiethylamine] and plan to communicate our findings as soon as possible,” they said.

“While the total exposure to these impurities for most patients was small, we are deeply concerned that patients were exposed to this impurity in the first place and that the presence of nitrosamines went undetected for a period of time,” Dr. Gottlieb and Dr. Woodcock said in the statement. Through ongoing and “exhaustive” efforts, they pledged the agency will resolve the problem and ensure it never happens again.

Meanwhile, the ongoing recalls have led to a shortage of valsartan, and other ARBs may soon follow suit. The agency hoped the one case of cancer per 8,000 patients analysis would help providers “balance the risk of patients ingesting low levels of the impurities ... for a short period of time” during shortages until a suitable replacement or alternative is found.

The problem surfaced last year when FDA was alerted to nitrosamine contamination in valsartan manufactured in China and marketed in the U.S. by generic pharmaceutical companies. Contamination has since been detected in generic irbesartan and losartan.

The impurities are generated “when specific chemicals and reaction conditions are present in the manufacturing process ... and may also result from the reuse of materials, such as solvents,” something “neither regulators nor industry fully understood” before. The agency has developed and shared new tests to detect nitrosamines. “Manufacturers using processes at risk for these impurities are expected to test for them to ensure that active ingredients and finished products are free of detectable levels,” it said.

Meanwhile, the recalls keep coming, the latest for losartan and hydrochlorothiazide combination tablets from Torrent Pharmaceuticals. The recalls are listed on FDA’s website.

aotto@mdedge.com

Although first detected in summer 2018, angiotensin II receptor blockers (ARBs) contaminated with nitrosamines have been on the market in the United States for 4 years, according to the Food and Drug Administration.

“FDA scientists estimate that, if 8,000 people took the highest daily valsartan dose (320 mg) that contained NDMA [N-Nitrosodimethylamine] for 4 years (the time we think the affected products had been on the U.S. market), there may be one additional case of cancer beyond the average cancer rate among those 8,000 Americans,” the agency said in a Jan. 25 update from Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research.

“The vast majority of patients exposed to NDMA through ARBs received much smaller amounts of the impurity than this worst-case scenario. Since not all ARBs are affected, it’s very likely that a patient taking an ARB for 4 years would not have always received one of the affected products. We’re still seeking to similarly quantify the risk from NDEA [N-Nitrosodiethylamine] and plan to communicate our findings as soon as possible,” they said.

“While the total exposure to these impurities for most patients was small, we are deeply concerned that patients were exposed to this impurity in the first place and that the presence of nitrosamines went undetected for a period of time,” Dr. Gottlieb and Dr. Woodcock said in the statement. Through ongoing and “exhaustive” efforts, they pledged the agency will resolve the problem and ensure it never happens again.

Meanwhile, the ongoing recalls have led to a shortage of valsartan, and other ARBs may soon follow suit. The agency hoped the one case of cancer per 8,000 patients analysis would help providers “balance the risk of patients ingesting low levels of the impurities ... for a short period of time” during shortages until a suitable replacement or alternative is found.

The problem surfaced last year when FDA was alerted to nitrosamine contamination in valsartan manufactured in China and marketed in the U.S. by generic pharmaceutical companies. Contamination has since been detected in generic irbesartan and losartan.

The impurities are generated “when specific chemicals and reaction conditions are present in the manufacturing process ... and may also result from the reuse of materials, such as solvents,” something “neither regulators nor industry fully understood” before. The agency has developed and shared new tests to detect nitrosamines. “Manufacturers using processes at risk for these impurities are expected to test for them to ensure that active ingredients and finished products are free of detectable levels,” it said.

Meanwhile, the recalls keep coming, the latest for losartan and hydrochlorothiazide combination tablets from Torrent Pharmaceuticals. The recalls are listed on FDA’s website.

aotto@mdedge.com

Sanofi hasn’t given up on its SGLT1/2 inhibitor sotagliflozin (Zynquista) for type 1 diabetes mellitus despite a recent 8-to-8 split decision on recommendation for approval from the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee.

In the company’s three trials, involving about 3,000 insulin-dependent adults treated for up to a year, the drug lowered hemoglobin A_1c a respectable 0.5% without increasing hypoglycemia risk; reduced glucose variability; and increased time in range, with some modest benefits in both weight loss and lower blood pressure. There was no sign of the increased amputation risk that has bedeviled the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana), already on the market for type 2 diabetes mellitus.

The fly in the ointment was diabetic ketoacidosis (DKA); the drug increased the risk eightfold versus placebo, and, although there were no DKA deaths and over 60% of patients resumed sotagliflozin after recovering, the cases were serious and sometimes occurred in patients with glucose levels as low as 150 mg/dL. Younger people and women seemed to be at higher risk, according to the data.

DKA risk was 4 cases per 100 patients/year, a 4% risk, and that was in the ideal setting of a trial, not everyday practice. The annual background risk of DKA is 1% or less in type 1 diabetes mellitus (T1DM).

“It’s got to be safer than this,” said committee chair Peter Wilson, MD, professor of cardiology and public health at Emory University, Atlanta.

Dr. Wilson voted to recommend approval but with the major caveat that Sanofi have a strong risk mitigation program in place, perhaps based on ketone monitoring to catch emerging DKA before people end up in the ED. That was a universal request among others who voted for recommendation; among those who voted against, the concern in large part was that, even with such a program, the risk of DKA was still too high.

“If they had already developed a mitigation program that had been piloted, and they showed us some data, there would have been more enthusiasm, but we didn’t have that,” he said in an interview after the hearing.

Sanofi did suggest possible risk mitigation strategies during the meeting. In a statement afterwards, spokesman Nicolas Kressmann said, “While we acknowledge the increase in incidence of DKA observed with the addition of sotagliflozin to insulin, we believe that the risks may be mitigated and managed with proper patient selection and education regarding appropriate ketone monitoring. We will continue to work with the FDA to ensure the agency has the data it needs to evaluate the safety and efficacy of sotagliflozin when used as an oral treatment together with insulin by adults with T1DM. We are confident in the data of our T1DM clinical program.”

Meanwhile, the company’s development for T2DMs is ongoing, with results from a number of trials expected later in 2019. Sotagliflozin would join canagliflozin and two other SGLT2 inhibitors already on the market for T2DM, none of which have been approved for T1DM disease. The approved drugs work by increasing renal glucose excretion.

A significant proportion of DKA cases in sotagliflozin’s T1DM trials were preceded by infections and other well-known triggers, “but there were a proportion of patients where they couldn’t identify the cause; it just kind of came out of the blue. Something about the medication lowers the threshold,” said panelist and endocrinologist Cecilia Low Wang, MD, director of the glucose management team at the University of Colorado Anschutz Medical Campus, Aurora, who voted against recommending approval.

“There’s definitely an increased risk” with other SGLT2 inhibitors, as well, when used off label for T1DM. “No one really knows why,” she said.

Dr. Wilson was also concerned that insulin wasn’t more tightly titrated in the placebo groups, which might have led to the 0.5% improvement seen with sotagliflozin, but “they wanted to have trials that were likely to be beneficial, so it’s reasonable to do what they did,” he said.

Overall, “we don’t really have many options for type 1, and many of us were sympathetic to the idea of increasing options.” In T1DM, “you can lose your concentration” on insulin dosing for a couple hours, “and the next thing you know you are going too high or too low and going off the road. These pills help smooth out your ups and downs. I would like to think [sotagliflozin] might be approved for a restricted group, for which we’ve really sorted out the ketone data,” he said.

Dr. Wilson and Dr. Low Wang did not have any disclosures.

aotto@mdedge.com

Sanofi hasn’t given up on its SGLT1/2 inhibitor sotagliflozin (Zynquista) for type 1 diabetes mellitus despite a recent 8-to-8 split decision on recommendation for approval from the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee.

In the company’s three trials, involving about 3,000 insulin-dependent adults treated for up to a year, the drug lowered hemoglobin A_1c a respectable 0.5% without increasing hypoglycemia risk; reduced glucose variability; and increased time in range, with some modest benefits in both weight loss and lower blood pressure. There was no sign of the increased amputation risk that has bedeviled the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana), already on the market for type 2 diabetes mellitus.

The fly in the ointment was diabetic ketoacidosis (DKA); the drug increased the risk eightfold versus placebo, and, although there were no DKA deaths and over 60% of patients resumed sotagliflozin after recovering, the cases were serious and sometimes occurred in patients with glucose levels as low as 150 mg/dL. Younger people and women seemed to be at higher risk, according to the data.

DKA risk was 4 cases per 100 patients/year, a 4% risk, and that was in the ideal setting of a trial, not everyday practice. The annual background risk of DKA is 1% or less in type 1 diabetes mellitus (T1DM).

“It’s got to be safer than this,” said committee chair Peter Wilson, MD, professor of cardiology and public health at Emory University, Atlanta.

Dr. Wilson voted to recommend approval but with the major caveat that Sanofi have a strong risk mitigation program in place, perhaps based on ketone monitoring to catch emerging DKA before people end up in the ED. That was a universal request among others who voted for recommendation; among those who voted against, the concern in large part was that, even with such a program, the risk of DKA was still too high.

“If they had already developed a mitigation program that had been piloted, and they showed us some data, there would have been more enthusiasm, but we didn’t have that,” he said in an interview after the hearing.

Sanofi did suggest possible risk mitigation strategies during the meeting. In a statement afterwards, spokesman Nicolas Kressmann said, “While we acknowledge the increase in incidence of DKA observed with the addition of sotagliflozin to insulin, we believe that the risks may be mitigated and managed with proper patient selection and education regarding appropriate ketone monitoring. We will continue to work with the FDA to ensure the agency has the data it needs to evaluate the safety and efficacy of sotagliflozin when used as an oral treatment together with insulin by adults with T1DM. We are confident in the data of our T1DM clinical program.”

Meanwhile, the company’s development for T2DMs is ongoing, with results from a number of trials expected later in 2019. Sotagliflozin would join canagliflozin and two other SGLT2 inhibitors already on the market for T2DM, none of which have been approved for T1DM disease. The approved drugs work by increasing renal glucose excretion.

A significant proportion of DKA cases in sotagliflozin’s T1DM trials were preceded by infections and other well-known triggers, “but there were a proportion of patients where they couldn’t identify the cause; it just kind of came out of the blue. Something about the medication lowers the threshold,” said panelist and endocrinologist Cecilia Low Wang, MD, director of the glucose management team at the University of Colorado Anschutz Medical Campus, Aurora, who voted against recommending approval.

“There’s definitely an increased risk” with other SGLT2 inhibitors, as well, when used off label for T1DM. “No one really knows why,” she said.

Dr. Wilson was also concerned that insulin wasn’t more tightly titrated in the placebo groups, which might have led to the 0.5% improvement seen with sotagliflozin, but “they wanted to have trials that were likely to be beneficial, so it’s reasonable to do what they did,” he said.

Overall, “we don’t really have many options for type 1, and many of us were sympathetic to the idea of increasing options.” In T1DM, “you can lose your concentration” on insulin dosing for a couple hours, “and the next thing you know you are going too high or too low and going off the road. These pills help smooth out your ups and downs. I would like to think [sotagliflozin] might be approved for a restricted group, for which we’ve really sorted out the ketone data,” he said.

Dr. Wilson and Dr. Low Wang did not have any disclosures.

aotto@mdedge.com

Sanofi hasn’t given up on its SGLT1/2 inhibitor sotagliflozin (Zynquista) for type 1 diabetes mellitus despite a recent 8-to-8 split decision on recommendation for approval from the Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee.

In the company’s three trials, involving about 3,000 insulin-dependent adults treated for up to a year, the drug lowered hemoglobin A_1c a respectable 0.5% without increasing hypoglycemia risk; reduced glucose variability; and increased time in range, with some modest benefits in both weight loss and lower blood pressure. There was no sign of the increased amputation risk that has bedeviled the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Invokana), already on the market for type 2 diabetes mellitus.

The fly in the ointment was diabetic ketoacidosis (DKA); the drug increased the risk eightfold versus placebo, and, although there were no DKA deaths and over 60% of patients resumed sotagliflozin after recovering, the cases were serious and sometimes occurred in patients with glucose levels as low as 150 mg/dL. Younger people and women seemed to be at higher risk, according to the data.

DKA risk was 4 cases per 100 patients/year, a 4% risk, and that was in the ideal setting of a trial, not everyday practice. The annual background risk of DKA is 1% or less in type 1 diabetes mellitus (T1DM).

“It’s got to be safer than this,” said committee chair Peter Wilson, MD, professor of cardiology and public health at Emory University, Atlanta.

Dr. Wilson voted to recommend approval but with the major caveat that Sanofi have a strong risk mitigation program in place, perhaps based on ketone monitoring to catch emerging DKA before people end up in the ED. That was a universal request among others who voted for recommendation; among those who voted against, the concern in large part was that, even with such a program, the risk of DKA was still too high.

“If they had already developed a mitigation program that had been piloted, and they showed us some data, there would have been more enthusiasm, but we didn’t have that,” he said in an interview after the hearing.

Sanofi did suggest possible risk mitigation strategies during the meeting. In a statement afterwards, spokesman Nicolas Kressmann said, “While we acknowledge the increase in incidence of DKA observed with the addition of sotagliflozin to insulin, we believe that the risks may be mitigated and managed with proper patient selection and education regarding appropriate ketone monitoring. We will continue to work with the FDA to ensure the agency has the data it needs to evaluate the safety and efficacy of sotagliflozin when used as an oral treatment together with insulin by adults with T1DM. We are confident in the data of our T1DM clinical program.”

Meanwhile, the company’s development for T2DMs is ongoing, with results from a number of trials expected later in 2019. Sotagliflozin would join canagliflozin and two other SGLT2 inhibitors already on the market for T2DM, none of which have been approved for T1DM disease. The approved drugs work by increasing renal glucose excretion.

A significant proportion of DKA cases in sotagliflozin’s T1DM trials were preceded by infections and other well-known triggers, “but there were a proportion of patients where they couldn’t identify the cause; it just kind of came out of the blue. Something about the medication lowers the threshold,” said panelist and endocrinologist Cecilia Low Wang, MD, director of the glucose management team at the University of Colorado Anschutz Medical Campus, Aurora, who voted against recommending approval.

“There’s definitely an increased risk” with other SGLT2 inhibitors, as well, when used off label for T1DM. “No one really knows why,” she said.

Dr. Wilson was also concerned that insulin wasn’t more tightly titrated in the placebo groups, which might have led to the 0.5% improvement seen with sotagliflozin, but “they wanted to have trials that were likely to be beneficial, so it’s reasonable to do what they did,” he said.

Overall, “we don’t really have many options for type 1, and many of us were sympathetic to the idea of increasing options.” In T1DM, “you can lose your concentration” on insulin dosing for a couple hours, “and the next thing you know you are going too high or too low and going off the road. These pills help smooth out your ups and downs. I would like to think [sotagliflozin] might be approved for a restricted group, for which we’ve really sorted out the ketone data,” he said.

Dr. Wilson and Dr. Low Wang did not have any disclosures.

aotto@mdedge.com

A proposal by the Trump Administration to pay for Medicare drugs administered in the physician office is not going over well with doctors.

monkeybusinessimages/thinkstockphotos.com

The Centers for Medicare & Medicaid Services in October 2018 issued an ”advance notice of proposed rulemaking with comment” outlining a test that would pay for Part B drugs with price points more closely aligned with international rates through the use of private sector vendors that would negotiate drug prices, procure the products, distribute them to physicians and hospitals, and take on the responsibility of billing Medicare.

Although the so-called International Pricing Index (IPI) model is not fully fleshed out in the regulatory filing, one of the key details that has been announced is that the demonstration project would have mandatory participation. This did not sit well with medical societies offering feedback to CMS.

The American Gastroenterological Association stated in comments filed with the agency that “AGA opposes mandatory physician participation and we urge CMS to implement the model on a voluntary basis.” AGA further noted that, while they support the Administration’s goal of reducing drug costs, “we are concerned that the model, as described, will make acquisition of Part B drugs more complex and will shift costs to physicians and practices, increasing administrative burden. Moreover, we are concerned that the IPI model may restrict access to clinically appropriate therapies for people with digestive diseases.”

And while the Community Oncology Alliance also spoke against making participation in the IPI model demonstration project mandatory, it went further with its criticism of the proposal.

“COA does not support the IPI Model as proposed in the pre-proposed rule published by [CMS] because we have serious concerns about its impact on cancer patient care and even its legality,” the group said on Dec. 31, 2018, comments filed with the agency, adding that “mandatory demonstration projects are clearly not in the charter of CMMI [Center for Medicare & Medicaid Innovation] as written into law by Congress. ... That would either be illegal or unconstitutional, with the latter case invalidating the section of the law that created and funded CMMI.”

The AGA, like other groups, also took exception to CMS’s “insinuation” in its regulatory preproposal that physicians select treatments based on reimbursement ahead of patient need. “CMS has repeatedly suggested that physicians prescribe therapies to patients not based on clinical evidence and judgment, but rather based on how much Medicare revenue it will generate for them. AGA objects to this premise. There is no objective evidence to support this idea.”

While none of the groups offered support for the IPI demonstration project, all offered suggestions on what could be done to improve on the details outlined in the advanced noticed of proposed rulemaking. AGA made recommendations, including making IPI Model participation voluntary; allowing individual physicians and physician groups to become model vendors, even if they intend to serve only their own practice or their own geographic region; prohibiting model vendors from implementing utilization management; and making model vendors responsible for collecting beneficiary cost-sharing. The American Medical Association in Dec. 20, 2018, comments to the agency took issue with the focus on single-source drugs and biologics indexed with international pricing, which could create access issues and have immediate adverse patient impacts.
 

gtwachtman@mdedge.com

A proposal by the Trump Administration to pay for Medicare drugs administered in the physician office is not going over well with doctors.

monkeybusinessimages/thinkstockphotos.com

The Centers for Medicare & Medicaid Services in October 2018 issued an ”advance notice of proposed rulemaking with comment” outlining a test that would pay for Part B drugs with price points more closely aligned with international rates through the use of private sector vendors that would negotiate drug prices, procure the products, distribute them to physicians and hospitals, and take on the responsibility of billing Medicare.

Although the so-called International Pricing Index (IPI) model is not fully fleshed out in the regulatory filing, one of the key details that has been announced is that the demonstration project would have mandatory participation. This did not sit well with medical societies offering feedback to CMS.

The American Gastroenterological Association stated in comments filed with the agency that “AGA opposes mandatory physician participation and we urge CMS to implement the model on a voluntary basis.” AGA further noted that, while they support the Administration’s goal of reducing drug costs, “we are concerned that the model, as described, will make acquisition of Part B drugs more complex and will shift costs to physicians and practices, increasing administrative burden. Moreover, we are concerned that the IPI model may restrict access to clinically appropriate therapies for people with digestive diseases.”

And while the Community Oncology Alliance also spoke against making participation in the IPI model demonstration project mandatory, it went further with its criticism of the proposal.

“COA does not support the IPI Model as proposed in the pre-proposed rule published by [CMS] because we have serious concerns about its impact on cancer patient care and even its legality,” the group said on Dec. 31, 2018, comments filed with the agency, adding that “mandatory demonstration projects are clearly not in the charter of CMMI [Center for Medicare & Medicaid Innovation] as written into law by Congress. ... That would either be illegal or unconstitutional, with the latter case invalidating the section of the law that created and funded CMMI.”

The AGA, like other groups, also took exception to CMS’s “insinuation” in its regulatory preproposal that physicians select treatments based on reimbursement ahead of patient need. “CMS has repeatedly suggested that physicians prescribe therapies to patients not based on clinical evidence and judgment, but rather based on how much Medicare revenue it will generate for them. AGA objects to this premise. There is no objective evidence to support this idea.”

While none of the groups offered support for the IPI demonstration project, all offered suggestions on what could be done to improve on the details outlined in the advanced noticed of proposed rulemaking. AGA made recommendations, including making IPI Model participation voluntary; allowing individual physicians and physician groups to become model vendors, even if they intend to serve only their own practice or their own geographic region; prohibiting model vendors from implementing utilization management; and making model vendors responsible for collecting beneficiary cost-sharing. The American Medical Association in Dec. 20, 2018, comments to the agency took issue with the focus on single-source drugs and biologics indexed with international pricing, which could create access issues and have immediate adverse patient impacts.
 

gtwachtman@mdedge.com

A proposal by the Trump Administration to pay for Medicare drugs administered in the physician office is not going over well with doctors.

monkeybusinessimages/thinkstockphotos.com

The Centers for Medicare & Medicaid Services in October 2018 issued an ”advance notice of proposed rulemaking with comment” outlining a test that would pay for Part B drugs with price points more closely aligned with international rates through the use of private sector vendors that would negotiate drug prices, procure the products, distribute them to physicians and hospitals, and take on the responsibility of billing Medicare.

Although the so-called International Pricing Index (IPI) model is not fully fleshed out in the regulatory filing, one of the key details that has been announced is that the demonstration project would have mandatory participation. This did not sit well with medical societies offering feedback to CMS.

The American Gastroenterological Association stated in comments filed with the agency that “AGA opposes mandatory physician participation and we urge CMS to implement the model on a voluntary basis.” AGA further noted that, while they support the Administration’s goal of reducing drug costs, “we are concerned that the model, as described, will make acquisition of Part B drugs more complex and will shift costs to physicians and practices, increasing administrative burden. Moreover, we are concerned that the IPI model may restrict access to clinically appropriate therapies for people with digestive diseases.”

And while the Community Oncology Alliance also spoke against making participation in the IPI model demonstration project mandatory, it went further with its criticism of the proposal.

“COA does not support the IPI Model as proposed in the pre-proposed rule published by [CMS] because we have serious concerns about its impact on cancer patient care and even its legality,” the group said on Dec. 31, 2018, comments filed with the agency, adding that “mandatory demonstration projects are clearly not in the charter of CMMI [Center for Medicare & Medicaid Innovation] as written into law by Congress. ... That would either be illegal or unconstitutional, with the latter case invalidating the section of the law that created and funded CMMI.”

The AGA, like other groups, also took exception to CMS’s “insinuation” in its regulatory preproposal that physicians select treatments based on reimbursement ahead of patient need. “CMS has repeatedly suggested that physicians prescribe therapies to patients not based on clinical evidence and judgment, but rather based on how much Medicare revenue it will generate for them. AGA objects to this premise. There is no objective evidence to support this idea.”

While none of the groups offered support for the IPI demonstration project, all offered suggestions on what could be done to improve on the details outlined in the advanced noticed of proposed rulemaking. AGA made recommendations, including making IPI Model participation voluntary; allowing individual physicians and physician groups to become model vendors, even if they intend to serve only their own practice or their own geographic region; prohibiting model vendors from implementing utilization management; and making model vendors responsible for collecting beneficiary cost-sharing. The American Medical Association in Dec. 20, 2018, comments to the agency took issue with the focus on single-source drugs and biologics indexed with international pricing, which could create access issues and have immediate adverse patient impacts.
 

gtwachtman@mdedge.com

The European Commission (EC) has expanded the approved indication for blinatumomab (Blincyto).

The drug is now approved in Europe to treat adults with Philadelphia chromosome–negative (Ph–), CD19-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission with minimal residual disease (MRD) of at least 0.1%.

Blinatumomab is already approved in Europe to treat adults with Ph–, CD19-positive relapsed/refractory BCP-ALL and children aged 1 year or older who have relapsed/refractory Ph–, CD19-positive BCP-ALL and have received at least two prior therapies or relapsed after allogeneic hematopoietic stem cell transplant.

The drug was approved in the United States in March 2018 for the treatment of adults and children with BCP-ALL in first or second complete remission with MRD of at least 0.1%.

The EC’s decision to approve blinatumomab in MRD-positive patients was supported by the phase 2 BLAST trial (Blood. 2018;131[14]:1522-31).

The EC’s approval is also based on a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).

That opinion, issued in November 2018, was a reversal of the opinion the committee issued in July 2018. At that time, the CHMP said the available data did not support approval for blinatumomab to treat MRD-positive BCP-ALL.

The CHMP acknowledged that blinatumomab produced MRD negativity in many patients in the BLAST trial but said there was no strong evidence that this led to improved survival. As a result, the CHMP said the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.

However, Amgen requested a reexamination of the CHMP’s opinion. During the reexamination, the CHMP reviewed all the data and consulted a group of experts.

The experts echoed the CHMP’s prior sentiment that there was no strong evidence of improved survival in MRD-positive patients treated with blinatumomab. However, they also said the data indicate a good response to blinatumomab, with around 78% of patients becoming negative for MRD after treatment.

Noting that MRD-positive patients have a high risk of relapse and few treatment options, the CHMP concluded that the benefits of blinatumomab outweigh its risks in this patient population.

The CHMP recommended expanding the approved indication for blinatumomab but also requested that Amgen provide data from ongoing studies of the drug in MRD-positive patients.

jensmith@mdedge.com

The European Commission (EC) has expanded the approved indication for blinatumomab (Blincyto).

The drug is now approved in Europe to treat adults with Philadelphia chromosome–negative (Ph–), CD19-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission with minimal residual disease (MRD) of at least 0.1%.

Blinatumomab is already approved in Europe to treat adults with Ph–, CD19-positive relapsed/refractory BCP-ALL and children aged 1 year or older who have relapsed/refractory Ph–, CD19-positive BCP-ALL and have received at least two prior therapies or relapsed after allogeneic hematopoietic stem cell transplant.

The drug was approved in the United States in March 2018 for the treatment of adults and children with BCP-ALL in first or second complete remission with MRD of at least 0.1%.

The EC’s decision to approve blinatumomab in MRD-positive patients was supported by the phase 2 BLAST trial (Blood. 2018;131[14]:1522-31).

The EC’s approval is also based on a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).

That opinion, issued in November 2018, was a reversal of the opinion the committee issued in July 2018. At that time, the CHMP said the available data did not support approval for blinatumomab to treat MRD-positive BCP-ALL.

The CHMP acknowledged that blinatumomab produced MRD negativity in many patients in the BLAST trial but said there was no strong evidence that this led to improved survival. As a result, the CHMP said the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.

However, Amgen requested a reexamination of the CHMP’s opinion. During the reexamination, the CHMP reviewed all the data and consulted a group of experts.

The experts echoed the CHMP’s prior sentiment that there was no strong evidence of improved survival in MRD-positive patients treated with blinatumomab. However, they also said the data indicate a good response to blinatumomab, with around 78% of patients becoming negative for MRD after treatment.

Noting that MRD-positive patients have a high risk of relapse and few treatment options, the CHMP concluded that the benefits of blinatumomab outweigh its risks in this patient population.

The CHMP recommended expanding the approved indication for blinatumomab but also requested that Amgen provide data from ongoing studies of the drug in MRD-positive patients.

jensmith@mdedge.com

The European Commission (EC) has expanded the approved indication for blinatumomab (Blincyto).

The drug is now approved in Europe to treat adults with Philadelphia chromosome–negative (Ph–), CD19-positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in first or second complete remission with minimal residual disease (MRD) of at least 0.1%.

Blinatumomab is already approved in Europe to treat adults with Ph–, CD19-positive relapsed/refractory BCP-ALL and children aged 1 year or older who have relapsed/refractory Ph–, CD19-positive BCP-ALL and have received at least two prior therapies or relapsed after allogeneic hematopoietic stem cell transplant.

The drug was approved in the United States in March 2018 for the treatment of adults and children with BCP-ALL in first or second complete remission with MRD of at least 0.1%.

The EC’s decision to approve blinatumomab in MRD-positive patients was supported by the phase 2 BLAST trial (Blood. 2018;131[14]:1522-31).

The EC’s approval is also based on a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).

That opinion, issued in November 2018, was a reversal of the opinion the committee issued in July 2018. At that time, the CHMP said the available data did not support approval for blinatumomab to treat MRD-positive BCP-ALL.

The CHMP acknowledged that blinatumomab produced MRD negativity in many patients in the BLAST trial but said there was no strong evidence that this led to improved survival. As a result, the CHMP said the benefits of blinatumomab do not outweigh its risks in MRD-positive BCP-ALL patients.

However, Amgen requested a reexamination of the CHMP’s opinion. During the reexamination, the CHMP reviewed all the data and consulted a group of experts.

The experts echoed the CHMP’s prior sentiment that there was no strong evidence of improved survival in MRD-positive patients treated with blinatumomab. However, they also said the data indicate a good response to blinatumomab, with around 78% of patients becoming negative for MRD after treatment.

Noting that MRD-positive patients have a high risk of relapse and few treatment options, the CHMP concluded that the benefits of blinatumomab outweigh its risks in this patient population.

The CHMP recommended expanding the approved indication for blinatumomab but also requested that Amgen provide data from ongoing studies of the drug in MRD-positive patients.

jensmith@mdedge.com