Video

CHICAGO – Immune therapy shows promise for use in the treatment of melanoma brain metastases, especially for treatment-naive patients, judging from the findings of a new phase II randomized study.

For patients with asymptomatic brain metastases from melanoma who had not had prior treatment, nivolumab combined with ipilimumab produced a 50% intracranial response rate after at least 12 weeks of therapy. When nivolumab alone was given to untreated patients, the intracranial response rate was 21%, Georgina Long MD, PhD, co–medical director of the Melanoma Institute Australia , said during a video interview at the annual meeting of the American Society of Clinical Oncology.

“If you look at progression-free survival by response, none of our complete responders have progressed,” said Dr. Long. “And this is with a median follow-up of 16.4 months.” The partial responders have also done well, with little progression, she said. “Remember, these patients usually survive only a few weeks.”

The Anti-PD1 Brain Collaboration study, a phase II clinical trial, enrolled patients with melanoma brain metastases at least 5 mm but less than 40 mm in diameter who had not received previous anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed cell death protein 1 (anti-PD-1), or anti-programmed death-ligand 1 (anti-PD-L1) therapies. Patients were permitted to have had previous BRAF and MEK inhibitor therapies. Asymptomatic patients who had no previous local brain therapy (i.e., radiation treatment or surgery) were randomized 1:1 to receive nivolumab alone, or nivolumab plus ipilimumab.

The nivolumab arm received 3 mg/kg by intravenous infusion every 2 weeks. The combination arm began with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for four doses. After this, they also received nivolumab 3 mg/kg monotherapy every 2 weeks.

The third cohort – a small group of 15 patients who received nivolumab alone – either had symptomatic brain metastases or leptomeningeal disease and could have had previous brain surgery or radiotherapy. Unlike the first two cohorts, they were also permitted to be on up to 10 mg/day of prednisone; these patients received nivolumab alone at 3 mg/kg every 2 weeks.

For all patients, immune therapy was given until the disease progressed, consent was withdrawn, or patients experienced unacceptable toxicity or they died.

“We were most interested in the randomized cohorts,” said Dr. Long. Interestingly, she said, ipilimumab became available in Australia when 27 patients were enrolled in the nivolumab arm and 26 to the combination arm. “So we stopped the monotherapy arm, and the rest of the 60 patients to be recruited all went into the combination arm,” she said. A total of 76 patients were recruited, 33 into the combination arm, 27 to the asymptomatic nivolumab monotherapy arm, and 16 to the symptomatic and/or previously treated arm.

Data analysis from the point of the data cut included 67 patients who were followed for a period ranging from 5 to 34 months. Intracranial disease was evaluated by gadolinium-enhanced MRI and modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

“The results of the trial were very interesting,” said Dr. Long. The nivolumab plus ipilimumab combo resulted in an overall 42% intracranial response rate, while nivolumab alone produced an overall intracranial response rate of 21%. However, patients in either arm who had prior BRAF or MEK inhibitor exposure “didn’t do too well on immunotherapy,” said Dr. Long, noting that the response rate was just 16% for these patients. These were, she said, “small numbers, but still, an interesting signal there.”

When comparing the secondary endpoint of extracranial response to intracranial response on a per-patient basis, Dr. Long and her collaborators could see that “the intracranial and extracranial results were mostly concordant.”

Analysis of the additional secondary endpoints of progression-free survival (PFS) and overall survival (OS) also showed an interesting pattern, said Dr. Long. After an initial drop-off period of about 5 months, the curves for patients in all arms have stabilized, so that patients who were responders are maintaining that response. The overall 6-month PFS rate for the combination cohort was 47%, with a durable response: “If you look at the curve, it’s flattened out since that stage, and we haven’t had any progression since that time,” said Dr. Long. The PFS rate was 29% for the cohort receiving nivolumab alone. “Activity is highest when nivolumab and ipilimumab are given upfront,” said Dr. Long.

For asymptomatic patients pretreated with BRAF or MEK inhibitors, “activity is low,” said Dr. Long, with an intracranial response rate of 16% in both cohorts.

Symptomatic patients who were more heavily pretreated fared even worse: “The activity of nivolumab monotherapy is low after multiple modality therapy or in leptomeningeal melanoma,” said Dr. Long. The intracranial response rate in the third cohort was just 6%.

The combination therapy cohort had the most treatment-related adverse events, with 96% of patients experiencing some adverse event. About half (12/26, 46%) had grade 3 or 4 events, and the same number had a serious adverse event. Seven patients (27%) discontinued therapy because of treatment-related adverse events in the combination study arm. However, said Dr. Long, this side effect profile is in keeping with what has been seen in other studies of combination therapy with nivolumab and ipilimumab. “There were not unexpected adverse events,” she said.

Dr. Long reported relationships with Bristol-Myers Squibb, Merck, and Roche.

koakes@frontlinemedcom.com

On Twitter @karioakes

CHICAGO – Immune therapy shows promise for use in the treatment of melanoma brain metastases, especially for treatment-naive patients, judging from the findings of a new phase II randomized study.

For patients with asymptomatic brain metastases from melanoma who had not had prior treatment, nivolumab combined with ipilimumab produced a 50% intracranial response rate after at least 12 weeks of therapy. When nivolumab alone was given to untreated patients, the intracranial response rate was 21%, Georgina Long MD, PhD, co–medical director of the Melanoma Institute Australia , said during a video interview at the annual meeting of the American Society of Clinical Oncology.

“If you look at progression-free survival by response, none of our complete responders have progressed,” said Dr. Long. “And this is with a median follow-up of 16.4 months.” The partial responders have also done well, with little progression, she said. “Remember, these patients usually survive only a few weeks.”

The Anti-PD1 Brain Collaboration study, a phase II clinical trial, enrolled patients with melanoma brain metastases at least 5 mm but less than 40 mm in diameter who had not received previous anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed cell death protein 1 (anti-PD-1), or anti-programmed death-ligand 1 (anti-PD-L1) therapies. Patients were permitted to have had previous BRAF and MEK inhibitor therapies. Asymptomatic patients who had no previous local brain therapy (i.e., radiation treatment or surgery) were randomized 1:1 to receive nivolumab alone, or nivolumab plus ipilimumab.

The nivolumab arm received 3 mg/kg by intravenous infusion every 2 weeks. The combination arm began with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for four doses. After this, they also received nivolumab 3 mg/kg monotherapy every 2 weeks.

The third cohort – a small group of 15 patients who received nivolumab alone – either had symptomatic brain metastases or leptomeningeal disease and could have had previous brain surgery or radiotherapy. Unlike the first two cohorts, they were also permitted to be on up to 10 mg/day of prednisone; these patients received nivolumab alone at 3 mg/kg every 2 weeks.

For all patients, immune therapy was given until the disease progressed, consent was withdrawn, or patients experienced unacceptable toxicity or they died.

“We were most interested in the randomized cohorts,” said Dr. Long. Interestingly, she said, ipilimumab became available in Australia when 27 patients were enrolled in the nivolumab arm and 26 to the combination arm. “So we stopped the monotherapy arm, and the rest of the 60 patients to be recruited all went into the combination arm,” she said. A total of 76 patients were recruited, 33 into the combination arm, 27 to the asymptomatic nivolumab monotherapy arm, and 16 to the symptomatic and/or previously treated arm.

Data analysis from the point of the data cut included 67 patients who were followed for a period ranging from 5 to 34 months. Intracranial disease was evaluated by gadolinium-enhanced MRI and modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

“The results of the trial were very interesting,” said Dr. Long. The nivolumab plus ipilimumab combo resulted in an overall 42% intracranial response rate, while nivolumab alone produced an overall intracranial response rate of 21%. However, patients in either arm who had prior BRAF or MEK inhibitor exposure “didn’t do too well on immunotherapy,” said Dr. Long, noting that the response rate was just 16% for these patients. These were, she said, “small numbers, but still, an interesting signal there.”

When comparing the secondary endpoint of extracranial response to intracranial response on a per-patient basis, Dr. Long and her collaborators could see that “the intracranial and extracranial results were mostly concordant.”

Analysis of the additional secondary endpoints of progression-free survival (PFS) and overall survival (OS) also showed an interesting pattern, said Dr. Long. After an initial drop-off period of about 5 months, the curves for patients in all arms have stabilized, so that patients who were responders are maintaining that response. The overall 6-month PFS rate for the combination cohort was 47%, with a durable response: “If you look at the curve, it’s flattened out since that stage, and we haven’t had any progression since that time,” said Dr. Long. The PFS rate was 29% for the cohort receiving nivolumab alone. “Activity is highest when nivolumab and ipilimumab are given upfront,” said Dr. Long.

For asymptomatic patients pretreated with BRAF or MEK inhibitors, “activity is low,” said Dr. Long, with an intracranial response rate of 16% in both cohorts.

Symptomatic patients who were more heavily pretreated fared even worse: “The activity of nivolumab monotherapy is low after multiple modality therapy or in leptomeningeal melanoma,” said Dr. Long. The intracranial response rate in the third cohort was just 6%.

The combination therapy cohort had the most treatment-related adverse events, with 96% of patients experiencing some adverse event. About half (12/26, 46%) had grade 3 or 4 events, and the same number had a serious adverse event. Seven patients (27%) discontinued therapy because of treatment-related adverse events in the combination study arm. However, said Dr. Long, this side effect profile is in keeping with what has been seen in other studies of combination therapy with nivolumab and ipilimumab. “There were not unexpected adverse events,” she said.

Dr. Long reported relationships with Bristol-Myers Squibb, Merck, and Roche.

koakes@frontlinemedcom.com

On Twitter @karioakes

CHICAGO – Immune therapy shows promise for use in the treatment of melanoma brain metastases, especially for treatment-naive patients, judging from the findings of a new phase II randomized study.

For patients with asymptomatic brain metastases from melanoma who had not had prior treatment, nivolumab combined with ipilimumab produced a 50% intracranial response rate after at least 12 weeks of therapy. When nivolumab alone was given to untreated patients, the intracranial response rate was 21%, Georgina Long MD, PhD, co–medical director of the Melanoma Institute Australia , said during a video interview at the annual meeting of the American Society of Clinical Oncology.

“If you look at progression-free survival by response, none of our complete responders have progressed,” said Dr. Long. “And this is with a median follow-up of 16.4 months.” The partial responders have also done well, with little progression, she said. “Remember, these patients usually survive only a few weeks.”

The Anti-PD1 Brain Collaboration study, a phase II clinical trial, enrolled patients with melanoma brain metastases at least 5 mm but less than 40 mm in diameter who had not received previous anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed cell death protein 1 (anti-PD-1), or anti-programmed death-ligand 1 (anti-PD-L1) therapies. Patients were permitted to have had previous BRAF and MEK inhibitor therapies. Asymptomatic patients who had no previous local brain therapy (i.e., radiation treatment or surgery) were randomized 1:1 to receive nivolumab alone, or nivolumab plus ipilimumab.

The nivolumab arm received 3 mg/kg by intravenous infusion every 2 weeks. The combination arm began with nivolumab 1 mg/kg and ipilimumab 3 mg/kg every 3 weeks for four doses. After this, they also received nivolumab 3 mg/kg monotherapy every 2 weeks.

The third cohort – a small group of 15 patients who received nivolumab alone – either had symptomatic brain metastases or leptomeningeal disease and could have had previous brain surgery or radiotherapy. Unlike the first two cohorts, they were also permitted to be on up to 10 mg/day of prednisone; these patients received nivolumab alone at 3 mg/kg every 2 weeks.

For all patients, immune therapy was given until the disease progressed, consent was withdrawn, or patients experienced unacceptable toxicity or they died.

“We were most interested in the randomized cohorts,” said Dr. Long. Interestingly, she said, ipilimumab became available in Australia when 27 patients were enrolled in the nivolumab arm and 26 to the combination arm. “So we stopped the monotherapy arm, and the rest of the 60 patients to be recruited all went into the combination arm,” she said. A total of 76 patients were recruited, 33 into the combination arm, 27 to the asymptomatic nivolumab monotherapy arm, and 16 to the symptomatic and/or previously treated arm.

Data analysis from the point of the data cut included 67 patients who were followed for a period ranging from 5 to 34 months. Intracranial disease was evaluated by gadolinium-enhanced MRI and modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

“The results of the trial were very interesting,” said Dr. Long. The nivolumab plus ipilimumab combo resulted in an overall 42% intracranial response rate, while nivolumab alone produced an overall intracranial response rate of 21%. However, patients in either arm who had prior BRAF or MEK inhibitor exposure “didn’t do too well on immunotherapy,” said Dr. Long, noting that the response rate was just 16% for these patients. These were, she said, “small numbers, but still, an interesting signal there.”

When comparing the secondary endpoint of extracranial response to intracranial response on a per-patient basis, Dr. Long and her collaborators could see that “the intracranial and extracranial results were mostly concordant.”

Analysis of the additional secondary endpoints of progression-free survival (PFS) and overall survival (OS) also showed an interesting pattern, said Dr. Long. After an initial drop-off period of about 5 months, the curves for patients in all arms have stabilized, so that patients who were responders are maintaining that response. The overall 6-month PFS rate for the combination cohort was 47%, with a durable response: “If you look at the curve, it’s flattened out since that stage, and we haven’t had any progression since that time,” said Dr. Long. The PFS rate was 29% for the cohort receiving nivolumab alone. “Activity is highest when nivolumab and ipilimumab are given upfront,” said Dr. Long.

For asymptomatic patients pretreated with BRAF or MEK inhibitors, “activity is low,” said Dr. Long, with an intracranial response rate of 16% in both cohorts.

Symptomatic patients who were more heavily pretreated fared even worse: “The activity of nivolumab monotherapy is low after multiple modality therapy or in leptomeningeal melanoma,” said Dr. Long. The intracranial response rate in the third cohort was just 6%.

The combination therapy cohort had the most treatment-related adverse events, with 96% of patients experiencing some adverse event. About half (12/26, 46%) had grade 3 or 4 events, and the same number had a serious adverse event. Seven patients (27%) discontinued therapy because of treatment-related adverse events in the combination study arm. However, said Dr. Long, this side effect profile is in keeping with what has been seen in other studies of combination therapy with nivolumab and ipilimumab. “There were not unexpected adverse events,” she said.

Dr. Long reported relationships with Bristol-Myers Squibb, Merck, and Roche.

koakes@frontlinemedcom.com

On Twitter @karioakes

BOSTON – Two phase III trials of the investigational monoclonal antibody erenumab show promising results in reducing – but not eliminating – days affected by migraines and related disruptions in daily life with limited side effects, representing “an entirely new way forward” in migraine prevention, according to Peter Goadsby, MD.

In May, shortly after the results were released at the annual meeting of the American Academy of Neurology, Amgen filed regulatory documents for erenumab with the Food and Drug Administration.

Erenumab, also known as AMG 334, “is going to be the first mechanism-specific, migraine-targeted preventive treatment approach ever,” Dr. Goadsby, a University of California, San Francisco, neurologist, predicted at the annual meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that is designed to block the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine.

Several drug makers are investigating CGRP-modulating treatments for migraine. Results suggest that the medications are “effective for episodic and migraine patients,” said Amaal Starling, MD, of the Mayo Clinic, Scottsdale, Ariz., who spoke about the drugs in a plenary session at the meeting. “They have rapid onset of efficacy, minimal side effects, and infrequent administration. All of these things may improve adherence.”

Dr. Goadsby is the lead author of the study reporting phase III results from the 24-week STRIVE trial, which tested two monthly subcutaneous doses of erenumab (70 mg and 140 mg) against placebo in a 1:1:1 ratio in 955 patients. The patients all had suffered from episodic migraine for at least a year.

“STRIVE has shown that the 70-mg and 140-mg doses are better than placebo at the regulatory endpoint and clinically relevant endpoints,” Dr. Goadsby said, “and there are improvements in function, everyday activities, and physical impairment. The overall frequency of adverse and serious events were comparable, even the same.”

The participants reported an average of 8.3 monthly migraine days (MMDs) at the beginning of the study. At the end, the number declined significantly by an average of 3.2 days (70-mg dose), 3.7 days (140-mg dose), and 1.8 days (placebo; P less than .001).

Half of those in the 140-mg group achieved at least a 50% reduction in MMDs, compared with 43% and 27% for the 70-mg and placebo groups, respectively (P less than .001).

The researchers also examined changes in scores regarding Physical Impairment (PI) and Impact on Everyday Activities (EA) as determined by the Migraine Physical Function Impact Diary. PI scores improved by 4.2, 4.8, and 2.4 points in the 70-mg, 140-mg, and placebo groups, respectively. EA scores improved by 5.5, 5.9, and 3.3 points, respectively (P less than .001).

The study authors reported that tolerability was similar for placebo and the drug. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and sinusitis.

The researchers at the AAN meeting also released the results of a second study known as ARISE, led by David W. Dodick, MD, of the Mayo Clinic, Phoenix, Ariz. This double-blind, 12-week trial randomly assigned 577 adults with episodic migraine to a monthly subcutaneous dose of a placebo or 70 mg of erenumab.

The patients reported an average of 8.3 MMDs at the beginning of the trial. Those who took the medication reported an average 2.9 fewer MMDs while those who took the placebo reported 1.8 fewer MMDs (P less than .001) at 9-12 weeks.

Forty percent of those who took the drug saw a decrease of at least half in MMDs, compared with 30% of those who took placebo (odds ratio, 1.6; P = .010).

The PI levels declined by at least 5 points in 27% of placebo patients and 33% of erenumab patients (P = .13). EA levels declined by at least 5 points in 36% of placebo patients and 40% of erenumab patients (P = .26)

There were similar levels of adverse events in both drug and placebo groups, led by upper respiratory tract infection, injection site pain, and nasopharyngitis.

The Mayo Clinic’s Dr. Starling said anti-CGRP medications may dramatically improve the world of preventive migraine treatments, which are recommended for a third of migraine patients. Only about 3%-13% use them, she said.

In the future, it may be possible to be able to identify and target “super-responders” whose MMDs dip by 75% or more in some cases.

But there are questions, she said. The drugs’ specific mechanism for blocking migraine is not yet clear, and it’s also not clear if the CGRP antagonists could push patients at risk of TIA or cardiac angina to have a stroke instead.

Dr. Starling discussed some of the implications of the CGRP antagonists in development in a video interview.

Both studies were funded by Amgen. Dr. Goadsby reported numerous grants and personal fees from multiple drug makers, including Amgen. Dr. Starling reported support from Amgen, eNeura, and Eli Lilly. Dr. Dodick disclosed many relationships with pharmaceutical companies developing or marketing drugs for headache and migraine, including Amgen.

BOSTON – Two phase III trials of the investigational monoclonal antibody erenumab show promising results in reducing – but not eliminating – days affected by migraines and related disruptions in daily life with limited side effects, representing “an entirely new way forward” in migraine prevention, according to Peter Goadsby, MD.

In May, shortly after the results were released at the annual meeting of the American Academy of Neurology, Amgen filed regulatory documents for erenumab with the Food and Drug Administration.

Erenumab, also known as AMG 334, “is going to be the first mechanism-specific, migraine-targeted preventive treatment approach ever,” Dr. Goadsby, a University of California, San Francisco, neurologist, predicted at the annual meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that is designed to block the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine.

Several drug makers are investigating CGRP-modulating treatments for migraine. Results suggest that the medications are “effective for episodic and migraine patients,” said Amaal Starling, MD, of the Mayo Clinic, Scottsdale, Ariz., who spoke about the drugs in a plenary session at the meeting. “They have rapid onset of efficacy, minimal side effects, and infrequent administration. All of these things may improve adherence.”

Dr. Goadsby is the lead author of the study reporting phase III results from the 24-week STRIVE trial, which tested two monthly subcutaneous doses of erenumab (70 mg and 140 mg) against placebo in a 1:1:1 ratio in 955 patients. The patients all had suffered from episodic migraine for at least a year.

“STRIVE has shown that the 70-mg and 140-mg doses are better than placebo at the regulatory endpoint and clinically relevant endpoints,” Dr. Goadsby said, “and there are improvements in function, everyday activities, and physical impairment. The overall frequency of adverse and serious events were comparable, even the same.”

The participants reported an average of 8.3 monthly migraine days (MMDs) at the beginning of the study. At the end, the number declined significantly by an average of 3.2 days (70-mg dose), 3.7 days (140-mg dose), and 1.8 days (placebo; P less than .001).

Half of those in the 140-mg group achieved at least a 50% reduction in MMDs, compared with 43% and 27% for the 70-mg and placebo groups, respectively (P less than .001).

The researchers also examined changes in scores regarding Physical Impairment (PI) and Impact on Everyday Activities (EA) as determined by the Migraine Physical Function Impact Diary. PI scores improved by 4.2, 4.8, and 2.4 points in the 70-mg, 140-mg, and placebo groups, respectively. EA scores improved by 5.5, 5.9, and 3.3 points, respectively (P less than .001).

The study authors reported that tolerability was similar for placebo and the drug. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and sinusitis.

The researchers at the AAN meeting also released the results of a second study known as ARISE, led by David W. Dodick, MD, of the Mayo Clinic, Phoenix, Ariz. This double-blind, 12-week trial randomly assigned 577 adults with episodic migraine to a monthly subcutaneous dose of a placebo or 70 mg of erenumab.

The patients reported an average of 8.3 MMDs at the beginning of the trial. Those who took the medication reported an average 2.9 fewer MMDs while those who took the placebo reported 1.8 fewer MMDs (P less than .001) at 9-12 weeks.

Forty percent of those who took the drug saw a decrease of at least half in MMDs, compared with 30% of those who took placebo (odds ratio, 1.6; P = .010).

The PI levels declined by at least 5 points in 27% of placebo patients and 33% of erenumab patients (P = .13). EA levels declined by at least 5 points in 36% of placebo patients and 40% of erenumab patients (P = .26)

There were similar levels of adverse events in both drug and placebo groups, led by upper respiratory tract infection, injection site pain, and nasopharyngitis.

The Mayo Clinic’s Dr. Starling said anti-CGRP medications may dramatically improve the world of preventive migraine treatments, which are recommended for a third of migraine patients. Only about 3%-13% use them, she said.

In the future, it may be possible to be able to identify and target “super-responders” whose MMDs dip by 75% or more in some cases.

But there are questions, she said. The drugs’ specific mechanism for blocking migraine is not yet clear, and it’s also not clear if the CGRP antagonists could push patients at risk of TIA or cardiac angina to have a stroke instead.

Dr. Starling discussed some of the implications of the CGRP antagonists in development in a video interview.

Both studies were funded by Amgen. Dr. Goadsby reported numerous grants and personal fees from multiple drug makers, including Amgen. Dr. Starling reported support from Amgen, eNeura, and Eli Lilly. Dr. Dodick disclosed many relationships with pharmaceutical companies developing or marketing drugs for headache and migraine, including Amgen.

BOSTON – Two phase III trials of the investigational monoclonal antibody erenumab show promising results in reducing – but not eliminating – days affected by migraines and related disruptions in daily life with limited side effects, representing “an entirely new way forward” in migraine prevention, according to Peter Goadsby, MD.

In May, shortly after the results were released at the annual meeting of the American Academy of Neurology, Amgen filed regulatory documents for erenumab with the Food and Drug Administration.

Erenumab, also known as AMG 334, “is going to be the first mechanism-specific, migraine-targeted preventive treatment approach ever,” Dr. Goadsby, a University of California, San Francisco, neurologist, predicted at the annual meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that is designed to block the calcitonin gene-related peptide (CGRP) receptor, which is linked to migraine.

Several drug makers are investigating CGRP-modulating treatments for migraine. Results suggest that the medications are “effective for episodic and migraine patients,” said Amaal Starling, MD, of the Mayo Clinic, Scottsdale, Ariz., who spoke about the drugs in a plenary session at the meeting. “They have rapid onset of efficacy, minimal side effects, and infrequent administration. All of these things may improve adherence.”

Dr. Goadsby is the lead author of the study reporting phase III results from the 24-week STRIVE trial, which tested two monthly subcutaneous doses of erenumab (70 mg and 140 mg) against placebo in a 1:1:1 ratio in 955 patients. The patients all had suffered from episodic migraine for at least a year.

“STRIVE has shown that the 70-mg and 140-mg doses are better than placebo at the regulatory endpoint and clinically relevant endpoints,” Dr. Goadsby said, “and there are improvements in function, everyday activities, and physical impairment. The overall frequency of adverse and serious events were comparable, even the same.”

The participants reported an average of 8.3 monthly migraine days (MMDs) at the beginning of the study. At the end, the number declined significantly by an average of 3.2 days (70-mg dose), 3.7 days (140-mg dose), and 1.8 days (placebo; P less than .001).

Half of those in the 140-mg group achieved at least a 50% reduction in MMDs, compared with 43% and 27% for the 70-mg and placebo groups, respectively (P less than .001).

The researchers also examined changes in scores regarding Physical Impairment (PI) and Impact on Everyday Activities (EA) as determined by the Migraine Physical Function Impact Diary. PI scores improved by 4.2, 4.8, and 2.4 points in the 70-mg, 140-mg, and placebo groups, respectively. EA scores improved by 5.5, 5.9, and 3.3 points, respectively (P less than .001).

The study authors reported that tolerability was similar for placebo and the drug. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and sinusitis.

The researchers at the AAN meeting also released the results of a second study known as ARISE, led by David W. Dodick, MD, of the Mayo Clinic, Phoenix, Ariz. This double-blind, 12-week trial randomly assigned 577 adults with episodic migraine to a monthly subcutaneous dose of a placebo or 70 mg of erenumab.

The patients reported an average of 8.3 MMDs at the beginning of the trial. Those who took the medication reported an average 2.9 fewer MMDs while those who took the placebo reported 1.8 fewer MMDs (P less than .001) at 9-12 weeks.

Forty percent of those who took the drug saw a decrease of at least half in MMDs, compared with 30% of those who took placebo (odds ratio, 1.6; P = .010).

The PI levels declined by at least 5 points in 27% of placebo patients and 33% of erenumab patients (P = .13). EA levels declined by at least 5 points in 36% of placebo patients and 40% of erenumab patients (P = .26)

There were similar levels of adverse events in both drug and placebo groups, led by upper respiratory tract infection, injection site pain, and nasopharyngitis.

The Mayo Clinic’s Dr. Starling said anti-CGRP medications may dramatically improve the world of preventive migraine treatments, which are recommended for a third of migraine patients. Only about 3%-13% use them, she said.

In the future, it may be possible to be able to identify and target “super-responders” whose MMDs dip by 75% or more in some cases.

But there are questions, she said. The drugs’ specific mechanism for blocking migraine is not yet clear, and it’s also not clear if the CGRP antagonists could push patients at risk of TIA or cardiac angina to have a stroke instead.

Dr. Starling discussed some of the implications of the CGRP antagonists in development in a video interview.

Both studies were funded by Amgen. Dr. Goadsby reported numerous grants and personal fees from multiple drug makers, including Amgen. Dr. Starling reported support from Amgen, eNeura, and Eli Lilly. Dr. Dodick disclosed many relationships with pharmaceutical companies developing or marketing drugs for headache and migraine, including Amgen.

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

WASHINGTON – Acute respiratory distress syndrome (ARDS) appears to exist in at least two major forms, and one of these, the hyperinflammatory form, seemed responsive to simvastatin in a post-hoc analysis of trial data.

The other version of ARDs is a hypoinflammatory form, which occurred in 70% of ARDS patients in most of the analyses that have been done.

Researchers classified the 540 ARDS patients enrolled in a 2014 study of simvastatin as either hyperinflammatory or hypoinflammatory. Separating out the hyperinflammatory patients created a subclass that responded to simvastatin, with a 13% absolute reduction in mortality during follow-up, compared with no response among patients in the hypoinflammatory group, Carolyn S. Calfee, MD, said at an international conference of the American Thoracic Society.

“Hyperinflammatory patients treated with simvastatin may have improved outcomes, compared with hypoinflammatory* patients treated with placebo,” said Dr. Calfee, a pulmonologist at the University of California, San Francisco.

The finding raises the possibility that simvastatin, as well as other statins, may be an effective treatment for selected patients with ARDS, but proving this requires new prospective, randomized trials in hyperinflammatory patients, Dr. Calfee said in a video interview.

Currently, the tests Dr. Calfee uses to distinguish hyperinflammatory and hypoinflammatory ARDS patients take about 6-8 hours to complete. A “point of care test to stratify patients in real time,” is needed to further study the various forms of ARDs, Dr. Calfee noted. A critical next step would be the development of a “practical, rapid, bedside assay” to ease identification of hyperinflammatory ARDS patients. “The work we’ve done prior seems to indicate that we are going to definitely need to measure biomarkers in order to identity these subgroups,” she noted.

Hypoinflammatory patients also merit study, she added. Although hyperinflammatory patients have significant worse mortality rates, the hypoinflammatory subclass includes about 70% of ARDS patients, “so we need to better understand how to potentially treat this group.”

Dr. Calfee and her associates first reported finding the two ARDS subclasses, what they also call subphenotypes or endotypes, in two separate cohorts of ARDS patients in a 2014 report (Lancet Resp Med. 2014 Aug;2[8]:611-20). Then, they confirmed the finding in a third ARDS cohort in a 2017 report (Amer J Resp Crit Care Med. 2017 Feb 1;195[3]:331-8). These reports have documented other characteristics of the hyperinflammatory ARDS subclass: hypotension, metabolic acidosis, more frequent treatment with vasopressors, and a higher prevalence of sepsis and shock. Concurrent with the 2017 report, an editorial hailed the finding as “the dawn of personalized medicine for ARDS” (Amer J resp Crit Care Med. 2017 Feb 1;195[3]: 280-1).

To build on this, Dr. Calfee and her associates applied their method for identifying ARDS subclasses to a different cohort of 540 patients enrolled in the The HARP (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction)–2 study, a multicenter UK and Irish study designed to test the efficacy of daily simvastatin treatment in a heterogeneous group of ARDS patients. A 2014 report of the study’s primary results showed no significant effect from simvastatin for increasing the number of ventilator-free days nor did the drug improve any other measured efficacy endpoints (New Engl J Med. 2014 Oct 30;371[18]:1695-703).

Applying a statistical analysis called “latent class analysis,” which is designed to recognize subclass groupings that might not be readily apparent, Dr. Calfee and her team first confirmed that, in this fourth cohort, the ARDS patients again split into a hyperinflammatory subclass, in this case including 188 (35%) of the cohort, and a hypoinflammatory subclass with 352 (65%) patients. The next step was to see what impact simvastatin treatment had in each of the two patient subclasses. They focused the analysis on a secondary outcome in HARP-2, 28-day survival.

They found that simvastatin produced no significant difference in 28-day survival, compared with placebo among the hypoinflammatory patients, but, in the hyperinflammatory subclass, 28-day survival was 68% for patients on simvastatin and 55% for those on placebo, a statistically significant difference, Dr. Calfee reported (Am J Resp Crit Care Med. 2017;195:A6749).

“I’m excited that we are seeing, for the first time, a different response to pharmacotherapy” after dividing ARDS patients into these two subclasses, she said. But, the work remains in an early stage, she cautioned. “We need to test treatments [like statins] prospectively.” The new finding for simvastatin “is not the same as showing benefit in a prospective, randomized trial.”

In the meantime, Dr. Calfee plans to apply the same analytic approach to data collected in another failed statin trial in ARDS patients, the SAILS trial. That study failed to show benefit from rosuvastatin treatment in an unselected population of patients with sepsis-associated ARDS (New Engl J Med. 2014 June 5;370[23]:2191-200).

Dr. Calfee is a consultant to Bayer, Boehringer Ingelheim, and GlaxoSmithKline. She received research funding from GlaxoSmithKline.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

*An earlier version of this article misquoted Dr. Calfee.

VANCOUVER – Although symptoms can start young in endometriosis – sometimes in adolescence – women often suffer for years from bowel problems, pain, dyspareunia, and other complications before the condition is recognized and addressed.

Endometriosis can be “a monster of a disease,” especially if it’s not recognized early, said Deborah Bush, cofounder and CEO of the patient advocacy group Endometriosis New Zealand.

To help, she and her colleagues started an education program in New Zealand to teach secondary school students how to recognize – and seek help – when menstrual symptoms fall outside the norm.

In an interview at the World Congress on Endometriosis, Ms. Bush explained the importance of such efforts, and the impact they’ve had in New Zealand over the past 20 years (Aust N Z J Obstet Gynaecol. 2017 Mar 28. doi: 10.1111/ajo.12614).

She also gave an example from her own endometriosis consulting practice of what it took to turn around a patient who had been suffering with the disease for 15 years. Treatment had to move far beyond pelvic lesions.

aotto@frontlinemedcom.com

VANCOUVER – Although symptoms can start young in endometriosis – sometimes in adolescence – women often suffer for years from bowel problems, pain, dyspareunia, and other complications before the condition is recognized and addressed.

Endometriosis can be “a monster of a disease,” especially if it’s not recognized early, said Deborah Bush, cofounder and CEO of the patient advocacy group Endometriosis New Zealand.

To help, she and her colleagues started an education program in New Zealand to teach secondary school students how to recognize – and seek help – when menstrual symptoms fall outside the norm.

In an interview at the World Congress on Endometriosis, Ms. Bush explained the importance of such efforts, and the impact they’ve had in New Zealand over the past 20 years (Aust N Z J Obstet Gynaecol. 2017 Mar 28. doi: 10.1111/ajo.12614).

She also gave an example from her own endometriosis consulting practice of what it took to turn around a patient who had been suffering with the disease for 15 years. Treatment had to move far beyond pelvic lesions.

aotto@frontlinemedcom.com

VANCOUVER – Although symptoms can start young in endometriosis – sometimes in adolescence – women often suffer for years from bowel problems, pain, dyspareunia, and other complications before the condition is recognized and addressed.

Endometriosis can be “a monster of a disease,” especially if it’s not recognized early, said Deborah Bush, cofounder and CEO of the patient advocacy group Endometriosis New Zealand.

To help, she and her colleagues started an education program in New Zealand to teach secondary school students how to recognize – and seek help – when menstrual symptoms fall outside the norm.

In an interview at the World Congress on Endometriosis, Ms. Bush explained the importance of such efforts, and the impact they’ve had in New Zealand over the past 20 years (Aust N Z J Obstet Gynaecol. 2017 Mar 28. doi: 10.1111/ajo.12614).

She also gave an example from her own endometriosis consulting practice of what it took to turn around a patient who had been suffering with the disease for 15 years. Treatment had to move far beyond pelvic lesions.

aotto@frontlinemedcom.com

VANCOUVER – To define the top 10 research priorities in endometriosis, researchers at the University of Edinburgh, Scotland, and their colleagues did something unusual in the world of medical science. They asked the women who have the disease.

More than 70% of the 1,225 people initially surveyed to define what most needs to be figured out in endometriosis were patients, and most of the rest were clinicians who take care of them. Patients were involved throughout an exhaustive process that whittled down nearly 5,000 initial suggestions to a list of 10 priorities.

The first priority is to determine if endometriosis can be cured, and the second task is to find its cause (Lancet. 2017 May 18. doi: 10.1016/S0140-6736(17)31344-2).

Women who have endometriosis said they want a noninvasive diagnostic test. They also want help managing the emotional and physical impacts of living with the disease, not simply treatments that focus on lesions, according to Andrew Horne, MBChB, PhD, a professor of gynecology and reproductive sciences at the University of Edinburgh, who led the efforts.

In an interview at the World Congress on Endometriosis, Dr. Horne explained why it’s critical to define the top research priorities and what doing so could mean for patients and doctors. He also explained the importance of a recent insight into the pathogenesis of endometriosis: It behaves like cancer.

aotto@frontlinemedcom.com

VANCOUVER – To define the top 10 research priorities in endometriosis, researchers at the University of Edinburgh, Scotland, and their colleagues did something unusual in the world of medical science. They asked the women who have the disease.

More than 70% of the 1,225 people initially surveyed to define what most needs to be figured out in endometriosis were patients, and most of the rest were clinicians who take care of them. Patients were involved throughout an exhaustive process that whittled down nearly 5,000 initial suggestions to a list of 10 priorities.

The first priority is to determine if endometriosis can be cured, and the second task is to find its cause (Lancet. 2017 May 18. doi: 10.1016/S0140-6736(17)31344-2).

Women who have endometriosis said they want a noninvasive diagnostic test. They also want help managing the emotional and physical impacts of living with the disease, not simply treatments that focus on lesions, according to Andrew Horne, MBChB, PhD, a professor of gynecology and reproductive sciences at the University of Edinburgh, who led the efforts.

In an interview at the World Congress on Endometriosis, Dr. Horne explained why it’s critical to define the top research priorities and what doing so could mean for patients and doctors. He also explained the importance of a recent insight into the pathogenesis of endometriosis: It behaves like cancer.

aotto@frontlinemedcom.com

VANCOUVER – To define the top 10 research priorities in endometriosis, researchers at the University of Edinburgh, Scotland, and their colleagues did something unusual in the world of medical science. They asked the women who have the disease.

More than 70% of the 1,225 people initially surveyed to define what most needs to be figured out in endometriosis were patients, and most of the rest were clinicians who take care of them. Patients were involved throughout an exhaustive process that whittled down nearly 5,000 initial suggestions to a list of 10 priorities.

The first priority is to determine if endometriosis can be cured, and the second task is to find its cause (Lancet. 2017 May 18. doi: 10.1016/S0140-6736(17)31344-2).

Women who have endometriosis said they want a noninvasive diagnostic test. They also want help managing the emotional and physical impacts of living with the disease, not simply treatments that focus on lesions, according to Andrew Horne, MBChB, PhD, a professor of gynecology and reproductive sciences at the University of Edinburgh, who led the efforts.

In an interview at the World Congress on Endometriosis, Dr. Horne explained why it’s critical to define the top research priorities and what doing so could mean for patients and doctors. He also explained the importance of a recent insight into the pathogenesis of endometriosis: It behaves like cancer.

aotto@frontlinemedcom.com

VANCOUVER – Although hysterectomy will never again be the go-to treatment for endometriosis that it once was, it has become clear in recent years that it still has a role to play.

In a video interview at the World Congress on Endometriosis, Ray Garry, MD, a recently retired professor of obstetrics and gynecology at the University of Western Australia, Perth, explained why – in a limited way – the pendulum is swinging back toward hysterectomy for a select group of women.

aotto@frontlinemedcom.com

VANCOUVER – Although hysterectomy will never again be the go-to treatment for endometriosis that it once was, it has become clear in recent years that it still has a role to play.

In a video interview at the World Congress on Endometriosis, Ray Garry, MD, a recently retired professor of obstetrics and gynecology at the University of Western Australia, Perth, explained why – in a limited way – the pendulum is swinging back toward hysterectomy for a select group of women.

aotto@frontlinemedcom.com

VANCOUVER – Although hysterectomy will never again be the go-to treatment for endometriosis that it once was, it has become clear in recent years that it still has a role to play.

In a video interview at the World Congress on Endometriosis, Ray Garry, MD, a recently retired professor of obstetrics and gynecology at the University of Western Australia, Perth, explained why – in a limited way – the pendulum is swinging back toward hysterectomy for a select group of women.

aotto@frontlinemedcom.com

VANCOUVER – Ongoing pregnancies and live births were substantially higher when oil-based contrast, instead of water-based contrast, was used for hysterosalpingography (HSG) in a randomized trial at 27 hospitals in the Netherlands.

It’s long been known that HSG, commonly used to assess reproductive tract patency, also improves fertility, perhaps by immunologic effects or simply by flushing debris and mucus out of the fallopian tubes. Until now, however, it’s been unclear if oil or water contrast boosts fertility the most.

To find out, investigators randomized 554 infertile women scheduled for HSG to poppy seed oil contrast (Lipiodol Ultra-Fluid, Guerbet) and 554 others to water contrast (Telebrix Hystero, Guerbet).

A total of 220 women in the oil group (39.7%), but 161 in the water group (29.1%), achieved ongoing pregnancies (rate ratio in favor of oil, 1.37; 95% CI, 1.16-1.61; P less than 0.001). Of 552 women in each of the groups, 214 in the oil group (38.8%) and 155 in the water group (28.1%) had live births (RR, 1.38; 95% CI, 1.17-1.64; P less than 0.001). Rates of adverse events were low and similar in the two groups. About three-quarters of the pregnancies were naturally conceived, and most of the rest resulted from intrauterine insemination. Only a few women in each group used in vitro fertilization (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1612337).

Three women in the oil group, but none in the water group, delivered a child with a congenital anomaly. “This finding is probably due to chance. The frequency of congenital anomalies with oil contrast was not greater than rates reported in the general population, and we are unaware of other data suggesting an increased risk of congenital anomalies with oil contrast,” the researchers said.

In an interview at the World Congress on Endometriosis, senior investigator Ben Mol, MD, PhD, a professor of obstetrics and gynecology at the University of Adelaide (Australia), shared his thoughts on how the new findings should be used in routine practice when women with endometriosis and other conditions experience difficulty conceiving.

There was no industry funding for the work. Dr. Mol reported personal fees from Guerbet unrelated to the study.

aotto@frontlinemedcom.com

VANCOUVER – Ongoing pregnancies and live births were substantially higher when oil-based contrast, instead of water-based contrast, was used for hysterosalpingography (HSG) in a randomized trial at 27 hospitals in the Netherlands.

It’s long been known that HSG, commonly used to assess reproductive tract patency, also improves fertility, perhaps by immunologic effects or simply by flushing debris and mucus out of the fallopian tubes. Until now, however, it’s been unclear if oil or water contrast boosts fertility the most.

To find out, investigators randomized 554 infertile women scheduled for HSG to poppy seed oil contrast (Lipiodol Ultra-Fluid, Guerbet) and 554 others to water contrast (Telebrix Hystero, Guerbet).

A total of 220 women in the oil group (39.7%), but 161 in the water group (29.1%), achieved ongoing pregnancies (rate ratio in favor of oil, 1.37; 95% CI, 1.16-1.61; P less than 0.001). Of 552 women in each of the groups, 214 in the oil group (38.8%) and 155 in the water group (28.1%) had live births (RR, 1.38; 95% CI, 1.17-1.64; P less than 0.001). Rates of adverse events were low and similar in the two groups. About three-quarters of the pregnancies were naturally conceived, and most of the rest resulted from intrauterine insemination. Only a few women in each group used in vitro fertilization (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1612337).

Three women in the oil group, but none in the water group, delivered a child with a congenital anomaly. “This finding is probably due to chance. The frequency of congenital anomalies with oil contrast was not greater than rates reported in the general population, and we are unaware of other data suggesting an increased risk of congenital anomalies with oil contrast,” the researchers said.

In an interview at the World Congress on Endometriosis, senior investigator Ben Mol, MD, PhD, a professor of obstetrics and gynecology at the University of Adelaide (Australia), shared his thoughts on how the new findings should be used in routine practice when women with endometriosis and other conditions experience difficulty conceiving.

There was no industry funding for the work. Dr. Mol reported personal fees from Guerbet unrelated to the study.

aotto@frontlinemedcom.com

VANCOUVER – Ongoing pregnancies and live births were substantially higher when oil-based contrast, instead of water-based contrast, was used for hysterosalpingography (HSG) in a randomized trial at 27 hospitals in the Netherlands.

It’s long been known that HSG, commonly used to assess reproductive tract patency, also improves fertility, perhaps by immunologic effects or simply by flushing debris and mucus out of the fallopian tubes. Until now, however, it’s been unclear if oil or water contrast boosts fertility the most.

To find out, investigators randomized 554 infertile women scheduled for HSG to poppy seed oil contrast (Lipiodol Ultra-Fluid, Guerbet) and 554 others to water contrast (Telebrix Hystero, Guerbet).

A total of 220 women in the oil group (39.7%), but 161 in the water group (29.1%), achieved ongoing pregnancies (rate ratio in favor of oil, 1.37; 95% CI, 1.16-1.61; P less than 0.001). Of 552 women in each of the groups, 214 in the oil group (38.8%) and 155 in the water group (28.1%) had live births (RR, 1.38; 95% CI, 1.17-1.64; P less than 0.001). Rates of adverse events were low and similar in the two groups. About three-quarters of the pregnancies were naturally conceived, and most of the rest resulted from intrauterine insemination. Only a few women in each group used in vitro fertilization (N Engl J Med. 2017 May 18. doi: 10.1056/NEJMoa1612337).

Three women in the oil group, but none in the water group, delivered a child with a congenital anomaly. “This finding is probably due to chance. The frequency of congenital anomalies with oil contrast was not greater than rates reported in the general population, and we are unaware of other data suggesting an increased risk of congenital anomalies with oil contrast,” the researchers said.

In an interview at the World Congress on Endometriosis, senior investigator Ben Mol, MD, PhD, a professor of obstetrics and gynecology at the University of Adelaide (Australia), shared his thoughts on how the new findings should be used in routine practice when women with endometriosis and other conditions experience difficulty conceiving.

There was no industry funding for the work. Dr. Mol reported personal fees from Guerbet unrelated to the study.

aotto@frontlinemedcom.com

BOSTON – A new study highlights the success, safety, and effectiveness of a new sutureless aortic valve device in patients with severe symptomatic aortic valve stenosis (AS).

The findings, reported at the annual meeting of the American Association for Thoracic Surgery, were based on a prospective, single-arm clinical trial approved under a Food and Drug Administration Investigational Device Exemption (IDE) that aimed to assess the safety and efficacy of a new bovine pericardial sutureless aortic valve in patients with severe AS undergoing aortic valve replacement with or without concomitant procedures. In this video interview, Michael Borger, MD, explains how the study was conducted and what the findings mean for future use of the sutureless aortic valve device.

agallegos@frontlinemedcom.com

On Twitter @legal_med

BOSTON – A new study highlights the success, safety, and effectiveness of a new sutureless aortic valve device in patients with severe symptomatic aortic valve stenosis (AS).

The findings, reported at the annual meeting of the American Association for Thoracic Surgery, were based on a prospective, single-arm clinical trial approved under a Food and Drug Administration Investigational Device Exemption (IDE) that aimed to assess the safety and efficacy of a new bovine pericardial sutureless aortic valve in patients with severe AS undergoing aortic valve replacement with or without concomitant procedures. In this video interview, Michael Borger, MD, explains how the study was conducted and what the findings mean for future use of the sutureless aortic valve device.

agallegos@frontlinemedcom.com

On Twitter @legal_med

BOSTON – A new study highlights the success, safety, and effectiveness of a new sutureless aortic valve device in patients with severe symptomatic aortic valve stenosis (AS).

The findings, reported at the annual meeting of the American Association for Thoracic Surgery, were based on a prospective, single-arm clinical trial approved under a Food and Drug Administration Investigational Device Exemption (IDE) that aimed to assess the safety and efficacy of a new bovine pericardial sutureless aortic valve in patients with severe AS undergoing aortic valve replacement with or without concomitant procedures. In this video interview, Michael Borger, MD, explains how the study was conducted and what the findings mean for future use of the sutureless aortic valve device.

agallegos@frontlinemedcom.com

On Twitter @legal_med

BOSTON – U.S. physicians chose to withdraw life-sustaining care from critically ill ischemic stroke patients at much higher rates in 2011 than in 2006, according to results of a new study, although overall percentages remain low.

The trend was bolstered by big jumps in “withdrawal of care” among patients who underwent thrombolysis or both thrombolysis and endovascular treatment: Over the 5-year period, their likelihood of having care withdrawn increased fivefold.

The study authors don’t know whether the trends have continued over the past 6 years, and it’s not clear why the rates rose so much from 2006 to 2011. The researchers speculate that the increase could be linked to disease severity and the preferences of patients and their families.

Whatever the case, study lead author Malik Muhammad Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, cautioned that prematurely withdrawing care can throw off stroke prognostication estimates that are already fuzzy. In an interview, he said this can then lead to “significant consequences, including suboptimal outcomes and higher risk of short-term mortality.”

Dr. Adil defines withdrawal of care as “discontinuation of life-sustaining interventions from a patient who is expected to die without this support.” These interventions include such treatments as intubation, mechanical ventilation, feeding tubes, antibiotics, and brain surgery, he said.

For the new study, researchers examined the Nationwide Inpatient Survey database for the years 2006-2011. They reported their findings at the annual meeting of the American Academy of Neurology.

The study reports the following regarding withdrawal of care among ischemic stroke patients:

• The rate grew in those who received neither thrombolysis nor endovascular treatment from 0.8% in 2006 to 3.0% in 2011 (P less than or equal to .0001).
• In those who received thrombolysis alone, the rate rose from 0.9% to 5.5% (P less than or equal to .0001).
• In those who received endovascular treatment alone, the rate increased from 2.8% to 9.0% (P = .0006).
• In patients who received both thrombolysis and endovascular treatment, the rate grew from 2.0% to 10.3% (P = .0009).

Dr. Adil said several factors can affect rates of withdrawal of care in ischemic stroke patients, such as the level of illness (patients receiving aggressive treatment are sicker), advance directives, and the decisions of family members. Some institutions may be more likely to push for withdrawal of care, too, he said. “At my institution, we are not aggressive with withdrawal of care, and I have seen a few better outcomes than expected,” he said.

Also, the lack of useful data regarding prognosis for these patients may lead to premature decisions regarding withdrawal of care, he said.

“We have few prognostic models/scores that predict mortality, and these models are not very sensitive and specific,” Dr. Adil said. “Often, physicians make these decisions based on their previous experiences. All of this leads to premature withdrawal of care. On the other hand, because of premature withdrawal of care, we do not have the data on long-term outcomes on these patients, leading to errors in prognostication.”

In an interview, Adam G. Kelly, MD, a neurologist at the University of Rochester (N.Y.) and chief of neurology at Highland Hospital in Rochester, said the study is important but lacks crucial information such as the circumstances surrounding the care decisions. He hasn’t noticed trends in withdrawal of care among his patients.

“It’s possible that providers have become better at documenting discussions with patients and families which allowed this information to be better captured,” he said. “As the authors mention, it’s also possible that providers are consciously or unconsciously delivering prognoses that are biased towards negative outcomes, leading patients and families to be more apt to choose a palliative approach.”

Dr. Kelly added that neurologists need to objectively offer prognoses in stroke cases. “When the outcome is in doubt, I recommend time-limited trials of interventions of mechanical ventilation, artificial feeding, and other high-intensity interventions to allow patients and families to make the decision they feel is best,” he said.

What about trends in the years since 2011? Dr. Adil said information regarding the years since 2011 wasn’t available to him, but he hopes to analyze the period from 2012 to 2016.

Dr. Adil discussed his study and its implications in a video interview.

No funding is reported. Dr. Adil reports no relevant disclosures.

cnnews@frontlinemedcom.com

BOSTON – U.S. physicians chose to withdraw life-sustaining care from critically ill ischemic stroke patients at much higher rates in 2011 than in 2006, according to results of a new study, although overall percentages remain low.

The trend was bolstered by big jumps in “withdrawal of care” among patients who underwent thrombolysis or both thrombolysis and endovascular treatment: Over the 5-year period, their likelihood of having care withdrawn increased fivefold.

The study authors don’t know whether the trends have continued over the past 6 years, and it’s not clear why the rates rose so much from 2006 to 2011. The researchers speculate that the increase could be linked to disease severity and the preferences of patients and their families.

Whatever the case, study lead author Malik Muhammad Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, cautioned that prematurely withdrawing care can throw off stroke prognostication estimates that are already fuzzy. In an interview, he said this can then lead to “significant consequences, including suboptimal outcomes and higher risk of short-term mortality.”

Dr. Adil defines withdrawal of care as “discontinuation of life-sustaining interventions from a patient who is expected to die without this support.” These interventions include such treatments as intubation, mechanical ventilation, feeding tubes, antibiotics, and brain surgery, he said.

For the new study, researchers examined the Nationwide Inpatient Survey database for the years 2006-2011. They reported their findings at the annual meeting of the American Academy of Neurology.

The study reports the following regarding withdrawal of care among ischemic stroke patients:

• The rate grew in those who received neither thrombolysis nor endovascular treatment from 0.8% in 2006 to 3.0% in 2011 (P less than or equal to .0001).
• In those who received thrombolysis alone, the rate rose from 0.9% to 5.5% (P less than or equal to .0001).
• In those who received endovascular treatment alone, the rate increased from 2.8% to 9.0% (P = .0006).
• In patients who received both thrombolysis and endovascular treatment, the rate grew from 2.0% to 10.3% (P = .0009).

Dr. Adil said several factors can affect rates of withdrawal of care in ischemic stroke patients, such as the level of illness (patients receiving aggressive treatment are sicker), advance directives, and the decisions of family members. Some institutions may be more likely to push for withdrawal of care, too, he said. “At my institution, we are not aggressive with withdrawal of care, and I have seen a few better outcomes than expected,” he said.

Also, the lack of useful data regarding prognosis for these patients may lead to premature decisions regarding withdrawal of care, he said.

“We have few prognostic models/scores that predict mortality, and these models are not very sensitive and specific,” Dr. Adil said. “Often, physicians make these decisions based on their previous experiences. All of this leads to premature withdrawal of care. On the other hand, because of premature withdrawal of care, we do not have the data on long-term outcomes on these patients, leading to errors in prognostication.”

In an interview, Adam G. Kelly, MD, a neurologist at the University of Rochester (N.Y.) and chief of neurology at Highland Hospital in Rochester, said the study is important but lacks crucial information such as the circumstances surrounding the care decisions. He hasn’t noticed trends in withdrawal of care among his patients.

“It’s possible that providers have become better at documenting discussions with patients and families which allowed this information to be better captured,” he said. “As the authors mention, it’s also possible that providers are consciously or unconsciously delivering prognoses that are biased towards negative outcomes, leading patients and families to be more apt to choose a palliative approach.”

Dr. Kelly added that neurologists need to objectively offer prognoses in stroke cases. “When the outcome is in doubt, I recommend time-limited trials of interventions of mechanical ventilation, artificial feeding, and other high-intensity interventions to allow patients and families to make the decision they feel is best,” he said.

What about trends in the years since 2011? Dr. Adil said information regarding the years since 2011 wasn’t available to him, but he hopes to analyze the period from 2012 to 2016.

Dr. Adil discussed his study and its implications in a video interview.

No funding is reported. Dr. Adil reports no relevant disclosures.

cnnews@frontlinemedcom.com

BOSTON – U.S. physicians chose to withdraw life-sustaining care from critically ill ischemic stroke patients at much higher rates in 2011 than in 2006, according to results of a new study, although overall percentages remain low.

The trend was bolstered by big jumps in “withdrawal of care” among patients who underwent thrombolysis or both thrombolysis and endovascular treatment: Over the 5-year period, their likelihood of having care withdrawn increased fivefold.

The study authors don’t know whether the trends have continued over the past 6 years, and it’s not clear why the rates rose so much from 2006 to 2011. The researchers speculate that the increase could be linked to disease severity and the preferences of patients and their families.

Whatever the case, study lead author Malik Muhammad Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, cautioned that prematurely withdrawing care can throw off stroke prognostication estimates that are already fuzzy. In an interview, he said this can then lead to “significant consequences, including suboptimal outcomes and higher risk of short-term mortality.”

Dr. Adil defines withdrawal of care as “discontinuation of life-sustaining interventions from a patient who is expected to die without this support.” These interventions include such treatments as intubation, mechanical ventilation, feeding tubes, antibiotics, and brain surgery, he said.

For the new study, researchers examined the Nationwide Inpatient Survey database for the years 2006-2011. They reported their findings at the annual meeting of the American Academy of Neurology.

The study reports the following regarding withdrawal of care among ischemic stroke patients:

• The rate grew in those who received neither thrombolysis nor endovascular treatment from 0.8% in 2006 to 3.0% in 2011 (P less than or equal to .0001).
• In those who received thrombolysis alone, the rate rose from 0.9% to 5.5% (P less than or equal to .0001).
• In those who received endovascular treatment alone, the rate increased from 2.8% to 9.0% (P = .0006).
• In patients who received both thrombolysis and endovascular treatment, the rate grew from 2.0% to 10.3% (P = .0009).

Dr. Adil said several factors can affect rates of withdrawal of care in ischemic stroke patients, such as the level of illness (patients receiving aggressive treatment are sicker), advance directives, and the decisions of family members. Some institutions may be more likely to push for withdrawal of care, too, he said. “At my institution, we are not aggressive with withdrawal of care, and I have seen a few better outcomes than expected,” he said.

Also, the lack of useful data regarding prognosis for these patients may lead to premature decisions regarding withdrawal of care, he said.

“We have few prognostic models/scores that predict mortality, and these models are not very sensitive and specific,” Dr. Adil said. “Often, physicians make these decisions based on their previous experiences. All of this leads to premature withdrawal of care. On the other hand, because of premature withdrawal of care, we do not have the data on long-term outcomes on these patients, leading to errors in prognostication.”

In an interview, Adam G. Kelly, MD, a neurologist at the University of Rochester (N.Y.) and chief of neurology at Highland Hospital in Rochester, said the study is important but lacks crucial information such as the circumstances surrounding the care decisions. He hasn’t noticed trends in withdrawal of care among his patients.

“It’s possible that providers have become better at documenting discussions with patients and families which allowed this information to be better captured,” he said. “As the authors mention, it’s also possible that providers are consciously or unconsciously delivering prognoses that are biased towards negative outcomes, leading patients and families to be more apt to choose a palliative approach.”

Dr. Kelly added that neurologists need to objectively offer prognoses in stroke cases. “When the outcome is in doubt, I recommend time-limited trials of interventions of mechanical ventilation, artificial feeding, and other high-intensity interventions to allow patients and families to make the decision they feel is best,” he said.

What about trends in the years since 2011? Dr. Adil said information regarding the years since 2011 wasn’t available to him, but he hopes to analyze the period from 2012 to 2016.

Dr. Adil discussed his study and its implications in a video interview.

No funding is reported. Dr. Adil reports no relevant disclosures.

cnnews@frontlinemedcom.com