Jake Remaly

PHILADELPHIA – Among patients with episodic migraine, 4.5 years of preventive treatment with erenumab is effective, safe, and well tolerated, according to interim data from an open-label extension study. “Erenumab was well tolerated and safe, with no safety signals detected over this period,” said Messoud Ashina, MD, PhD, professor of neurology at the University of Copenhagen. Dr. Ashina presented the interim data from a 5-year, open-label extension study of erenumab at the annual meeting of the American Headache Society.

Erenumab is a monoclonal antibody that targets and blocks the calcitonin gene-related peptide (CGRP) receptor. In May 2018, the Food and Drug Administration approved erenumab for the preventive treatment of migraine in adults. The treatment, marketed as Aimovig, is administered once monthly by self-injection.

During the open-label study, patients initially received 70 mg of erenumab monthly. After approximately 2 years, patients switched to 140 mg of erenumab monthly. The researchers’ interim efficacy analysis included all patients on 140 mg of erenumab with data about monthly migraine days after more than 4 years of treatment. The safety analysis included all patients who enrolled in the open-label treatment period and received at least one dose of erenumab.

Of 250 patients who increased the erenumab dose from 70 mg to 140 mg, a total of 221 (88%) completed the open-label treatment period or remained on 140 mg after more than 4 years. Patients’ average number of monthly migraine days at study baseline was 8.7, and the average change from baseline to the most recent month in the interim analysis was –5.8.

During the most recent month of assessment, 77% of patients had at least a 50% reduction in monthly migraine days from baseline, 56% had at least a 75% reduction, and 33% had a 100% reduction.

Mean change from baseline in acute migraine‐specific medication treatment days was –4.6, from a baseline of 6.1.

Among the 383 patients who entered the open-label treatment period and received at least one dose of erenumab (mean age, 41.3; 79% female), the median erenumab exposure was 58.5 months. The exposure‐adjusted incidence of adverse events per 100 patient‐years was 124.9, and the three most frequent adverse events (per 100 patient-years) were nasopharyngitis (10.9), upper respiratory tract infection (6.8), and influenza (4.7). The exposure‐adjusted incidence rate per 100 patient‐years for constipation was 1.3 (9/383) for 70-mg erenumab and 2.6 (15/250) for 140-mg erenumab.

“The exposure‐adjusted incidence rate per 100 patient‐years of serious adverse events was 3.8, similar to the rate observed for erenumab and placebo during the placebo‐controlled periods of studies,” the researchers said.

The study was sponsored by Amgen, and several study authors are employees of Amgen or Novartis, the companies that market erenumab. Dr. Ashina is a consultant for Amgen, Novartis, and other companies.

[email protected]

SOURCE: Ashina M et al. AHS 2019, Abstract IOR10.

PHILADELPHIA – Among patients with episodic migraine, 4.5 years of preventive treatment with erenumab is effective, safe, and well tolerated, according to interim data from an open-label extension study. “Erenumab was well tolerated and safe, with no safety signals detected over this period,” said Messoud Ashina, MD, PhD, professor of neurology at the University of Copenhagen. Dr. Ashina presented the interim data from a 5-year, open-label extension study of erenumab at the annual meeting of the American Headache Society.

Erenumab is a monoclonal antibody that targets and blocks the calcitonin gene-related peptide (CGRP) receptor. In May 2018, the Food and Drug Administration approved erenumab for the preventive treatment of migraine in adults. The treatment, marketed as Aimovig, is administered once monthly by self-injection.

During the open-label study, patients initially received 70 mg of erenumab monthly. After approximately 2 years, patients switched to 140 mg of erenumab monthly. The researchers’ interim efficacy analysis included all patients on 140 mg of erenumab with data about monthly migraine days after more than 4 years of treatment. The safety analysis included all patients who enrolled in the open-label treatment period and received at least one dose of erenumab.

Of 250 patients who increased the erenumab dose from 70 mg to 140 mg, a total of 221 (88%) completed the open-label treatment period or remained on 140 mg after more than 4 years. Patients’ average number of monthly migraine days at study baseline was 8.7, and the average change from baseline to the most recent month in the interim analysis was –5.8.

During the most recent month of assessment, 77% of patients had at least a 50% reduction in monthly migraine days from baseline, 56% had at least a 75% reduction, and 33% had a 100% reduction.

Mean change from baseline in acute migraine‐specific medication treatment days was –4.6, from a baseline of 6.1.

Among the 383 patients who entered the open-label treatment period and received at least one dose of erenumab (mean age, 41.3; 79% female), the median erenumab exposure was 58.5 months. The exposure‐adjusted incidence of adverse events per 100 patient‐years was 124.9, and the three most frequent adverse events (per 100 patient-years) were nasopharyngitis (10.9), upper respiratory tract infection (6.8), and influenza (4.7). The exposure‐adjusted incidence rate per 100 patient‐years for constipation was 1.3 (9/383) for 70-mg erenumab and 2.6 (15/250) for 140-mg erenumab.

“The exposure‐adjusted incidence rate per 100 patient‐years of serious adverse events was 3.8, similar to the rate observed for erenumab and placebo during the placebo‐controlled periods of studies,” the researchers said.

The study was sponsored by Amgen, and several study authors are employees of Amgen or Novartis, the companies that market erenumab. Dr. Ashina is a consultant for Amgen, Novartis, and other companies.

[email protected]

SOURCE: Ashina M et al. AHS 2019, Abstract IOR10.

PHILADELPHIA – Among patients with episodic migraine, 4.5 years of preventive treatment with erenumab is effective, safe, and well tolerated, according to interim data from an open-label extension study. “Erenumab was well tolerated and safe, with no safety signals detected over this period,” said Messoud Ashina, MD, PhD, professor of neurology at the University of Copenhagen. Dr. Ashina presented the interim data from a 5-year, open-label extension study of erenumab at the annual meeting of the American Headache Society.

Erenumab is a monoclonal antibody that targets and blocks the calcitonin gene-related peptide (CGRP) receptor. In May 2018, the Food and Drug Administration approved erenumab for the preventive treatment of migraine in adults. The treatment, marketed as Aimovig, is administered once monthly by self-injection.

During the open-label study, patients initially received 70 mg of erenumab monthly. After approximately 2 years, patients switched to 140 mg of erenumab monthly. The researchers’ interim efficacy analysis included all patients on 140 mg of erenumab with data about monthly migraine days after more than 4 years of treatment. The safety analysis included all patients who enrolled in the open-label treatment period and received at least one dose of erenumab.

Of 250 patients who increased the erenumab dose from 70 mg to 140 mg, a total of 221 (88%) completed the open-label treatment period or remained on 140 mg after more than 4 years. Patients’ average number of monthly migraine days at study baseline was 8.7, and the average change from baseline to the most recent month in the interim analysis was –5.8.

During the most recent month of assessment, 77% of patients had at least a 50% reduction in monthly migraine days from baseline, 56% had at least a 75% reduction, and 33% had a 100% reduction.

Mean change from baseline in acute migraine‐specific medication treatment days was –4.6, from a baseline of 6.1.

Among the 383 patients who entered the open-label treatment period and received at least one dose of erenumab (mean age, 41.3; 79% female), the median erenumab exposure was 58.5 months. The exposure‐adjusted incidence of adverse events per 100 patient‐years was 124.9, and the three most frequent adverse events (per 100 patient-years) were nasopharyngitis (10.9), upper respiratory tract infection (6.8), and influenza (4.7). The exposure‐adjusted incidence rate per 100 patient‐years for constipation was 1.3 (9/383) for 70-mg erenumab and 2.6 (15/250) for 140-mg erenumab.

“The exposure‐adjusted incidence rate per 100 patient‐years of serious adverse events was 3.8, similar to the rate observed for erenumab and placebo during the placebo‐controlled periods of studies,” the researchers said.

The study was sponsored by Amgen, and several study authors are employees of Amgen or Novartis, the companies that market erenumab. Dr. Ashina is a consultant for Amgen, Novartis, and other companies.

[email protected]

SOURCE: Ashina M et al. AHS 2019, Abstract IOR10.

Adults with low levels of hemoglobin and adults with high levels of hemoglobin have an increased risk of developing dementia over 12 years of follow-up, compared with adults with midrange levels, according to a population-based study in the Netherlands.

This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.

Ton Everaers, Erasmus Medical Center

“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.

Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.

A population-based cohort study

To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).

During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.

“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.

About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.

Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).

A U-shaped association

The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.

The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.

A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.

Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”

The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.

[email protected]

SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.

Adults with low levels of hemoglobin and adults with high levels of hemoglobin have an increased risk of developing dementia over 12 years of follow-up, compared with adults with midrange levels, according to a population-based study in the Netherlands.

This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.

Ton Everaers, Erasmus Medical Center

“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.

Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.

A population-based cohort study

To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).

During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.

“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.

About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.

Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).

A U-shaped association

The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.

The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.

A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.

Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”

The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.

[email protected]

SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.

Adults with low levels of hemoglobin and adults with high levels of hemoglobin have an increased risk of developing dementia over 12 years of follow-up, compared with adults with midrange levels, according to a population-based study in the Netherlands.

This U-shaped association “may relate to differences in white matter integrity and cerebral perfusion,” the researchers wrote in Neurology.

Ton Everaers, Erasmus Medical Center

“With around 10% of people over age 65 having anemia in the Americas and Europe and up to 45% in African and southeast Asian countries, these results could have important implications for the burden of dementia,” said study author M. Arfan Ikram, MD, PhD, in a news release. Dr. Ikram is a professor of epidemiology at Erasmus Medical Center in Rotterdam, the Netherlands.

Prior studies have found that low hemoglobin levels are associated with adverse health outcomes, such as coronary heart disease, stroke, and mortality, but data about the relationship between hemoglobin levels and dementia risk have been limited.

A population-based cohort study

To examine the long-term association of hemoglobin levels and anemia with risk of dementia, Dr. Ikram and coauthors analyzed data from the Rotterdam Study, an ongoing population-based cohort study in the Netherlands that started in 1990. Their analysis included data from 12,305 participants without dementia who had serum hemoglobin measured at baseline (mean age, 64.6 years; 57.7% women).

During a mean follow-up of 12.1 years, 1,520 participants developed dementia, 1,194 of whom had Alzheimer’s disease.

“Both low and high hemoglobin levels were associated with increased dementia risk,” the authors wrote. Compared with participants in the middle quintile of hemoglobin levels (8.57-8.99 mmol/L), participants in the lowest quintile (less than 8.11 mmol/L) had a hazard ratio of dementia of 1.29, and participants in the highest quintile (greater than 9.40 mmol/L) had an HR of 1.20.

About 6% of the participants had anemia – that is, a hemoglobin level of less than 8.1 mmol/L for men and less than 7.5 mmol/L for women. Anemia was associated with a 34% increased risk of dementia and a 41% increased risk of Alzheimer’s disease.

Of the 745 people with anemia, 128 developed dementia, compared with 1,392 of the 11,560 people who did not have anemia (17% vs. 12%).

A U-shaped association

The researchers also examined hemoglobin in relation to vascular brain disease, structural connectivity, and global cerebral perfusion among 5,267 participants without dementia who had brain MRI. White matter hyperintensity volume and hemoglobin had a U-shaped association, similar to that for dementia and hemoglobin. In addition, hemoglobin inversely correlated to cerebral perfusion.

The results remained consistent after adjustment for factors such as smoking, high blood pressure, high cholesterol, and alcohol use.

A limitation of the study is that the participants lived in the Netherlands and were primarily of European descent, so the results may not apply to other populations, the authors wrote.

Dr. Ikram noted that the study does not prove that low or high hemoglobin levels cause dementia. “More research is needed to determine whether hemoglobin levels play a direct role in this increased risk or whether these associations can be explained by underlying issues or other vascular or metabolic changes.”

The study was supported by the Netherlands Cardiovascular Research Initiative; Erasmus Medical Centre; Erasmus University Rotterdam; Netherlands Organization for Scientific Research; Netherlands Organization for Health Research and Development; Research Institute for Diseases in the Elderly; Netherlands Genomic Initiative; Dutch Ministry of Education, Culture, and Science; Dutch Ministry of Health, Welfare, and Sports; European Commission; Municipality of Rotterdam; Netherlands Consortium for Healthy Aging; and Dutch Heart Foundation. The authors reported no relevant disclosures.

[email protected]

SOURCE: Ikram MA et al. Neurology. 2019 Jul 31. doi: 10.1212/WNL.0000000000008003.

Endovascular thrombectomy may benefit patients with stroke with large infarcts, an analysis suggests. The intervention may be more likely to benefit patients who “are treated early and have a core volume less than 100 cm³,” researchers reported in JAMA Neurology.

American Heart Association

Clinical trials evaluating thrombectomy have largely excluded patients with large ischemic cores. To examine whether thrombectomy produces reasonable functional and safety outcomes in patients with stroke with large infarcts, compared with medical management alone, the investigators conducted a prespecified secondary analysis of data from the Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) study.

A nonrandomized study

Amrou Sarraj, MD, of the University of Texas, Houston, and his coauthors analyzed data from 105 patients in the prospective, multicenter cohort study, which enrolled patients between January 2016 and February 2018. Their analysis included data from patients who had large ischemic cores on CT (Alberta Stroke Program Early CT Score, 0-5) or on CT perfusion images (an ischemic core volume of at least 50 cm³). The SELECT study included patients with moderate to severe stroke and anterior circulation large-vessel occlusion who presented up to 24 hours from the time they last were known to be well. In the SELECT study, local investigators decided whether patients received endovascular thrombectomy or medical management alone in a nonrandomized fashion.

The 105 patients had a median age of 66 years, and 43% were female. Of the patients with large infarcts, 62 (59%) received endovascular thrombectomy plus medical management, and the rest received medical management alone.

At 90 days, 31% of the patients who received endovascular thrombectomy achieved functional independence (modified Rankin Scale score of 0-2), compared with 14% of patients who received medical management alone (odds ratio, 3.27). In addition, endovascular thrombectomy was associated with better functional outcome, less infarct growth (44 vs. 98 mL), and smaller final infarct volume (97 vs. 190 mL).

The rates of neurologic worsening and symptomatic intracerebral hemorrhage were similar in both treatment groups, while mortality was lower among patients who received thrombectomy (29% vs. 42%). The likelihood of functional independence with endovascular thrombectomy decreased by 40% with each 1-hour delay in treatment and by 42% with each 10-cm³ increase in stroke volume.

Of 10 patients with core volumes greater than 100 cm³ who received endovascular thrombectomy, none had a favorable outcome.

“Although the odds of good outcomes for patients with large cores who received [endovascular thrombectomy] markedly decline with increasing core size and time to treatment, these data suggest potential benefits,” Dr. Sarraj and colleagues concluded. “Randomized clinical trials are needed.”

The authors noted that the results “did not reach significance after adjusting for baseline imbalances” and that “the small sample size limits the power of this analysis.”

The study was funded by an unrestricted grant from Stryker Neurovascular to the University of Texas. Dr. Sarraj is a consultant, speaker bureau member, and advisory board member for Stryker and is the principal investigator for a planned randomized, controlled trial (SELECT 2) funded by an unrestricted grant from Stryker to his institution. In addition, he is a site principal investigator for the TREVO Registry and DEFUSE 3 trials. Coauthors reported financial ties with Stryker and various device and pharmaceutical companies.

[email protected]

SOURCE: Sarraj A et al. JAMA Neurol. 2019 Jul 29. doi: 10.1001/jamaneurol.2019.2109.


 

Endovascular thrombectomy may benefit patients with stroke with large infarcts, an analysis suggests. The intervention may be more likely to benefit patients who “are treated early and have a core volume less than 100 cm³,” researchers reported in JAMA Neurology.

American Heart Association

Clinical trials evaluating thrombectomy have largely excluded patients with large ischemic cores. To examine whether thrombectomy produces reasonable functional and safety outcomes in patients with stroke with large infarcts, compared with medical management alone, the investigators conducted a prespecified secondary analysis of data from the Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) study.

A nonrandomized study

Amrou Sarraj, MD, of the University of Texas, Houston, and his coauthors analyzed data from 105 patients in the prospective, multicenter cohort study, which enrolled patients between January 2016 and February 2018. Their analysis included data from patients who had large ischemic cores on CT (Alberta Stroke Program Early CT Score, 0-5) or on CT perfusion images (an ischemic core volume of at least 50 cm³). The SELECT study included patients with moderate to severe stroke and anterior circulation large-vessel occlusion who presented up to 24 hours from the time they last were known to be well. In the SELECT study, local investigators decided whether patients received endovascular thrombectomy or medical management alone in a nonrandomized fashion.

The 105 patients had a median age of 66 years, and 43% were female. Of the patients with large infarcts, 62 (59%) received endovascular thrombectomy plus medical management, and the rest received medical management alone.

At 90 days, 31% of the patients who received endovascular thrombectomy achieved functional independence (modified Rankin Scale score of 0-2), compared with 14% of patients who received medical management alone (odds ratio, 3.27). In addition, endovascular thrombectomy was associated with better functional outcome, less infarct growth (44 vs. 98 mL), and smaller final infarct volume (97 vs. 190 mL).

The rates of neurologic worsening and symptomatic intracerebral hemorrhage were similar in both treatment groups, while mortality was lower among patients who received thrombectomy (29% vs. 42%). The likelihood of functional independence with endovascular thrombectomy decreased by 40% with each 1-hour delay in treatment and by 42% with each 10-cm³ increase in stroke volume.

Of 10 patients with core volumes greater than 100 cm³ who received endovascular thrombectomy, none had a favorable outcome.

“Although the odds of good outcomes for patients with large cores who received [endovascular thrombectomy] markedly decline with increasing core size and time to treatment, these data suggest potential benefits,” Dr. Sarraj and colleagues concluded. “Randomized clinical trials are needed.”

The authors noted that the results “did not reach significance after adjusting for baseline imbalances” and that “the small sample size limits the power of this analysis.”

The study was funded by an unrestricted grant from Stryker Neurovascular to the University of Texas. Dr. Sarraj is a consultant, speaker bureau member, and advisory board member for Stryker and is the principal investigator for a planned randomized, controlled trial (SELECT 2) funded by an unrestricted grant from Stryker to his institution. In addition, he is a site principal investigator for the TREVO Registry and DEFUSE 3 trials. Coauthors reported financial ties with Stryker and various device and pharmaceutical companies.

[email protected]

SOURCE: Sarraj A et al. JAMA Neurol. 2019 Jul 29. doi: 10.1001/jamaneurol.2019.2109.


 

Endovascular thrombectomy may benefit patients with stroke with large infarcts, an analysis suggests. The intervention may be more likely to benefit patients who “are treated early and have a core volume less than 100 cm³,” researchers reported in JAMA Neurology.

American Heart Association

Clinical trials evaluating thrombectomy have largely excluded patients with large ischemic cores. To examine whether thrombectomy produces reasonable functional and safety outcomes in patients with stroke with large infarcts, compared with medical management alone, the investigators conducted a prespecified secondary analysis of data from the Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) study.

A nonrandomized study

Amrou Sarraj, MD, of the University of Texas, Houston, and his coauthors analyzed data from 105 patients in the prospective, multicenter cohort study, which enrolled patients between January 2016 and February 2018. Their analysis included data from patients who had large ischemic cores on CT (Alberta Stroke Program Early CT Score, 0-5) or on CT perfusion images (an ischemic core volume of at least 50 cm³). The SELECT study included patients with moderate to severe stroke and anterior circulation large-vessel occlusion who presented up to 24 hours from the time they last were known to be well. In the SELECT study, local investigators decided whether patients received endovascular thrombectomy or medical management alone in a nonrandomized fashion.

The 105 patients had a median age of 66 years, and 43% were female. Of the patients with large infarcts, 62 (59%) received endovascular thrombectomy plus medical management, and the rest received medical management alone.

At 90 days, 31% of the patients who received endovascular thrombectomy achieved functional independence (modified Rankin Scale score of 0-2), compared with 14% of patients who received medical management alone (odds ratio, 3.27). In addition, endovascular thrombectomy was associated with better functional outcome, less infarct growth (44 vs. 98 mL), and smaller final infarct volume (97 vs. 190 mL).

The rates of neurologic worsening and symptomatic intracerebral hemorrhage were similar in both treatment groups, while mortality was lower among patients who received thrombectomy (29% vs. 42%). The likelihood of functional independence with endovascular thrombectomy decreased by 40% with each 1-hour delay in treatment and by 42% with each 10-cm³ increase in stroke volume.

Of 10 patients with core volumes greater than 100 cm³ who received endovascular thrombectomy, none had a favorable outcome.

“Although the odds of good outcomes for patients with large cores who received [endovascular thrombectomy] markedly decline with increasing core size and time to treatment, these data suggest potential benefits,” Dr. Sarraj and colleagues concluded. “Randomized clinical trials are needed.”

The authors noted that the results “did not reach significance after adjusting for baseline imbalances” and that “the small sample size limits the power of this analysis.”

The study was funded by an unrestricted grant from Stryker Neurovascular to the University of Texas. Dr. Sarraj is a consultant, speaker bureau member, and advisory board member for Stryker and is the principal investigator for a planned randomized, controlled trial (SELECT 2) funded by an unrestricted grant from Stryker to his institution. In addition, he is a site principal investigator for the TREVO Registry and DEFUSE 3 trials. Coauthors reported financial ties with Stryker and various device and pharmaceutical companies.

[email protected]

SOURCE: Sarraj A et al. JAMA Neurol. 2019 Jul 29. doi: 10.1001/jamaneurol.2019.2109.


 

PHILADELPHIA – Nineteen percent of patients with migraine use opioids to treat migraine, according to a survey of more than 21,000 patients in 2018. People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.

Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.

To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.

The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.

“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.

Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.

There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.

Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.

Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.

[email protected]

PHILADELPHIA – Nineteen percent of patients with migraine use opioids to treat migraine, according to a survey of more than 21,000 patients in 2018. People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.

Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.

To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.

The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.

“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.

Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.

There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.

Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.

Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.

[email protected]

PHILADELPHIA – Nineteen percent of patients with migraine use opioids to treat migraine, according to a survey of more than 21,000 patients in 2018. People with 4 or more migraine headache days per month are more likely to use opioids, compared with people with fewer migraine headache days per month, researchers said. Opioid use for migraine “remains alarmingly high,” the investigators said at the annual meeting of the American Headache Society.

Although opioid use for the treatment of migraine typically is discouraged, studies indicate that it is common. Evidence suggests that opioids may increase the risk of progression from episodic to chronic migraine.

To evaluate opioid use in people with migraine, Sait Ashina, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center in Boston, and the research colleagues analyzed data from 21,143 people with migraine who participated in the OVERCOME (Observational Survey of the Epidemiology, Treatment and Care of Migraine), a Web-based study of a representative U.S. sample. OVERCOME enrolled participants in the fall of 2018.

The researchers classified self-reported opioid use for migraine as current use in the past 12 months, former use, or never. Participants had a mean age of 42 years, and 74% were female. The researchers used a multivariable logistic regression model adjusted for age and sex in their analyses.

“Strikingly, we were able to find 19% of people with migraine were reporting current use of opioids,” Dr. Ashina said.

Among 12,299 patients with 0-3 migraine headache days per month, 59% were never, 26% former, and 15% current users of opioids for migraine. Among 8,844 patients with 4 or more migraine headache days per month, 44.9% were never, 31.2% former, and 23.9% current users of opioids for migraine.

There was an increased likelihood of opioid use for migraine in people with pain comorbidities such as back pain, neck pain, and fibromyalgia and in people with anxiety and depression.

Approximately 30%-40% of those who used opioids for migraine were using strong opioids, as defined by the World Health Organization, Dr. Ashina noted. Preliminary analyses indicate that patients tended to receive opioids in a primary care setting, he said.

Eli Lilly funded the OVERCOME study. Dr. Ashina has consulted for Novartis, Amgen, Promius, Supernus, Satsuma, and Allergan. He is on the Editorial Advisory Board for Neurology Reviews.

[email protected]

PHILADELPHIA – A surprisingly large number of patients with migraine who first seek care for migraine in a primary care setting receive an initial migraine diagnosis from a neurologist, said Alice R. Pressman, PhD at the annual meeting of the American Headache Society.

Dr. Pressman, executive director of research, development, and dissemination for Sutter Health, and her research colleagues analyzed data from primary care patients who sought care for migraine in the Sutter Health healthcare network in Northern California. They found that women were 10% more likely than men to consult a neurologist and that Asian patients had a longer time to a first neurology encounter for migraine, compared with Caucasian patients.

“Those who sought care from neurology had more severe migraine symptomology, disability, and comorbidities,” the researchers reported. Furthermore, patients with migraine seen by neurologists were more likely to receive prescriptions for acute and preventive migraine medications, compared with patients only seen by primary care physicians.

The study, known as the Migraine Signature Study, used electronic health records (EHR) and patient-reported questionnaire data to examine the clinical experiences and care of patients with migraine.

The primary care population consisted of 1.4 million adults with at least one office visit to primary care in 2013-2017. Using the validated Migraine Probability Algorithm, the researchers identified approximately 94,000 patients who sought care for migraine.

The investigators also invited 38,536 patients to complete an online survey about migraine criteria, symptomology, health resource utilization, and patient-reported outcomes such as disability, acute treatment optimization, cutaneous allodynia, depression, anxiety, and posttraumatic stress disorder (PTSD).

Of the patients who sought care for migraine, 72,624 patients did not receive migraine care from neurology, and 21,525 did.

Patients with migraine care from a neurologist were more likely to have at least one acute migraine medication order (89.4% vs. 80.6%), at least one preventive migraine medication order (78.6% vs. 49.1%), and any migraine medication order (95.3% vs. 85.9%). In addition, those with at least one medication order in the primary care setting had fewer orders per person per year, compared with those with at least one medication order in the neurology setting (1.1 vs. 1.6).

About one-third of the patients who sought care for migraine had no migraine encounters in the first 12 months of the study. Of the more than 33,000 patients with first migraine consults, approximately two-thirds did not receive a neurology consultation during the study and received their migraine diagnosis in the primary care setting.

Of the 31% of patients with first migraine consults in primary care who later had a neurology consult, two-thirds received a migraine diagnosis from neurology. “The high rate of initial migraine diagnosis within neurology was surprising among this sample with primary care encounters first,” the researchers said.

The investigators also examined patient-reported outcomes from 391 respondents who received migraine care from neurology and 399 respondents who received migraine care from primary care. “Patients who consulted a neurologist were likely to report moderate-to-severe disability, poor acute treatment optimization, and major depression,” they said. “Allodynia, anxiety, and PTSD did not differ by type of provider.”

Confounding may have influenced the results, and the researchers plan to assess factors such as headache frequency and severity using patient-reported survey data in future analyses.

The Migraine Signature Study was supported by Amgen, Inc.

[email protected]

PHILADELPHIA – A surprisingly large number of patients with migraine who first seek care for migraine in a primary care setting receive an initial migraine diagnosis from a neurologist, said Alice R. Pressman, PhD at the annual meeting of the American Headache Society.

Dr. Pressman, executive director of research, development, and dissemination for Sutter Health, and her research colleagues analyzed data from primary care patients who sought care for migraine in the Sutter Health healthcare network in Northern California. They found that women were 10% more likely than men to consult a neurologist and that Asian patients had a longer time to a first neurology encounter for migraine, compared with Caucasian patients.

“Those who sought care from neurology had more severe migraine symptomology, disability, and comorbidities,” the researchers reported. Furthermore, patients with migraine seen by neurologists were more likely to receive prescriptions for acute and preventive migraine medications, compared with patients only seen by primary care physicians.

The study, known as the Migraine Signature Study, used electronic health records (EHR) and patient-reported questionnaire data to examine the clinical experiences and care of patients with migraine.

The primary care population consisted of 1.4 million adults with at least one office visit to primary care in 2013-2017. Using the validated Migraine Probability Algorithm, the researchers identified approximately 94,000 patients who sought care for migraine.

The investigators also invited 38,536 patients to complete an online survey about migraine criteria, symptomology, health resource utilization, and patient-reported outcomes such as disability, acute treatment optimization, cutaneous allodynia, depression, anxiety, and posttraumatic stress disorder (PTSD).

Of the patients who sought care for migraine, 72,624 patients did not receive migraine care from neurology, and 21,525 did.

Patients with migraine care from a neurologist were more likely to have at least one acute migraine medication order (89.4% vs. 80.6%), at least one preventive migraine medication order (78.6% vs. 49.1%), and any migraine medication order (95.3% vs. 85.9%). In addition, those with at least one medication order in the primary care setting had fewer orders per person per year, compared with those with at least one medication order in the neurology setting (1.1 vs. 1.6).

About one-third of the patients who sought care for migraine had no migraine encounters in the first 12 months of the study. Of the more than 33,000 patients with first migraine consults, approximately two-thirds did not receive a neurology consultation during the study and received their migraine diagnosis in the primary care setting.

Of the 31% of patients with first migraine consults in primary care who later had a neurology consult, two-thirds received a migraine diagnosis from neurology. “The high rate of initial migraine diagnosis within neurology was surprising among this sample with primary care encounters first,” the researchers said.

The investigators also examined patient-reported outcomes from 391 respondents who received migraine care from neurology and 399 respondents who received migraine care from primary care. “Patients who consulted a neurologist were likely to report moderate-to-severe disability, poor acute treatment optimization, and major depression,” they said. “Allodynia, anxiety, and PTSD did not differ by type of provider.”

Confounding may have influenced the results, and the researchers plan to assess factors such as headache frequency and severity using patient-reported survey data in future analyses.

The Migraine Signature Study was supported by Amgen, Inc.

[email protected]

PHILADELPHIA – A surprisingly large number of patients with migraine who first seek care for migraine in a primary care setting receive an initial migraine diagnosis from a neurologist, said Alice R. Pressman, PhD at the annual meeting of the American Headache Society.

Dr. Pressman, executive director of research, development, and dissemination for Sutter Health, and her research colleagues analyzed data from primary care patients who sought care for migraine in the Sutter Health healthcare network in Northern California. They found that women were 10% more likely than men to consult a neurologist and that Asian patients had a longer time to a first neurology encounter for migraine, compared with Caucasian patients.

“Those who sought care from neurology had more severe migraine symptomology, disability, and comorbidities,” the researchers reported. Furthermore, patients with migraine seen by neurologists were more likely to receive prescriptions for acute and preventive migraine medications, compared with patients only seen by primary care physicians.

The study, known as the Migraine Signature Study, used electronic health records (EHR) and patient-reported questionnaire data to examine the clinical experiences and care of patients with migraine.

The primary care population consisted of 1.4 million adults with at least one office visit to primary care in 2013-2017. Using the validated Migraine Probability Algorithm, the researchers identified approximately 94,000 patients who sought care for migraine.

The investigators also invited 38,536 patients to complete an online survey about migraine criteria, symptomology, health resource utilization, and patient-reported outcomes such as disability, acute treatment optimization, cutaneous allodynia, depression, anxiety, and posttraumatic stress disorder (PTSD).

Of the patients who sought care for migraine, 72,624 patients did not receive migraine care from neurology, and 21,525 did.

Patients with migraine care from a neurologist were more likely to have at least one acute migraine medication order (89.4% vs. 80.6%), at least one preventive migraine medication order (78.6% vs. 49.1%), and any migraine medication order (95.3% vs. 85.9%). In addition, those with at least one medication order in the primary care setting had fewer orders per person per year, compared with those with at least one medication order in the neurology setting (1.1 vs. 1.6).

About one-third of the patients who sought care for migraine had no migraine encounters in the first 12 months of the study. Of the more than 33,000 patients with first migraine consults, approximately two-thirds did not receive a neurology consultation during the study and received their migraine diagnosis in the primary care setting.

Of the 31% of patients with first migraine consults in primary care who later had a neurology consult, two-thirds received a migraine diagnosis from neurology. “The high rate of initial migraine diagnosis within neurology was surprising among this sample with primary care encounters first,” the researchers said.

The investigators also examined patient-reported outcomes from 391 respondents who received migraine care from neurology and 399 respondents who received migraine care from primary care. “Patients who consulted a neurologist were likely to report moderate-to-severe disability, poor acute treatment optimization, and major depression,” they said. “Allodynia, anxiety, and PTSD did not differ by type of provider.”

Confounding may have influenced the results, and the researchers plan to assess factors such as headache frequency and severity using patient-reported survey data in future analyses.

The Migraine Signature Study was supported by Amgen, Inc.

[email protected]

PHILADELPHIA – Mindfulness-based cognitive therapy tailored for migraine may reduce migraine-related disability, even as the number of headache days and pain intensity remain unchanged, according to randomized clinical trial results.

“The fact that people can improve how they live their daily life even with the same amount of headache days and the same pain intensity is remarkable,” said study investigator Elizabeth K. Seng, PhD, associate professor of psychology at Yeshiva University and research associate professor of neurology at Albert Einstein College of Medicine, both in New York. “I think this gives us a little bit of a clue about when to use these kinds of treatments.”

Dr. Seng presented findings from the phase 2b pilot trial at the annual meeting of the American Headache Society.

To study the efficacy of mindfulness-based cognitive therapy for migraine, Dr. Seng and her research colleagues recruited participants with migraine in the New York City area between 2015 and 2018. In all, 60 patients were randomized to receive 8 weekly individual 75-minute mindfulness-based cognitive therapy for migraine sessions or 8 weeks on a wait list with treatment as usual.

Primary outcomes were Month 0 to Month 4 changes in perceived disability, measured using the Henry Ford Disability Inventory (HDI) and functional disability measured using the Migraine Disability Assessment Scale (MIDAS). Secondary outcomes included changes in headache days per 30 days and headache pain intensity.

Participants had a mean age of about 40 years, about 92% were women, and approximately half of the patients had chronic migraine. Participants had an average baseline HDI of 51.4, and 83.3% had MIDAS scores indicating severe disability. Patients averaged 10.4 headache attack days per month, and mean headache attack severity on a 0-10 scale was 6.2. Attrition did not significantly differ between the mindfulness-based cognitive therapy and control groups.

Patients who received mindfulness-based cognitive therapy for migraine experienced an approximately 15-point reduction on the HDI scale at 4 months, whereas wait-listed patients did not experience much of a change, Dr. Seng said. The difference between groups was statistically significant.

At 4 months, a smaller proportion of patients in the mindfulness-based cognitive therapy group had a MIDAS score of 21 or greater, but the difference between groups was not statistically significant. The data indicate a large effect that the study was underpowered to detect, Dr. Seng said.

A planned subgroup analysis found that mindfulness-based cognitive therapy produced changes in disability that were greater in patients with episodic migraine, compared with patients with chronic migraine. A reduction in MIDAS scores was statistically significant among patients with episodic migraine.

During the trial, one patient experienced increased headache frequency and intensity and changed their preventive treatment regimen, which investigators considered unrelated to mindfulness-based cognitive therapy. In addition, one patient experienced flooding – a vivid recollection of a traumatic event – which is an expected effect of meditation and relaxation therapy, Dr. Seng said. The patient completed the study and was satisfied with the mindfulness-based cognitive therapy training, she said.

“Preliminary evidence suggests that mindfulness-based cognitive therapy could be recommended to reduce headache-related disability in people with episodic migraine or people who have some kind of effective prevention on board, but they are still experiencing high levels of disability,” Dr. Seng said.

Although flooding may occur in patients with a trauma history who use meditation and relaxation, the techniques still may be useful, Dr. Seng said. “In the VA setting, we use meditation and relaxation all the time. But it helps to forewarn patients that they might experience distressful flooding and [to provide] techniques that they can use to reduce the impact of that.”

[email protected]

PHILADELPHIA – Mindfulness-based cognitive therapy tailored for migraine may reduce migraine-related disability, even as the number of headache days and pain intensity remain unchanged, according to randomized clinical trial results.

“The fact that people can improve how they live their daily life even with the same amount of headache days and the same pain intensity is remarkable,” said study investigator Elizabeth K. Seng, PhD, associate professor of psychology at Yeshiva University and research associate professor of neurology at Albert Einstein College of Medicine, both in New York. “I think this gives us a little bit of a clue about when to use these kinds of treatments.”

Dr. Seng presented findings from the phase 2b pilot trial at the annual meeting of the American Headache Society.

To study the efficacy of mindfulness-based cognitive therapy for migraine, Dr. Seng and her research colleagues recruited participants with migraine in the New York City area between 2015 and 2018. In all, 60 patients were randomized to receive 8 weekly individual 75-minute mindfulness-based cognitive therapy for migraine sessions or 8 weeks on a wait list with treatment as usual.

Primary outcomes were Month 0 to Month 4 changes in perceived disability, measured using the Henry Ford Disability Inventory (HDI) and functional disability measured using the Migraine Disability Assessment Scale (MIDAS). Secondary outcomes included changes in headache days per 30 days and headache pain intensity.

Participants had a mean age of about 40 years, about 92% were women, and approximately half of the patients had chronic migraine. Participants had an average baseline HDI of 51.4, and 83.3% had MIDAS scores indicating severe disability. Patients averaged 10.4 headache attack days per month, and mean headache attack severity on a 0-10 scale was 6.2. Attrition did not significantly differ between the mindfulness-based cognitive therapy and control groups.

Patients who received mindfulness-based cognitive therapy for migraine experienced an approximately 15-point reduction on the HDI scale at 4 months, whereas wait-listed patients did not experience much of a change, Dr. Seng said. The difference between groups was statistically significant.

At 4 months, a smaller proportion of patients in the mindfulness-based cognitive therapy group had a MIDAS score of 21 or greater, but the difference between groups was not statistically significant. The data indicate a large effect that the study was underpowered to detect, Dr. Seng said.

A planned subgroup analysis found that mindfulness-based cognitive therapy produced changes in disability that were greater in patients with episodic migraine, compared with patients with chronic migraine. A reduction in MIDAS scores was statistically significant among patients with episodic migraine.

During the trial, one patient experienced increased headache frequency and intensity and changed their preventive treatment regimen, which investigators considered unrelated to mindfulness-based cognitive therapy. In addition, one patient experienced flooding – a vivid recollection of a traumatic event – which is an expected effect of meditation and relaxation therapy, Dr. Seng said. The patient completed the study and was satisfied with the mindfulness-based cognitive therapy training, she said.

“Preliminary evidence suggests that mindfulness-based cognitive therapy could be recommended to reduce headache-related disability in people with episodic migraine or people who have some kind of effective prevention on board, but they are still experiencing high levels of disability,” Dr. Seng said.

Although flooding may occur in patients with a trauma history who use meditation and relaxation, the techniques still may be useful, Dr. Seng said. “In the VA setting, we use meditation and relaxation all the time. But it helps to forewarn patients that they might experience distressful flooding and [to provide] techniques that they can use to reduce the impact of that.”

[email protected]

PHILADELPHIA – Mindfulness-based cognitive therapy tailored for migraine may reduce migraine-related disability, even as the number of headache days and pain intensity remain unchanged, according to randomized clinical trial results.

“The fact that people can improve how they live their daily life even with the same amount of headache days and the same pain intensity is remarkable,” said study investigator Elizabeth K. Seng, PhD, associate professor of psychology at Yeshiva University and research associate professor of neurology at Albert Einstein College of Medicine, both in New York. “I think this gives us a little bit of a clue about when to use these kinds of treatments.”

Dr. Seng presented findings from the phase 2b pilot trial at the annual meeting of the American Headache Society.

To study the efficacy of mindfulness-based cognitive therapy for migraine, Dr. Seng and her research colleagues recruited participants with migraine in the New York City area between 2015 and 2018. In all, 60 patients were randomized to receive 8 weekly individual 75-minute mindfulness-based cognitive therapy for migraine sessions or 8 weeks on a wait list with treatment as usual.

Primary outcomes were Month 0 to Month 4 changes in perceived disability, measured using the Henry Ford Disability Inventory (HDI) and functional disability measured using the Migraine Disability Assessment Scale (MIDAS). Secondary outcomes included changes in headache days per 30 days and headache pain intensity.

Participants had a mean age of about 40 years, about 92% were women, and approximately half of the patients had chronic migraine. Participants had an average baseline HDI of 51.4, and 83.3% had MIDAS scores indicating severe disability. Patients averaged 10.4 headache attack days per month, and mean headache attack severity on a 0-10 scale was 6.2. Attrition did not significantly differ between the mindfulness-based cognitive therapy and control groups.

Patients who received mindfulness-based cognitive therapy for migraine experienced an approximately 15-point reduction on the HDI scale at 4 months, whereas wait-listed patients did not experience much of a change, Dr. Seng said. The difference between groups was statistically significant.

At 4 months, a smaller proportion of patients in the mindfulness-based cognitive therapy group had a MIDAS score of 21 or greater, but the difference between groups was not statistically significant. The data indicate a large effect that the study was underpowered to detect, Dr. Seng said.

A planned subgroup analysis found that mindfulness-based cognitive therapy produced changes in disability that were greater in patients with episodic migraine, compared with patients with chronic migraine. A reduction in MIDAS scores was statistically significant among patients with episodic migraine.

During the trial, one patient experienced increased headache frequency and intensity and changed their preventive treatment regimen, which investigators considered unrelated to mindfulness-based cognitive therapy. In addition, one patient experienced flooding – a vivid recollection of a traumatic event – which is an expected effect of meditation and relaxation therapy, Dr. Seng said. The patient completed the study and was satisfied with the mindfulness-based cognitive therapy training, she said.

“Preliminary evidence suggests that mindfulness-based cognitive therapy could be recommended to reduce headache-related disability in people with episodic migraine or people who have some kind of effective prevention on board, but they are still experiencing high levels of disability,” Dr. Seng said.

Although flooding may occur in patients with a trauma history who use meditation and relaxation, the techniques still may be useful, Dr. Seng said. “In the VA setting, we use meditation and relaxation all the time. But it helps to forewarn patients that they might experience distressful flooding and [to provide] techniques that they can use to reduce the impact of that.”

[email protected]

Among patients with osteoporosis who have diminished long-term response to bisphosphonate therapy, the addition of eldecalcitol may reduce bone turnover markers and increase bone mineral density, according a study in Osteoporosis and Sarcopenia.

Bisphosphonates may increase bone mineral density, but their efficacy “can diminish over longer treatment periods, and bone mineral density plateaus and even decreases have been encountered regardless of the bisphosphonate usage,” said lead study author Mikio Kamimura, MD, PhD, a researcher at the Kamimura Orthopedic Clinic’s Center of Osteoporosis and Spinal Disorders in Matsumoto, Japan, and colleagues.

Eldecalcitol is an active vitamin D₃ derivative approved in Japan for the treatment of osteoporosis. A prior study suggested that bisphosphonate therapy combined with eldecalcitol is more effective than bisphosphonate therapy combined with alfacalcidol, another vitamin D analog, for the treatment of osteoporosis (Tohoku J Exp Med. 2015 Dec;237[4]:339-43.). Investigators had not studied the additive effects of eldecalcitol in patients who are poor responders to long-term bisphosphonate therapy, however.

To examine this question, researchers in Japan conducted a prospective cohort study. Dr. Kamimura and colleagues analyzed data from 42 postmenopausal Japanese women with primary osteoporosis who were poor responders to bisphosphonates – that is, their low lumbar bone mineral density or bilateral total hip bone mineral density did not apparently increase with chronic bisphosphonate treatment over 2 years. The patients had an average age of about 73 years. They received bisphosphonate therapy with alendronate, risedronate, or minodronate. During the study, participants added daily oral eldecalcitol 0.75 mcg/day after breakfast.

The researchers measured markers of bone formation and bone resorption before bisphosphonate therapy, before adding eldecalcitol, and 4 months after starting eldecalcitol. They also assessed measures of bone mineral density.

Serum bone alkaline phosphatase, a bone formation marker, and urinary N-terminal telopeptide of type I collagen, a bone resorption marker, significantly decreased with bisphosphonate therapy. Added eldecalcitol decreased both bone turnover markers further.

Average low lumbar bone mineral density increase rate was 0.2% from 2 to 1 years before eldecalcitol administration, −0.7% during the year before eldecalcitol administration, and 2.9% during 1 year of eldecalcitol therapy. Similarly, mean increase rates of bilateral total hip bone mineral density were 0.2%, −0.7%, and 1.2%, respectively. Mean femoral neck bone mineral density increase rate was 1.1% after eldecalcitol administration, whereas the cohort had no gains with bisphosphonate therapy alone.

In osteoporotic patients exhibiting a poor response to long-term bisphosphonate therapy, the addition of eldecalcitol may represent “a good treatment option,” the authors concluded.

The small sample size, short follow-up period, and lack of evaluation of fracture prevention are limitations of the study, and further studies are needed to confirm these results, the researchers acknowledged.

The authors reported no relevant conflicts of interest.
[email protected]

SOURCE: Kamimura M et al. Osteoporos Sarcopenia. 2019 Jun 28. doi: 10.1016/j.afos.2019.06.001.

Among patients with osteoporosis who have diminished long-term response to bisphosphonate therapy, the addition of eldecalcitol may reduce bone turnover markers and increase bone mineral density, according a study in Osteoporosis and Sarcopenia.

Bisphosphonates may increase bone mineral density, but their efficacy “can diminish over longer treatment periods, and bone mineral density plateaus and even decreases have been encountered regardless of the bisphosphonate usage,” said lead study author Mikio Kamimura, MD, PhD, a researcher at the Kamimura Orthopedic Clinic’s Center of Osteoporosis and Spinal Disorders in Matsumoto, Japan, and colleagues.

Eldecalcitol is an active vitamin D₃ derivative approved in Japan for the treatment of osteoporosis. A prior study suggested that bisphosphonate therapy combined with eldecalcitol is more effective than bisphosphonate therapy combined with alfacalcidol, another vitamin D analog, for the treatment of osteoporosis (Tohoku J Exp Med. 2015 Dec;237[4]:339-43.). Investigators had not studied the additive effects of eldecalcitol in patients who are poor responders to long-term bisphosphonate therapy, however.

To examine this question, researchers in Japan conducted a prospective cohort study. Dr. Kamimura and colleagues analyzed data from 42 postmenopausal Japanese women with primary osteoporosis who were poor responders to bisphosphonates – that is, their low lumbar bone mineral density or bilateral total hip bone mineral density did not apparently increase with chronic bisphosphonate treatment over 2 years. The patients had an average age of about 73 years. They received bisphosphonate therapy with alendronate, risedronate, or minodronate. During the study, participants added daily oral eldecalcitol 0.75 mcg/day after breakfast.

The researchers measured markers of bone formation and bone resorption before bisphosphonate therapy, before adding eldecalcitol, and 4 months after starting eldecalcitol. They also assessed measures of bone mineral density.

Serum bone alkaline phosphatase, a bone formation marker, and urinary N-terminal telopeptide of type I collagen, a bone resorption marker, significantly decreased with bisphosphonate therapy. Added eldecalcitol decreased both bone turnover markers further.

Average low lumbar bone mineral density increase rate was 0.2% from 2 to 1 years before eldecalcitol administration, −0.7% during the year before eldecalcitol administration, and 2.9% during 1 year of eldecalcitol therapy. Similarly, mean increase rates of bilateral total hip bone mineral density were 0.2%, −0.7%, and 1.2%, respectively. Mean femoral neck bone mineral density increase rate was 1.1% after eldecalcitol administration, whereas the cohort had no gains with bisphosphonate therapy alone.

In osteoporotic patients exhibiting a poor response to long-term bisphosphonate therapy, the addition of eldecalcitol may represent “a good treatment option,” the authors concluded.

The small sample size, short follow-up period, and lack of evaluation of fracture prevention are limitations of the study, and further studies are needed to confirm these results, the researchers acknowledged.

The authors reported no relevant conflicts of interest.
[email protected]

SOURCE: Kamimura M et al. Osteoporos Sarcopenia. 2019 Jun 28. doi: 10.1016/j.afos.2019.06.001.

Among patients with osteoporosis who have diminished long-term response to bisphosphonate therapy, the addition of eldecalcitol may reduce bone turnover markers and increase bone mineral density, according a study in Osteoporosis and Sarcopenia.

Bisphosphonates may increase bone mineral density, but their efficacy “can diminish over longer treatment periods, and bone mineral density plateaus and even decreases have been encountered regardless of the bisphosphonate usage,” said lead study author Mikio Kamimura, MD, PhD, a researcher at the Kamimura Orthopedic Clinic’s Center of Osteoporosis and Spinal Disorders in Matsumoto, Japan, and colleagues.

Eldecalcitol is an active vitamin D₃ derivative approved in Japan for the treatment of osteoporosis. A prior study suggested that bisphosphonate therapy combined with eldecalcitol is more effective than bisphosphonate therapy combined with alfacalcidol, another vitamin D analog, for the treatment of osteoporosis (Tohoku J Exp Med. 2015 Dec;237[4]:339-43.). Investigators had not studied the additive effects of eldecalcitol in patients who are poor responders to long-term bisphosphonate therapy, however.

To examine this question, researchers in Japan conducted a prospective cohort study. Dr. Kamimura and colleagues analyzed data from 42 postmenopausal Japanese women with primary osteoporosis who were poor responders to bisphosphonates – that is, their low lumbar bone mineral density or bilateral total hip bone mineral density did not apparently increase with chronic bisphosphonate treatment over 2 years. The patients had an average age of about 73 years. They received bisphosphonate therapy with alendronate, risedronate, or minodronate. During the study, participants added daily oral eldecalcitol 0.75 mcg/day after breakfast.

The researchers measured markers of bone formation and bone resorption before bisphosphonate therapy, before adding eldecalcitol, and 4 months after starting eldecalcitol. They also assessed measures of bone mineral density.

Serum bone alkaline phosphatase, a bone formation marker, and urinary N-terminal telopeptide of type I collagen, a bone resorption marker, significantly decreased with bisphosphonate therapy. Added eldecalcitol decreased both bone turnover markers further.

Average low lumbar bone mineral density increase rate was 0.2% from 2 to 1 years before eldecalcitol administration, −0.7% during the year before eldecalcitol administration, and 2.9% during 1 year of eldecalcitol therapy. Similarly, mean increase rates of bilateral total hip bone mineral density were 0.2%, −0.7%, and 1.2%, respectively. Mean femoral neck bone mineral density increase rate was 1.1% after eldecalcitol administration, whereas the cohort had no gains with bisphosphonate therapy alone.

In osteoporotic patients exhibiting a poor response to long-term bisphosphonate therapy, the addition of eldecalcitol may represent “a good treatment option,” the authors concluded.

The small sample size, short follow-up period, and lack of evaluation of fracture prevention are limitations of the study, and further studies are needed to confirm these results, the researchers acknowledged.

The authors reported no relevant conflicts of interest.
[email protected]

SOURCE: Kamimura M et al. Osteoporos Sarcopenia. 2019 Jun 28. doi: 10.1016/j.afos.2019.06.001.

PHILADELPHIA – Mothers with migraine are more likely to have babies with colic, according to research presented at the annual meeting of the American Headache Society. Fathers with migraine are not more likely to have children with colic, however. These findings may have implications for the care of mothers with migraine and their children, said Amy Gelfand, MD, associate professor of neurology at the University of California, San Francisco.

Smaller studies have suggested associations between migraine and colic. To examine this relationship in a large, national sample, Dr. Gelfand and her research colleagues conducted a cross-sectional survey of biological parents of 4- to 8-week-olds in the United States. The researchers analyzed data from 1,419 participants – 827 mothers and 592 fathers – who completed online surveys in 2017 and 2018.

Parents provided information about their and their infants’ health. The investigators identified migraineurs using modified International Classification of Headache Disorders 3rd edition criteria and determined infant colic by response to the question, “Has your baby cried for at least 3 hours on at least 3 days in the last week?”

In all, 33.5% of the mothers had migraine or probable migraine, and 20.8% of the fathers had migraine or probable migraine. Maternal migraine was associated with increased odds of infant colic (odds ratio, 1.7). Among mothers with migraine and headache frequency of 15 or more days per month, the likelihood of having an infant with colic was even greater (OR, 2.5).

“The cause of colic is unknown, yet colic is common, and these frequent bouts of intense crying or fussiness can be particularly frustrating for parents, creating family stress and anxiety,” Dr. Gelfand said in a news release. “New moms who are armed with knowledge of the connection between their own history of migraine and infant colic can be better prepared for these often difficult first months of a baby and new mother’s journey.”

[email protected]

PHILADELPHIA – Mothers with migraine are more likely to have babies with colic, according to research presented at the annual meeting of the American Headache Society. Fathers with migraine are not more likely to have children with colic, however. These findings may have implications for the care of mothers with migraine and their children, said Amy Gelfand, MD, associate professor of neurology at the University of California, San Francisco.

Smaller studies have suggested associations between migraine and colic. To examine this relationship in a large, national sample, Dr. Gelfand and her research colleagues conducted a cross-sectional survey of biological parents of 4- to 8-week-olds in the United States. The researchers analyzed data from 1,419 participants – 827 mothers and 592 fathers – who completed online surveys in 2017 and 2018.

Parents provided information about their and their infants’ health. The investigators identified migraineurs using modified International Classification of Headache Disorders 3rd edition criteria and determined infant colic by response to the question, “Has your baby cried for at least 3 hours on at least 3 days in the last week?”

In all, 33.5% of the mothers had migraine or probable migraine, and 20.8% of the fathers had migraine or probable migraine. Maternal migraine was associated with increased odds of infant colic (odds ratio, 1.7). Among mothers with migraine and headache frequency of 15 or more days per month, the likelihood of having an infant with colic was even greater (OR, 2.5).

“The cause of colic is unknown, yet colic is common, and these frequent bouts of intense crying or fussiness can be particularly frustrating for parents, creating family stress and anxiety,” Dr. Gelfand said in a news release. “New moms who are armed with knowledge of the connection between their own history of migraine and infant colic can be better prepared for these often difficult first months of a baby and new mother’s journey.”

[email protected]

PHILADELPHIA – Mothers with migraine are more likely to have babies with colic, according to research presented at the annual meeting of the American Headache Society. Fathers with migraine are not more likely to have children with colic, however. These findings may have implications for the care of mothers with migraine and their children, said Amy Gelfand, MD, associate professor of neurology at the University of California, San Francisco.

Smaller studies have suggested associations between migraine and colic. To examine this relationship in a large, national sample, Dr. Gelfand and her research colleagues conducted a cross-sectional survey of biological parents of 4- to 8-week-olds in the United States. The researchers analyzed data from 1,419 participants – 827 mothers and 592 fathers – who completed online surveys in 2017 and 2018.

Parents provided information about their and their infants’ health. The investigators identified migraineurs using modified International Classification of Headache Disorders 3rd edition criteria and determined infant colic by response to the question, “Has your baby cried for at least 3 hours on at least 3 days in the last week?”

In all, 33.5% of the mothers had migraine or probable migraine, and 20.8% of the fathers had migraine or probable migraine. Maternal migraine was associated with increased odds of infant colic (odds ratio, 1.7). Among mothers with migraine and headache frequency of 15 or more days per month, the likelihood of having an infant with colic was even greater (OR, 2.5).

“The cause of colic is unknown, yet colic is common, and these frequent bouts of intense crying or fussiness can be particularly frustrating for parents, creating family stress and anxiety,” Dr. Gelfand said in a news release. “New moms who are armed with knowledge of the connection between their own history of migraine and infant colic can be better prepared for these often difficult first months of a baby and new mother’s journey.”

[email protected]

Serum biomarkers of inflammation may help identify which athletes will take longer to recover after a sport-related concussion, research suggests. Levels of interleukin-6 (IL-6) and IL-1 receptor antagonist (IL-1RA) are significantly elevated 6 hours after concussion, and higher IL-6 levels are associated with slower recovery, according to a study of 41 high school and college football players with concussion. The findings were published online ahead of print July 3 in Neurology.

“With so many people sustaining concussions and a sizeable number of them having prolonged symptoms and recovery, any tools we can develop to help determine who would be at greater risk of problems would be very beneficial,” said study author Timothy B. Meier, PhD, assistant professor of neurosurgery at the Medical College of Wisconsin in Milwaukee, in a news release. “These results are a crucial first step.”

Symptoms of sport-related concussion typically resolve within 1-2 weeks but may last longer. Although prior studies have focused on biomarkers that are specific to brain injury, nonspecific inflammatory markers also may hold promise in predicting recovery after a mild traumatic brain injury, the authors said.

To examine whether acute elevations in serum inflammatory markers predict symptom recovery following sport-related concussion, Dr. Meier and his research colleagues enrolled 857 high school and college football players into a prospective cohort study. They included in their analyses 41 concussed athletes and 43 matched control athletes with an average age of 18 years. None of the concussed athletes lost consciousness, two had posttraumatic amnesia, and one had retrograde amnesia. The concussed athletes had a mean symptom duration of 8.86 days.

The researchers measured serum levels of IL-6, IL-1RA, IL-1 beta, IL-10, tumor necrosis factor, C-reactive protein, and interferon-gamma and recorded Sport Concussion Assessment Tool, 3rd edition, symptom severity scores.

Participants with concussion underwent testing at the start of the season, within 6 hours of injury, 24-48 hours after injury, and at 8, 15, and 45 days after injury. Control athletes underwent testing at similar times.

Among athletes with concussion, IL-1RA and IL-6 were elevated at 6 hours, compared with all other postinjury visits and with controls. IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion with an area under the receiver operating characteristic curve of 0.79 for IL-6 and 0.79 for IL-1RA. Furthermore, IL-6 levels at 6 hours significantly correlated with symptom duration, “with a 1-unit increase in natural log-transformed IL-6 associated with 39% lower hazard of symptom recovery,” the researchers reported.

The extent to which these results generalize to females, youth athletes, or athletes who develop postconcussion syndrome is unclear, and larger studies may be needed to adequately assess inflammatory markers as clinical biomarkers of sport-related concussion, the authors noted.

“Eventually, these results may help us better understand the relationship between injury and inflammation and potentially lead to new treatments,” Dr. Meier said.

The research was supported by the U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, National Institute of Mental Health, and the National Center for Advancing Translational Sciences. The authors had no relevant disclosures.

[email protected]

SOURCE: Nitta ME et al. Neurology. 2019 Jul 3. doi: 10.1212/WNL.0000000000007864.

Serum biomarkers of inflammation may help identify which athletes will take longer to recover after a sport-related concussion, research suggests. Levels of interleukin-6 (IL-6) and IL-1 receptor antagonist (IL-1RA) are significantly elevated 6 hours after concussion, and higher IL-6 levels are associated with slower recovery, according to a study of 41 high school and college football players with concussion. The findings were published online ahead of print July 3 in Neurology.

“With so many people sustaining concussions and a sizeable number of them having prolonged symptoms and recovery, any tools we can develop to help determine who would be at greater risk of problems would be very beneficial,” said study author Timothy B. Meier, PhD, assistant professor of neurosurgery at the Medical College of Wisconsin in Milwaukee, in a news release. “These results are a crucial first step.”

Symptoms of sport-related concussion typically resolve within 1-2 weeks but may last longer. Although prior studies have focused on biomarkers that are specific to brain injury, nonspecific inflammatory markers also may hold promise in predicting recovery after a mild traumatic brain injury, the authors said.

To examine whether acute elevations in serum inflammatory markers predict symptom recovery following sport-related concussion, Dr. Meier and his research colleagues enrolled 857 high school and college football players into a prospective cohort study. They included in their analyses 41 concussed athletes and 43 matched control athletes with an average age of 18 years. None of the concussed athletes lost consciousness, two had posttraumatic amnesia, and one had retrograde amnesia. The concussed athletes had a mean symptom duration of 8.86 days.

The researchers measured serum levels of IL-6, IL-1RA, IL-1 beta, IL-10, tumor necrosis factor, C-reactive protein, and interferon-gamma and recorded Sport Concussion Assessment Tool, 3rd edition, symptom severity scores.

Participants with concussion underwent testing at the start of the season, within 6 hours of injury, 24-48 hours after injury, and at 8, 15, and 45 days after injury. Control athletes underwent testing at similar times.

Among athletes with concussion, IL-1RA and IL-6 were elevated at 6 hours, compared with all other postinjury visits and with controls. IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion with an area under the receiver operating characteristic curve of 0.79 for IL-6 and 0.79 for IL-1RA. Furthermore, IL-6 levels at 6 hours significantly correlated with symptom duration, “with a 1-unit increase in natural log-transformed IL-6 associated with 39% lower hazard of symptom recovery,” the researchers reported.

The extent to which these results generalize to females, youth athletes, or athletes who develop postconcussion syndrome is unclear, and larger studies may be needed to adequately assess inflammatory markers as clinical biomarkers of sport-related concussion, the authors noted.

“Eventually, these results may help us better understand the relationship between injury and inflammation and potentially lead to new treatments,” Dr. Meier said.

The research was supported by the U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, National Institute of Mental Health, and the National Center for Advancing Translational Sciences. The authors had no relevant disclosures.

[email protected]

SOURCE: Nitta ME et al. Neurology. 2019 Jul 3. doi: 10.1212/WNL.0000000000007864.

Serum biomarkers of inflammation may help identify which athletes will take longer to recover after a sport-related concussion, research suggests. Levels of interleukin-6 (IL-6) and IL-1 receptor antagonist (IL-1RA) are significantly elevated 6 hours after concussion, and higher IL-6 levels are associated with slower recovery, according to a study of 41 high school and college football players with concussion. The findings were published online ahead of print July 3 in Neurology.

“With so many people sustaining concussions and a sizeable number of them having prolonged symptoms and recovery, any tools we can develop to help determine who would be at greater risk of problems would be very beneficial,” said study author Timothy B. Meier, PhD, assistant professor of neurosurgery at the Medical College of Wisconsin in Milwaukee, in a news release. “These results are a crucial first step.”

Symptoms of sport-related concussion typically resolve within 1-2 weeks but may last longer. Although prior studies have focused on biomarkers that are specific to brain injury, nonspecific inflammatory markers also may hold promise in predicting recovery after a mild traumatic brain injury, the authors said.

To examine whether acute elevations in serum inflammatory markers predict symptom recovery following sport-related concussion, Dr. Meier and his research colleagues enrolled 857 high school and college football players into a prospective cohort study. They included in their analyses 41 concussed athletes and 43 matched control athletes with an average age of 18 years. None of the concussed athletes lost consciousness, two had posttraumatic amnesia, and one had retrograde amnesia. The concussed athletes had a mean symptom duration of 8.86 days.

The researchers measured serum levels of IL-6, IL-1RA, IL-1 beta, IL-10, tumor necrosis factor, C-reactive protein, and interferon-gamma and recorded Sport Concussion Assessment Tool, 3rd edition, symptom severity scores.

Participants with concussion underwent testing at the start of the season, within 6 hours of injury, 24-48 hours after injury, and at 8, 15, and 45 days after injury. Control athletes underwent testing at similar times.

Among athletes with concussion, IL-1RA and IL-6 were elevated at 6 hours, compared with all other postinjury visits and with controls. IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours postconcussion with an area under the receiver operating characteristic curve of 0.79 for IL-6 and 0.79 for IL-1RA. Furthermore, IL-6 levels at 6 hours significantly correlated with symptom duration, “with a 1-unit increase in natural log-transformed IL-6 associated with 39% lower hazard of symptom recovery,” the researchers reported.

The extent to which these results generalize to females, youth athletes, or athletes who develop postconcussion syndrome is unclear, and larger studies may be needed to adequately assess inflammatory markers as clinical biomarkers of sport-related concussion, the authors noted.

“Eventually, these results may help us better understand the relationship between injury and inflammation and potentially lead to new treatments,” Dr. Meier said.

The research was supported by the U.S. Department of Defense, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, National Institute of Mental Health, and the National Center for Advancing Translational Sciences. The authors had no relevant disclosures.

[email protected]

SOURCE: Nitta ME et al. Neurology. 2019 Jul 3. doi: 10.1212/WNL.0000000000007864.

SEATTLE – Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years, according to an interim analysis of phase 4 study data.

A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”

The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.

Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.

In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.

“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
 

The FLUENT study

Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.

Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.

Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.

The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.

FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
 

Immune cell subsets

In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.

CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”

Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.

“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
 

A measure of CNS injury

In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.

Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.

The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.

Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
 

Adverse events

No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.

Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).

Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

[email protected]

SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.

SEATTLE – Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years, according to an interim analysis of phase 4 study data.

A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”

The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.

Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.

In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.

“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
 

The FLUENT study

Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.

Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.

Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.

The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.

FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
 

Immune cell subsets

In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.

CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”

Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.

“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
 

A measure of CNS injury

In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.

Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.

The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.

Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
 

Adverse events

No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.

Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).

Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

[email protected]

SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.

SEATTLE – Neutrophil levels may decline in patients with relapsing multiple sclerosis (MS) who have been on fingolimod for 2 or more years, according to an interim analysis of phase 4 study data.

A decrease in neutrophils over 6 months in a cohort of fingolimod treatment–experienced patients “was a surprise, at least to me,” said study investigator Bruce Cree, MD, PhD, professor of neurology at UCSF Weill Institute for Neurosciences, University of California, San Francisco. Why levels of these innate immune cells decreased in patients who had been on the drug for years “remains to be understood,” Dr. Cree said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “This is something that deserves further investigation ... to understand if that neutrophil count will continue to drop down over time or whether it ultimately plateaus.”

The decline in neutrophils in this cohort of patients continuously treated for at least 2 years was “only about 9%,” from an average of 3,698.56 cells per microliter at study baseline to 3,336.13 cells per microliter at 6 months.

Among fingolimod-naive patients who initiated treatment during the study, neutrophils decreased from 4,058.48 cells per microliter at baseline to 3,475.09 cells per microliter at 6 months, about 14%.

In the treatment-experienced patients, other immune cell subsets remained relatively stable over the 6-month period.

“If we are trying to understand the impact of fingolimod ultimately on propensity for development of opportunistic infection, of course we are focused almost exclusively on adaptive immunity,” Dr. Cree said. “But perhaps we are forgetting that innate immunity might be also extremely important for protecting ourselves against infection.”
 

The FLUENT study

Dr. Cree presented interim, 6-month data from the ongoing, open-label FLUENT study, which is a 12-month, prospective, multicenter, nonrandomized study to assess changes in the immune cell profiles of patients with relapsing MS who receive fingolimod. The study includes a cohort of treatment-experienced patients and a cohort of treatment-naive patients.

Fingolimod is a once-daily oral sphingosine 1–phosphate receptor modulator that prevents egress of lymphocytes from lymph nodes. Since its FDA approval in 2010, rare opportunistic infections, including progressive multifocal leukoencephalopathy (PML), have been reported in patients taking fingolimod.

Investigators did not assess changes in innate and adaptive components of the immune system during fingolimod treatment in the pivotal clinical trials, and the relationship between anti-JCV antibody index and immune cell subsets during fingolimod treatment is not known. Immunologic profiling may help gauge patients’ treatment response and risk of infection.

The FLUENT study’s primary outcome is change from baseline to month 6 in peripheral blood cellular components of the innate and adaptive immune system. Secondary endpoints include change in the immune cell subtype profile at months 3 and 12; anti-JCV antibody status at months 3, 6, and 12; change in anti-JCV antibody index at months 3, 6, and 12; and clinical variables. In addition, the investigators plan to examine changes in serum neurofilament light chain (NfL) levels at months 3, 6, and 12.

FLUENT includes a cohort of fingolimod-naive patients and a cohort of patients who have received continuous, commercially available fingolimod 0.5 mg/day for at least 2 years and plan to continue the drug during the 1-year study. The interim analysis included data from 166 fingolimod-naive patients (median age, 41 years; 77.7% female) and 216 fingolimod-experienced patients (median age, 50 years; 73.1% female). About 70% of patients in the fingolimod-naive cohort had had a relapse in the past 2 years, compared with about 22% of patients in the treatment-experienced cohort. Investigators began enrolling patients in September 2017.
 

Immune cell subsets

In the fingolimod-naive cohort, changes in immune cell subsets were expected and characteristic. Overall CD4+ count declined from baseline to month 6, and the decrease was “driven primarily by a decline in CD4+ naive T cells and CD4+ central memory T cells.” CD4+ effector memory cells, CD4+ Th1 cells, CD4+ Th2 cells, and CD4+ Th17 cells were less affected. “The effector cells do not have an expression of CCR7 [C-C chemokine receptor type 7] so they tend not to hone to the lymph nodes anyway,” Dr. Cree said.

CD8+ cells followed a similar pattern. “The overall count goes down, but perhaps not as much as with the CD4+ cells. The central memory and naive cells are affected a little bit more than the effector memory cells,” Dr. Cree said. “Then we see a comparable pattern with B cells. The absolute CD19+ counts go down. They’re driven by a decline in the naive cells. ... with less of a decline in memory cells and almost no decline in regulatory cells.”

Among innate immune cells, monocytes increased slightly, neutrophils declined, as expected, and natural killer cells declined slightly.

“When you turn your attention to ... those patients who have been on fingolimod, you do not see these changes for the lymphocytes,” Dr. Cree said. “Those lymphocytes are already sequestered, and we are really not seeing much of a change over time at all.”
 

A measure of CNS injury

In the treatment-naive cohort, serum neurofilament light chain (NfL) declined, but this measure did not change by much in the treatment-experienced cohort.

Among patients already on fingolimod, the serum NfL reduction “that would be anticipated as a therapeutic benefit from fingolimod is already being realized,” he said.

The serum NfL levels in the treatment-naive cohort at 6 months were similar to those of the treatment-experienced cohort at baseline, which indicates that “the impact of fingolimod in reducing circulating neurofilament – a marker of central nervous system injury – is seen within 6 months of treatment and likely persists as patients continue on fingolimod therapy,” Dr. Cree said.

Baseline anti-JCV antibody index was about the same for the treatment-naive and treatment-experienced cohorts (1.28 vs. 1.39, respectively), and this measure did not meaningfully change over 6 months in either cohort.
 

Adverse events

No new adverse events were identified in this interim analysis. Most common adverse events occurred more frequently in the treatment-naive cohort than in the treatment-experienced cohort, including headache (7.2% vs. 1.9%), upper respiratory tract infection (4.2% vs. 1.9%), pain in extremity (4.2% vs. 1.4%), lymphopenia (4.8% vs. 0.5%), anxiety (3.6% vs. 1.4%), fatigue (3.6% vs. 1.4%), nausea (3.0% vs. 0.9%), dizziness (3.0% vs. 0.5%), hypoesthesia (3.0% vs. 0.5%), and tremor (3.0% vs. 0%). An exception was falls, which occurred in 3.0% of the treatment-naive cohort and 4.6% of the treatment-experienced cohort.

Serious adverse events were about equal between the two groups (4.2% of the treatment-naive group and 5.1% of the treatment-experienced group), and adverse events leading to treatment discontinuation were more common in the fingolimod-naive cohort (10.2% vs. 5.6%).

Novartis funded the study, and four of the authors are Novartis employees. Dr. Cree disclosed consulting fees from Novartis and other pharmaceutical companies. His coauthors disclosed consulting fees, speaking fees, research support, and serving on advisory boards for pharmaceutical companies, including Novartis.

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SOURCE: Mao-Draayer Y et al. CMSC 2019. Abstract DXM03.