AAN Annual Meeting

PHILADELPHIA – Dalfampridine was shown to improve walking ability and balance in patients with progressive and relapsing-remitting multiple sclerosis, according to data presented at the annual meeting of the American Academy of Neurology.

For a more integrated assessment of dalfampridine’s effect on patients’ walking abilities over a longer period of time, Dr. Jan Lycke of the University of Gothenberg (Sweden) and his associates randomized 132 patients with MS and an Expanded Disability Status Scale score of 4-7 to 24 weeks of dalfampridine or placebo in the double-blind trial called MOBILE (Exploratory Study to Assess the Effect of Fampridine on Walking Ability and Balance in Patients With Multiple Sclerosis).

The study was conducted in Canada and European countries with prolonged-release fampridine (Fampyra), known as dalfampridine (Ampyra) in the United States. Dalfampridine was approved in the United States in 2010 as the first oral medication for MS based on its ability to improve walking speed, although it has since been associated with seizures in some patients in doses above the recommended 10 mg twice daily.

The 68 patients who took dalfampridine 10 mg twice daily and the 64 in the placebo group were assessed using the Multiple Sclerosis Walking Scale-12 (MSWS-12), the Multiple Sclerosis Impact Scale-29 (MSIS-29), the Timed Up and Go (TUG), and the Berg Balance Scale (BBS).

Nearly half of patients in the treatment arm (49% vs. 28.1% on placebo; P = .015) reached or exceeded the clinically meaningful threshold of at least an 8-point improvement on the MSWS-12, beginning in weeks 2-4 and then sustained throughout the study period, Dr. Lycke said.

"There was a median improvement change in the [TUG] measurement of at least 10%-15% [47.1% vs. 30.2% placebo; P = .026], which was sustained throughout the treatment period," he told the audience. A 15% or greater improvement of the TUG score was considered clinically meaningful. This cohort had similar improvement rates over baseline for BBS scores, he said.

Dalfampridine treatment led to greater median treatment differences from baseline to week 24, compared with placebo, on the MSWS-12 (–3.27; 95% confidence interval, –7.59-1.19), TUG speed (9.64%; 95% CI, 2.05%-16.48%), BBS score (1.50; 95% CI, 0.00-2.93), and MSIS-29 physical subscale (–3.30; 95% CI, –7.68-0.98). After treatment discontinuation at week 24, the measurements returned to baseline levels.

No seizures were recorded during the trial, Dr. Lycke said.

The trial was sponsored by Biogen Idec, which holds a licensing agreement with Acorda Therapeutics to market prolonged-released fampridine outside of the United States. Dr. Lycke had numerous disclosures, including Biogen Idec, Genzyme, Novartis, and Teva.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Dalfampridine was shown to improve walking ability and balance in patients with progressive and relapsing-remitting multiple sclerosis, according to data presented at the annual meeting of the American Academy of Neurology.

For a more integrated assessment of dalfampridine’s effect on patients’ walking abilities over a longer period of time, Dr. Jan Lycke of the University of Gothenberg (Sweden) and his associates randomized 132 patients with MS and an Expanded Disability Status Scale score of 4-7 to 24 weeks of dalfampridine or placebo in the double-blind trial called MOBILE (Exploratory Study to Assess the Effect of Fampridine on Walking Ability and Balance in Patients With Multiple Sclerosis).

The study was conducted in Canada and European countries with prolonged-release fampridine (Fampyra), known as dalfampridine (Ampyra) in the United States. Dalfampridine was approved in the United States in 2010 as the first oral medication for MS based on its ability to improve walking speed, although it has since been associated with seizures in some patients in doses above the recommended 10 mg twice daily.

The 68 patients who took dalfampridine 10 mg twice daily and the 64 in the placebo group were assessed using the Multiple Sclerosis Walking Scale-12 (MSWS-12), the Multiple Sclerosis Impact Scale-29 (MSIS-29), the Timed Up and Go (TUG), and the Berg Balance Scale (BBS).

Nearly half of patients in the treatment arm (49% vs. 28.1% on placebo; P = .015) reached or exceeded the clinically meaningful threshold of at least an 8-point improvement on the MSWS-12, beginning in weeks 2-4 and then sustained throughout the study period, Dr. Lycke said.

"There was a median improvement change in the [TUG] measurement of at least 10%-15% [47.1% vs. 30.2% placebo; P = .026], which was sustained throughout the treatment period," he told the audience. A 15% or greater improvement of the TUG score was considered clinically meaningful. This cohort had similar improvement rates over baseline for BBS scores, he said.

Dalfampridine treatment led to greater median treatment differences from baseline to week 24, compared with placebo, on the MSWS-12 (–3.27; 95% confidence interval, –7.59-1.19), TUG speed (9.64%; 95% CI, 2.05%-16.48%), BBS score (1.50; 95% CI, 0.00-2.93), and MSIS-29 physical subscale (–3.30; 95% CI, –7.68-0.98). After treatment discontinuation at week 24, the measurements returned to baseline levels.

No seizures were recorded during the trial, Dr. Lycke said.

The trial was sponsored by Biogen Idec, which holds a licensing agreement with Acorda Therapeutics to market prolonged-released fampridine outside of the United States. Dr. Lycke had numerous disclosures, including Biogen Idec, Genzyme, Novartis, and Teva.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Dalfampridine was shown to improve walking ability and balance in patients with progressive and relapsing-remitting multiple sclerosis, according to data presented at the annual meeting of the American Academy of Neurology.

For a more integrated assessment of dalfampridine’s effect on patients’ walking abilities over a longer period of time, Dr. Jan Lycke of the University of Gothenberg (Sweden) and his associates randomized 132 patients with MS and an Expanded Disability Status Scale score of 4-7 to 24 weeks of dalfampridine or placebo in the double-blind trial called MOBILE (Exploratory Study to Assess the Effect of Fampridine on Walking Ability and Balance in Patients With Multiple Sclerosis).

The study was conducted in Canada and European countries with prolonged-release fampridine (Fampyra), known as dalfampridine (Ampyra) in the United States. Dalfampridine was approved in the United States in 2010 as the first oral medication for MS based on its ability to improve walking speed, although it has since been associated with seizures in some patients in doses above the recommended 10 mg twice daily.

The 68 patients who took dalfampridine 10 mg twice daily and the 64 in the placebo group were assessed using the Multiple Sclerosis Walking Scale-12 (MSWS-12), the Multiple Sclerosis Impact Scale-29 (MSIS-29), the Timed Up and Go (TUG), and the Berg Balance Scale (BBS).

Nearly half of patients in the treatment arm (49% vs. 28.1% on placebo; P = .015) reached or exceeded the clinically meaningful threshold of at least an 8-point improvement on the MSWS-12, beginning in weeks 2-4 and then sustained throughout the study period, Dr. Lycke said.

"There was a median improvement change in the [TUG] measurement of at least 10%-15% [47.1% vs. 30.2% placebo; P = .026], which was sustained throughout the treatment period," he told the audience. A 15% or greater improvement of the TUG score was considered clinically meaningful. This cohort had similar improvement rates over baseline for BBS scores, he said.

Dalfampridine treatment led to greater median treatment differences from baseline to week 24, compared with placebo, on the MSWS-12 (–3.27; 95% confidence interval, –7.59-1.19), TUG speed (9.64%; 95% CI, 2.05%-16.48%), BBS score (1.50; 95% CI, 0.00-2.93), and MSIS-29 physical subscale (–3.30; 95% CI, –7.68-0.98). After treatment discontinuation at week 24, the measurements returned to baseline levels.

No seizures were recorded during the trial, Dr. Lycke said.

The trial was sponsored by Biogen Idec, which holds a licensing agreement with Acorda Therapeutics to market prolonged-released fampridine outside of the United States. Dr. Lycke had numerous disclosures, including Biogen Idec, Genzyme, Novartis, and Teva.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – A proposed revision of the neuromyelitis optica diagnostic criteria takes into account newly appreciated variations in how the disease can present clinically.

If adopted, the new criteria would offer diagnostic pathways for patients who have symptoms, but who might or might not have the serum antibodies usually associated with the disorder, Dr. Dean Wingerchuk said at the annual meeting of the American Academy of Neurology.

They reflect the current understanding of neuromyelitis optica as a spectrum of clinical symptoms, said Dr. Wingerchuk, professor of neurology at the Mayo Clinic, Scottsdale, Ariz. Neuromyelitis optica spectrum disorder (NMOSD) was identified in 2007 – 1 year after the existing diagnostic criteria were published.

In the new guidelines, "we wanted to encompass all patients who would have previously been diagnosed as having neuromyelitis optica or NMOSD," he said. A new stratification of antibody positive or antibody negative reflects the fact that not all patients are seropositive at presentation, particularly early in the disease course; that antibody testing is not available or reliable everywhere; and that as-yet-unidentified antibodies might be implicated in the disorder.

The workgroup that authored the document consisted of 18 members from nine countries. It began its work in 2011. The proposed criteria still need to be prospectively validated before they could be widely adopted, noted Dr. Wingerchuk, who was a primary author of the 2006 criteria.

The existing criteria require the presence of transverse myelitis, optic neuritis, and at least two of the following:

• Brain MRI imaging findings that are nondiagnostic for multiple sclerosis.

• A spinal cord lesion extending over three or more vertebral segments.

• Seropositivity for NMO-IgG.

The newly proposed criteria have been expanded to include six different core characteristics: optic neuritis; acute myelitis; area postrema syndrome (nausea, vomiting, and hiccups); other brain stem syndromes; symptomatic narcolepsy or acute diencephalic syndrome with MRI findings; and symptomatic cerebral syndrome with MRI findings.

Antibody-positive patients need to show at least one of these core characteristics, with no other better explanation for their symptoms.

The bar is a little higher for antibody-negative patients. They need to show at least two of the core characteristics, meeting the following requirements:

• At least one of the core symptoms must be optic neuritis, myelitis, or area postrema syndrome.

• The core characteristics must be disseminated in space.

• MRI findings must distinguish NMOSD from multiple sclerosis or other demyelinating disorders.

Prospective validation will require follow-up of patients who are seropositive at diagnosis but present with less common syndromes, and detailed descriptions of seronegative groups to determine whether they eventually convert to a clinical NMOSD, Dr. Wingerchuk said.

The project is being funded by the Guthy-Jackson Charitable Foundation. Dr. Wingerchuk disclosed that he has received financial compensation on an adjudication committee for an NMO trial that was sponsored by MedImmune.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – A proposed revision of the neuromyelitis optica diagnostic criteria takes into account newly appreciated variations in how the disease can present clinically.

If adopted, the new criteria would offer diagnostic pathways for patients who have symptoms, but who might or might not have the serum antibodies usually associated with the disorder, Dr. Dean Wingerchuk said at the annual meeting of the American Academy of Neurology.

They reflect the current understanding of neuromyelitis optica as a spectrum of clinical symptoms, said Dr. Wingerchuk, professor of neurology at the Mayo Clinic, Scottsdale, Ariz. Neuromyelitis optica spectrum disorder (NMOSD) was identified in 2007 – 1 year after the existing diagnostic criteria were published.

In the new guidelines, "we wanted to encompass all patients who would have previously been diagnosed as having neuromyelitis optica or NMOSD," he said. A new stratification of antibody positive or antibody negative reflects the fact that not all patients are seropositive at presentation, particularly early in the disease course; that antibody testing is not available or reliable everywhere; and that as-yet-unidentified antibodies might be implicated in the disorder.

The workgroup that authored the document consisted of 18 members from nine countries. It began its work in 2011. The proposed criteria still need to be prospectively validated before they could be widely adopted, noted Dr. Wingerchuk, who was a primary author of the 2006 criteria.

The existing criteria require the presence of transverse myelitis, optic neuritis, and at least two of the following:

• Brain MRI imaging findings that are nondiagnostic for multiple sclerosis.

• A spinal cord lesion extending over three or more vertebral segments.

• Seropositivity for NMO-IgG.

The newly proposed criteria have been expanded to include six different core characteristics: optic neuritis; acute myelitis; area postrema syndrome (nausea, vomiting, and hiccups); other brain stem syndromes; symptomatic narcolepsy or acute diencephalic syndrome with MRI findings; and symptomatic cerebral syndrome with MRI findings.

Antibody-positive patients need to show at least one of these core characteristics, with no other better explanation for their symptoms.

The bar is a little higher for antibody-negative patients. They need to show at least two of the core characteristics, meeting the following requirements:

• At least one of the core symptoms must be optic neuritis, myelitis, or area postrema syndrome.

• The core characteristics must be disseminated in space.

• MRI findings must distinguish NMOSD from multiple sclerosis or other demyelinating disorders.

Prospective validation will require follow-up of patients who are seropositive at diagnosis but present with less common syndromes, and detailed descriptions of seronegative groups to determine whether they eventually convert to a clinical NMOSD, Dr. Wingerchuk said.

The project is being funded by the Guthy-Jackson Charitable Foundation. Dr. Wingerchuk disclosed that he has received financial compensation on an adjudication committee for an NMO trial that was sponsored by MedImmune.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – A proposed revision of the neuromyelitis optica diagnostic criteria takes into account newly appreciated variations in how the disease can present clinically.

If adopted, the new criteria would offer diagnostic pathways for patients who have symptoms, but who might or might not have the serum antibodies usually associated with the disorder, Dr. Dean Wingerchuk said at the annual meeting of the American Academy of Neurology.

They reflect the current understanding of neuromyelitis optica as a spectrum of clinical symptoms, said Dr. Wingerchuk, professor of neurology at the Mayo Clinic, Scottsdale, Ariz. Neuromyelitis optica spectrum disorder (NMOSD) was identified in 2007 – 1 year after the existing diagnostic criteria were published.

In the new guidelines, "we wanted to encompass all patients who would have previously been diagnosed as having neuromyelitis optica or NMOSD," he said. A new stratification of antibody positive or antibody negative reflects the fact that not all patients are seropositive at presentation, particularly early in the disease course; that antibody testing is not available or reliable everywhere; and that as-yet-unidentified antibodies might be implicated in the disorder.

The workgroup that authored the document consisted of 18 members from nine countries. It began its work in 2011. The proposed criteria still need to be prospectively validated before they could be widely adopted, noted Dr. Wingerchuk, who was a primary author of the 2006 criteria.

The existing criteria require the presence of transverse myelitis, optic neuritis, and at least two of the following:

• Brain MRI imaging findings that are nondiagnostic for multiple sclerosis.

• A spinal cord lesion extending over three or more vertebral segments.

• Seropositivity for NMO-IgG.

The newly proposed criteria have been expanded to include six different core characteristics: optic neuritis; acute myelitis; area postrema syndrome (nausea, vomiting, and hiccups); other brain stem syndromes; symptomatic narcolepsy or acute diencephalic syndrome with MRI findings; and symptomatic cerebral syndrome with MRI findings.

Antibody-positive patients need to show at least one of these core characteristics, with no other better explanation for their symptoms.

The bar is a little higher for antibody-negative patients. They need to show at least two of the core characteristics, meeting the following requirements:

• At least one of the core symptoms must be optic neuritis, myelitis, or area postrema syndrome.

• The core characteristics must be disseminated in space.

• MRI findings must distinguish NMOSD from multiple sclerosis or other demyelinating disorders.

Prospective validation will require follow-up of patients who are seropositive at diagnosis but present with less common syndromes, and detailed descriptions of seronegative groups to determine whether they eventually convert to a clinical NMOSD, Dr. Wingerchuk said.

The project is being funded by the Guthy-Jackson Charitable Foundation. Dr. Wingerchuk disclosed that he has received financial compensation on an adjudication committee for an NMO trial that was sponsored by MedImmune.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – Correctly identifying the onset of multiple sclerosis in childhood and adolescence can pose a difficult diagnostic challenge, but predictive factors including older age, female gender, and the presence of persistent lesions on MRI are more likely to point to a first attack of MS.

In an interview at the annual meeting of the American Academy of Neurology, Dr. Brenda Banwell of the University of Pennsylvania, Philadelphia, talked with Dr. Timothy Vartanian of New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, about the diagnostic keys to differentiating monophasic illnesses such as acute disseminated encephalomyelitis from the onset of multiple sclerosis.

PHILADELPHIA – Correctly identifying the onset of multiple sclerosis in childhood and adolescence can pose a difficult diagnostic challenge, but predictive factors including older age, female gender, and the presence of persistent lesions on MRI are more likely to point to a first attack of MS.

In an interview at the annual meeting of the American Academy of Neurology, Dr. Brenda Banwell of the University of Pennsylvania, Philadelphia, talked with Dr. Timothy Vartanian of New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, about the diagnostic keys to differentiating monophasic illnesses such as acute disseminated encephalomyelitis from the onset of multiple sclerosis.

PHILADELPHIA – Correctly identifying the onset of multiple sclerosis in childhood and adolescence can pose a difficult diagnostic challenge, but predictive factors including older age, female gender, and the presence of persistent lesions on MRI are more likely to point to a first attack of MS.

In an interview at the annual meeting of the American Academy of Neurology, Dr. Brenda Banwell of the University of Pennsylvania, Philadelphia, talked with Dr. Timothy Vartanian of New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, about the diagnostic keys to differentiating monophasic illnesses such as acute disseminated encephalomyelitis from the onset of multiple sclerosis.

PHILADELPHIA – An orexin receptor antagonist – the first drug to affect a neural system that promotes wakefulness – has proven safe and effective for up to 1 year in a pooled analysis of three phase III studies of patients with insomnia.

The drug (suvorexant) significantly improved both subjective and objective measures of sleep, including sleep onset, total sleep time, and wakefulness after sleep, Dr. W. Joseph Herring said at the annual meeting of the American Academy of Neurology.

Based on these data, the manufacturer, Merck, proceeded last year to preliminary talks with the Food and Drug Administration. The committee considering suvorexant recommended that Merck focus on the smaller of two proposed dose ranges – 20 mg for people up to 64 years of age, and 15 mg for those aged 65 years and older.

Although the proposed higher doses of 40 mg for younger patients and 30 mg for older patients, were deemed safe and effective, the lower dose recommendation by the FDA is consistent with its "usual recommendations to go with lower doses of sleep medications," said Dr. Herring, Merck’s executive director of neuroscience clinical research. "So this 15/20-mg regimen is the most likely to be clinically relevant to prescribers."

The orexin neural system was discovered in the late 1990s, Dr. Herring noted. Orexin neurons release two neuropeptides that interact with downstream receptors that promote wakefulness. Secretion follows a circadian rhythm. Suvorexant orexin antagonists block the activity of this wake-signaling system, allowing sleep to occur.

So far, studies have investigated the drug in almost 3,000 patients; 160 of these were treated for at least a year. The three phase III trials comprised more than 275,000 exposure nights. Most of the patients were women; 46% of the patients were aged 65 years or older.

Sleep was measured by subjective assessment and objective scales, including polysomnography.

In the two efficacy studies, the higher doses decreased time to persistent sleep by 15 minutes on the first night; the lower doses did so by 10 minutes. By 3 months, the high-dose group’s decreased time to persistent sleep was 5 minutes; the low dose group’s time was lowered to 4 minutes.

On the first night, the high-dose drug reduced wakefulness after sleep by 40 minutes; the low-dose drug did so by 35 minutes. After 3 months, the reductions were similar (about 25 minutes).

When the night was divided into thirds, both doses decreased wakefulness significantly and about equally, especially in the second and third fractions of the night.

In the subgroup of 160 patients who were treated for at least 12 months, the drugs showed persistent efficacy overall, although the high doses were somewhat more effective, Dr. Herring said.

A multivariate regression analysis found that, compared with placebo, patients who took the high dose were 2.4 times more likely to be considered responders at 1 month and 1.8 times more likely to be responders at 3 months. Those who took the low dose were 1.8 times more likely to respond at 1 and 3 months.

"The drugs really proved about equal in the chances of a good response," said Dr. Herring.

Although there were more adverse events in the active groups than in the placebo groups – and more in the high-dose groups, compared with the low-dose groups – suvorexant was considered safe, he said. The discontinuation rates for drug-related adverse events in the high-dose, low-dose, and placebo groups were 4%, 3%, and 2%, respectively.

The most common issues were next-day somnolence (3% for placebo, 7% with the low dose, and 11% for the high dose, respectively); headache (6%, 7%, and 7%, respectively); and fatigue (2%, 2%, and 4%, respectively).

Few serious adverse events were reported. These included one case of suicidal ideation each in the placebo and low-dose groups, and eight cases in the high-dose group. Dr. Herring said these were mild to moderate and of short duration.

There were no cases of falls or cataplexy, although two patients taking the high dose showed complex sleep behaviors.

Neither of the doses was associated with withdrawal symptoms or clinically significant insomnia rebound during the washout periods. "The drug appears to have a low potential for abuse," Dr. Herring noted.

Merck sponsored the studies. Dr. Herring is a full-time employee of the company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – An orexin receptor antagonist – the first drug to affect a neural system that promotes wakefulness – has proven safe and effective for up to 1 year in a pooled analysis of three phase III studies of patients with insomnia.

The drug (suvorexant) significantly improved both subjective and objective measures of sleep, including sleep onset, total sleep time, and wakefulness after sleep, Dr. W. Joseph Herring said at the annual meeting of the American Academy of Neurology.

Based on these data, the manufacturer, Merck, proceeded last year to preliminary talks with the Food and Drug Administration. The committee considering suvorexant recommended that Merck focus on the smaller of two proposed dose ranges – 20 mg for people up to 64 years of age, and 15 mg for those aged 65 years and older.

Although the proposed higher doses of 40 mg for younger patients and 30 mg for older patients, were deemed safe and effective, the lower dose recommendation by the FDA is consistent with its "usual recommendations to go with lower doses of sleep medications," said Dr. Herring, Merck’s executive director of neuroscience clinical research. "So this 15/20-mg regimen is the most likely to be clinically relevant to prescribers."

The orexin neural system was discovered in the late 1990s, Dr. Herring noted. Orexin neurons release two neuropeptides that interact with downstream receptors that promote wakefulness. Secretion follows a circadian rhythm. Suvorexant orexin antagonists block the activity of this wake-signaling system, allowing sleep to occur.

So far, studies have investigated the drug in almost 3,000 patients; 160 of these were treated for at least a year. The three phase III trials comprised more than 275,000 exposure nights. Most of the patients were women; 46% of the patients were aged 65 years or older.

Sleep was measured by subjective assessment and objective scales, including polysomnography.

In the two efficacy studies, the higher doses decreased time to persistent sleep by 15 minutes on the first night; the lower doses did so by 10 minutes. By 3 months, the high-dose group’s decreased time to persistent sleep was 5 minutes; the low dose group’s time was lowered to 4 minutes.

On the first night, the high-dose drug reduced wakefulness after sleep by 40 minutes; the low-dose drug did so by 35 minutes. After 3 months, the reductions were similar (about 25 minutes).

When the night was divided into thirds, both doses decreased wakefulness significantly and about equally, especially in the second and third fractions of the night.

In the subgroup of 160 patients who were treated for at least 12 months, the drugs showed persistent efficacy overall, although the high doses were somewhat more effective, Dr. Herring said.

A multivariate regression analysis found that, compared with placebo, patients who took the high dose were 2.4 times more likely to be considered responders at 1 month and 1.8 times more likely to be responders at 3 months. Those who took the low dose were 1.8 times more likely to respond at 1 and 3 months.

"The drugs really proved about equal in the chances of a good response," said Dr. Herring.

Although there were more adverse events in the active groups than in the placebo groups – and more in the high-dose groups, compared with the low-dose groups – suvorexant was considered safe, he said. The discontinuation rates for drug-related adverse events in the high-dose, low-dose, and placebo groups were 4%, 3%, and 2%, respectively.

The most common issues were next-day somnolence (3% for placebo, 7% with the low dose, and 11% for the high dose, respectively); headache (6%, 7%, and 7%, respectively); and fatigue (2%, 2%, and 4%, respectively).

Few serious adverse events were reported. These included one case of suicidal ideation each in the placebo and low-dose groups, and eight cases in the high-dose group. Dr. Herring said these were mild to moderate and of short duration.

There were no cases of falls or cataplexy, although two patients taking the high dose showed complex sleep behaviors.

Neither of the doses was associated with withdrawal symptoms or clinically significant insomnia rebound during the washout periods. "The drug appears to have a low potential for abuse," Dr. Herring noted.

Merck sponsored the studies. Dr. Herring is a full-time employee of the company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – An orexin receptor antagonist – the first drug to affect a neural system that promotes wakefulness – has proven safe and effective for up to 1 year in a pooled analysis of three phase III studies of patients with insomnia.

The drug (suvorexant) significantly improved both subjective and objective measures of sleep, including sleep onset, total sleep time, and wakefulness after sleep, Dr. W. Joseph Herring said at the annual meeting of the American Academy of Neurology.

Based on these data, the manufacturer, Merck, proceeded last year to preliminary talks with the Food and Drug Administration. The committee considering suvorexant recommended that Merck focus on the smaller of two proposed dose ranges – 20 mg for people up to 64 years of age, and 15 mg for those aged 65 years and older.

Although the proposed higher doses of 40 mg for younger patients and 30 mg for older patients, were deemed safe and effective, the lower dose recommendation by the FDA is consistent with its "usual recommendations to go with lower doses of sleep medications," said Dr. Herring, Merck’s executive director of neuroscience clinical research. "So this 15/20-mg regimen is the most likely to be clinically relevant to prescribers."

The orexin neural system was discovered in the late 1990s, Dr. Herring noted. Orexin neurons release two neuropeptides that interact with downstream receptors that promote wakefulness. Secretion follows a circadian rhythm. Suvorexant orexin antagonists block the activity of this wake-signaling system, allowing sleep to occur.

So far, studies have investigated the drug in almost 3,000 patients; 160 of these were treated for at least a year. The three phase III trials comprised more than 275,000 exposure nights. Most of the patients were women; 46% of the patients were aged 65 years or older.

Sleep was measured by subjective assessment and objective scales, including polysomnography.

In the two efficacy studies, the higher doses decreased time to persistent sleep by 15 minutes on the first night; the lower doses did so by 10 minutes. By 3 months, the high-dose group’s decreased time to persistent sleep was 5 minutes; the low dose group’s time was lowered to 4 minutes.

On the first night, the high-dose drug reduced wakefulness after sleep by 40 minutes; the low-dose drug did so by 35 minutes. After 3 months, the reductions were similar (about 25 minutes).

When the night was divided into thirds, both doses decreased wakefulness significantly and about equally, especially in the second and third fractions of the night.

In the subgroup of 160 patients who were treated for at least 12 months, the drugs showed persistent efficacy overall, although the high doses were somewhat more effective, Dr. Herring said.

A multivariate regression analysis found that, compared with placebo, patients who took the high dose were 2.4 times more likely to be considered responders at 1 month and 1.8 times more likely to be responders at 3 months. Those who took the low dose were 1.8 times more likely to respond at 1 and 3 months.

"The drugs really proved about equal in the chances of a good response," said Dr. Herring.

Although there were more adverse events in the active groups than in the placebo groups – and more in the high-dose groups, compared with the low-dose groups – suvorexant was considered safe, he said. The discontinuation rates for drug-related adverse events in the high-dose, low-dose, and placebo groups were 4%, 3%, and 2%, respectively.

The most common issues were next-day somnolence (3% for placebo, 7% with the low dose, and 11% for the high dose, respectively); headache (6%, 7%, and 7%, respectively); and fatigue (2%, 2%, and 4%, respectively).

Few serious adverse events were reported. These included one case of suicidal ideation each in the placebo and low-dose groups, and eight cases in the high-dose group. Dr. Herring said these were mild to moderate and of short duration.

There were no cases of falls or cataplexy, although two patients taking the high dose showed complex sleep behaviors.

Neither of the doses was associated with withdrawal symptoms or clinically significant insomnia rebound during the washout periods. "The drug appears to have a low potential for abuse," Dr. Herring noted.

Merck sponsored the studies. Dr. Herring is a full-time employee of the company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – Which comes first, the migraine or the anxiety and depression? At the annual meeting of the American Academy of Neurology, Dr. Deborah Friedman, professor of neurology at the University of Texas Southwestern Medical Center, Dallas, suggests that patients can use cognitive-behavioral therapy rather than medication to best address the migraine-related anxiety and depression, possibly improving their ability to cope with their migraine by allowing them better insight into its impact.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Which comes first, the migraine or the anxiety and depression? At the annual meeting of the American Academy of Neurology, Dr. Deborah Friedman, professor of neurology at the University of Texas Southwestern Medical Center, Dallas, suggests that patients can use cognitive-behavioral therapy rather than medication to best address the migraine-related anxiety and depression, possibly improving their ability to cope with their migraine by allowing them better insight into its impact.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Which comes first, the migraine or the anxiety and depression? At the annual meeting of the American Academy of Neurology, Dr. Deborah Friedman, professor of neurology at the University of Texas Southwestern Medical Center, Dallas, suggests that patients can use cognitive-behavioral therapy rather than medication to best address the migraine-related anxiety and depression, possibly improving their ability to cope with their migraine by allowing them better insight into its impact.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – A simple, three-item screening tool significantly increased headache diagnoses and triptan prescriptions, and significantly decreased opioid prescriptions, based on data from a 5-week intervention at two primary care clinics.

The screen can be administered by a medical assistant and is highly accurate for diagnosing migraine, Dr. Kevin Brennan said at the annual meeting of the American Academy of Neurology.

Of more than 16,000 patients with headache who were referred to a specialty headache clinic from primary care, up to 65% were already taking opioid pain medications, while as few as 10% were taking triptans, said Dr. Brennan, director of the Headache Physiology Laboratory at the University of Utah, Salt Lake City. The problem is inaccurate diagnosis and coding, he said.

"The predominant code for these referred patients was 784, which is a symptom code for headache, and provides no diagnostic utility. If you don’t diagnose, there is a much lower likelihood of appropriately treating," he explained.

The university’s headache clinic receives most of its patients from 10 primary care practices in the region. Over a 2-year period (2008-2010), there were more than 50,000 headache visits in these practices. Of these, approximately 17,000 arrived at the specialty clinic with an actual headache diagnosis, Dr. Brennan said.

The numbers were revealed after an anecdotal observation that many patients were arriving for specialty treatment with a symptom code instead of a diagnosis code, and already taking inappropriate medications.

Dr. Brennan and his colleagues launched a quality improvement project to attempt to boost both appropriate diagnoses and appropriate treatments.

About a third of the referred patients were taking opiates at the time of referral. Other inappropriate medications were antianxiety drugs, barbiturates, antidepressants, antiemetics, nonsteroidal anti-inflammatories, benzodiazepines, decongestants, and muscle relaxants. Only 9% of the referred patients were taking a triptan.

"We wanted to see why we were getting so many of these patients," Dr. Brennan said. "And when we started looking at the medications and diagnostic codes, our initial reaction was ... something I can’t say."

The data showed that headache simply was not being diagnosed. Instead, the most common code was the one that identifies headache as a symptom, Dr. Brennan explained.

To address the problem, the headache research team implemented an easy migraine screen into the patients’ electronic medical records. The ID Migraine algorithm is a three-item screen that can be administered by a medical assistant. It showed 81% sensitivity and 75% specificity for migraine in a validation study.

If a patient answers yes to the three questions (headache disability, nausea, and sensitivity to light), the likelihood of migraine is very, very high, Dr. Brennan said. If the screen is positive, a treatment and medication algorithm is displayed.

The screen was piloted at two clinics during a 5-week period in 2013. The clinics were chosen because they had the best rates of headache diagnostic coding. Prior to the intervention, 41% of the codes were the 784 headache symptom code, 17% of patients received a triptan, and 18% of patients received an opioid.

Five weeks later, the symptom code was reduced to 33% of headache encounters – a 20% improvement. There was a 36% relative increase in the number of triptan prescriptions and a 37% decrease in the number of opioid prescriptions.

The underdiagnosis of headache at the primary care level boils down to one thing, Dr. Brennan said: Time – or the lack of it.

"There’s not enough time in medical school to learn about headache," he said, noting that doctors in training spend an average of 3 hours on headache during an entire school career. Neither do most primary care doctors have enough time during a typical office visit to address headaches. And the idea remains entrenched that headache patients are "difficult" and that migraine is hard to diagnose, he added.

"Right now, we’re herding cats," Dr. Brennan said. "We’re trying to work with the medical directors and get them to implement [screening]. But they still come back saying, ‘Migraine is so hard to diagnose.’ With this system, it’s not hard," he said. "Headache is primary care. It’s more common than asthma and diabetes combined. There’s no excuse for not diagnosing it."

There was no outside funding for the study. Dr. Brennan had no financial disclosures.

msullivan@frontlinemedcom.com

PHILADELPHIA – A simple, three-item screening tool significantly increased headache diagnoses and triptan prescriptions, and significantly decreased opioid prescriptions, based on data from a 5-week intervention at two primary care clinics.

The screen can be administered by a medical assistant and is highly accurate for diagnosing migraine, Dr. Kevin Brennan said at the annual meeting of the American Academy of Neurology.

Of more than 16,000 patients with headache who were referred to a specialty headache clinic from primary care, up to 65% were already taking opioid pain medications, while as few as 10% were taking triptans, said Dr. Brennan, director of the Headache Physiology Laboratory at the University of Utah, Salt Lake City. The problem is inaccurate diagnosis and coding, he said.

"The predominant code for these referred patients was 784, which is a symptom code for headache, and provides no diagnostic utility. If you don’t diagnose, there is a much lower likelihood of appropriately treating," he explained.

The university’s headache clinic receives most of its patients from 10 primary care practices in the region. Over a 2-year period (2008-2010), there were more than 50,000 headache visits in these practices. Of these, approximately 17,000 arrived at the specialty clinic with an actual headache diagnosis, Dr. Brennan said.

The numbers were revealed after an anecdotal observation that many patients were arriving for specialty treatment with a symptom code instead of a diagnosis code, and already taking inappropriate medications.

Dr. Brennan and his colleagues launched a quality improvement project to attempt to boost both appropriate diagnoses and appropriate treatments.

About a third of the referred patients were taking opiates at the time of referral. Other inappropriate medications were antianxiety drugs, barbiturates, antidepressants, antiemetics, nonsteroidal anti-inflammatories, benzodiazepines, decongestants, and muscle relaxants. Only 9% of the referred patients were taking a triptan.

"We wanted to see why we were getting so many of these patients," Dr. Brennan said. "And when we started looking at the medications and diagnostic codes, our initial reaction was ... something I can’t say."

The data showed that headache simply was not being diagnosed. Instead, the most common code was the one that identifies headache as a symptom, Dr. Brennan explained.

To address the problem, the headache research team implemented an easy migraine screen into the patients’ electronic medical records. The ID Migraine algorithm is a three-item screen that can be administered by a medical assistant. It showed 81% sensitivity and 75% specificity for migraine in a validation study.

If a patient answers yes to the three questions (headache disability, nausea, and sensitivity to light), the likelihood of migraine is very, very high, Dr. Brennan said. If the screen is positive, a treatment and medication algorithm is displayed.

The screen was piloted at two clinics during a 5-week period in 2013. The clinics were chosen because they had the best rates of headache diagnostic coding. Prior to the intervention, 41% of the codes were the 784 headache symptom code, 17% of patients received a triptan, and 18% of patients received an opioid.

Five weeks later, the symptom code was reduced to 33% of headache encounters – a 20% improvement. There was a 36% relative increase in the number of triptan prescriptions and a 37% decrease in the number of opioid prescriptions.

The underdiagnosis of headache at the primary care level boils down to one thing, Dr. Brennan said: Time – or the lack of it.

"There’s not enough time in medical school to learn about headache," he said, noting that doctors in training spend an average of 3 hours on headache during an entire school career. Neither do most primary care doctors have enough time during a typical office visit to address headaches. And the idea remains entrenched that headache patients are "difficult" and that migraine is hard to diagnose, he added.

"Right now, we’re herding cats," Dr. Brennan said. "We’re trying to work with the medical directors and get them to implement [screening]. But they still come back saying, ‘Migraine is so hard to diagnose.’ With this system, it’s not hard," he said. "Headache is primary care. It’s more common than asthma and diabetes combined. There’s no excuse for not diagnosing it."

There was no outside funding for the study. Dr. Brennan had no financial disclosures.

msullivan@frontlinemedcom.com

PHILADELPHIA – A simple, three-item screening tool significantly increased headache diagnoses and triptan prescriptions, and significantly decreased opioid prescriptions, based on data from a 5-week intervention at two primary care clinics.

The screen can be administered by a medical assistant and is highly accurate for diagnosing migraine, Dr. Kevin Brennan said at the annual meeting of the American Academy of Neurology.

Of more than 16,000 patients with headache who were referred to a specialty headache clinic from primary care, up to 65% were already taking opioid pain medications, while as few as 10% were taking triptans, said Dr. Brennan, director of the Headache Physiology Laboratory at the University of Utah, Salt Lake City. The problem is inaccurate diagnosis and coding, he said.

"The predominant code for these referred patients was 784, which is a symptom code for headache, and provides no diagnostic utility. If you don’t diagnose, there is a much lower likelihood of appropriately treating," he explained.

The university’s headache clinic receives most of its patients from 10 primary care practices in the region. Over a 2-year period (2008-2010), there were more than 50,000 headache visits in these practices. Of these, approximately 17,000 arrived at the specialty clinic with an actual headache diagnosis, Dr. Brennan said.

The numbers were revealed after an anecdotal observation that many patients were arriving for specialty treatment with a symptom code instead of a diagnosis code, and already taking inappropriate medications.

Dr. Brennan and his colleagues launched a quality improvement project to attempt to boost both appropriate diagnoses and appropriate treatments.

About a third of the referred patients were taking opiates at the time of referral. Other inappropriate medications were antianxiety drugs, barbiturates, antidepressants, antiemetics, nonsteroidal anti-inflammatories, benzodiazepines, decongestants, and muscle relaxants. Only 9% of the referred patients were taking a triptan.

"We wanted to see why we were getting so many of these patients," Dr. Brennan said. "And when we started looking at the medications and diagnostic codes, our initial reaction was ... something I can’t say."

The data showed that headache simply was not being diagnosed. Instead, the most common code was the one that identifies headache as a symptom, Dr. Brennan explained.

To address the problem, the headache research team implemented an easy migraine screen into the patients’ electronic medical records. The ID Migraine algorithm is a three-item screen that can be administered by a medical assistant. It showed 81% sensitivity and 75% specificity for migraine in a validation study.

If a patient answers yes to the three questions (headache disability, nausea, and sensitivity to light), the likelihood of migraine is very, very high, Dr. Brennan said. If the screen is positive, a treatment and medication algorithm is displayed.

The screen was piloted at two clinics during a 5-week period in 2013. The clinics were chosen because they had the best rates of headache diagnostic coding. Prior to the intervention, 41% of the codes were the 784 headache symptom code, 17% of patients received a triptan, and 18% of patients received an opioid.

Five weeks later, the symptom code was reduced to 33% of headache encounters – a 20% improvement. There was a 36% relative increase in the number of triptan prescriptions and a 37% decrease in the number of opioid prescriptions.

The underdiagnosis of headache at the primary care level boils down to one thing, Dr. Brennan said: Time – or the lack of it.

"There’s not enough time in medical school to learn about headache," he said, noting that doctors in training spend an average of 3 hours on headache during an entire school career. Neither do most primary care doctors have enough time during a typical office visit to address headaches. And the idea remains entrenched that headache patients are "difficult" and that migraine is hard to diagnose, he added.

"Right now, we’re herding cats," Dr. Brennan said. "We’re trying to work with the medical directors and get them to implement [screening]. But they still come back saying, ‘Migraine is so hard to diagnose.’ With this system, it’s not hard," he said. "Headache is primary care. It’s more common than asthma and diabetes combined. There’s no excuse for not diagnosing it."

There was no outside funding for the study. Dr. Brennan had no financial disclosures.

msullivan@frontlinemedcom.com

PHILADELPHIA - Adherence to migraine prophylactics drops off sharply within a few months of the initial prescription and falls even farther by 1 year, based on claims data from approximately 8,700 patients.

By 6 months, only 30% of patients were adherent to their preventive medications, defined as taking them as directed at least 80% of the time, Zsolt Hepp, Pharm.D., said at the annual meeting of the American Academy of Neurology. By 12 months, adherence dropped to about 20%; fewer than 1 in 5 patients.

"Adherence rates were alarmingly low," said Dr. Hepp, a researcher for Allergan. "And no matter what class of drugs we looked at, the rates were similar."

Dr. Hepp and his colleagues conducted a retrospective analysis using 2007-2012 claims data from the Truven Health Analytics MarketScan Database. The system contains Medicare, supplemental, and Medicaid claims for more 40 million unique patients per year. Patients, who were at least 18 years old, were diagnosed with chronic migraine, and who initiated an oral migraine prophylactic medication between 2008-2012 were included in the analysis.

The initial study group comprised more than 76,000 patients, but exclusion criteria narrowed it to about 8,700, as the researchers tried to pinpoint prescriptions that were solely for migraine. Since most of the 14 medications investigated have different primary indications, the team excluded patients with a diagnosis for that another indication (depression, for example) within a year prior to the migraine diagnosis.

The analysis also included only patients who had full, unlapsed insurance coverage during the year of interest; many in the original cohort were excluded because of such lapses.

The 14 commonly prescribed migraine medications in the study included four recommended by the American Academy of Neurology as first-line preventives.

The drugs examined were antidepressants (nortriptyline and amitriptyline, citalopram, sertraline, fluoxetine, paroxetine, and venlafaxine), beta-blockers (propranolol, metoprolol, atenolol, and nadolol), and anticonvulsants (divalproex, gabapentin, and topiramate).

The majority of patients were women, with a mean age of 40 years. Most (59%) were employed full time. Common comorbidities included nonmigraine headache (54%), cancer (22%), hypertension (18%), depression (18%), sleep disorders (11%), and gastroesophageal reflux disease (11%).

The adherence rates were surprisingly similar across drug classes, Dr. Hepp noted. Overall adherence rates using the Medication Possession Ratio hovered at 28%-29% at 6 months and 19%-21% at 12 months.

When broken down by individual drug, the antidepressants had the highest rates of adherence at 6 months. Venlafaxine and fluoxetine topped the list, with 37% of patients adherent at 6 months. However, by 12 months, adherence had dropped to 28% for venlafaxine and 22% for fluoxetine.

"All of these medications need to be taken at least once daily – and sometimes several times a day – to really maintain their effectiveness," Dr. Hepp noted. "This is the first real-world analysis of the U.S. migraine population, and we feel the results are generalizable to that population."

Unfortunately, he said, a claims database doesn’t give any insight into why patients stop taking their medication. One view came up during the discussion period, however.

"People don’t want to take drugs that make them gain weight or feel stupid," one discussant said bluntly.

Dr. Hepp added that this low adherence was not surprising, in light of research that shows similar problems with other chronic diseases.

A 2009 study examined six different chronic conditions, including hypertension and diabetes, he said. "By far the best adherence rates were for diabetes, and that was only about 60% by 12 months."

Although the claims database revealed nothing about the factors driving the lack of adherence, data from previous studies suggest that side effects and dissatisfaction are likely suspects, Dr. Hepp said. His own previous study on the reasons for discontinuation in clinical trials of three migraine treatments showed that "a significant portion of the discontinued patients decided to stop treatment due to side effects," he said in an interview. I actually have another publication that was a systematic literature review of adherence manuscripts.

"Another study by Blumenfeld et al. 2013 found that top reasons for discontinuation of oral migraine prophyalctics were side effects and treatment satisfaction," he said. "It’s likely that these other studies highlight the very reason(s) why we saw the level of nonadherence in our study," he said. "Our results most certainly call attention to the large gap in the treatment of this highly burdened population, and at the very least this study calls for further research and hopefully the integration of adherence into future clincial trials for migraine prevention tretaments."

Allergan sponsored the study. Dr Hepp is a full-time employee of that company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA - Adherence to migraine prophylactics drops off sharply within a few months of the initial prescription and falls even farther by 1 year, based on claims data from approximately 8,700 patients.

By 6 months, only 30% of patients were adherent to their preventive medications, defined as taking them as directed at least 80% of the time, Zsolt Hepp, Pharm.D., said at the annual meeting of the American Academy of Neurology. By 12 months, adherence dropped to about 20%; fewer than 1 in 5 patients.

"Adherence rates were alarmingly low," said Dr. Hepp, a researcher for Allergan. "And no matter what class of drugs we looked at, the rates were similar."

Dr. Hepp and his colleagues conducted a retrospective analysis using 2007-2012 claims data from the Truven Health Analytics MarketScan Database. The system contains Medicare, supplemental, and Medicaid claims for more 40 million unique patients per year. Patients, who were at least 18 years old, were diagnosed with chronic migraine, and who initiated an oral migraine prophylactic medication between 2008-2012 were included in the analysis.

The initial study group comprised more than 76,000 patients, but exclusion criteria narrowed it to about 8,700, as the researchers tried to pinpoint prescriptions that were solely for migraine. Since most of the 14 medications investigated have different primary indications, the team excluded patients with a diagnosis for that another indication (depression, for example) within a year prior to the migraine diagnosis.

The analysis also included only patients who had full, unlapsed insurance coverage during the year of interest; many in the original cohort were excluded because of such lapses.

The 14 commonly prescribed migraine medications in the study included four recommended by the American Academy of Neurology as first-line preventives.

The drugs examined were antidepressants (nortriptyline and amitriptyline, citalopram, sertraline, fluoxetine, paroxetine, and venlafaxine), beta-blockers (propranolol, metoprolol, atenolol, and nadolol), and anticonvulsants (divalproex, gabapentin, and topiramate).

The majority of patients were women, with a mean age of 40 years. Most (59%) were employed full time. Common comorbidities included nonmigraine headache (54%), cancer (22%), hypertension (18%), depression (18%), sleep disorders (11%), and gastroesophageal reflux disease (11%).

The adherence rates were surprisingly similar across drug classes, Dr. Hepp noted. Overall adherence rates using the Medication Possession Ratio hovered at 28%-29% at 6 months and 19%-21% at 12 months.

When broken down by individual drug, the antidepressants had the highest rates of adherence at 6 months. Venlafaxine and fluoxetine topped the list, with 37% of patients adherent at 6 months. However, by 12 months, adherence had dropped to 28% for venlafaxine and 22% for fluoxetine.

"All of these medications need to be taken at least once daily – and sometimes several times a day – to really maintain their effectiveness," Dr. Hepp noted. "This is the first real-world analysis of the U.S. migraine population, and we feel the results are generalizable to that population."

Unfortunately, he said, a claims database doesn’t give any insight into why patients stop taking their medication. One view came up during the discussion period, however.

"People don’t want to take drugs that make them gain weight or feel stupid," one discussant said bluntly.

Dr. Hepp added that this low adherence was not surprising, in light of research that shows similar problems with other chronic diseases.

A 2009 study examined six different chronic conditions, including hypertension and diabetes, he said. "By far the best adherence rates were for diabetes, and that was only about 60% by 12 months."

Although the claims database revealed nothing about the factors driving the lack of adherence, data from previous studies suggest that side effects and dissatisfaction are likely suspects, Dr. Hepp said. His own previous study on the reasons for discontinuation in clinical trials of three migraine treatments showed that "a significant portion of the discontinued patients decided to stop treatment due to side effects," he said in an interview. I actually have another publication that was a systematic literature review of adherence manuscripts.

"Another study by Blumenfeld et al. 2013 found that top reasons for discontinuation of oral migraine prophyalctics were side effects and treatment satisfaction," he said. "It’s likely that these other studies highlight the very reason(s) why we saw the level of nonadherence in our study," he said. "Our results most certainly call attention to the large gap in the treatment of this highly burdened population, and at the very least this study calls for further research and hopefully the integration of adherence into future clincial trials for migraine prevention tretaments."

Allergan sponsored the study. Dr Hepp is a full-time employee of that company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA - Adherence to migraine prophylactics drops off sharply within a few months of the initial prescription and falls even farther by 1 year, based on claims data from approximately 8,700 patients.

By 6 months, only 30% of patients were adherent to their preventive medications, defined as taking them as directed at least 80% of the time, Zsolt Hepp, Pharm.D., said at the annual meeting of the American Academy of Neurology. By 12 months, adherence dropped to about 20%; fewer than 1 in 5 patients.

"Adherence rates were alarmingly low," said Dr. Hepp, a researcher for Allergan. "And no matter what class of drugs we looked at, the rates were similar."

Dr. Hepp and his colleagues conducted a retrospective analysis using 2007-2012 claims data from the Truven Health Analytics MarketScan Database. The system contains Medicare, supplemental, and Medicaid claims for more 40 million unique patients per year. Patients, who were at least 18 years old, were diagnosed with chronic migraine, and who initiated an oral migraine prophylactic medication between 2008-2012 were included in the analysis.

The initial study group comprised more than 76,000 patients, but exclusion criteria narrowed it to about 8,700, as the researchers tried to pinpoint prescriptions that were solely for migraine. Since most of the 14 medications investigated have different primary indications, the team excluded patients with a diagnosis for that another indication (depression, for example) within a year prior to the migraine diagnosis.

The analysis also included only patients who had full, unlapsed insurance coverage during the year of interest; many in the original cohort were excluded because of such lapses.

The 14 commonly prescribed migraine medications in the study included four recommended by the American Academy of Neurology as first-line preventives.

The drugs examined were antidepressants (nortriptyline and amitriptyline, citalopram, sertraline, fluoxetine, paroxetine, and venlafaxine), beta-blockers (propranolol, metoprolol, atenolol, and nadolol), and anticonvulsants (divalproex, gabapentin, and topiramate).

The majority of patients were women, with a mean age of 40 years. Most (59%) were employed full time. Common comorbidities included nonmigraine headache (54%), cancer (22%), hypertension (18%), depression (18%), sleep disorders (11%), and gastroesophageal reflux disease (11%).

The adherence rates were surprisingly similar across drug classes, Dr. Hepp noted. Overall adherence rates using the Medication Possession Ratio hovered at 28%-29% at 6 months and 19%-21% at 12 months.

When broken down by individual drug, the antidepressants had the highest rates of adherence at 6 months. Venlafaxine and fluoxetine topped the list, with 37% of patients adherent at 6 months. However, by 12 months, adherence had dropped to 28% for venlafaxine and 22% for fluoxetine.

"All of these medications need to be taken at least once daily – and sometimes several times a day – to really maintain their effectiveness," Dr. Hepp noted. "This is the first real-world analysis of the U.S. migraine population, and we feel the results are generalizable to that population."

Unfortunately, he said, a claims database doesn’t give any insight into why patients stop taking their medication. One view came up during the discussion period, however.

"People don’t want to take drugs that make them gain weight or feel stupid," one discussant said bluntly.

Dr. Hepp added that this low adherence was not surprising, in light of research that shows similar problems with other chronic diseases.

A 2009 study examined six different chronic conditions, including hypertension and diabetes, he said. "By far the best adherence rates were for diabetes, and that was only about 60% by 12 months."

Although the claims database revealed nothing about the factors driving the lack of adherence, data from previous studies suggest that side effects and dissatisfaction are likely suspects, Dr. Hepp said. His own previous study on the reasons for discontinuation in clinical trials of three migraine treatments showed that "a significant portion of the discontinued patients decided to stop treatment due to side effects," he said in an interview. I actually have another publication that was a systematic literature review of adherence manuscripts.

"Another study by Blumenfeld et al. 2013 found that top reasons for discontinuation of oral migraine prophyalctics were side effects and treatment satisfaction," he said. "It’s likely that these other studies highlight the very reason(s) why we saw the level of nonadherence in our study," he said. "Our results most certainly call attention to the large gap in the treatment of this highly burdened population, and at the very least this study calls for further research and hopefully the integration of adherence into future clincial trials for migraine prevention tretaments."

Allergan sponsored the study. Dr Hepp is a full-time employee of that company.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – Presumed consent for emergency thrombolysis is ethical and practical, according to the results of a population-based survey.

In an online survey of 1,100 adults aged 50 years or older, 76.9% said they would want intravenous tissue plasminogen activator for stroke. Of those surveyed, 76.0% also said they would want cardiopulmonary resuscitation for cardiac arrest. If they were unable to give informed consent in either situation, the desire for emergency thrombolysis remained essentially unchanged at 78.1%, while even more (83.6%) respondents said they would want CPR, Dr. Winston Chiong reported at the annual meeting of the American Academy of Neurology. The findings also appear in the April 23 issue of JAMA (2014;311:1689-91).

"The presumption is that ‘reasonable people’ in the middle of [an acute ischemic stroke] cascade would want thrombolytic treatment," Dr. Chiong told the platform science session blitz audience. "But this presumption has been controversial because thrombolysis has no short-term mortality benefit, unlike CPR."

In 2011, the AAN endorsed emergency thrombolysis under presumption of consent; in 2013, the American Heart Association and the American Stroke Association followed suit.

Dr. Chiong, whose interest lies in decision making and how it is affected by aging and neurodegenerative disease, said the findings provide empirical data that this presumption is justified.

He and his colleagues at the University of California, San Francisco, Memory and Aging Center randomly assigned survey participants to read one of two hypothetical scenarios. In the first, they saw themselves being brought to a hospital after having a severe acute ischemic stroke. In the second, they saw themselves have an out-of-hospital cardiac arrest that was treated by paramedics.

The stroke group was given a graphical depiction of the potential risks and benefits of treatment with thrombolysis, while the cardiac arrest group was told of the potential outcomes after paramedic-initiated CPR.

Each group was then asked whether they would want the respective treatment for their imagined scenario.

In the stroke group, 419 of 545 participants (76.9%) wanted thrombolysis, while 422 of 555 respondents (76.0%) wanted CPR for sudden cardiac arrest. Female sex, being divorced, and having less education were associated with refusing thrombolysis; poorer physical health, previous stroke, and possession of a health care advance directive was associated with refusal of CPR.

"In a clinical scenario involving an incapacitated patient where the treatment preferences are unknown and no surrogate decision maker can be found within the treatment window, we found equally strong ethical grounds for presuming thrombolysis of stroke as for presumed consent of CPR in cardiac arrest," Dr. Chiong said.

However, he underscored that despite there being a "pragmatic ethical and legal" basis for presumed consent, it is important to remember there are still a quarter of older adults who would not want the treatment if unable to consent.

"I spend a lot of time thinking about these things," he said, "The presumption of consent should not be taken to fully replace informed consent," particularly if there is some existing evidence of the patient’s wishes or if there is some question about the effectiveness of the intervention.

This study was supported in part by the American Brain Foundation Clinical Research Training Fellowship Program and grants from the National Science Foundation, the National Institute on Aging, and the National Center for Advancing Translational Sciences.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Presumed consent for emergency thrombolysis is ethical and practical, according to the results of a population-based survey.

In an online survey of 1,100 adults aged 50 years or older, 76.9% said they would want intravenous tissue plasminogen activator for stroke. Of those surveyed, 76.0% also said they would want cardiopulmonary resuscitation for cardiac arrest. If they were unable to give informed consent in either situation, the desire for emergency thrombolysis remained essentially unchanged at 78.1%, while even more (83.6%) respondents said they would want CPR, Dr. Winston Chiong reported at the annual meeting of the American Academy of Neurology. The findings also appear in the April 23 issue of JAMA (2014;311:1689-91).

"The presumption is that ‘reasonable people’ in the middle of [an acute ischemic stroke] cascade would want thrombolytic treatment," Dr. Chiong told the platform science session blitz audience. "But this presumption has been controversial because thrombolysis has no short-term mortality benefit, unlike CPR."

In 2011, the AAN endorsed emergency thrombolysis under presumption of consent; in 2013, the American Heart Association and the American Stroke Association followed suit.

Dr. Chiong, whose interest lies in decision making and how it is affected by aging and neurodegenerative disease, said the findings provide empirical data that this presumption is justified.

He and his colleagues at the University of California, San Francisco, Memory and Aging Center randomly assigned survey participants to read one of two hypothetical scenarios. In the first, they saw themselves being brought to a hospital after having a severe acute ischemic stroke. In the second, they saw themselves have an out-of-hospital cardiac arrest that was treated by paramedics.

The stroke group was given a graphical depiction of the potential risks and benefits of treatment with thrombolysis, while the cardiac arrest group was told of the potential outcomes after paramedic-initiated CPR.

Each group was then asked whether they would want the respective treatment for their imagined scenario.

In the stroke group, 419 of 545 participants (76.9%) wanted thrombolysis, while 422 of 555 respondents (76.0%) wanted CPR for sudden cardiac arrest. Female sex, being divorced, and having less education were associated with refusing thrombolysis; poorer physical health, previous stroke, and possession of a health care advance directive was associated with refusal of CPR.

"In a clinical scenario involving an incapacitated patient where the treatment preferences are unknown and no surrogate decision maker can be found within the treatment window, we found equally strong ethical grounds for presuming thrombolysis of stroke as for presumed consent of CPR in cardiac arrest," Dr. Chiong said.

However, he underscored that despite there being a "pragmatic ethical and legal" basis for presumed consent, it is important to remember there are still a quarter of older adults who would not want the treatment if unable to consent.

"I spend a lot of time thinking about these things," he said, "The presumption of consent should not be taken to fully replace informed consent," particularly if there is some existing evidence of the patient’s wishes or if there is some question about the effectiveness of the intervention.

This study was supported in part by the American Brain Foundation Clinical Research Training Fellowship Program and grants from the National Science Foundation, the National Institute on Aging, and the National Center for Advancing Translational Sciences.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – Presumed consent for emergency thrombolysis is ethical and practical, according to the results of a population-based survey.

In an online survey of 1,100 adults aged 50 years or older, 76.9% said they would want intravenous tissue plasminogen activator for stroke. Of those surveyed, 76.0% also said they would want cardiopulmonary resuscitation for cardiac arrest. If they were unable to give informed consent in either situation, the desire for emergency thrombolysis remained essentially unchanged at 78.1%, while even more (83.6%) respondents said they would want CPR, Dr. Winston Chiong reported at the annual meeting of the American Academy of Neurology. The findings also appear in the April 23 issue of JAMA (2014;311:1689-91).

"The presumption is that ‘reasonable people’ in the middle of [an acute ischemic stroke] cascade would want thrombolytic treatment," Dr. Chiong told the platform science session blitz audience. "But this presumption has been controversial because thrombolysis has no short-term mortality benefit, unlike CPR."

In 2011, the AAN endorsed emergency thrombolysis under presumption of consent; in 2013, the American Heart Association and the American Stroke Association followed suit.

Dr. Chiong, whose interest lies in decision making and how it is affected by aging and neurodegenerative disease, said the findings provide empirical data that this presumption is justified.

He and his colleagues at the University of California, San Francisco, Memory and Aging Center randomly assigned survey participants to read one of two hypothetical scenarios. In the first, they saw themselves being brought to a hospital after having a severe acute ischemic stroke. In the second, they saw themselves have an out-of-hospital cardiac arrest that was treated by paramedics.

The stroke group was given a graphical depiction of the potential risks and benefits of treatment with thrombolysis, while the cardiac arrest group was told of the potential outcomes after paramedic-initiated CPR.

Each group was then asked whether they would want the respective treatment for their imagined scenario.

In the stroke group, 419 of 545 participants (76.9%) wanted thrombolysis, while 422 of 555 respondents (76.0%) wanted CPR for sudden cardiac arrest. Female sex, being divorced, and having less education were associated with refusing thrombolysis; poorer physical health, previous stroke, and possession of a health care advance directive was associated with refusal of CPR.

"In a clinical scenario involving an incapacitated patient where the treatment preferences are unknown and no surrogate decision maker can be found within the treatment window, we found equally strong ethical grounds for presuming thrombolysis of stroke as for presumed consent of CPR in cardiac arrest," Dr. Chiong said.

However, he underscored that despite there being a "pragmatic ethical and legal" basis for presumed consent, it is important to remember there are still a quarter of older adults who would not want the treatment if unable to consent.

"I spend a lot of time thinking about these things," he said, "The presumption of consent should not be taken to fully replace informed consent," particularly if there is some existing evidence of the patient’s wishes or if there is some question about the effectiveness of the intervention.

This study was supported in part by the American Brain Foundation Clinical Research Training Fellowship Program and grants from the National Science Foundation, the National Institute on Aging, and the National Center for Advancing Translational Sciences.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

PHILADELPHIA – A telemedicine program for patients with acute ischemic stroke increased the use of recombinant tissue plasminogen activator by as much as 13% in the year after implementation.

Most of the 13 hospitals in the retrospective study significantly increased their recombinant tissue plasminogen activator (rTPA) use, Dr. Jeffrey C. Wagner said at the annual meeting of the American Academy of Neurology. Three didn’t benefit, however, and one hospital actually experienced a significant decrease in rTPA administration.

rTPA "is the only treatment proven to benefit patients during acute ischemic stroke," said Dr. Wagner, a stroke specialist at Blue Sky Neurology in Denver.

"We obviously need more research to discover why these hospitals didn’t benefit more dramatically," he said.

The study population included patients aged 18 years and older who were admitted with a primary diagnosis of acute ischemic stroke and discharged between July 1, 2006, and Dec. 31, 2012; more than 15,000 patients were included in the retrospective analysis. Outcomes were extracted from a national claims database, and the hospitals had a minimum of 1 year of data available before and after implementing a telemedicine program. The hospitals represented a variety of patient demographics. About two-thirds were rural; approximately half were small, defined as fewer than 200 beds. The hospitals were located in the Northeastern, Southern, and Western portions of the United States.

The primary outcome was the percentage of patients treated with rTPA before and after telemedicine implementation.

Overall, rTPA administration increased significantly, from 4.5% to 7.3% after a telemedicine program was introduced. The increase was similar whether patients were admitted to the hospital or whether they were transferred to a stroke center.

There were, however, significant outcome differences among the hospitals according to size. Overall the use of rTPA in smaller hospitals increased from 1% to 7% after implementing a telemedicine program, compared with an increase from 5.4% to 7% in larger hospitals. Those results were similar when patients were stratified as inpatients or transferred patients.

Two hospitals increased rTPA use by more than 10%; five hospitals increased rTPA use by 5%-10%, and three hospitals increased rTPA use by 0-5%.

However, the rTPA use in three hospitals remained virtually identical; two administered no rTPA either before or after implementing a telemedicine program, and rTPA use in the third hospital increase from none to less than 2%. In addition, one of the largest hospitals in the study actually saw a 14% decrease in rTPA use, a finding Dr. Wagner was hard pressed to explain.

"In my experience, there’s a huge integrated system required for telemedicine to work well, from the EMS [emergency medical services] people calling in a stroke alert in advance to the emergency doctors activating the telemedicine system. My theory would be that there might not have been complete buy-in from the staff."

The three hospitals that didn’t experience any benefit were the smallest in the cohort – a factor that probably contributed to their lack of results, he added.

"My theory here is that they spanned the largest area of geography, so having telemedicine might not improve rTPA usage, because the real issue was not being able to get patients there in time," he said.

The study was funded by Genentech. Dr. Wagner had no additional disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – A telemedicine program for patients with acute ischemic stroke increased the use of recombinant tissue plasminogen activator by as much as 13% in the year after implementation.

Most of the 13 hospitals in the retrospective study significantly increased their recombinant tissue plasminogen activator (rTPA) use, Dr. Jeffrey C. Wagner said at the annual meeting of the American Academy of Neurology. Three didn’t benefit, however, and one hospital actually experienced a significant decrease in rTPA administration.

rTPA "is the only treatment proven to benefit patients during acute ischemic stroke," said Dr. Wagner, a stroke specialist at Blue Sky Neurology in Denver.

"We obviously need more research to discover why these hospitals didn’t benefit more dramatically," he said.

The study population included patients aged 18 years and older who were admitted with a primary diagnosis of acute ischemic stroke and discharged between July 1, 2006, and Dec. 31, 2012; more than 15,000 patients were included in the retrospective analysis. Outcomes were extracted from a national claims database, and the hospitals had a minimum of 1 year of data available before and after implementing a telemedicine program. The hospitals represented a variety of patient demographics. About two-thirds were rural; approximately half were small, defined as fewer than 200 beds. The hospitals were located in the Northeastern, Southern, and Western portions of the United States.

The primary outcome was the percentage of patients treated with rTPA before and after telemedicine implementation.

Overall, rTPA administration increased significantly, from 4.5% to 7.3% after a telemedicine program was introduced. The increase was similar whether patients were admitted to the hospital or whether they were transferred to a stroke center.

There were, however, significant outcome differences among the hospitals according to size. Overall the use of rTPA in smaller hospitals increased from 1% to 7% after implementing a telemedicine program, compared with an increase from 5.4% to 7% in larger hospitals. Those results were similar when patients were stratified as inpatients or transferred patients.

Two hospitals increased rTPA use by more than 10%; five hospitals increased rTPA use by 5%-10%, and three hospitals increased rTPA use by 0-5%.

However, the rTPA use in three hospitals remained virtually identical; two administered no rTPA either before or after implementing a telemedicine program, and rTPA use in the third hospital increase from none to less than 2%. In addition, one of the largest hospitals in the study actually saw a 14% decrease in rTPA use, a finding Dr. Wagner was hard pressed to explain.

"In my experience, there’s a huge integrated system required for telemedicine to work well, from the EMS [emergency medical services] people calling in a stroke alert in advance to the emergency doctors activating the telemedicine system. My theory would be that there might not have been complete buy-in from the staff."

The three hospitals that didn’t experience any benefit were the smallest in the cohort – a factor that probably contributed to their lack of results, he added.

"My theory here is that they spanned the largest area of geography, so having telemedicine might not improve rTPA usage, because the real issue was not being able to get patients there in time," he said.

The study was funded by Genentech. Dr. Wagner had no additional disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

PHILADELPHIA – A telemedicine program for patients with acute ischemic stroke increased the use of recombinant tissue plasminogen activator by as much as 13% in the year after implementation.

Most of the 13 hospitals in the retrospective study significantly increased their recombinant tissue plasminogen activator (rTPA) use, Dr. Jeffrey C. Wagner said at the annual meeting of the American Academy of Neurology. Three didn’t benefit, however, and one hospital actually experienced a significant decrease in rTPA administration.

rTPA "is the only treatment proven to benefit patients during acute ischemic stroke," said Dr. Wagner, a stroke specialist at Blue Sky Neurology in Denver.

"We obviously need more research to discover why these hospitals didn’t benefit more dramatically," he said.

The study population included patients aged 18 years and older who were admitted with a primary diagnosis of acute ischemic stroke and discharged between July 1, 2006, and Dec. 31, 2012; more than 15,000 patients were included in the retrospective analysis. Outcomes were extracted from a national claims database, and the hospitals had a minimum of 1 year of data available before and after implementing a telemedicine program. The hospitals represented a variety of patient demographics. About two-thirds were rural; approximately half were small, defined as fewer than 200 beds. The hospitals were located in the Northeastern, Southern, and Western portions of the United States.

The primary outcome was the percentage of patients treated with rTPA before and after telemedicine implementation.

Overall, rTPA administration increased significantly, from 4.5% to 7.3% after a telemedicine program was introduced. The increase was similar whether patients were admitted to the hospital or whether they were transferred to a stroke center.

There were, however, significant outcome differences among the hospitals according to size. Overall the use of rTPA in smaller hospitals increased from 1% to 7% after implementing a telemedicine program, compared with an increase from 5.4% to 7% in larger hospitals. Those results were similar when patients were stratified as inpatients or transferred patients.

Two hospitals increased rTPA use by more than 10%; five hospitals increased rTPA use by 5%-10%, and three hospitals increased rTPA use by 0-5%.

However, the rTPA use in three hospitals remained virtually identical; two administered no rTPA either before or after implementing a telemedicine program, and rTPA use in the third hospital increase from none to less than 2%. In addition, one of the largest hospitals in the study actually saw a 14% decrease in rTPA use, a finding Dr. Wagner was hard pressed to explain.

"In my experience, there’s a huge integrated system required for telemedicine to work well, from the EMS [emergency medical services] people calling in a stroke alert in advance to the emergency doctors activating the telemedicine system. My theory would be that there might not have been complete buy-in from the staff."

The three hospitals that didn’t experience any benefit were the smallest in the cohort – a factor that probably contributed to their lack of results, he added.

"My theory here is that they spanned the largest area of geography, so having telemedicine might not improve rTPA usage, because the real issue was not being able to get patients there in time," he said.

The study was funded by Genentech. Dr. Wagner had no additional disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal