Headache & Migraine

LOS ANGELES—Ubrogepant may relieve the pain of acute migraine attacks, as well as other bothersome migraine-related symptoms, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The drug is well-tolerated and does not raise significant safety concerns, according to the researchers.

Ubrogepant is a novel, oral antagonist of the calcitonin gene-related peptide (CGRP) receptor that Allergan is developing for the acute treatment of migraine. Joel Trugman, MD, Director of Clinical Development for Allergan, and colleagues conducted a phase III study to examine the efficacy, safety, and tolerability of ubrogepant, compared with placebo, for the acute treatment of a single migraine attack.

Assessing Two Doses of Ubrogepant

In this multicenter, double-blind, parallel-group study, adult patients with a history of migraine with or without aura were randomized in equal groups to placebo, 50 mg of ubrogepant, or 100 mg of ubrogepant. Patients had as many as 60 days to treat a single migraine attack of moderate or severe headache pain intensity. The study’s two primary efficacy end points were pain freedom at two hours after initial dose and absence of the most bothersome migraine-associated symptom (MBS) at two hours after initial dose. Participants identified the MBS at the time of the treated attack. The investigators also assessed ubrogepant’s safety and tolerability.

Dr. Trugman and colleagues randomized 1,672 patients. Of this population, 1,436 participants were included in the safety population, and 1,327 were included in the modified-intention-to-treat efficacy analysis. The latter efficacy analysis included patients who received one or more dose of ubrogepant, recorded baseline headache severity, and recorded one or more postdose headache severity or MBS measurement at or before two hours.

Ubrogepant Was Superior to Placebo

The population’s mean age was 40.7. Most participants were Caucasian (82.4%) and female (87.5%). The MBS identified at the time of treatment were photophobia (56.4%), phonophobia (22.3%), and nausea (20.9%). At two hours after the initial dose, the percentage of patients achieving pain freedom was 19.2% for the 50-mg group, 21.2% for the 100-mg group, and 11.8% for controls. The percentage of patients achieving absence of MBS was 38.6% for the 50-mg group, 37.7% for the 100-mg group, and 27.8% for controls. The differences between the active and control groups were statistically significant for both end points.

Ubrogepant also yielded significantly improved results on secondary end points, compared with placebo. Approximately 61% of patients who took ubrogepant achieved pain relief at two hours, compared with 49% of controls. About 36% of patients in the 50-mg group and 38% of patients in the 100-mg group achieved sustained pain relief at two to 24 hours, compared with 21% of controls. In addition, the 100-mg dose of ubrogepant yielded statistically significant differences on sustained pain freedom at two to 24 hours and on absence of photophobia at two hours, compared with placebo.

The adverse-event profile of ubrogepant was similar to that of placebo. The most common adverse events within 48 hours of dosing were nausea, somnolence, and dry mouth. The incidence of each of these adverse events was less than 5%.

This study was supported by Allergan.

LOS ANGELES—Ubrogepant may relieve the pain of acute migraine attacks, as well as other bothersome migraine-related symptoms, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The drug is well-tolerated and does not raise significant safety concerns, according to the researchers.

Ubrogepant is a novel, oral antagonist of the calcitonin gene-related peptide (CGRP) receptor that Allergan is developing for the acute treatment of migraine. Joel Trugman, MD, Director of Clinical Development for Allergan, and colleagues conducted a phase III study to examine the efficacy, safety, and tolerability of ubrogepant, compared with placebo, for the acute treatment of a single migraine attack.

Assessing Two Doses of Ubrogepant

In this multicenter, double-blind, parallel-group study, adult patients with a history of migraine with or without aura were randomized in equal groups to placebo, 50 mg of ubrogepant, or 100 mg of ubrogepant. Patients had as many as 60 days to treat a single migraine attack of moderate or severe headache pain intensity. The study’s two primary efficacy end points were pain freedom at two hours after initial dose and absence of the most bothersome migraine-associated symptom (MBS) at two hours after initial dose. Participants identified the MBS at the time of the treated attack. The investigators also assessed ubrogepant’s safety and tolerability.

Dr. Trugman and colleagues randomized 1,672 patients. Of this population, 1,436 participants were included in the safety population, and 1,327 were included in the modified-intention-to-treat efficacy analysis. The latter efficacy analysis included patients who received one or more dose of ubrogepant, recorded baseline headache severity, and recorded one or more postdose headache severity or MBS measurement at or before two hours.

Ubrogepant Was Superior to Placebo

The population’s mean age was 40.7. Most participants were Caucasian (82.4%) and female (87.5%). The MBS identified at the time of treatment were photophobia (56.4%), phonophobia (22.3%), and nausea (20.9%). At two hours after the initial dose, the percentage of patients achieving pain freedom was 19.2% for the 50-mg group, 21.2% for the 100-mg group, and 11.8% for controls. The percentage of patients achieving absence of MBS was 38.6% for the 50-mg group, 37.7% for the 100-mg group, and 27.8% for controls. The differences between the active and control groups were statistically significant for both end points.

Ubrogepant also yielded significantly improved results on secondary end points, compared with placebo. Approximately 61% of patients who took ubrogepant achieved pain relief at two hours, compared with 49% of controls. About 36% of patients in the 50-mg group and 38% of patients in the 100-mg group achieved sustained pain relief at two to 24 hours, compared with 21% of controls. In addition, the 100-mg dose of ubrogepant yielded statistically significant differences on sustained pain freedom at two to 24 hours and on absence of photophobia at two hours, compared with placebo.

The adverse-event profile of ubrogepant was similar to that of placebo. The most common adverse events within 48 hours of dosing were nausea, somnolence, and dry mouth. The incidence of each of these adverse events was less than 5%.

This study was supported by Allergan.

LOS ANGELES—Ubrogepant may relieve the pain of acute migraine attacks, as well as other bothersome migraine-related symptoms, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The drug is well-tolerated and does not raise significant safety concerns, according to the researchers.

Ubrogepant is a novel, oral antagonist of the calcitonin gene-related peptide (CGRP) receptor that Allergan is developing for the acute treatment of migraine. Joel Trugman, MD, Director of Clinical Development for Allergan, and colleagues conducted a phase III study to examine the efficacy, safety, and tolerability of ubrogepant, compared with placebo, for the acute treatment of a single migraine attack.

Assessing Two Doses of Ubrogepant

In this multicenter, double-blind, parallel-group study, adult patients with a history of migraine with or without aura were randomized in equal groups to placebo, 50 mg of ubrogepant, or 100 mg of ubrogepant. Patients had as many as 60 days to treat a single migraine attack of moderate or severe headache pain intensity. The study’s two primary efficacy end points were pain freedom at two hours after initial dose and absence of the most bothersome migraine-associated symptom (MBS) at two hours after initial dose. Participants identified the MBS at the time of the treated attack. The investigators also assessed ubrogepant’s safety and tolerability.

Dr. Trugman and colleagues randomized 1,672 patients. Of this population, 1,436 participants were included in the safety population, and 1,327 were included in the modified-intention-to-treat efficacy analysis. The latter efficacy analysis included patients who received one or more dose of ubrogepant, recorded baseline headache severity, and recorded one or more postdose headache severity or MBS measurement at or before two hours.

Ubrogepant Was Superior to Placebo

The population’s mean age was 40.7. Most participants were Caucasian (82.4%) and female (87.5%). The MBS identified at the time of treatment were photophobia (56.4%), phonophobia (22.3%), and nausea (20.9%). At two hours after the initial dose, the percentage of patients achieving pain freedom was 19.2% for the 50-mg group, 21.2% for the 100-mg group, and 11.8% for controls. The percentage of patients achieving absence of MBS was 38.6% for the 50-mg group, 37.7% for the 100-mg group, and 27.8% for controls. The differences between the active and control groups were statistically significant for both end points.

Ubrogepant also yielded significantly improved results on secondary end points, compared with placebo. Approximately 61% of patients who took ubrogepant achieved pain relief at two hours, compared with 49% of controls. About 36% of patients in the 50-mg group and 38% of patients in the 100-mg group achieved sustained pain relief at two to 24 hours, compared with 21% of controls. In addition, the 100-mg dose of ubrogepant yielded statistically significant differences on sustained pain freedom at two to 24 hours and on absence of photophobia at two hours, compared with placebo.

The adverse-event profile of ubrogepant was similar to that of placebo. The most common adverse events within 48 hours of dosing were nausea, somnolence, and dry mouth. The incidence of each of these adverse events was less than 5%.

This study was supported by Allergan.

LOS ANGELES—Significantly more patients with chronic migraine versus episodic migraine report cardiovascular, respiratory, gastrointestinal, psychiatric, and sleep-related symptoms and conditions, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.

Certain comorbidities, including allergies, insomnia, and neck pain, have relative frequencies in chronic migraine that are at least 10% greater than in episodic migraine. “Mechanisms explaining this association might include direct causality (eg, chronic migraine causes the comorbidity), reverse causality (eg, the condition increases chronic migraine risk), and shared genetic or environmental risk factors,” said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in New York, and colleagues. Detection bias also may contribute to the association, they said.

Examining Relative Frequencies

Migraineurs often present with concomitant conditions that may exacerbate the disease, and many comorbidities occur more frequently in chronic migraine than in episodic migraine. To replicate and extend research on comorbid medical conditions in a systematically recruited sample of people with episodic and chronic migraine, Dr. Lipton and colleagues analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, a prospective web-based survey designed to characterize self-reported headache symptoms and severity in a representative sample of people with migraine in the United States.

The CaMEO study included a comorbidities-and-endophenotypes module that asked respondents whether they ever had specific symptoms or conditions and, if present, whether they had been confirmed or diagnosed by a doctor. The investigators analyzed self-reported data for symptoms easily identified by respondents and physician-diagnosed data for conditions that required a medical diagnosis. The researchers used chi-squared analysis to compare the relative frequencies of symptoms and conditions. Percentages for female-specific conditions (eg, polycystic ovary syndrome) were calculated by comparison with female migraineurs. Dr. Lipton and colleagues presented data about respiratory, sleep disorder, cardiovascular, and gastrointestinal comorbidities in one study and data about pain, psychiatric, and endocrine or neurologic comorbidities in another study.

In all, 16,763 CaMEO respondents with migraine received the comorbidities-and-endophenotypes module, and 12,810 provided valid responses. The analysis included 1,111 respondents (8.7%) with chronic migraine (ie, 15 or more headache days per month for more than three months) and 11,699 (91.3%) with episodic migraine (ie, fewer than 15 headache days per month). Compared with the episodic migraine group, the chronic migraine group had a similar mean age (41.3 vs 41.9), was more likely to be female (74.2% vs 81.5%), was more likely to be white (84.0% vs 88.7%), and had a higher mean BMI (27.7 kg/m2 vs 28.7 kg/m2). Compared with respondents with episodic migraine, respondents with chronic migraine more frequently reported allodynia, generalized anxiety disorder, and major depression and had a greater mean Migraine Disability Assessment Scale (MIDAS) score.

A Range of Symptoms and Conditions

Of the 31 respiratory, sleep disorder, cardiovascular, and gastrointestinal comorbidities assessed, the relative frequencies were significantly higher in chronic migraine for 93.5%. The following five conditions or groups of conditions had relative frequencies at least 10% higher in chronic migraine than episodic migraine: allergies, hay fever, or allergic rhinitis (61.2% vs 51.2%); sinusitis or sinus infection (63.5% vs 52.7%); insomnia (50.2% vs 35.6%); vertigo, dizziness, or balance problems (29.7% vs 17.8%); and gastroesophageal reflux disease (24.4% vs 14.3%).

Of the 28 pain, psychiatric, and endocrine or neurologic comorbidities assessed, the relative frequencies were significantly higher in chronic migraine for 85.7%. The following five conditions had relative frequencies more than 10% higher in chronic migraine than in episodic migraine: chronic back pain (37.6% vs 22.5%), chronic pain (22.2% vs 7.4%), neck pain (55.3% vs 38.1%), anxiety (42.2% vs 25.7%), and depression (45.6% vs 28.1%).

The Likelihood of Medication Overuse

Of the eight endocrine or neurologic comorbidities assessed (ie, hyperhidrosis, diabetes, seizures, spasticity, underactive thyroid or thyroid medication, cervical dystonia, gout, and polycystic ovary syndrome), all but gout and polycystic ovary syndrome had significantly higher relative frequencies in chronic migraine.

When the researchers used latent class analysis to identify natural subgroups of migraine based on profiles of comorbidities and concomitant conditions, they found that a subgroup with the most comorbidities was more likely to include individuals with chronic migraine (23.1% vs 4.8%) and had greater proportions of individuals with grade IV MIDAS scores (ie, severe disability; 48.1% vs 15.1%), allodynia (67.6% vs 38.3%), medication overuse (36.4% vs 8.9%), and aura (40.1% vs 23.9%), compared with a subgroup with the fewest comorbidities.

The studies were funded by Allergan.

—Jake Remaly

Suggested Reading

Adams AM, Serrano D, Buse DC, et al. The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7):563-578.

LOS ANGELES—Significantly more patients with chronic migraine versus episodic migraine report cardiovascular, respiratory, gastrointestinal, psychiatric, and sleep-related symptoms and conditions, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.

Certain comorbidities, including allergies, insomnia, and neck pain, have relative frequencies in chronic migraine that are at least 10% greater than in episodic migraine. “Mechanisms explaining this association might include direct causality (eg, chronic migraine causes the comorbidity), reverse causality (eg, the condition increases chronic migraine risk), and shared genetic or environmental risk factors,” said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in New York, and colleagues. Detection bias also may contribute to the association, they said.

Examining Relative Frequencies

Migraineurs often present with concomitant conditions that may exacerbate the disease, and many comorbidities occur more frequently in chronic migraine than in episodic migraine. To replicate and extend research on comorbid medical conditions in a systematically recruited sample of people with episodic and chronic migraine, Dr. Lipton and colleagues analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, a prospective web-based survey designed to characterize self-reported headache symptoms and severity in a representative sample of people with migraine in the United States.

The CaMEO study included a comorbidities-and-endophenotypes module that asked respondents whether they ever had specific symptoms or conditions and, if present, whether they had been confirmed or diagnosed by a doctor. The investigators analyzed self-reported data for symptoms easily identified by respondents and physician-diagnosed data for conditions that required a medical diagnosis. The researchers used chi-squared analysis to compare the relative frequencies of symptoms and conditions. Percentages for female-specific conditions (eg, polycystic ovary syndrome) were calculated by comparison with female migraineurs. Dr. Lipton and colleagues presented data about respiratory, sleep disorder, cardiovascular, and gastrointestinal comorbidities in one study and data about pain, psychiatric, and endocrine or neurologic comorbidities in another study.

In all, 16,763 CaMEO respondents with migraine received the comorbidities-and-endophenotypes module, and 12,810 provided valid responses. The analysis included 1,111 respondents (8.7%) with chronic migraine (ie, 15 or more headache days per month for more than three months) and 11,699 (91.3%) with episodic migraine (ie, fewer than 15 headache days per month). Compared with the episodic migraine group, the chronic migraine group had a similar mean age (41.3 vs 41.9), was more likely to be female (74.2% vs 81.5%), was more likely to be white (84.0% vs 88.7%), and had a higher mean BMI (27.7 kg/m2 vs 28.7 kg/m2). Compared with respondents with episodic migraine, respondents with chronic migraine more frequently reported allodynia, generalized anxiety disorder, and major depression and had a greater mean Migraine Disability Assessment Scale (MIDAS) score.

A Range of Symptoms and Conditions

Of the 31 respiratory, sleep disorder, cardiovascular, and gastrointestinal comorbidities assessed, the relative frequencies were significantly higher in chronic migraine for 93.5%. The following five conditions or groups of conditions had relative frequencies at least 10% higher in chronic migraine than episodic migraine: allergies, hay fever, or allergic rhinitis (61.2% vs 51.2%); sinusitis or sinus infection (63.5% vs 52.7%); insomnia (50.2% vs 35.6%); vertigo, dizziness, or balance problems (29.7% vs 17.8%); and gastroesophageal reflux disease (24.4% vs 14.3%).

Of the 28 pain, psychiatric, and endocrine or neurologic comorbidities assessed, the relative frequencies were significantly higher in chronic migraine for 85.7%. The following five conditions had relative frequencies more than 10% higher in chronic migraine than in episodic migraine: chronic back pain (37.6% vs 22.5%), chronic pain (22.2% vs 7.4%), neck pain (55.3% vs 38.1%), anxiety (42.2% vs 25.7%), and depression (45.6% vs 28.1%).

The Likelihood of Medication Overuse

Of the eight endocrine or neurologic comorbidities assessed (ie, hyperhidrosis, diabetes, seizures, spasticity, underactive thyroid or thyroid medication, cervical dystonia, gout, and polycystic ovary syndrome), all but gout and polycystic ovary syndrome had significantly higher relative frequencies in chronic migraine.

When the researchers used latent class analysis to identify natural subgroups of migraine based on profiles of comorbidities and concomitant conditions, they found that a subgroup with the most comorbidities was more likely to include individuals with chronic migraine (23.1% vs 4.8%) and had greater proportions of individuals with grade IV MIDAS scores (ie, severe disability; 48.1% vs 15.1%), allodynia (67.6% vs 38.3%), medication overuse (36.4% vs 8.9%), and aura (40.1% vs 23.9%), compared with a subgroup with the fewest comorbidities.

The studies were funded by Allergan.

—Jake Remaly

Suggested Reading

Adams AM, Serrano D, Buse DC, et al. The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7):563-578.

LOS ANGELES—Significantly more patients with chronic migraine versus episodic migraine report cardiovascular, respiratory, gastrointestinal, psychiatric, and sleep-related symptoms and conditions, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.

Certain comorbidities, including allergies, insomnia, and neck pain, have relative frequencies in chronic migraine that are at least 10% greater than in episodic migraine. “Mechanisms explaining this association might include direct causality (eg, chronic migraine causes the comorbidity), reverse causality (eg, the condition increases chronic migraine risk), and shared genetic or environmental risk factors,” said Richard B. Lipton, MD, Edwin S. Lowe Chair in Neurology at Albert Einstein College of Medicine in New York, and colleagues. Detection bias also may contribute to the association, they said.

Examining Relative Frequencies

Migraineurs often present with concomitant conditions that may exacerbate the disease, and many comorbidities occur more frequently in chronic migraine than in episodic migraine. To replicate and extend research on comorbid medical conditions in a systematically recruited sample of people with episodic and chronic migraine, Dr. Lipton and colleagues analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study, a prospective web-based survey designed to characterize self-reported headache symptoms and severity in a representative sample of people with migraine in the United States.

The CaMEO study included a comorbidities-and-endophenotypes module that asked respondents whether they ever had specific symptoms or conditions and, if present, whether they had been confirmed or diagnosed by a doctor. The investigators analyzed self-reported data for symptoms easily identified by respondents and physician-diagnosed data for conditions that required a medical diagnosis. The researchers used chi-squared analysis to compare the relative frequencies of symptoms and conditions. Percentages for female-specific conditions (eg, polycystic ovary syndrome) were calculated by comparison with female migraineurs. Dr. Lipton and colleagues presented data about respiratory, sleep disorder, cardiovascular, and gastrointestinal comorbidities in one study and data about pain, psychiatric, and endocrine or neurologic comorbidities in another study.

In all, 16,763 CaMEO respondents with migraine received the comorbidities-and-endophenotypes module, and 12,810 provided valid responses. The analysis included 1,111 respondents (8.7%) with chronic migraine (ie, 15 or more headache days per month for more than three months) and 11,699 (91.3%) with episodic migraine (ie, fewer than 15 headache days per month). Compared with the episodic migraine group, the chronic migraine group had a similar mean age (41.3 vs 41.9), was more likely to be female (74.2% vs 81.5%), was more likely to be white (84.0% vs 88.7%), and had a higher mean BMI (27.7 kg/m2 vs 28.7 kg/m2). Compared with respondents with episodic migraine, respondents with chronic migraine more frequently reported allodynia, generalized anxiety disorder, and major depression and had a greater mean Migraine Disability Assessment Scale (MIDAS) score.

A Range of Symptoms and Conditions

Of the 31 respiratory, sleep disorder, cardiovascular, and gastrointestinal comorbidities assessed, the relative frequencies were significantly higher in chronic migraine for 93.5%. The following five conditions or groups of conditions had relative frequencies at least 10% higher in chronic migraine than episodic migraine: allergies, hay fever, or allergic rhinitis (61.2% vs 51.2%); sinusitis or sinus infection (63.5% vs 52.7%); insomnia (50.2% vs 35.6%); vertigo, dizziness, or balance problems (29.7% vs 17.8%); and gastroesophageal reflux disease (24.4% vs 14.3%).

Of the 28 pain, psychiatric, and endocrine or neurologic comorbidities assessed, the relative frequencies were significantly higher in chronic migraine for 85.7%. The following five conditions had relative frequencies more than 10% higher in chronic migraine than in episodic migraine: chronic back pain (37.6% vs 22.5%), chronic pain (22.2% vs 7.4%), neck pain (55.3% vs 38.1%), anxiety (42.2% vs 25.7%), and depression (45.6% vs 28.1%).

The Likelihood of Medication Overuse

Of the eight endocrine or neurologic comorbidities assessed (ie, hyperhidrosis, diabetes, seizures, spasticity, underactive thyroid or thyroid medication, cervical dystonia, gout, and polycystic ovary syndrome), all but gout and polycystic ovary syndrome had significantly higher relative frequencies in chronic migraine.

When the researchers used latent class analysis to identify natural subgroups of migraine based on profiles of comorbidities and concomitant conditions, they found that a subgroup with the most comorbidities was more likely to include individuals with chronic migraine (23.1% vs 4.8%) and had greater proportions of individuals with grade IV MIDAS scores (ie, severe disability; 48.1% vs 15.1%), allodynia (67.6% vs 38.3%), medication overuse (36.4% vs 8.9%), and aura (40.1% vs 23.9%), compared with a subgroup with the fewest comorbidities.

The studies were funded by Allergan.

—Jake Remaly

Suggested Reading

Adams AM, Serrano D, Buse DC, et al. The impact of chronic migraine: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study methods and baseline results. Cephalalgia. 2015;35(7):563-578.

LOS ANGELES—Patients who have tried and failed other preventive therapies may find that erenumab can prevent their migraines, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor.

Current oral preventive therapies are associated with low adherence rates due to their lack of efficacy or poor tolerability. Therefore, researchers thought it important to assess the safety and efficacy of erenumab in patients who had failed multiple therapies. A previous post hoc analysis of the STRIVE study showed that patients who had failed two prior preventives responded to erenumab. “Their odds ratio was far greater than [that of] those who were previous preventive naïve,” said Peter J. Goadsby, MD, PhD, who presented the newest erenumab data in the Emerging Science plenary session. Dr. Goadsby is a Professor of Neurology at Kings College London and the University of California, San Francisco.

The LIBERTY Study

The LIBERTY study was a phase IIIb, randomized, double-blind, placebo-controlled trial thta assessed erenumab in patients who had failed at least two and not more than four prior preventives. A total of 246 patients with episodic migraine were randomized one to one to an injection of erenumab (140 mg) or placebo once per month for three months. There were 125 patients in the placebo arm and 121 in the erenumab arm. The primary end point was the proportion of patients achieving a 50% or greater reduction in mean monthly migraine days (MMDs) during weeks nine to 12 (ie, month three) of the study. Secondary end points included change from baseline to month three in MMDs and monthly acute migraine-specific medication days (MSMDs) and safety and tolerability.

At baseline, 39% of participants had been treated unsuccessfully with two other medications, 38% with three medications, and 23% with four medications. On average, participants had nine migraine days per month and used an acute migraine drug to stop an attack five times per month.

At week 12, the proportion of patients achieving a 50% or greater reduction in MMDs was higher in those treated with erenumab versus placebo (30.3% vs 13.7%). At week 12, there were greater reductions in MMDs and MSMDs with erenumab versus placebo. The safety and tolerability of erenumab were comparable to those of placebo. No patients in the erenumab group discontinued treatment due to adverse events.

Hope for Refractory Patients?

LIBERTY is the first dedicated study to address a problem that is all too common in neurology, said Dr. Goadsby. “It is hard to deal with patients who have failed prior preventives.” Erenumab, he said, is the first of the CGRP monoclonal antibodies to “control migraine and prevent migraine in patients who are so disabled and whom we cannot treat with current medicine.”

“Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief,” said Dr. Reuter. “More research is now needed to understand who is most likely to benefit from this new treatment.”

The study was supported by Novartis Pharma.

—Glenn S. Williams

LOS ANGELES—Patients who have tried and failed other preventive therapies may find that erenumab can prevent their migraines, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor.

Current oral preventive therapies are associated with low adherence rates due to their lack of efficacy or poor tolerability. Therefore, researchers thought it important to assess the safety and efficacy of erenumab in patients who had failed multiple therapies. A previous post hoc analysis of the STRIVE study showed that patients who had failed two prior preventives responded to erenumab. “Their odds ratio was far greater than [that of] those who were previous preventive naïve,” said Peter J. Goadsby, MD, PhD, who presented the newest erenumab data in the Emerging Science plenary session. Dr. Goadsby is a Professor of Neurology at Kings College London and the University of California, San Francisco.

The LIBERTY Study

The LIBERTY study was a phase IIIb, randomized, double-blind, placebo-controlled trial thta assessed erenumab in patients who had failed at least two and not more than four prior preventives. A total of 246 patients with episodic migraine were randomized one to one to an injection of erenumab (140 mg) or placebo once per month for three months. There were 125 patients in the placebo arm and 121 in the erenumab arm. The primary end point was the proportion of patients achieving a 50% or greater reduction in mean monthly migraine days (MMDs) during weeks nine to 12 (ie, month three) of the study. Secondary end points included change from baseline to month three in MMDs and monthly acute migraine-specific medication days (MSMDs) and safety and tolerability.

At baseline, 39% of participants had been treated unsuccessfully with two other medications, 38% with three medications, and 23% with four medications. On average, participants had nine migraine days per month and used an acute migraine drug to stop an attack five times per month.

At week 12, the proportion of patients achieving a 50% or greater reduction in MMDs was higher in those treated with erenumab versus placebo (30.3% vs 13.7%). At week 12, there were greater reductions in MMDs and MSMDs with erenumab versus placebo. The safety and tolerability of erenumab were comparable to those of placebo. No patients in the erenumab group discontinued treatment due to adverse events.

Hope for Refractory Patients?

LIBERTY is the first dedicated study to address a problem that is all too common in neurology, said Dr. Goadsby. “It is hard to deal with patients who have failed prior preventives.” Erenumab, he said, is the first of the CGRP monoclonal antibodies to “control migraine and prevent migraine in patients who are so disabled and whom we cannot treat with current medicine.”

“Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief,” said Dr. Reuter. “More research is now needed to understand who is most likely to benefit from this new treatment.”

The study was supported by Novartis Pharma.

—Glenn S. Williams

LOS ANGELES—Patients who have tried and failed other preventive therapies may find that erenumab can prevent their migraines, according to a study presented at the 70th Annual Meeting of the American Academy of Neurology. Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor.

Current oral preventive therapies are associated with low adherence rates due to their lack of efficacy or poor tolerability. Therefore, researchers thought it important to assess the safety and efficacy of erenumab in patients who had failed multiple therapies. A previous post hoc analysis of the STRIVE study showed that patients who had failed two prior preventives responded to erenumab. “Their odds ratio was far greater than [that of] those who were previous preventive naïve,” said Peter J. Goadsby, MD, PhD, who presented the newest erenumab data in the Emerging Science plenary session. Dr. Goadsby is a Professor of Neurology at Kings College London and the University of California, San Francisco.

The LIBERTY Study

The LIBERTY study was a phase IIIb, randomized, double-blind, placebo-controlled trial thta assessed erenumab in patients who had failed at least two and not more than four prior preventives. A total of 246 patients with episodic migraine were randomized one to one to an injection of erenumab (140 mg) or placebo once per month for three months. There were 125 patients in the placebo arm and 121 in the erenumab arm. The primary end point was the proportion of patients achieving a 50% or greater reduction in mean monthly migraine days (MMDs) during weeks nine to 12 (ie, month three) of the study. Secondary end points included change from baseline to month three in MMDs and monthly acute migraine-specific medication days (MSMDs) and safety and tolerability.

At baseline, 39% of participants had been treated unsuccessfully with two other medications, 38% with three medications, and 23% with four medications. On average, participants had nine migraine days per month and used an acute migraine drug to stop an attack five times per month.

At week 12, the proportion of patients achieving a 50% or greater reduction in MMDs was higher in those treated with erenumab versus placebo (30.3% vs 13.7%). At week 12, there were greater reductions in MMDs and MSMDs with erenumab versus placebo. The safety and tolerability of erenumab were comparable to those of placebo. No patients in the erenumab group discontinued treatment due to adverse events.

Hope for Refractory Patients?

LIBERTY is the first dedicated study to address a problem that is all too common in neurology, said Dr. Goadsby. “It is hard to deal with patients who have failed prior preventives.” Erenumab, he said, is the first of the CGRP monoclonal antibodies to “control migraine and prevent migraine in patients who are so disabled and whom we cannot treat with current medicine.”

“Our results show that people who thought their migraines were difficult to prevent may actually have hope of finding pain relief,” said Dr. Reuter. “More research is now needed to understand who is most likely to benefit from this new treatment.”

The study was supported by Novartis Pharma.

—Glenn S. Williams

LOS ANGELES—Noninvasive vagus nerve stimulation (nVNS) is a rapidly effective, well-tolerated, and practical option for the acute treatment of episodic migraine, according to the results of PRESTO, a multicenter, randomized, sham-controlled, double-blind trial presented at the 70th Annual Meeting of the American Academy of Neurology. “There are multiple options for nVNS in the acute treatment of migraine,” said Cristina Tassorelli, MD, PhD, Professor of Neurology at the University of Pavia and Director of the Headache Science Centre at the Casimiro Mondino National Neurological Institute of Pavia in Italy. “It can be used alone because it is effective, it can be used in combination with drugs because we do not expect any significant interactions, and it is also indicated in patients who have developed medication overuse.”

Neuromodulation for Migraine

The aim of the PRESTO trial was to evaluate the efficacy, safety, and tolerability of gammaCore, an nVNS device, for the acute treatment of migraine. The handheld gammaCore device is already FDA cleared for the acute treatment of pain associated with episodic cluster headache and migraine headache in adults. PRESTO was the trial that supported the FDA clearance of gammaCore for migraine.

Following an observational period of four weeks, patients enrolled in PRESTO were randomized to nVNS or sham stimulation for four weeks or until five attacks were treated. Following this period, patients entered the open-label period for another four weeks or five additional attacks.

Low-intensity current, which induced a tingling sensation on the skin that was similar to the sensation of the active stimulation, was used for the sham stimulation. Patients were instructed to treat their attack early with two two-minute stimulations, one for each side of the neck. At 15 minutes, patients assessed the intensity of their pain. If pain was still present, another set of two stimulations was self-administered. A second assessment of pain occurred at 120 minutes, with the possibility of administering another stimulation. Rescue medication use before 120 minutes was considered to indicate treatment failure.

Patients with episodic migraine with or without aura were recruited from 10 Italian tertiary headache centers. A total of 285 patients were enrolled, and 248 randomized: 122 to the active arm and 126 to the sham arm. A total of 117 patients completed the double-blind period in the active arm, and 123 patients in the sham arm. “We had a few discontinuations in both arms, one of which was due to the device,” Dr. Tassorelli and colleagues noted. “Demographic and baseline characteristics show typical pictures of patients with episodic migraine,” Dr. Tassorelli said. Study subjects were mostly young, mostly female, and mostly experiencing migraine without aura. Subjects had a mean of five attacks of migraine per month, a mean of six days of headache per month, and a mean monthly intake of five acute migraine medications. One-third of the patients were on stable prophylactic medications. About 40% of the patients were having moderate pain when they treated their first attack. One-third of them were experiencing mild pain, while 23% were experiencing severe pain in the active group and 15% were having severe pain in the sham group.

Stimulation Reduced Pain

The primary end point of the study was pain freedom at 120 minutes for the first attack. The investigators found a significant difference between the two arms at 30 minutes that became more evident at 60 minutes. At 120 minutes, there was a difference, “but we lost the statistical significance,” Dr. Tassorelli reported. “However, a more refined, post hoc repeated-measure analysis showed that the group treated with the active stimulation had significantly more pain relief than the sham stimulation over the 120-minute period.”

One of the secondary outcome measures was headache response for the first attack, meaning a transition from severe or moderate pain to mild or no pain. “There was some difference at 30 minutes, although it was not significant. It was almost significant at 60 minutes, and it was definitely significant between groups in favor of the active nVNS at 120 minutes,” Dr. Tassorelli said.

The rate of participants who had a therapeutic response for 50% of attacks or more at 120 minutes speaks to the consistency of the response. Almost half of the patients responded to nVNS at 120 minutes for 50% or more of all treated attacks—47.6% achieved mild or no pain at 120 minutes in the treatment group versus 32.3% in the sham group; 32.4% achieved pain freedom at 120 minutes in the treatment group versus 18.2% in the sham group.

“We did not have many adverse events in this study,” Dr. Tassorelli said. Adverse effects of nVNS, mainly application site discomfort, were infrequent, mild, and transitory. No serious adverse events were recorded, and none of the patients in the active treatment group discontinued treatment due to adverse events.

In summary, nVNS “proved superior to sham for pain freedom at 30 minutes and at 60 minutes, but not at 120 minutes, which was our primary end point,” said Dr. Tassorelli and colleagues. “However, repeated-measures analysis validated the primary end point, indicating the superiority of active stimulation over sham through 120 minutes. This study provides class one evidence for the efficacy of nVNS in the acute treatment of episodic migraine.”

This study was sponsored by electroCore.

—Glenn S. Williams

LOS ANGELES—Noninvasive vagus nerve stimulation (nVNS) is a rapidly effective, well-tolerated, and practical option for the acute treatment of episodic migraine, according to the results of PRESTO, a multicenter, randomized, sham-controlled, double-blind trial presented at the 70th Annual Meeting of the American Academy of Neurology. “There are multiple options for nVNS in the acute treatment of migraine,” said Cristina Tassorelli, MD, PhD, Professor of Neurology at the University of Pavia and Director of the Headache Science Centre at the Casimiro Mondino National Neurological Institute of Pavia in Italy. “It can be used alone because it is effective, it can be used in combination with drugs because we do not expect any significant interactions, and it is also indicated in patients who have developed medication overuse.”

Neuromodulation for Migraine

The aim of the PRESTO trial was to evaluate the efficacy, safety, and tolerability of gammaCore, an nVNS device, for the acute treatment of migraine. The handheld gammaCore device is already FDA cleared for the acute treatment of pain associated with episodic cluster headache and migraine headache in adults. PRESTO was the trial that supported the FDA clearance of gammaCore for migraine.

Following an observational period of four weeks, patients enrolled in PRESTO were randomized to nVNS or sham stimulation for four weeks or until five attacks were treated. Following this period, patients entered the open-label period for another four weeks or five additional attacks.

Low-intensity current, which induced a tingling sensation on the skin that was similar to the sensation of the active stimulation, was used for the sham stimulation. Patients were instructed to treat their attack early with two two-minute stimulations, one for each side of the neck. At 15 minutes, patients assessed the intensity of their pain. If pain was still present, another set of two stimulations was self-administered. A second assessment of pain occurred at 120 minutes, with the possibility of administering another stimulation. Rescue medication use before 120 minutes was considered to indicate treatment failure.

Patients with episodic migraine with or without aura were recruited from 10 Italian tertiary headache centers. A total of 285 patients were enrolled, and 248 randomized: 122 to the active arm and 126 to the sham arm. A total of 117 patients completed the double-blind period in the active arm, and 123 patients in the sham arm. “We had a few discontinuations in both arms, one of which was due to the device,” Dr. Tassorelli and colleagues noted. “Demographic and baseline characteristics show typical pictures of patients with episodic migraine,” Dr. Tassorelli said. Study subjects were mostly young, mostly female, and mostly experiencing migraine without aura. Subjects had a mean of five attacks of migraine per month, a mean of six days of headache per month, and a mean monthly intake of five acute migraine medications. One-third of the patients were on stable prophylactic medications. About 40% of the patients were having moderate pain when they treated their first attack. One-third of them were experiencing mild pain, while 23% were experiencing severe pain in the active group and 15% were having severe pain in the sham group.

Stimulation Reduced Pain

The primary end point of the study was pain freedom at 120 minutes for the first attack. The investigators found a significant difference between the two arms at 30 minutes that became more evident at 60 minutes. At 120 minutes, there was a difference, “but we lost the statistical significance,” Dr. Tassorelli reported. “However, a more refined, post hoc repeated-measure analysis showed that the group treated with the active stimulation had significantly more pain relief than the sham stimulation over the 120-minute period.”

One of the secondary outcome measures was headache response for the first attack, meaning a transition from severe or moderate pain to mild or no pain. “There was some difference at 30 minutes, although it was not significant. It was almost significant at 60 minutes, and it was definitely significant between groups in favor of the active nVNS at 120 minutes,” Dr. Tassorelli said.

The rate of participants who had a therapeutic response for 50% of attacks or more at 120 minutes speaks to the consistency of the response. Almost half of the patients responded to nVNS at 120 minutes for 50% or more of all treated attacks—47.6% achieved mild or no pain at 120 minutes in the treatment group versus 32.3% in the sham group; 32.4% achieved pain freedom at 120 minutes in the treatment group versus 18.2% in the sham group.

“We did not have many adverse events in this study,” Dr. Tassorelli said. Adverse effects of nVNS, mainly application site discomfort, were infrequent, mild, and transitory. No serious adverse events were recorded, and none of the patients in the active treatment group discontinued treatment due to adverse events.

In summary, nVNS “proved superior to sham for pain freedom at 30 minutes and at 60 minutes, but not at 120 minutes, which was our primary end point,” said Dr. Tassorelli and colleagues. “However, repeated-measures analysis validated the primary end point, indicating the superiority of active stimulation over sham through 120 minutes. This study provides class one evidence for the efficacy of nVNS in the acute treatment of episodic migraine.”

This study was sponsored by electroCore.

—Glenn S. Williams

LOS ANGELES—Noninvasive vagus nerve stimulation (nVNS) is a rapidly effective, well-tolerated, and practical option for the acute treatment of episodic migraine, according to the results of PRESTO, a multicenter, randomized, sham-controlled, double-blind trial presented at the 70th Annual Meeting of the American Academy of Neurology. “There are multiple options for nVNS in the acute treatment of migraine,” said Cristina Tassorelli, MD, PhD, Professor of Neurology at the University of Pavia and Director of the Headache Science Centre at the Casimiro Mondino National Neurological Institute of Pavia in Italy. “It can be used alone because it is effective, it can be used in combination with drugs because we do not expect any significant interactions, and it is also indicated in patients who have developed medication overuse.”

Neuromodulation for Migraine

The aim of the PRESTO trial was to evaluate the efficacy, safety, and tolerability of gammaCore, an nVNS device, for the acute treatment of migraine. The handheld gammaCore device is already FDA cleared for the acute treatment of pain associated with episodic cluster headache and migraine headache in adults. PRESTO was the trial that supported the FDA clearance of gammaCore for migraine.

Following an observational period of four weeks, patients enrolled in PRESTO were randomized to nVNS or sham stimulation for four weeks or until five attacks were treated. Following this period, patients entered the open-label period for another four weeks or five additional attacks.

Low-intensity current, which induced a tingling sensation on the skin that was similar to the sensation of the active stimulation, was used for the sham stimulation. Patients were instructed to treat their attack early with two two-minute stimulations, one for each side of the neck. At 15 minutes, patients assessed the intensity of their pain. If pain was still present, another set of two stimulations was self-administered. A second assessment of pain occurred at 120 minutes, with the possibility of administering another stimulation. Rescue medication use before 120 minutes was considered to indicate treatment failure.

Patients with episodic migraine with or without aura were recruited from 10 Italian tertiary headache centers. A total of 285 patients were enrolled, and 248 randomized: 122 to the active arm and 126 to the sham arm. A total of 117 patients completed the double-blind period in the active arm, and 123 patients in the sham arm. “We had a few discontinuations in both arms, one of which was due to the device,” Dr. Tassorelli and colleagues noted. “Demographic and baseline characteristics show typical pictures of patients with episodic migraine,” Dr. Tassorelli said. Study subjects were mostly young, mostly female, and mostly experiencing migraine without aura. Subjects had a mean of five attacks of migraine per month, a mean of six days of headache per month, and a mean monthly intake of five acute migraine medications. One-third of the patients were on stable prophylactic medications. About 40% of the patients were having moderate pain when they treated their first attack. One-third of them were experiencing mild pain, while 23% were experiencing severe pain in the active group and 15% were having severe pain in the sham group.

Stimulation Reduced Pain

The primary end point of the study was pain freedom at 120 minutes for the first attack. The investigators found a significant difference between the two arms at 30 minutes that became more evident at 60 minutes. At 120 minutes, there was a difference, “but we lost the statistical significance,” Dr. Tassorelli reported. “However, a more refined, post hoc repeated-measure analysis showed that the group treated with the active stimulation had significantly more pain relief than the sham stimulation over the 120-minute period.”

One of the secondary outcome measures was headache response for the first attack, meaning a transition from severe or moderate pain to mild or no pain. “There was some difference at 30 minutes, although it was not significant. It was almost significant at 60 minutes, and it was definitely significant between groups in favor of the active nVNS at 120 minutes,” Dr. Tassorelli said.

The rate of participants who had a therapeutic response for 50% of attacks or more at 120 minutes speaks to the consistency of the response. Almost half of the patients responded to nVNS at 120 minutes for 50% or more of all treated attacks—47.6% achieved mild or no pain at 120 minutes in the treatment group versus 32.3% in the sham group; 32.4% achieved pain freedom at 120 minutes in the treatment group versus 18.2% in the sham group.

“We did not have many adverse events in this study,” Dr. Tassorelli said. Adverse effects of nVNS, mainly application site discomfort, were infrequent, mild, and transitory. No serious adverse events were recorded, and none of the patients in the active treatment group discontinued treatment due to adverse events.

In summary, nVNS “proved superior to sham for pain freedom at 30 minutes and at 60 minutes, but not at 120 minutes, which was our primary end point,” said Dr. Tassorelli and colleagues. “However, repeated-measures analysis validated the primary end point, indicating the superiority of active stimulation over sham through 120 minutes. This study provides class one evidence for the efficacy of nVNS in the acute treatment of episodic migraine.”

This study was sponsored by electroCore.

—Glenn S. Williams

First Anti-CGRP Monoclonal Antibody Gains FDA Approval

The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.

FDA Approves Gilenya for Pediatric Use

The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.

FDA Approves Treatment for CIDP

The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.

DBS Device Approved for Refractory Epilepsy

The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.

FDA Issues Warning About Lamictal

The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.

First Anti-CGRP Monoclonal Antibody Gains FDA Approval

The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.

FDA Approves Gilenya for Pediatric Use

The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.

FDA Approves Treatment for CIDP

The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.

DBS Device Approved for Refractory Epilepsy

The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.

FDA Issues Warning About Lamictal

The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.

First Anti-CGRP Monoclonal Antibody Gains FDA Approval

The FDA approved Aimovig (erenumab-aooe) for the preventive treatment of migraine in adults. Aimovig is the first FDA-approved preventive migraine treatment in a new class of drugs that blocks the activity of calcitonin gene-related peptide (CGRP). The treatment is given by once-monthly self-injections. Aimovig’s effectiveness was evaluated in three placebo-controlled clinical trials. The first included 955 patients with episodic migraine. Over six months, treated patients had, on average, one to two fewer monthly migraine days than controls. The second study included 577 patients with episodic migraine. Over three months, treated patients had, on average, one fewer migraine day per month than controls. The third study evaluated 667 patients with chronic migraine. Over three months, treated patients had, on average, 2.5 fewer monthly migraine days than controls. Aimovig is marketed by Amgen.

FDA Approves Gilenya for Pediatric Use

The FDA has approved Gilenya (fingolimod) for the treatment of children and adolescents between the ages of 10 and 18 with relapsing forms of multiple sclerosis (MS), making it the first disease-modifying therapy indicated for these young patients. The approval extends the age range for the drug, which was previously approved for patients age 18 and older with relapsing MS. Gilenya was granted Breakthrough Therapy status in December 2017 for this pediatric indication. The approval was supported by PARADIGMS, a double-blind, randomized, multicenter phase III safety and efficacy study of Gilenya versus interferon beta-1a. In this study, oral Gilenya reduced the annualized relapse rate by approximately 82% for as long as two years, compared with interferon beta-1a intramuscular injections in adolescents with relapsing MS. Gilenya is marketed by Novartis.

FDA Approves Treatment for CIDP

The FDA has approved Hizentra (immune globulin subcutaneous [human] 20% liquid) as the first subcutaneous immunoglobulin (SCIg) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment. The approval was based on the phase III PATH study, which was the largest controlled clinical study of patients with CIDP to date. The percentage of patients experiencing CIDP relapse or withdrawal for any other reason during SCIg treatment was significantly lower with Hizentra (38.6% on low-dose Hizentra [0.2 g/kg weekly], 32.8% on high-dose Hizentra [0.4 g/kg weekly]) than with placebo (63.2%). Treated patients reported fewer systemic adverse reactions per infusion, compared with IVIg treatment (2.7% vs 9.8%, respectively). Approximately 93% of infusions caused no adverse reactions. Hizentra is marketed by CSL Behring.

DBS Device Approved for Refractory Epilepsy

The FDA granted premarket approval for Medtronic’s deep brain stimulation (DBS) therapy as adjunctive treatment for reducing the frequency of partial-onset seizures in patients age 18 or older who are refractory to three or more antiepileptic drugs. The approval is based on the blinded phase and seven-year follow-up data from the SANTE trial, which included 110 patients. The median total seizure frequency reduction from baseline was 40.4% in implanted patients versus 14.5% for the placebo group at three months and 75% at seven years with ongoing open-label therapy. Twenty subjects (18%) had at least one six-month seizure-free period between implant and year seven, including eight subjects (7%) who were seizure-free for the preceding two years. Seizure severity and quality-of-life scales showed statistically significant improvement from baseline to year seven. No significant cognitive declines or worsening of depression were noted.

FDA Issues Warning About Lamictal

The FDA recently warned that Lamictal (lamotrigine), frequently used for treating seizures and bipolar disorder, can cause a rare but serious immune system reaction called hemophagocytic lymphohistiocytosis (HLH), which can be life-threatening. HLH typically presents as a persistent fever, usually greater than 101° F, and can lead to severe problems with blood cells and vital organs. Health care professionals should be aware that prompt recognition and early treatment are important for improving HLH outcomes and decreasing mortality. Diagnosis is often complicated because early signs and symptoms, such as rash and fever, are not specific. HLH also may be confused with other serious immune-related adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS). The FDA is requiring a change to the drug’s prescribing information and drug labeling.

The Food and Drug Administration has approved Aimovig (erenumab-aooe), delivered once a month via injection, for the prevention of migraines in adults.

Aimovig is the first FDA-approved treatment developed to prevent migraines by blocking the calcitonin gene–related peptide receptor.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

The Food and Drug Administration has approved Aimovig (erenumab-aooe), delivered once a month via injection, for the prevention of migraines in adults.

Aimovig is the first FDA-approved treatment developed to prevent migraines by blocking the calcitonin gene–related peptide receptor.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

The Food and Drug Administration has approved Aimovig (erenumab-aooe), delivered once a month via injection, for the prevention of migraines in adults.

Aimovig is the first FDA-approved treatment developed to prevent migraines by blocking the calcitonin gene–related peptide receptor.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

Abdominal migraine is a common cause of chronic and recurrent abdominal pain in children, according to a recent review. It is characterized by paroxysms of moderate to severe abdominal pain that is midline, periumbilical, or diffuse in location and accompanied by other symptoms including headache, anorexia, nausea, vomiting, or pallor. Despite the presence of comprehensive diagnostic criteria, it continues to be an underdiagnosed entity. Key points include:

• The average age of diagnosis is 3 to 10 years with peak incidence at 7 years.
• Most of the patients have a personal or family history of migraine.
• Pathophysiology of the condition is believed to be similar to that of other functional gastrointestinal disorders and cephalic migraine; it is also well recognized as a type of pediatric migraine variant.
• A careful history, thorough physical examination, and use of well-defined, symptom-based guidelines are needed to make a diagnosis.
• Although it resolves completely in most of the patients, these patients have a strong propensity to develop migraine later in life.
• Nonpharmacologic treatment options, including avoidance of triggers, behavior therapy, and dietary modifications should be the initial line of management.

Pediatric abdominal migraine: current perspectives on a lesser known entity. [Published online ahead of print April 24, 2018]. Pediatric Health Med Ther. doi:10.2147%2FPHMT.S127210.

Abdominal migraine is a common cause of chronic and recurrent abdominal pain in children, according to a recent review. It is characterized by paroxysms of moderate to severe abdominal pain that is midline, periumbilical, or diffuse in location and accompanied by other symptoms including headache, anorexia, nausea, vomiting, or pallor. Despite the presence of comprehensive diagnostic criteria, it continues to be an underdiagnosed entity. Key points include:

• The average age of diagnosis is 3 to 10 years with peak incidence at 7 years.
• Most of the patients have a personal or family history of migraine.
• Pathophysiology of the condition is believed to be similar to that of other functional gastrointestinal disorders and cephalic migraine; it is also well recognized as a type of pediatric migraine variant.
• A careful history, thorough physical examination, and use of well-defined, symptom-based guidelines are needed to make a diagnosis.
• Although it resolves completely in most of the patients, these patients have a strong propensity to develop migraine later in life.
• Nonpharmacologic treatment options, including avoidance of triggers, behavior therapy, and dietary modifications should be the initial line of management.

Pediatric abdominal migraine: current perspectives on a lesser known entity. [Published online ahead of print April 24, 2018]. Pediatric Health Med Ther. doi:10.2147%2FPHMT.S127210.

Abdominal migraine is a common cause of chronic and recurrent abdominal pain in children, according to a recent review. It is characterized by paroxysms of moderate to severe abdominal pain that is midline, periumbilical, or diffuse in location and accompanied by other symptoms including headache, anorexia, nausea, vomiting, or pallor. Despite the presence of comprehensive diagnostic criteria, it continues to be an underdiagnosed entity. Key points include:

• The average age of diagnosis is 3 to 10 years with peak incidence at 7 years.
• Most of the patients have a personal or family history of migraine.
• Pathophysiology of the condition is believed to be similar to that of other functional gastrointestinal disorders and cephalic migraine; it is also well recognized as a type of pediatric migraine variant.
• A careful history, thorough physical examination, and use of well-defined, symptom-based guidelines are needed to make a diagnosis.
• Although it resolves completely in most of the patients, these patients have a strong propensity to develop migraine later in life.
• Nonpharmacologic treatment options, including avoidance of triggers, behavior therapy, and dietary modifications should be the initial line of management.

Pediatric abdominal migraine: current perspectives on a lesser known entity. [Published online ahead of print April 24, 2018]. Pediatric Health Med Ther. doi:10.2147%2FPHMT.S127210.

Athletes with a pre-injury migraine history may be at an elevated risk for a protracted return to school after concussion, especially girls and women, according to a recent study. High school and collegiate athletes (n=1265; 42% female) who sustained a sport-related concussion were monitored by athletic trainers using a web-based surveillance system that collects information about concussion recovery. Researchers found:

• There were 117 athletes (9.2%) who reported a pre-injury migraine history.
• Athletes with a history of migraine took a median of 6 days to return to academics and 15.5 days to return to athletics, while those with no migraine history took a median of 5 days to return to academics and 14 days to return to athletics.
• There were no statistically significant differences in days to return to school or athletics between the groups.
• However, a lower percentage of athletes with a history of migraine had returned to school after 7 days, 14 days, and 21 days post-injury.
• Stratifying the analyses by sex showed that this effect was significant in girls and women with pre-existing migraines, but not boys and men with pre-existing migraines.

Pre-injury migraine history as a risk factor for prolonged return to school and sports following concussion. [Published online ahead of print May 5, 2018]. J Neurotrauma. doi:10.1089/neu.2017.5443.

Athletes with a pre-injury migraine history may be at an elevated risk for a protracted return to school after concussion, especially girls and women, according to a recent study. High school and collegiate athletes (n=1265; 42% female) who sustained a sport-related concussion were monitored by athletic trainers using a web-based surveillance system that collects information about concussion recovery. Researchers found:

• There were 117 athletes (9.2%) who reported a pre-injury migraine history.
• Athletes with a history of migraine took a median of 6 days to return to academics and 15.5 days to return to athletics, while those with no migraine history took a median of 5 days to return to academics and 14 days to return to athletics.
• There were no statistically significant differences in days to return to school or athletics between the groups.
• However, a lower percentage of athletes with a history of migraine had returned to school after 7 days, 14 days, and 21 days post-injury.
• Stratifying the analyses by sex showed that this effect was significant in girls and women with pre-existing migraines, but not boys and men with pre-existing migraines.

Pre-injury migraine history as a risk factor for prolonged return to school and sports following concussion. [Published online ahead of print May 5, 2018]. J Neurotrauma. doi:10.1089/neu.2017.5443.

Athletes with a pre-injury migraine history may be at an elevated risk for a protracted return to school after concussion, especially girls and women, according to a recent study. High school and collegiate athletes (n=1265; 42% female) who sustained a sport-related concussion were monitored by athletic trainers using a web-based surveillance system that collects information about concussion recovery. Researchers found:

• There were 117 athletes (9.2%) who reported a pre-injury migraine history.
• Athletes with a history of migraine took a median of 6 days to return to academics and 15.5 days to return to athletics, while those with no migraine history took a median of 5 days to return to academics and 14 days to return to athletics.
• There were no statistically significant differences in days to return to school or athletics between the groups.
• However, a lower percentage of athletes with a history of migraine had returned to school after 7 days, 14 days, and 21 days post-injury.
• Stratifying the analyses by sex showed that this effect was significant in girls and women with pre-existing migraines, but not boys and men with pre-existing migraines.

Pre-injury migraine history as a risk factor for prolonged return to school and sports following concussion. [Published online ahead of print May 5, 2018]. J Neurotrauma. doi:10.1089/neu.2017.5443.

Circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity that was not better accounted for by the amount of sleep, according to a recent study. Twenty women with chronic migraine (CM) and 20 age‐matched healthy controls (HC) completed a protocol that included a 7-day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. Researchers compared CM vs HC on sleep parameters and circadian factors. Subsequently, they examined associations between dim‐light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). They found:

• CM and HC did not differ on measures of sleep or circadian phase.
• Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49) and later sleep episode (r = .47).
• In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine‐related disability (r = .48).
• These relationships remained significant after adjusting for total sleep time.

Can Circadian dysregulation exacerbate migraines? [Published online ahead of print May 4, 2018]. Headache. doi:10.1111/head.13310.

Circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity that was not better accounted for by the amount of sleep, according to a recent study. Twenty women with chronic migraine (CM) and 20 age‐matched healthy controls (HC) completed a protocol that included a 7-day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. Researchers compared CM vs HC on sleep parameters and circadian factors. Subsequently, they examined associations between dim‐light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). They found:

• CM and HC did not differ on measures of sleep or circadian phase.
• Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49) and later sleep episode (r = .47).
• In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine‐related disability (r = .48).
• These relationships remained significant after adjusting for total sleep time.

Can Circadian dysregulation exacerbate migraines? [Published online ahead of print May 4, 2018]. Headache. doi:10.1111/head.13310.

Circadian misalignment and delayed sleep timing are associated with higher migraine frequency and severity that was not better accounted for by the amount of sleep, according to a recent study. Twenty women with chronic migraine (CM) and 20 age‐matched healthy controls (HC) completed a protocol that included a 7-day sleep assessment at home using wrist actigraphy followed by a circadian phase assessment using salivary melatonin. Researchers compared CM vs HC on sleep parameters and circadian factors. Subsequently, they examined associations between dim‐light melatonin onset (DLMO), the midpoint of the sleep episode, and the phase angle (time from DLMO to sleep midpoint) with the number of migraine days per month and the migraine disability assessment scale (MIDAS). They found:

• CM and HC did not differ on measures of sleep or circadian phase.
• Within the CM group, more frequent migraine days per month was significantly correlated with DLMO (r = .49) and later sleep episode (r = .47).
• In addition, a greater phase angle (ie, circadian misalignment) was significantly correlated with more severe migraine‐related disability (r = .48).
• These relationships remained significant after adjusting for total sleep time.

Can Circadian dysregulation exacerbate migraines? [Published online ahead of print May 4, 2018]. Headache. doi:10.1111/head.13310.