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– Now that erenumab has won approval as the first-in-class calcitonin gene-related peptide inhibitor for prevention of episodic and chronic migraine, a flurry of new studies shedding light on how the drug might best be used in clinical practice emerged as a highlight of the annual meeting of the American Headache Society.

Erenumab (Aimovig) is a fully human monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. It was approved by the Food and Drug Administration at 140 and 70 mg monthly by subcutaneous injection on the strength of the required 12-week, double-blind, placebo-controlled clinical trial data. Among the fresh data presented at the headache meeting was reassuring evidence of the monoclonal antibody’s continued high degree of safety and tolerability for episodic migraine after more than 3 years of therapy, as well as a suggestion that the biologic’s efficacy for chronic migraine was not only sustained but actually increased over the course of a 1-year study.

Also, erenumab appears to be a novel treatment option for patients who have previously failed adequate trials of two to four standard preventive therapies. In addition, it has now demonstrated efficacy in reducing overuse of acute migraine drugs such as triptans, ergots, and opioids.

Here are the highlights:
 

One-year safety and efficacy for chronic migraine

Stewart J. Tepper, MD, presented results of a 1-year, open-label extension study that began after participants completed a pivotal 12-week, placebo-controlled, double-blind, randomized trial whose findings have been published (Lancet Neurol. 2017 Jun;16[6]:425-34). At the end of the 12-week, double-blind period, the mean number of monthly migraine days (MMD) in the erenumab group had dropped by 6.6 days from 18.1 at baseline. Subsequently, after 52 weeks of open-label erenumab at 140 mg monthly, that figure had further improved to 10.5 fewer MMDs than at baseline.

Bruce Jancin/MDedge News
Dr. Stewart J. Tepper

“That’s encouraging for our patients in that we will be able to tell them that if you’re a responder, you’re likely to show some continued improvement over time,” observed Dr. Tepper, professor of neurology and director of the headache clinic at Dartmouth University in Hanover, N.H.

During 527 patient-years of open-label therapy, at least a 50% reduction in MMDs was achieved by 67% of patients in the 140-mg group and 53% in the 70-mg group.

“I think it’s also important to look at the rate of 75% or greater reduction in MMDs, which is the responder rate most closely linked to a drop in disability. That rate at 52 weeks was 42% at 140 mg and 27% at 70 mg,” the neurologist continued.

At week 52, 12.7% of patients on erenumab at 140 mg monthly had no migraines at all during the previous month.

The mean number of acute migraine-specific medication days per month decreased by about 4 days in the erenumab group during the 12-week, double-blind trial and continued to fall during the open-label extension study, with a mean reduction from baseline of 6.7 days at week 52.

“That’s clearly sustained efficacy, and it looks like some accumulating efficacy,” Dr. Tepper said.

Safety and tolerability continued to be excellent, as in the parent 12-week study.

“One of the very interesting findings we saw which differentiates erenumab from, say, onabotulinumtoxinA, is that if you looked at the patients who were on placebo during the 12 weeks of the double-blind study and then looked at the first month they went on erenumab, they caught up immediately to the patients who’d been receiving the monoclonal antibody from the beginning. That’s unlike onabotulinumtoxinA in the regulatory trials, where the patients who initially received placebo never quite caught up to those who received active therapy from the beginning,” he said.

Dr. Tepper emphasized that a clear-eyed view of an open-label study needs to recognize that only responders would have stayed in the erenumab study for a full 52 weeks, so the results paint an overly rosy picture of overall efficacy. Even so, he found the results impressive. Of 609 patients who enrolled in the study, 74% completed it.

“It’s a very encouraging 1-year study for erenumab,” he concluded.

 

 

Safety and tolerability for episodic migraine at 3-plus years

Among 383 episodic migraine patients who enrolled in an ongoing 5-year, open-label extension study of erenumab after completing a 12-week, placebo-controlled, double-blind clinical trial, there have been no new safety signals at a mean 3.2 years of follow-up. The incidence rates and types of adverse events remain indistinguishable from placebo as noted in the parent 12-week double-blind trial, with the exception of an increased rate of mild injection site reactions, reported Daniel D. Mikol, MD, PhD, executive medical director for global neuroscience development at Amgen in Thousand Oaks, Calif.

Bruce Jancin/MDedge News
Dr. Daniel D. Mikol

Erenumab proves effective in patients who have failed multiple preventive therapies

Jan Klatt, MD, presented the results of the 12-week, double-blind portion of the phase 3b LIBERTY study, the first clinical trial specifically designed to assess the effects of CGRP-directed therapy in patients who have previously failed to respond to and/or tolerate two to four currently available preventive medications at adequate doses for at least 2-3 months.

Bruce Jancin/MDedge News
Dr. Jan Klatt

The rationale for the trial was straightforward: “There is a particularly high unmet need in patients who have failed currently available preventive therapies, and who are usually considered difficult to treat,” explained Dr. Klatt of Novartis in Basel, Switzerland.

LIBERTY included 246 such patients with episodic migraine who were randomized to 12 weeks of erenumab at 140 mg monthly or placebo. The primary endpoint – the proportion of patients with at least a 50% reduction in MMDs during weeks 9-12 from the baseline of 9.3 – occurred in 30.3% of the erenumab group, significantly better than the 13.7% rate with placebo, with an adjusted odds ratio of 2.73 for success with erenumab. An open-label extension study is ongoing.

A clear separation was already evident at week 4 of the randomized trial, a prespecified secondary endpoint. A 50% or greater reduction in MMDs was seen at that point in 23.5% of the erenumab group versus 4.8% in placebo-treated controls, for a response odds ratio of 6.16. A 75% or greater reduction in MMDs during weeks 9-12 occurred in 11.8% of the erenumab group and 4% of controls. A 100% response rate – that is, no migraines during weeks 9-12 – occurred in 5.9% of the active treatment arm and none of the controls. Outcomes on two novel patient-reported outcomes – the Migraine Physical Function Impact Diary–physical impairment and –everyday activities subscales – were also significantly better in the active treatment arm.

Treatment outcomes with erenumab were similar regardless of which drug classes patients had previously failed on, the three most common of which were beta-blockers, topiramate, and amitriptyline, which is approved for migraine prevention in Europe, where the LIBERTY trial was conducted.

One audience member observed that the 13.7% primary endpoint placebo response rate was far lower than typically seen in double-blind migraine trials.

“This is something we see quite consistently,” Dr. Klatt replied. “Once you proceed to this kind of more difficult-to-treat population, your placebo response rates drop to really low levels. It’s probably due to the fact that those patients have low expectations for any new therapy.”

 

 

Erenumab quells acute migraine medication overuse

Dr. Tepper presented a separate analysis of the 52-week, open-label extension study of erenumab, this time comparing outcomes in 252 chronic migraine patients who met criteria for acute medication overuse (AMO) at baseline and 357 who did not. Overuse was defined via International Headache Society criteria: The use of triptans, ergots, or combination analgesics on 10 or more days per month, or simple analgesics on at least 15 days monthly. Combination analgesics feature a simple analgesic plus opiates or butalbital.

“The bottom line here is that the drug worked about the same and in a very encouraging way in the AMO and nonoveruse patients,” he said. “This is obviously something that’s very, very important to us because we’d like to take our patients who are overusing acute migraine medications and use the monoclonal antibody as a way of getting them off overuse and into episodic migraine.”

After 52 weeks of open-label erenumab, 61% of the non-AMO group and 56% of those with baseline AMO had at least a 50% reduction from baseline in MMDs. The use of acute migraine-specific medications fell by 3.7 days in the non-AMO group and by 6.7 days in those with AMO at baseline.
 

Safety in patients with stable angina

Although no signal of any cardiovascular issues arose in four randomized, double-blind clinical trials or in the long-term extension studies, it was appropriate to take a more focused look at erenumab’s effects in a high-risk population with stable angina and proven ischemic coronary artery disease. That’s because CGRP is a neuropeptide that not only affects migraine, it also acts as a cytoprotective mediator released by cardiac nerve fibers during myocardial ischemia. Thus, erenumab posed a theoretic cardiovascular risk, explained Christophe Depre, MD, PhD, of Amgen.

He presented a 12-week, randomized, double-blind study in which 89 patients with stable angina were assigned to a single IV infusion of 140 mg of erenumab or placebo followed by an exercise treadmill test. Reassuringly, the CGRP inhibitor had no adverse effect on exercise time, time to onset of at least 1 mm of ST segment depression. Nor did it affect heart rate or blood pressure during or after exercise.

Dr. Tepper reported serving as a consultant to numerous pharmaceutical and medical device companies, including Amgen and Novartis, which sponsored the erenumab studies. Dr. Depre and Dr. Mikol are Amgen employees, while Dr. Klatt is employed by Novartis.

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– Now that erenumab has won approval as the first-in-class calcitonin gene-related peptide inhibitor for prevention of episodic and chronic migraine, a flurry of new studies shedding light on how the drug might best be used in clinical practice emerged as a highlight of the annual meeting of the American Headache Society.

Erenumab (Aimovig) is a fully human monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. It was approved by the Food and Drug Administration at 140 and 70 mg monthly by subcutaneous injection on the strength of the required 12-week, double-blind, placebo-controlled clinical trial data. Among the fresh data presented at the headache meeting was reassuring evidence of the monoclonal antibody’s continued high degree of safety and tolerability for episodic migraine after more than 3 years of therapy, as well as a suggestion that the biologic’s efficacy for chronic migraine was not only sustained but actually increased over the course of a 1-year study.

Also, erenumab appears to be a novel treatment option for patients who have previously failed adequate trials of two to four standard preventive therapies. In addition, it has now demonstrated efficacy in reducing overuse of acute migraine drugs such as triptans, ergots, and opioids.

Here are the highlights:
 

One-year safety and efficacy for chronic migraine

Stewart J. Tepper, MD, presented results of a 1-year, open-label extension study that began after participants completed a pivotal 12-week, placebo-controlled, double-blind, randomized trial whose findings have been published (Lancet Neurol. 2017 Jun;16[6]:425-34). At the end of the 12-week, double-blind period, the mean number of monthly migraine days (MMD) in the erenumab group had dropped by 6.6 days from 18.1 at baseline. Subsequently, after 52 weeks of open-label erenumab at 140 mg monthly, that figure had further improved to 10.5 fewer MMDs than at baseline.

Bruce Jancin/MDedge News
Dr. Stewart J. Tepper

“That’s encouraging for our patients in that we will be able to tell them that if you’re a responder, you’re likely to show some continued improvement over time,” observed Dr. Tepper, professor of neurology and director of the headache clinic at Dartmouth University in Hanover, N.H.

During 527 patient-years of open-label therapy, at least a 50% reduction in MMDs was achieved by 67% of patients in the 140-mg group and 53% in the 70-mg group.

“I think it’s also important to look at the rate of 75% or greater reduction in MMDs, which is the responder rate most closely linked to a drop in disability. That rate at 52 weeks was 42% at 140 mg and 27% at 70 mg,” the neurologist continued.

At week 52, 12.7% of patients on erenumab at 140 mg monthly had no migraines at all during the previous month.

The mean number of acute migraine-specific medication days per month decreased by about 4 days in the erenumab group during the 12-week, double-blind trial and continued to fall during the open-label extension study, with a mean reduction from baseline of 6.7 days at week 52.

“That’s clearly sustained efficacy, and it looks like some accumulating efficacy,” Dr. Tepper said.

Safety and tolerability continued to be excellent, as in the parent 12-week study.

“One of the very interesting findings we saw which differentiates erenumab from, say, onabotulinumtoxinA, is that if you looked at the patients who were on placebo during the 12 weeks of the double-blind study and then looked at the first month they went on erenumab, they caught up immediately to the patients who’d been receiving the monoclonal antibody from the beginning. That’s unlike onabotulinumtoxinA in the regulatory trials, where the patients who initially received placebo never quite caught up to those who received active therapy from the beginning,” he said.

Dr. Tepper emphasized that a clear-eyed view of an open-label study needs to recognize that only responders would have stayed in the erenumab study for a full 52 weeks, so the results paint an overly rosy picture of overall efficacy. Even so, he found the results impressive. Of 609 patients who enrolled in the study, 74% completed it.

“It’s a very encouraging 1-year study for erenumab,” he concluded.

 

 

Safety and tolerability for episodic migraine at 3-plus years

Among 383 episodic migraine patients who enrolled in an ongoing 5-year, open-label extension study of erenumab after completing a 12-week, placebo-controlled, double-blind clinical trial, there have been no new safety signals at a mean 3.2 years of follow-up. The incidence rates and types of adverse events remain indistinguishable from placebo as noted in the parent 12-week double-blind trial, with the exception of an increased rate of mild injection site reactions, reported Daniel D. Mikol, MD, PhD, executive medical director for global neuroscience development at Amgen in Thousand Oaks, Calif.

Bruce Jancin/MDedge News
Dr. Daniel D. Mikol

Erenumab proves effective in patients who have failed multiple preventive therapies

Jan Klatt, MD, presented the results of the 12-week, double-blind portion of the phase 3b LIBERTY study, the first clinical trial specifically designed to assess the effects of CGRP-directed therapy in patients who have previously failed to respond to and/or tolerate two to four currently available preventive medications at adequate doses for at least 2-3 months.

Bruce Jancin/MDedge News
Dr. Jan Klatt

The rationale for the trial was straightforward: “There is a particularly high unmet need in patients who have failed currently available preventive therapies, and who are usually considered difficult to treat,” explained Dr. Klatt of Novartis in Basel, Switzerland.

LIBERTY included 246 such patients with episodic migraine who were randomized to 12 weeks of erenumab at 140 mg monthly or placebo. The primary endpoint – the proportion of patients with at least a 50% reduction in MMDs during weeks 9-12 from the baseline of 9.3 – occurred in 30.3% of the erenumab group, significantly better than the 13.7% rate with placebo, with an adjusted odds ratio of 2.73 for success with erenumab. An open-label extension study is ongoing.

A clear separation was already evident at week 4 of the randomized trial, a prespecified secondary endpoint. A 50% or greater reduction in MMDs was seen at that point in 23.5% of the erenumab group versus 4.8% in placebo-treated controls, for a response odds ratio of 6.16. A 75% or greater reduction in MMDs during weeks 9-12 occurred in 11.8% of the erenumab group and 4% of controls. A 100% response rate – that is, no migraines during weeks 9-12 – occurred in 5.9% of the active treatment arm and none of the controls. Outcomes on two novel patient-reported outcomes – the Migraine Physical Function Impact Diary–physical impairment and –everyday activities subscales – were also significantly better in the active treatment arm.

Treatment outcomes with erenumab were similar regardless of which drug classes patients had previously failed on, the three most common of which were beta-blockers, topiramate, and amitriptyline, which is approved for migraine prevention in Europe, where the LIBERTY trial was conducted.

One audience member observed that the 13.7% primary endpoint placebo response rate was far lower than typically seen in double-blind migraine trials.

“This is something we see quite consistently,” Dr. Klatt replied. “Once you proceed to this kind of more difficult-to-treat population, your placebo response rates drop to really low levels. It’s probably due to the fact that those patients have low expectations for any new therapy.”

 

 

Erenumab quells acute migraine medication overuse

Dr. Tepper presented a separate analysis of the 52-week, open-label extension study of erenumab, this time comparing outcomes in 252 chronic migraine patients who met criteria for acute medication overuse (AMO) at baseline and 357 who did not. Overuse was defined via International Headache Society criteria: The use of triptans, ergots, or combination analgesics on 10 or more days per month, or simple analgesics on at least 15 days monthly. Combination analgesics feature a simple analgesic plus opiates or butalbital.

“The bottom line here is that the drug worked about the same and in a very encouraging way in the AMO and nonoveruse patients,” he said. “This is obviously something that’s very, very important to us because we’d like to take our patients who are overusing acute migraine medications and use the monoclonal antibody as a way of getting them off overuse and into episodic migraine.”

After 52 weeks of open-label erenumab, 61% of the non-AMO group and 56% of those with baseline AMO had at least a 50% reduction from baseline in MMDs. The use of acute migraine-specific medications fell by 3.7 days in the non-AMO group and by 6.7 days in those with AMO at baseline.
 

Safety in patients with stable angina

Although no signal of any cardiovascular issues arose in four randomized, double-blind clinical trials or in the long-term extension studies, it was appropriate to take a more focused look at erenumab’s effects in a high-risk population with stable angina and proven ischemic coronary artery disease. That’s because CGRP is a neuropeptide that not only affects migraine, it also acts as a cytoprotective mediator released by cardiac nerve fibers during myocardial ischemia. Thus, erenumab posed a theoretic cardiovascular risk, explained Christophe Depre, MD, PhD, of Amgen.

He presented a 12-week, randomized, double-blind study in which 89 patients with stable angina were assigned to a single IV infusion of 140 mg of erenumab or placebo followed by an exercise treadmill test. Reassuringly, the CGRP inhibitor had no adverse effect on exercise time, time to onset of at least 1 mm of ST segment depression. Nor did it affect heart rate or blood pressure during or after exercise.

Dr. Tepper reported serving as a consultant to numerous pharmaceutical and medical device companies, including Amgen and Novartis, which sponsored the erenumab studies. Dr. Depre and Dr. Mikol are Amgen employees, while Dr. Klatt is employed by Novartis.

 

– Now that erenumab has won approval as the first-in-class calcitonin gene-related peptide inhibitor for prevention of episodic and chronic migraine, a flurry of new studies shedding light on how the drug might best be used in clinical practice emerged as a highlight of the annual meeting of the American Headache Society.

Erenumab (Aimovig) is a fully human monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor. It was approved by the Food and Drug Administration at 140 and 70 mg monthly by subcutaneous injection on the strength of the required 12-week, double-blind, placebo-controlled clinical trial data. Among the fresh data presented at the headache meeting was reassuring evidence of the monoclonal antibody’s continued high degree of safety and tolerability for episodic migraine after more than 3 years of therapy, as well as a suggestion that the biologic’s efficacy for chronic migraine was not only sustained but actually increased over the course of a 1-year study.

Also, erenumab appears to be a novel treatment option for patients who have previously failed adequate trials of two to four standard preventive therapies. In addition, it has now demonstrated efficacy in reducing overuse of acute migraine drugs such as triptans, ergots, and opioids.

Here are the highlights:
 

One-year safety and efficacy for chronic migraine

Stewart J. Tepper, MD, presented results of a 1-year, open-label extension study that began after participants completed a pivotal 12-week, placebo-controlled, double-blind, randomized trial whose findings have been published (Lancet Neurol. 2017 Jun;16[6]:425-34). At the end of the 12-week, double-blind period, the mean number of monthly migraine days (MMD) in the erenumab group had dropped by 6.6 days from 18.1 at baseline. Subsequently, after 52 weeks of open-label erenumab at 140 mg monthly, that figure had further improved to 10.5 fewer MMDs than at baseline.

Bruce Jancin/MDedge News
Dr. Stewart J. Tepper

“That’s encouraging for our patients in that we will be able to tell them that if you’re a responder, you’re likely to show some continued improvement over time,” observed Dr. Tepper, professor of neurology and director of the headache clinic at Dartmouth University in Hanover, N.H.

During 527 patient-years of open-label therapy, at least a 50% reduction in MMDs was achieved by 67% of patients in the 140-mg group and 53% in the 70-mg group.

“I think it’s also important to look at the rate of 75% or greater reduction in MMDs, which is the responder rate most closely linked to a drop in disability. That rate at 52 weeks was 42% at 140 mg and 27% at 70 mg,” the neurologist continued.

At week 52, 12.7% of patients on erenumab at 140 mg monthly had no migraines at all during the previous month.

The mean number of acute migraine-specific medication days per month decreased by about 4 days in the erenumab group during the 12-week, double-blind trial and continued to fall during the open-label extension study, with a mean reduction from baseline of 6.7 days at week 52.

“That’s clearly sustained efficacy, and it looks like some accumulating efficacy,” Dr. Tepper said.

Safety and tolerability continued to be excellent, as in the parent 12-week study.

“One of the very interesting findings we saw which differentiates erenumab from, say, onabotulinumtoxinA, is that if you looked at the patients who were on placebo during the 12 weeks of the double-blind study and then looked at the first month they went on erenumab, they caught up immediately to the patients who’d been receiving the monoclonal antibody from the beginning. That’s unlike onabotulinumtoxinA in the regulatory trials, where the patients who initially received placebo never quite caught up to those who received active therapy from the beginning,” he said.

Dr. Tepper emphasized that a clear-eyed view of an open-label study needs to recognize that only responders would have stayed in the erenumab study for a full 52 weeks, so the results paint an overly rosy picture of overall efficacy. Even so, he found the results impressive. Of 609 patients who enrolled in the study, 74% completed it.

“It’s a very encouraging 1-year study for erenumab,” he concluded.

 

 

Safety and tolerability for episodic migraine at 3-plus years

Among 383 episodic migraine patients who enrolled in an ongoing 5-year, open-label extension study of erenumab after completing a 12-week, placebo-controlled, double-blind clinical trial, there have been no new safety signals at a mean 3.2 years of follow-up. The incidence rates and types of adverse events remain indistinguishable from placebo as noted in the parent 12-week double-blind trial, with the exception of an increased rate of mild injection site reactions, reported Daniel D. Mikol, MD, PhD, executive medical director for global neuroscience development at Amgen in Thousand Oaks, Calif.

Bruce Jancin/MDedge News
Dr. Daniel D. Mikol

Erenumab proves effective in patients who have failed multiple preventive therapies

Jan Klatt, MD, presented the results of the 12-week, double-blind portion of the phase 3b LIBERTY study, the first clinical trial specifically designed to assess the effects of CGRP-directed therapy in patients who have previously failed to respond to and/or tolerate two to four currently available preventive medications at adequate doses for at least 2-3 months.

Bruce Jancin/MDedge News
Dr. Jan Klatt

The rationale for the trial was straightforward: “There is a particularly high unmet need in patients who have failed currently available preventive therapies, and who are usually considered difficult to treat,” explained Dr. Klatt of Novartis in Basel, Switzerland.

LIBERTY included 246 such patients with episodic migraine who were randomized to 12 weeks of erenumab at 140 mg monthly or placebo. The primary endpoint – the proportion of patients with at least a 50% reduction in MMDs during weeks 9-12 from the baseline of 9.3 – occurred in 30.3% of the erenumab group, significantly better than the 13.7% rate with placebo, with an adjusted odds ratio of 2.73 for success with erenumab. An open-label extension study is ongoing.

A clear separation was already evident at week 4 of the randomized trial, a prespecified secondary endpoint. A 50% or greater reduction in MMDs was seen at that point in 23.5% of the erenumab group versus 4.8% in placebo-treated controls, for a response odds ratio of 6.16. A 75% or greater reduction in MMDs during weeks 9-12 occurred in 11.8% of the erenumab group and 4% of controls. A 100% response rate – that is, no migraines during weeks 9-12 – occurred in 5.9% of the active treatment arm and none of the controls. Outcomes on two novel patient-reported outcomes – the Migraine Physical Function Impact Diary–physical impairment and –everyday activities subscales – were also significantly better in the active treatment arm.

Treatment outcomes with erenumab were similar regardless of which drug classes patients had previously failed on, the three most common of which were beta-blockers, topiramate, and amitriptyline, which is approved for migraine prevention in Europe, where the LIBERTY trial was conducted.

One audience member observed that the 13.7% primary endpoint placebo response rate was far lower than typically seen in double-blind migraine trials.

“This is something we see quite consistently,” Dr. Klatt replied. “Once you proceed to this kind of more difficult-to-treat population, your placebo response rates drop to really low levels. It’s probably due to the fact that those patients have low expectations for any new therapy.”

 

 

Erenumab quells acute migraine medication overuse

Dr. Tepper presented a separate analysis of the 52-week, open-label extension study of erenumab, this time comparing outcomes in 252 chronic migraine patients who met criteria for acute medication overuse (AMO) at baseline and 357 who did not. Overuse was defined via International Headache Society criteria: The use of triptans, ergots, or combination analgesics on 10 or more days per month, or simple analgesics on at least 15 days monthly. Combination analgesics feature a simple analgesic plus opiates or butalbital.

“The bottom line here is that the drug worked about the same and in a very encouraging way in the AMO and nonoveruse patients,” he said. “This is obviously something that’s very, very important to us because we’d like to take our patients who are overusing acute migraine medications and use the monoclonal antibody as a way of getting them off overuse and into episodic migraine.”

After 52 weeks of open-label erenumab, 61% of the non-AMO group and 56% of those with baseline AMO had at least a 50% reduction from baseline in MMDs. The use of acute migraine-specific medications fell by 3.7 days in the non-AMO group and by 6.7 days in those with AMO at baseline.
 

Safety in patients with stable angina

Although no signal of any cardiovascular issues arose in four randomized, double-blind clinical trials or in the long-term extension studies, it was appropriate to take a more focused look at erenumab’s effects in a high-risk population with stable angina and proven ischemic coronary artery disease. That’s because CGRP is a neuropeptide that not only affects migraine, it also acts as a cytoprotective mediator released by cardiac nerve fibers during myocardial ischemia. Thus, erenumab posed a theoretic cardiovascular risk, explained Christophe Depre, MD, PhD, of Amgen.

He presented a 12-week, randomized, double-blind study in which 89 patients with stable angina were assigned to a single IV infusion of 140 mg of erenumab or placebo followed by an exercise treadmill test. Reassuringly, the CGRP inhibitor had no adverse effect on exercise time, time to onset of at least 1 mm of ST segment depression. Nor did it affect heart rate or blood pressure during or after exercise.

Dr. Tepper reported serving as a consultant to numerous pharmaceutical and medical device companies, including Amgen and Novartis, which sponsored the erenumab studies. Dr. Depre and Dr. Mikol are Amgen employees, while Dr. Klatt is employed by Novartis.

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