What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

What is your experience with prescribing preventive medication for your patients with migraine?

Roughly 40% of patients living with migraine should be on preventive medication or other treatment, but probably fewer than 15% of patients with migraine are currently receiving therapy. There are several reasons for this: General physicians rarely put patients on preventive medication unless they are interested in or knowledgeable about headache, and the older preventive medicines that neurologists and headache specialists have used for many years have a lot of potential side effects and do not begin to work quickly.

It takes approximately 2 to 3 months for preventive medication to become effective, and many patients need to be slowly titrated up to an effective dose. By the time patients reach a steady state over a few weeks, if it is still not working well, they must slowly taper it and try something else. This is  what often occurs with older preventive migraine medications—especially one of the most commonly used preventives, topiramate (Topamax). This drug was first indicated for epilepsy and then later for mood stabilization. Though it has good efficacy in reducing migraine attacks, it has many possible side effects, some of them troublesome. I often had multiple calls from patients in their first month of taking it complain of memory or word-finding issues and tingling in the extremities. More serious adverse events can be increased pressure in the eyes, such as glaucoma, and kidney stones. I often get referrals from other neurologists and headache specialists regarding patients who have failed multiple preventive medicines; 90% percent of these referrals need to be switched to the newer, more costly calcitonin gene-related peptide (CGRP)-blocking preventative medications, if insurance companies will cover them. 

What categories of migraine preventive drugs do you generally prescribe your patients?

Of the older medications, most are epilepsy medicines, beta blockers, antidepressants, or cardiac medications such as angiotensin receptor blockers (candesartan). Of the newer medications, I use 1 of the 4 injectable monoclonal antibodies (mAbs), or 1 of the 2 gepants.

Older migraine preventive medication

Anticonvulsants (epilepsy medications)

Anticonvulsants are used for the treatment of several conditions, including epilepsy and pain control, but some can help reduce migraine attacks. These medicines, like all drugs, have the potential to cause side effects, especially topiramate; this medicine often causes paresthesia or tingling in the extremities as well as trouble with speech and memory, kidney stones, pancreatitis, and weight loss. The weight loss side effect of this drug has made it more appealing for some patients who had previously gained 10 to 15 pounds taking antidepressant medication to treat their migraine. I personally thought it was the most effective of all the preventive migraine medications if the patient could tolerate it.

Beta Blockers

Beta blockers cause the heart rate to decrease and also lower blood pressure. Most of my migraine patients are healthy females in their 20s and 30s and, when taking a beta blocker, can get short of breath when they exercise. These medications can also cause some depression and gastrointestinal issues and raise cholesterol levels.

Antidepressants

The type of antidepressants that I normally prescribe for migraine prevention are the tricyclic antidepressants. The one that has the best data in the literature and is often prescribed is amitriptyline (Elavil); I prefer a cousin to this medicine, nortriptyline. I prescribe tricyclics because many of my migraine patients have 2 other comorbid problems: depression and trouble staying asleep at night. Amitriptyline tends to cause drowsiness and can help patients sleep. It can also cause dry mouth, trouble urinating (especially in men), constipation, weight gain, and can slow patients down mentally, so it should not be prescribed to elderly patients. These antidepressants should be prescribed in very low doses and taken an hour before bedtime. The dose should be increased gradually over several weeks to help reduce adverse events. The best dose for migraine is often lower than the antidepressant dose, so sometimes a depressed patient needs 2 types of antidepressants. The typical dose for migraine prevention is about 50 to 75 mg. For depression, it is about 150 mg.

The patient would then need to increase their dose gradually for a month and remain on the target dose for at least another month. At the end of 2 months, they would have some idea whether it was working for them. If it was not, I might increase the dose even further. It is important to set expectations with patients at the beginning of treatment and tell them it is going to take 2 to 3 months to see if it works.  If it does not work, I tell them, we will have to try another one, and that is going to take 2 or 3 months as well, until we can switch to the newer medications, which start to work in the first month, often in the first few days. 

Why wouldn’t we just start with the newer preventives? Insurance companies require patients to fail, on average, 2 categories of the older medications before they will pay for the newer ones. Medicare usually only covers the older generic medications.

New migraine preventive medications

Monoclonal Antibodies

mAbs that block CGRP for the prevention of migraine, such as erenumab, fremanezumab, galcanezumab, and eptinezumab, target either the CGRP ligand itself or block the receptor to CGRP. This class of medication became available about 5 years ago. The first one approved was erenumab (Aimovig). It was tried by a lot of headache specialists, many neurologists, and then some general physicians once it came to market. It is the only one in its class that grabs the ligand CGRP and prevents it from docking on its receptor. Recently, 5-year safety data indicated it is extremely safe with only a few side effects, (it has been shown to cause some constipation and hypertension). It does, however, tend to lower the number of migraine days per month by about 40% to 50%. At the beginning of erenumab’s availability, researchers took patients that had 8 to 22 days of migraine per month and put them in double-blind, placebo-controlled, randomized trials. They found that some patients' migraine days went down gradually to 10 to 12 days from 20 migraine days per month. Erenumab works quickly, and most patients improve within 2 weeks.

Fremanezumab (AJOVY™) was the second mAb approved, followed pretty quickly by the third, galcanezumab (Emgality™). All 3 of these mAbs are administered once a month by a subcutaneous injection from an autoinjector. If a patient takes 3 fremanezumab injections in 1 day, they do not have to repeat that dose for 3 months. The upside of these 3 treatments is that the patient can self-administer the medication at home with few, if any, adverse events; the downside is they are expensive medications, costing about $600 per month. 

Shortly thereafter, a fourth mAb, eptinezumab (VYEPTI™), was brought to market. Unlike the other 3 mAbs, it is administered as an intravenous infusion. The patient must come to an office or infusion center for a 30-minute intravenous infusion, which is not as convenient as treating themselves with an autoinjector at home. Eptinezumab is a strong medication that is often prescribed when other treatments are not effective. Each of the 4 mAbs has its own possible adverse events, but these are few and usually mild. The mAbs have a half-life of about 28 to 32 days; it takes 5 to 6 months after an injection for these mAbs to be metabolized by the reticuloendothelial system. 

Gepants

The gepants are small molecule CGRP receptor blockers with much shorter half-lives than mAbs. They work by blocking the CGRP receptor so the CGRP ligand cannot dock there and cause vasodilation and increased pain transmission. Gepants have half-lives of 6 to 12 hours and can be used to treat a migraine acutely. Several drug companies studied the effects of taking a gepant every day or every other day, showing it can also be used as a migraine preventive medication. Ubrogepant (Ubrelvy®) was the first gepant to receive approval from the US Food and Drug Administration (FDA), but it was authorized only for acute care. Rimegepant (Nurtec®) was the second gepant approved, initially for acute treatment and later becoming the first gepant approved for migraine prevention. The same tablet can be used for acute care or for prevention. Preventive treatment consists of one 75 mg oral disintegrating tablet taken every second day. It works quite well as a preventive and has very few side effects. Nausea and abdominal discomfort occur in < 3% of patients. Some patients prefer to take a pill every other day over having an injection once per month or once every 3 months. It makes more sense for a woman of childbearing potential to take a drug with very short half-life vs one that lasts for 5 to 6 months in case she decides to become pregnant (or unexpectedly becomes pregnant).

A third gepant, atogepant (Qulipta™), was later approved, but only for prevention. It is available in 3 different strengths: 10 mg, 30 mg, and 60 mg. I tend to prescribe the 60-mg strength, and the dose is 1 pill every day. 

If you compare rimegepant, which is taken once every other day, and atogepant, taken once daily, the latter tends to have slightly more side effects of nausea, drowsiness, and constipation, whereas rimegepant has been shown to have fewer side effects in double-blind, randomized studies. Like all gepants, it is quite effective and fast acting. 

The goal of preventive medications is to decrease the frequency, severity, and duration of migraine attacks. Effective treatment can increase responsiveness to acute migraine therapy and improve the quality of life in patients suffering from migraine. Every patient is different and thus the side effects they experience vary. With time and patience, most patients find the relief from migraine they have been desperately seeking through the preventive medicines discussed above. This is a good time to have migraine, if you can get in to see a knowledgeable doctor and your insurance company cooperates. When I started my neurology practice 51 years ago, we had few preventives, and none approved by the FDA. Now we have several older, approved preventives—4 newer mAbs, and 2 newer gepants—as well as several devices, which we will discuss in the future.

Introduction

The first Janus kinase (JAK) inhibitor received regulatory approval for the treatment of psoriatic arthritis (PsA) more than 5 years ago. Although there are limited comparative data between this and other JAK inhibitors approved or in development for the treatment of PsA, it is reasonable to anticipate variability in therapeutic effect and the risk of adverse events between different JAK inhibitors. So far, there have been considerable differences in the relative selectivity of each agent on the 4 JAK isoform enzymes, JAK1, JAK2, JAK3, and TYK2. This selectivity determines the downstream signal transducers and activators of transcription proteins (JAK-STAT [signal transducer and activator of transcription] pathway) that ultimately mediate both anti-inflammatory and off-target effects. In this review of JAK inhibitors in PsA, differences between JAK inhibitors will be explored for their potential impact on benefit-to-risk ratio while treating PsA.  

Background

Data from the National Psoriasis Foundation (NPF) estimates that 8 million individuals in the United States have psoriasis.¹ PsA, an inflammatory spondyloarthritis associated with psoriasis, develops in about 30% of these individuals, but precise epidemiology on this subset of psoriasis patients is complicated by missed and delayed diagnoses. Of patients with psoriasis, only about 15% of patients with PsA have joint inflammation at the time or in advance of skin lesions.² This might explain delays in diagnosis. In one study, 15% of patients treated for psoriasis were found to have concomitant but unrecognized PsA.³ 

PsA was first classified as a distinct pathologic condition only about 50 years ago, even though skeletal remains indicate that this disease existed in early civilizations.² Based on consensus that PsA deserved definition as a distinct entity, the Classification Criteria for Psoriatic Arthritis (CASPAR) were published in 2006.⁴ By these criteria, cumulative points are allotted for clinical signs of skin, nail, and joint involvement, as well as radiographic signs in patients judged to have inflammatory disease in the joints, spine, or entheses to classify them as having PsA. 

There are numerous recommendations for the treatment of PsA, including those issued by the American College of Rheumatology (ACR),⁵ the European Alliance of Associations for Rheumatology (EULAR),⁶ and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).⁷ Although generally compatible with the others, the GRAPPA recommendations, which are the most recent, have addressed the heterogeneity of PsA by recommending therapies for specific disease domains, such as the skin, nail, and joint manifestations.

For treatment of PsA, the available drug classes for moderate-to-severe disease include immunomodulators, such as methotrexate, biologics that inhibit cytokines, such as tumor necrosis factor (TNF) and the interleukin (IL) cytokines IL-17, 1L-23, and IL12/IL-23, phosphodiesterase-4 (PDE4) inhibitors, and JAK inhibitors. In the GRAPPA recommendations, JAK inhibitors are listed along with other targeted therapies as first-line choices for peripheral arthritis, axial disease, enthesitis, dactylitis, and plaque psoriasis. 

JAK Inhibitors and PsA

There are multiple ways to classify JAK inhibitors. Tofacitinib, the first JAK inhibitor approved for PsA, is labeled a first-generation agent because it is relatively nonselective for the 4 JAK isoforms.⁸ Second-generation agents, such as upadacitinib, have been distinguished from tofacitinib, baricitinib, and other first-generation drugs by greater relative selectivity on the JAK1 enzyme. Other drugs in development for PsA target different JAK isoforms. Deucravacitinib, for example, which was approved for psoriasis after a favorable phase 3 trial⁹ and has shown promise for PsA in a phase 2 trial, is selective for the TYK2 isoform.¹⁰ A rapidly growing list of JAK inhibitors with different selectivity profiles, including dual JAK inhibitory effects, are being explored in a host of inflammatory diseases.

The relationship between selectivity on specific JAK isoforms, anti-inflammatory effects, and off-target effects is not fully understood.⁸ In addition, characteristics beyond JAK selectivity have potential pharmacologic importance. For example, JAK inhibitors can be classified as ATP competitive inhibitors and allosteric inhibitors, both of which are reversible binding modes.⁸ Within each of these subcategories, the site of kinase binding has the potential to influence clinical activity.⁸

JAK Inhibitors: Clinical Experience in PsA 

Tofacitinib, a first-generation JAK inhibitor, initially licensed for use in the treatment of rheumatoid arthritis (RA), received regulatory approval for PsA on the basis of the OPAL Beyond trial.¹¹ Approval of upadacitinib for PsA followed about 4 years later on the basis of the SELECT PsA-1 trial.¹² The primary endpoint in both of these studies was proportion of patients with an ACR response, signifying degree of improvement from baseline, of ≥20%. For the JAK inhibitors, the ACR20 rates were about 50% and 70% in the tofacitinib and upadacitinib phase 3 trials, respectively. Other JAK inhibitors have been evaluated in PsA but none so far are approved in the United States.

Despite experimental evidence supporting the hypothesis that JAK1 selectivity is clinically relevant to the treatment of PsA and other spondyloarthritides,¹³ there is no level 1 evidence of an efficacy or safety advantage for second- relative to first-generation JAK inhibitors. A small number of indirect comparisons, such as one employing a network Bayesian analysis to compare these drugs for the treatment of RA,¹⁴ have supported a clinical advantage for JAK1 selectivity, but head-to-head comparisons are needed to confirm differences. 

Prescribing information for both tofacitinib and upadacitinib in PsA and other indications include a black box warning for risk of serious adverse events, including major adverse cardiac events (MACE) and thromboembolism. The warning is based on the placebo-controlled ORAL trial with tofacitinib in RA.¹⁵ The study population was enhanced for risk with eligibility that required older age and the presence of cardiovascular risk factors. In this high-risk RA population, tofacitinib was associated with modest increases in serious adverse events, including MACE and thromboembolism, relative to placebo over several years of follow-up. A similar trial has not been conducted with upadacitinib or in patients with PsA.  

In a phase 3 trial with the TYK2-selective deucravacitinib in psoriasis, there was no increase in the rate of MACE or thromboembolism.⁹ When granted regulatory approval for psoriasis, the product information did not include a black box warning, differentiating it from other currently available JAK inhibitors. It has not yet been proven whether the absence of serious adverse events in the phase 3 psoriasis and phase 2 PsA trials with deucravacitinib are related to TYK2 JAK enzyme selectivity. 

Although TYK2 is closely associated with upregulation of IL-23 and other inflammatory cytokines implicated in the pathophysiology of PSA, the JAK-STAT signaling pathway is incompletely understood.⁸ Moreover, all of the JAK inhibitors synthesized so far have relative rather than absolute selectivity for any specific JAK isoform. This complicates the ability to attribute benefits and risks to the inhibition of any single JAK enzyme isoform and amplifies the need for comparative studies. 

While other JAK inhibitors have reached late stages of development for the treatment of PsA, such as filgotinib (a JAK1 selective drug) and brepocitinib (which is selective for both JAK1 and TYK2),^16,17 it is appropriate to emphasize that currently available JAK inhibitors are effective and acceptably safe for PsA. The goal of continued drug development is the potential to develop agents with even greater efficacy but with a lower risk of off-target effects. Currently, the black box warnings included in the labeling of tofacitinib and upadacitinib give pause, leading many clinicians to move to these agents after an inadequate response to biologics. Newer therapies in the JAK inhibitor class free of serious adverse effects might reverse the order, given the preference of many patients for oral agents. 

The JAK inhibitor development program is rich not just for inflammatory diseases and autoimmune diseases, but for myeloproliferative diseases and neoplasms. JAK inhibitors are already identified in the GRAPPA recommendations as appropriate first-line options for most manifestations of PsA, including joint and skin involvement, but newer drugs with a more favorable JAK selectivity or other pharmacologic characteristics and decreased adverse risks might make these a more dominant treatment choice. 

Summary

Relative selectivity for JAK isoforms promises therapies that are both more effective and safer for PsA as well as other inflammatory diseases. This promise is now being explored in experimental trials testing therapies with variable degrees of selectivity in the context of other characteristics, such as kinase binding, with the potential to influence clinical effects. However, the promise will not be fulfilled until large clinical trials, particularly comparative trials, can confirm the importance of JAK isoform selectivity. If specific types of selectivity prove relevant to the benefit-to-risk ratio of JAK inhibitors in PsA, it may alter the current order of treatment preferences for this disease.

Introduction

The first Janus kinase (JAK) inhibitor received regulatory approval for the treatment of psoriatic arthritis (PsA) more than 5 years ago. Although there are limited comparative data between this and other JAK inhibitors approved or in development for the treatment of PsA, it is reasonable to anticipate variability in therapeutic effect and the risk of adverse events between different JAK inhibitors. So far, there have been considerable differences in the relative selectivity of each agent on the 4 JAK isoform enzymes, JAK1, JAK2, JAK3, and TYK2. This selectivity determines the downstream signal transducers and activators of transcription proteins (JAK-STAT [signal transducer and activator of transcription] pathway) that ultimately mediate both anti-inflammatory and off-target effects. In this review of JAK inhibitors in PsA, differences between JAK inhibitors will be explored for their potential impact on benefit-to-risk ratio while treating PsA.  

Background

Data from the National Psoriasis Foundation (NPF) estimates that 8 million individuals in the United States have psoriasis.¹ PsA, an inflammatory spondyloarthritis associated with psoriasis, develops in about 30% of these individuals, but precise epidemiology on this subset of psoriasis patients is complicated by missed and delayed diagnoses. Of patients with psoriasis, only about 15% of patients with PsA have joint inflammation at the time or in advance of skin lesions.² This might explain delays in diagnosis. In one study, 15% of patients treated for psoriasis were found to have concomitant but unrecognized PsA.³ 

PsA was first classified as a distinct pathologic condition only about 50 years ago, even though skeletal remains indicate that this disease existed in early civilizations.² Based on consensus that PsA deserved definition as a distinct entity, the Classification Criteria for Psoriatic Arthritis (CASPAR) were published in 2006.⁴ By these criteria, cumulative points are allotted for clinical signs of skin, nail, and joint involvement, as well as radiographic signs in patients judged to have inflammatory disease in the joints, spine, or entheses to classify them as having PsA. 

There are numerous recommendations for the treatment of PsA, including those issued by the American College of Rheumatology (ACR),⁵ the European Alliance of Associations for Rheumatology (EULAR),⁶ and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).⁷ Although generally compatible with the others, the GRAPPA recommendations, which are the most recent, have addressed the heterogeneity of PsA by recommending therapies for specific disease domains, such as the skin, nail, and joint manifestations.

For treatment of PsA, the available drug classes for moderate-to-severe disease include immunomodulators, such as methotrexate, biologics that inhibit cytokines, such as tumor necrosis factor (TNF) and the interleukin (IL) cytokines IL-17, 1L-23, and IL12/IL-23, phosphodiesterase-4 (PDE4) inhibitors, and JAK inhibitors. In the GRAPPA recommendations, JAK inhibitors are listed along with other targeted therapies as first-line choices for peripheral arthritis, axial disease, enthesitis, dactylitis, and plaque psoriasis. 

JAK Inhibitors and PsA

There are multiple ways to classify JAK inhibitors. Tofacitinib, the first JAK inhibitor approved for PsA, is labeled a first-generation agent because it is relatively nonselective for the 4 JAK isoforms.⁸ Second-generation agents, such as upadacitinib, have been distinguished from tofacitinib, baricitinib, and other first-generation drugs by greater relative selectivity on the JAK1 enzyme. Other drugs in development for PsA target different JAK isoforms. Deucravacitinib, for example, which was approved for psoriasis after a favorable phase 3 trial⁹ and has shown promise for PsA in a phase 2 trial, is selective for the TYK2 isoform.¹⁰ A rapidly growing list of JAK inhibitors with different selectivity profiles, including dual JAK inhibitory effects, are being explored in a host of inflammatory diseases.

The relationship between selectivity on specific JAK isoforms, anti-inflammatory effects, and off-target effects is not fully understood.⁸ In addition, characteristics beyond JAK selectivity have potential pharmacologic importance. For example, JAK inhibitors can be classified as ATP competitive inhibitors and allosteric inhibitors, both of which are reversible binding modes.⁸ Within each of these subcategories, the site of kinase binding has the potential to influence clinical activity.⁸

JAK Inhibitors: Clinical Experience in PsA 

Tofacitinib, a first-generation JAK inhibitor, initially licensed for use in the treatment of rheumatoid arthritis (RA), received regulatory approval for PsA on the basis of the OPAL Beyond trial.¹¹ Approval of upadacitinib for PsA followed about 4 years later on the basis of the SELECT PsA-1 trial.¹² The primary endpoint in both of these studies was proportion of patients with an ACR response, signifying degree of improvement from baseline, of ≥20%. For the JAK inhibitors, the ACR20 rates were about 50% and 70% in the tofacitinib and upadacitinib phase 3 trials, respectively. Other JAK inhibitors have been evaluated in PsA but none so far are approved in the United States.

Despite experimental evidence supporting the hypothesis that JAK1 selectivity is clinically relevant to the treatment of PsA and other spondyloarthritides,¹³ there is no level 1 evidence of an efficacy or safety advantage for second- relative to first-generation JAK inhibitors. A small number of indirect comparisons, such as one employing a network Bayesian analysis to compare these drugs for the treatment of RA,¹⁴ have supported a clinical advantage for JAK1 selectivity, but head-to-head comparisons are needed to confirm differences. 

Prescribing information for both tofacitinib and upadacitinib in PsA and other indications include a black box warning for risk of serious adverse events, including major adverse cardiac events (MACE) and thromboembolism. The warning is based on the placebo-controlled ORAL trial with tofacitinib in RA.¹⁵ The study population was enhanced for risk with eligibility that required older age and the presence of cardiovascular risk factors. In this high-risk RA population, tofacitinib was associated with modest increases in serious adverse events, including MACE and thromboembolism, relative to placebo over several years of follow-up. A similar trial has not been conducted with upadacitinib or in patients with PsA.  

In a phase 3 trial with the TYK2-selective deucravacitinib in psoriasis, there was no increase in the rate of MACE or thromboembolism.⁹ When granted regulatory approval for psoriasis, the product information did not include a black box warning, differentiating it from other currently available JAK inhibitors. It has not yet been proven whether the absence of serious adverse events in the phase 3 psoriasis and phase 2 PsA trials with deucravacitinib are related to TYK2 JAK enzyme selectivity. 

Although TYK2 is closely associated with upregulation of IL-23 and other inflammatory cytokines implicated in the pathophysiology of PSA, the JAK-STAT signaling pathway is incompletely understood.⁸ Moreover, all of the JAK inhibitors synthesized so far have relative rather than absolute selectivity for any specific JAK isoform. This complicates the ability to attribute benefits and risks to the inhibition of any single JAK enzyme isoform and amplifies the need for comparative studies. 

While other JAK inhibitors have reached late stages of development for the treatment of PsA, such as filgotinib (a JAK1 selective drug) and brepocitinib (which is selective for both JAK1 and TYK2),^16,17 it is appropriate to emphasize that currently available JAK inhibitors are effective and acceptably safe for PsA. The goal of continued drug development is the potential to develop agents with even greater efficacy but with a lower risk of off-target effects. Currently, the black box warnings included in the labeling of tofacitinib and upadacitinib give pause, leading many clinicians to move to these agents after an inadequate response to biologics. Newer therapies in the JAK inhibitor class free of serious adverse effects might reverse the order, given the preference of many patients for oral agents. 

The JAK inhibitor development program is rich not just for inflammatory diseases and autoimmune diseases, but for myeloproliferative diseases and neoplasms. JAK inhibitors are already identified in the GRAPPA recommendations as appropriate first-line options for most manifestations of PsA, including joint and skin involvement, but newer drugs with a more favorable JAK selectivity or other pharmacologic characteristics and decreased adverse risks might make these a more dominant treatment choice. 

Summary

Relative selectivity for JAK isoforms promises therapies that are both more effective and safer for PsA as well as other inflammatory diseases. This promise is now being explored in experimental trials testing therapies with variable degrees of selectivity in the context of other characteristics, such as kinase binding, with the potential to influence clinical effects. However, the promise will not be fulfilled until large clinical trials, particularly comparative trials, can confirm the importance of JAK isoform selectivity. If specific types of selectivity prove relevant to the benefit-to-risk ratio of JAK inhibitors in PsA, it may alter the current order of treatment preferences for this disease.

Introduction

The first Janus kinase (JAK) inhibitor received regulatory approval for the treatment of psoriatic arthritis (PsA) more than 5 years ago. Although there are limited comparative data between this and other JAK inhibitors approved or in development for the treatment of PsA, it is reasonable to anticipate variability in therapeutic effect and the risk of adverse events between different JAK inhibitors. So far, there have been considerable differences in the relative selectivity of each agent on the 4 JAK isoform enzymes, JAK1, JAK2, JAK3, and TYK2. This selectivity determines the downstream signal transducers and activators of transcription proteins (JAK-STAT [signal transducer and activator of transcription] pathway) that ultimately mediate both anti-inflammatory and off-target effects. In this review of JAK inhibitors in PsA, differences between JAK inhibitors will be explored for their potential impact on benefit-to-risk ratio while treating PsA.  

Background

Data from the National Psoriasis Foundation (NPF) estimates that 8 million individuals in the United States have psoriasis.¹ PsA, an inflammatory spondyloarthritis associated with psoriasis, develops in about 30% of these individuals, but precise epidemiology on this subset of psoriasis patients is complicated by missed and delayed diagnoses. Of patients with psoriasis, only about 15% of patients with PsA have joint inflammation at the time or in advance of skin lesions.² This might explain delays in diagnosis. In one study, 15% of patients treated for psoriasis were found to have concomitant but unrecognized PsA.³ 

PsA was first classified as a distinct pathologic condition only about 50 years ago, even though skeletal remains indicate that this disease existed in early civilizations.² Based on consensus that PsA deserved definition as a distinct entity, the Classification Criteria for Psoriatic Arthritis (CASPAR) were published in 2006.⁴ By these criteria, cumulative points are allotted for clinical signs of skin, nail, and joint involvement, as well as radiographic signs in patients judged to have inflammatory disease in the joints, spine, or entheses to classify them as having PsA. 

There are numerous recommendations for the treatment of PsA, including those issued by the American College of Rheumatology (ACR),⁵ the European Alliance of Associations for Rheumatology (EULAR),⁶ and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).⁷ Although generally compatible with the others, the GRAPPA recommendations, which are the most recent, have addressed the heterogeneity of PsA by recommending therapies for specific disease domains, such as the skin, nail, and joint manifestations.

For treatment of PsA, the available drug classes for moderate-to-severe disease include immunomodulators, such as methotrexate, biologics that inhibit cytokines, such as tumor necrosis factor (TNF) and the interleukin (IL) cytokines IL-17, 1L-23, and IL12/IL-23, phosphodiesterase-4 (PDE4) inhibitors, and JAK inhibitors. In the GRAPPA recommendations, JAK inhibitors are listed along with other targeted therapies as first-line choices for peripheral arthritis, axial disease, enthesitis, dactylitis, and plaque psoriasis. 

JAK Inhibitors and PsA

There are multiple ways to classify JAK inhibitors. Tofacitinib, the first JAK inhibitor approved for PsA, is labeled a first-generation agent because it is relatively nonselective for the 4 JAK isoforms.⁸ Second-generation agents, such as upadacitinib, have been distinguished from tofacitinib, baricitinib, and other first-generation drugs by greater relative selectivity on the JAK1 enzyme. Other drugs in development for PsA target different JAK isoforms. Deucravacitinib, for example, which was approved for psoriasis after a favorable phase 3 trial⁹ and has shown promise for PsA in a phase 2 trial, is selective for the TYK2 isoform.¹⁰ A rapidly growing list of JAK inhibitors with different selectivity profiles, including dual JAK inhibitory effects, are being explored in a host of inflammatory diseases.

The relationship between selectivity on specific JAK isoforms, anti-inflammatory effects, and off-target effects is not fully understood.⁸ In addition, characteristics beyond JAK selectivity have potential pharmacologic importance. For example, JAK inhibitors can be classified as ATP competitive inhibitors and allosteric inhibitors, both of which are reversible binding modes.⁸ Within each of these subcategories, the site of kinase binding has the potential to influence clinical activity.⁸

JAK Inhibitors: Clinical Experience in PsA 

Tofacitinib, a first-generation JAK inhibitor, initially licensed for use in the treatment of rheumatoid arthritis (RA), received regulatory approval for PsA on the basis of the OPAL Beyond trial.¹¹ Approval of upadacitinib for PsA followed about 4 years later on the basis of the SELECT PsA-1 trial.¹² The primary endpoint in both of these studies was proportion of patients with an ACR response, signifying degree of improvement from baseline, of ≥20%. For the JAK inhibitors, the ACR20 rates were about 50% and 70% in the tofacitinib and upadacitinib phase 3 trials, respectively. Other JAK inhibitors have been evaluated in PsA but none so far are approved in the United States.

Despite experimental evidence supporting the hypothesis that JAK1 selectivity is clinically relevant to the treatment of PsA and other spondyloarthritides,¹³ there is no level 1 evidence of an efficacy or safety advantage for second- relative to first-generation JAK inhibitors. A small number of indirect comparisons, such as one employing a network Bayesian analysis to compare these drugs for the treatment of RA,¹⁴ have supported a clinical advantage for JAK1 selectivity, but head-to-head comparisons are needed to confirm differences. 

Prescribing information for both tofacitinib and upadacitinib in PsA and other indications include a black box warning for risk of serious adverse events, including major adverse cardiac events (MACE) and thromboembolism. The warning is based on the placebo-controlled ORAL trial with tofacitinib in RA.¹⁵ The study population was enhanced for risk with eligibility that required older age and the presence of cardiovascular risk factors. In this high-risk RA population, tofacitinib was associated with modest increases in serious adverse events, including MACE and thromboembolism, relative to placebo over several years of follow-up. A similar trial has not been conducted with upadacitinib or in patients with PsA.  

In a phase 3 trial with the TYK2-selective deucravacitinib in psoriasis, there was no increase in the rate of MACE or thromboembolism.⁹ When granted regulatory approval for psoriasis, the product information did not include a black box warning, differentiating it from other currently available JAK inhibitors. It has not yet been proven whether the absence of serious adverse events in the phase 3 psoriasis and phase 2 PsA trials with deucravacitinib are related to TYK2 JAK enzyme selectivity. 

Although TYK2 is closely associated with upregulation of IL-23 and other inflammatory cytokines implicated in the pathophysiology of PSA, the JAK-STAT signaling pathway is incompletely understood.⁸ Moreover, all of the JAK inhibitors synthesized so far have relative rather than absolute selectivity for any specific JAK isoform. This complicates the ability to attribute benefits and risks to the inhibition of any single JAK enzyme isoform and amplifies the need for comparative studies. 

While other JAK inhibitors have reached late stages of development for the treatment of PsA, such as filgotinib (a JAK1 selective drug) and brepocitinib (which is selective for both JAK1 and TYK2),^16,17 it is appropriate to emphasize that currently available JAK inhibitors are effective and acceptably safe for PsA. The goal of continued drug development is the potential to develop agents with even greater efficacy but with a lower risk of off-target effects. Currently, the black box warnings included in the labeling of tofacitinib and upadacitinib give pause, leading many clinicians to move to these agents after an inadequate response to biologics. Newer therapies in the JAK inhibitor class free of serious adverse effects might reverse the order, given the preference of many patients for oral agents. 

The JAK inhibitor development program is rich not just for inflammatory diseases and autoimmune diseases, but for myeloproliferative diseases and neoplasms. JAK inhibitors are already identified in the GRAPPA recommendations as appropriate first-line options for most manifestations of PsA, including joint and skin involvement, but newer drugs with a more favorable JAK selectivity or other pharmacologic characteristics and decreased adverse risks might make these a more dominant treatment choice. 

Summary

Relative selectivity for JAK isoforms promises therapies that are both more effective and safer for PsA as well as other inflammatory diseases. This promise is now being explored in experimental trials testing therapies with variable degrees of selectivity in the context of other characteristics, such as kinase binding, with the potential to influence clinical effects. However, the promise will not be fulfilled until large clinical trials, particularly comparative trials, can confirm the importance of JAK isoform selectivity. If specific types of selectivity prove relevant to the benefit-to-risk ratio of JAK inhibitors in PsA, it may alter the current order of treatment preferences for this disease.

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Two months of supplementation with omega-3 fatty acids had favorable effects on inflammatory and anti-inflammatory markers in patients with episodic migraine.

Major finding: After 2 months of treatment, the serum concentration of anti-inflammatory interleukin-4 (IL-4) was significantly increased (P = .010) whereas that of proinflammatory interferon gamma was significantly decreased (P = .001) in the omega-3 supplementation vs placebo group. The serum concentration of transforming growth factor beta or IL-17 was not significantly different between the groups.

Study details: The data come from a randomized controlled trial including 40 patients with episodic migraine who were randomly assigned to receive omega-3 supplementation (2 capsules/day; each capsule containing 600 mg eicosapentaenoic acid and 300 mg docosahexaenoic acid; n = 20) or placebo (paraffin oil capsules; n = 20) for 2 months.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Djalali M et al. The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: A randomized, double-blind, placebo-controlled trial. Immunopharmacol Immunotoxicol. 2023 (Apr 26). doi: 10.1080/08923973.2023.2196600

Key clinical point: Maternal migraine diagnosis is associated with a higher risk for several childhood cancers in offspring.

Major finding: A significant positive association was observed between maternal migraine and the risk for non-Hodgkin lymphoma (odds ratio [OR] 1.70; 95% CI 1.01-2.86), central nervous system tumors (OR 1.31; 95% CI 1.02-1.68; particularly glioma: OR 1.64; 95% CI 1.12-2.40), neuroblastoma (OR 1.75; 95% CI 1.00-3.08), and osteosarcoma (OR 2.60; 95% CI 1.18-5.76).

Study details: This study included children age < 20 years with cancers (cases) and birth year- and sex-matched (25:1) children without cancers (control individuals).

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Orimoloye HT et al. Maternal migraine and risk of pediatric cancers. Pediatr Blood Cancer. 2023 (Apr 26). doi: 10.1002/pbc.30385

Key clinical point: Maternal migraine diagnosis is associated with a higher risk for several childhood cancers in offspring.

Major finding: A significant positive association was observed between maternal migraine and the risk for non-Hodgkin lymphoma (odds ratio [OR] 1.70; 95% CI 1.01-2.86), central nervous system tumors (OR 1.31; 95% CI 1.02-1.68; particularly glioma: OR 1.64; 95% CI 1.12-2.40), neuroblastoma (OR 1.75; 95% CI 1.00-3.08), and osteosarcoma (OR 2.60; 95% CI 1.18-5.76).

Study details: This study included children age < 20 years with cancers (cases) and birth year- and sex-matched (25:1) children without cancers (control individuals).

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Orimoloye HT et al. Maternal migraine and risk of pediatric cancers. Pediatr Blood Cancer. 2023 (Apr 26). doi: 10.1002/pbc.30385

Key clinical point: Maternal migraine diagnosis is associated with a higher risk for several childhood cancers in offspring.

Major finding: A significant positive association was observed between maternal migraine and the risk for non-Hodgkin lymphoma (odds ratio [OR] 1.70; 95% CI 1.01-2.86), central nervous system tumors (OR 1.31; 95% CI 1.02-1.68; particularly glioma: OR 1.64; 95% CI 1.12-2.40), neuroblastoma (OR 1.75; 95% CI 1.00-3.08), and osteosarcoma (OR 2.60; 95% CI 1.18-5.76).

Study details: This study included children age < 20 years with cancers (cases) and birth year- and sex-matched (25:1) children without cancers (control individuals).

Disclosures: This study was supported by the US National Institutes of Health. The authors declared no conflicts of interest.

Source: Orimoloye HT et al. Maternal migraine and risk of pediatric cancers. Pediatr Blood Cancer. 2023 (Apr 26). doi: 10.1002/pbc.30385

Key clinical point: This meta-analysis demonstrated a significant bidirectional association between psoriasis and migraine, with greater severity of psoriasis being associated with an increasingly higher risk of developing migraine.

Major finding: Presence vs absence of psoriasis was associated with 1.69-fold higher odds of prevalent migraine (pooled odds ratio [OR] 1.69; 95% CI 1.26-2.28), with the risk for incident migraine being significantly higher in patients with mild (incidence rate ratio [IRR] 1.37; 95% CI 1.30-1.44) and severe (IRR 1.55; 95% CI 1.29-1.86) psoriasis and psoriatic arthritis (IRR 1.92; 95% CI 1.65-2.23). Moreover, presence vs absence of migraine was associated with 1.88-fold higher odds of prevalent psoriasis (OR 1.88; 95% CI 1.32-3.67).

Study details: Findings are from a systematic review and meta-analysis of 10 studies including 6,745,968 participants.

Disclosures: This study did not declare the funding source. The authors declared no conflicts of interest.

Source: Huang IH et al. Bidirectional associations between psoriasis and migraine: A systematic review and meta-analysis. J Dtsch Dermatol Ges. 2023;21(5):493-502 (Apr 17). doi: 10.1111/ddg.14994

Key clinical point: This meta-analysis demonstrated a significant bidirectional association between psoriasis and migraine, with greater severity of psoriasis being associated with an increasingly higher risk of developing migraine.

Major finding: Presence vs absence of psoriasis was associated with 1.69-fold higher odds of prevalent migraine (pooled odds ratio [OR] 1.69; 95% CI 1.26-2.28), with the risk for incident migraine being significantly higher in patients with mild (incidence rate ratio [IRR] 1.37; 95% CI 1.30-1.44) and severe (IRR 1.55; 95% CI 1.29-1.86) psoriasis and psoriatic arthritis (IRR 1.92; 95% CI 1.65-2.23). Moreover, presence vs absence of migraine was associated with 1.88-fold higher odds of prevalent psoriasis (OR 1.88; 95% CI 1.32-3.67).

Study details: Findings are from a systematic review and meta-analysis of 10 studies including 6,745,968 participants.

Disclosures: This study did not declare the funding source. The authors declared no conflicts of interest.

Source: Huang IH et al. Bidirectional associations between psoriasis and migraine: A systematic review and meta-analysis. J Dtsch Dermatol Ges. 2023;21(5):493-502 (Apr 17). doi: 10.1111/ddg.14994

Key clinical point: This meta-analysis demonstrated a significant bidirectional association between psoriasis and migraine, with greater severity of psoriasis being associated with an increasingly higher risk of developing migraine.

Major finding: Presence vs absence of psoriasis was associated with 1.69-fold higher odds of prevalent migraine (pooled odds ratio [OR] 1.69; 95% CI 1.26-2.28), with the risk for incident migraine being significantly higher in patients with mild (incidence rate ratio [IRR] 1.37; 95% CI 1.30-1.44) and severe (IRR 1.55; 95% CI 1.29-1.86) psoriasis and psoriatic arthritis (IRR 1.92; 95% CI 1.65-2.23). Moreover, presence vs absence of migraine was associated with 1.88-fold higher odds of prevalent psoriasis (OR 1.88; 95% CI 1.32-3.67).

Study details: Findings are from a systematic review and meta-analysis of 10 studies including 6,745,968 participants.

Disclosures: This study did not declare the funding source. The authors declared no conflicts of interest.

Source: Huang IH et al. Bidirectional associations between psoriasis and migraine: A systematic review and meta-analysis. J Dtsch Dermatol Ges. 2023;21(5):493-502 (Apr 17). doi: 10.1111/ddg.14994

Key clinical point: Cross-sectional study confirms a significant association of migraine history with the severity of vasomotor symptoms (VMS) and hypertension in midlife women, potentially helping to identify those at risk for severe menopause symptoms.

Major finding: The likelihood of severe or very severe vs no hot flashes (adjusted odds ratio [aOR] 1.34; P = .007) and risk for hypertension (aOR 1.31; P = .002) were significantly higher among women with vs without a history of migraine.

Study details: Findings are from a cross-sectional study including 5708 women aged between 45 and 60 years, of whom 23.7% had a history of migraine.

Disclosures: This study was partially supported by a grant from the National Institute on Aging. Dr. Kling and Dr. Kapoor declared serving as consultants for various sources.

Source: Faubion SS et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98(5):701-712 (May 1). doi: 10.1016/j.mayocp.2023.01.010.

Key clinical point: Cross-sectional study confirms a significant association of migraine history with the severity of vasomotor symptoms (VMS) and hypertension in midlife women, potentially helping to identify those at risk for severe menopause symptoms.

Major finding: The likelihood of severe or very severe vs no hot flashes (adjusted odds ratio [aOR] 1.34; P = .007) and risk for hypertension (aOR 1.31; P = .002) were significantly higher among women with vs without a history of migraine.

Study details: Findings are from a cross-sectional study including 5708 women aged between 45 and 60 years, of whom 23.7% had a history of migraine.

Disclosures: This study was partially supported by a grant from the National Institute on Aging. Dr. Kling and Dr. Kapoor declared serving as consultants for various sources.

Source: Faubion SS et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98(5):701-712 (May 1). doi: 10.1016/j.mayocp.2023.01.010.

Key clinical point: Cross-sectional study confirms a significant association of migraine history with the severity of vasomotor symptoms (VMS) and hypertension in midlife women, potentially helping to identify those at risk for severe menopause symptoms.

Major finding: The likelihood of severe or very severe vs no hot flashes (adjusted odds ratio [aOR] 1.34; P = .007) and risk for hypertension (aOR 1.31; P = .002) were significantly higher among women with vs without a history of migraine.

Study details: Findings are from a cross-sectional study including 5708 women aged between 45 and 60 years, of whom 23.7% had a history of migraine.

Disclosures: This study was partially supported by a grant from the National Institute on Aging. Dr. Kling and Dr. Kapoor declared serving as consultants for various sources.

Source: Faubion SS et al. Association of migraine and vasomotor symptoms. Mayo Clin Proc. 2023;98(5):701-712 (May 1). doi: 10.1016/j.mayocp.2023.01.010.

Key clinical point: Patients with migraine who recovered from COVID-19 showed an increase in the frequency of headache attacks, level of anxiety, and use of antimigraine drugs.

Major finding: Among patients with migraine, those with vs without a history of COVID-19 showed a significant increase in the frequency of headache attacks (P = .01), level of anxiety (P = .002), and use of antimigraine drugs (P = .04) after recovering from COVID-19, with no significant difference being observed in the headache intensity (P = .51) and the dynamics of the Beck Depression scale score (P = .09).

Study details: Findings are from a retrospective study including 133 patients aged 18-55 years with chronic and episodic migraine and with (n = 95) or without (n = 38) a history of COVID-19.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Hrytsenko O et al. The impact of the COVID-19 pandemic on patients with migraine. SAGE Open Med. 2023 (Apr 28). doi: 10.1177/20503121231170726

Key clinical point: Patients with migraine who recovered from COVID-19 showed an increase in the frequency of headache attacks, level of anxiety, and use of antimigraine drugs.

Major finding: Among patients with migraine, those with vs without a history of COVID-19 showed a significant increase in the frequency of headache attacks (P = .01), level of anxiety (P = .002), and use of antimigraine drugs (P = .04) after recovering from COVID-19, with no significant difference being observed in the headache intensity (P = .51) and the dynamics of the Beck Depression scale score (P = .09).

Study details: Findings are from a retrospective study including 133 patients aged 18-55 years with chronic and episodic migraine and with (n = 95) or without (n = 38) a history of COVID-19.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Hrytsenko O et al. The impact of the COVID-19 pandemic on patients with migraine. SAGE Open Med. 2023 (Apr 28). doi: 10.1177/20503121231170726

Key clinical point: Patients with migraine who recovered from COVID-19 showed an increase in the frequency of headache attacks, level of anxiety, and use of antimigraine drugs.

Major finding: Among patients with migraine, those with vs without a history of COVID-19 showed a significant increase in the frequency of headache attacks (P = .01), level of anxiety (P = .002), and use of antimigraine drugs (P = .04) after recovering from COVID-19, with no significant difference being observed in the headache intensity (P = .51) and the dynamics of the Beck Depression scale score (P = .09).

Study details: Findings are from a retrospective study including 133 patients aged 18-55 years with chronic and episodic migraine and with (n = 95) or without (n = 38) a history of COVID-19.

Disclosures: This study did not receive any funding. The authors declared no potential conflicts of interest.

Source: Hrytsenko O et al. The impact of the COVID-19 pandemic on patients with migraine. SAGE Open Med. 2023 (Apr 28). doi: 10.1177/20503121231170726

Key clinical point: The alpha-calcitonin gene-related peptide (CGRP) level was significantly elevated in patients with chronic migraine (CM) vs control individuals, which eventually normalized after treatment with CGRP monoclonal antibodies (mAb) and correlated with clinical response.

Major finding: The significantly higher alpha-CGRP levels in patients with CM vs control individuals (P = .004) normalized at 2 weeks (median 40.4 pg/mL; 95% CI 35.6-48.1 pg/mL) and 3 months (median 40.9 pg/mL; 95% CI 36.3-45.9 pg/mL) post-treatment with a CGRP mAb. A significant correlation was observed between decrease in monthly migraine days at the third month and absolute decrease in alpha-CGRP content at the same time-point (P = .02).

Study details: The data come from an observational study including 103 patients with CM who initiated treatment with CGRP mAb and 78 matched control individuals.

Disclosures: This study was supported by the Instituto de Salud Carlos III, IDIVAL Spain, and Lilly grant. J Pascual and V González-Quintanilla declared receiving advisory or speaker honoraria from various sources, including Lilly. Other authors declared no conflicts of interest.

Source: Gárate G et al. Serum alpha and beta-CGRP levels in chronic migraine patients before and after monoclonal antibodies against CGRP or its receptor. Ann Neurol. 2023 (Apr 11). doi: 10.1002/ana.26658

Key clinical point: The alpha-calcitonin gene-related peptide (CGRP) level was significantly elevated in patients with chronic migraine (CM) vs control individuals, which eventually normalized after treatment with CGRP monoclonal antibodies (mAb) and correlated with clinical response.

Major finding: The significantly higher alpha-CGRP levels in patients with CM vs control individuals (P = .004) normalized at 2 weeks (median 40.4 pg/mL; 95% CI 35.6-48.1 pg/mL) and 3 months (median 40.9 pg/mL; 95% CI 36.3-45.9 pg/mL) post-treatment with a CGRP mAb. A significant correlation was observed between decrease in monthly migraine days at the third month and absolute decrease in alpha-CGRP content at the same time-point (P = .02).

Study details: The data come from an observational study including 103 patients with CM who initiated treatment with CGRP mAb and 78 matched control individuals.

Disclosures: This study was supported by the Instituto de Salud Carlos III, IDIVAL Spain, and Lilly grant. J Pascual and V González-Quintanilla declared receiving advisory or speaker honoraria from various sources, including Lilly. Other authors declared no conflicts of interest.

Source: Gárate G et al. Serum alpha and beta-CGRP levels in chronic migraine patients before and after monoclonal antibodies against CGRP or its receptor. Ann Neurol. 2023 (Apr 11). doi: 10.1002/ana.26658

Key clinical point: The alpha-calcitonin gene-related peptide (CGRP) level was significantly elevated in patients with chronic migraine (CM) vs control individuals, which eventually normalized after treatment with CGRP monoclonal antibodies (mAb) and correlated with clinical response.

Major finding: The significantly higher alpha-CGRP levels in patients with CM vs control individuals (P = .004) normalized at 2 weeks (median 40.4 pg/mL; 95% CI 35.6-48.1 pg/mL) and 3 months (median 40.9 pg/mL; 95% CI 36.3-45.9 pg/mL) post-treatment with a CGRP mAb. A significant correlation was observed between decrease in monthly migraine days at the third month and absolute decrease in alpha-CGRP content at the same time-point (P = .02).

Study details: The data come from an observational study including 103 patients with CM who initiated treatment with CGRP mAb and 78 matched control individuals.

Disclosures: This study was supported by the Instituto de Salud Carlos III, IDIVAL Spain, and Lilly grant. J Pascual and V González-Quintanilla declared receiving advisory or speaker honoraria from various sources, including Lilly. Other authors declared no conflicts of interest.

Source: Gárate G et al. Serum alpha and beta-CGRP levels in chronic migraine patients before and after monoclonal antibodies against CGRP or its receptor. Ann Neurol. 2023 (Apr 11). doi: 10.1002/ana.26658

Key clinical point: Switching calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) may benefit patients with episodic migraine (EM) or chronic migraine (CM) who had failed to respond to the first CGRP-mAb or experienced a loss of efficacy over time.

Major finding: Overall, 71.9% of patients responded to the first CGRP-mAb, 42.3% of those who did not respond or experienced a loss of efficacy over time to the first CGRP-mAb responded to the second CGRP-mAb, and 28.6% of patients who received the third CGRP-mAb showed a response.

Study details: Findings are from a retrospective, real-world case series including 171 patients with EM or CM who received one (n = 137), two (n = 27), or all three(n = 7) CGRP-mAb as migraine preventive therapy.

Disclosures: This study received no specific funding from any source. Some authors declared receiving personal fees, unrestricted grants, honoraria, or travel grants from various sources.

Source: Kaltseis K et al. Monoclonal antibodies against CGRP (R): Non-responders and switchers: Real world data from an Austrian case series. BMC Neurol. 2023;23(1):174 (Apr 28). doi: 10.1186/s12883-023-03203-9

Key clinical point: Switching calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) may benefit patients with episodic migraine (EM) or chronic migraine (CM) who had failed to respond to the first CGRP-mAb or experienced a loss of efficacy over time.

Major finding: Overall, 71.9% of patients responded to the first CGRP-mAb, 42.3% of those who did not respond or experienced a loss of efficacy over time to the first CGRP-mAb responded to the second CGRP-mAb, and 28.6% of patients who received the third CGRP-mAb showed a response.

Study details: Findings are from a retrospective, real-world case series including 171 patients with EM or CM who received one (n = 137), two (n = 27), or all three(n = 7) CGRP-mAb as migraine preventive therapy.

Disclosures: This study received no specific funding from any source. Some authors declared receiving personal fees, unrestricted grants, honoraria, or travel grants from various sources.

Source: Kaltseis K et al. Monoclonal antibodies against CGRP (R): Non-responders and switchers: Real world data from an Austrian case series. BMC Neurol. 2023;23(1):174 (Apr 28). doi: 10.1186/s12883-023-03203-9

Key clinical point: Switching calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) may benefit patients with episodic migraine (EM) or chronic migraine (CM) who had failed to respond to the first CGRP-mAb or experienced a loss of efficacy over time.

Major finding: Overall, 71.9% of patients responded to the first CGRP-mAb, 42.3% of those who did not respond or experienced a loss of efficacy over time to the first CGRP-mAb responded to the second CGRP-mAb, and 28.6% of patients who received the third CGRP-mAb showed a response.

Study details: Findings are from a retrospective, real-world case series including 171 patients with EM or CM who received one (n = 137), two (n = 27), or all three(n = 7) CGRP-mAb as migraine preventive therapy.

Disclosures: This study received no specific funding from any source. Some authors declared receiving personal fees, unrestricted grants, honoraria, or travel grants from various sources.

Source: Kaltseis K et al. Monoclonal antibodies against CGRP (R): Non-responders and switchers: Real world data from an Austrian case series. BMC Neurol. 2023;23(1):174 (Apr 28). doi: 10.1186/s12883-023-03203-9

Key clinical point: A higher proportion of patients with episodic migraine (EM), chronic migraine (CM), or treatment-resistant migraine receiving galcanezumab vs placebo achieved a ≥50% response within the first 3 months of treatment, which was sustained for 4-6 months.

Major finding: Galcanezumab vs placebo was associated with higher odds of clinical response in patients with EM (120 mg galcanezumab: odds ratio [OR] 2.7) and CM (120 mg galcanezumab: OR 19.4; all P < .001), with a higher proportion of galcanezumab- vs placebo-treated patients maintaining ≥50% response for 3-6 months of the double-blind treatment period (P < .001).

Study details: This post hoc analysis included 3348 patients with EM (EVOLVE-1 and EVOLVE-2 trials), CM (REGAIN trial), or EM or CM with 2-4 prior treatment failures (CONQUER trial) who received galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA. Three authors declared being employees of Eli Lilly. SJ Tepper declared ties with various sources, including Eli Lilly.

Source: Tepper SJ et al. Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine. Headache. 2023 (May 3). doi: 10.1111/head.14494

Key clinical point: A higher proportion of patients with episodic migraine (EM), chronic migraine (CM), or treatment-resistant migraine receiving galcanezumab vs placebo achieved a ≥50% response within the first 3 months of treatment, which was sustained for 4-6 months.

Major finding: Galcanezumab vs placebo was associated with higher odds of clinical response in patients with EM (120 mg galcanezumab: odds ratio [OR] 2.7) and CM (120 mg galcanezumab: OR 19.4; all P < .001), with a higher proportion of galcanezumab- vs placebo-treated patients maintaining ≥50% response for 3-6 months of the double-blind treatment period (P < .001).

Study details: This post hoc analysis included 3348 patients with EM (EVOLVE-1 and EVOLVE-2 trials), CM (REGAIN trial), or EM or CM with 2-4 prior treatment failures (CONQUER trial) who received galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA. Three authors declared being employees of Eli Lilly. SJ Tepper declared ties with various sources, including Eli Lilly.

Source: Tepper SJ et al. Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine. Headache. 2023 (May 3). doi: 10.1111/head.14494

Key clinical point: A higher proportion of patients with episodic migraine (EM), chronic migraine (CM), or treatment-resistant migraine receiving galcanezumab vs placebo achieved a ≥50% response within the first 3 months of treatment, which was sustained for 4-6 months.

Major finding: Galcanezumab vs placebo was associated with higher odds of clinical response in patients with EM (120 mg galcanezumab: odds ratio [OR] 2.7) and CM (120 mg galcanezumab: OR 19.4; all P < .001), with a higher proportion of galcanezumab- vs placebo-treated patients maintaining ≥50% response for 3-6 months of the double-blind treatment period (P < .001).

Study details: This post hoc analysis included 3348 patients with EM (EVOLVE-1 and EVOLVE-2 trials), CM (REGAIN trial), or EM or CM with 2-4 prior treatment failures (CONQUER trial) who received galcanezumab or placebo.

Disclosures: This study was funded by Eli Lilly and Company or one of its subsidiaries, Indianapolis, IN, USA. Three authors declared being employees of Eli Lilly. SJ Tepper declared ties with various sources, including Eli Lilly.

Source: Tepper SJ et al. Sustained response of galcanezumab in migraine prevention: Patient-level data from a post hoc analysis in patients with episodic or chronic migraine. Headache. 2023 (May 3). doi: 10.1111/head.14494