Clinical Edge Journal Scan

There is a tremendous amount of atopic dermatitis (AD) research underway. This month, we have several interesting articles to present.

Silverberg and colleagues described a very well-designed, vehicle-controlled, randomized 8-week study of a topical formulation of a purified strain of Nitrosomonas eutropha, an ammonia-oxidizing bacterium. In theory, this bacterium may reduce Staphylococcus aureus. The study compared two concentrations of the bacterium vs vehicle delivered as a spray twice per day. Study participants were adults with AD affecting 10%-40% of body surface area.

The study found "meaningful" improvements in itch and objective signs of disease, with clear separation between both doses of the bacterial spray compared with vehicle. At week 4, about 23% of participants treated with the bacterium were clear or almost clear (with a 2-point improvement) compared with 12% in the vehicle group (for comparison, in a phase 2 study comparing topical ruxolitinib with 0.1% triamcinolone cream, there was a 25% clear or almost clear rate [with 2-point improvement] in the triamcinolone-treated individuals).

Though an "all-natural" bacterial approach to managing AD may be appealing to some, it sounded like magic to me. But this well-done study makes it seem like the bacterial approach could be more promising than I had thought. This study also reported about twice as many adverse events (including gastrointestinal issues) with the bacterium-treated participants compared with those who received vehicle, adding to my belief that the bacterial product has efficacy. Whether any other topical will be more effective and safer than is topical triamcinolone remains to be seen. I'm still pessimistic about topicals because of patients' poor adherence to topical treatment, but perhaps an easy-to-use spray that isn't associated with patients' fear of "steroids" will be helpful.

I love articles like this one from Chen and colleagues. They analyzed data on hundreds of thousands of patients with and without AD. Adults with AD had a "significantly increased risk" of developing venous thromboembolism compared with adults without AD. The huge sample size of their study seems compelling. That huge sample size allows detection of effects so small that they may be clinically insignificant.

They report that patients with AD had a venous thromboembolism at a rate of 1.05/1000 patients-years; the rate was 0.82 for patients without AD. From that, we can calculate that there would be an additional 23 patients with venous thromboembolism for every 100,000 patient-years or about one more venous thromboembolism in the AD group in every 4000 patient-years. Though the finding was statistically significant, I don't think it is clinically meaningful.

The authors correctly conclude that "vascular examination and consultation with the emergency department, cardiologists, or pulmonologists are indicated for patients with AD who present with relevant symptoms (eg, unexplained dyspnea, chest tightness, and limb swelling)." But it is probably also true that vascular examination and consultation with the emergency department, cardiologists, or pulmonologists are indicated for patients without AD who present with those symptoms. I think the authors might have been on solid ground if they had concluded that there was a statistically significant but clinically insignificant increased risk for venous thromboembolism in patients with AD.

Eichenfeld and colleagues examined the use of topical crisaborole once per day as a maintenance treatment for patients with mild to moderate AD. The study compared patients given topical crisaborole with those randomly assigned to vehicle. The active treatment was effective because topical crisaborole treated patients had longer times to the first flare following treatment and fewer flares over the 1 year of treatment. The differences were not huge, but I think they were clinically meaningful. I'm guessing that the topical crisaborole maintenance treatment would have been even more effective had it been used regularly. The study did not, as far as I could tell, assess how well the treatment was used.

An interesting aspect of this study is that it began with nearly 500 participants who started on twice daily topical crisaborole. The 270 patients who responded to the treatment (achieving clear or almost clear with at least a 2-point improvement) were enrolled in the 1-year maintenance phase. Thus, the participants in the maintenance phase were preselected for patients who respond to topical crisaborole. We don't know why they were responders (I, of course, expect it is because they selected for patients who are better than others are at using a topical treatment), but it may be best not to try to generalize these results and assume this form of maintenance treatment would work equally well in a population who achieve initial success with an oral therapy regimen (for example, a quick course of oral prednisone).

Dupilumab was a revolutionary treatment for AD. I didn't think that I'd ever see a more effective treatment. It's so safe too! It has been a first-line treatment for AD since its introduction. Now, we also have oral Janus kinase inhibitor options. Blauvelt and colleagues examined what happens when patients who have been on dupilumab are switched to a high dose (30 mg/d) of upadacitinib (the standard starting dose of upadacitinib is 15 mg/d). Though dupilumab is very effective, upadacitinib is more so. After 4 weeks of switching to upadacitinib, nearly half the patients were completely clear of AD compared with only 16.0% after 24 weeks of dupilumab! The authors point out, optimistically, that "No new safety risks were observed." Though there were no cancers, gastrointestinal perforations, major adverse cardiovascular events, or venous thromboembolic events, there were cases of eczema herpeticum and zoster in patients treated with upadacitinib. Having upadacitinib available for patients who fail dupilumab is a clear benefit; the role of upadacitinib before dupilumab seems less clear.

Patients doing great on dupilumab for AD may be wondering: Do I still need to take it every 2 weeks? Spekhorst and colleagues may have the answer. They describe the response to tapering dupilumab in patients who had been on the drug for at least 1 year with well-controlled disease for at least 6 months. Patients in the study then continued dupilumab with the longest possible dosing interval while maintaining control of their AD.

Generally, patients maintained good control of their AD, with only a small increase in mean disease severity and in concomitant use of topical steroids. For the patients who attempted prolongation, 83% successfully continued dupilumab treatment with a prolonged interval. Not at all surprisingly, the authors calculated that prolonging the interval between dosing led to large savings in cost.

One of the nice features of dupilumab treatment is that loss of response over time seems unusual. Perhaps there is a low propensity for forming antidrug antibodies when dupilumab is used in the standard every 2-week dosing regimen. I don't know whether antidrug antibodies would be more likely with the intermittent dosing regimen. But now that we have other good systemic treatment options for AD, losing dupilumab efficacy would not be as critical a problem as it used to be. I also want to point out that patients' adherence to injection treatment, though better than adherence to topicals, is far from perfect. It's likely that many patients have already been prolonging the interval between taking their treatments. If you want to know, just ask them. The way I like to phrase the question is: "Are you keeping the extra injectors you've accumulated refrigerated like you are supposed to?"

There is a tremendous amount of atopic dermatitis (AD) research underway. This month, we have several interesting articles to present.

Silverberg and colleagues described a very well-designed, vehicle-controlled, randomized 8-week study of a topical formulation of a purified strain of Nitrosomonas eutropha, an ammonia-oxidizing bacterium. In theory, this bacterium may reduce Staphylococcus aureus. The study compared two concentrations of the bacterium vs vehicle delivered as a spray twice per day. Study participants were adults with AD affecting 10%-40% of body surface area.

The study found "meaningful" improvements in itch and objective signs of disease, with clear separation between both doses of the bacterial spray compared with vehicle. At week 4, about 23% of participants treated with the bacterium were clear or almost clear (with a 2-point improvement) compared with 12% in the vehicle group (for comparison, in a phase 2 study comparing topical ruxolitinib with 0.1% triamcinolone cream, there was a 25% clear or almost clear rate [with 2-point improvement] in the triamcinolone-treated individuals).

Though an "all-natural" bacterial approach to managing AD may be appealing to some, it sounded like magic to me. But this well-done study makes it seem like the bacterial approach could be more promising than I had thought. This study also reported about twice as many adverse events (including gastrointestinal issues) with the bacterium-treated participants compared with those who received vehicle, adding to my belief that the bacterial product has efficacy. Whether any other topical will be more effective and safer than is topical triamcinolone remains to be seen. I'm still pessimistic about topicals because of patients' poor adherence to topical treatment, but perhaps an easy-to-use spray that isn't associated with patients' fear of "steroids" will be helpful.

I love articles like this one from Chen and colleagues. They analyzed data on hundreds of thousands of patients with and without AD. Adults with AD had a "significantly increased risk" of developing venous thromboembolism compared with adults without AD. The huge sample size of their study seems compelling. That huge sample size allows detection of effects so small that they may be clinically insignificant.

They report that patients with AD had a venous thromboembolism at a rate of 1.05/1000 patients-years; the rate was 0.82 for patients without AD. From that, we can calculate that there would be an additional 23 patients with venous thromboembolism for every 100,000 patient-years or about one more venous thromboembolism in the AD group in every 4000 patient-years. Though the finding was statistically significant, I don't think it is clinically meaningful.

The authors correctly conclude that "vascular examination and consultation with the emergency department, cardiologists, or pulmonologists are indicated for patients with AD who present with relevant symptoms (eg, unexplained dyspnea, chest tightness, and limb swelling)." But it is probably also true that vascular examination and consultation with the emergency department, cardiologists, or pulmonologists are indicated for patients without AD who present with those symptoms. I think the authors might have been on solid ground if they had concluded that there was a statistically significant but clinically insignificant increased risk for venous thromboembolism in patients with AD.

Eichenfeld and colleagues examined the use of topical crisaborole once per day as a maintenance treatment for patients with mild to moderate AD. The study compared patients given topical crisaborole with those randomly assigned to vehicle. The active treatment was effective because topical crisaborole treated patients had longer times to the first flare following treatment and fewer flares over the 1 year of treatment. The differences were not huge, but I think they were clinically meaningful. I'm guessing that the topical crisaborole maintenance treatment would have been even more effective had it been used regularly. The study did not, as far as I could tell, assess how well the treatment was used.

An interesting aspect of this study is that it began with nearly 500 participants who started on twice daily topical crisaborole. The 270 patients who responded to the treatment (achieving clear or almost clear with at least a 2-point improvement) were enrolled in the 1-year maintenance phase. Thus, the participants in the maintenance phase were preselected for patients who respond to topical crisaborole. We don't know why they were responders (I, of course, expect it is because they selected for patients who are better than others are at using a topical treatment), but it may be best not to try to generalize these results and assume this form of maintenance treatment would work equally well in a population who achieve initial success with an oral therapy regimen (for example, a quick course of oral prednisone).

Dupilumab was a revolutionary treatment for AD. I didn't think that I'd ever see a more effective treatment. It's so safe too! It has been a first-line treatment for AD since its introduction. Now, we also have oral Janus kinase inhibitor options. Blauvelt and colleagues examined what happens when patients who have been on dupilumab are switched to a high dose (30 mg/d) of upadacitinib (the standard starting dose of upadacitinib is 15 mg/d). Though dupilumab is very effective, upadacitinib is more so. After 4 weeks of switching to upadacitinib, nearly half the patients were completely clear of AD compared with only 16.0% after 24 weeks of dupilumab! The authors point out, optimistically, that "No new safety risks were observed." Though there were no cancers, gastrointestinal perforations, major adverse cardiovascular events, or venous thromboembolic events, there were cases of eczema herpeticum and zoster in patients treated with upadacitinib. Having upadacitinib available for patients who fail dupilumab is a clear benefit; the role of upadacitinib before dupilumab seems less clear.

Patients doing great on dupilumab for AD may be wondering: Do I still need to take it every 2 weeks? Spekhorst and colleagues may have the answer. They describe the response to tapering dupilumab in patients who had been on the drug for at least 1 year with well-controlled disease for at least 6 months. Patients in the study then continued dupilumab with the longest possible dosing interval while maintaining control of their AD.

Generally, patients maintained good control of their AD, with only a small increase in mean disease severity and in concomitant use of topical steroids. For the patients who attempted prolongation, 83% successfully continued dupilumab treatment with a prolonged interval. Not at all surprisingly, the authors calculated that prolonging the interval between dosing led to large savings in cost.

One of the nice features of dupilumab treatment is that loss of response over time seems unusual. Perhaps there is a low propensity for forming antidrug antibodies when dupilumab is used in the standard every 2-week dosing regimen. I don't know whether antidrug antibodies would be more likely with the intermittent dosing regimen. But now that we have other good systemic treatment options for AD, losing dupilumab efficacy would not be as critical a problem as it used to be. I also want to point out that patients' adherence to injection treatment, though better than adherence to topicals, is far from perfect. It's likely that many patients have already been prolonging the interval between taking their treatments. If you want to know, just ask them. The way I like to phrase the question is: "Are you keeping the extra injectors you've accumulated refrigerated like you are supposed to?"

There is a tremendous amount of atopic dermatitis (AD) research underway. This month, we have several interesting articles to present.

Silverberg and colleagues described a very well-designed, vehicle-controlled, randomized 8-week study of a topical formulation of a purified strain of Nitrosomonas eutropha, an ammonia-oxidizing bacterium. In theory, this bacterium may reduce Staphylococcus aureus. The study compared two concentrations of the bacterium vs vehicle delivered as a spray twice per day. Study participants were adults with AD affecting 10%-40% of body surface area.

The study found "meaningful" improvements in itch and objective signs of disease, with clear separation between both doses of the bacterial spray compared with vehicle. At week 4, about 23% of participants treated with the bacterium were clear or almost clear (with a 2-point improvement) compared with 12% in the vehicle group (for comparison, in a phase 2 study comparing topical ruxolitinib with 0.1% triamcinolone cream, there was a 25% clear or almost clear rate [with 2-point improvement] in the triamcinolone-treated individuals).

Though an "all-natural" bacterial approach to managing AD may be appealing to some, it sounded like magic to me. But this well-done study makes it seem like the bacterial approach could be more promising than I had thought. This study also reported about twice as many adverse events (including gastrointestinal issues) with the bacterium-treated participants compared with those who received vehicle, adding to my belief that the bacterial product has efficacy. Whether any other topical will be more effective and safer than is topical triamcinolone remains to be seen. I'm still pessimistic about topicals because of patients' poor adherence to topical treatment, but perhaps an easy-to-use spray that isn't associated with patients' fear of "steroids" will be helpful.

I love articles like this one from Chen and colleagues. They analyzed data on hundreds of thousands of patients with and without AD. Adults with AD had a "significantly increased risk" of developing venous thromboembolism compared with adults without AD. The huge sample size of their study seems compelling. That huge sample size allows detection of effects so small that they may be clinically insignificant.

They report that patients with AD had a venous thromboembolism at a rate of 1.05/1000 patients-years; the rate was 0.82 for patients without AD. From that, we can calculate that there would be an additional 23 patients with venous thromboembolism for every 100,000 patient-years or about one more venous thromboembolism in the AD group in every 4000 patient-years. Though the finding was statistically significant, I don't think it is clinically meaningful.

The authors correctly conclude that "vascular examination and consultation with the emergency department, cardiologists, or pulmonologists are indicated for patients with AD who present with relevant symptoms (eg, unexplained dyspnea, chest tightness, and limb swelling)." But it is probably also true that vascular examination and consultation with the emergency department, cardiologists, or pulmonologists are indicated for patients without AD who present with those symptoms. I think the authors might have been on solid ground if they had concluded that there was a statistically significant but clinically insignificant increased risk for venous thromboembolism in patients with AD.

Eichenfeld and colleagues examined the use of topical crisaborole once per day as a maintenance treatment for patients with mild to moderate AD. The study compared patients given topical crisaborole with those randomly assigned to vehicle. The active treatment was effective because topical crisaborole treated patients had longer times to the first flare following treatment and fewer flares over the 1 year of treatment. The differences were not huge, but I think they were clinically meaningful. I'm guessing that the topical crisaborole maintenance treatment would have been even more effective had it been used regularly. The study did not, as far as I could tell, assess how well the treatment was used.

An interesting aspect of this study is that it began with nearly 500 participants who started on twice daily topical crisaborole. The 270 patients who responded to the treatment (achieving clear or almost clear with at least a 2-point improvement) were enrolled in the 1-year maintenance phase. Thus, the participants in the maintenance phase were preselected for patients who respond to topical crisaborole. We don't know why they were responders (I, of course, expect it is because they selected for patients who are better than others are at using a topical treatment), but it may be best not to try to generalize these results and assume this form of maintenance treatment would work equally well in a population who achieve initial success with an oral therapy regimen (for example, a quick course of oral prednisone).

Dupilumab was a revolutionary treatment for AD. I didn't think that I'd ever see a more effective treatment. It's so safe too! It has been a first-line treatment for AD since its introduction. Now, we also have oral Janus kinase inhibitor options. Blauvelt and colleagues examined what happens when patients who have been on dupilumab are switched to a high dose (30 mg/d) of upadacitinib (the standard starting dose of upadacitinib is 15 mg/d). Though dupilumab is very effective, upadacitinib is more so. After 4 weeks of switching to upadacitinib, nearly half the patients were completely clear of AD compared with only 16.0% after 24 weeks of dupilumab! The authors point out, optimistically, that "No new safety risks were observed." Though there were no cancers, gastrointestinal perforations, major adverse cardiovascular events, or venous thromboembolic events, there were cases of eczema herpeticum and zoster in patients treated with upadacitinib. Having upadacitinib available for patients who fail dupilumab is a clear benefit; the role of upadacitinib before dupilumab seems less clear.

Patients doing great on dupilumab for AD may be wondering: Do I still need to take it every 2 weeks? Spekhorst and colleagues may have the answer. They describe the response to tapering dupilumab in patients who had been on the drug for at least 1 year with well-controlled disease for at least 6 months. Patients in the study then continued dupilumab with the longest possible dosing interval while maintaining control of their AD.

Generally, patients maintained good control of their AD, with only a small increase in mean disease severity and in concomitant use of topical steroids. For the patients who attempted prolongation, 83% successfully continued dupilumab treatment with a prolonged interval. Not at all surprisingly, the authors calculated that prolonging the interval between dosing led to large savings in cost.

One of the nice features of dupilumab treatment is that loss of response over time seems unusual. Perhaps there is a low propensity for forming antidrug antibodies when dupilumab is used in the standard every 2-week dosing regimen. I don't know whether antidrug antibodies would be more likely with the intermittent dosing regimen. But now that we have other good systemic treatment options for AD, losing dupilumab efficacy would not be as critical a problem as it used to be. I also want to point out that patients' adherence to injection treatment, though better than adherence to topicals, is far from perfect. It's likely that many patients have already been prolonging the interval between taking their treatments. If you want to know, just ask them. The way I like to phrase the question is: "Are you keeping the extra injectors you've accumulated refrigerated like you are supposed to?"

Key clinical point: Galcanezumab was safe and effective in a patient population severely impaired by chronic migraine (CM) and medication overuse headache (MOH).

Major finding: Galcanezumab led to a significant reduction in migraine days per month, painkillers per month, number of days on medication, numeric rating scale scores, 6-item Headache Impact Test scores, and Migraine Disability Assessment questionnaire scores (all P < .001), with improvements being the greatest during the first 3 months of treatment. Adverse events were mostly mild, with only one case of treatment discontinuation because of severe low back pain.

Study details: The data come from a single-center, prospective study including 78 patients with CM and MOH who received galcanezumab.

Disclosures: This study did not report the funding source. S Guerzoni and C Baraldi declared receiving honoraria from various sources. L Pani declared serving as the Chief Scientific Officer of EDRA-LSWR Publishing Company and Inpeco SA Total Lab Automation Company and had ties to other sources. Other authors declared no conflicts of interest.

Source: Guerzoni S et al. Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population. Brain Behav. 2023;13:e2799 (May 19). doi: 10.1002/brb3.2799

Key clinical point: Galcanezumab was safe and effective in a patient population severely impaired by chronic migraine (CM) and medication overuse headache (MOH).

Major finding: Galcanezumab led to a significant reduction in migraine days per month, painkillers per month, number of days on medication, numeric rating scale scores, 6-item Headache Impact Test scores, and Migraine Disability Assessment questionnaire scores (all P < .001), with improvements being the greatest during the first 3 months of treatment. Adverse events were mostly mild, with only one case of treatment discontinuation because of severe low back pain.

Study details: The data come from a single-center, prospective study including 78 patients with CM and MOH who received galcanezumab.

Disclosures: This study did not report the funding source. S Guerzoni and C Baraldi declared receiving honoraria from various sources. L Pani declared serving as the Chief Scientific Officer of EDRA-LSWR Publishing Company and Inpeco SA Total Lab Automation Company and had ties to other sources. Other authors declared no conflicts of interest.

Source: Guerzoni S et al. Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population. Brain Behav. 2023;13:e2799 (May 19). doi: 10.1002/brb3.2799

Key clinical point: Galcanezumab was safe and effective in a patient population severely impaired by chronic migraine (CM) and medication overuse headache (MOH).

Major finding: Galcanezumab led to a significant reduction in migraine days per month, painkillers per month, number of days on medication, numeric rating scale scores, 6-item Headache Impact Test scores, and Migraine Disability Assessment questionnaire scores (all P < .001), with improvements being the greatest during the first 3 months of treatment. Adverse events were mostly mild, with only one case of treatment discontinuation because of severe low back pain.

Study details: The data come from a single-center, prospective study including 78 patients with CM and MOH who received galcanezumab.

Disclosures: This study did not report the funding source. S Guerzoni and C Baraldi declared receiving honoraria from various sources. L Pani declared serving as the Chief Scientific Officer of EDRA-LSWR Publishing Company and Inpeco SA Total Lab Automation Company and had ties to other sources. Other authors declared no conflicts of interest.

Source: Guerzoni S et al. Galcanezumab for the treatment of chronic migraine and medication overuse headache: Real-world clinical evidence in a severely impaired patient population. Brain Behav. 2023;13:e2799 (May 19). doi: 10.1002/brb3.2799

Key clinical point: Ketogenic diet (KD) significantly improved sleep complaints in patients with migraine, irrespective of migraine improvements and anthropometric modifications.

Major finding: Migraine intensity, headache frequency, and the severity of headache-related disability improved significantly after 3 months of KD therapy (all P < .001) along with a significant decrease in the rate of insomnia (before vs after treatment: 60% vs 40%; P < .001) and number of patients experiencing poor sleep (reduced to half at follow-up; P < .001). The modifications in sleep features showed no correlation with migraine improvements and anthropometric changes.

Study details: This study included 70 patients with migraine who received KD as a preventive therapy for migraine.

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

Source: Merlino G et al. Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control. Sleep Med. 2023;107:196-201 (May 9). doi: 10.1016/j.sleep.2023.05.006

Key clinical point: Ketogenic diet (KD) significantly improved sleep complaints in patients with migraine, irrespective of migraine improvements and anthropometric modifications.

Major finding: Migraine intensity, headache frequency, and the severity of headache-related disability improved significantly after 3 months of KD therapy (all P < .001) along with a significant decrease in the rate of insomnia (before vs after treatment: 60% vs 40%; P < .001) and number of patients experiencing poor sleep (reduced to half at follow-up; P < .001). The modifications in sleep features showed no correlation with migraine improvements and anthropometric changes.

Study details: This study included 70 patients with migraine who received KD as a preventive therapy for migraine.

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

Source: Merlino G et al. Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control. Sleep Med. 2023;107:196-201 (May 9). doi: 10.1016/j.sleep.2023.05.006

Key clinical point: Ketogenic diet (KD) significantly improved sleep complaints in patients with migraine, irrespective of migraine improvements and anthropometric modifications.

Major finding: Migraine intensity, headache frequency, and the severity of headache-related disability improved significantly after 3 months of KD therapy (all P < .001) along with a significant decrease in the rate of insomnia (before vs after treatment: 60% vs 40%; P < .001) and number of patients experiencing poor sleep (reduced to half at follow-up; P < .001). The modifications in sleep features showed no correlation with migraine improvements and anthropometric changes.

Study details: This study included 70 patients with migraine who received KD as a preventive therapy for migraine.

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

Source: Merlino G et al. Sleep of migraine patients is ameliorated by ketogenic diet, independently of pain control. Sleep Med. 2023;107:196-201 (May 9). doi: 10.1016/j.sleep.2023.05.006

Key clinical point: The risk of developing Alzheimer’s disease (AD) dementia is significantly higher in individuals with vs without migraine, with younger age, obesity, and chronic migraine being significant risk factors for AD dementia among individuals with migraine.

Major finding: A prior history of migraine is a significant risk factor for AD dementia (hazard ratio [HR] 1.32; 95% CI 1.30-1.35). The risk was prominently higher among individuals with vs without migraine who were younger (HR 1.58; 95% CI 1.52-1.64) and had obesity (HR 1.39; 95% CI 1.35-1.43) and among those with chronic vs episodic migraine (CM HR 1.48, 95% CI 1.44-1.52; vs EM HR 1.26, 95% CI 1.27-1.29).

Study details: This retrospective, nationwide cohort study included individuals without (n = 5,863,348) and with (n = 212,836) migraine.

Disclosures: This study was supported by grants from the National Research Foundation funded by the Ministry of Education, the Technology Development Program funded by the Ministry of SMEs and Startups (Korea), and others. The authors declared no conflicts of interest.

Source: Kim J et al. Association between migraine and Alzheimer’s disease: A nationwide cohort study. Front Aging Neurosci. 2023;15:1196185 (May 25). doi: 10.3389/fnagi.2023.1196185

Key clinical point: The risk of developing Alzheimer’s disease (AD) dementia is significantly higher in individuals with vs without migraine, with younger age, obesity, and chronic migraine being significant risk factors for AD dementia among individuals with migraine.

Major finding: A prior history of migraine is a significant risk factor for AD dementia (hazard ratio [HR] 1.32; 95% CI 1.30-1.35). The risk was prominently higher among individuals with vs without migraine who were younger (HR 1.58; 95% CI 1.52-1.64) and had obesity (HR 1.39; 95% CI 1.35-1.43) and among those with chronic vs episodic migraine (CM HR 1.48, 95% CI 1.44-1.52; vs EM HR 1.26, 95% CI 1.27-1.29).

Study details: This retrospective, nationwide cohort study included individuals without (n = 5,863,348) and with (n = 212,836) migraine.

Disclosures: This study was supported by grants from the National Research Foundation funded by the Ministry of Education, the Technology Development Program funded by the Ministry of SMEs and Startups (Korea), and others. The authors declared no conflicts of interest.

Source: Kim J et al. Association between migraine and Alzheimer’s disease: A nationwide cohort study. Front Aging Neurosci. 2023;15:1196185 (May 25). doi: 10.3389/fnagi.2023.1196185

Key clinical point: The risk of developing Alzheimer’s disease (AD) dementia is significantly higher in individuals with vs without migraine, with younger age, obesity, and chronic migraine being significant risk factors for AD dementia among individuals with migraine.

Major finding: A prior history of migraine is a significant risk factor for AD dementia (hazard ratio [HR] 1.32; 95% CI 1.30-1.35). The risk was prominently higher among individuals with vs without migraine who were younger (HR 1.58; 95% CI 1.52-1.64) and had obesity (HR 1.39; 95% CI 1.35-1.43) and among those with chronic vs episodic migraine (CM HR 1.48, 95% CI 1.44-1.52; vs EM HR 1.26, 95% CI 1.27-1.29).

Study details: This retrospective, nationwide cohort study included individuals without (n = 5,863,348) and with (n = 212,836) migraine.

Disclosures: This study was supported by grants from the National Research Foundation funded by the Ministry of Education, the Technology Development Program funded by the Ministry of SMEs and Startups (Korea), and others. The authors declared no conflicts of interest.

Source: Kim J et al. Association between migraine and Alzheimer’s disease: A nationwide cohort study. Front Aging Neurosci. 2023;15:1196185 (May 25). doi: 10.3389/fnagi.2023.1196185

Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).

Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.

Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).

Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.

Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160

Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).

Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.

Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).

Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.

Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160

Key clinical point: Use of opioids is still prevalent among patients with migraine, thus indicating non-adherence to evidence-based international guidelines; moreover, the opioid use is more frequent and prolonged among patients with chronic migraine (CM) than among those with episodic migraine (EM).

Major finding: Overall, 13.4% of patients reported ever using an opioid for headache, with 46.3% using opioids occasionally, whereas 27.0% and 11.3% reported using them for >1 month and >1 year, respectively. Additionally, 2.4% of participants used opioids without a prescription. Patients with CM vs EM reported more frequent (21.6% vs 11.7%; P < .001) and prolonged (>1 month: 33.6% vs 24.4%; P < .003; >1 year: 17.7% vs 8.7%; P < .001) opioid use.

Study details: Findings are from a cross-sectional questionnaire-based study including 3712 patients with migraine (CM n = 629; EM n = 3,083).

Disclosures: This study did not receive any funding. GM Terwindt declared receiving consultancy support and independent support from various sources. No other conflicts of interest were declared.

Source: van Welie RF, van Welie FC, et al. Characterizing opioid use in a Dutch cohort with migraine. Cephalalgia. 2023;43(5) (May 11). doi: 10.1177/03331024231174160

Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.

Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.

Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.

Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.

Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2

Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.

Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.

Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.

Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.

Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2

Key clinical point: Switching to fremanezumab may provide clinical benefits in patients with difficult-to-treat episodic or chronic migraine who have not responded to prior monoclonal antibody (mAb) therapy targeting the calcitonin gene-related peptide (anti-CGRP) pathway.

Major finding: Overall, 42.8% of patients achieved a 50% reduction in the monthly migraine days (MMD) after switching to fremanezumab. The MMD decreased from 13.6 to 7.2 (P < .0001), Migraine Disability Assessment scores were reduced from 73.3 to 50.3 (P = .0014), and acute migraine medication use decreased from 9.7 to 4.9 days/month (P < .0001) after 3 months of fremanezumab therapy.

Study details: This subgroup analysis of the real-world, non-interventional Finesse study included 153 patients with episodic or chronic migraine who switched to fremanezumab from other anti-CGRP mAb treatments.

Disclosures: This study was funded by TEVA GmbH. Two authors declared being employees of TEVA GmbH. Several authors, including the lead author, declared serving as consultants or on advisory or speaker boards or receiving research grants from various sources, including TEVA GmbH.

Source: Straube A et al. Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: A subgroup analysis of the Finesse Study. J Headache Pain. 2023;24:59 (May 23). doi: 10.1186/s10194-023-01593-2

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.

Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.

Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).

Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.

Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.

Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.

Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).

Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.

Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2

Key clinical point: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAb) are a safe and effective treatment option for patients age > 65 years with migraine and who did not respond to ≥3 prior migraine preventive medications.

Major finding: At 6 months, monthly migraine days, monthly headache days, and monthly acute medication intake days reduced by 10.1 days (P = .0001), 10.5 days (P < .001), and 9.4 days (P < .001), respectively. Nearly 25.3% of the patients experienced adverse effects at some point during follow-up, which were mostly mild in severity.

Study details: The data come from an observational retrospective study including 162 patients age > 65 years with migraine who did not respond to ≥3 migraine preventive medications and were treated with any one of the three anti-CGRP mAb (erenumab, galcanezumab, or fremanezumab).

Disclosures: This study did not receive any specific grant. Several authors, including the lead author, reported receiving honoraria for consulting, speaking, or advisory board participation; research funding; or travel funding from various sources.

Source: Muñoz-Vendrell A et al. Effectiveness and safety of anti-CGRP monoclonal antibodies in patients over 65 years: A real-life multicentre analysis of 162 patients. J Headache Pain. 2023;24:63 (Jun 2). doi: 10.1186/s10194-023-01585-2

Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.

Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).

Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.

Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.

Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322

Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.

Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).

Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.

Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.

Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322

Key clinical point: The perimenstrual period was associated with an increased susceptibility to migraine without aura exclusively in both women who experienced migraine with and without aura; hence, the study recommended that only attacks without aura should be considered for a perimenstrual migraine diagnosis.

Major finding: A significant interaction was observed between the perimenstrual window and migraine subtype for migraine attack occurrence (P = .022), with the effect of the perimenstrual window being greater among women with migraine without aura (odds ratio [OR] 1.57; 95% CI 1.45-1.69) vs with aura (OR 1.36; 95% CI 1.24-1.49). Women with migraine with vs without aura showed similar increase in migraine attacks without aura during the perimenstrual window (P = .224).

Study details: This longitudinal electronic diary study included 526 premenopausal women diagnosed with migraine with or without aura.

Disclosures: This study was supported by ZonMw and the Dutch Brain Foundation. Five authors, including the lead author, declared receiving independent support from the study funders. Some authors declared receiving consultancy and independent support from various sources.

Source: Verhagen IE et al. Migraine with and without aura in relation to the menstrual cycle and other hormonal milestones: A prospective cohort study. Cephalalgia. 2023;43(6) (May 31). doi: 10.1177/03331024231164322

Key clinical point: Galcanezumab showed significant efficacy after the first week of treatment, and the treatment efficacy after the first week was a significant predictor of the response rate at 3 months.

Major finding: The mean changes in weekly response rates (RR) at 1, 2, 3, and 4 weeks after galcanezumab initiation were 44.6%, 31.4%, 26.0%, and 32.6%, respectively, with the improvement being greatest at 1 week (P < .001) and the RR at 1 week being the only predictive factor for ≥50% RR at 3 months (adjusted odds ratio 1.029; P = .002). Adverse events were mostly mild.

Study details: This retrospective, observational study included 55 patients with high-frequency episodic migraine or chronic migraine who received galcanezumab treatment (an initial loading dose of 240 mg followed by a dose of 120 mg monthly for at least 2 months).

Disclosures: This study did not receive any funding. Four authors declared receiving lecture fees from various sources. No other conflicts of interest were declared.

Source: Suzuki K et al. Could efficacy at 1 week after galcanezumab administration for patients with migraine predict responders at 3 months? A real world study. J Neurol. 2023 (May 23). doi: 10.1007/s00415-023-11788-x

Key clinical point: Galcanezumab showed significant efficacy after the first week of treatment, and the treatment efficacy after the first week was a significant predictor of the response rate at 3 months.

Major finding: The mean changes in weekly response rates (RR) at 1, 2, 3, and 4 weeks after galcanezumab initiation were 44.6%, 31.4%, 26.0%, and 32.6%, respectively, with the improvement being greatest at 1 week (P < .001) and the RR at 1 week being the only predictive factor for ≥50% RR at 3 months (adjusted odds ratio 1.029; P = .002). Adverse events were mostly mild.

Study details: This retrospective, observational study included 55 patients with high-frequency episodic migraine or chronic migraine who received galcanezumab treatment (an initial loading dose of 240 mg followed by a dose of 120 mg monthly for at least 2 months).

Disclosures: This study did not receive any funding. Four authors declared receiving lecture fees from various sources. No other conflicts of interest were declared.

Source: Suzuki K et al. Could efficacy at 1 week after galcanezumab administration for patients with migraine predict responders at 3 months? A real world study. J Neurol. 2023 (May 23). doi: 10.1007/s00415-023-11788-x

Key clinical point: Galcanezumab showed significant efficacy after the first week of treatment, and the treatment efficacy after the first week was a significant predictor of the response rate at 3 months.

Major finding: The mean changes in weekly response rates (RR) at 1, 2, 3, and 4 weeks after galcanezumab initiation were 44.6%, 31.4%, 26.0%, and 32.6%, respectively, with the improvement being greatest at 1 week (P < .001) and the RR at 1 week being the only predictive factor for ≥50% RR at 3 months (adjusted odds ratio 1.029; P = .002). Adverse events were mostly mild.

Study details: This retrospective, observational study included 55 patients with high-frequency episodic migraine or chronic migraine who received galcanezumab treatment (an initial loading dose of 240 mg followed by a dose of 120 mg monthly for at least 2 months).

Disclosures: This study did not receive any funding. Four authors declared receiving lecture fees from various sources. No other conflicts of interest were declared.

Source: Suzuki K et al. Could efficacy at 1 week after galcanezumab administration for patients with migraine predict responders at 3 months? A real world study. J Neurol. 2023 (May 23). doi: 10.1007/s00415-023-11788-x

Key clinical point: Among patients with chronic migraine, the use of concomitant oral treatments (CT) with onabotulinumtoxinA (BoNTA) was not associated with any unexpected tolerability concerns; however, BoNTA plus CT specifically for migraine vs BoNTA alone led to lesser reduction in monthly headache days (MHD).

Major finding: The reduction in MHD after 2-4 cycles of BoNTA treatment was significantly lower among patients receiving BoNTA plus CT for migraine vs BoNTA alone (P < .05). Side effects occurred in 20.3% of patients receiving BoNTA plus CT for migraine, with only 4.1% experiencing significant interference with functioning.

Study details: This retrospective study included 178 patients with chronic migraine who received prophylactic BoNTA with or without CT with a potential effect on migraine.

Disclosures: This study received only the open access funding enabled by Projekt DEAL. Several authors declared receiving honoraria and research funding, serving on advisory boards, or having other ties with various sources. Three authors, including the lead author, declared no conflicts of interest.

Source: Overeem LH et al. A retrospective real-life multicenter study on concurrent oral preventive treatments in patients with chronic migraine treated with onabotulinumtoxinA. CNS Drugs. 2023;37:453-465 (May 22). doi: 10.1007/s40263-023-01001-y

Key clinical point: Among patients with chronic migraine, the use of concomitant oral treatments (CT) with onabotulinumtoxinA (BoNTA) was not associated with any unexpected tolerability concerns; however, BoNTA plus CT specifically for migraine vs BoNTA alone led to lesser reduction in monthly headache days (MHD).

Major finding: The reduction in MHD after 2-4 cycles of BoNTA treatment was significantly lower among patients receiving BoNTA plus CT for migraine vs BoNTA alone (P < .05). Side effects occurred in 20.3% of patients receiving BoNTA plus CT for migraine, with only 4.1% experiencing significant interference with functioning.

Study details: This retrospective study included 178 patients with chronic migraine who received prophylactic BoNTA with or without CT with a potential effect on migraine.

Disclosures: This study received only the open access funding enabled by Projekt DEAL. Several authors declared receiving honoraria and research funding, serving on advisory boards, or having other ties with various sources. Three authors, including the lead author, declared no conflicts of interest.

Source: Overeem LH et al. A retrospective real-life multicenter study on concurrent oral preventive treatments in patients with chronic migraine treated with onabotulinumtoxinA. CNS Drugs. 2023;37:453-465 (May 22). doi: 10.1007/s40263-023-01001-y

Key clinical point: Among patients with chronic migraine, the use of concomitant oral treatments (CT) with onabotulinumtoxinA (BoNTA) was not associated with any unexpected tolerability concerns; however, BoNTA plus CT specifically for migraine vs BoNTA alone led to lesser reduction in monthly headache days (MHD).

Major finding: The reduction in MHD after 2-4 cycles of BoNTA treatment was significantly lower among patients receiving BoNTA plus CT for migraine vs BoNTA alone (P < .05). Side effects occurred in 20.3% of patients receiving BoNTA plus CT for migraine, with only 4.1% experiencing significant interference with functioning.

Study details: This retrospective study included 178 patients with chronic migraine who received prophylactic BoNTA with or without CT with a potential effect on migraine.

Disclosures: This study received only the open access funding enabled by Projekt DEAL. Several authors declared receiving honoraria and research funding, serving on advisory boards, or having other ties with various sources. Three authors, including the lead author, declared no conflicts of interest.

Source: Overeem LH et al. A retrospective real-life multicenter study on concurrent oral preventive treatments in patients with chronic migraine treated with onabotulinumtoxinA. CNS Drugs. 2023;37:453-465 (May 22). doi: 10.1007/s40263-023-01001-y