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Strong support for early use of anti-CGRP mAbs including results from the largest real world mAb study and economic analyses, and latest gepant data for migraine prevention and acute treatment, were among 2024’s clinical research highlights for Professor Koen Paemeleire, from Ghent University Hospital, Belgium. “We’ve seen a huge wave of publications on the CGRP …

Novel agents targeting the vasoactive signalling molecule, pituitary adenylate cyclase-activating polypeptide (PACAP), may be used as an alternative to anti-CGRP therapies or in combination, if promising initial results are confirmed, suggested Professor Messoud Ashina, Copenhagen University Hospital, Copenhagen, Denmark, during his plenary lecture at the congress.1 This follows new data showing that PACAP-28, one of …

New data from the Phase 3 SPACE trial show that fremanezumab significantly reduced monthly migraine days (MMD) in children and adolescents aged 6-17 years with episodic migraine and there were no emergent safety signals. In the study of 237 participants, there was a significantly greater reduction in MMD with fremanezumab than placebo at 12 weeks …

Further evidence of migraine reduction with CGRP mAbs following a drug holiday comes from a retrospective, open-label, real world study of 337 outpatients treated from 2019 to 2023. Of these, 175 were treated with erenumab, 93 with galcanezumab, and 69 with fremanezumab. At baseline, monthly migraine days (MMDs) were 21 ± 7.2, with a median …

Approximately one in three women with menstrual migraine reported positive responses to gepant treatment in a real world survey of adult patients prescribed gepants at the Jefferson Headache Center, Philadelphia, USA, between June 2020 and July 2024. Of 3545 invitations to participate, 478 (13.4%) individuals (age 49.9±14.5 years, 429 (89.7%) Caucasian, 19 (4.0%) African American) …

CGRP mAb therapy appears safe and effective in patients with migraine and comorbid autoimmune disease (AD)1,2 and in patients taking immunosuppressant drugs,3 and such comorbidities and medication use should not preclude CGRP mAb treatment. However, further research is needed on the full clinical implications. These were the conclusions of the authors of a series of studies …

As many as half of patients taking CGRP mAbs may report constipation but much depends on constipation history, and few patients need to stop treatment. These are the main findings from real world studies carried out in the UK and Portugal.1,2 In the UK single-centre, retrospective audit of patients with chronic, refractory migraine who received …

In the Phase 3 Sunrise trial carried out in a predominantly Asian population with chronic migraine, eptinezumab has been shown to significantly reduce monthly migraine days (MMDs). Over weeks 1 through 12, mean reductions in MMDs from baseline were -7.5 with eptinezumab 300 mg and -7.2 with eptinezumab 100 mg compared to -4.8 days with …

Migraine deterioration during an erenumab treatment holiday is reversible, according to data from the APOLLON long-term, flexible dosing, safety and tolerability study during which patients were able to interrupt treatment once for a drug holiday of up to 24 weeks.1 In the study, 108/701 (15.4%) patients with episodic or chronic migraine who had successfully completed …

Dual therapy with a CGRP ligand mAb and a small molecule CGRP antagonist can improve migraine symptom control by significantly reducing headache severity and aura symptoms, without significant adverse events. This is the conclusion of a retrospective matched cohort study of 90 adults with chronic migraine taking anti-CGRP therapy, 28 of whom used dual therapy …

Following inadequate initial treatment response, switching to a different CGRP mAb reduces monthly migraine days compared to returning to standard care, according to results of a controlled cohort study of 67 patients who discontinued their erenumab or fremanezumab treatment within three months of initiation. Three months after treatment discontinuation, there was a reduction of 3.9 …

Atogepant users are significantly less likely to switch to another branded preventive treatment within one year of treatment initiation than CGRP mAb users, an analysis of US claims data from over 5000 patients starting treatment from October 2022 to June 2023 has shown. The study included 641 patients who initiated treatment with atogepant and 3,594 …

Patients with high frequency episodic migraine (HFEM) treated with erenumab in the Phase 4 EMBRACE study reported significantly fewer hours with a moderate or severe headache each month, and less impact of migraine on usual activities, physical, social and emotional functioning compared to those treated with placebo. In the 510 participants with HFEM receiving erenumab …

Real world data from 25 centres contributing to the I-GRAINE registry in Italy, highlight the clinical efficacy and safety of CGRP mAbs at all adult ages and have led researchers to support their suitability in older patients with potential contraindications to other preventive agents for migraine. A total of 1890 patients with migraine took part …

Patients with ≥50% migraine response to eptinezumab 100 mg or 300 mg over weeks 1–12 continue to show improvements in monthly migraine days (MMD), headache-related impact, presenteeism, and percentage of severe migraine attacks over 72 weeks. A post hoc analysis of long term DELIVER results in 865 patients has shown that ≥50% responders treated with …

The efficacy of anti-CGRP therapies (CGRP mAbs and gepants) in migraine is well established.1 However, the precise mechanisms of action are unclear and the question of whether a central or peripheral mechanism is responsible for their efficacy remains unresolved. Dr Kuan-Po Peng, from the Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Germany, reviews the …

The recognition that a migraine starts neurobiologically, 1-10 electrophysiologically, 11-14 and symptomatically, 15-22 hours to days before the headache, has provided insights into the mechanisms of attack initiation and migraine pathogenesis.23 Neurologist, Dr Nazia Karsan, who works as a postdoctoral researcher in the Headache Group at King’s College London, UK, discusses recent progress in mechanism …

Top-line data from the Phase 3 SPACE trial support the efficacy and safety of fremanezumab for the prevention of episodic migraine in children and adolescents. The trial met its primary endpoint, with fremanezumab showing a statistically significantly greater reduction in monthly migraine days over 12 weeks compared with placebo. Safety data were consistent with those …

New research has shown that CGRP signalling primes interactions between meningeal lymphatic vessels (MLVs) and immune cells, supporting a previously unrecognised role for the lymphatic system in chronic migraine. “Our study has highlighted the importance of the brain’s lymphatic system in the pathophysiology of migraine pain,” said Professor Kathleen M. Caron, UNC School of Medicine, Chapel …

CGRP inhibition is associated with decreased rates of acne and rosacea compared with no inhibition or indirect inhibition in patients experiencing migraine. This is the finding from a cohort study using data from the TriNetX US Collaborative Network of 62 healthcare organisations carried out in May 2024.1 Using 1-year Cox proportional hazards models with 95% …

Atogepant is effective in preventing chronic migraine (CM), with and without acute medication overuse, according to results of a subgroup analysis of the PROGRESS trial. Of 755 study participants in the modified intent-to-treat population, 500 (66.2%) met criteria for acute medication overuse at baseline. The least squares mean difference (LSMD) (95% CI) from placebo in …

Pausing and reintroducing CGRP mAbs after 12 months of continuous use, as required by some reimbursement agencies, reduces treatment effectiveness, according to results of the fourth interim analysis of the Phase 4 PEARL trial of 220 adults with episodic or chronic migraine using fremanezumab. In the study, 196 patients stopped treatment after a mean 11.2 …

CGRP mAbs induce positive modulation of functional connectivity in the delta and theta bands in patients who respond to treatment. This is the finding from a prospective, real world, open label study in 62 patients with migraine (35 with chronic migraine) who underwent high density (HD)-EEG recordings at baseline and three and six months after …

Galcanezumab effectively reduces migraine days in patients with medication overuse headache (MOH), irrespective of whether it is combined with prednisone. Results of a prospective observational study of 75 patients with MOH which compared the effectiveness and safety of galcanezumab alone, galcanezumab+prednisone and prednisone alone, showed significant reductions in median monthly headache days (MHD) in all …

Many CGRP mAb responders who are defined as ‘late’ may in fact be ‘slow’, ie. they achieve a meaningful response at three months and improve with time. This is the conclusion of a prospective analysis of 332 outpatients with migraine, 283 (85.2%) of whom continued CGRP mAb treatment (erenumab, fremanezumab or galcanezumab) for six months. …

Over half of patients in a real world observational study carried out in Spain had a sustained response to CGRP mAbs (erenumab, fremanezumab and galcanezumab) after two years of treatment. In the study, 148 patients were included, 108 (73%) with chronic migraine. Median baseline monthly headache days (MHD) and monthly migraine days (MMD) were 18 …

Two thirds of patients using onabotulinumtoxinA to prevent chronic migraine (CM) appear to benefit from adding atogepant to their treatment. In a real world study of 234 patients with CM treated with onabotulinumtoxinA for at least one year, with a stable response for two consecutive 12 week periods between treatments, 211 completed a further 12 …

Secondary endpoint data reported from a Phase 3 study of a single dose of rimegepant 75 mg ODT in patients with migraine in China and South Korea have confirmed the efficacy of acute treatment for up to 48 hours (NCT04574362).1 In the study of 1,340 patients with 2-8 moderate or severe migraine attacks per month, …

A machine learning model developed by researchers at a US tertiary headache centre can accurately predict response to CGRP mAbs nearly 80% of the time. A deep neural network, TabNet, was trained using 145 variables based on results of questionnaires completed by 4260 adult patients with migraine during their initial and follow up headache consultations …

Eptinezumab did not reduce the frequency of episodic cluster headache (eCH) in the two weeks after treatment but improvements were seen in weekly ≥50% responder rates and patient-perceived disease improvement. These were the main findings of the Phase 3, placebo controlled ALLEVIATE trial (NCT04688775) of eptinezumab 400 mg i.v in 231 patients with eCH.1 Over …

Women and Hispanic patients with chronic migraine, and those living in some poorer areas, missed out on CGRP mAb and gepant prescriptions during roll-out at a large US migraine centre, according to results of a retrospective cohort study using data adapted from the Stanford deidentified instance of the Observational Medical Outcomes Partnership Common Data Model …

Reductions in cortical thickness and decreased functional connectivity seen in patients with migraine who respond to CGRP mAbs may indicate recovery from maladaptive neural activity in the visual, sensory and pain regions and normalisation of the hyperreactive/hyperexcitable state seen in migraine. This was the conclusion of Dr Edina Szabo from Beth Israel Deaconess Medical Center …

Macrophages and inducible nitric oxide synthase (iNOS) may contribute to the downstream effects of CGRP in migraine, according to results of a preclinical study of the impact of depleting macrophages and inhibiting iNOS prior to dural treatment with CGRP. In the study, intraperitoneal injections of clodronate liposomes (150 μL, IP) to deplete macrophages, or the …

Real world pregnancy registers have been established for fremanezumab, ubrogepant and atogepant, and interim data are reassuring.1,2 The fremanezumab migraine registry was established in the USA in 2020 (www.tevamigrainepregnancyregistry.com) and, as of 28 April 2023, 12 patients were enrolled – 10 in the fremanezumab cohort (nine prospective and one retrospective) and 2 in comparison group …

New data from the largest real world study of CGRP mAbs in patients with high-frequency episodic or chronic migraine (CM) have shown that more frequent and disabling migraines reduce the likelihood of a good response – underlining the importance of earlier treatment.1 In the European multicentre, prospective study, 5818 patients with a median 20 monthly …

Over 70% of patients with episodic migraine who respond initially to atogepant treatment achieve a sustained response with continued treatment, according to post hoc analyses of results from the ADVANCE trial and a separate open label long term safety study (LTS).1 The findings are comparable with recently reported long term data from the PROGRESS and …

Aquipta (atogepant) can be prescribed for migraine prevention free of charge on the National Health Service (NHS) in England, following a recommendation by the National Institute for Health and Care Excellence (NICE). Adults who have at least four migraine days per month and have previously failed on at least three preventive medicines are eligible for treatment. Physicians …

Erenumab may have potential for relieving the facial redness and flushing of rosacea, according to results of a small, open label study of 30 individuals with the condition. Study participants received monthly erenumab 140 mg sc for 12 weeks at the Danish Headache Center, Copenhagen, Denmark.  Mean days of moderate to extreme flushing were reduced …

Interim data from an open label 156 week extension study of atogepant 60 mg support its long term efficacy and safety for prevention of chronic and episodic migraine at 48 weeks. In the study of 595 patients from the earlier Phase 2 ELEVATE and PROGRESS trials, monthly migraine days (MMDs) improved by a mean 8.5 …

Early response to eptinezumab in patients who have failed on two to four previous preventive migraine treatments is sustained over 18 months, according to results of a post hoc analysis of the Phase 3 DELIVER trial. Of participants who achieved ≥50% response over the first dosing interval (weeks 1-12), 61% of those on eptinezumab 100 …

Approximately 30% of patients with migraine switch CGRP mAbs at least once, and of those prescribed gepants approximately 30% will have at least two agents, according to results of a retrospective case series analysis of nearly 3000 patients diagnosed with migraine and seen by care providers at the Jefferson Headache Center, Philadelphia, USA, between 2018 …

New research has supported the potential of fremanezumab and ubrogepant to act centrally as well as peripherally, though further studies are needed to understand the clinical implications of the results.1,2 In a study of 25 healthy volunteers, a single dose of fremanezumab 900 mg iv was administered, and plasma and CSF levels were measured for …

Acute treatment with zavegepant nasal spray, up to eight doses per month for up to 52 weeks, has been shown to reduce the use of analgesics such as ibuprofen, aspirin, paracetamol, and naproxen in patients with migraine. In a post-hoc, sub group analysis of a phase 2/3, 1-year, open label safety study in 603 participants …

The American Headache Society (AHS) has recommended that anti-CGRP therapies should be considered as first line treatment for migraine prevention.1 In a new consensus statement based on a comprehensive review of clinical trial and real-world experience, the AHS concluded that the evidence supporting the efficacy, tolerability, and safety of CGRP-targeting therapies for migraine prevention is …

A decrease in neural activity in distinct regions of the brain following erenumab 70 mg has been reported in a placebo-controlled, double-blind, randomised study of 40 patients with migraine who underwent fMRI scanning. This change was seen mainly in individuals who showed a clinical benefit from the anti-CGRP treatment. Seven out of 21 patients in …

Gepants have additional effects on CGRP-induced vasorelaxation when used with erenumab, supporting their efficacy in treating migraine attacks in patients already using erenumab as prophylaxis. These are the findings of a study investigating the effects of combination treatment in human coronary artery (HCA) and human middle meningeal artery (HMMA) segments. pA2 or pKb values were calculated to …

People with high frequency episodic migraine (HFEM) and chronic migraine (CM) who are typically excluded from randomised controlled trials (RCTs) of anti-CGRP therapies responded as well to galcanezumab over a 12-month period as those who took part in pivotal clinical trials of the drug, according to real world data from the Galca-Only Registry.1 Of the …

CGRP mAbs reduce migraine aura days as well as migraine headache days, according to data from a pilot prospective observational cohort study of 14 patients with migraine aura treated with erenumab, fremanezumab or galcanezumab and followed up for 12 months. Mean monthly aura days were reduced from a median of 13 at baseline (interquartile range: …

A change in reimbursement policy in Germany allowing earlier use of CGRP mAbs in patients with at least four migraine days per month has led to more treatment responders in clinical practice.1 Results of a retrospective cohort study of CGRP-mAb naïve patients with episodic or chronic migraine, showed a higher ≥ 50% responder rate in …

Only 16 out of 29 European countries taking part in a recent survey provided reimbursement for CGRP mAbs. In general (hospital based) neurologists were permitted to prescribe CGRP mAbs, and sometimes this was extended to headache or pain specialists. Eligibility criteria for patients ranged from at least four monthly migraine days to criteria for chronic …