Gene-related Peptide Monoclonal Antibodies Research Articles

Efficacy and Tolerability of Anti-CGRP Monoclonal Antibodies in Patients Aged ≥ 65 Years With Daily or Nondaily Migraine.

Despite decreasing prevalence of migraine with advancing age, there remains a significant proportion of individuals aged ≥65 years with migraine. Treatment of this population is difficult and they are often excluded from clinical trials, limiting evidence regarding migraine treatment outcomes. Our objective is to assess the efficacy and tolerability of anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) therapies (erenumab, fremanezumab, and galcanezumab) in patients ≥65 years (O65) compared with patients <65 (U65) with daily or nondaily migraine. This observational study uses retrospective data from the electronic medical records of patients who were treated with an anti-CGRP mAb between June 2018 and November 2021. Efficacy was determined through a reduction in monthly migraine days (MMDs) and Headache Impact Test (HIT-6) scores from baseline to posttreatment. Tolerability was examined through the number of adverse events reported per group. Mann-Whitney tests were used to compare the efficacy and tolerability of U65 and O65 patients overall and separated into daily and nondaily migraine groups. The dataset consisted of U65 (n = 2,707; median [interquartile range]; 45.4 [35.8-53.8] years) or O65 (n = 304; 69.5 [67.3-73.3] years) and further separated into daily (n = 1,303) and nondaily (n = 1,708) migraine. There was no difference (p = 0.57) in the median MMD reduction between U65 (10 days [0.0-17.0]) and O65 (10 days [0.0-16.5]). Similarly, no difference was found among patients with nondaily migraine (p = 0.82) and patients with daily migraine (p = 0.59). HIT-6 scores decreased from severe to moderate/substantial impact for all groups. The daily and nondaily groups showed differences in meeting the 50% improvement threshold (nondaily U65, 67% vs daily U65, 54%, p < 0.0001; nondaily O65, 65% vs daily O65, 49%, p = 0.008). Side effects were reported (829/3,011), with a higher incidence in the U65 (22% O65, 28% U65). The most common side effects for both groups were injection site reaction/rash (40%) and constipation (25%). This retrospective analysis provides real-world evidence that there is no difference in the efficacy and tolerability of treatment with erenumab, fremanezumab, and galcanezumab in patients O65 when compared with patients U65 both with daily or nondaily migraine. These data may help guide the choice of migraine treatment in older populations.

One-Year Compliance After Calcitonin Gene-Related Peptide Monoclonal Antibody Therapy for Migraine Patients in a Real-World Setting: A Multicenter Cross-Sectional Study

Background: Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are a breakthrough migraine treatment, but long-term compliance under limited public insurance coverage has not been well known. This study explores one-year treatment patterns and outcomes of CGRP mAbs using real-world data. Methods: This multicenter retrospective study included migraine patients treated with CGRP monoclonal antibodies (CGRP mAbs) from July 2022 to June 2023. Treatment discontinuation was defined as a gap of over 60 days between injections. Among patients with 12 months of follow-up, adherence was measured using the Proportion of Days Covered (PDC), calculated as the ratio of days covered to the follow-up duration, with PDC ≥ 80% indicating good adherence. Efficacy was also assessed, defined as a ≥50% reduction in monthly headache days and acute medication use. Results: The study included 140 patients (mean age 44.6 ± 12.1 years; 82.9% female). Migraine without aura was predominant (93.6%), and 65.0% had chronic migraine. CGRP mAbs discontinuation occurred in 71.4% of patients, primarily due to headache improvement (22.9%) or lack of efficacy (15.0%). Among 81 patients with 12 months of follow-up, good adherence was observed in 40.7% of patients. Among these patients, 60.6% achieved a ≥50% reduction in monthly headache days, and 51.9% showed a ≥50% reduction in monthly acute medication use. Conclusions: More than two-thirds of patients discontinued the CGRP mAb within 1 year, so these findings emphasize the need for strategies to improve adherence and optimize follow-up plans to enhance patient support.

Medication underuse in real-life practice: the impact of galcanezumab towards achieving very low frequency episodic migraine in a southeast Asian middle-income nation

BackgroundMigraine progression, particularly from episodic to chronic migraine (CM), increases disease burden and healthcare costs. Understanding the new concept of “Medication Underuse Headache” should encourage the health care provider to consider early intervention with calcitonin gene-related peptide (CGRP) monoclonal antibodies. Galcanezumab given early in the course of the disease, may prevent migraine chronification and have a robust response, moreso than when initiated in later stages of migraine. We aimed to determine the efficacy of galcanezumab in achieving very low-frequency episodic migraine (VLFEM) among patients with high-frequency episodic migraine (HFEM) and CM in a real world-setting in Thailand.MethodsA single-center, retrospective real-world, cohort study was conducted between 2023 and 2024. Adults aged 18 years or more who were diagnosed with HFEM or CM were included in this trial and categorized into two groups: galcanezumab and oral migraine preventive medication (OMPM). In the galcanezumab group, oral preventive medications were slowly tapered off within 3 months. The primary outcome was the differences in percentage of patients achieving VLFEM at months 3 and 6 between the two groups. Secondary outcomes included the differences in migraine class improvement, sustained response, and headache day reduction.ResultsA total of 62 patients (31 in each group) were included: median age was 36.5 (IQR: 29.0–48.0) and 82% were female. There were no significant differences in the baseline demographic features between the two groups. The cumulative incidence of patients achieving VLFEM was significantly higher among the galcanezumab group compared to OMPM group (45.2% vs. 19.4% at month 3 and 52.9% vs. 32.4% at month 6, p = 0.03). After 6 months of follow-up, patients with HFEM who received galcanezumab were significantly more likely to achieve any improvements in migraine class compared to those who received OMPM (92.9% vs. 46.7%, p = 0.01). Among 15 patients who achieved VLFEM at month 3, 81.8% (9/11) of those who received galcanezumab and 50.0% (2/4) of those who received OMPM were able to sustain VLFEM at month 6.ConclusionsThis study emphasizes the benefit of early anti-CGRP therapy initiation, especially in patients with fewer headache days, and highlights the need for accessible migraine-specific treatments in low- to middle-income countries.

Efficacy and Safety of Switching Between Anti-CGRP Monoclonal Antibodies: A Detailed Monthly and Long-term Follow-up Study and Literature Review

Objective Switching from one anti-calcitonin gene-related peptide monoclonal antibody (CGRP mAb) to another can be beneficial for treating patients with migraine who do not respond well to the first CGRP mAb. However, detailed and long-term follow-up reports of both efficacy and safety remain insufficient. We conducted a case-series analysis of patients with migraine who switched from galcanezumab to erenumab, both belonging to the class of CGRP mAbs. Methods We conducted a single-center retrospective real-world study. Patients with migraine who first received galcanezumab for ≥3 months and then switched to erenumab at Keio University Hospital were enrolled to investigate changes in monthly migraine days (MMD), response rate, and adverse effects (e.g., injection-site reactions). Additionally, we performed a narrative review of the literature on switching CGRP mAbs. Results Among the nine patients enrolled, the 50% response rate for MMD was 33% at 3 months after switching. Two patients (22%) initially responded at the 3-month assessment, but later reverted to baseline MMD levels. Switching from galcanezumab to erenumab increased the frequency of constipation, which was typically managed using laxatives. Participants who experienced injection-site reactions tended to exhibit similar reactions regardless of the type of CGRP mAb used. Five patients (56%) demonstrated an improvement in satisfaction after erenumab initiation at least once. A literature review revealed that the characteristics of the cohorts varied among studies. Conclusions Switching from galcanezumab to erenumab was effective in some patients, while it was associated with some tolerable side effects, and it improved patient satisfaction in approximately half of the patients, despite interindividual diversity in responses and fluctuating responses after switching, which warrants further investigation.

Assessing the occurrence of hypertension in patients receiving calcitonin gene-related peptide monoclonal antibodies for episodic and chronic migraine: a systematic review and meta-analysis.

Calcitonin gene-related peptide (CGRP) monoclonal antibodies in the treatment of episodic and chronic migraine was invetigated. A comprehensive literature search was conducted in Ovid Medline, Web of Science and Embase databases from their inception until April 2024 for randomized controlled trials comparing CGRP monoclonal antibodies with placebo or other active treatments in adults with episodic or chronic migraine. The primary outcome assessed was the incidence of hypertension, and secondary outcomes were tolerability, acceptability and adverse events. Data analysis was performed using a random-effects model, and the strength of evidence was evaluated using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach. A total of eleven studies involving 9729 participants were found eligible and included for data analysis. The results revealed that the pooled odds ratio for the incidence of hypertension in patients receiving CGRP monoclonal antibodies compared to placebo was (95% confidence interval (CI): 0.60, 2.21; I2 = 32%), suggesting no significant increase in hypertension risk. Moreover, no significant differences were observed in tolerability or acceptability between the CGRP monoclonal antibody and placebo groups. However, the overall risk of total adverse events was significantly higher in the CGRP monoclonal antibody group (odds ratio (OR): 1.13; 95% CI: 0.97, 1.33; I2 = 56%; p = 0.01). These findings indicate that CGRP monoclonal antibodies are well-tolerated and present a generally safe option for treating episodic and chronic migraine. Although there was no significant increase in the incidence of hypertension, a slight rise in overall adverse events was observed. Consequently, CGRP monoclonal antibodies may be considered a viable treatment option for patients who have not found other treatments effective or tolerable, or who have contraindications to alternative therapies. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk, registration number: CRD42024554897).

Direct Comparison of Treatment Outcome Between the Botulinum Toxin and Calcitonin Gene-Related Peptide Monoclonal Antibody in Migraine Patients.

Migraine is a genetic disorder characterized by recurrent episodes of headache that are throbbing in nature. The objective of this study was to directly compare the efficacy and safety of anti-calcitonin gene-related peptide (anti-CGRP) and botulinum neurotoxin (BoNT) for the preventive treatment of chronic migraine. This quasi-experimental comparative study was conducted on 80 "chronic migraine patients" at King Fahad University Hospital, Dammam, KSA. Chronic migraineurs were divided into two groups (40 patients/group) and were treated with the standard doses of BoNT (group I) and anti-CGRP (group II). All the patients filled out the migraine pain scale, migraine disability assessment score, headache impact test (HIT-6), and adverse drug event questionnaire before the start and at the end of 9 months of treatment. Most of the patients were females (76.3% vs. 23.8%) and were suffering from migraine for more than 24 months (66%). The mean age of the participants was 39.07 ± 10.01 years. Both BoNT and anti-CGRP groups showed a statistically significant decrease in mean HIT-6 and pain scores after 9 months of intervention. A direct comparison between the two treatment groups showed that the anti-CGRP drug caused a higher decrease in HIT-6 and pain scores as compared to the botulinum drug, but the difference was not statistically significant (P = 0.075 and 0.07, respectively). The most common adverse effect was "headache", reported by 45% and 40% of patients, followed by "pain at the site of injection" reported by 27.5% and 32.5% of BoNT and anti-CGRP groups, respectively. The two groups did not differ significantly in the frequency of adverse effects such as nausea, vomiting, visual problems, etc., except "joint stiffness". A significantly higher number of anti-CGRP patients experienced joint stiffness as compared to the BoNT group (17.5% vs. 0%, P = 0.006). A direct comparison between the two treatments indicated that neither of the two interventions is statistically superior to the other in terms of efficacy and both are equally effective in the management of migraine. However, BoNT can be preferred over anti-CGRP because of its cost-effectiveness.

Scoping Review: The Effects of Interrupted Onabotulinumtoxin A Treatment for Chronic Migraine Prevention During the COVID-19 Pandemic.

To systematically examine the literature on the clinical consequences of inadvertent delays in scheduled onabotulinumtoxin A (OTA) therapy for chronic migraine during the COVID-19 pandemic and assess recommendations when access to OTA is limited. The coronavirus (COVID-19) pandemic was unprecedented in its impact on the global medical community. Most healthcare institutions in the United States (US) and the world had begun significantly limiting elective procedures, undermining management of many debilitating chronic conditions. OTA injections, were similarly involuntarily postponed, leading to significant setbacks in symptom control. A comprehensive literature search was conducted on databases of Medline and Embase with search timeframe defined as the point of database inception to March 1st, 2024, and the search was performed on March 2nd, 2024. The search strategy was independently formulated by two authors (QR and CR) and was reviewed and approved by all authors of the article after appropriate amendments. A total of nine articles met the defined inclusion criteria. They collectively demonstrated marked delays in OTA treatment with decline in migraine symptom control measured in the form of migraine intensity, frequency, as well as patient satisfaction in disease management. Quality of care in the form of follow-ups also appeared compromised. Alternative strategies of telemedicine and the administration of calcitonin gene-related peptide monoclonal antibodies (CGRP mAb) were adopted in place of conventional treatment. The COVID-19 pandemic had caused marked clinical deterioration in the migraine patient populations across US, Europe, and the Middle East. Strategies employed to circumvent this limitation included the adoption of remote consultation via telemedicine as well as the use of pharmacological agents such as CGRP antagonists. In the event of a reoccurrence of a worldwide pandemic, strategies should be implemented to prevent the cessation of needed treatment for those suffering from chronic migraine.

Switching from ligand to receptor anti-calcitonin gene-related peptide (CGRP) antibodies or vice versa in non-responders: A controlled cohort study.

Limited options exist for migraine prevention after stopping anti-calcitonin gene-related peptide monoclonal antibodies. A systematic review examining the benefits of switching between different classes (ligand vs. receptor monoclonal antibody) is essential, alongside well-designed real-world studies. In this cohort study 67 patients were included, who discontinued their first treatment with erenumab or fremanezumab. Patients (n = 31) switched to another monoclonal antibody class within 3 months, whilst those in the control group (n = 36) received standard care. Allocation to either group relied largely on the availability of alternative monoclonal antibody treatments, introducing pseudo-random allocation. Changes in monthly migraine days were compared between groups 3 months post-discontinuation of the first monoclonal antibody or initiation of a different monoclonal antibody class. A multivariate regression model was conducted that accounted for potential confounding factors. The groups were comparable at baseline and poor treatment response was the main reason for treatment discontinuation of the first monoclonal antibody. The switching cohort experienced a reduction of 3.9 monthly migraine days (95% confidence interval -6.4, -1.3, p = 0.004) compared with the control group. Transitioning to a different anti-calcitonin gene-related peptide monoclonal class yields reduction in monthly migraine days compared to returning to standard care for patients with inadequate initial treatment response.

The Impact of COVID-19 on Migraine: The Patients' Perspective.

The COVID-19 pandemic represents a global health phenomenon that will sadly remain part of our history. It had innumerable consequences for society and people's lives. With different mechanisms, COVID-19 has been pointed out as a factor in the pathophysiology of several secondary disorders or the deterioration of pre-existing conditions. Migraine is a frequent disorder that can be influenced by several conditions, including psychologically stressful conditions or infectious diseases. The purpose of the present study is to gain insight into the influence of COVID-19 on the clinical characteristics of patients with migraine. A self-administrable questionnaire has been developed, asking for migraine features before and after COVID-19 infection. One hundred and two patients who had been infected at least once were included. After COVID-19 infection, 54 reported the worsening of migraine, 45 noticed no variation, and 3 reported an improvement. After the infection, 21 patients changed preventive therapy due to the loss of efficacy of the previous one. The most effective treatments in this subpopulation were gene-related peptide monoclonal antibodies. The presented data confirm that the influence of COVID-19 is heterogeneous in patients with migraine, but new treatments may be effective in controlling the symptoms among those who report a worsening of the disease.

One-Year and Five-Year Outcomes in Medication Overuse Headache: A Real-World Study.

Medication overuse headache (MOH) is one of the global health-related problems that imposes significant morbidity. Effective management requires the abrupt cessation of the overused medications, transition therapy in the initial days, and initiation of preventive treatment. The objective of this study is to provide one-year and five-year follow-ups of study participants diagnosed with chronic migraine and MOH. The study will examine the efficacy of withdrawal therapy, the use of conventional preventive medication, and the use of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies. We conducted a single-center, prospective, and descriptive study at a tertiary center in Brazil. The population was included by convenience sampling of consecutive subjects diagnosed with chronic migraine and MOH. Demographics and clinical data at baseline and one-year and five-year follow-ups were collected in the clinical records. Among 142 subjects, 116 were females and 26 were males, with a mean age of 42.1±14.3. They were followed for five years. The diagnosis was performed at the mean age of 24.9±14.7 years after the headache onset, and the time with headache ≥15 days per month was 6.3±7.6 years. On baseline, the average number of headache days per month (HDM) was 25.2±5.9. There was a reduction in HDM. At one-year and five-year follow-ups, a ≥75% reduction in HDM was observed, respectively, in 51.4% and 70.4% of the sample. The five-year follow-up of chronic migraine and MOH treated with the discontinuation of excessive medication, the use of preventative pharmacological agents, and the optional inclusion of anti-CGRP pathway monoclonal antibody led to a significant decrease in the initial occurrence of HDM.

Cerebral Artery Vasoconstriction After Galcanezumab Loading Dose for Migraine Prevention: A Case Report.

Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies that target CGRP ligands or receptors, may cause a very rare side effect of reversible cerebral vasoconstriction syndrome (RCVS). This study is a case report of a patient who developed cerebral artery vasoconstriction documented on serial brain magnetic resonance angiography (MRA) scans without the typical manifestations of RCVS following galcanezumab loading dose. Case report: A 40-year-old female patient with high-frequency episodic migraine with visual aura on topiramate 100mg/day developed transient numbness of the right upper and lower extremities and right face without headache and a normal neurological examination 10min after a loading dose of galcanezumab, which resolved over the next 2days. Magnetic resonance angiography brain imaging showed segmental arterial constriction of both middle cerebral arteries in the M1-2 segments and both posterior cerebral arteries in the P1-2 segments, which partial resolved in a subsequent study by the end of 6months. There were no other supporting examination data, such as transcranial Doppler, which might provide additional information on the progression and improvement of the vasoconstriction. Her differential diagnosis included prolonged migraine sensory aura without headache, RCVS, or cerebral vasoconstriction secondary to the effect of an anti-CGRP monoclonal antibody. Further research needs to be conducted.

Onabotulinumtoxin A for the Treatment of Post-Traumatic Headache: Is It Better than Anti-CGRP Antibodies?

Post-traumatic headache (PTH) is a common and debilitating consequence of traumatic brain injury (TBI), often resembling migraine and tension-type headaches. Despite its prevalence, the optimal treatment for PTH remains unclear, with current strategies largely extrapolated from other headache disorders. This review evaluates the use of onabotulinumtoxin A (ONA) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the treatment of PTH. A comprehensive literature search was conducted on PubMed, including studies published up to September 2024, focusing on the efficacy, safety, and mechanisms of onabotulinumtoxin A and anti-CGRP mAbs in PTH. Both clinical trials and observational studies were reviewed. ONA, widely recognized for its efficacy in chronic migraine, has shown limited benefits in PTH with only one trial involving abobotulinumtoxin A in a cohort of 40 subjects. A phase 2 trial with fremanezumab, an anti-CGRP monoclonal antibody, failed to demonstrate significant efficacy in PTH, raising questions about the utility of targeting CGRP in this condition. ONA may offer advantages over anti-CGRP mAbs, not only in terms of its broader mechanism of action but also in cost-effectiveness and higher patient adherence. Both ONA and anti-CGRP mAbs are potential options for the management of PTH, but the current evidence is insufficient to establish clear guidelines. The negative results from the fremanezumab trial suggest that CGRP inhibition may not be sufficient for treating PTH, whereas onabotulinumtoxin A's ability to target multiple pain pathways may make it a more promising candidate.

Monitoring Pregnancies Exposed to Galcanezumab for Migraine in a United States Administrative Claims Database.

Galcanezumab is a calcitonin gene-related peptide monoclonal antibody indicated for migraine prevention in adults. Due to the long half-life of galcanezumab and the prevalence of migraine in women of childbearing age, galcanezumab exposure may occur during pregnancy. However, real-world use and safety of galcanezumab during pregnancy has not been fully described. To help fill this gap, galcanezumab has two ongoing pregnancy safety studies, one of which is an insurance claims database study. This database study is actively identifying and following pregnancies exposed to galcanezumab using commercial claims from the Healthcare Integrated Research Database (HIRD). Patient accrual is planned from September 2018 to June 2026, with a final study report planned for December 2027. This study requires 430 galcanezumab-exposed pregnancies with linked infants to reach power for comparative analysis of major congenital malformations. Recent monitoring of patient accrual, including data from 28 September 2018 to 31 January 2023, identified 207 galcanezumab-exposed pregnancies in women with migraine in the HIRD, of which 110 were live births and 73 of which were linked to an infant. This represents an annual accrual rate of approximately 17 pregnancies linked to infants, which is substantially lower than the 55 required annually to reach target size within current regulatory-committed study timelines. The accrual of a sufficient number of galcanezumab-exposed pregnancies represents a substantial, but not uncommon, barrier to conducting comparative analyses in pregnancy studies. Potential solutions that would allow for timely dissemination of important safety information to patients and providers may be available.

Calcitonin Gene-Related Peptide Monoclonal Antibodies: Key Lessons from Real-World Evidence.

The advent of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway has transformed the management of migraine, offering newfound optimism for clinicians and individuals with episodic migraine (EM) and chronic migraine (CM). While randomized controlled trials (RCTs) have provided crucial insights into the effectiveness and safety profiles of these treatments, their translation into real-world clinical practice remains a challenge. This review aims to conduct a comprehensive assessment of real-world studies, offering valuable insights tailored for practical application in clinical settings. We conducted a comprehensive literature search in PubMed, SCOPUS, and MEDLINE for real-life studies on erenumab, fremanezumab, and galcanezumab. Abstracts underwent rigorous screening by two reviewers for relevance. Data extraction from selected articles was performed using a standardized form, with verification by a second reviewer. Data synthesis was narrative, following PRISMA guidelines. Our search included 61 pertinent studies conducted between 2019 and 1 March 2024. Real-world study designs demonstrated notable variability in the selection and inclusion of migraine patients, influenced by factors such as attack frequency, data collection criteria, and primary/secondary objectives. Key findings commonly reported considerable improvements in efficacy outcomes (migraine frequency, analgesic use, pain severity, and disability), high responder rates, and optimal safety and tolerability profiles. Real-world evidence underscores the role of anti-CGRP mAbs as targeted therapies for both CM and EM patients. The overall results indicate that the effectiveness and tolerability of anti-CGRP mAbs in real-world applications may exceed those observed in RCTs, an extraordinary finding in clinical neurology.

Patients' Experiences During the Long Journey Before Initiating Migraine Prevention with a Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody (mAb).

Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody). This is a cross-sectional, self-reported, online survey of subjects in Lilly's Emgality® Patient Support Program in 2022. Questionnaires collected insights into subjects' prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs. Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2years (±11.9) at diagnosis and 40.6 (±12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (±4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects. People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey. Graphical abstract available for this article.

Persistence, effectiveness, and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies in patients with chronic migraine.

To evaluate, in patients with chronic migraine (CM) in real-world conditions, the persistence, effectiveness, and tolerability of erenumab, fremanezumab, and galcanezumab anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) and the persistence and effects of switching. Anti-CGRP mAbs represent a novel therapeutic approach to the management of CM; however, real-world data on persistence, effectiveness, and tolerability, especially after switching, are scarce. This was a retrospective observational cohort study including all patients with CM treated with erenumab, fremanezumab, and/or galcanezumab in a tertiary hospital between January 2019 and December 2022. Treatment persistence was measured as the number of days between treatment start and end dates or the end of follow-up and also as a percentage of persistent patients at 3, 6, and 12 months; effectiveness as a ≥50% reduction in monthly migraine days (MMD); and tolerability as the number and type of adverse events. Included were 281 patients (383 treatments) with CM (91.5% [257/281] female) receiving anti-CGRP mAbs. Median (interquartile range [IQR]) treatment persistence was 267 (103-550) days. At 12 months, persistence was greater for the first (66.7%) compared to the second (49.8%) and third (37.2%) anti-CGRP mAb treatments (hazard ratio [HR] = 1.93, 95% confidence interval [CI]: 1.35-2.74; HR = 2.75, 95% CI: 1.69-4.47, respectively). Persistence minimum observed median (IQR) was also greater for the first (291 [112-594] days) compared to both the second (188 [90-403] days; p < 0.001) and third (167 [89-352] days; p < 0.001) anti-CGRP mAb treatments. For the first anti-CGRP mAb treatment, there were no differences in persistence among the different drugs. In terms of effectiveness of the first, second, and third anti-CGRP mAb treatments, a ≥50% reduction in MMD was achieved by 57.6% (117/203), 25.0% (11/44), and 11.8% (2/17) of patients, respectively, at 3 months, and by 55.8% (87/156), 29.6% (8/27), and 12.5% (1/8) of patients, respectively, at 6 months. At 12 months, no significant effectiveness differences were observed among anti-CGRP mAb treatments. As for tolerability, 55 adverse events were reported by 43 (15.3%) patients, mostly mild and leading to treatment discontinuation in only 14 (5.0%) patients. The most common adverse events were constipation, injection site reaction, and pruritus. Erenumab patients (3%, 3/99) experienced a higher rate of discontinuation for constipation. Our findings showed a 12-month higher treatment persistence with the use of a first anti-CGRP mAb treatment when the switch to a second treatment was due to ineffectiveness or severe side events. This persistence was lower after a second or third anti-CGRP. Additionally, in terms of effectiveness, the first anti-CGRP treatment achieved a higher response in terms of ≥50% reduction in MMD; however, some patients may benefit from a switching strategy. Finally, the tolerability profile for anti-CGRP mAbs was favorable. Further studies are needed to identify predictors of response after switching from the first anti-CGRP mAb treatment.

Genetic variants associated with response to anti-CGRP monoclonal antibody therapy in a chronic migraine Han Chinese population

BackgroundAnti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine.MethodsWe conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database.ResultsSix single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10− 7): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10− 9). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure.ConclusionThe identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology.Trial registrationNot applicable.

Effectiveness and safety of pharmacological prophylaxis for chronic migraine: a systematic review and network meta-analysis.

Chronic migraine (CM) significantly impacts both the physical and mental health of patients. Current studies on the safety and effectiveness of different pharmacological prophylaxis interventions for CM are limited. To address this gap, we conducted a network meta-analysis (NMA) to compare and rank the efficacy and safety of various drugs in preventing CM. Two independent researchers systematically searched four databases from their inception to August 1, 2023, to identify eligible randomized controlled trials (RCTs). Subsequently, they performed data extraction and assessed the risk of bias. A NMA was then performed. Continuous outcomes and binary outcomes were displayed as weighted mean difference (WMD) and risk ratio (RR), respectively, and corresponding 95% confidence intervals (CI) were reported. The surface under the cumulative ranking curve (SUCRA) was used to rank each intervention separately. 24 RCTs involving 8789 patients were included. Compared to placebo, Botulinum toxin A demonstrated the most significant effect in reducing the monthly migraine days for CM patients (MD = 3.88, 95% CI 0.48, 7.28); in terms of improving the response rate by a 50% reduction in monthly migraine days, Topiramate (RR = 50.06, 95% CI 3.18, 787.30) was the most effective; there was no statistically significant difference between all preventive drugs and placebo in improving the migraine disability assessment (MIDAS) score; in terms of the incidence of adverse events, Eptinezumab (RR = 1.09, 95% CI 0.8, 1.54) exhibited the highest safety profile. Among all the drugs for the preventive drugs for CM, Botulinum toxin A has the best efficacy and safety profile, closely followed by calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs).

Triptan non-response in a London tertiary headache centre: What can we learn? A retrospective study.

Triptans revolutionized the acute treatment of migraine; however, varied responses to triptans, as a result of poor efficacy and tolerability, are reported. A standardized definition of triptan non-response was recently proposed by the European Headache Federation (EHF). There is currently limited data available on the prevalence of triptan non-response. We used clinic letters over a two-year duration to evaluate the triptan response and triptan efficacy or tolerability failure, or both, in a London-based tertiary headache service. In total, 419 adult migraine patients (females: 83.8%, age: 46 ± 18years, chronic migraine: 88.5%) were included in a service evaluation. In line with the EHF definitions, "triptan non-response" was seen in 63.8% of patients (264/414), whereas 37.7% of patients (156/414) had failed at least two triptans (EHF "triptan resistant") and 4.6% of patients (19/414) had failed at least three triptans, including a subcutaneous formulation (EHF "triptan refractory"). Notably, 21.3% of patients (88/414) had failed at least three triptans inclusive and exclusive of subcutaneous triptan use. Advancing age (p < 0.001) and the presence of medication overuse (p = 0.006) increased the probability of triptan response, whereas an increased number of failed preventives (p < 0.001) and the use of calcitonin gene-related peptide monoclonal antibodies (p = 0.022) increased the probability of triptan non-response. The largest proportion of patients responded to eletriptan (49.5%), followed by nasal zolmitriptan (44.4%) and rizatriptan (35.7%). Our findings highlight an alarming prevalence of triptan non-response among adult migraineurs receiving treatment in a London-based tertiary headache service. It is imperative for clinicians to explore methods to optimize acute medication efficacy, whether this comprises changing to a triptan with a superior response rate, advocating for early intervention or considering alternative acute medication classes, such as gepants or ditans.

Are we closer to achieving precision medicine for migraine treatment? A narrative review.

The term 'precision medicine' encompasses strategies to optimize diagnosis and outcome prediction and to tailor treatment for individual patients, in consideration of their unique characteristics. The greater availability of multifaceted datasets and strategies to model such data have made precision medicine increasingly possible in recent years. Precision medicine is especially needed in the migraine field since the response to migraine treatments is not universal amongst all individuals with migraine. To provide a narrative review describing contributions to achieving precision medicine for migraine treatment. A search of PubMed for English language articles of human participants published from 2005 to January 2024 was conducted to identify articles that reported research contributing to precision medicine for migraine treatment. The published literature was categorized and summarized according to the type of data that were included: clinical phenotypes, genomics, proteomics, physiologic measures, and brain imaging. Published studies have investigated characteristics associated with acute and preventive treatment responses, such as nonsteroidal anti-inflammatory drugs, triptans, onabotulinumtoxinA, and anti-calcitonin gene-related peptide monoclonal antibodies, in patients with episodic or chronic migraine. There is evidence that clinical, genetic, epigenetic, proteomic, physiologic, and brain imaging features might associate with migraine treatment outcomes, although inconsistencies for such findings clearly exist. The published literature suggests that there are clinical and biological features which associate with, and might be useful for predicting, migraine treatment responses. To achieve precision medicine for migraine treatment, further research is needed that validates and expands on existing findings and tests the accuracy and value of migraine treatment prediction models in clinical settings.