Calcitonin Gene-related Peptide Monoclonal Antibodies Research Articles

Long-Term Outcome After Discontinuation of CGRP-Targeting Therapy for Migraine.

Calcitonin gene-related peptide (CGRP)-targeting agents are potential candidates for disease-modifying migraine drugs. However, most studies on CGRP-targeting agents have assessed efficacy outcomes rather than long-term effects after discontinuation. This review aimed to synthesize and scrutinize the latest clinical data on the outcomes after the discontinuation of CGRP-targeting therapy in patients with episodic and chronic migraine, with a particular focus on chronic migraine. Real-world studies involving patients with migraine have reported consistent findings of worsened headache frequency and quality of life after the discontinuation of CGRP monoclonal antibodies (CGRP mAbs). Although many patients maintain improvements for up to 4months after discontinuation compared to baseline (before starting CGRP mAbs), no studies have evaluated the effects of stopping treatment for > 5months, which is the five-half-life of CGRP mAbs. Several studies have suggested that patients treated with CGRP receptor mAbs experience more rapid deterioration than those treated with CGRP ligand mAbs after discontinuing CGRP mAbs. The results of real-world studies suggest that for many patients with migraine, the benefits of CGRP mAbs diminish months after discontinuation. Therefore, anti-CGRP therapies may not be considered disease-modifying. However, the comprehensive assessment of the disease-modifying potential of these drugs requires studies with extended treatment and cessation durations.

Nonspecific oral medications versus anti-calcitonin gene-related peptide monoclonal antibodies for migraine: Asystematic review and meta-analysis of randomized controlled trials.

To compare calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) versus nonspecific oral migraine preventives (NOEPs). Insurers mandate step therapy with NOEPs before approving CGRP mAbs. Databases were searched for class I or II randomized controlled trials (RCTs) comparing CGRP mAbs or NOEPs versus placebo for migraine prevention in adults. The primary outcome measure was monthly migraine days (MMD) or moderate to severe headache days. Twelve RCTs for CGRP mAbs, 5 RCTs for topiramate, and 3 RCTs for divalproex were included in the meta-analysis. There was high certainty that CGRP mAbs are more effective than placebo, with weighted mean difference (WMD; 95% confidence interval) of -1.64 (-1.99 to -1.28) MMD, which is compatible with small effect size (Cohen's d -0.25 [-0.34 to -0.16]). Certainty of evidence that topiramate or divalproex is more effective than placebo was very low and low, respectively (WMD -1.45 [-1.52 to -1.38] and -1.65 [-2.30 to -1.00], respectively; Cohen's d -1.25 [-2.47 to -0.03] and -0.48 [-0.67 to -0.29], respectively). Trial sequential analysis showed that information size was adequate and that CGRP mAbs had clear benefit versus placebo. Network meta-analysis showed no statistically significant difference between CGRP mAbs and topiramate (WMD -0.19 [-0.56 to 0.17]) or divalproex (0.01 [-0.73 to 0.75]). No significant difference was seen between topiramate or divalproex (0.21 [-0.45 to 0.86]). There is high certainty that CGRP mAbs are more effective than placebo, but the effect size is small. When feasible, CGRP mAbs may be prescribed as first-line preventives; topiramate or divalproex could be as effective but are less well tolerated. The findings of this study support the recently published 2024 position of the American Headache Society on the use of CGRP mAbs as the first-line treatment.

Benefit-Risk Assessment Based on Number Needed to Treat and Number Needed to Harm: Atogepant vs Calcitonin Gene–Related Peptide Monoclonal Antibodies (P5-12.007)

Benefit-Risk Assessment Based on Number Needed to Treat and Number Needed to Harm: Atogepant vs Calcitonin Gene–Related Peptide Monoclonal Antibodies (P5-12.007)

Research priorities for randomised controlled trials in chronic migraine preventive medication: A stakeholder consensus workshop

Background Chronic migraine is a disabling condition that can substantially impact on quality of life. People with chronic migraine have headaches on at least 15 days of every month. Preventative medications aiming to reduce number of days with migraine are available, but high-quality randomised evidence is lacking for many drugs, and it is unclear which medications should be prioritised for research. There is also no existing evidence about patient and clinicians’ priorities for research. Methods We undertook a consensus workshop with patient and healthcare professional stakeholders, using nominal group technique, to understand these stakeholders’ priorities for future randomised controlled trials. We reached a consensus on a set of research recommendations for the field. Results Eight people with chronic migraine and eleven healthcare professionals took part in an online workshop. Comparisons of calcitonin gene-related peptide monoclonal antibodies (CGRP MAbs) and OnabotulinumtoxinA (BTA) were a top priority for our group. Candesartan and Flunarizine were the top drugs the group wanted to compare against placebo. Conclusions These research recommendations should guide researchers in the field, and funders when prioritising commissioned research and assessing funding applications. Particular areas to explore further are Candesartan or Flunarizine versus placebo, and comparing and combining CGRP MAbs with other medications.

Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland

ObjectivesCalcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. MethodsData were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. ResultsBetween September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. ConclusionsThis study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest.

Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.

Women show increased prevalence and severity of migraine compared to men. Whether small molecule calcitonin gene-related peptide receptor (CGRP-R) antagonists (i.e., gepants) and monoclonal antibodies targeting either the CGRP-R or the CGRP peptide might show sexually dimorphic outcomes for acute and preventive therapy has not been established. We conducted a subpopulation analysis of available published data from FDA reviews to evaluate potential sex differences in the response rates of ubrogepant, rimegepant and zavegepant for acute migraine therapy. Available data from FDA reviews of erenumab, fremanezumab, galcanezumab and eptinezumab, approved CGRP-R and CGRP monoclonal antibodies and of atogepant were examined for prevention outcomes based on patient sex. Preventive outcomes were analyzed separately for patients with episodic migraine and chronic migraine. In women, the three approved gepants produced statistically significant drug effects regardless of dose tested on the FDA mandated co-primary endpoints, the proportion of patients achieving two-hour pain-freedom and the proportion of patients free of their most bothersome symptom at two hours post-dose. In women, the average placebo-subtracted two-hour pain-freedom proportion was 9.5% (CI: 7.4 to 11.6) and the average numbers needed to treat was 11. The free from most bothersome symptom at two hours outcomes were also significant in women. The gepant drugs did not reach statistically significant effects on the two-hour pain-freedom endpoint in the men, with an average drug effect of 2.8% (CI: -2.5 to 8.2) and an average number needed to treat of 36. For freedom from most bothersome symptom at two hours post-dose endpoint, differences were not significant in male patients. The treatment effect in each of the gepant studies was always numerically greater in women than in men. In evaluation of prevention outcomes with the antibodies or atogepant using the change from the specified primary endpoint (e.g., monthly migraine days), the observed treatment effect for episodic migraine patients almost always favored drug over placebo in both women and men. For chronic migraine patients the treatment effects of antibodies were similar in men and women and always favored the drug treated group.Conclusion/Interpretation: Small molecule CGRP-R antagonists are effective in acute migraine therapy in women but available data do not demonstrate effectiveness in men. CGRP-targeting therapies are effective for migraine prevention in both male and female episodic migraine patients but possible sex differences remain uncertain. In male and female chronic migraine patients, CGRP/CGRP-R antibodies were similarly effective. The data highlight possible differential effects of CGRP targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women.

Reduced plasma calcitonin gene-related peptide level identified in cluster headache: A prospective and controlled study.

The role of calcitonin gene-related peptide (CGRP) in the cyclic pattern of cluster headache is unclear. To acquire biological insight and to comprehend why only episodic cluster headache responds to CGRP monoclonal antibodies, we examined whether plasma CGRP changes between disease states (i.e. bout, remission and chronic) and controls. The present study is a prospective case-control study. Participants with episodic cluster headache were sampled twice (bout and remission). Participants with chronic cluster headache and controls were sampled once. CGRP concentrations were measured in plasma with a validated radioimmunoassay. Plasma was collected from 201 participants diagnosed with cluster headache according to the International Classification of Headache Disorders, 3rd edition, and from 100 age- and sex-matched controls. Overall, plasma CGRP levels were significantly lower in participants with cluster headache compared to controls (p < 0.05). In episodic cluster headache, CGRP levels were higher in bout than in remission (mean difference: 17.1 pmol/L, 95% confidence interval = 9.8-24.3, p < 0.0001). CGRP levels in bout were not different from chronic cluster headache (p = 0.266). Plasma CGRP is unsuitable as a diagnostic biomarker of cluster headache or its disease states. The identified reduced CGRP levels suggest that CGRPs role in cluster headache is highly complex and future investigations are needed into the modulation of CGRP and its receptors.

Effectiveness of Switching CGRP Monoclonal Antibodies in Non-Responder Patients in the UAE: A Retrospective Study.

Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) have shown promising effectiveness in migraine management compared to other preventative treatment options. Many questions remain regarding switching between antibody classes as a treatment option in patients with migraine headaches. This preliminary retrospective real-world study explored the treatment response of patients who switched between CGRP mAb classes due to lack of efficacy or poor tolerability. A total of 53 patients with migraine headache switched between three of the CGRP mAbs types due to lack of efficacy of the original prescribed CGRP mAbs, specifically eptinezumab, erenumab, and galcanezumab. Fremanezumab was not included due to unavailability in the UAE. Galcanezumab and eptinezumab target the CGRP ligand (CGRP/L), while erenumab targets CGRP receptors (CGRP/R). The analysis of efficacy demonstrated that some improvements were seen in both class switch cohorts (CGRP/R to CGRP/L and CGRP/L to CGRP/R). The safety of switching between CGRP classes was well observed, as any adverse events presented before the class switch did not lead to the discontinuation of treatment following the later switch. The findings of this study suggest that switching between different classes of CGRP mAbs is a potentially safe and clinically viable practice that may have some applications for those experiencing side effects on their current CGRP mAb or those witnessing suboptimal response.

Update on gepants for the treatment of chronic migraine.

Chronic migraine (CM) is a profoundly debilitating condition that has detrimental clinical and social outcomes. Over the past two decades, novel small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, known as gepants, and CGRP monoclonal antibodies (mAbs) have been developed, ushering in a new era of migraine-specific treatment. In this review, we discuss the literature investigating the role of gepants for the treatment of CM. Numerous completed and ongoing clinical studies have conclusively demonstrated the safety, tolerability, and efficacy of several gepants for the acute treatment of migraine. However, preventive trials involving gepants have focused on patients with episodic migraine, with atogepant being the only gepant approved for CM prevention by the US Food and Drug Administration at the time of writing. Although some preliminary positive results have been reported, further research is still required to achieve additional advancements in the future. In summary, the effectiveness of gepants for treating individuals with CM are highly expected. This review highlights the development and current progress of gepants for the treatment of CM, focusing both on their role as acute abortive agents and preventive measures and on their concomitant use with other antimigraine medications, such as CGRP mAbs or triptans.

Real-world effectiveness of erenumab in Japanese patients with migraine

BackgroundReal-world evidence of erenumab effectiveness in migraine patients in Asia with various comorbidities and multiple previous medication failures is still limited. MethodsA 6-month single-center cohort study of 45 patients with episodic or chronic migraine (CM) treated with erenumab was conducted. In the cohort, 60.0% were switching from other calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs), and 66.7% had ≥4 prophylaxis failures. The change in monthly migraine days (MMDs) from baseline and percentages of responders after treatment were calculated. Weekly migraine days (WMDs) were obtained at baseline and at months 1, 2 and 3 and were compared between weeks 2 and 4. ResultsIn total, 36%, 47%, and 63% of patients had a ≥30% response at 1, 3, and 6 months, respectively. The cumulative percentage of patients achieving a ≥30% response over 6 months was 85%. Early responders (average ≥ 30% response at 1–3 months) accounted for 37.8%, 55.6%, and 25.9% of the total, CGRP mAb-naïve, and CGRP mAb-switching groups, respectively. Late responders (average < 30% response at 1–3 months and average ≥ 30% response at 4–6 months) accounted for 46.4%, 37.5%, and 58.8% of nonearly responders in the total, CGRP mAb-naïve, and CGRP mAb-switching groups, respectively. Mild adverse reactions were observed in 5 patients (11.1%). Wearing-off, defined as an increase in the number of WMDs ≥2 between week 2 and week 4, was observed in 2.4–12.5% at months 1–3. ConclusionErenumab was effective in migraine patients. At least 4–6 months may be preferable for efficacy evaluation in patients switching to erenumab from other CGRP mAbs.

Comparison of Treatment Patterns in Patients with Migraine Initiating Calcitonin Gene-Related Peptide Monoclonal Antibodies: A Retrospective Real-World US Study.

Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are indicated for migraine prevention in the United States. Limited data comparing real-world treatment patterns for CGRP mAbs are available. To compare the treatment patterns among patients with migraine initiating galcanezumab, fremanezumab, and erenumab. This retrospective study included adult patients with one or more claims for a self-injectable CGRP mAb (galcanezumab, fremanezumab, or erenumab), with continuous enrollment in medical and pharmacy benefits for 12 months pre-index and 6 and 12 months post-index using MerativeTM MarketScan® Commercial and Medicare databases from May 2017 through March 2021. Propensity-score matching was used to address confounding by observed covariates. Outcomes analyzed included proportion of days covered (PDC), medication-possession ratio (MPR), persistence (≤60-day gap), treatment discontinuation, and switch to a non-index drug. Descriptive X2 and t-test analyses were conducted. At the 12-month follow-up, matched galcanezumab and fremanezumab cohorts each comprised 2674 patients and the galcanezumab and erenumab cohorts 3503 each. The mean (SD) PDC and MPR were both 0.6 (0.3) across all cohorts. Based on PDC ≥0.80 and MPR ≥0.80, a greater proportion of galcanezumab vs fremanezumab (46.2% vs 43.7%, p=0.053; 46.8% vs 44.3%, p=0.053) and galcanezumab vs erenumab (46.2% vs 44%, p=0.156; 46.7% vs 44.5%, p=0.262), respectively, initiators were adherent. Compared to galcanezumab, fremanezumab (248.0 days vs 236.5 days, p=0.001), and erenumab (247.8 days vs 241.7 days, p=0.061) initiators had lower mean persistence. Galcanezumab initiators were less likely to discontinue treatment than fremanezumab (47.8% vs 51.7%, p=0.005) and erenumab (47.7% vs 50.2%, p=0.040) initiators. Across cohorts, most switchers initiated onabotulinum toxin A as subsequent treatment. Similar results were observed for 6-month follow-up cohorts. Patients with migraine who initiated treatment with galcanezumab showed higher persistence and lower treatment discontinuation rates than those initiating either fremanezumab or erenumab.

Tolerability of calcitonin gene-related peptide monoclonal antibodies and other monoclonal antibodies in adults with concurrent migraine and other medical conditions

Background/Hypothesis: Calcitonin gene-related peptide monoclonal antibodies (CGRP mabs) are relatively new preventive treatments in adult migraine. Co-morbid medical conditions such as autoimmune or other neurologic/oncologic disorders are not uncommon in migraine patients and some exhibit notable co-morbidity such as asthma. These clinical conditions may necessitate concomitant treatment with another monoclonal antibody with a different mechanism of action other than the CGRP pathway in some individuals with migraine. Methods: We report a retrospective case series in 23 patients identified from our headache clinic treated concurrently with a CGRP monoclonal antibody and other monoclonal antibody for another medical condition. These other medical conditions were neurologic, oncologic, or autoimmune conditions. These patients were evaluated for tolerability, safety, and stability of disease processes including their migraine response. Results/Conclusion: We did not find evidence of new adverse or serious adverse side effects with coadministration of CGRP and non-CGRP monoclonal antibodies during our study time period of 13 months, for the duration of overlap between treatments (between 3 and 12 months).

Twelve-month efficacy of CGRP monoclonal antibodies and predictive value of short-term response: results of an Australian multicentre study

IntroductionClinical trials show that calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are effective preventative treatments for chronic migraine. Their efficacy over longer time periods and in cohorts originally excluded from...

Adverse and serious adverse events incidence of pharmacological interventions for managing chronic and episodic migraine in adults: a systematic review.

Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs. We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC). Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs. Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations. CRD42021265993.

Early Effect of Calcitonin Gene-related Peptide Monoclonal Antibodies in Migraine with Medication Overuse: A Single-center Retrospective Study.

Objective Calcitonin gene-related peptide (CGRP)-(receptor) monoclonal antibody (mAb) has been reported to reduce the frequency of medication overuse in patients with migraine. The present study investigated whether or not CGRP-mAb treatment shows early effectiveness for medication overuse headache (MOH) in Japan. Methods We retrospectively reviewed 34 patients with MOH who received preventive treatment with CGRP-mAb from June 2021 to October 2022. The International Classification of Headache Disorders, 3rd edition was used to diagnose MOH. This study was conducted at the Department of Neurology, Saitama Medical University. Patients were recruited from this specialized headache outpatient center. Results In total, 69 patients with migraine had newly introduced CGRP-mAb, and 34 patients had MOH (49.3%). The mean±standard deviation patient age was 44±15.5 years old. The study population included 24 women (70.6%). The types of CGRP-mAb used were galcanezumab in 16 patients (47.0%), fremanezumab in 10 (29.4%), and erenumab in 8 (23.5%). The mean disease duration was 19.6±13.1 years. The types of migraine diagnosis were chronic migraine in 28 patients (82.4%) and migraine with aura in 11 patients (32.4%). The mean number of headache days in the month before administration of CGRP-mAb was 22±7.7 days; 1 month after administration, the MHD was 16.9±9.1 days. The change in MHD was -5.7 days (22.7%), indicating significant improvement (p<0.05). Conclusion CGRP-mAb has been suggested as a preventive treatment for patients with MOH. Further investigation of the long-term efficacy of CGRP-mAb for MOH is needed.

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have a 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors have a 50% responder rate ranging from 56 to 71%. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

Use of Calcitonin Gene-Related Peptide Monoclonal Antibodies for the Treatment of Migraines in Individuals With Multiple Sclerosis

Abstract Background: Migraines are a common comorbidity and source of disability in patients with chronic inflammatory diseases like multiple sclerosis (MS). Recently, therapeutic agents for episodic and chronic migraine known as calcitonin gene-related peptide (CGRP) inhibitors have shown to effectively control migraine attacks and improve quality of life in the general population. This study explored the use of these novel agents in individuals with comorbid MS. Methods: This was a retrospective, population-based cohort study at the University of South Florida’s neurology clinic; it evaluated individuals with both MS and migraine. Results: A total of 27 individuals with MS and chronic or episodic migraine who received treatment with a CGRP monoclonal antibody were identified. Of these, 63% reported a reduction in their migraine frequency of greater than 75%. Concurrent use of a disease modifying therapy (DMT) for MS occurred in 82% of patients, and in 37% of these, the DMT used was also a monoclonal antibody. Adverse effects from CGRP monoclonal antibodies were mild and occurred in only 11% of patients, and no patient experienced worsening of their MS symptoms during cotreatment over the duration of the study. Conclusions: Our study showed a significant reduction in migraine frequency and a favorable adverse event profile for individuals with comorbid MS who took CGRP monoclonal antibodies and experienced no worsening of MS symptoms. In individuals with MS, CGRP monoclonal antibodies seem to be a safe and effective therapy for episodic or chronic migraine.

Efficacy and Safety of Anti-calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies in Preventing Migraines: A Systematic Review.

The neuropeptide calcitonin gene-related peptide (CGRP) is an essential pathophysiological treatment for migraines. A unique class of medications called CGRP monoclonal antibodies target CGRP and its receptor and have demonstrated promising benefits in the treatment and prevention of migraines. This study sought to identify and assess the quality of existing systematic reviews about the effectiveness of CGRP antibodies for preventing migraines, as well as systematically review and synthesize the evidence on these topics. This included the four Food and Drug Administration (FDA)-approved medications erenumab, galcanezumab, fremanezumab, and eptinezumab. The effectiveness and safety of these monoclonal antibodies in preventing migraines should also be examined in light of patient characteristics, and any gaps in the body of knowledge should be noted in order to suggest new lines of investigation. Data gathering included a thorough search of internet databases (PubMed, Cochrane Library, Web of Science, and Scopus) for relevant research released between 2018 and 2023. The findings imply that CGRP monoclonal antibodies are efficient and secure for preventing migraines and may be considered a first-line alternative for treating migraines and drug misuse. The results further imply that combination treatment with CGRP antibodies and onabotulinumtoxinA may enhance the prevention of migraine in adults. With suggestions for more studies to find and address these variables, the significance of genetic and epigenetic factors in the progression of pediatric patients' acute postoperative pain to chronic postsurgical pain is underlined. All four anti-CGRP monoclonal antibodies, erenumab, fremanezumab, galcanezumab, and eptinezumab, were shown to be safe and effective for the prevention of migraine when the research additionally looked at their individual effectiveness and safety. Additionally, the study discovered considerable variances in effectiveness amongst various groups. However, further investigation is required to establish the best time and dosage and the effect of patient characteristics on the effectiveness and safety of these medications.

Beyond the Guidelines: A Narrative Review of Treatments on the Horizon for Migraine in Children and Adolescents.

Migraine is common in children and adolescents and can cause significant disability. There are relatively limited evidence-based treatment options available, especially when compared to treatment of migraine in adults. The Pediatric Research Equity Act requires the study of a new drug or biologic in pediatric populations. As such it is mandatory that the newest migraine treatment options available for adults be evaluated in children and adolescents. It will take years before results from clinical trials in pediatric patients become available. In the meantime, there is eagerness among clinicians to seek out the existing evidence that may help provide clarity on utilization of the newer migraine therapies in children and adolescents as many of the currently available, guideline-recommended treatments do not provide benefit for all patients. In this narrative review, literature regarding onabotulinumtoxinA, neuromodulatory devices, calcitonin gene-related peptide (CGRP) monoclonal antibodies, 5-hydroxytryptamine (1F) agonists (i.e. ditans), and CGRP small molecule receptor antagonists (i.e. gepants) for treatment of migraine in children and adolescents will be summarized.

An exploratory comparative case series of calcitonin gene-related peptide monoclonal antibodies in patients with migraine with rosacea.

Rosacea is associated with &amp;gt; 50% of cases of migraine. Recent data have shown that calcitonin gene-related peptide (CGRP) is elevated in rosacea skin. CGRP monoclonal antibodies (mAbs) prevent migraine with known safety profiles, but their effect on rosacea is not known. This exploratory retrospective study examined rosacea in patients with migraines, before and after CGRP mAbs. Of 13 eligible patients on stable or unchanged concurrent rosacea medications, the majority experienced improvement after receiving CGRP mAbs. Mean (SD) rosacea severity scores for the periods before and while on CGRP mAbs were, respectively, 1.19 (0.65) and 0.58 (0.70) (P = 0.01). Prospective, placebo-controlled clinical trials are needed to further assess the use of CGRP mAbs in rosacea.