Gene-related Peptide Monoclonal Antibodies Research Articles

Safety and Tolerability of Combining CGRP Monoclonal Antibodies with Gepants in Patients with Migraine: A Retrospective Study.

The introduction of clacitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) has revolutionized the treatment of migraines. In clinical practice gepants might be considered as a valid option to treat acute attacks in patients with migraine who are treated with mAbs. However, the safety and tolerability of such a combination is not well addressed in the real-world setting. We designed this study to evaluate the safety and tolerability of combining CGRP mAbs with gepants in the management of migraines. This was a retrospective, real-world, exploratory study. The participants included within the study were adult (≥ 18years) patients diagnosed with migraine. Screening for patients who were treated with at least one GCRP mAbs was done. Data was collected from one site, the American Center for Psychiatry and Neurology, Abu Dhabi UAE. A total of 516 patients taking CGRP mAbs were identified. Extracted data from patients' electronic medical records included patient demographics, migraine characteristics, prescribed treatments, and adverse events (AEs). The tolerability and safety of the combination therapy was evaluated on the basis of documented AEs. Among the identified 516 patients, 234 were administered gepants in addition to the CRGP mAb (215, rimegepant; 19, ubrogepant). Eleven of the 234 patients switched from rimegepant to urogepant as a result of lack of efficacy; one patient switched from urogepant to zolmitriptan because of the lack of insurance coverage of the former medication. Among all the patients included in this study, three AEs were documented. These AEs were generally mild and transient and hence did not lead to discontinuation of treatment. Moreover, 42 of the 234 (17.9%) patients were switched from one class of CGRP mAbs to another at least once while continuing treatment with the assigned gepants. The findings of this study demonstrate that combining CGRP mAbs with gepants is a safe and well-tolerated treatment approach for migraine. Future studies are warranted to further validate these findings and explore long-term outcomes.

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.

Preventive treatment patterns in the adult migraine population: an observational UK study over 7 years

BackgroundCalcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are recommended by the United Kingdom National Institute of Health and Care Excellence for the prevention of migraine as treatment beyond third line. We report migraine prevalence and preventive treatment patterns in the adult United Kingdom primary care population over a 7.5-year period, focusing on patients ceasing ≥ 3 oral preventive medication classes.MethodsStudy populations were retrieved from the Clinical Practice Research Datalink GOLD database (study period: 19 September 2012 to 1 January 2020; inclusion criteria: ≥12 months follow-up, current-in-dataset, adult on 1 January 2020). Patients who used ≥ 1 oral preventive medication with ≥ 3-year follow-up after first prescription were considered preventive treatment users; class cessation was defined as cessation without evidence of restart within 6 months from end-of-supply date.ResultsOn 1 January 2020, 3.0% of the total study population were diagnosed with migraine (n = 81,190/2,664,306); of these, 42.4% were preventive treatment users (n = 34,448/81,190). The most frequently used oral migraine preventive medication classes were beta-blockers (n = 14,713), tricyclic antidepressants (n = 14,415) and antiepileptics (n = 6497). Among preventive treatment users, 7.7% (n = 2653/34,448) ceased ≥ 3 oral preventive medication classes; of these, 21.7% (n = 576/2653) had been referred to a neurologist.ConclusionsCompared to existing population-based estimates of migraine prevalence, our data further corroborates that a considerable proportion of patients with migraine do not seek treatment. Among those who sought primary care within a 7.5-year period, almost half received empirical oral preventive treatment. Importantly, nearly 1 of 10 preventive treatment users ceased ≥ 3 oral preventive medication classes, highlighting a need for additional therapeutic options. These patients may benefit from CGRP antagonists and/or injectable onabotulinumtoxinA; however, only a minority was referred to specialist care, where these options would be more available.Trial RegistrationNot applicable.

Adverse event reporting of four anti-Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: a real-world study based on the FDA adverse event reporting system.

Background: Anti-Calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) have shown significant efficacy in preventing migraine. However, there have been limited reports of adverse events (AEs) after marketing, particularly for eptinezumab launched in 2020. The study aimed to mine and analyze the AE signals with four anti-CGRP mAbs from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to gain insights into the safety profile of these medications post-marketing. Methods: All AE reports on the four anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab, and eptinezumab) were retrieved from the FAERS database from the first quarter (Q1) of 2018 to Q1 of 2023. Disproportionality analysis was measured by reporting odd ratio (ROR) and Bayesian confidence propagation neural network (BCPNN) to identify potential AE signals. Comparisons were made between the four drugs in terms of AEs. Results: A total of 38,515 reports of erenumab, 19,485 reports of galcanezumab, 5,332 reports of fremanezumab, and 2,460 reports of eptinezumab were obtained, mostly reported in the second to third year after launch in the market. The common AEs to erenumab included constipation (17.93%), injection site pain (14.08%), and alopecia (7.23%). The AEs that occurred more frequently with galcanezumab included injection site pain (24.37%), injection site erythema (5.35%), and injection site haemorrhage (4.97%). Common AEs related to fremanezumab were injection site pain (13.10%), injection site erythema (7.02%), and injection site pruritus (5.47%). Fatigue (13.54%), throat irritation (9.02%), and pruritus (8.20%) were the most common AEs with eptinezumab. In addition, there are new AEs that were not listed in the drug instructions but occurred concurrently with multiple drugs, such as Raynaud's phenomenon, weight increase, menstrual disorders, throat tightness, and paraesthesia oral. Conclusion: Common AE signals of the four anti-CGRP mAbs and new AE signals were found to provide a reference for clinical drug selection in clinical practice.

Switching anti-CGRP monoclonal antibodies in chronic migraine: real-world observations of erenumab, fremanezumab and galcanezumab

ObjectivesThe anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAb) are effective in migraine; however, few studies have examined the benefit of switching from one anti-CGRP-mAb to another. In order to better inform...

Real-world Efficacy of Erenumab on Migraine-associated Symptoms and Patient-reported Satisfaction Levels: A Retrospective Study in Japan.

Objective In randomized clinical trials and real-world studies, calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), including erenumab, have demonstrated efficacy for migraine prevention. However, there have been no real-world studies focusing on erenumab in East Asia that investigated its efficacy on migraine-associated symptoms and patient-reported satisfaction levels. Methods This single-center, observational, retrospective, real-world study examined patients who received at least three doses of erenumab at Keio University Hospital, Tokyo, Japan, between December 2021 and March 2023 as their first CGRP mAb treatment in a real-world setting. The patients were administered 70 mg of erenumab monthly. We assessed changes in monthly migraine days (MMDs), responder rates, migraine-associated symptoms including photophobia, phonophobia, nausea/vomiting, and patient-reported satisfaction levels. In addition, injection site reactions and other adverse events were recorded to investigate safety. Results Nineteen patients were considered eligible for the analysis. At 3 months, erenumab decreased MMDs by 6.6 (95% confidence interval, 2.3-10.8; p<0.01). The 50% responder rate was 42%. A total of 83% (n=15), 56% (n=10), and 71% (n=10) of patients reported either improvement in or disappearance of photophobia, phonophobia, and nausea/vomiting, respectively, and 44% (n=8) and 28% (n=5) answered "very satisfied" and "somewhat satisfied", respectively, with erenumab treatment, leaving only 28% (n=5) as "unsatisfied". Injection site reactions (n=6, 32%) and constipation (n=4, 21%) were frequent adverse events. Conclusion In a real-world setting in Japan, erenumab proved to be effective in not only reducing migraine and headache frequency but also improving migraine-associated symptoms and satisfying the majority of patients.

Constipation as a possible predictor of poor treatment response in chronic migraine: A retrospective study of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies and the impact of switching

Constipation as a possible predictor of poor treatment response in chronic migraine: A retrospective study of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies and the impact of switching

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...

Treatment Patterns, Healthcare Resource Utilization, and Direct Costs Among Patients Initiating Concomitant Use of a Calcitonin Gene-Related Peptide Monoclonal Antibody (CGRP mAb) and Novel Acute Medication in the United States.

To describe treatment patterns, all-cause and migraine-related healthcare resource utilization (HCRU), and direct costs among people with migraine treated with concomitant calcitonin gene-related peptide monoclonal antibody (CGRP mAb) and novel acute migraine medications (ubrogepant, rimegepant, lasmiditan) in the United States (US). This retrospective, observational cohort study utilized data from the IBM MarketScan® Research Databases and included adults initiating CGRP mAb or novel acute migraine medication as index medications between May 01, 2018, and Feb 28, 2021. All-cause and migraine-related HCRU (number of visits) and costs at baseline (12 months pre-index) and at follow-up (12 months post-index) were descriptively analyzed; differences between values at follow-up and baseline were reported. Of 4,167 included in the analysis (mean [SD] age: 43.7 [11.2] years), 89.2% were women, and 59.7% had chronic migraine. Adherence to the indexed CGRP mAb was 47% (using proportion of days covered [PDC]) and 80.1% (using medication possession ratio [MPR]); mean (SD) persistence was 273.4 (115.3) days). At follow-up, 43.9% of the patients discontinued their index preventive medication of which 80.2% switched to a different preventive migraine medication; 17.0% restarted their index preventive medication. Reductions in all-cause inpatient HCRU, all-cause inpatient and outpatient costs, and migraine-related outpatient HCRU were observed at follow-up vs. baseline, whereas increases in all-cause outpatient HCRU, all-cause medication costs, migraine-related inpatient HCRU, and migraine-related inpatient, outpatient, and medication costs were observed. In this study, observed treatment patterns with the indexed CGRP mAb were consistent with prior reports. Concomitant treatment with CGRP mAb and novel acute migraine medications led to reductions in some outcomes of HCRU and direct costs, however, increases were also observed. Treatment utilization, reductions in HCRU and cost savings identified in this study in favor of concomitant CGRP mAb and novel acute medications may help clinicians and other healthcare decision makers assessing appropriate therapeutic options for migraine management.

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.

Real-World Use of Ubrogepant as Acute Treatment for Migraine with an Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody: Results from COURAGE.

Although acute and preventive treatments for migraine are commonly given in combination, data on the real-world effectiveness of ubrogepant as an acute treatment when used with an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (with or without onabotulinumtoxinA) are limited. This analysis sought to evaluate the real-world effectiveness, treatment satisfaction, and optimization of ubrogepant for the acute treatment of migraine when used in combination with an anti-CGRP monoclonal antibody, with or without concomitant onabotulinumtoxinA. This prospective, multiple-attack, open-label, observational study (COURAGE) assessed meaningful pain relief (MPR), return to normal function (RNF), treatment satisfaction, and acute treatment optimization of ubrogepant (50 or 100mg) when combined with an anti-CGRP monoclonal antibody, onabotulinumtoxinA, or both in adult users of Migraine Buddy, a migraine tracking application. In the ubrogepant and anti-CGRP monoclonal antibody arm (n = 245), following the first ubrogepant-treated attack, 61.6% (151/245) and 80.4% (197/245) of ubrogepant-treated participants achieved MPR at 2 and 4h post-dose, respectively, and 34.7% (85/245) and 55.5% (136/245) achieved RNF at 2 and 4h post-dose, respectively. Across up to 10 ubrogepant-treated attacks (N = 1153), MPR was achieved in 51.3% (592/1153) and 73.5% (847/1153) at 2 and 4h post-dose, respectively. RNF was achieved by 32.2% (371/1153) and 53.2% (613/1153) at 2 and 4h post-dose. After 30days, 72.7% (168/231) of participants reported satisfaction (using a 7-point scale) with ubrogepant when used in combination with an anti-CGRP monoclonal antibody, and 79.7% (184/231) of participants achieved acute treatment optimization (defined as moderate-maximum treatment efficacy using the Migraine Treatment Optimization Questionnaire-4). Real-world ubrogepant use with an anti-CGRP monoclonal antibody was associated with MPR, RNF, satisfaction, and acute treatment optimization.

Patterns of anti-CGRP mAbs use and variation of triptan consumption following treatment initiation: A descriptive drug utilization study in the Tuscany region, Italy.

To describe the pattern of anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) utilization in the Tuscany region, Italy, and the variation of triptan consumption after treatment initiation. Given the recent commercialization of anti-CGRP mAbs as migraine preventive medications, real-world evidence on their patterns of utilization and their impact on migraine abortive medication use is still limited. A retrospective, descriptive, cohort study on the real-world utilization of anti-CGRP mAbs was performed using the population-based regional administrative database of Tuscany. Patients with ≥1 anti-CGRP mAb dispensing (namely erenumab, galcanezumab, fremanezumab) between April 1, 2019, and September 30, 2021, were identified. The first dispensing was the cohort entry (CE). New users (NUs) were patients with no anti-CGRP mAb dispensing before CE. Kaplan-Meier (KM) curves were plotted to describe the cumulative probability of remaining with the initial anti-CGRP mAb during a 15-month follow-up period as a measure of treatment persistence. Among NUs with ≥2 triptan dispensings during the 6 months before CE (i.e., baseline), the mean monthly number of triptan dosage units dispensed was measured in five consecutive follow-up time windows (months 1-3, 4-6, 7-9, 10-12, 13-15) and the difference from the baseline was calculated. A total of 624 NUs (erenumab = 295, galcanezumab = 223, fremanezumab = 106) were identified, of whom 188 (78%) were women. Mean age was 49.2 years (standard deviation [SD] = 12.6). The survival to discontinuation at 6, 12, and 15 months was about 69%, 48%, and 6%, respectively. The survival to switch was about 6% at 15 months. The observed variation of triptan consumption at 3/6/9/12/15 months and the corresponding SD was -4.4 [8.2]/-5.2 [9.0]/-5.5 [9.2]/-5.4 [9.2]/-4.5 [10.0], respectively. Patient demographics reflect the place of these medications in therapy. Overall, findings seem to indicate a favorable tolerability and effectiveness profile. Further studies are warranted to better establish the long-term comparative effectiveness, safety, and cost effectiveness of anti-CGRP mAbs compared to other preventive medications.

A retrospective analysis of migraine prophylaxis with anti-CGRP monoclonal antibodies at the hospital of Lithuanian University of Health Sciences Kaunas Clinics

Background. Migraine is a primary headache disorder described by episodic attacks that can progress to chronic migraine. Preventive treatment of anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) is currently being widely investigated worldwide.Materials and methods. A total of 85 patients with migraine were enrolled in a retrospective study conducted in 2019-2021. Demographic and clinical data were collected and analyzed. Subjects were divided into groups by migraine course: chronic migraine (CM) and episodic migraine (EM), and according to the medicine used (erenumab, fremanezumab). Treatment efficacy was assessed at 3 and 6 months after the start of treatment. A reduction of &gt;50% in monthly headache days (MHDs) was considered a good response. Statistical analysis was performed using IBM SPSS statistics 27.0, the χ² test of homogeneity, Fisher’s exact, Student’s t, and Mann-Whitney tests.Results. Of the 85 migraine patients, 75 (88.2%) were women. EM was diagnosed in 33 (38.8%) and CM in 52 (61.2%) patients. After treatment, the number of MHDs was significantly reduced in both anti-CGRP mAbs therapy groups (p&lt;0.001). The response to anti-CGRP mAbs was similar between the EM and CM groups. A slightly better response was achieved with fremanezumab than erenumab (83.3% vs. 73.1% at 3 months; 83.3% vs. 65.7% at 6 months), but the difference was not significant (p=0.541; p=0.149). In 24 (58.5%) patients initially given 70 mg erenumab, after a median follow-up of 3 months (interquartile range: 2-6) it was decided to increase the dose of erenumab to 140 mg due to insufficient effect. The initial dose was increased more often in patients with chronic migraine (p=0.027).Conclusions. Erenumab and fremanezumab are equally effective and equivalent for both migraine types. It was observed that more than half of the patients required a dose increase when treated with erenumab 70 mg, especially in CM group.

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.

Translated article] Consensus recommendations on the preventive treatment of migraine

ObjectiveThe objectives are to know the opinion of neurologists and hospital pharmacists on those aspects still under debate regarding the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine. To identify those controversies that still exist. To propose agreed recommendations for improvement of care. And to promote access of clinicians and patients to these new treatments in the prevention of migraine with biological drugs, in order to improve patient care and follow-up. MethodologyRecommendations for the use of biological drugs in the prevention of migraine were identified and evaluated through the Delphi consensus methodology, proposing 88 statements grouped into 3 themes: a clinical module that deals with the management of biological treatments in migraine; a patient module that discusses patient education and adherence improvement strategies; and a coordination module that includes statements related to strategies to improve joint work between the two groups. The 9-point Likert ordinal scale was used to score these recommendations and, subsequently, the data was statistically analysed through different metrics. ResultsAfter both rounds of voting, consensus was reached in agreement on 71 of the 88 statements (80.7%), leaving 1 statement (1.1%) with consensus in disagreement and 16 remaining as indeterminate (18.2%). ConclusionsThe high degree of consensus indicates that the opinion of neurologists and hospital pharmacists on the role of anti-Calcitonin Gene-related Peptide monoclonal antibodies in the preventive treatment of migraine is very similar and allows identifying those controversies that still exist, to improve the care and follow-up of patients with migraine.

Switching between anti-calcitonin gene-related peptide monoclonal antibodies: A comparison of monthly and quarterly dosing

BackgroundAnti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have dramatically changed preventive treatment options for patients with migraine. Although there is emerging real-world evidence on the use of CGRPmAbs globally, the change in efficacy and safety after switching between CGRPmAbs owing to patients' frequency of hospital visits preference remains unknown. MethodsWe conducted a single-centre, retrospective, real-world study of patients with migraine who first received galcanezumab for 3 or 4 months and then switched to fremanezumab at Keio University Hospital. We investigated changes in monthly migraine days (MMD), responder rate, and adverse effects such as injection site reactions. ResultsMMD increased only by 0.7 (95% CI, −4.1–5.5; p = 0.748) after 4 months of treatment with fremanezumab (6.1, 95% CI, 2.3–9.9) compared to before switching (5.4, 95% CI, 2.2–8.6). Furthermore, switching from galcanezumab to fremanezumab produced only minor adverse events, such as injection site reactions. ConclusionsAfter switching from galcanezumab to fremanezumab out of the desire to visit the hospital less often, the reduction in MMD compared to baseline was sustained, and no serious adverse effects were observed.

Combined Prophylaxis of Chronic Migraine with OnabotulinumtoxinA and Anti-CGRP Antibodies

Objective: To evaluate the efficacy of adding large molecule anti-calcitonin gene-related peptide monoclonal antibodies (mAbs) to onabotulinumtoxinA (OBT-A) for chronic migraine prevention. Background: Chronic migraine (CM) is a highly prevalent, debilitating disorder that leads to personal, social, and economic burdens. Both OBT-A and mAbs are proven safe and effective in chronic migraine prevention. The use of combination therapy has not been formally studied but may prove more effective than either monotherapy alone in select patients. Methods: This is a retrospective chart review of patients with chronic migraine, treated with OBT-A, who received additional mAb preventative therapy. The primary endpoint was migraine headache days per month (MHD) after 3 months of combined therapy. Secondary endpoints included total headache days per month, headache intensity, disability level, and use of abortive medications. Results: Of 1503 patients reviewed, 133 met inclusion criteria. At 3 months of combined therapy, mean reduction of MHD from baseline was 6.2 (95% CI 4.91 to 7.49, p &lt; 0.0001). Nearly 2/3rd of patients (60.9%) experienced ≥ 50% MHD reduction. Fewer patients reported high disability level (14.6% [17/126], compared to 29.4%) and high headache intensity (13.0% [16/119], compared to 51.3%) at 3 months (all p &lt; 0.0001). A reduction in abortive medication doses needed and discontinuation of concomitant oral preventative medications was also noted in 15.8% and 6.8% of patients, respectively. Conclusions: Combined therapy with OBT-A and mAbs is well-tolerated, effective in further reducing migraine frequency, and may improve quality of life for patients with CM refractory to monotherapy.