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Migraine is a potentially disabling disorder, yet it remains underdiagnosed and undertreated. The release of the neuropeptide calcitonin gene-related peptide (CGRP) in the trigemino-cerebrovascular system plays a vital role in the evolution of migraine. It enhances peripheral sensitization by mediating neurogenic inflammation and also influences central sensitization. The majority of the drug classes available for migraine prophylaxis are nonspecific and associated with numerous side effects and drug interactions. Anti-CGRP monoclonal antibodies (mAb) are an innovative therapeutic class that fulfills the need for more efficacious and tolerable preventive therapy. While erenumab is a mAb to the CGRP receptor, eptinezumab, fremanezumab, and galcanezumab bind to the CGRP molecule. They decrease the number of headache days and improve disability. Upper respiratory tract infection, nausea, constipation, pain at the site of injection, and fatigue are the associated side effects. CGRP mAbs are an excellent advancement in translational research and are a promising addition in migraine therapy. This article discusses the recent advances in the development of the CGRP mAbs.

Abstract Background Many migraine patients do not respond adequately to conventional preventive treatments and are therefore described as treatment/medically resistant or difficult to treat cases. Calcitonin gene-related peptide monoclonal antibodies are a relatively novel molecular treatment for episodic and chronic migraine that have been shown to be effective in short duration clinical trials in approximately 40–50% of all chronic migraine patients. Patient Related Outcome Measures (PROM) or Quality of Life (QoL) questionnaires are used to help measure response to treatment in migraine. Although some open label extension studies have become available for erenumab, there is a lack of real-world data pertaining to quality of life in the medium to long-term for chronic and treatment resistant migraine patients. Methods A total of 177 treatment resistant CM patients were started on erenumab (70 mg or 140 mg subcutaneous injection every 4 weeks) in our three specialist Headache Clinics. Of these, 174 had their first injection between December 2018 and October 2019. All patients were evaluated with the following PROM: the Headache Impact Test− 6, Migraine Associated Disability Assessment test and Migraine-Specific QoL Questionnaire, before starting treatment with erenumab and at intervals of 3–12 months after starting treatment. The decision to continue treatment was based on subjective clinical improvement of at least 30% (as reported by the patient), supported with diaries and QoL questionnaires. We present here the QoL measurements for this group of 177 patients. Prior preventive migraine treatments included conventional oral prophylactic medications (such as topiramate, candesartan, propranolol, or amitriptyline), at least two cycles of PREEMPT protocol onabotulinumtoxin A or (in a small number of cases) neuromodulation with single pulse Transcranial Magnetic Stimulation. Results Of the 177 patients who started treatment with erenumab, 68/177 (38.4%) stopped during the first year, either due to lack of efficacy (no significant benefit or only minimal improvement) and/or possible side effects. 109/177 (61.6%) patients reported clinically significant improvement after 6–12 months and wished to stay on treatment. Twelve of these 109 patients subsequently stopped treatment in the period between 1 year and up to June 2021 (mainly due to a worsening of their migraine). Therefore, a total of 97/177 patients (54.8%) remained on treatment as of June 2021 (duration of treatment 17–30 months, median of 25 months). Conclusion Approximately 55% of treatment resistant or difficult to treat CM patients who trialled erenumab in our clinics reported a subjective benefit and were still on treatment after 17–30 months.

Abstact Background DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. Methods DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18–65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. Results At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was − 8.2 days for erenumab and − 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: − 1.57 [95%CI: − 2.83, − 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (− 5.34 vs − 4.66) and mMIDAS scores (− 14.67 vs − 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). Conclusion DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. Trial registration NCT03867201

Abstract Objective HER-MES was the first head-to-head, phase 4 trial to assess the tolerability and effectiveness of erenumab against standard of care treatment (topiramate). This post hoc analysis compared the efficacy of erenumab with topiramate in patients who completed the trial on study medication. Methods Post hoc sensitivity analysis was performed using the full analysis set. Outcomes assessed included the proportion of patients with a ≥50% reduction in monthly migraine days (MMD) from baseline (50% responder rate), over the last 3 months (months 4, 5, and 6) of the double-blind treatment phase (DBTP), the 50% responder rate during the first month of the DBTP, and change from baseline in MMD during the DBTP. Multiple imputation was done for efficacy values of patients who discontinued study treatment. Results Patients (N = 777) were randomly assigned (1:1) to either 70 or 140 mg/month erenumab (N = 389) or 50–100 mg/day topiramate (N = 388). Of these, 334 patients (85.9%) receiving erenumab, and 231 patients (59.5%) receiving topiramate completed the DBTP on study medication. Patients on study medication until the end of the DBTP received a mean dose of 119 mg/month for erenumab and 92 mg/day for topiramate. At month 1, a significantly greater proportion of patients receiving erenumab (39.2%) reported ≥50% reduction in MMD from baseline compared with those receiving topiramate (24.0%; p

Abstract Background The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting. Methods An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months. Results In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p

Abstract Background Controlled and real-world evidence have demonstrated the efficacy of calcitonin gene related peptide (CGRP) monoclonal antibodies (MABs) in migraine. However, data on the over-one-year sustained effectiveness of CGRP MABs in resistant chronic migraine (CM) is sparse. Methods This is a two-year real-world prospective analysis of an ongoing single centre audit conducted in patients with resistant CM. Patients received monthly erenumab for six months before assessing its effectiveness. Responders were considered those who achieved at least 30% reduction in monthly migraine days (MMD) by month 6, compared to baseline. Secondary outcomes were also analysed, including changes of the Headache Impact Test version 6 (HIT-6). Results One hundred sixty-four patients [135 (82.3%) females; mean age 46 SD 14) years] were included in the audit and 160 patients analysed. Patients had failed a mean of 8.4 preventive treatments at baseline. At month 6, 76 patients (48%) were 30% responders to erenumab, 50 patients (31%) were 50% responders and 25 (15%) were 75% responders. The mean reduction in MMD at month 6 was 7.5 days compared to baseline (P

Background: Erenumab has demonstrated effectiveness for prevention of migraine attacks, but the treatment is costly, and a considerable proportion of patients do not respond to it. The Registry for Migraine study (REFORM) was initiated to discover biomarkers that can predict response to erenumab in patients with migraine. The specific objective was to investigate differences in erenumab efficacy based on clinical information, blood-based biomarkers, structural and functional magnetic resonance imaging (MRI), and response to intravenous infusion of calcitonin gene-related peptide (CGRP). In this first report of the REFORM study, we provide a comprehensive description of the study methodology, and present the baseline characteristics of the study population. Methods: The REFORM study was a single-center, prospective, longitudinal cohort study in adults with migraine who were scheduled to receive preventive treatment with erenumab as part of a separate, open-label, single-arm phase IV trial. The study included four periods: a 2-week screening period (Weeks -6 to -5), 4-week baseline period (Week -4 to Day 1), 24-week treatment period (Day 1 to Week 24), and a 24-week follow-up period without treatment (Week 25 to Week 48). Demographic and clinical characteristics were recorded using a semi-structured interview, whilst outcome data were obtained using a headache diary, patient-reported outcomes, blood sampling, brain MRI, and responsiveness to intravenous infusion of CGRP. Results: The study enrolled 751 participants, with a mean age ± SD of 43.8 ± 12.2 years, of which 88.8% (n = 667) were female. At enrollment, 64.7% (n = 486) were diagnosed with chronic migraine, and 30.2% (n = 227) had history of aura. The mean monthly migraine days (MMDs) was 14.5 ± 7.0. Concomitant preventive medications were used by 48.5% (n = 364) of the participants, and 39.9% (n = 300) had failed ≥ 4 preventive medications. Conclusion: The REFORM study enrolled a population with a high migraine burden and frequent use of concomitant medications. The baseline characteristics were representative of patients with migraine in specialized headache clinics. Future publications will report the results of the investigations presented in this article. Trial registration: The study and sub-studies were registered on ClinicalTrials.gov (NCT04592952; NCT04603976; and NCT04674020). [ABSTRACT FROM AUTHOR]

Migraine is considered one of the most disabling diseases. Currently, there are few studies on clinical migraine treatment based on sex-related differences, despite the important role of sex in migraine. Our aim was to evaluate gender bias in published clinical trials on monoclonal antibodies (erenumab, galcanezumab, fremanezumab and eptinezumab). We performed a systematic review of controlled clinical trials of erenumab, galcanezumab, fremanezumab and eptinezumab, searching the PubMed/MEDLINE database for articles published before December 2021. The search identified 760 articles, 25 of which met the inclusion criteria. Of all the patients included in these trials, 85.1% were women. Only one study had female lead authors. Two of the 25 studies included a sex-based analysis of the primary endpoint. None of the articles discussed the results separately for men and for women. The proportion of men recruited in trials is scarce and more studies are needed to guarantee the safety and tolerability of monoclonal antibodies used in male migraine. As observed in our study, despite the high number of women recruited, only 2 studies analysed the results separately by sex. Thus, a potential risk of gender bias was found in these clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: With the increased use of erenumab and other calcitonin gene‐related peptide antagonists for migraine prevention, increased evidence on long‐term efficacy and real‐world effectiveness is needed. Some reports of a wearing‐off effect or waning efficacy over time have been observed with erenumab use. Objective: This study evaluated the change in efficacy of erenumab after initial established benefits for migraine prevention in a veteran population. Methods: This retrospective chart review evaluated patients who were prescribed erenumab for migraine prevention at a Veterans Affairs neurology clinic between June 1, 2018, and May 31, 2021. Patients with an initial 50% or greater reduction in mean monthly headache days (MHDs) by 12 weeks after erenumab 70 mg initiation were then followed forward to determine the change in MHDs until erenumab dose was increased, changed to galcanezumab, or by November 30, 2021, to ensure a minimum 6‐month follow‐up for all patients. Results: Ninety‐three patients were included for analysis. A significant reduction in mean MHDs from 16.1 to 5.7 days was found by 12 weeks after erenumab 70 mg initiation (p < 0.0001). Following this initial response to erenumab, 69% of patients experienced a significant increase in MHDs over an average time of 7.8 months and required a subsequent dose increase to erenumab 140 mg or change to galcanezumab. The remaining 31% of patients continued erenumab 70 mg monthly with a further nonstatistically significant decline in MHDs. Conclusions: A decrease in efficacy with the long‐term use of erenumab was observed for the majority of patients evaluated in this analysis. This suggests that patients with initial benefits on lower dose erenumab should be monitored for change to effectiveness. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with New Daily Persistent Headache and Persistent Post-Traumatic Headache belong to a heterogeneous group of primary and secondary headache disorders, with the common clinical feature that these conditions start abruptly, continue unabated, and are refractory to conventional migraine preventive treatments. Objective: This is a real-world, medium-term audit to explore whether erenumab improves quality of life in a pooled group of 82 abrupt-onset, unremitting and treatment refractory patients, where the diagnosis is new daily persistent headache and persistent post-traumatic headache in the majority of cases. Methods: Eighty-two patients were treated with erenumab every 28 days over a two to three-year period, beginning in December 2018. These patients were "longstanding chronic" and refractory with a median of eight (IQR 4–12) prior failed migraine preventive treatments and median duration of disease of seven (IQR 3–11) years. The starting dose of erenumab was 70 mg in 79% of cases and 140 mg in the remaining patients (individuals with a BMI of more than 30). All patients were asked to complete three migraine specific Quality of Life questionnaires or Patient Reported Outcome Measures before starting treatment and typically at 3–12 intervals until the end of June 2021 or cessation of treatment. The Patient Reported Outcome Measures included: Headache Impact Test-6, Migraine Associated Disability Assessment test and Migraine-Specific Quality-of-Life Questionnaire. Patients generally only stayed on treatment after 6–12 months if there was deemed to be an improvement of at least 30% and there were no significant side effects. The longest treated cases have quality of life data for 30 months after starting erenumab. Results: Of the 82 patients, 29 (35%) had improvement in Quality of Life scores, with no significant side effects, and wished to stay on treatment. Fifty-three patients (65%) stopped treatment during the first 6–25 months due to lack of efficacy and/or patient reported side effects (n = 33 and n = 17, respectively) or a combination of both, pregnancy planning (n = 2), and lost to follow up (n = 1). Conclusion: Significant improvements in Quality of Life scores were recorded by one-third of patients over a period of 11–30 months, with a 35% persistence after a median of 26 months of treatment. This contrasts with our recently published, treatment resistant, chronic migraine cohort where the persistence with erenumab treatment was almost 55% after a median time of 25 months. [ABSTRACT FROM AUTHOR]

Background and purpose: Based on their pharmacological target, two classes of calcitonin‐gene‐related peptide (CGRP) monoclonal antibodies (mAbs) have been identified: antibodies against the CGRP ligand—galcanezumab, fremanezumab, eptinezumab—and antibodies against the CGRP receptor (CGRP‐R), erenumab. The aim of the present study was to compare anti‐CGRP versus anti‐CGRP‐R mAbs in patients with high frequency episodic and chronic migraine. Methods: All patients on monthly treatment with anti‐CGRP mAbs with an available 6 months' follow‐up at January 2022 were included. Data on efficacy outcome were collected following one (T1), three (T3) and six (T6) months of treatment, and included monthly headache/migraine days, the Migraine Disability Assessment Scale (MIDAS) and Headache Impact Test 6 (HIT‐6) scores, pain intensity, analgesics consumption and response rates (>50% headache days reduction compared to baseline). Results: In all, 152 patients were enrolled, of whom 68 were in treatment with anti‐CGRP mAbs (49 galcanezumab, 19 fremanezumab) and 84 with the anti‐CGRP‐R (erenumab). MIDAS scores were significantly lower in the anti‐CGRP group at T1 and T3 (respectively p < 0.02 and p < 0.03) as well as the number of mean migraine days at T3 (p < 0.01). At T3 and T6 outcome measures were comparable, although a significantly higher percentage of super‐responders was found in the anti‐CGRP group (respectively p < 0.04 and p < 0.05), with a similar overall percentage of responders. Conclusions: The present study on a real‐world sample confirms the beneficial effect of both anti‐CGRP and anti‐CGRP‐R mAbs, with a more favorable outcome for anti‐CGRP antibodies. [ABSTRACT FROM AUTHOR]

Objective: Assess the long‐term efficacy and safety of erenumab in patients with chronic migraine with acute medication overuse. Background: Overuse of acute medication in patients with chronic migraine has been linked to greater pain intensity and disability and may diminish the effectiveness of preventive therapies. Methods: This 52‐week open‐label extension study followed a 12‐week double‐blind placebo‐controlled study in which patients with chronic migraine were randomized 3:2:2 to placebo or once‐monthly erenumab 70 mg or 140 mg. Patients were stratified by region and medication overuse status. Patients received erenumab 70 mg or 140 mg throughout or switched from erenumab 70 to 140 mg (based on protocol amendment to augment safety data at higher dose). Efficacy was assessed in patients with and without medication overuse at parent study baseline. Results: Of 609 patients enrolled in the extension study, 252/609 (41.4%) met the criteria for medication overuse at parent study baseline. At Week 52, the mean change in monthly migraine days from parent study baseline was −9.3 (95% confidence interval: −10.4, −8.1 days) in the medication overuse subgroup versus −9.3 (−10.1, −8.5 days) in the non‐medication overuse subgroup (combined erenumab doses); proportion of patients achieving ≥50% reduction in monthly migraine days at Week 52 was 55.9% (90/161; 48.2%, 63.3%) versus 61.3% (136/222; 54.7%, 67.4%), respectively. Among baseline users of acute migraine‐specific medication, the mean change in monthly migraine‐specific medication days at Week 52 was −7.4 (−8.3, −6.4 days) in the medication overuse subgroup versus −5.4 (−6.1, −4.7 days) in the non–medication overuse subgroup. Most patients (197/298; 66.1%) in the medication overuse subgroup transitioned to non‐overuse status by Week 52. Erenumab 140 mg was associated with numerically greater efficacy than erenumab 70 mg across all endpoints. No new safety signals were identified. Conclusion: Long‐term erenumab treatment demonstrated sustained efficacy and safety in patients with chronic migraine with and without acute medication overuse. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness and safety of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine, through real‐world data. Background: Monoclonal antibodies (mAbs) targeting the calcitonin gene–related peptide (CGRP) pathway have been tested extensively in several clinical trials for both episodic and chronic migraine, showing high effectiveness, safety, and tolerability; however, there are no prospective real‐world studies intending to compare their efficacy and safety. Methods: This is a prospective observational cohort study comparing the effectiveness and safety profiles of galcanezumab, fremanezumab, and erenumab for the treatment of chronic and episodic migraine. We enrolled 140 patients at the Headache Centre of University Federico II of Naples, with a history of multiple failed treatments with validated migraine preventatives. Framenezumab, erenumab, or galcanezumab were administered for 12 months. The mean monthly days with headache, Migraine Disability Assessment (MIDAS) score, and adverse events were evaluated during the run‐in period and every 3 months by reviewing standardized paper patient headache diaries. Results: We found a mean reduction of migraine monthly days from baseline of −12.0 (−9.8, −14.1) in the galcanezumab group, −12.3 (−10.2, −14.3) in the fremanezumab group, and −10.8 (−8.5, −13.1) in the erenumab group (for all, p < 0.001). We found a mean reduction of MIDAS score of −32.6 (−26.6, −38.5) in the galcanezumab group, −33.4 (−28.0, −38.9) in the fremanezumab group, and −29.2 (−23.0, −35.4) in the erenumab group (for all, p < 0.001). We found no significant differences between mAbs in the reduction of mean monthly days with headache and MIDAS score. We found a more rapid effect of galcanezumab and erenumab compared to fremanezumab in medication overuse headache patients after 3 months of treatment (−10.8 and −11.1 vs. −4.0 days; p = 0.029). Conclusion: Our results confirm the therapeutic benefits of anti‐CGRP mAbs. There is no evidence that suggests that one antibody may be superior to the others in terms of effectiveness, both in chronic and episodic patients. [ABSTRACT FROM AUTHOR]

Objective: To report the effcacy of different anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) on headache frequency, intensity, and duration. Background: Blockade of CGRP receptors or neuropeptide with anti-CGRPmAbs have been successfully used for several years for the prevention of chronic and episodic migraine. The response is usually assessed by improvement seen in the number of days with headache per month. However, clinical praxis indicates that sole reliance on the frequency of headaches might be insuffcient to interpret the effcacy of these treatments. Methods: Retrospective review of a case with a meticulous headache diary who has tried three different anti-CGRP mAbs for chronic migraine prevention. Results: The patient has been diagnosed with chronic migraine and was first treated with erenumab, followed by fremanezumab and thereafter galcanezumab due to several reasons. In addition to significant improvement in all three parameters analyzed with anti-CGRP mAb treatment, the most important and valuable effect on the patient's quality of life was decreased duration and frequency of headaches. At present, the patient is receiving fremanezumab treatment with an excellent tolerability. Conclusion: There is a clear need for careful follow-up and detailed daily records of headaches showing the frequency, duration, and severity for the evaluation of anti-CGRP mAbs treatment. This study shows the importance of this information in order formedical professionals tomake an informed decision regarding the best course of anti-CGRP mAbs treatment in cases of side effects or lack of effcacy. [ABSTRACT FROM AUTHOR]

The introduction of monoclonal antibodies (mAbs) directed against the calcitonin gene-related peptide (CGRP), or its receptor (CGRPr), revolutionized migraine management due to their high efficacy and few side effects. Data suggest that the CGRP may even be implicated in circadian rhythm, but studies about the effect of anti-CGRP treatments on sleep are still lacking. The aim of the present study was to assess the effect of erenumab (70 and 140 mg per month), a human mAb directed against CGRPr, on chronotype in chronic migraineurs; secondly, we assessed its efficacy, safety, and the effects on anxiety and depression. Sleep was evaluated using self-administrable questionnaires investigating chronotype, sleep quality, and daytime sleepiness. Migraine diaries and several self-administrable questionnaires regarding headache impact and psychological correlates were evaluated every 3 months during 12 months of treatment. Eighty-eight patients were included; most of them showed a significant reduction in headache frequency and an improvement in psychological symptoms. Moreover, an initial change in chronotype was observed at the three-month assessment from a morning chronotype to an intermediate one; a similar trend remained in the other evaluations, even if it did not reach a statistical significance. Lastly, patients who responded to the treatment showed a progressive sleep efficiency reduction. The present real-life study hypothesized the influence of erenumab on chronotype, representing a link between circadian rhythm, CGRP, and migraine. [ABSTRACT FROM AUTHOR]

Background: Real-world data on the effectiveness of calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) in migraine patients are needed. Methods: We performed a single-center, real-world study with an observation period of up to 12 months (mean 7.5 ± 3.4 months) after CGRP mAb administration. A total of 228 Japanese patients with episodic or chronic migraine (age, 45.9 ± 13.2 years; 184F; 45 erenumab; 60 galcanezumab; 123 fremanezumab) who were treated with CGRP mAbs for at least three months were ultimately included in this study. Results: In the total cohort, after CGRP mAb treatment, mean monthly migraine days decreased by 7.2 ± 4.8, 8.3 ± 4.7, and 9.5 ± 5.0 at three, six and 12 months, respectively. The ≥50% monthly migraine day reduction rates at three, six and 12 months were 48.2%, 61.0% and 73.7%, respectively. In the logistic regression analysis, the presence of osmophobia and fewer baseline monthly migraine days contributed to ≥50% responders at three, six and 12 months. The ≥50% responders at three or six months were useful in predicting ≥50% responders at 12 months. In subgroups of patients with difficult-to-treat migraine (those with medication overuse headache or psychiatric comorbidities) and previous CGRP mAb users, monthly migraine days were substantially reduced over 12 months. There was no difference in monthly migraine day reduction over 12 months among three different CGRP mAbs. Adverse reactions were observed in 28 (12.3%) patients, with injection site reactions being the most common (n = 22) though generally mild in severity. Conclusion: This real-world study confirmed the efficacy and safety of three different CGRP mAbs for prophylactic treatment of patients with migraine. [ABSTRACT FROM AUTHOR]

Migraine is one of the most disabling disorders in the world, associated with poor quality of life. Migraine prevention strategies have increasingly evolved since monoclonal antibodies against the calcitonin gene-related peptide (CGRP), or its receptor, were identified. CGRP is the ideal target of monoclonal antibodies (mAbs). In particular, erenumab is the mAb that has shown good therapeutic efficacy in reducing pain intensity and having high tolerability. In this study, we aimed to investigate the efficacy of erenumab on both cognitive performance and psychological well-being. This was a pilot study with a retrospective design that included 14 subjects (2 males and 12 females), with a mean age of 52.29 ± 9.62, who attended the Headache and Migraine outpatient clinic of the IRCCS Centro Neurolesi Bonino-Pulejo of Messina. The evaluation consisted of measuring cognitive and psychological functioning. Comparing clinical and psychometric test scores between baseline and follow-up, we found a significant improvement in both cognitive performance and quality of life. We also observed a decrease in migraine disability. Our findings have shown improvements in global cognitive performance and quality of life in migraine patients taking erenumab. [ABSTRACT FROM AUTHOR]

Objective: To assess whether dual therapy with erenumab and onabotulinumtoxinA (BoNTA) was more effective than erenumab alone in chronic migraine. Background: Calcitonin gene‐related peptide (CGRP) is crucial in migraine. Erenumab binds to the canonical CGRP receptor in Aδ‐fibers, and BoNTA prevents the release of CGRP from meningeal and extracranial C‐fibers. It is still unknown whether dual therapy is more effective. Methods: This was a retrospective study in a Headache Unit. There was a thorough revision of charts of patients receiving erenumab from December 2019 to March 2021. The cohort was divided into three groups according to BoNTA at the start of erenumab: (1) WBT: were on BoNTA and maintained it as dual therapy; (2) WoBT: were on BoNTA and discontinued; (3) NoBT: were not on BoNTA. Primary endpoint was reduction in monthly headache days (MHD) at 12 weeks. Secondary endpoints were percent improvement and ≥50% reduction in MHD. Results: Of 237 charts reviewed, 187 met the inclusion criteria. Seventy‐three (39%) were included in WBT, 44 (23.5%) in WoBT, and 70 (37.4%) in NoBT. The reduction in MHD was less with dual therapy [WBT 4.7 ± 7.68, WoBT 5.12 ± 7.98 (p = 0.80), NoBT 8.21 ± 7.84 p = 0.009]. The percentage of improvement was higher in the erenumab‐alone group [NoBT 35%, WoBT 22.3% (p = 0.92), WBT 21.7% (p = 0.001)]. The probability of achieving a ≥ 50% reduction in MHD was lower in WBT than in WoBT (OR 0.66, p = 0.35) and in the NoBT group (OR 0.57, p = 0.14). Conclusions: Our findings suggest that dual therapy is less effective than erenumab alone. However, since the design has multiple limitations, further prospective studies are required to validate these data. [ABSTRACT FROM AUTHOR]

Background Vestibular migraine is considered the most common cause of recurrent vertigo for which specific treatments are missing. Monoclonal antibodies against calcitonin gene-related peptide, are effective in preventing migraine. Since CGRP is also detected in human cochlear and vestibular organs it may also play a role in vestibular physiology. Methods This is a prospective observational cohort study, aiming at evaluating the efficacy of erenumab, fremanezumab or galcanezumab for the treatment of fifty vestibular migraine patients. We assessed mean monthly days with headache and dizziness/vestibular symptoms, pain intensity and migraine-related clinical burden occurring for 18 months. Results Response to treatment was excellent as 45 (90%) patients had at least a 50% reduction in vertigo frequency, 43 (86%) had at least a 50% reduction in headache frequency, and 40 (80%) a MIDAS reduction of at least 50%. Overall, 39 (78%) patients had a concomitant reduction of all three parameters. Mean monthly days with dizziness/vestibular symptoms showed an overall significant decrease from a mean of 10.3-1.9 at baseline to 0.8-0.3 days, difference 9.5 (CI 95% 3.6, 15.4; p<0.001) after twelve months. Conclusion We show that anti-CGRP mAbs may be effective in the treatment of Vestibular Migraine. Their use should be encouraged early in the disease course to allow for a better symptom control and quality of life improvement. [ABSTRACT FROM AUTHOR]

Background: Several novel treatments targeting the calcitonin gene-related peptide pathway have been developed for migraine. We evaluated the efficacy of these medications, including atogepant, rimegepant, erenumab, eptinezumab, fremanezumab, and galcanezumab, for the prevention of migraine via network meta-analysis. Methods: Databases, including MEDLINE via PubMed, EMBASE, and Cochrane central, were systematically reviewed, and all eligible phase 3 randomised controlled trials were included. Results: Nineteen studies (n=14,584 participants) were included. Studies included episodic (n=11) and chronic (n=4) migraine or both (n=4). All interventions, except for eptinzumab 30 mg, significantly reduced mean monthly migraine days compared to placebo. All medications had a higher -50% responder rate than placebo and results were statistically significant in those with the subcutaneous or intravenous route of administrations, but not with the oral one. All medications significantly reduced mean monthly headache days, although no data for this outcome was available for rimegepant, and mean monthly acute medication days, with no data for eptinezumab. Conclusion: The results show that medications targeting calcitonin gene-related peptide were effective in preventing migraine compared to placebo. Considering limitations of single studies, different populations such as episodic and chronic migraine, and the absence of head-to-head trials, all novel treatments decreased mean monthly migraine and headache days, and showed higher 50%, 75% and 100% responder rates than placebo. [ABSTRACT FROM AUTHOR]

Background: Safety data on the use of migraine preventive monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) system in pregnancy are limited. Methods: Updated pharmacovigilance assessment of the safety reports related to pregnancy associated with erenumab, galcanezumab, fremanezumab and eptinezumab, retrieved from VigiBaseVR as of 31 December 2021. As primary outcome, the whole group of monoclonal antibodies targeting the CGRP system was considered and sex and age subgroup disproportionality analyses using the reporting odds ratio (ROR) were conducted. Results: 286 safety reports were found: 116 (40.6%) on erenumab, 125 (43.7%) on galcanezumab, 39 (13.6%) on fremanezumab, 6 (2.1%) on eptinezumab. One hundred and forty-nine (52.1%) safety reports reported only drug exposure in relation to pregnancy while 137 (47.9%) also included -1 pregnancy outcomes: maternal outcomes (n=64), spontaneous abortion (n=63), foetal growth restriction (n=1), prematurity (n=8), neonatal outcomes (n=13), and poor breastfeeding (n=1). No specific patterns of maternal, foetal and neonatal toxicity were observed. Spontaneous abortion was not disproportionally more frequently reported with erenumab, galcanezumab, fremanezumab and eptinezumab compared with the entire database (ROR 1.1, 95% confidence interval, CI, 0.8-1.5), the entire database since 2018 (ROR 1.3, 95% CI 1.0-1.8), and triptans (ROR 1.2, 95% CI 0.8-1.9). Conclusions: This updated safety analysis on erenumab, galcanezumab, fremanezumab and eptinezumab in pregnancy showed no signals of foeto-maternal toxicity according to VigiBaseVR safety reports. [ABSTRACT FROM AUTHOR]

Background and purpose: Response predictors to erenumab (ERE) in migraine patients would benefit their clinical management. We investigate associations between patients' clinical characteristics and polymorphisms at calcitonin receptor‐like receptor (CALCRL) and receptor activity‐modifying protein 1 (RAMP1) genes and response to ERE treatment measured as clinically meaningful improvement on the Headache Impact Test‐6 (HIT‐6) score. Methods: This post hoc analysis of a prospective, multicenter, investigator‐initiated study involves 110 migraine patients starting ERE 70 mg/month. Demographics, medical history, and migraine‐related burden measured by HIT‐6 score were collected during 3 months before and after ERE start. Selected polymorphic variants of CALCRL and RAMP1 genes were determined using real‐time polymerase chain reaction. Logistic regression models identified independent predictors for response to ERE, defined as HIT‐6 score improvement ≥ 8 points (HIT‐6 responders [HIT‐6 RESP] vs. HIT‐6 nonresponders). Results: At Month 3, 58 (52.7%) patients were HIT‐6 RESP. Comorbid hypertension predicted a lower probability of being HIT‐6 RESP (odds ratio [OR] = 0.160, 95% confidence interval [CI] = 0.047–0.548, p = 0.003). Compared to major alleles, minor alleles CALCRL rs6710852G and RAMP rs6431564G conferred an increased probability of being HIT‐6 RESP (for each G allele: OR = 2.82, 95% CI = 1.03–7.73, p = 0.043; OR = 2.10, 95% CI = 1.05–4.22, p = 0.037). RAMP1 rs13386048A and RAMP1 rs12465864G decreased this probability (for each rs13386048A, OR = 0.53, 95% CI = 0.28–0.98, p = 0.042; for each rs12465864G, OR = 0.32, 95% CI = 0.13–0.75, p = 0.009). A genetic risk score based on the presence and number of identified risk alleles was independently associated with HIT‐6 RESP (OR = 0.49, 95% CI = 0.33–0.72, p = 0.0003), surviving Bonferroni correction. Conclusions: Response to ERE was associated with comorbid hypertension and specific allelic variants in CALCRL and RAMP1 genes. Results require confirmation in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Self-injectable calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) auto-injectors and non-CGRP oral medications are currently available for migraine prevention in Japan. This study elicited the preferences for self-injectable CGRP mAbs and non-CGRP oral medications and determined differences in the relative importance of auto-injector attributes for patients and physicians in Japan. Methods: Japanese adults with episodic (EM) or chronic (CM) migraine and physicians who treat migraine completed an online discrete choice experiment (DCE), asking participants to choose a hypothetical treatment they preferred between two self-injectable CGRP mAb auto-injectors and a non-CGRP oral medication. The treatments were described by seven treatment attributes, with attribute levels varying between questions. DCE data were analyzed using a random-constant logit model to estimate relative attribution importance (RAI) scores and predicted choice probabilities (PCP) of CGRP mAb profiles. Results: A total of 601 patients (79.2% with EM, 60.1% female, mean age: 40.3 years) and 219 physicians (mean length of practice: 18.3 years) completed the DCE. About half (50.5%) of patients favored CGRP mAb auto-injectors, while others were skeptical of (20.2%) or averse (29.3%) to them. Patients most valued needle removal (RAI = 33.8%), shorter injection duration (RAI = 32.1%), and auto-injector base shape and need for skin pinching (RAI = 23.2%). Most physicians (87.8%) favored auto-injectors over non-CGRP oral medications. Physicians most valued less-frequent dosing RAI = 32.7%), shorter injection duration (30.4%), and longer storage outside the fridge (RAI = 20.3%). A profile comparable to galcanezumab showed a higher likelihood of being chosen by patients (PCP = 42.8%) than profiles comparable to erenumab (PCP = 28.4%) and fremanezumab (PCP = 28.8%). The PCPs of the three profiles were similar among physicians. Conclusion: Many patients and physicians preferred CGRP mAb auto-injectors over non-CGRP oral medications and preferred a treatment profile similar to galcanezumab. Our results may encourage physicians in Japan to consider patient preferences when recommending migraine preventive treatments. [ABSTRACT FROM AUTHOR]

Background: Due to the recent introduction of new biologic drugs for chronic migraine, a global evaluation in real clinical practice is necessary. Objective: The objective was to evaluate the effectiveness and safety in real clinical practice of drugs targeting the calcitonin gene-related peptide receptor (CGRPr) in patients with chronic migraine. Methods: Single-center, restrospective study (2019-2022), including patients with chronic migraine treated with erenumab, galcanezumab, or fremanezumab. Effectiveness variables were recorded, namely, number of migraine headache days per month (MHD), Migraine Disability Assessment Scale (MIDAS) score, and Headache Impact Test–6 (HIT-6) score, assessing changes at week 12, 24 from baseline. Toxicity was recorded following the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Results: In all, 104 patients were included (46.2% erenumab, 41.3% galcanezumab, 12.5% fremanezumab). A reduction in MHD, MIDAS, and HIT-6 was achieved at weeks 12 and 24 with erenumab (p75% at week 24 than those intensified; P = 0.041). There was no difference in efficacy (P = 0.154) or improvement in quality of life (P = 0.783, P = 0.150), but there was greater toxicity (P < 0.001) among nonresponders with erenumab 70 mg versus erenumab 140 mg. Conclusions: The results confirm the effectiveness and safety of anticalcitonin gene-related peptide (CGRP) drugs in real clinical practice. However, the study shows little benefit from erenumab intensification, with similar effectiveness and worse tolerability than the standard dose. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of pharmacological treatments for adults with chronic migraine. Methods We undertook systematic literature searches using terms for migraine/headache and prophylactic drug interventions, combined with economic/cost terms where appropriate. Using inclusion and exclusion criteria, two reviewers independently assessed the citations and abstracts, and full-text articles were retrieved. A review of study characteristics and methodological quality was assessed. Results Sixteen citations met the inclusion criteria and were model-based cost-utility studies evaluating: Botox (n = 6); Erenumab (n = 8); Fremanezumab (n = 2); and Galcanezumab (n = 1) as the main treatment. They varied in their use of comparators, perspective, and model type. Botox was cost-effective compared to placebo with an incremental cost-effectiveness ratio (ICER) ranging between £15,028 (€17,720) and £16,598 (€19,572). Erenumab, Fremanezumab and Galcanezumab when compared to Botox, was associated with ICERs ranging between £59,712 ($81,080) and £182,128 (€218,870), with the ICERs above the most common willingness-to-pay thresholds (WTPs). But they were cost-effective within the commonly used WTPs among the population for whom the previous treatments including Botox were failed. Three studies compared the cost-effectiveness of Erenumab against the placebo and found that Erenumab was dominant. All studies performed sensitivity analyses to check the robustness of their results. None of the findings from the included articles were generalisable and none of the included studies fulfilled all the criteria mentioned in the CHEERS 2022 reporting checklist and Phillips’s checklist for economic models. Conclusions Evidence to support the cost-effectiveness of pharmacological treatments of chronic migraine in the adult population using Botox and Erenumab were identified. Our findings suggest that both Botox and Erenumab, are cost-effective compared to placebo; although Erenumab had more incremental economic benefits compared to Botox, the ICERs were above the most common willingness-to-pay thresholds. Hence, Erenumab might be an acceptable treatment for chronic migraine for patients whom other treatments such as Botox do not work. Further research is needed to help characterise the data to adequately structure and parameterise an economic model to support decision-making for chronic migraine therapies.

Background: Migraine is one of the neurological diseases that have a negative impact on subjects’ productivity and daily activity of patients. Introducing monoclonal antibodies as a valuable option for resolving the persistent problem of migraine is still under investigation. The current study aimed to evaluate the efficacy and safety profile related to Erenumab. Methods: A prospective study for clinical data collection and analysis from recruited therapy-refractory migraine subjects were carried through 6 months for each subject. All subjects received Erenumab 70 mg monthly. Each patient provided the clinical data monthly starting from 0 months and for the next 6 months. Migraine disability assessment (MIDAS) questionnaire was used for evaluation of the Erenumab efficacy every 3 months. In addition, data regarding adverse effects, migraine triggers, and the impact of previous COVID-19 on migraine severity were collected and analyzed. Results: Ninety subjects were recruited in the study. Erenumab injections resulted in a significant (p

Abstract Background Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, has demonstrated efficacy and safety in the prevention of episodic and chronic migraine. There exists an unmet need to establish the safety of erenumab in older individuals, in view of existing multiple comorbidities, polypharmacy, and age-related physiological changes. This pooled analysis of five large migraine-prevention studies examined the safety of erenumab stratified across age groups, particularly in older populations. Methods Pooled and age-stratified analysis of safety data from the 12-week double-blind treatment phase (DBTP) of five randomized, placebo-controlled Phase 2 and 3 studies of erenumab in participants with episodic or chronic migraine across the age groups

Introduction: The development of monoclonal antibodies against calcitonin gene-related peptide has represented a revolution in the treatment of migraine. Erenumab was the first of these drugs to be available in clinical practice in our setting. Methods: We performed a prospective study of patients from real clinical practice, measuring efficacy (headache days per month and migraine days per month), safety, and disease impact; data were collected at the onset of treatment with erenumab and at 3, 6, 9, and 12 months. Results: Our sample included 31 patients diagnosed with refractory migraine, presenting a mean of 18.5 headache days and 13.2 migraine days per month. A response rate of 50% was obtained in 58.6%, 65.2%, 69.2%, and 62.5% of patients at 3, 6, 9, and 12 months, respectively. According to Patient Global Impression of Change scale scores, 64.5% of patients rated their clinical improvement as good or excellent at 3 months, 65.2% at 6 months, 84.6% at 9 months, and 100% of cases at 12 months follow-up. A total of 45% of patients experienced mild adverse reactions, the most frequent being constipation. No severe adverse reactions were reported. Conclusions: Erenumab is an effective and safe option for the prevention of episodic and chronic migraine. Our results are similar to those obtained in real-world studies; however, results require confirmation in larger numbers of patients. Resumen: Introducción: El tratamiento de la migraña ha experimentado una revolución tras el desarrollo de anticuerpos monoclonales (AcM) contra el péptido relacionado con el gen de la calcitonina (CGRP). Erenumab ha sido el primero de estos fármacos disponibles en la práctica clínica en nuestro medio. Métodos: Estudio prospectivo de práctica clínica real en el que se recogen las variables de eficacia (días con cefalea al mes: DCM y días con migraña al mes: DMM), seguridad e impacto al inicio del tratamiento con erenumab y a los 3,6,9 y 12 meses. Resultados: Se obtuvieron resultados en 31 pacientes diagnosticados de migraña refractaria que presentaban de media 18,5 DCM y 13,2 DMM. Se obtuvo una tasa de respuesta del 50% en el 58,6%, 65,2%, 69,2% y 62,5% de los casos a los 3, 6, 9 y 12 meses, respectivamente. Los pacientes consideraban que habían presentado una mejoría clínica buena o excelente en la escala PGIC en el 64,5% de los casos a los 3 meses, 65,2% a los 6 meses, 84,6% a los 9 meses y 100% de los casos a los 12 meses de seguimiento. En total el 45% de los pacientes presentaron efectos adversos leves, siendo el más frecuente el estreñimiento. No se registró ningún efecto secundario grave. Conclusiones: Erenumab es una opción eficaz y segura para la prevención de migraña episódica y crónica. Nuestros resultados son similares a los obtenidos en estudios de vida real pero estos resultados deberán confirmarse con mayor número de casos.

Abstract Background Calcitonin gene-related peptide (CGRP) inhibitors have been developed as options for treatment of chronic and episodic migraine. We present our experience of the use of erenumab in a tertiary headache centre. Methods This was a prospective clinical audit of all patients commenced on erenumab following a locally agreed pathway and criteria over a consecutive period. Patients received monthly erenumab 140 mg for 3 months. Data were collected prospectively at baseline and 3 months follow up. Results One hundred three patients were commenced on erenumab during the study period. Patients had tried a median of 7 previous prophylactics, including onabotulinum toxin A in 94%. At 3 months there was a reduction in median total (28 to 20, 29% reduction, p

ObjectiveTo report the efficacy of different anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) on headache frequency, intensity, and duration.BackgroundBlockade of CGRP receptors or neuropeptide with anti-CGRP mAbs have been successfully used for several years for the prevention of chronic and episodic migraine. The response is usually assessed by improvement seen in the number of days with headache per month. However, clinical praxis indicates that sole reliance on the frequency of headaches might be insufficient to interpret the efficacy of these treatments.MethodsRetrospective review of a case with a meticulous headache diary who has tried three different anti-CGRP mAbs for chronic migraine prevention.ResultsThe patient has been diagnosed with chronic migraine and was first treated with erenumab, followed by fremanezumab and thereafter galcanezumab due to several reasons. In addition to significant improvement in all three parameters analyzed with anti-CGRP mAb treatment, the most important and valuable effect on the patient's quality of life was decreased duration and frequency of headaches. At present, the patient is receiving fremanezumab treatment with an excellent tolerability.ConclusionThere is a clear need for careful follow-up and detailed daily records of headaches showing the frequency, duration, and severity for the evaluation of anti-CGRP mAbs treatment. This study shows the importance of this information in order for medical professionals to make an informed decision regarding the best course of anti-CGRP mAbs treatment in cases of side effects or lack of efficacy.

Background: Therapeutic options for migraine prevention in non-responders to monoclonal antibodies (mAbs) targeting Calcitonin Gene-Related Peptide (CGRP) and its receptor are often limited. Real-world data have shown that non-responders to the CGRP-receptor mAb erenumab may benefit from switching to a CGRP ligand mAb. However, it remains unclear whether, vice versa, erenumab is effective in non-responders to CGRP ligand mAbs. In this study, we aim to assess the efficacy of erenumab in patients who have previously failed a CGRP ligand mAb. Methods: This monocentric retrospective cohort study included patients with episodic or chronic migraine in whom a non-response (<30% reduction of monthly headache days during month 3 of treatment compared to baseline) to the CGRP ligand mAbs galcanezumab or fremanezumab led to a switch to erenumab, and who had received at least 3 administrations of erenumab. Monthly headache days were retrieved from headache diaries to assess the ≥30% responder rates and the absolute reduction of monthly headache days at 3 and 6 months of treatment with erenumab in this cohort. Results: From May 2019 to July 2022, we identified 20 patients who completed 3 months of treatment with erenumab after non-response to a CGRP ligand mAb. Fourteen patients continued treatment for ≥6 months. The ≥30% responder rate was 35% at 3 months, and 45% at 6 months of treatment with erenumab, respectively. Monthly headache days were reduced from 18.6 ± 5.9 during baseline by 4.1 ± 3.1 days during month 3, and by 7.0 ± 4.8 days during month 6 compared to the month before treatment with erenumab (p < 0.001, respectively). Responders and non-responders to erenumab did not differ with respect to demographic or headache characteristics. Conclusion: Switching to erenumab in non-responders to a CGRP ligand mAb might be beneficial in a subgroup of resistant patients, with increasing responder rates after 6 months of treatment. Larger prospective studies should aim to predict which subgroup of patients benefit from a switch. [ABSTRACT FROM AUTHOR]

Background: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) are a favourable option for patients with migraine who experience distressful headache disability and fail to respond to traditional preventive treatment options. However, since CGRPmAb has been available for only 2 years in Japan, the difference between good and poor responders remains unknown. We aimed to investigate the clinical characteristics of patients with migraine in Japan who responded well to CGRPmAb based on real-world data. Methods: We analysed patients who visited Keio University Hospital, Tokyo, Japan, between the 12th of August 2021 and 31st of August 2022, and were prescribed one of three CGRPmAbs (erenumab, galcanezumab, and fremanezumab) for more than 3 months. We recorded the patients' basic migraine characteristics, such as pain quality, monthly migraine days (MMD)/monthly headache days (MHD), and the number of prior treatment failures. We defined good responders as patients whose MMDs decreased by more than 50% after 3 months of treatment and other patients as poor responders. We compared the baseline migraine characteristics between the two groups and performed logistic regression analysis based on the items that showed statistically significant differences. Results: In total, 101 patients were considered eligible for the responder analysis (galcanezumab: 57 (56%), fremanezumab: 31 (31%), and erenumab: 13 (13%)). After 3 months of treatment, 55 (54%) patients achieved ≥ 50% reduction in MMDs. Comparisons between ≥ 50% responders and non-responders revealed that age was significantly higher (p = 0.003), and MHD and total prior treatment failures were significantly lower (p = 0.027, 0.040, respectively), in responders than in non-responders. Age was a positive predictive factor, and the total number of prior treatment failures and past medical history of immuno-rheumatologic diseases were negative predictive factors of CGRPmAb responsiveness in Japanese patients with migraine. Conclusions: Patients with migraine who are older, with fewer prior treatment failures and no past history of immuno-rheumatologic disease, may respond well to CGRPmAbs. [ABSTRACT FROM AUTHOR]

Background: Medication-overuse headache is highly prevalent in tertiary care centers. It may be a cause or consequence of the overuse of symptomatic medications for migraine attacks. Objective: We aimed to compare the efficacy of anti-CGRP monoclonal antibodies (mAbs) added to conventional pharmacological treatments in patients with chronic migraine (CM) and medication overuse headache (MOH). Methods: A cross-sectional, prospective, randomized, open study with real- world comparison groups of patients was carried out. The sample consisted of 200 patients with CM and MOH, who received the same approach to withdraw overused medications, started preventative treatment, and either did or did not receive mAbs. Results: A total of 172 patients (126 women and 46 men) were included in the study and divided into two groups: group one consisting of 58 patients (control) and group two of 114 patients who used mAbs added to conventional pharmacological agents. The mean age was 44.1 ± 13.6 years, ranging from 18 to 78 years. In the 3 months follow-up after starting the treatment, both groups presented headache frequency reduction, but those with monoclonal antibodies had a significantly higher reduction in the number of headache days and symptomatic medication intake when compared to the control (p < 0.0001). Conclusions: The addition of an anti-CGRP monoclonal antibody to the treatment formedication overuse headaches in chronicmigraineursmay result in decreasing headache frequency and symptomatic medication use when compared to conventional treatments with drugs. [ABSTRACT FROM AUTHOR]

Background: Direct comparisons of the tolerability and safety of migraine preventive treatments targeting the calcitonin gene-related peptide pathway are lacking. This study aimed to compare the safety and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies and gepants in migraine prevention. Methods: A network meta-analysis of phase 3 randomized controlled trials assessing the safety and tolerability of anticalcitonin gene-related peptide monoclonal antibodies (erenumab, eptinezumab, fremanezumab, or galcanezumab) and gepants (atogepant, rimegepant) in migraine prevention was performed. Primary outcomes were treatment-emergent adverse events and serious adverse events. Secondary outcomes included any adverse events, adverse events leading to treatment discontinuation and individual adverse events. Results: We included 19 randomized controlled trials, comprising 14,584 patients. Atogepant 120mg (OR 2.22, 95% CI [1.26, 3.91]) and galcanezumab 240 mg (OR 1.63, 95% CI [1.33, 2.00]) showed the largest odds of treatment-emergent adverse events compared to placebo. While eptinezumab 30 mg had greater odds of adverse events leading to treatment discontinuation (OR 2.62, 95% CI [1.03,6.66]). No significant differences in serious adverse events were found between active treatments and placebo. Eptinezumab was associated with the lowest odds of treatment-emergent adverse events and serious adverse events compared to placebo, whereas erenumab was associated with the lowest odds of any adverse events and quarterly fremanezumab with the lowest odds of treatment discontinuation due to adverse events. Conclusion: Monoclonal antibodies targeting the calcitonin gene-related peptide pathway and gepants are a safe and well tolerated option for migraine prevention. [ABSTRACT FROM AUTHOR]

Objective: To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk. Background: Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene‐related peptide pathway in migraine management, particularly in a patient population with pre‐existing CV risk factors. Methods: Data pooled from four double‐blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10‐year risk of cardiac, cerebrovascular, and peripheral artery disease as no‐risk‐factors, low‐risk (>0% to ≤10%), moderate‐risk (>10% to ≤20%), and high‐risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE). Results: There was no apparent difference between placebo‐ (N = 1032) and erenumab‐treatment groups (70 mg, N = 885; 140 mg, N = 504) in clinical worsening of BP category from baseline to Months 1–3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long‐term analysis. Erenumab‐treated patients with high and moderate 10‐year CV risk (N = 107) did not experience any ICCAEs during the double‐blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low‐risk erenumab group (N = 273). There were no increases in AEs during the long‐term extensions of up to 5 years (N = 2499; 3482 patient‐years of exposure to erenumab) with exposure‐adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient‐years) for no risk factor (N = 1805), low (N = 492), moderate (N = 121), and high (N = 81) 10‐year CV risk groups, respectively. Conclusions: Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10‐year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess erenumab efficacy in migraine disability and intensity throughout the first treatment cycle, discontinuation, and the first 6 months of re-treatment in patients with high-frequency episodic migraine. The study design was retrospective and observational. Inclusion criteria were the following: diagnosis of high-frequency episodic migraine and ongoing treatment with erenumab 140 mg currently at their second treatment cycle. Data regarding migraine frequency, disability (MIDAS score), and severity of attacks (NRS score) were collected quarterly. Twenty-five patients were enrolled. At the end of the first treatment cycle, compared to baseline, a significant improvement of MIDAS scores was found (13.5 ± 11.1 vs. 72.5 ± 32.1; p = 0.005), with a subsequent worsening during treatment suspension (30.1 ± 26.9; p = 0.03). Pain intensity remained unmodified during the first treatment cycle (NRS score baseline: 7.6 ± 0.9 vs. 12 months: 7.5 ± 0.7; p = 0.13). During re-treatment, MIDAS scores documented a new significant improvement, reaching the same level at 6 months of re-treatment as at the end of the first cycle (30.1 ± 26.9 vs. 12.9 ± 5.4; p = 0.03). A significant improvement, compared to baseline, was observed for pain intensity during re-treatment (6.8 ± 2.2 vs. 5.6 ± 0.9 at RT3 vs. 5.2 ± 1.4 at RT6; p = 0.05). In conclusion, during re-treatment with erenumab 140 mg, migraine pain intensity and disability documented a significant and progressive improvement. Our data confirm the long-term efficacy, although in a very limited case series, of monoclonal antibodies targeting CGRP beyond headache frequency reduction. [ABSTRACT FROM AUTHOR]

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