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Background and purpose: HER‐MES was the first head‐to‐head study of erenumab against topiramate (standard of care). This post hoc analysis of the HER‐MES study evaluated the effect of erenumab versus topiramate on patient‐reported outcomes at week 24. Methods: Adult patients with episodic or chronic migraine (n = 777) were randomized (1:1) to monthly subcutaneous erenumab (n = 389) or daily oral topiramate (n = 388). Migraine‐related disability, as measured by the Headache Impact Test 6 (HIT‐6) and Short Form 36 Health Survey version 2 (SF‐36v2), was analysed in the entire study cohort and true completers. Results: In the erenumab group (vs. topiramate), significant improvements were reported in Headache Impact Test 6 total scores (composite populations, −10.88 vs. −7.72; true completers, −11.92 vs. −10.61) and a higher proportion of patients achieved a ≥5‐point reduction from baseline with erenumab (composite populations, 72.2% vs. 53.9%; true completers, 79.64% vs. 71.43%). The adjusted mean change from baseline in the SF‐36v2 score was greater with erenumab for both physical component summary (composite population, 5.48 vs. 3.63; true completers, 5.95 vs. 5.23) and mental component summary (composite populations, 1.00 vs. −1.18; true completers, 1.74 vs. −0.33). A higher proportion of patients on erenumab versus topiramate had a ≥5‐point improvement in SF‐36v2 for the physical component summary (composite populations, 47.7% vs. 37.4%; true completers, 52.1% vs. 48.9%) and mental component summary (composite populations, 25.3% vs. 16.8%; true completers, 27.3% vs. 17.7%). Conclusions: This post hoc analysis demonstrated that patients treated with erenumab had significant improvements in headache impact and quality of life as measured by patient‐reported outcomes versus patients treated with topiramate. [ABSTRACT FROM AUTHOR]

Introduction: To provide real-world insights into migraine patient population in Germany treated with erenumab, focusing on the prescription patterns and reasons for the initial dosage choice. Methods: SPECTRE was an observational, non-interventional, multicenter, open-label, single-arm study in patients treated with erenumab according to approved local dose and guidelines. The study enrolled adult patients (n = 571; Germany: 105 sites) with migraine who had received erenumab for not more than 3 months before the start of the study. Results: The mean (standard deviation) patient age was 45.0 (12.3) years, and most patients were female (89.0%), Caucasian (97.6%), and non-smokers (85.1%). The starting dose of erenumab was 70 mg in 68.5% of patients and 140 mg in 31.5%. The proportion of patients with 140 mg as the starting dose was the highest (43.5%) in those aged 30–40 years. The most common reason for starting a higher dose of erenumab 140 mg was severity of migraine (47.4%). During the observational period, the proportion of patients taking erenumab 140 mg increased to 64.6% (visit 5; V5) after 12 months. Due to attrition of patients towards the end of the study (V9: 90 participants), data at V9 must be interpreted with caution. At least one dose change was performed in 45.3% of patients (i.e., erenumab 70 to 140 mg or 140 to 70 mg), 21.2% of patients attempted at least once to discontinue treatment (i.e., period with erenumab discontinuation and no other antibody treatment for migraine prevention), and 15.3% discontinued erenumab treatment, mainly because of no or insufficient treatment response (13.5%). The mean time until the first omission attempt was 332.3 (range 37–633) days. Constipation (12.1%) was the most frequently reported adverse event, in line with the summary of product characteristics (SmPC) of erenumab. Conclusion: Most patients with migraine were prescribed erenumab 70 mg as the starting dose. No new safety signals were observed for erenumab versus the previous trials. Plain Language Summary: Erenumab, a fully human monoclonal antibody against the calcitonin gene-related peptide receptor, was approved by the US Food and Drug Administration (FDA) and the European Medicines Agency for the prevention of migraine in adults as a monthly treatment with a 70 mg and 140 mg dose. SPECTRE was a multicenter, open-label, prospective non-interventional observational study in patients treated with erenumab as per local approved dose and clinical practice. The study was aimed at providing real-world insights into migraine patient population in Germany treated with erenumab, focusing on the prescription patterns and reasons for the initial dosage choice. Of the 571 enrolled patients (mean age: 45.0 years; Germany: 105 sites), 556 were included in the full and safety analysis. In the majority of the patients (68.5%) erenumab was initiated using the lower starting dose of 70 mg (erenumab 140 mg: 31.5% of patients). Patients (43.5%) who started with erenumab 140 mg were most frequently 30–40 years old, which represents the second youngest age group in the study. In total, 776 adverse events (AE) were reported in 294 patients (52.9%). According to the Summary of Product Characteristics of erenumab, the most frequent AE was constipation (12.1%). Safety data were in accordance with the known safety profile of erenumab. Data from the SPECTRE study reveal the real-world treatment patterns and disease characteristics of migraine patients in Germany who were treated with erenumab. [ABSTRACT FROM AUTHOR]

Background: Monoclonal antibodies targeting calcitonin gene-related peptide (anti-CGRP mAbs) have shown clinical effectiveness and safety in randomized clinical studies. However, long-term studies in clinical practice remain limited. Aim: To assess the long-term effectiveness, clinical predictors and safety of three anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab) in resistant migraine patients. Method: A single-center retrospective study was conducted from December 2019 to June 2023 involving 120 resistant migraine patients who received at least a month of anti-CGRP mAbs treatment. Patients completed a headache diary that included monthly acute medication intake (MAM), monthly migraine days (MMD), adverse events as well as completed Patient-Reported Outcome questionnaires (MIDAS [Migraine Disability Assessment] and Headache Impact Test 6 [HIT-6]). The number of patients achieving a ≥ 50% reduction in monthly migraine days was determined and classified as ≥ 50% responders, and baseline parameters and logistic regression between responders and non-responders were analyzed to identify potential predictors of response. Adverse events were registered in every follow-up. Results: Treatment with anti-CGRP mAbs led to reductions in MIDAS, HIT-6, MMD and MAM from baseline to 6–24 months. At 6–12 months, responders (61% and 57%, respectively) exhibited lower baseline MMD and MAM. Medication overuse was associated with non-responders from 6 to 24 months and it was identified as a negative predictor of treatment effectiveness (OR 0.23, 95% CI 0.07–0.74; p = 0.014). Conclusion: Anti-CGRP mAbs prove effectiveness and safety over a 24-month period in a RM population. Patients with no medication overuse and lower basal MMDs and MAM may respond better to anti-CGRP mAbs. [ABSTRACT FROM AUTHOR]

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

Introduction: The term 'refractory migraine' (RM) is commonly used in clinical settings; however, it is not recognized in the International Classification of Headache Disorders, third edition. A growing need for a shared definition of refractoriness has been highlighted by a multidisciplinary expert group. Although definitions for RM currently exist, the key parameters for the definition of refractoriness (e.g., unresponsiveness to treatment, high frequency, severe disability, or all of these features) remain contentious. Thus, a consensus on the definition of RM is crucial. Methods: Calcitonin gene‐related peptide (CGRP) is a neuropeptide that plays an important role in migraine pathophysiology and is a target for migraine preventive therapies. Monoclonal antibodies targeting the CGRP (i.e., galcanezumab, fremanezumab, and eptinezumab) and its receptor (erenumab) have shown consistent efficacy for migraine prophylaxis with excellent safety profiles. Their effect on refractory cases has also been reported, offering promise to the many patients who have not found relief with existing treatments. Therefore, we anticipate a paradigm shift in migraine treatment. Results: Following the widespread use of monoclonal antibodies targeting the CGRP and its receptor, the European Headache Federation proposed a definition for two subsets of difficult‐to‐treat migraine—resistant and refractory migraine—that considers both the frequency and disability caused by single and frequent attacks. Conclusion: We expect that this definition will help resolve previous conflicts that have limited the use of earlier definitions. [ABSTRACT FROM AUTHOR]

Background: While monoclonal antibodies (mAbs) targeting the CGRP pathway have revolutionized migraine management due to their improved tolerance and adherence, concerns remain about their potential impact on blood pressure (BP), especially in older patients, due to CGRP-mediated vasodilation blockade. Given the growing use of these therapies in older populations, assessing their cardiovascular (CV) safety is of paramount importance. Methods: This multicentric observational prospective study focused on migraine sufferers aged ≥ 60 who began erenumab, galcanezumab, or fremanezumab for prevention. Baseline, three-month, and twelve-month BP measurements were collected. Changes in antihypertensive medication and "Newly or Worsened Hypertensive" patients (NWHP) were assessed. Results: Among 155 patients receiving anti-CGRP mAbs (40 Erenumab, 47 Galcanezumab, 68 Fremanezumab), 42.5% had hypertension history and 39% were on antihypertensive treatment. No significant systolic or diastolic BP changes occurred at any time point compared to baseline (all p > 0.05), with no differences between the three groups. After one year, 20/155 (12.9%) patients were considered NWHP; 11/20 had prior hypertension, and 5/11 adjusted antihypertensive therapy. Among 9/20 newly hypertensive patients, 5/9 had a single measurement above the normal threshold with no requirement for new pharmacological therapy. A higher baseline BP value was associated with increased BP (p = 0.002). Conclusions: The study concludes that treatment with anti-CGRP mAbs over one year does not significantly affect BP in patients aged ≥ 60, nor does it increase the incidence of hypertension compared to general population trends. Nonetheless, continuous monitoring and further long-term studies are necessary to fullya scertain the cardiovascular safety of these medications in the elderly. [ABSTRACT FROM AUTHOR]

ABSTRACT Pyoderma gangrenosum (PG) is a rare necrotizing neutrophilic dermatosis driven by monokines and cytokines elaborated by monocytes and autoreactive T cells, respectively. Th1‐mediated autoimmune disorders and myeloproliferative disease are among the potential disease associations. More recently, certain medications were implicated, including TNF‐alpha inhibitors, rituximab, and IL‐17A inhibitors, such as secukinumab, where the development of PG is held to represent a cutaneous immune adverse effect. We present two patients who developed an autoinflammatory syndrome resembling PG in the setting of drug therapy with agents exhibiting an IL‐17A inhibitory effect. The drugs were erunumab in one and secukinumab in the other. One patient received the anti‐calcitonin gene‐related peptide targeted therapy, erenumab, for migraine prophylaxis. While this drug has not been previously implicated in the development of PG, it can cause IL‐17A blockade. The other patient was on secukinumab, a monoclonal antibody that selectively targets IL‐17A. We documented a microenvironment enriched in IL‐17A, emphasizing that the blockade impacts the functionality of the receptor as opposed to a quantitative reduction in IL‐17A production by T cells. Qualitative functional IL‐17A blockade could result in a paradoxical increase in IL‐23, a pro‐inflammatory cytokine that may contribute to the influx of neutrophils pathogenetically implicated in PG. [ABSTRACT FROM AUTHOR]

Background: Migraine patients unresponsive to calcitonin gene-related peptide (CGRP)(-receptor, -R) monoclonal antibodies (mAbs) may benefit from switching between CGRP(-R) mAbs. However, some patients do not tolerate or respond to any subcutaneous mAbs. This study evaluates the efficacy of the intravenous CGRP mAb eptinezumab in these therapy-refractory patients. Methods: In this retrospective cohort study, patients with migraine who previously failed erenumab and at least one CGRP mAb (fremanezumab and/or galcanezumab) received eptinezumab 100 mg, followed by a second dose of 100 mg or 300 mg after 12 weeks. Monthly headache days, monthly migraine days, acute medication days, and migraine pain intensity were recorded from standardized headache diaries during the four weeks before the first infusion (baseline), and during weeks 9–12 and 21–24 of treatment. Patient-reported outcomes were analyzed at baseline, weeks 12, and 24. Results: From January 2023 to February 2024, 41 patients received eptinezumab 100 mg. Of these, 38 (93%) received a second infusion after 12 weeks, with 29 (71%) increasing the dose to 300 mg. The percentage of patients with a ≥30% reduction rate in monthly migraine days was 23.1% at week 12 and 29.7% at week 24. Monthly migraine days decreased from 16.3 ± 8.0 at baseline to 15.4 ± 8.1 days during weeks 9–12 and 14.4 ± 8.0 days during weeks 21–24 (p = 0.07). During weeks 21–24, 38.5% reported a clinically meaningful reduction in HIT-6 scores and 52.4% in MIDAS scores. No adverse events were reported. Conclusions: Eptinezumab may be an effective and well-tolerated option for some treatment-refractory migraine patients unresponsive to subcutaneous CGRP-(R) mAbs. [ABSTRACT FROM AUTHOR]

Introduction: Erenumab-aooe is approved for the preventive treatment of migraine in adults. Recent publications have evaluated migraine medication use during the 6 months after starting erenumab, but longer-term follow-up data are limited. The objective of this study was to describe 12-month medication use and changes in healthcare resource utilization (HRU) and associated direct costs among patients initiating erenumab. Methods: We identified adult patients with an erenumab claim in the Merative MarketScan Commercial and Medicare Databases from May 2018 through September 2019. Eligible patients had ≥ 12 months of continuous medical and pharmacy coverage before (pre-index period) and after (post-index period) the index date (first erenumab claim) in addition to pre-index evidence of migraine. Patients were stratified by post-index-period adherence to erenumab, defined as ≥ 80% of days covered (adherent) or < 80% of days covered (non-adherent). Outcomes were measured pre- and post-index, and differences between these periods were described. Results: Among 7528 eligible patients, the mean (standard deviation) age was 45.1 (11.4) years and 85.4% were female; 38.5% of patients were adherent to erenumab. Most patients used acute or traditional migraine-preventive medications pre-index, with reductions in use observed post-index (acute medication was used by 95.6% of patients pre-index, compared to 92.3% post-index; traditional preventive medication was used by 89.6% of patients pre-index, compared to 81.9% post-index). Reductions were observed for HRU of emergency room visits (− 3.8%) and brain- and other head-imaging studies (− 7.5%). Overall costs associated with acute and traditional preventive medications were reduced (− $764), but costs for HRU increased slightly ($76). When stratifying by adherence and combining costs for acute and traditional preventive medications and HRU, adherent patients had cost decreases (− $1947), while non-adherent patients had cost increases ($101). Conclusion: Most patients initiating erenumab had prior use of acute and traditional migraine-preventive therapies. The reduction in acute and traditional migraine-preventive medication use and HRU over the 12-month follow-up supports the long-term clinical benefits of erenumab in the real-world setting. [ABSTRACT FROM AUTHOR]

Background and Objectives: Migraine is a chronic neurological disorder affecting approximately 14% of the global population. Beyond physical pain, migraines significantly impact individuals' quality of life, influencing education, employment, and income levels. Topiramate, a second-generation antiepileptic medication, has demonstrated notable efficacy in reducing the occurrence of chronic migraine. Over the past three decades, extensive research has implicated the neuropeptide calcitonin gene-related peptide (CGRP) in migraine pathogenesis. Erenumab, the first FDA-approved CGRP inhibitor, received approval in 2018. This study aims to compare the clinical efficacy of Erenumab and Topiramate for migraine prevention. Materials and Methods: We conducted a retrospective cohort study of adults with episodic or chronic migraine over a 12-month period, comparing Erenumab (n = 52) and Topiramate (n = 56). Outcomes assessed included changes in the Migraine Disability Assessment (MIDAS) scores from baseline over the last three months of treatment and the proportion of patients achieving a ≥50% reduction in MIDAS scores by the end of the study. Results: The Erenumab group showed significant improvement, with nearly 79% of patients achieving a 50% reduction in their MIDAS score, with a mean reduction of 3.76. Notably, only two patients (3.8.5) discontinued treatment due to adverse events. In contrast, the Topiramate group had over 15% of patients achieve a 50% reduction in MIDAS scores, with a mean reduction of 5.89, and a had discontinuation rate of 14.2% due to adverse events. Conclusions: Both Topiramate and Erenumab are effective for migraine prevention. However, Topiramate has lower tolerability and more side effects, while Erenumab offers better tolerability and safety at a higher cost. Treatment decisions should be individualized based on patient needs, efficacy, safety, and cost considerations. [ABSTRACT FROM AUTHOR]

Abstract Introduction To provide real-world insights into migraine patient population in Germany treated with erenumab, focusing on the prescription patterns and reasons for the initial dosage choice. Methods SPECTRE was an observational, non-interventional, multicenter, open-label, single-arm study in patients treated with erenumab according to approved local dose and guidelines. The study enrolled adult patients (n = 571; Germany: 105 sites) with migraine who had received erenumab for not more than 3 months before the start of the study. Results The mean (standard deviation) patient age was 45.0 (12.3) years, and most patients were female (89.0%), Caucasian (97.6%), and non-smokers (85.1%). The starting dose of erenumab was 70 mg in 68.5% of patients and 140 mg in 31.5%. The proportion of patients with 140 mg as the starting dose was the highest (43.5%) in those aged 30–40 years. The most common reason for starting a higher dose of erenumab 140 mg was severity of migraine (47.4%). During the observational period, the proportion of patients taking erenumab 140 mg increased to 64.6% (visit 5; V5) after 12 months. Due to attrition of patients towards the end of the study (V9: 90 participants), data at V9 must be interpreted with caution. At least one dose change was performed in 45.3% of patients (i.e., erenumab 70 to 140 mg or 140 to 70 mg), 21.2% of patients attempted at least once to discontinue treatment (i.e., period with erenumab discontinuation and no other antibody treatment for migraine prevention), and 15.3% discontinued erenumab treatment, mainly because of no or insufficient treatment response (13.5%). The mean time until the first omission attempt was 332.3 (range 37–633) days. Constipation (12.1%) was the most frequently reported adverse event, in line with the summary of product characteristics (SmPC) of erenumab. Conclusion Most patients with migraine were prescribed erenumab 70 mg as the starting dose. No new safety signals were observed for erenumab versus the previous trials.

Abstract Background Efficacy and safety of human monoclonal antibody erenumab used for migraine prophylaxis have been shown in clinical studies. APOLLON is an open-label, multi-center, single arm study, which permits dose adjustments of erenumab and includes an option for a drug holiday. The findings contribute to the accumulating long-term evidence regarding erenumab’s tolerability and safety profile in individuals experiencing episodic and chronic migraines. Methods The study population consisted of adult patients with episodic or chronic migraine, who had successfully completed the HER-MES study (NCT03828539). Patients were treated with erenumab for 128 weeks at a flexible dose of either 70 mg or 140 mg. Treatment discontinuation attempts were allowed as voluntary single treatment interruption (‘drug holiday’) of up to 24 weeks. Results 701 patients were enrolled in APOLLON. The exposure associated incidence rate (EAIR) of adverse events (AEs) (N = 601) per 100 subject years was 101.71 (95% CI [92.28; 111.14]) meaning a patient could expect having about one adverse event per each year of treatment. EAIR was higher in females (n = 524, EAIR: 104.40, 95% CI [93.93; 114.86]) than in males (n = 77, EAIR: 86.55, 95% CI [65.39; 107.71]) and increased with initial monthly migraine days (MMD) and prior prophylactic treatment failures. A total of 155 patients discontinued erenumab treatment during open-label treatment phase. Of these, 29 were due to AEs (4.1% of total cohort) and out of these 65.5% (N = 19) were considered treatment-related. Safety parameters were in line with HER-MES data and did not reveal new safety signals. Drug holidays were realized by 108 patients (15.4%), of which 64.8% (N = 70) returned to treatment. The mean number of monthly headache days (MHDs), MMDs, and days with acute headache medication significantly increased during drug holiday. After resumption of erenumab treatment, a rapid reduction of the migraine parameters was observed. Conclusions APOLLON provides long-term safety and tolerability data confirming the beneficial safety profile of erenumab over a period of 128 weeks. In addition, reversibility of migraine deterioration during drug holiday was shown and most patients returned to their treatment with similar response rates compared to initial treatment. Trial registration ClinicalTrials.gov ID: NCT04084314 ( https://clinicaltrials.gov/study/NCT04084314 ), First submitted: 2019-09-06.

Abstract Introduction Erenumab-aooe is approved for the preventive treatment of migraine in adults. Recent publications have evaluated migraine medication use during the 6 months after starting erenumab, but longer-term follow-up data are limited. The objective of this study was to describe 12-month medication use and changes in healthcare resource utilization (HRU) and associated direct costs among patients initiating erenumab. Methods We identified adult patients with an erenumab claim in the Merative MarketScan Commercial and Medicare Databases from May 2018 through September 2019. Eligible patients had ≥ 12 months of continuous medical and pharmacy coverage before (pre-index period) and after (post-index period) the index date (first erenumab claim) in addition to pre-index evidence of migraine. Patients were stratified by post-index-period adherence to erenumab, defined as ≥ 80% of days covered (adherent) or

Abstract Background Management of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year. Methods A retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed. Results All groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy. Conclusions Our data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO. Trial registration No registration, retrospective analysis. Graphical Abstract

Background: Efficacy and safety of human monoclonal antibody erenumab used for migraine prophylaxis have been shown in clinical studies. APOLLON is an open-label, multi-center, single arm study, which permits dose adjustments of erenumab and includes an option for a drug holiday. The findings contribute to the accumulating long-term evidence regarding erenumab's tolerability and safety profile in individuals experiencing episodic and chronic migraines. Methods: The study population consisted of adult patients with episodic or chronic migraine, who had successfully completed the HER-MES study (NCT03828539). Patients were treated with erenumab for 128 weeks at a flexible dose of either 70 mg or 140 mg. Treatment discontinuation attempts were allowed as voluntary single treatment interruption ('drug holiday') of up to 24 weeks. Results: 701 patients were enrolled in APOLLON. The exposure associated incidence rate (EAIR) of adverse events (AEs) (N = 601) per 100 subject years was 101.71 (95% CI [92.28; 111.14]) meaning a patient could expect having about one adverse event per each year of treatment. EAIR was higher in females (n = 524, EAIR: 104.40, 95% CI [93.93; 114.86]) than in males (n = 77, EAIR: 86.55, 95% CI [65.39; 107.71]) and increased with initial monthly migraine days (MMD) and prior prophylactic treatment failures. A total of 155 patients discontinued erenumab treatment during open-label treatment phase. Of these, 29 were due to AEs (4.1% of total cohort) and out of these 65.5% (N = 19) were considered treatment-related. Safety parameters were in line with HER-MES data and did not reveal new safety signals. Drug holidays were realized by 108 patients (15.4%), of which 64.8% (N = 70) returned to treatment. The mean number of monthly headache days (MHDs), MMDs, and days with acute headache medication significantly increased during drug holiday. After resumption of erenumab treatment, a rapid reduction of the migraine parameters was observed. Conclusions: APOLLON provides long-term safety and tolerability data confirming the beneficial safety profile of erenumab over a period of 128 weeks. In addition, reversibility of migraine deterioration during drug holiday was shown and most patients returned to their treatment with similar response rates compared to initial treatment. Trial registration: ClinicalTrials.gov ID: NCT04084314 (https://clinicaltrials.gov/study/NCT04084314), First submitted: 2019-09-06. [ABSTRACT FROM AUTHOR]

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

Objective Background Methods Results Conclusions To assess changes in real‐world use of acute and preventive medications for migraine over a 12‐month follow‐up period in the United States following initiation of the anti‐calcitonin gene‐related peptide (CGRP) pathway monoclonal antibody (mAb) erenumab.Early assessments of real‐world use of acute and preventive medications for migraine after initiation of erenumab have been limited to 6 months of follow‐up.This retrospective cohort study used data from the IQVIA open‐source longitudinal prescription (LRx) and medical (Dx) claims databases. Adult patients with an initial claim (index date) for erenumab between May 2018 and April 2020 were identified.Among 201,176 patients who met inclusion criteria, the mean (standard deviation [SD]) age was 47.5 (13.8) years and 85.6% (n = 172,153) were female. Most patients used one or more acute (88.4%; n = 177,795) and one or more traditional preventive (86.1%; n = 173,225) medications during the 12‐month pre‐index period. Adherence to erenumab (proportion of days covered [PDC] ≥0.80) was 40.2% (n = 80,927) with an overall mean (SD) PDC of 0.60 (0.34). Among all patients, 70.0% (n = 140,809) discontinued erenumab. After accounting for 24.7% (n = 49,720) of patients who restarted erenumab, discontinuation without reinitiation was observed in 45.3% (n = 91,089) of total patients. Switching to a different anti‐CGRP pathway mAb was observed in 13.1% (n = 26,446) of total patients. Among 177,795 patients with pre‐index use of one or more acute migraine medication class, 86.5% (n = 153,788) had post‐index use of the same class, and 56.7% (87,134/153,788) of them discontinued one or more class of acute medication in the 12‐month follow‐up period. Similarly, among 173,225 patients with pre‐index use of one or more traditional migraine preventive medication class, 67.7% (n = 117,274) had post‐index use of the same class, and 46.7% (54,790/117,274) of them discontinued one or more class of traditional preventive medication in the 12‐month follow‐up period.In this long‐term study, we observed the discontinuation of both acute and preventive medications for migraine post‐erenumab initiation. [ABSTRACT FROM AUTHOR]

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

Objective: The objective of this systematic review and meta-analysis was to determine whether patients with episodic (EM) or chronic migraine (CM), who were treated with anti-CGRP antibodies, showed a reversal from medication overuse (MO) or medication overuse headache (MOH) status at their baseline to non-overuse status. Furthermore, this study aimed to establish which acute headache medication (AHM) categories responded more effectively to anti-CGRP antibodies. Methods: A systematic search was conducted in the PubMed database for relevant studies from January 2013 to September 2023. We included phase three randomized controlled trials to examine the role of anti-CGRP antibodies in patients with EM or CM and their MO status. A meta-analysis was conducted to find the association between anti-CGRP antibodies and the number of EM and CM patients with MO or MOH at baseline that reverted to non-MO status or below the MOH threshold. Results: The initial search yielded a total of 345 studies. After removing duplicates and screening with inclusion criteria, 5 studies fulfilled our conditions. Each study reviewed the response to changes in the MO status of patients after receiving anti-CGRP antibodies, including eptinezumab, fremanezumab, galcanezumab, and erenumab, compared to placebo. Our study analyzed three AHM categories: triptans, simple analgesics, and multiple drugs. The overall relative risk (RR) was 1.44 (95% CI, 1.31 to 1.59; p < 0.001). The RRs for triptans, simple analgesics, and multi-drug groups were 1.71 (95% CI, 1.53 to 1.91; p < 0.001), 1.10 (95% CI, 0.83 to 1.47; p = 0.5), and 1.29 (95%CI 1.14 to 1.46; p < 0.001) respectively. Conclusion: The meta-analysis has shown that anti-CGRP antibodies were statistically significant in transitioning from MO or MOH status to non-MO status or below the MOH threshold (RR = 1.44) for all included studies and all AHM categories except for simple analgesics. Patients from the triptan group had the highest RR of 1.71 with a p-value < 0.001, while the simple analgesics group had an RR of 1.10, however, with a p-value > 0.05. Interestingly, this analysis can be interpreted as that anti-CGRP antibodies might not be effective in reducing simple analgesics use in EM or CM patients. Further studies are needed to investigate these matters. [ABSTRACT FROM AUTHOR]

Background: There are limited real-world data in Switzerland examining the impact of erenumab, a fully human IgG2 monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, on migraine-related quality of life. Objective: This 18-month interim analysis of 172 patients with episodic or chronic migraine from the SQUARE study provides first prospective insights on the impact of mandatory erenumab treatment interruption, following Swiss-reimbursement requirements, in a real-world clinical setting in Switzerland. Findings: Recruited patients receiving 70 or 140 mg erenumab underwent treatment interruption on average 11.2 months after therapy onset with a mean duration of 4 months. There were sustained improvements in mean monthly migraine days (MMD) and migraine disability (mMIDAS) during initial treatment with erenumab. Treatment interruption was associated with a temporary worsening of condition. Symptoms ameliorated upon therapy reuptake reaching improvements similar to pre-break within 3 months. Conclusions: Treatment interruption was associated with a temporary worsening of condition, which improved again after therapy restart. [ABSTRACT FROM AUTHOR]

Migraine is a prevalent headache disorder with a significant impact on the quality of life. This study aims to investigate the effectiveness and safety of erenumab, mAb targeting the CGRP receptor, in treating chronic (CM) and episodic (EM) migraine in clinical practice Kuwait, providing region-specific insights to treatment options. This was a prospective observational cohort study of patients diagnosed with EM or CM treated with erenumab. The primary outcome of the study was to assess the proportion of patients achieving ≥ 50% reduction in monthly mean migraine days, and several changes including the mean number of monthly migraine days, the frequency of analgesic use, attack severity, AEs, and QoL. The study included 151 patients with a mean age of 44.0±11.4 years, and 81.9% female. The primary outcome was achieved in 74.2% of patients, with a significant (p < 0.001) reduction in headache frequency, pain severity, analgesic use, and improvement in QoL. Age and duration of migraine were significant predictors of achieving a ≥ 50% reduction in headache frequency after therapy (OR = 0.955; p = 0.009) and (OR = 0.965; p = 0.025), respectively. Treatment compliance was observed in 76.2% of patients, and 24.5% discontinued treatment. Constipation was the most commonly reported AEs (6.0%), and conservative management was the most common approach to managing AEs. Erenumab was effective in reducing the frequency and severity of migraine attacks and improving QoL, and safe with manageable AEs in a real-world setting in Kuwait. Further research is needed to better understand erenumab's effectiveness and safety in different populations and settings, as well as to compare it with other migraine prophylactic treatments. [ABSTRACT FROM AUTHOR]

Objective Background Methods Results Conclusions We assessed whether the effectiveness of monoclonal antibodies (mAbs) targeting the calcitonin gene‐related peptide (CGRP) pathway changes according to the duration of chronic migraine (CM) over 12 months.In most patients, CM is a progressive disease starting with episodic migraine. Longer CM duration might be associated with more difficult treatment, probably because the mechanisms underlying chronicization are strengthened. Therefore, early treatment of CM could lead to better outcomes compared with later treatment.This cohort study included individuals with CM treated with anti‐CGRP mAbs in two tertiary headache centers from April 2019 to May 2023. The primary outcome included a change in monthly migraine days (MMDs) from baseline to the third trimester of treatment, 10–12 months. Secondary outcomes established whether response to anti‐CGRP mAbs has a more rapid onset in individuals with shorter CM duration compared with longer duration; they included change in MMDs, monthly headache days (MHDs), and days and number of intakes of acute medication during each trimester compared to baseline. Additional outcomes included persisting MMDs, MHDs, and days and number of intakes of acute medication during each trimester of treatment. Patients were compared across tertiles of the overall CM duration.The study included 335 individuals with CM, with a median (interquartile range [IQR]) age of 48 (39–57) years; 270 (80.6%) were women. Patients in the highest tertile of CM duration (aged 18–60 years) were older than patients in the lower duration tertiles (0–7 years and 8–18 years, respectively), with a median (IQR) age of 56 (48–64) years compared with 42 (31–50) years, and 48 (39–56)years, respectively (p = 0.025); however, this difference was likely due to a correlation between age and disease duration. The change in MMDs from baseline to the last trimester of treatment (10–12 months) was comparable across tertiles of CM duration (median [IQR] −12 [−18 to −5] days, −12 [−17 to −6] days, and −12 [−18 to −4] days; p = 0.946). No difference emerged in secondary outcomes, suggesting a similar time to onset of anti‐CGRP mAbs effect across all tertiles of CM duration.Our data showed that anti‐CGRP mAbs are effective and have a rapid onset of action in CM regardless of disease duration. [ABSTRACT FROM AUTHOR]

Background: This preliminary retrospective cohort study investigates the potential additive prophylactic effect of erenumab, a fully human monoclonal antibody that blocks the calcitonin gene-related peptide receptor, in combination with ongoing onabotulinumtoxin A (onaBoNT-A) treatment in patients suffering from chronic migraine. Methods: The study included 218 patients and investigated the effects of adding erenumab to the existing treatment regimen. The primary outcome was the MIDAS (Migraine Disability Assessment) score assessed 3 months after the introduction of erenumab. Results: The results indicated a significant improvement of the MIDAS score, suggesting a reduction in migraine-related disability following the addition of erenumab to onaBoNT-A. In the inter group comparison, dual therapy showed a significantly greater reduction of the MIDAS when compared to a switch from onaBoNT-A to erenumab monotherapy, but not compared to initiation of onaBoNT-A monotherapy. It is hypothesized that the observed additive effects are due to the independent modes of action of erenumab and onabotulinumtoxin A. Conclusion: This study suggests that the combination of erenumab with onaBoNT-A may offer an improved approach for the treatment of chronic migraine in selected patients. However, the results highlight the need for prospective, controlled studies to validate these findings and determine the optimal combination of treatments tailored to the individual patient. [ABSTRACT FROM AUTHOR]

Background: Management of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year. Methods: A retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed. Results: All groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy. Conclusions: Our data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO. Trial registration: No registration, retrospective analysis. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this real‐life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion. Background: The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment. Methods: Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non‐steroidal anti‐inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis. Results: A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre‐treatment in MHDs (28.0 vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non‐converters than in converters, as was the percentage of patients with anxiety. Conclusions: High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion. [ABSTRACT FROM AUTHOR]

Background. Migraine is the second most incapacitating disease and is accompanied by multiple comorbidities, especially in chronic migraines. Migraine treatment and improvement of the patients’ quality of life are an important clinical issue. The calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are the first target therapy for migraine. To date, there are no published data on the duration of effect after using mAbs. Aim. To determine the effect duration after cessation of erenumab treatment in patients with migraine. Methods. The study included 64 patients with migraine, who received at least three doses of erenumab; treatment was stopped when reduction of the headache frequency by at least 30% was achieved. The frequency of headache and migraine were assessed 1, 3 and 6 months after the end of treatment. Results. There was a significant increase in the frequency of headache compared to the values reported at the end of treatment, however, the rates were still significantly lower compared to the baseline values. In some patients, no increase in headache frequency following discontinuation of treatment was observed.

Abstract Background Migraine lacks biomarkers that can trace the biological pathways of the disease and predict the effectiveness of treatments. Monoclonal antibodies targeting calcitonin gene-related peptide pathway – including erenumab – offer the opportunity of investigating potential migraine biomarkers due to their specific mechanism of action in preventing both episodic (EM) and chronic (CM) migraine. Our study aims at evaluating the expression levels of circulating microRNAs (miRNAs) according to migraine type, before and after treatment with erenumab and based on treatment response, in order to identify miRNAs with potential role as epigenetic biomarkers. Methods The study included women aged 25–50 years with EM or CM treated with erenumab according to clinical indications. MiRNAs expression levels were assessed before (baseline) and after a 16-week treatment with erenumab, 140 mg every four weeks (post-treatment). An extensive miRNAs profiling was performed by qRT-PCR in small, pooled groups of ≤ 8 women each, classified according to migraine frequency (EM and CM) and the degree of response to erenumab. The expression levels of selected miRNAs were also validated using single miRNA assays in each woman with EM and CM. Results During the study, 36 women with migraine (19 with EM and 17 with CM) out of 40 who were initially screened, performed the assessment of miRNA expression at baseline and post-treatment, Erenumab treatment significantly improved migraine burden in both EM and CM. MiRNA profiling revealed differential expression levels of a wide set of miRNAs (hsa-let-7d-3p, hsa-miR-106b-3p, hsa-miR-122-5p, hsa-miR-143-3p, hsa-miR-144-3p, hsa-miR-16-5p, hsa-miR-181a-5p, hsa-miR-221-3p, hsa-miR-25-3p, hsa-miR-29b-2-5p, hsa-miR-326, miR-363-3p, hsa-miR-424-5p, hsa-miR-485-3p, hsa-miR-532-5p, hsa-miR-543, hsa-miR-629-5p, hsa-miR-660-5p, hsa-miR-92a-3p) depending on treatment response. Among them, single miRNA assays confirmed the progressive decrease of hsa-miR-143-3p expression levels in relation to increasing response to erenumab in women with EM (7 with low, 6 with medium, and 6 with high response; p = 0.02). Additionally, single assays showed higher hsa-miR-34a-5p and hsa-miR-382-5p expression levels at baseline in women with CM compared with those with EM (p = 0.0002 and p = 0.0007, respectively), as well as their expression level decrease in women with CM from baseline to follow-up (p = 0.04 and p = 0.02, respectively). Conclusions Our study suggests that targeting the CGRP pathway in migraine changes the expression levels of certain miRNAs. These miRNA levels are linked to the levels of response to CGRP receptor blockage. Future research challenges include assigning specific functions to the modulated miRNAs to unravel pathways modulated by the disease and the treatment. Trial registration The study was registered in clinicaltrials.gov with code NCT04659226 and in the Novartis database with code CAMG334AIT05T.

Background and Purpose: Multiple drugs targeting the calcitonin gene‐related peptide (CGRP) receptor have been developed for migraine treatment. Here, the effect of the monoclonal antibody erenumab on CGRP‐induced vasorelaxation was investigated in human isolated blood vessels, as well as the effect of combining erenumab with the small molecule drugs, namely rimegepant, olcegepant, or sumatriptan. Experimental Approach: Concentration–response curves to CGRP, adrenomedullin or pramlintide were constructed in human coronary artery (HCA) and human middle meningeal artery (HMMA) segments, incubated with or without erenumab and/or olcegepant. pA2 or pKb values were calculated to determine the potency of erenumab in both tissues. To study whether acutely acting antimigraine drugs exerted additional CGRP‐blocking effects on top of erenumab, HCA segments were incubated with a maximally effective concentration of erenumab (3 μM), precontracted with KCl and exposed to CGRP, followed by rimegepant, olcegepant, or sumatriptan in increasing concentrations. Key Results: Erenumab shifted the concentration‐response curve to CGRP in both vascular tissues. However, in HCA, the Schild plot slope was significantly smaller than unity, whereas this was not the case in HMMA, indicating different CGRP receptor mechanisms in these tissues. In HCA, rimegepant, olcegepant and sumatriptan exerted additional effects on CGRP on top of a maximal effect of erenumab. Conclusions and Implications: Gepants have additional effects on top of erenumab for CGRP‐induced relaxation and could be effective in treating migraine attacks in patients already using erenumab as prophylaxis. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusions Erenumab is a fully human monoclonal antibody that selectively targets the calcitonin gene–related peptide receptor. It has been proven to be safe and efficacious in patients with episodic migraine (EM) and chronic migraine (CM) as demonstrated in phase 2 and 3 clinical trials including patients from Europe, Japan, and the United States. Reversion from CM to EM, as indicated by a reduction in the frequency of headache days, is an important indicator for efficacy outcome, though it has not been analyzed widely in patients with CM to date.Primary results of the DRAGON study demonstrated the efficacy and safety of erenumab in patients with CM from China and other Asian countries. This post hoc analysis evaluated the rate of reversion from CM to EM in the overall population and in subgroups of patients defined by baseline demographic and clinical characteristics (age, body mass index, gender, prior preventive treatment failure, medication overuse status, and disease duration).Reversion from CM to EM was defined as a reduction in headache frequency to < 45 headache days over the 12 weeks of the double‐blind treatment period. In addition, migraine‐related disability and disease impact on functional impairment were assessed within each treatment group in reverters and non‐reverters using the Headache Impact Test‐6 (HIT‐6), Migraine Physical Function Impact Diary (MPFID), and modified Migraine Disability Assessment (mMIDAS).Overall, 557 patients with CM were randomized to monthly erenumab 70 mg (n = 279) or placebo (n = 278), of whom 52.3% (146 of 279) treated with erenumab reverted from CM to EM compared to 41.0% (114 of 278) in the placebo group (odds ratio [OR] 1.59, 95% confidence interval: 1.1–2.2; p = 0.007). Treatment with erenumab resulted in a greater mean change (standard error) from baseline in the HIT‐6 total score for reverters versus non‐reverters compared to placebo (erenumab: −9.5 [0.6] vs. −5.1 [0.5]; placebo: −8.9 [0.7] vs. −4.9 [0.5]). A similar pattern was observed for mMIDAS score in erenumab treatment groups versus placebo (erenumab: −22.1 [1.2] vs. −6.3 [1.8]; placebo: −19.9 [1.3] vs. −7.9 [1.6]). Substantial improvements were reported in MPFID‐Physical Impairment (PI) and Everyday Activities (EA) scores in reverters versus non‐reverters in erenumab treatment groups (MPFID‐PI: −5.9 [0.3] vs. −1.9 [0.6]; MPFID‐EA: −7.9 [0.4] vs. −3.4 [0.6]) and in placebo (MPFID‐PI: −5.4 [0.4] vs. −1.0 [0.5]; MPFID‐EA: −7.1 [0.5] vs. −3.2 [0.5]).This analysis demonstrated that a greater proportion of patients treated with erenumab reverted from CM to EM compared to patients treated with placebo. The reversion from CM to EM was reflected by the greater improvements in patient‐reported outcomes in the erenumab group. [ABSTRACT FROM AUTHOR]

Background: Migraine lacks biomarkers that can trace the biological pathways of the disease and predict the effectiveness of treatments. Monoclonal antibodies targeting calcitonin gene-related peptide pathway – including erenumab – offer the opportunity of investigating potential migraine biomarkers due to their specific mechanism of action in preventing both episodic (EM) and chronic (CM) migraine. Our study aims at evaluating the expression levels of circulating microRNAs (miRNAs) according to migraine type, before and after treatment with erenumab and based on treatment response, in order to identify miRNAs with potential role as epigenetic biomarkers. Methods: The study included women aged 25–50 years with EM or CM treated with erenumab according to clinical indications. MiRNAs expression levels were assessed before (baseline) and after a 16-week treatment with erenumab, 140 mg every four weeks (post-treatment). An extensive miRNAs profiling was performed by qRT-PCR in small, pooled groups of ≤ 8 women each, classified according to migraine frequency (EM and CM) and the degree of response to erenumab. The expression levels of selected miRNAs were also validated using single miRNA assays in each woman with EM and CM. Results: During the study, 36 women with migraine (19 with EM and 17 with CM) out of 40 who were initially screened, performed the assessment of miRNA expression at baseline and post-treatment, Erenumab treatment significantly improved migraine burden in both EM and CM. MiRNA profiling revealed differential expression levels of a wide set of miRNAs (hsa-let-7d-3p, hsa-miR-106b-3p, hsa-miR-122-5p, hsa-miR-143-3p, hsa-miR-144-3p, hsa-miR-16-5p, hsa-miR-181a-5p, hsa-miR-221-3p, hsa-miR-25-3p, hsa-miR-29b-2-5p, hsa-miR-326, miR-363-3p, hsa-miR-424-5p, hsa-miR-485-3p, hsa-miR-532-5p, hsa-miR-543, hsa-miR-629-5p, hsa-miR-660-5p, hsa-miR-92a-3p) depending on treatment response. Among them, single miRNA assays confirmed the progressive decrease of hsa-miR-143-3p expression levels in relation to increasing response to erenumab in women with EM (7 with low, 6 with medium, and 6 with high response; p = 0.02). Additionally, single assays showed higher hsa-miR-34a-5p and hsa-miR-382-5p expression levels at baseline in women with CM compared with those with EM (p = 0.0002 and p = 0.0007, respectively), as well as their expression level decrease in women with CM from baseline to follow-up (p = 0.04 and p = 0.02, respectively). Conclusions: Our study suggests that targeting the CGRP pathway in migraine changes the expression levels of certain miRNAs. These miRNA levels are linked to the levels of response to CGRP receptor blockage. Future research challenges include assigning specific functions to the modulated miRNAs to unravel pathways modulated by the disease and the treatment. Trial registration: The study was registered in clinicaltrials.gov with code NCT04659226 and in the Novartis database with code CAMG334AIT05T. [ABSTRACT FROM AUTHOR]

Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs involving migraine patients treated with monoclonal antibodies targeting the calcitonin gene-related peptide system (anti-CGRP MAbs) are currently lacking. Our aim was to analyze the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs. Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA guidelines, for relevant RCTs in either episodic or chronic migraine prevention. Additionally, an adapted version of the 2010 CONSORT statement checklist was utilized. The ROBvis online tool was used to document the risk of bias. Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7–100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning "missing information" arising from the inadequate reporting. Specifically, 50% of the studies (N = 16) were categorized as having inadequate information regarding the randomization process. Conclusions: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology. [ABSTRACT FROM AUTHOR]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of cerebral small vessel disease, caused by a mutation in the NOTCH3 gene on chromosome 19. The main clinical features include migraine (often with aura), early onset, recurrent subcortical ischemic strokes, mood disturbances, and cognitive impairment, frequently leading to dementia and disability with a reduction in life expectancy. Cerebral chronic global hypoperfusion, due to impaired cerebrovascular reactivity, seems to play a primary role in CADASIL. Migraine is the most common early feature of the disease, and to date, there are no consensus guidelines for treatment. Given the vasomodulatory influence of many antimigraine drugs, there is concern about their use in this disease. In particular, the calcitonin gene-related peptide (CGRP) system serves as a vasodilatory protective mechanism during cerebral and cardiac ischemia. Blocking this system could exacerbate ischemic events. Herein, we describe two CADASIL patients who were treated with the calcitonin gene-related peptide (CGRP) receptor antagonist erenumab for chronic migraine, reporting a significant reduction in the frequency of attacks and intensity of pain, and an improvement in quality of life without adverse effects. [ABSTRACT FROM AUTHOR]

Objectives: Migraine is a neurological disease with a high frequency of incidence. The new monoclonal antibodies selective for the calcitonin gene-related peptide and its ligand (anti-CGRP mAbs) have been marketed both in the USA and EU based on the positive efficacy results in the prevention of migraine. This search has been carried out with the aim of collecting real-world evidence on the effectiveness of anti-CGRP mAbs, performing a cost-savings analysis, and comparing performances among anti-CGRP mAbs medicines marketed in the American and European market. Methods: The literature review has been performed in PubMed database on 31 December 2022; the cost of the unitary dose of anti-CGRP mAbs has been extracted consulting an American national database. Results: The results confirm efficacy and good tolerability of anti-CGRP mAbs, determining a difference in the purchase price. In fact, all extracted studies showed a protective risk factor exposure in monthly migraine days reduction for all the anti-CGRP mAbs, whereas the cost analysis showed that using eptinezumab, in a quarter there is a cost saving of at least $425 per patient, compared with the other anti-CGRP mAbs. Conclusions: With equal efficacy and equal safety, anti-CGRP mAbs should be prescribed also regard to the cost established at the negotiation, making sure to guarantee the best treatment to the patients, but at the same time impacting as little as possible to the healthcare services resources. [ABSTRACT FROM AUTHOR]

Background: About 15% to one third of migraineurs experience aura symptoms. Aura is a reversible focal neurological phenomenon involving visual, sensory, speech, and motor symptoms that usually precede migraine pain. Monoclonal antibodies against calcitonin-related peptide (anti- CGRP mAbs) are effective in preventing chronic and episodic migraine, but little is known about their effectiveness on specifically preventing migraine with aura. Methods: This is a pilot prospective observational cohort study, aiming at evaluating the effectiveness and safety of Erenumab, Fremanezumab or Galcanezumab for the treatment of migraine aura. We enrolled 14 patients at the Headache Centre of University Federico II of Naples. Duration of follow-up was 12 months. We assessed mean monthly days with aura symptoms, with or without subsequent headache, as well as mean monthly days with headache and mean monthly MIDAS score, by reviewing standardized paper patient headache diaries every three months. Results: A significant decrease in mean monthly aura days was observed throughout the observation period (median baseline: 13, interquartile range: 4–16; after 12 months: 1, interquartile range: 0–3, p < 0.001). We observed a statistically significant decrease in mean monthly headache days as well (median baseline 21, interquartile range: 16–30; after 12 months: 5, interquartile range: 4–7, p < 0.001). During the 12-month treatment period, none of the 14 patients reported mild or serious adverse events. Conclusion: Our findings suggest that anti-CGRP mAbs are highly effective in migraine with aura, both in reducing mean monthly aura days and mean monthly days with headache. [ABSTRACT FROM AUTHOR]

Objective: To explore the rate of hypertension incoming in patients treated with monoclonal antibodies against the calcitonin gene-related peptide. Background: The monoclonal antibodies blocking the calcitonin gene-related peptide are unquestionable effective in the prevention of migraine. Despite this, the development of hypertension has been detected in some patients. Methods: This was a retrospective study conducted at the University Hospital of Modena. Patients were visited quarterly up to 1 year. Results: Globally, no significant increase in the blood pressure was detected. The 5.7% of the patients developed a significant increase in their blood pressure. In particular, patients with a pre-existing hypertension were more likely to have a significant increase in the blood pressure. Conclusion: The risk of developing hypertension during a treatment with anti-calcitonin gene-related peptide monoclonal antibodies seems low. Anyway, patients with a pre-existing hypertension should be cautiously monitored because they are more likely to develop hypertension. [ABSTRACT FROM AUTHOR]

To describe long-term (24-month) treatment patterns of patients initiating galcanezumab versus standard of care (SOC) preventive migraine treatments including anticonvulsants, beta-blockers, antidepressants, and onabotulinumtoxinA using administrative claims data. This retrospective cohort study, which used Optum de-identified Market Clarity data, included adults with migraine with ≥1 claim for galcanezumab or SOC preventive migraine therapy (September 1, 2018 − March 31, 2020) and continuous database enrollment for 12 months before (baseline) and 24 months after (follow-up) the index date (date of first claim). Baseline patient demographics, clinical characteristics, and treatment patterns were analyzed after 24-month follow-up, including adherence (measured as the proportion of days covered [PDC]), persistence, discontinuation (≥60-day gap), restart, and treatment switch. Propensity score matching (1:1) was used to balance the galcanezumab and SOC cohorts. The study included 2307 matched patient pairs with 24-month follow-up. The mean age across cohorts was 44.5 years (females: ∼87%). Patients in the galcanezumab versus SOC cohort demonstrated greater treatment adherence (PDC: 48% vs. 38%), with more patients considered adherent (PDC ≥80%: 26.6% vs. 20.7%) and persistent (322.1 vs. 236.4 d) (all p <.001). After 24-month follow-up, fewer galcanezumab-treated patients had discontinued compared with SOC-treated patients (80.1% vs. 84.7%; p <.001), of which 41.3% and 39.6% switched to a non-index medication, respectively. The most prevalent medication patients switched to in both cohorts was erenumab. Significantly greater proportions of patients who initiated galcanezumab versus SOC medications switched to fremanezumab (p <.001) and onabotulinumtoxinA (p =.016). Patients who initiated galcanezumab for migraine prevention had higher treatment adherence and persistence compared with those who initiated SOC medications after 24-month follow-up. Only few patients (3 − 13%) with migraine, who qualify for preventive treatment, are using them. Conventional preventive treatments have not been developed specifically for migraine treatment, and more than half of the patients stop using them prematurely. Calcitonin gene-related peptide monoclonal antibodies such as galcanezumab, fremanezumab, and erenumab are newer treatments that provide migraine-specific preventive treatment. Prior studies have compared 6- to 12-month migraine medication use by patients starting galcanezumab versus those starting traditional standard of care (SOC) migraine preventive medications. We compared long-term (24-month) migraine medication use in patients starting galcanezumab versus those starting SOC migraine preventive medications to confirm if the results are sustained over a longer period. Over 24 months, patients who used galcanezumab followed the prescribed treatment regimen to a greater extent compared with those who used SOC medications (48% vs. 38%, respectively). Additionally, patients using galcanezumab continued treatment for a longer time compared with those using SOC. Over 24 months, about 85% of patients stopped taking SOC medications, while around 80% of patients stopped taking galcanezumab. Our findings indicate that patients with migraine are more likely to continue using galcanezumab as a preventive treatment for a longer period compared with SOC medications. This study helps identify gaps in the preventive treatment of migraine and provides insights on how they are not being used enough. [ABSTRACT FROM AUTHOR]

Background: Chronic migraine (CM) is a disabling and hard-to-treat condition, associated with high disability and high cost. Among the preventive treatments, botulinum toxin A (BoNT-a) and monoclonal antibodies against the calcitonin gene-related protein (anti-CGRP mAbs) are the only disease-specific ones. The assessment of the disease burden is complex, and among others, tools such as the allodynia symptoms checklist (ASC-12) and headache impact test (HIT-6) are very useful. This exploratory study analysed the impact of these two therapies on migraine burden. Methods: The RAMO study was a multicentre, observational, retrospective investigation conducted in two headache centres: the Fondazione IRCCS Istituto Neurologico Carlo Besta (Milan) and the Fondazione Policlinico Campus Bio-Medico (Rome). This study involved patients with chronic migraine treated with mAbs or BoNT-A. We conducted a subgroup exploratory analysis on HIT-6 and ASC-12 scores in the two groups. The Wilcoxon rank-sum test, Fisher's exact test, and ANOVA were performed. Results: Of 126 patients, 36 on mAbs and 90 on BoNT-A had at least one available follow-up. mAbs resulted in a mean reduction of −11.1 and −11.4 points, respectively, in the HIT-6 at 6 and 12 months, while BoNT-A was reduced −3.2 and −3.6 points, respectively; the mAbs arm resulted in mean reductions in ASC-12 at 6 and 12 months of follow-up of −5.2 and −6.0 points, respectively, while BoNT-A showed lesser mean changes of −0.5 and −0.9 points, respectively. The adjusted analysis confirmed our results. Conclusions: In this exploratory analysis, anti-CGRP mAbs showed superior effectiveness for HIT-6 and ASC12 compared to BoNT-A. Reductions in terms of month headache days (MHD), migraine disability assessment test (MIDAS), and migraine acute medications (MAM) were clinically relevant for both treatments. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: This was a retrospective, real-world, exploratory study. The participants included within the study were adult (≥ 18 years) 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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Abstract Background The reimbursement of erenumab in Spain and other European countries is currently restricted because of the cost of this novel therapy to patients with migraine who have experienced previous failures to traditional preventive treatments. However, this reimbursement policy should be preferably based on cost-effectiveness studies, among other criteria. This study performed a cost-effectiveness analysis of erenumab versus topiramate for the prophylactic treatment of episodic migraine (EM) and versus placebo for chronic migraine (CM). Methods A Markov model with a 10-year time horizon, from the perspective of the Spanish National Healthcare System, was constructed based on data from responder and non-responder patients. A responder was defined as having a minimum 50% reduction in the number of monthly migraine days (MMD). A hypothetical cohort of patients with EM with one or more prior preventive treatment failures and patients with CM with more than two treatment failures was considered. The effectiveness score was measured as an incremental cost per quality-adjusted life year (QALY) gained and cost per migraine day (MD) avoided. Data from clinical outcomes and patient characteristics were obtained from erenumab clinical trials (NCT02066415, STRIVE, ARISE, LIBERTY and HER-MES). Deterministic and probabilistic sensitivity analyses were performed to validate the robustness of the model. Results After a 10-year follow-up, the estimated QALYs were 5.88 and 6.11 for patients with EM treated with topiramate and erenumab, respectively. Erenumab showed an incremental cost per patient of €4,420 vs topiramate. For CM patients, erenumab resulted in 0.756 QALYs gained vs placebo; and an incremental cost of €1,814. Patients treated with erenumab achieved reductions in MD for both EM and CM (172 and 568 MDs, respectively). The incremental cost per QALY gained with erenumab was below the Spanish threshold of €30,000/QALY for both health and societal perspectives (EM €19,122/QALY and CM €2,398/QALY). Conclusions Erenumab is cost-effective versus topiramate as a preventive treatment for EM and versus placebo for patients with CM from the perspective of the Spanish National Health System.

Abstract Introduction 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. Methods This was a retrospective, real-world, exploratory study. The participants included within the study were adult (≥ 18 years) 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. Results 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. Conclusion 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.

Abstract Background Chronic migraine (CM) is a disabling condition with high prevalence in the general population. Until the recent approval of monoclonal antibodies targeting the calcitonin gene-related peptide (Anti-CGRP mAbs), OnabotulinumtoxinA (BoNT-A) was the only treatment specifically approved for CM prophylaxis. Direct comparisons between the two treatments are not available so far. Methods We performed an observational, retrospective, multicenter study in Italy to compare the real-world effectiveness of Anti-CGRP mAbs and BoNT-A. Patients with CM who had received either treatment according to Italian prescribing regulations were extracted from available clinical databases. Efficacy outcomes included the change from baseline in monthly headache days (MHD), MIgraine Disability ASsessment test (MIDAS), and monthly acute medications (MAM) evaluated at 6 and 12 months of follow-up. The primary outcome was MHD change from baseline at 12 months. Safety outcomes included serious adverse events (SAE) and treatment discontinuation. Unadjusted and adjusted models were used for the analyses. Results Two hundred sixteen potentially eligible patients were screened; 183 (86 Anti-CGRP mAbs; 97 BoNT-A) were included. One hundred seventy-one (80 Anti-CGRP mAbs; 91 BoNT-A) and 154 (69 Anti-CGRP mAbs; 85 BoNT-A) patients were included in the efficacy analysis at 6 and 12 months of follow-up, respectively. Anti-CGRP mAbs and BoNT-A both resulted in a mean MHD reduction at 6 (-11.5 and -7.2 days, respectively; unadjusted mean difference -4.3; 95%CI -6.6 to -2.0; p = 0.0003) and 12 months (-11.9 and -7.6, respectively; unadjusted mean difference -4.4; 95%CI -6.8 to -2.0; p = 0.0002) of follow-up. Similar results were observed after adjusting for baseline confounders. Anti-CGRP mAbs showed a significant MIDAS (-31.7 and -19.2 points, p = 0.0001 and p = 0.0296, respectively) and MAM reduction (-5.1 and -3.1 administrations, p = 0.0023 and p = 0.0574, respectively) compared to BoNT-A at 6 and 12 months. No SAEs were reported. One patient receiving fremanezumab discontinued treatment due to arthralgia. Treatment discontinuations, mainly for inefficacy, were comparable. Conclusion Both Anti-CGRP mAbs and BoNT-A were effective in CM patients with Anti-CGRP mAbs presenting higher effect magnitude, with comparable safety. Still, BoNT-A remains a valuable option for CM patients with contraindications to Anti-CGRP mAbs or for frail categories who are candidates to local therapy with limited risk of systemic administration. Graphical Abstract

Oralee J Varnado,1 Brenna L Brady,2 Anthony J Zagar,1 Yvonne P Robles,2 Margaret Hoyt1 1Eli Lilly and Company, Indianapolis, IN, USA; 2Merative, Ann Arbor, MI, USACorrespondence: Oralee J VarnadoValue, Evidence, and Outcomes, Eli Lilly and Company, Lilly Corporate Center, 893 Delaware Street, Indianapolis, IN, 46285, USA, Tel +1 317 277 0599, Email varnado_oralee_johnson@lilly.comBackground: 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.Objective: To compare the treatment patterns among patients with migraine initiating galcanezumab, fremanezumab, and erenumab.Methods: 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.Results: 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.Conclusion: Patients with migraine who initiated treatment with galcanezumab showed higher persistence and lower treatment discontinuation rates than those initiating either fremanezumab or erenumab.Plain Language Summary: What was known before? Calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are medicines developed for migraine prevention. CGRP mAbs bind to the CGRP ligand or receptor and limit pain associated with migraine attacks. Currently, three self-injectable CGRP mAbs are approved for prevention: erenumab, fremanezumab, and galcanezumab. Use of erenumab, fremanezumab, and galcanezumab can slow or stop migraine-related symptoms and reduce migraine-related disability.What does this study add? This study describes how migraine medications are used in the US by patients with migraine who started using galcanezumab, fremanezumab, or erenumab for migraine treatment. Over a period of 12 months, patients who started treatment for migraine with galcanezumab were more likely to continue their treatment than those who started using either fremanezumab or erenumab. At 12 months, fewer patients who started galcanezumab were likely to discontinue their treatment than patients who started using either fremanezumab or erenumab. Among patients who discontinued and switched, most patients switched to Botox A, a non-CGRP treatment. Among patients who switched to a different CGRP mAb, most patients in the fremanezumab and erenumab groups switched to galcanezumab, while most patients in the galcanezumab group switched to erenumab.Interpretation: These findings suggest that patients remained on galcanezumab longer and were less likely to discontinue.Keywords: CGRP mAb, erenumab, fremanezumab, galcanezumab, treatment patterns, migraine

Background and Objectives: Migraine is a chronic neurological disorder affecting approximately 14% of the global population. Beyond physical pain, migraines significantly impact individuals’ quality of life, influencing education, employment, and income levels. Topiramate, a second-generation antiepileptic medication, has demonstrated notable efficacy in reducing the occurrence of chronic migraine. Over the past three decades, extensive research has implicated the neuropeptide calcitonin gene-related peptide (CGRP) in migraine pathogenesis. Erenumab, the first FDA-approved CGRP inhibitor, received approval in 2018. This study aims to compare the clinical efficacy of Erenumab and Topiramate for migraine prevention. Materials and Methods: We conducted a retrospective cohort study of adults with episodic or chronic migraine over a 12-month period, comparing Erenumab (n = 52) and Topiramate (n = 56). Outcomes assessed included changes in the Migraine Disability Assessment (MIDAS) scores from baseline over the last three months of treatment and the proportion of patients achieving a ≥50% reduction in MIDAS scores by the end of the study. Results: The Erenumab group showed significant improvement, with nearly 79% of patients achieving a 50% reduction in their MIDAS score, with a mean reduction of 3.76. Notably, only two patients (3.8.5) discontinued treatment due to adverse events. In contrast, the Topiramate group had over 15% of patients achieve a 50% reduction in MIDAS scores, with a mean reduction of 5.89, and a had discontinuation rate of 14.2% due to adverse events. Conclusions: Both Topiramate and Erenumab are effective for migraine prevention. However, Topiramate has lower tolerability and more side effects, while Erenumab offers better tolerability and safety at a higher cost. Treatment decisions should be individualized based on patient needs, efficacy, safety, and cost considerations.

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

Erenumab, a fully human monoclonal antibody targeting the calcitonin gene‐related peptide receptor, is efficacious and safe for prevention of attacks of migraine in adults. This phase I, randomized, open‐label, multiple‐dose study evaluated the safety, tolerability, and pharmacokinetics (PK) of erenumab in children and adolescents with migraine. The initial treatment phase lasted 12 weeks, followed by an optional 40‐week extension phase for adolescents. Primary end points were PK of erenumab, incidence of treatment‐emergent adverse events (TEAEs), and changes in clinical and laboratory assessments. Participants received erenumab 35 mg (n = 4), 70 mg (n = 17), or 140 mg (n = 32) q4w. The mean age was 14.1 years. Of the 53 participants, 48 (90.6%) completed the initial treatment phase and 36 (67.9%) received erenumab during the extension phase. Mean exposures to erenumab based on the maximum observed concentration and the area under the drug concentration–time curve during the dosing interval increased approximately dose‐proportionally. A total of 42 participants (79.2%) reported TEAEs (307.2 per 100 participant‐years); and four (7.5%) reported serious TEAEs not considered treatment‐related. The most common TEAEs were upper respiratory tract infection, headache, and vomiting. No clinically significant changes were reported in vital signs, electrocardiograms, and laboratory and neurological assessments. Overall, the observed PK profile of erenumab in children and adolescents with migraine is consistent with that in adults when body weight differences are taken into consideration. The safety profile of erenumab in children and adolescents is consistent with that in adults. [ABSTRACT FROM AUTHOR]

Background: Migraine imposes a substantial global burden, impacting patients and society. Pharmacotherapy, as a primary treatment, entails specific adverse reactions. Emphasizing these reactions is pivotal for improving treatment strategies and enhancing patients' well-being. Thus, we conducted a comprehensive bibliometric and visual analysis of relevant literature. Methodology: We conducted a comprehensive search on the Science Citation Index Expanded within the Web of Science, restricting the literature for analysis based on criteria such as document type, publication date, and language. Subsequently, we utilized various analytical tools, including VOSviewer, Scimago Graphica, the R package 'bibliometrix', CiteSpace, and Excel programs, for a meticulous examination and systematic organization of data concerning journals, authors, countries/regions, institutions, keywords, and references. Results: By August 31, 2023, the literature was distributed across 379 journals worldwide, authored by 4,235 individuals from 1726 institutions. It featured 2,363 keywords and 38,412 references. 'HEADACHE' led in publication count, with 'SILBERSTEIN S' as the most prolific author. The United States ranked highest in publication volume, with 'UNIV COPENHAGEN' leading among institutions. Conclusion: Our research findings indicate that researchers in the field continue to maintain a focus on the calcitonin gene-related peptide (CGRP) system and explore diverse mechanisms for drug development through the application of novel biotechnological approaches. Furthermore, it is imperative to enhance the assessment of clinical trial outcomes, consistently monitor the efficacy and safety of prominent drugs such as Erenumab and Fremanezumab. There is a need for further evaluation of acute and preventive treatments tailored to different populations and varying types of migraine. [ABSTRACT FROM AUTHOR]