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Change from baseline in MMD across patient subgroups. BL, baseline; CGRP, calcitonin gene-related peptide; CM, chronic migraine; EM, episodic migraine; GAD, generalized anxiety disorder; mAb, monoclonal antibody; MDD, major depressive disorder; MMD, monthly migraine days; MO, medication overuse. aNumber of patients with available assessment at each time point
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Background
Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. R...
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Background:
Erenumab, a fully human monoclonal antibody that targets the calcitonin gene-related peptide receptor, has demonstrated efficacy and safety in the prevention of episodic and chronic migraine. There exists an unmet need to establish the safety of erenumab in older individuals, in view of existing multiple comorbidities, polypharmacy, an...
Citations
... Finally, the response was also negatively influenced by the two main comorbidities suffered by our patients, anxiety-depression and/or fibromyalgia, though only the presence of anxiety-depression was actually associated with a poorer response after the multivariate analysis. Again, our results concur with those found in previous work [36], though the efficacy of fremanezumab in patients with anxiety-depression has been demonstrated in controlled [37] and real-life studies [38]. ...
Background: Fremanezumab was the third CGRP antibody available in our hospital. This examination of our experience with fremanezumab is focused on identifying the predictors of response. Methods: This was a prospective observational study in which we included high-frequency episodic/chronic migraine (HF/CM) patients who were prescribed fremanezumab during the year 2023. Our research involved collecting data on their demographic details, diagnoses made, treatments received, prophylactic measures taken in the past, and any comorbid conditions present. The number of headaches was documented for one quarter prior to and after the initiation of fremanezumab. Results: Eighty-nine patients received fremanezumab (86.5% female, 45.8 ± 12.5 years old, 70.1% naive). The headache days decreased from 21.1 ± 7.6 to 12.4 ± 11.2 days during the initial three months of the treatment, and a total of 55 patients (61.8%) exhibited a response rate of ≥50%. Six out of ten patients refractory to erenumab for at least 6 months responded to fremanezumab. Totals of 17 and 26 patients had been treated at least with galcanezumab or erenumab. The elements influencing non-response were as follows: prior failure to respond to both erenumab and galcanezumab (p < 0.0001), HF/CM length (11.9 ± 7.1 years in non-responders vs. 5.8 ± 4.8 in responders; p < 0.001), the presence of fibromyalgia (p < 0.001), anxiety–depression (p < 0.001), an almost daily headache baseline (>28 days/month) (p < 0.0001), and analgesic overuse (p < 0.0001). The response rate was unaffected by age and experience. After a multivariate logistic analysis, almost daily headaches (p < 0.001), a length of HF/CM > 6 years (p = 0.015), and anxiety–depression (p = 0.017) remained significant. Fremanezumab showed excellent tolerance. Conclusions: These real-life results confirm the efficacy of fremanezumab. The main factors associated with a lack of response were almost daily/daily headaches and a disease duration > 6 years. Half of the patients who failed to respond to erenumab improved on fremanezumab, making it sensible to switch to a treatment with a different mechanism of action, but trying a third anti-CGRP treatment in patients with no response to both a receptor-targeted and a ligand-targeted CGRP antibody hardly seems justifiable from our experience.
... Several subsequent RWE data confirmed the effectiveness of fremanezumab in both EM and CM preventive treatment [50][51][52][53]. The durations of these studies varied from 3 [54] to more than 12 months [55]. ...
... Youn [106] Prospective series N = 21, age = 49 (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) Ihara and colleagues retrospectively studied 15 patients (13 females) who received galcanezumab for 3 or 4 months and switched to fremanezumab due to personal preferences. Thirteen patients switched to quarterly and two to monthly fremanezumab administrations. ...
Introduction:
When a first anti-CGRP monoclonal antibody (anti-CGRP mAb) fails, switching to a different anti-CGRP mAb is an option often considered, despite the fact that this approach is not yet systemically studied.
Methods:
We present the findings of a systematic review conducted according to the PRISMA recommendations on published studies - of any design - investigating the clinical outcomes after switching for any reason to different anti-CGRP mAbs.
Results:
The literature search retrieved 76 records, while 19 papers were eventually reviewed. Most studies were retrospective and/or had a small sample size. A significant proportion of participants experienced an improved treatment response after switching between different anti-CGRP mAbs. Specifically, according to prospective studies' results, the median MMDs were reduced by 12.8 days after 6 months of switching, while up to 48% of episodic and 36% of the chronic migraine patients achieved a >50% response rate.
Conclusions:
Switching between different anti-CGRP mAbs may be beneficial, at least for some patients, and should be considered when therapy with a first anti-CGRP mAb fails for any reason. Larger prospective studies, employing standardized protocols for switching or comparative effectiveness trials between mAbs, are anticipated to elucidate this issue further.
... Fremanezumab, a humanized mAb that selectively targets both isoforms of CGRP, is US Food and Drug Administration (FDA)-approved for both quarterly and monthly subcutaneous dosing in adults [8]. Fremanezumab has demonstrated effectiveness over 6-12 months in the reduction of monthly migraine days (MMD) and monthly headache days (MHD) of at least moderate severity, along with improvements in disability outcomes, in Phase 3 extension studies and real-world studies in patients with migraine [6,[9][10][11][12][13]. These improvements in clinical symptoms have been observed with both monthly and quarterly fremanezumab dosing regimens in patients with episodic migraine (EM) and chronic migraine (CM), including those with multiple prior migraine preventive treatment failures, psychiatric comorbidities, and acute medication overuse in a real-world setting [10,11]. ...
... Fremanezumab has demonstrated effectiveness over 6-12 months in the reduction of monthly migraine days (MMD) and monthly headache days (MHD) of at least moderate severity, along with improvements in disability outcomes, in Phase 3 extension studies and real-world studies in patients with migraine [6,[9][10][11][12][13]. These improvements in clinical symptoms have been observed with both monthly and quarterly fremanezumab dosing regimens in patients with episodic migraine (EM) and chronic migraine (CM), including those with multiple prior migraine preventive treatment failures, psychiatric comorbidities, and acute medication overuse in a real-world setting [10,11]. ...
... Ongoing improvements were observed in the long-term extension study in patients with CM (n = 1110), with average reductions in MMD over 12 months of − 7.2 to − 8.0 days [6]. In a recent US-based chart review, reductions of − 7.9 MMD at Month 3 and − 10.1 MMD at Month 6 were reported for patients with CM (n = 587) [11]. Similar to the findings of the current study, improvements in migraine symptoms with fremanezumab treatment have been previously shown to be accompanied by corresponding reductions in acute and preventive medication use, along with reductions in migraine-related HCRU [28][29][30][31]. ...
Fremanezumab, a monoclonal antibody (mAb) targeting the calcitonin gene-related peptide (CGRP) pathway, and gepants, small molecule CGRP receptor antagonists, are both approved for the treatment of migraine or its symptoms. This study assessed effectiveness, tolerability, and migraine-related healthcare resource utilization (HCRU) after the addition of fremanezumab for preventive migraine treatment in patients using gepants for acute treatment.
Data were extracted during a retrospective chart review from electronic medical records from the Dent Neurologic Institute. Eligible patients were ≥ 18 years old, using gepants (rimegepant or ubrogepant), who initiated fremanezumab between January 1, 2020, and May 1, 2021 (index date: date of fremanezumab initiation) and continued concomitant use of gepants and fremanezumab for ≥ 1 month (post-index; between 7–9 months of follow-up). Outcomes included monthly migraine days (MMD), adverse events (AEs), reasons for discontinuation, and migraine-related HCRU.
A total of 55 patients [female, 93%; mean (SD) age, 43.5 (13.5) years] met the inclusion criteria. All patients were diagnosed with chronic migraine. Patients had an average (SD) MMD of 15.8 (7.4) at the index date. Average (SE) change in MMD from index date to post-index was − 6.5 (1.0) days (p < 0.0001). Five patients (9.1%) experienced AEs post-index; no serious AEs (SAEs) were reported. The number of migraine-related medications used decreased from the index date to post-index by a mean of 0.6 for preventive medications (p = 0.070), and 0.8 for acute medications (p = 0.050). The number of outpatient office-based visits also decreased [mean (SD): 6 months pre-index, 5.8 (4.4) vs. 6 months post-index, 4.1 (4.0); p < 0.0001].
The addition of fremanezumab preventively to gepants for acute migraine treatment was effective, resulted in fewer outpatient office visits, and yielded no SAEs or AEs that were novel to these migraine medication classes.
... We agree with previous theses that pain catastrophizing may indicate a clinical phenotype with heightened expression of altered central sensitization and consequential coping mechanisms leading to an overall decrease in quality of life (Sciruicchio et al., 2019). Identifying the various factors that drive the progression of chronic migraine is crucial to developing effective prevention strategies (Driessen et al., 2022). Other real-world studies demonstrated that CGRP antibodies were able to exert an excellent clinical response across subgroups of migraine patients with comorbid psychological traits, mainly anxiety, and depression (Smitherman et al., 2020;Pelzer et al., 2023b). ...
Background:
We aimed to assess the impact of pain catastrophizing, measured using the Italian version of the Pain Catastrophizing Scale (PCS), on the clinical response of patients with chronic migraine to anti-CGRP monoclonal antibodies combined with a multidisciplinary approach, including psychological treatment.
Methods:
Twenty-five outpatients from the SS. Antonio e Biagio e Cesare Arrigo headache clinic were randomly assigned to receive Galcanezumab, Erenumab, or Fremanezumab. Their clinical response was evaluated over six months using several measures, including the reduction in the number of migraine days per month and quality of life assessments via the Headache Impact Test (HIT-6), Migraine Disability Assessment Score questionnaire (MIDAS), and Beck Inventory Scale (BDI-II) for comorbid depression.
Results:
We established a strong correlation between HIT-6 and PCS, with coefficients of 0.81 and 0.88 at T1 and T2, respectively. Additionally, there was no significant correlation between PCS and other scales, such as MIDAS, nor with any pharmacological therapies.
Conclusion:
This study underscores the importance of a multidisciplinary approach, including psychological follow-up, for a specific clinical phenotype of chronic migraine patients prone to catastrophizing. However, further data are needed to support these findings.
... A large number of clinical studies have demonstrated that TCM particularly acupuncture, can achieve significant results in treating migraines, providing both short-term and long-term relief [31,32]. Acupuncture, one of the most popular therapies in TCM, involves the use of metal needles to stimulate specific acupoints on the body to treat various diseases [33,34]. These acupoints, which include the fourteen meridian points, extra-meridian points, and Ashi points, are unique locations on the body where the qi of the zang-fu organs and meridians converge. ...
... We identified eight relevant articles focusing on fremanezumab in RWE studies, involving 1776 patients (701 with EM and 1075 with CM; 397 males and 1379 females; medication overuse: 579), with a mean age ranging from 38.5 to 49.5 years (Table 5) [6,[45][46][47][48][49][50][51]. Among these studies, seven were prospective and one was retrospective ( Figure 3). ...
... Of the prospective studies, two were conducted at single centers [49,50], while five were multi-center studies. The retrospective studies were multi-center [46]. The durations of the studies varied, with three lasting 3 months [45,48,49], three lasting 6 months [46,47,50], and two extending to 12 months [6,51]. ...
... The retrospective studies were multi-center [46]. The durations of the studies varied, with three lasting 3 months [45,48,49], three lasting 6 months [46,47,50], and two extending to 12 months [6,51]. ...
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.
... We identified 8 relevant articles focusing on fremanezumab in RWE studies, involving 1,776 patients (701 with EM and 1,075 with CM; 397 males and 1,379 females; medication overuse: 579), with a mean age ranging from 38.5 to 49.5 years (Table 2) [6,[39][40][41][42][43][44][45]. Among these studies, 7 were prospective and 1 was retrospective ( Figure 3). ...
... Of the prospective studies, 2 were conducted at single centers [43,44], while 5 were multi-center studies. The retrospective studies was multi-center [40]. The durations of the studies varied, with 3 lasting 3 months [39,42,43], 3 lasting 6 months [40,41,44], and 2 extending to 12 months [6,45]. ...
... The retrospective studies was multi-center [40]. The durations of the studies varied, with 3 lasting 3 months [39,42,43], 3 lasting 6 months [40,41,44], and 2 extending to 12 months [6,45]. (Table 2). ...
Background The advent of monoclonal antibodies (mAbs) targeting 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 e 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 55 pertinent studies conducted between 2019 and 2023. 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, disability), high responder rates, and optimal safety and tolerability profiles. Conclusion 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 unprecedented finding in clinical neurology.
... Recruiting studies of fremanezumab on sleep improvement (NCT04693533) and two other studies for the preventive treatment of episodic and chronic migraine in pediatric patients are still ongoing (NCT04530110, NCT04464707). RWS of fremanezumab have demonstrated its efficacy and tolerability regardless of migraine type or prior exposure to a different CGRP monoclonal antibody (55)(56)(57). RWS have also disclosed greater efficacy than randomized controlled trials (RCT), with rare treatment emergent adverse events, which were mostly mild conditions such as pain, rash or pruritus, flu-like symptoms, and hair loss (56,58,59). Additionally, significant reductions in antidepressant and anxiolytic medication use have been observed (60). ...
Migraine, a prevalent neurological disorder, affects approximately 14.1% of the global population and disproportionately impacts females. This debilitating condition significantly compromises quality of life, productivity, and incurs high healthcare costs, presenting a challenge not only to individuals but to societal structures as a whole. Despite advances in our understanding of migraine pathophysiology, treatment options remain limited, necessitating ongoing research into effective therapies. This review delves into the complexity of migraine management, examining the roles of genetic predisposition, environmental influences, personalized treatment approaches, comorbidities, efficacy and safety of existing acute and preventive treatments. It further explores the continuum between migraine and tension-type headaches and discusses the intricacies of treating various migraine subtypes, including those with and without aura. We emphasize the recent paradigm shift toward trigeminovascular activation and the release of vasoactive substances, such as calcitonin gene-related peptide (CGRP), which offer novel therapeutic targets. We assess groundbreaking clinical trials, pharmacokinetic and pharmacodynamic perspectives, safety, tolerability, and the real-world application of CGRP monoclonal antibodies and gepants. In the face of persisting treatment barriers such as misdiagnosis, medication overuse headaches, and limited access to specialist care, we discuss innovative CGRP-targeted strategies, the high cost and scarcity of long-term efficacy data, and suggest comprehensive solutions tailored to Turkiye and developing countries. The review offers strategic recommendations including the formulation of primary care guidelines, establishment of specialized outpatient clinics, updating physicians on novel treatments, enhancing global accessibility to advanced therapies, and fostering patient education. Emphasizing the importance of lifestyle modifications and holistic approaches, the review underscores the potential of mass media and patient groups in disseminating critical health information and shaping the future of migraine management.
... Причем при ежемесячном введении препарата снижение через 12 недель составило 12,6 дня. Критерием эффективности лечения мигрени считается уменьшение числа дней с головной болью на ≥50% (респондеры) [46][47][48][49][50][51][52]. Через 3 месяца терапии фреманезумабом снижение числа дней с мигренью ≥50%, ≥75% и 100% имело место у 70%, 26% и 4% пациентов соответственно (рис. ...
... Публикаций, оценивающих опыт применения фреманезумаба при ХМ с ЛИГБ в сравнении с эренумабом, довольно мало. Также недостаточное внимание уделяется и динамике коморбидных психоэмоциональных нарушений на фоне новой терапии мигрени [46][47][48][49][50][51][52][53][54]. ...
... В сопоставимом исследовании FRIEND (46 пациентов с ХМ) через 3 месяца лечения среднее число дней с мигренью снизилось на 9,4 дня в месяц [46]. В ретроспективном исследовании M. Driessen применение фреманезумаба при ХМ привело к снижению среднемесячного числа дней с мигренью через 3 месяца на 7,9 дня [47]. В исследовании P. МсAllister отмечено снижение с 22,2 до 8,2 дня с мигренью в месяц, при среднем периоде наблюдения 12,8 месяца [48]. ...
Цель. Оценка степени выраженности психоэмоциональных нарушений, динамики лекарственного абузуса у пациентов с хронической мигренью (ХМ) на фоне терапии фреманезумабом в условиях реальной клинической практики. Материалы и методы. В рамках трехмесячного открытого проспективного исследования 27 пациентам (78% женщин, средний возраст 41 год) с ХМ проводилась терапия фреманезумабом в суммарной дозировке 675 мг (одномоментно или по 225 мг ежемесячно). В динамике оценивались изменение числа дней с мигренью в месяц, а также степень влияния на лекарственно-индуцированную головную боль (ЛИГБ) и выраженность психоэмоциональных нарушений по данным опросников и шкал (госпитальная шкала тревоги и депрессии, шкала депрессии Бека, опросник Спилбергера – Ханина), регистрировались возможные нежелательные явления (НЯ). Результаты. Снижение числа дней с мигренью в месяц на ≥50% через 12 недель терапии фреманезумабом было отмечено у 70% пациентов, средняя частота приступов мигрени снизилась на 11,6 дня в месяц (p<0,01). Отмечено уменьшение числа пациентов с ЛИГБ с 89% до 15% (p<0,01) без детоксикационной терапии. Положительная динамика отмечалась по данным нейропсихологического тестирования преимущественно в виде снижения степени тревоги и в меньшей степени депрессии. НЯ встречались в четверти случаев (26%), не привели к прекращению лечения. Заключение. В условиях реальной клинической практики подтверждена высокая эффективность фреманезумаба в отношении ХМ и сопутствующей ЛИГБ, отмечена положительная динамика коморбидных тревожных и депрессивных расстройств.
Purpose. To assess the degree of severity of psychoemotional disorders and drug abuse trends in patients with chronic migraine (CM) on the background of fremanezumabtherapy in real clinical practice. Materials and methods. As part of a three-month open-label prospective study, 27 patients (78% being women, mean age of 41 years) with CM were treated with fremanezumab at a total dosage of 675 mg (single dose or 225 mg monthly). Over time, changes in the number of migraine days per month were assessed, as well as the degree of influence on medication-overuse headache (MOH) and the severity of psychoemotional disorders according to questionnaires and scales (Hospital Anxiety and Depression Scale, Beck Depression Inventory, Spielberger – Hanin Questionnaire), Possible adverse events (AEs) were recorded. Results. A reduction in the number of migraine days per month by ≥50% after 12 weeks of fremanezumab therapy was observed in 70% of patients, and the average frequency of migraine attacks decreased by 11.6 days per month (p<0.01). There was a decrease in the number of patients with MOH from 89% to 15% (p<0.01) without detoxification therapy. Positive trends were registered according to neuropsychological testing results, mainly as a decrease in the degree of anxiety and, to a lesser extent, in depression. AEs occurred in a quarter of cases (26%) and did not lead to treatment discontinuation. Conclusion. In real clinical practice, the high effectiveness of fremanezumab against CM and concomitant MOH was confirmed, and positive trends of comorbid anxiety and depressive disorders were noted.
... Recent retrospective chart reviews have demonstrated substantial clinical benefit of fremanezumab for patients with migraine and AMO, major depressive disorder (MDD), generalized anxiety disorder (GAD), or prior migraine preventive treatment failures [29,30]. Such chart review studies are limited by the data available in the electronic medical record (i.e., HCRU and costs cannot be analyzed). ...
... Prior studies have demonstrated the realworld clinical benefit of fremanezumab for patients within this patient population. Driessen et al. found that fremanezumab treatment demonstrated sustained reductions in monthly migraine days over 6 months in a subgroup of patients with MDD or GAD, a subgroup with AMO, and subgroups with an unsatisfactory response to multiple migraine preventive treatments in a retrospective online, clinician panelbased chart review [29,30]. The current study expands upon those findings to demonstrate reductions in migraine-related acute and preventive migraine medication use and migrainerelated inpatient and outpatient office visits, as would be expected to follow with reductions in migraine symptoms. ...
Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed.
Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had ≥ 12 months of continuous enrollment prior to initiation (preindex period) and ≥ 6 months of data following initiation (postindex period; variable follow-up after 6 months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex.
In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US858) to US974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6 months postindex.
Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab.
Graphical abstract available for this article.
