Social Impact of Prophylactic Migraine Treatments in Germany: A State-Transition and Open Cohort Approach.

OBJECTIVES: Migraine is a highly prevalent neurological disorder. The most characteristic symptom of migraine is moderate to severe recurrent headache along with other neurological symptoms. In this study, we modeled the potential reduction in migraine days and corresponding avoided productivity losses if erenumab was prescribed to the patient population indicated for prophylactic migraine treatment (≥ 4 monthly migraine days [MMDs]) in Germany from 2020 to the end of 2027. METHODS: We simulated the incremental benefits of erenumab against the standard of care. Response rates, transition probabilities, discontinuation rates, and productivity estimates were derived from the erenumab clinical trial program. Patients had a probability of residing in 1 of 7 states, given the MMDs in addition to the probability of death. Based on accrued MMDs in every cycle, days of absenteeism and presenteeism for paid and unpaid work were derived. Paid work was monetized according to gross value added using the human capital approach, whereas unpaid work was valuated according to the proxy good method. In addition, downstream macroeconomic effects were captured using value-added multipliers. Direct medical costs were concomitantly calculated. RESULTS: Our results show that prescribing erenumab for the indicated population in Germany could lead to a reduction of 166 million migraine days annually and reduce productivity losses in the range of €27 billion. This includes €13.1 billion from direct productivity and €13.5 billion from economic value chain effects. CONCLUSIONS: This study highlights the macroeconomic effects of a systematic introduction of novel inhibitors of the calcitonin gene-related peptide pathway for migraine in Germany.

Hypertension: A new safety risk for patients treated with erenumab.

OBJECTIVE: To identify and analyze postmarketing case reports of elevated blood pressure (BP) associated with erenumab use. METHODS: A retrospective analysis of postmarketing (spontaneous) case reports of erenumab-associated elevated BP submitted to the FDA Adverse Event Reporting System from May 17, 2018 through April 30, 2020. A case of elevated BP was defined as (a) an initiation of a pharmacological intervention or emergency department visit or hospitalization for emergent de novo or worsening of preexisting hypertension, or (b) BP measurement of ≥140 mm Hg systolic or ≥90 mm Hg diastolic with or without baseline BP measurement reported. Reports of elevated BP associated with erenumab use were analyzed for baseline and demographic information, latency, drug-event causal association, and clinical outcome. RESULTS: Sixty-one cases of elevated BP were identified, 86% (49/57) were women and the median age was 56 [range 24-88] years. Forty-one cases were associated with a serious outcome per regulatory criteria, including seven that specified hospitalization. No case reported an outcome of death. The median systolic BP increase was 39 (interquartile range (IQR) 32, 59) mm Hg and median diastolic BP increase was 28 (IQR 18, 41) mm Hg. A total of 27/61 (44%) cases reported treatment for elevated BP (i.e., pharmacologic intervention or emergency department visit/hospitalization). Elevated BP occurred most frequently (28/61, 46%) within a week of the first dose of erenumab. Nineteen cases (19/61, 31%) reported a history of preexisting hypertension. CONCLUSIONS: This case series suggest an association between elevated BP and use of erenumab. In light of our findings, the erenumab (Aimovig) prescribing information was amended to include hypertension in the Warnings and Precautions section.

Erenumab patient characteristics, medication adherence, and treatment patterns in the United States.

OBJECTIVE: To describe patient characteristics, adherence, and treatment patterns, among adult migraine patients in the United States prescribed erenumab. BACKGROUND: Migraine is a highly prevalent and debilitating disease characterized by recurrent attacks of moderate to severe headache accompanied by non-headache symptoms. Erenumab is a first-in-class calcitonin gene-related peptide receptor (CGRP-R) antagonist indicated for migraine prophylaxis in adults. METHODS: This retrospective longitudinal cohort study used IQVIA's open-source longitudinal pharmacy (LRx) and medical (Dx) claims databases to identify adult migraine patients with an initial claim (index date) for erenumab between May 1, 2018 and April 30, 2019. Patients were required to have ≥180 days of follow-up. Erenumab dosing patterns, persistence, and adherence (using medication possession ratio [MPR] and proportion of days covered [PDC]), and discontinuation of other commonly prescribed acute and prophylactic anti-migraine therapies were assessed. Dose changes in acute therapies after initiation of erenumab were assessed in a subset of patients with an adequate trial of erenumab (≥2 additional erenumab claims within the 80 days following the index claim). RESULTS: A total of 64,174 patients met the study criteria. Mean (SD) age was 48 (13) years and 85.2% (n = 54,656) were female. The initial erenumab dose was 70 mg for the majority of patients (65.1%; n = 41,790); most (81.4%; n = 34,019) maintained their index dose during follow-up. Overall, 30.8% (n = 19,797) of patients had a PDC ≥ 0.80 and 41.7% (n = 26,769) had a MPR ≥ 0.80. Discontinuation rates of acute and other prophylactic migraine therapies after initiation of erenumab (among users of the respective therapies) were 48.7% (22,965/47,190) and 36.1% (16,602/46,006), respectively. Dose decreases among triptan, ergot compound, opioid, and barbiturate users were observed after initiation of erenumab. CONCLUSIONS: Almost all patients had prior use of acute or preventive therapy. Adherence to erenumab was higher than traditional oral prophylactic migraine therapies; however, overall adherence was still suboptimal. The decrease in use of acute and preventive prescription medications following initiation of erenumab suggests effectiveness in the real-world setting.

Improvements in pain, medication use and quality of life in onabotulinumtoxinA-resistant chronic migraine patients following erenumab treatment - real world outcomes.

BACKGROUND: The CGRP antagonists offer a novel therapeutic approach in migraine. Their utility in patients with severe forms of chronic migraine is a subject of particular interest. We present outcomes of 9 months of erenumab treatment in a cohort of patients with difficult-to-control chronic migraine, all of whom had prior unsatisfactory response to onabotulinumtoxinA. METHODS: We offered erenumab to 98 patients with a prior unsatisfactory response to onabotulinumtoxinA. Eighty of 98 had trialled greater occipital nerve injections (82%), 32/98 peripheral neurostimulation (33%) and 18/98 intravenous dihydroergotamine (18%). Thirty eight of 98 (39%) met the definition of triptan overuse and 43/98 (44%) analgesic overuse. All patients met the EHF criteria for 'resistant migraine'. Outcome measures (recorded monthly) included days with headache limiting activities of daily living ("red"), not limiting ("amber"), headache free ("green"), and requiring triptans or other analgesics. Quality of life scores - headache impact test 6 (HIT-6), patient health questionnaire 9 (PHQ-9) and pain disability index (PDI) - were also measured. RESULTS: Mean number of red days improved by - 6.4 days (SE 0.67, 95%CI - 7.7 to - 5.1, p=0.001) at 3 months; - 6.8 days (SE 0.96, 95%CI - 8.80 to - 4.9, p=0.001) at 6 months and - 6.5 days (SE 0.86, 95%CI - 8.3 to - 4.8, p=0.001) at 9 months. Repeated measures ANOVA confirmed improvements in the number of red (p=0.001), green (p=0.001), triptan (p=0.001) and painkiller days (p=0.001) as well as scores of the HIT-6 (p=0.001), PHQ-9 (p=0.001), and PDI (p=0.001) across the duration of study. CONCLUSION: We observed improvements in pain, medication use and quality of life in onabotulinumtoxinA-resistant chronic migraine patients following erenumab treatment.

Aimovig for Migraine Prevention: The New Kid May Have Trouble Fitting in.

Aimovig (erenumab-aooe), codeveloped by Amgen and Novartis, has been recently approved for the prevention of migraines. Its mechanism of action is different than other migraine medications. But perhaps more interestingly, it is the first drug recently developed specifically for migraine prevention.

Erenumab for episodic migraine.

In this review, the authors provide an overview of erenumab, a monoclonal antibody used for the preventative treatment of episodic migraine by targeting the CGRP pathway. Randomized controlled trials have shown that erenumab is associated with a statistically significant decrease in monthly migraine days in patients with episodic migraine at monthly doses of 70 or 140 mg when given for a period of 9-12 weeks. Post hoc analyses have also shown long-term maintenance of efficacy. Clinical trials have found erenumab at doses of both 70 and 140 mg to have a favorable safety profile. Erenumab faces significant limitations because of its high financial cost. Additional long-term real-world data are needed to understand the role of erenumab in the treatment of migraine.

In this review, the authors give an overview of erenumab, an injectable medication used to prevent migraine headaches. Erenumab has been proven to be significantly effective in patients with episodic migraines when used at doses of 70 or 140 mg. Furthermore, studies have shown sustained benefit starting as early as the first week of treatment as well as improvement in patients' quality of life. Erenumab has been found to be as safe as placebo in some studies, but there have been some reports of a link to high blood pressure and constipation. However, because of its high cost, patients still face significant barriers to access to erenumab. Additional long-term real-world data are needed to understand the current role of erenumab in the treatment of migraine.

Molecular Insight into Recognition of the CGRPR Complex by Migraine Prevention Therapy Aimovig (Erenumab).

Calcitonin-gene-related peptide (CGRP) plays a key role in migraine pathophysiology. Aimovig (erenumab; erenumab-aooe in the United States) is the only US Food and Drug Administration (FDA)-approved monoclonal antibody (mAb) therapy against the CGRP receptor (CGRPR) for the prevention of migraine. Aimovig is also the first FDA-approved mAb against a G-protein-coupled receptor (GPCR). Here, we report the architecture and functional attributes of erenumab critical for its potent antagonism against CGRPR. The crystal structure of erenumab in complex with CGRPR reveals a direct ligand-blocking mechanism, enabled by a remarkable 21-residue-long complementary determining region (CDR)-H3 loop, which adopts a tyrosine-rich helix-turn tip and projects into the deep interface of the calcitonin receptor-like receptor (CLR) and RAMP1 subunits of CGRPR. Furthermore, erenumab engages with residues specific to CLR and RAMP1, providing the molecular basis for its exquisite selectivity. Such structural insights reveal the drug action mechanism of erenumab and shed light on developing antibody therapeutics targeting GPCRs.

Erenumab in the treatment of migraine.

Migraine is a highly prevalent neurological pain syndrome, and its management is limited due to side effects posed by current preventive therapies. Calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. In recent years, research has been dedicated to the development of monoclonal antibodies against CGRP and CGRP receptors for the treatment of migraine. This review will focus on the first US FDA-approved CGRP-receptor monoclonal antibody developed for the prevention of migraine: erenumab. Two Phase II trials (one for episodic migraine and one for chronic migraine) and two Phase III trials for episodic migraine have been published demonstrating the efficacy and safety of erenumab in the prevention of migraine.