Erenumab 140mg/1ml solution for injection pre-filled disposable devices

BACKGROUND: Migraine is a highly prevalent and disabling disease, affecting nearly 14% of the global population. Preventive medications involve drugs like beta-adrenergic blockers, antidepressants, and anticonvulsants. However, these drugs lacked effectiveness, and patients showed poor tolerance and low adherence to them. Erenumab, a calcitonin gene-related peptide receptor blocker, has recently shown promising results in migraine management. In this meta-analysis, the efficacy of Erenumab is investigated by employing a subgroup analysis approach. METHODS: We conducted a systematic search of six electronic databases until July 2024. Review Manager 5.4 software was utilized for the analysis, based on either weighted mean difference (MD) and standard deviation (SD) for continuous outcomes or risk ratio (RR) for dichotomous outcomes, with a confidence interval (CI) of 95%. A P-value < 0.05 indicated statistical significance. The study was registered on PROSPERO with registration number CRD42024573300. Additionally, we conducted subgroup analyses and assessed the quality of evidence using GRADE. RESULTS: A total of 20 randomized controlled trials (n = 5212) were included in our analysis. At three months, Erenumab showed statistically significant improvements in monthly migraine days (MMD), monthly acute migraine-specific medication days (MSMD), Headache Impact Test (HIT-6) score, and ≥ 50% reduction from baseline in MMD (MD: -1.78, 95% CI: [-2.37 to -1.20], P < 0.00001), (MD: -1.36, 95% CI: [-1.92 to -0.81], P < 0.00001), (MD: -2.83, 95% CI: [-3.83 to -1.82], P < 0.00001), and (RR: 1.52, 95% CI: [1.31 to 1.76], P < 0.00001), respectively. Subgroup analysis revealed that Erenumab was significantly more effective in patients with prior preventive treatment failures compared to patients with no prior failure. No significant difference in Erenumab`s response existed between episodic and chronic migraine or between 140 and 70 mg, except for MSMD in dose subgrouping. Only constipation emerged as a significant adverse effect in the Erenumab group. CONCLUSIONS: This meta-analysis found that Erenumab significantly reduced migraine attack frequency, medication days, and physical impairment. It was more effective for patients with prior treatment failures. The 140 mg dose showed better MSMD reduction than 70 mg. Erenumab's safety profile was similar to that of placebo, with only constipation noted as significant.

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BACKGROUND: The use of monoclonal antibodies targeting Calcitonin Gene-Related Peptide (CGRP) is an established treatment for chronic migraine (CM). However, its efficacy in CM patients with medication overuse headache (MOH) remains underexplored, and data on the safety and patient compliance of standard-to-high doses, especially Eptinezumab and Erenumab, over at least three months are limited. OBJECTIVE: This study aims to evaluate the efficacy and safety of anti-CGRP therapy (Eptinezumab and Erenumab) in CM and MOH patients. Specifically, it assesses changes in monthly migraine days (MMDs) after 12 weeks, risk of treatment-emergent adverse events (TEAEs) leading to discontinuation, serious TEAEs, common adverse effects, and MOH remission at 6 months. METHODS: A systematic search of PubMed, Cochrane, and Scopus databases identified randomized controlled trials (RCTs) evaluating standard or high dose anti-CGRP therapy in CM patients strictly with MOH. Studies included were required to report a ≥ 50% reduction in MMDs after ≥ 12 weeks, serious TEAEs, TEAEs leading to discontinuation, common adverse events, and MOH remission at 6 months. Heterogeneity was assessed using I² statistics and a random-effects model. RESULTS: Three RCTs with 769 patients receiving standard-to-high dose anti-CGRP monoclonal antibodies (Eptinezumab and Erenumab) for ≥ 12 weeks were included. Anti-CGRP therapy significantly increased the likelihood of a ≥ 50% reduction in MMDs compared to placebo (OR: 2.43; 95% CI: 1.68-3.51; p < 0.00001). No substantial differences were found in TEAEs leading to discontinuation, nasopharyngitis, upper respiratory tract infections, or serious TEAEs between the anti-CGRP and placebo groups. The likelihood of MOH remission was approximately double in the anti-CGRP group (OR: 1.97; 95% CI: 1.40-2.78; p = 0.0001). CONCLUSION: Standard-to-high dose anti-CGRP therapies (eptinezumab, erenumab) effectively reduce monthly migraine days and improve MOH remission rates with minimal adverse effects, showing good tolerability in CM patients with MOH.

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To evaluate the long-term safety (≥12 months) of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) or its receptor in migraine prevention by synthesising evidence from clinical trials and real-world studies. We focus on drug discontinuation due to adverse events and the type and frequency of adverse events. This is the first review to analyse the effects of the long-term use of all anti-CGRP (receptor) mAbs, aiming to provide novel insights for clinical practice and future treatment strategies. We systematically searched PubMed, Cochrane Library, and ClinicalTrials.gov for studies with ≥12 months of anti-CGRP (receptor) mAb use between January 2013 and April 2025. A random-effects meta-analysis of proportions (logit transformation, inverse variance weighting, restricted maximum likelihood) was performed to estimate pooled discontinuation and adverse event rates. Risk of bias was assessed using the ROBINS-I score. From a total of 1,499 records, 14 met the inclusion criteria and were eligible for data analysis. These 14 records corresponded to 11 individual studies with observational durations all exceeding 12 months. Seven studies investigated erenumab, two eptinezumab, and one each fremanezumab and galcanezumab. All studies were judged to have a severe risk of bias due to their underlying design. The overall pooled proportion of treatment discontinuation for any reason among patients receiving anti-CGRP (receptor) mAbs was 23%, whereas the pooled proportion of discontinuation specifically due to adverse events was substantially lower at 3%. Time-trend analysis showed that adverse event–related discontinuation remained low (<5%) beyond the first year, while overall adverse event incidence was high at baseline (>70%) but did not further increase with prolonged follow-up. Evidence on long-term use of anti-CGRP (receptor) mAbs over 12 months remains limited, but our analysis indicates good tolerability with consistently low adverse event-related discontinuation, no emergent safety signals, and largely non-serious, stable adverse event profiles. However, heterogeneity and study-level bias warrant cautious interpretation, highlighting the need for long-term clinical studies and continued real-world surveillance (e.g. registries). Not applicable.

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Importance: Patients with migraine often cycle through multiple nonspecific preventive medications due to poor tolerability and/or inadequate efficacy leading to low adherence and increased disease burden. Objective: To compare the efficacy, tolerability, patient adherence, and patient satisfaction between erenumab and nonspecific oral migraine preventive medications (OMPMs) in patients with episodic migraine (EM) who had previously failed 1 or 2 preventive treatments. Design, Setting, and Participants: The 12-month prospective, interventional, global, multicenter, active-controlled, randomized clinical trial comparing sustained benefit of 2 treatment paradigms (erenumab qm vs oral prophylactics) in adult episodic migraine patients (APPRAISE) trial was a 12-month open-label, multicenter, active-controlled, phase 4 randomized clinical trial conducted from May 15, 2019, to October 1, 2021. This pragmatic trial was conducted at 84 centers across 17 countries. Overall, participants 18 years or older with a 12-month or longer history of migraine, and 4 or more but fewer than 15 monthly migraine days (MMDs) were included. Interventions: Patients were randomized (2:1) to receive erenumab or OMPMs. Dose adjustment was permitted (label dependent). Main Outcomes and Measures: The primary end point was the proportion of patients completing 1 year of the initially assigned treatment and achieving a reduction of 50% or greater from baseline in MMDs at month 12. Secondary end points included the cumulative mean change from baseline in MMDs during the treatment period and the proportion of responders according to the Patients' Global Impression of Change (PGIC) scale at month 12 for patients taking the initially assigned treatment. Results: A total of 866 patients were screened, of whom 245 failed the screening and 621 completed the screening and baseline period. Of the 621 randomized patients (mean [SD] age, 41.3 [11.2] years; 545 female [87.8%]; 413 [66.5%] in the erenumab group; 208 [33.5%] in the OMPM group), 523 (84.2%) completed the treatment phase, and 98 (15.8%) discontinued the study. At month 12, significantly more patients assigned to erenumab vs OMPM achieved the primary end point (232 of 413 [56.2%] vs 35 of 208 [16.8%]; odds ratio [OR], 6.48; 95% CI, 4.28-9.82; P <.001). Compared with OMPMs, treatment with erenumab showed higher responder rate (314 of 413 [76.0%] vs 39 of 208 [18.8%]; OR, 13.75; 95% CI, 9.08-20.83; P <.001) on the PGIC scale (≥5 at month 12). Significant reduction in cumulative average MMDs was reported with erenumab treatment vs OMPM treatment (-4.32 vs -2.65; treatment difference [SE]: -1.67 [0.35] days; P < .001). Substantially fewer patients in the erenumab arm compared with the OMPM arm switched medication (9 of 413 [2.2%] vs 72 of 208 [34.6%]) and discontinued treatment due to adverse events (12 of 408 [2.9%] vs 48 of 206 [23.3%]). No new safety signals were identified. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that earlier use of erenumab in patients with EM who failed 1 or 2 previous preventive treatments provided greater and sustained efficacy, safety, and adherence than continuous OMPM. Trial Registration: ClinicalTrials.gov Identifier: NCT03927144.

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Importance: Calcitonin gene-related peptide (CGRP) is involved in the pathophysiology of cluster headache (CH). Prophylactic pharmacologic treatment options for chronic CH (CCH) are limited. The potential effects of erenumab, a CGRP receptor antagonist monoclonal antibody, in treating CCH have not been assessed. Objective: To evaluate the superiority of erenumab compared with placebo in the prophylaxis of CCH. Design, Setting, and Participants: A 12-week, double-blind, placebo-controlled randomized clinical trial (CHERUB01) was conducted at 11 sites in Germany from December 2, 2021, to September 27, 2023. Participants (aged 18-65 years) had a diagnosis of CCH, had no previous sufficient response to standard CCH prophylactic medications approved in Germany, and had experienced at least 9 attacks during screening. Intervention: Loading dose of erenumab (280 mg subcutaneously) or matching placebo in a 1:1 randomization, followed by another dose of erenumab (140 mg subcutaneously) or placebo 4 weeks later. Main Outcomes and Measures: The primary end point was the reduction of mean weekly CH attacks from baseline over weeks 5 and 6. Key secondary end points were 50% responder rates and changes in Patient Global Impression of Improvement (PGI-I) scores. Safety and tolerability were also assessed. A bayesian analysis scheme was used for statistical analysis. Results: This study randomized 81 participants (mean [SD] age, 48.9 [10.4] years; 60 men [74.1%]) with CCH (mean [SD], 21.5 [9.7] attacks per week) to erenumab (n = 41) or placebo (n = 40). Recruitment was stopped prematurely due to insufficient patient numbers meeting the inclusion criteria within the planned recruitment period. The primary end point was not met over weeks 5 and 6 of the double-blind phase because the mean (SD) reduction of weekly CH attacks was -7.3 (8.6) per week for erenumab and -5.9 (10.5) per week for placebo (group difference, -1.5 [95% credible interval [CrI], -5.7 to 2.8]). At weeks 5 and 6, the percentage of participants with a 50% or greater reduction in CH attacks was not significantly different between the erenumab (13 [31.7%]) and placebo (18 [45.0%]) groups (odds ratio, 0.5 [95% CrI, 0.2-1.5]). PGI-I scores were also not different between groups. More participants reported adverse events with erenumab than placebo (27 [65.9%] vs 17 [42.5%]), which were mostly of mild or moderate intensity. Conclusions and Relevance: In this clinical trial of patients with CCH, blockade of the CGRP receptor with erenumab was not successful in the prophylaxis of attacks. Future studies should revisit the role of CGRP in CCH. Trial Registration: ClinicalTrials.gov Identifier: NCT04970355; EudraCT Number: 2020-004399-16.

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