OBJECTIVE: To evaluate the efficacy of monthly or quarterly fremanezumab in patients with chronic migraine or episodic migraine and documented inadequate response to 2, 3, or 4 classes of prior migraine preventive medications. METHODS: This is an exploratory analysis of a randomized, double-blind, placebo-controlled, phase 3b trial for patients with chronic migraine or episodic migraine and inadequate response to 2 to 4 prior migraine preventive medication classes randomized (1:1:1) to fremanezumab (quarterly or monthly) or placebo. In this exploratory analysis, changes from baseline in the monthly average number of migraine days during 12 weeks of double-blind treatment and adverse events were evaluated for predefined subgroups of patients by number of prior preventive medication classes with inadequate response. RESULTS: Overall, 414, 265, and 153 patients had inadequate response to 2, 3, and 4 preventive medication classes, respectively. Changes from baseline in monthly average migraine days during 12 weeks were significantly greater with fremanezumab compared with placebo for patients with documented inadequate response to 2 classes (least-squares mean difference vs placebo [95% confidence interval]: quarterly, -2.9 [-3.83, -1.98]; monthly, -3.7 [-4.63, -2.75]), 3 classes (quarterly, -3.3 [-4.65, -1.95]; monthly, -3.0 [-4.25, -1.66]), and 4 classes (quarterly, -5.3 [-7.38, -3.22]; monthly, -5.4 [-7.35, -3.48]) of migraine preventive medications (all p < 0.001). No significant treatment-by-subgroup interactions were observed for any outcome (p interaction > 0.20 for all). Adverse events were comparable for placebo and fremanezumab. CONCLUSION: Significant improvements in efficacy were observed with fremanezumab compared with placebo, even in patients who had previously experienced inadequate response to 4 different classes of migraine preventive medications.ClinicalTrials.gov identifier: NCT03308968.

• Klíčová slova
• CGRP, Chronic migraine, episodic migraine, treatment failure,
• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• migréna farmakoterapie   prevence a kontrola   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monoklonální protilátky aplikace a dávkování   terapeutické užití   MeSH
• senioři MeSH
• terapie neúspěšná MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• fremanezumab MeSH Prohlížeč
• monoklonální protilátky MeSH

BACKGROUND: The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment. METHODS: Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1-12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1-12. Safety was assessed through adverse events reported. RESULTS: Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1-12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported. CONCLUSION: PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries.Trial registration: encepp.eu: EUPAS35111.

• Klíčová slova
• Calcitonin gene-related peptide, chronic, episodic, real-world data, real-world evidence,
• MeSH
• bolesti hlavy MeSH
• dospělí MeSH
• lidé MeSH
• migréna * farmakoterapie   prevence a kontrola   MeSH
• monoklonální protilátky * MeSH
• prospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• pozorovací studie MeSH
• Názvy látek
• fremanezumab MeSH Prohlížeč
• monoklonální protilátky * MeSH

INTRODUCTION: Assessing the impact of migraine preventive treatments on acute medication consumption is important in clinical evaluation. The number of acute medication intakes per each monthly migraine day (MMD) could provide insights on migraine burden and represent a new proxy of treatment effectiveness in clinical trials and real-life studies. We evaluated the effect of monoclonal antibodies acting on calcitonin gene-related peptide (CGRP) pathway on the consumption of migraine acute medication in real-life. METHODS: In two headache centers in Prague (CZ), we included and followed up to 6 months consecutive patients treated with MoAbs acting on CGRP (erenumab or fremanezumab). For each month of treatment, we reported monthly drug intake (MDI) in doses of any medication, migraine-specific (MS), and non-migraine-specific (non-MS) medications, and computed a ratio between MMDs and MDI, i.e., Migraine Medication Index (MMI) for MS and non-MS medications. RESULTS: We included 90 patients (91.1% women) with a median age of 47 [interquartile range (IQR) 42-51] years; 81 (90.0%) treated with erenumab and 9 (10.0%) with fremanezumab. Median MMDs decreased from 11 (IQR 8-14) at baseline to 4 (IQR 2-5) at Month 3 (p < 0.001 vs. baseline) and 3 (IQR 2-6) at Month 6 (p < 0.001 vs. baseline). Median MDI decreased from 15 drug intakes (IQR 11-20) at baseline to four drug intakes (IQR 2-7) at Month 3 (p < 0.001) and four drug intakes (IQR 2-7) at Month 6 (p < 0.001).The corresponding MDIs for MS medications were 10 (IQR 6-14) at baseline, 3 (IQR 1-5, p < 0.001) at Month 3, and 2 (IQR 0-4, p < 0.001) at Month 6. Monthly drug intakes for non-MS medications were 4 (IQR 0-9) at baseline, 1 (IQR 0-3, p < 0.001) at Month 3 and at Month 6.Median MMI decreased from 1.32 (IQR 1.11-1.68) at baseline to 1.00 (IQR 1.00-1.50, p < 0.001) at Month 3 and 1.00 (IQR 1.00-1.34, p < 0.001) at Month 6. CONCLUSIONS: We confirmed that MoAbs acting on CGRP pathway decrease acute migraine medication consumption. We proposed a new index that can be easily applied in clinical practice to quantify migraine burden and its response to acute medication. Our index could help optimizing migraine acute treatment in clinical practice.

• Klíčová slova
• calcitonin gene-related peptide (CGRP), medication, migraine acute treatment, monoclonal antibodies, real-life,
• Publikační typ
• časopisecké články MeSH