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Effect of Erenumab on Functional Outcomes in Patients with Episodic Migraine J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-324396 on 5 January 2021. Downloaded from Original research Effect of erenumab on functional outcomes in patients with episodic migraine in whom 2–4 preventives were not useful: results from the LIBERTY study Michel Lanteri- Minet,1,2 Peter J Goadsby ,3 Uwe Reuter,4 Shihua Wen,5 Peggy Hours- Zesiger,6 Michel D Ferrari,7 Jan Klatt 6 ► Additional material is ABSTRACT versus placebo in patients in whom 2–4 preventives published online only. To view Objective To evaluate the effect of erenumab on had not been useful from the Phase 3b LIBERTY please visit the journal online study on patient- reported, functional outcomes. (http:// dx. doi. org/ 10. 1136/ patient-reported, functional outcomes in patients with jnnp- 2020- 324396). episodic migraine (EM) in whom 2–4 preventives were These include outcomes assessing the impact of not useful from the Phase 3b LIBERTY study. migraine on everyday activities and work produc- 1Pain Department and FHU Methods As previously reported, 246 patients with tivity as well as those assessing, physical and func- InovPain, CHU Nice – Côte Azur EM with 2–4 prior failed preventives were randomised tional impairment. An improvement in these areas Université, Nice, France 2INSERM U1107 Migraine 1:1 to subcutaneous erenumab 140 mg or placebo every indicates improved quality of life for patients. and Trigeminal Pain, Auvergne 4 weeks for 12 weeks. This analysis evaluated Migraine University, Clermont- Ferrand, Physical Function Impact Diary (MPFID), Headache France METHODS 3 Impact Test (HIT-6) and Work Productivity and Activity King’s College London, NIHR/ Standard protocol approvals, registrations and Wellcome Trust King’s CRF, Impairment (WPAI) scores at Week 12. P values were London, UK nominal without multiplicity adjustment. patient consents 4Department of Neurology, Results Erenumab significantly improved MPFID- The LIBERTY study is registered with Clini- Charite Universitatsmedizin Physical Impairment (PI) and Everyday Activities (EA) calTrials.gov (NCT03096834). The final study Berlin, Berlin, Germany scores versus placebo (treatment difference (TD) (95% CI) protocol, informed consent form and accompa- 5Novartis Pharmaceuticals Corp, nying materials provided to study patients were copyright. East Hanover, New Jersey, USA MPFID-PI: −3.5 (−5.7 to –1.2) (p=0.003); MPFID-EA: 6Novartis Pharma AG, Basel, −3.9 (−6.1 to –1.7)) (p<0.001) at 12 weeks. Patients on reviewed and approved by an independent ethics Switzerland erenumab were more likely to have a ≥5- point reduction committee or relevant institutional review board 7 Department of Neurology, in MPFID score (OR vs placebo (95% CI) MPFID- EA: 2.1 at all participating sites. This study was conducted Leiden University Medical in accordance with International Council for Center, Leiden, the Netherlands (1.2 to 3.6); MPFID-PI: 2.5 (1.4 to 4.5)). A similar trend was observed for HIT-6 (TD: −3.0; p<0.001); significantly Harmonisation Good Clinical Practice guidelines. All patients provided written informed consent. All Correspondence to higher proportions of patients on erenumab reported Dr Michel Lanteri- Minet, Pain a ≥5- point reduction (OR (95% CI): 2.4 (1.4 to 4.1)). centres complied with local regulations. Department and FHU InovPain, In three out of four WPAI domains, erenumab showed Centre Hospitalier Universitaire improvement versus placebo. de Nice, Nice 06003, France; Study design Conclusion At 12 weeks, erenumab was efficacious on lanteri- minet. m@ chu- nice. fr This analysis was based on data from the Phase http://jnnp.bmj.com/ functional outcomes in patients with EM in whom 2–4 3b, 12- week, randomised, double- blind, placebo- Received 25 June 2020 preventives were not useful. controlled, multicentre, parallel group LIBERTY Revised 10 November 2020 Trial registration details ClinicalTrials. gov identifier: study conducted from 20 March 2017 until 27 Accepted 8 December 2020 NCT03096834. Published Online First 5 January October 2017, in 16 countries across Europe and 2021 Australia involving patients with EM in whom 2–4 preventives were not useful. The study design is 7 INTRODUCTION reported elsewhere. Briefly, the study included a on September 29, 2021 by guest. Protected Erenumab is a fully human monoclonal antibody screening phase (0 to 2 weeks), baseline phase (4 that inhibits the canonical calcitonin gene- related weeks), double-blind treatment phase (12 weeks), peptide (CGRP) receptor.1 Clinical studies have an ongoing open- label treatment phase (156 weeks) demonstrated the efficacy and safety of erenumab in and a safety follow-up phase (12 weeks). patients with episodic migraine (EM)2 3 and chronic Patients were randomised to receive placebo or migraine (CM)4 including in those with prior erenumab 140 mg subcutaneously in a 1:1 ratio, preventive migraine treatment failures.5 6 Results once every 4 weeks for 12 weeks. Patients who © Author(s) (or their from the Phase 3b LIBERTY study confirmed that completed the 12-week double-blind treatment employer(s)) 2021. Re- use permitted under CC BY-NC . No erenumab is a potential treatment for the manage- phase of the LIBERTY study were eligible to partici- commercial re-use . See rights ment of patients with EM in whom 2–4 preventives pate in an ongoing open- label treatment phase. The and permissions. Published were not useful.7 results of the extension phase will be reported sepa- by BMJ. An important component of migraine manage- rately. This article reports results from the 12- week To cite: Lanteri- Minet M, ment is to evaluate headache- related functional double-blind treatment phase. Goadsby PJ, Reuter U, et al. J impairment reported by patients and measured by Patients completed PRO questionnaires using an Neurol Neurosurg Psychiatry patient- reported outcomes (PROs).8 The aim of electronic diary (eDiary) platform. PRO question- 2021;92:466–472. this analysis was to evaluate the effect of erenumab naires were administered to patients either at home 466 Lanteri- Minet M, et al. J Neurol Neurosurg Psychiatry 2021;92:466–472. doi:10.1136/jnnp-2020-324396 Migraine J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-324396 on 5 January 2021. Downloaded from or during visits to the clinic at baseline and during the double- daily activities because of headache, feeling ‘fed up’ or irritated blind treatment phase. because of headache and headaches limiting ability to concen- trate or work on daily activities. No recall period is specified for Inclusion criteria and previous preventive failures the first three items, while the past 4 weeks is used for the last Patients aged 18 to 65 years, with EM (4 to 14 migraine days three items. HIT-6 scores are categorised into four grades, repre- per month)9 were included in the LIBERTY study.7 Eligible senting little or no impact (49 or less), some impact (50 to 55), patients had (1) failed 2–4 prior preventive treatments: propran- substantial impact (56 to 59) and severe impact (60 to 78) due olol/metoprolol, topiramate, flunarizine, valproate/divalproex, to headache; higher scores suggest negative impact. The thresh- amitriptyline, venlafaxine, lisinopril, candesartan or other olds for minimally important intergroup differences are well 14 15 locally approved preventives (cinnarizine in the Czech Republic; established;­−1.5­for­EM ­and­−2.3­for­CM. In an individual indoramine in France; nadolol in Spain; oxetorone in France; patient, a reduction of 5 points is usually considered clinically 16 and pizotifen in Austria, the Czech Republic, France, the Nether- meaningful with negative change indicating improvement. lands, Sweden and the UK); (2) failed or were not suitable for at Functional impairment in patients with migraine was measured least one of: propranolol/metoprolol, topiramate or flunarizine; using change in HIT-6 score from baseline to Week 12, and and (3) failed or were not suitable for valproate/divalproex. percentage­of­patients­with­a­≥5-­point­reduction­in­total­HIT-6­ Efficacy failure was defined as no meaningful reduction in score between baseline and Week 12. frequency of migraine attacks after administration of drugs for 10 at least 2 to 3 months, at generally accepted therapeutic doses Work Productivity and Activity Index within the 5 years before screening. Tolerability failure was The Work Productivity and Activity Index (WPAI) (change from defined as documented discontinuation due to adverse events at baseline at Week 12), a commonly used scale that assesses work any previous time. For the purposes of this study, being deemed productivity and economic consequences of various disease unsuitable for treatment was defined as a patient being consid- states, was also evaluated. Although a headache-specific version ered to be ineligible for a treatment for medical reasons such exists, few trials have used the WPAI to assess the effects of as contraindications or precautions included in local labels, preventive treatment.17 national guidelines or other locally binding documents, or other In the WPAI- Headache tool, patients are asked six questions medically relevant reasons as confirmed by the treating physi- about work and activity impairment due to headache, including cian. Treatment failure and unsuitability were assessed on the hours worked and hours missed in the last 7 days. WPAI scores 7 basis of the patient’s medical history and medical judgement. are based on 1-item (presenteeism, activity impairment), 2-items (absenteeism) and multiple items (overall work productivity); a Outcomes score cannot be calculated if there is a missing response to the copyright. The primary and secondary efficacy endpoints of the LIBERTY corresponding item. The questionnaire was collected weekly study have been reported previously.7 and took approximately 10 min to complete at home. Due to the design of the questionnaire, patients who were not employed Migraine Physical Function Impact Diary or who were employed but with extensive ‘no-work status’ Additional endpoints including change from baseline in scores were not included in the analysis.
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