Fremanezumab for preventing migraine: <scp>NICE</scp> guidance

The National Institute for Health and Care Excellence (NICE) published, on 3 June 2020, a Technology appraisal guidance (TAG) the use of fremanezumab preventing migraine.1 Migraine is common disabling primary headache disorder2, affecting 10% men 22% women.4 prevalence migraine climbs to peak at 40 years age then declines in both sexes.5, 6 It ranked as seventh highest cause disability globally7 responsible 2.9% all life lost disability.7 In meta-analysis published 2018, globally, second lived with adults under 50 years.8 without aura can be summarised high impact, episodic associated symptoms features (see Table 1). typically lasts 4 72 hours patients are symptom free between each bout migraine.2, Positive visual symptoms: - small bright dots/stars, zigzag or jagged lines, flashes light, flickering white spots, colored dots/spots curved circular ‘bean-like’ forms like crescent C-shaped round 67% report least one positive phenomenon B: One more following fully reversible 1. Visual 2. Sensory 3. Speech and/or language 4. Motor 5. Brainstem 6. Retinal Negative scotoma, black dots, hemianopia, tunnel vision, anopia 38% negative C: Headache has >2 characteristics a. Unilateral location b. Pulsating quality c. Moderate severe pain intensity d. Aggravation by causing avoidance routine physical activity (eg walking, climbing stairs) At spreads gradually over ≥5 minutes Two occur succession Each individual 5–60 unilateral accompanied, followed within 60 Disturbances perception (DVP): blurred/foggy ‘like looking through heat waves water’ deformed images (alteration shape objects) snow, fractured oscillopsia, corona phenomena alteration distance (things look close far away) 45% DVP D: During >1 Nausea vomiting Photophobia phonophobia Patients typical experience visual, sensory motor developing several resolving hour. Those described 1).2, Chronic (CM) defined International Society (IHS) occurring 15 days month, 8 having 2).2 CM affects approximately 2% population11 reduced (QOL)12 increased risk anxiety, depression, chronic health care resource.11 On ≥8 days/month >3 months, fulfilling any Criteria C 1.1 B 1.2 Believed patient onset relieved triptan ergot derivative IHS also state that 50% diagnosed revert when acute treatments stopped.2 phase 2 trials comparisons were made frequency (HFEM) CM, where HFEM was as:16 • month months 14 probable could take standard preventative before study medication no than per maximum opioid barbiturate use. Early studies demonstrated link calcitonin gene-related peptide (CGRP),15 much debate CGRP blockers treatment migraine.15 receptors found central peripheral nervous systems, most importantly trigeminovascular pathways.15 Humans have two isoforms – -αCGRP -βCGRP β-CGRP spinal afferents, enteric system. receptor three subunits activity-modifying protein 1 (RAMP1), calcitonin-like (CLR) component (RCP).15 Gepants first class drugs act antagonist. olcegepant, which effective but had low oral bioavailability.15 Following proof concept olcegepant five other gepants studied, including telcagepant, ubrogepant , rimegepant, BI 44370 TA MK-3207. Further development suspended liver toxicity repeat exposure. Anti-CGRP monoclonal antibodies (mAbs) target ligand its canonical receptor.16 They specificity degraded cleared reticuloendothelial system involvement kidney.16 Drug interactions minimal, they do not cross blood brain barrier significant amounts require parenteral administration. mAbs long half-life six weeks allowing administration either monthly quarterly.16 potential produce neutralising possibility hypersensitivity injection site. (a-CGRP mAbs) been engineered minimise this response site reactions extensively studied.16 There four a-CGRP preventive approved FDA date erenumab, galcanezumab 3) different IgG subtypes, methods administration, bioavailability, cell line presence murine proteins.16 important difference fourth targets receptor. All effective, well tolerated safe II III trials. Mammalian (Chinese hamster ovary) Fremanezumab humanised IgG2a antibody potently selectively binds ligand. administered subcutaneously. dose 225mg quarterly 675mg. studied (HALO) migraine.16 targeting unlikely need titration, speed dosing regimen. tolerability profile similar placebo lack serious adverse events, likely enhance long-term outcomes, better concordance compliance. current evidence shows overuse (MOH) given reduction use, absence active management MOH. A series clinical trials17-19 sustained improvement days, headache-related up 12 migraine. Another study20 showed migraine-specific life, overall status, patients’ global impression change productivity compared placebo. Adverse event (AE) assessment included monitoring, laboratory testing, checking vital signs, 12-lead ECGs, examination mental using Columbia-Suicide Severity Rating Scale (C-SSRS), electronic.19 AEs reported 84–89% groups, being reactions, reason stop treatment. leading stopping occurred 3% 5% patients, AE events 5–7% across groups.19 NICE accepted impact level migraine, an effect wellbeing ability work.1 recognised clinically meaningful, whereas 30% meaningful.1 Expert opinion recommended failed reasonable threshold consideration fremanezumab, trial further agents may side-effects.1 This mirrors botulinum toxin type (Botox).21 able respond access Botox.21 that: subgroup internationally FOCUS provides relevant But does reflect eligible practice differences doses affect applicability results comparative effectiveness unknown Botox discontinuation rates higher expected Which cost-effectiveness No conflicts interest declared. Dr Fontebasso member British Association Study Headache, American Society.