Assessing preparedness for Alzheimer disease‐modifying therapies in Australasian health care systems

• DOI: 10.5694/mja2.51880
• Publication Date: 2023-03-19T14:01:12Z
• Authors: Amy Brodtmann; David Darby; Carly Oboudiyat; Colin J Mahoney; Campbell Le Heron; Peter K Panegyres; Bruce Brew
• Keywords: Preparedness; Healthcare system

Therapeutic advancement is well underway, and the medical community needs to keep pace A further potential disease-modifying therapy (DMT), lecanemab, was approved by FDA for treatment of early Alzheimer disease in January 2023, with accompanying media releases on both licensing company's commitment safety appropriate pricing.4, 5 An application approval has been lodged Australia. These therapies are costly not without risk. Three deaths have reported related lecanemab.6 Patients receiving DMT require frequent monitoring MRI brain scans (four or more per year), as there a high rate clinically significant amyloid-related imaging abnormalities (ARIA), oedema (ARIA-E) macro- microhaemorrhages (ARIA-H). Although most cases ARIA asymptomatic, close mandated.7 So far, these associated increased volume loss (ie, atrophy). In addition, they fortnightly monthly intravenous infusions, infusion reactions common.2, 4 There an estimated 487 500 persons living all forms dementia Australia, at least half whom disease.8 Are we ready DMTs Australasia? this article, consider readiness community, highlight gaps our health care systems, provide recommendations increasing workforce capacity capability. We note that aducanumab meets only first (and weakest) criteria: it uncontestably removes cortical fibrillar amyloid.2, 9, 10 Lecanemab strongly positive its primary (change from baseline 18 months Clinical Dementia Rating Scale Sum Boxes [CDR-SOB], –0.45) secondary endpoints amyloid burden PET, –59.1 centiloids),4 but one- two-point change CDR-SOB regarded minimally important difference.11 debates prompted much introspection clinicians involved people dementia, especially regarding capacity.9 The introduction effective would likely changes delivery care. propose should incorporate consideration ramifications beyond issue drug efficacy. At present, patients any monoclonal antibody diagnosis validation PET cerebrospinal fluid (CSF) biomarker testing12 — neither which available universal Australia New Zealand. socio-economic implications major consideration.13 prior economic analyses had negligible clinical benefit improvement outcomes considerable cost,14 may be different lecanemab.5 Supportive current gold standard treatment, including symptomatic treatments non-pharmacological therapies. It fortunate multidisciplinary team model accepted practice care,15 models will modification. Physicians need upskilling cognitive disorders. Neurologists, geriatricians, psychiatrists poised upskilling, working general practitioners, neuropsychologists, other clinicians. large sector structured education molecular diagnostics. rapid access clinicians, neuroradiologists, advanced neuroimaging, CSF blood capabilities. Early specific subtypes finally horizon.16, 17 phenotypes do always match underlying pathology dementias,18 obtaining shown definitively management.19 Blood biomarkers look next five years. Furthermore, abnormal alone raise management issues, asymptomatic (amyloid causing decline) excluded trials (eg, those multiple microhaemorrhages). Moreover, optimal duration currently known. Guidelines detection developed12 honing updating. Reporting needed radiology skilled managed haemorrhage. Medicare codes generated purposes treatments. Precision medicine determine risk response expand. Apolipoprotein E (APOE) genotypes already known impact some anti-amyloid treatments.7 APOE Ɛ4 carriers faster progression than allele carriers, potentially affecting tests reimbursed Zealand, also concerned about consequences genetic testing life insurance.20 Genetic counselling before required states territories. Most late phase 3 development two four weekly infusions.2, Multiple sclerosis, another common neurological disease, could serve implementation. sclerosis past decades transformed prognosis, requiring restructure provision. Conservative estimates demand represent fivefold increase compared sclerosis. Infusion now part armamentarium many chronic diseases ancillary staffing manage complexities scheduling biweekly scans, complications arising. largely treated diagnosed memory clinics. Victoria network geriatrician-staffed Cognitive, Memory Services. Specialist public neurology services rare and, historically, relied heavily private rooms physicians psychiatrists. Only 15% Australian receive clinic, hospital settings.21 informal Fellowships ten years, position accredited Zealand Association Neurologists 2015. This oversubscribed since then, waiting list three years requests subspecialty trainees suggesting great expertise. sensitive lack Australasian fact advocacy groups applauded accelerated lecanemab United States. new pathology-specific DMTs. Other trials, results expected end 2023 ClinicalTrials.gov NCT04437511, NCT04388254, NCT04592874). pace. thank members Cognitive Neurology who contributed discussion consultation article. Open publishing facilitated Monash University, Wiley - University agreement via Council Librarians. Amy Brodtmann received fees consultancy Biogen Roche Eisai Scientific Advisory Boards. Bruce Brew reports speaker AbbVie, Janssen Viiv; Board; grants Biogen. Peter Panegyres David Darby Board aducanumab, investigator ENGAGE EMBARK trials. gantenerumab. Not commissioned; externally peer reviewed.