Antiamyloid Monoclonal Antibody Therapy for Alzheimer Disease: Emerging Issues in Neurology

Abstract

With recent data demonstrating that lecanemab treatment can slow cognitive and functional decline in early symptomatic Alzheimer disease (AD), it is widely anticipated that this drug and potentially other monoclonal antibody infusions targeting β-amyloid protein will imminently be realistic options for some patients with AD. Given that these new antiamyloid monoclonal antibodies (mAbs) are associated with nontrivial risks and burdens of treatment that are radically different from current mainstays of AD management, effectively and equitably translating their use to real-world clinical care will require systematic and practice-specific modifications to existing workflows and infrastructure. In this Emerging Issues in Neurology article, we provide practical guidance for a wide audience of neurology clinicians on logistic adaptations and decision making around emerging antiamyloid mAbs. Specifically, we briefly summarize the rationale and available evidence supporting antiamyloid mAb use in AD to facilitate appropriate communication with patients and care partners on potential benefits. We also discuss pragmatic approaches to optimizing patient selection and treatment monitoring, with a particular focus on the value of incorporating shared decision making and multidisciplinary collaboration. In addition, we review some of the recognized limitations of current knowledge and highlight areas of future evolution to guide the development of sustainable and flexible models for treatment and follow-up. As the field enters a new era with disease-modifying treatment options for AD, it will be critical for neurology practices to prepare and continually innovate to ensure optimal outcomes for patients.

Figure 1. A Pragmatic Model for Clinical Implementation of Antiamyloid Monoclonal Antibody Therapies for Alzheimer Disease

Comprehensive advanced planning, multidisciplinary stakeholder engagement, and iterative adaptations are all critical for neurology practices to sustainably incorporate antiamyloid monoclonal antibody therapies into viable options for qualifying patients with Alzheimer disease. Practice-specific choices on appropriate patient selection, drug administration protocols, and processes for treatment monitoring all have the potential to affect response to treatment for patients and risks of complications from treatment for patients and health systems. This clinical decision making will benefit from remaining dynamic to changes at the practice level (e.g., capacity for safety MRIs), research level (e.g., identification of new risk factors for ARIA), and patient level (e.g., clinical progression or other factors precluding further therapy). ARIA = amyloid-related imaging abnormalities; EMR = electronic medical record; MCI = mild cognitive impairment.

Figure 2. Potential Template for Patient Education on Antiamyloid Monoclonal Antibody Therapies for Alzheimer Disease

Almost all patients with Alzheimer disease will have initial interest in a new treatment option for a progressive, devastating disorder. Patient-friendly educational tools may assist with automated handling of initial inquiries, setting appropriate expectations, and transitioning discussions beyond simple drug availability and toward a broader consideration of treatment aims, risks, burdens, and alternatives.

Figure 3. Suggested Management Based on ARIA Radiologic Severity and Clinical Condition

A suggested framework for managing imaging findings of ARIA is displayed, with differentiations by clinical and radiologic severity noted. Grading of radiographic ARIA is based on the US Food and Drug Administration prescribing label for lecanemab as follows: (ARIA-E) mild—one site of sulcal or cortical/subcortical FLAIR hyperintensity measuring <5 cm; moderate—one site of FLAIR hyperintensity measuring 5–10 cm or more than 1 site of FLAIR hyperintensity each measuring <10 cm; and severe—any site of FLAIR hyperintensity measuring >10 cm; (ARIA-H) mild—≤4 treatment-emergent microhemorrhages or 1 focal area of superficial siderosis; moderate—5–9 treatment-emergent microhemorrhages or 2 focal areas of superficial siderosis; and severe—10 or more treatment-emergent microhemorrhages or 3 or more focal areas of superficial siderosis. Importantly, practice and provider-specific clinical decision making that is appropriately individualized to the patient will be inherent to optimizing management of complications of therapy with antiamyloid monoclonal antibodies for Alzheimer disease. ARIA = amyloid-related imaging abnormalities; ARIA-E = ARIA with edema/effusion; ARIA-H = ARIA with microhemorrhage/hemosiderosis; FLAIR = fluid-attenuated inversion recovery.