A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease.

O'Bryant SE1, Zhang F2, Johnson LA1, Hall J1, Edwards M3, Grammas P4, Oh E5,6, Lyketsos CG6, Rissman RA7,8.

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Abstract

BACKGROUND:

To date, the therapeutic paradigm for Alzheimer's disease (AD) focuses on a single intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy. Here we test a precision-medicine approach to AD therapy.

OBJECTIVE:

To determine if a baseline, blood-based proteomic companion diagnostic predicts response to NSAID therapy.

METHODS:

Proteomic assays of plasma from a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to rofecoxib (25 mg once daily), naproxen (220 mg twice-daily) or placebo.

RESULTS:

474 participants with mild-to-moderate AD were screened with 351 enrolled into the trial. Using support vector machine (SVM) analyses, 89% of the subjects randomized to either NSAID treatment arms were correctly classified using a general NSAID companion diagnostic. Drug-specific companion diagnostics yielded 98% theragnostic accuracy in the rofecoxib arm and 97% accuracy in the naproxen arm.

CONCLUSION:

Inflammatory-based companion diagnostics have significant potential to identify select patients with AD who have a high likelihood of responding to NSAID therapy. This work provides empirical support for a precision medicine model approach to treating AD.