Title | A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | O'Bryant, SE, Zhang, F, Johnson, LA, Hall, J, Edwards, M, Grammas, P, Oh, E, Lyketsos, CG, Rissman, RA |
Journal | J Alzheimers Dis |
Volume | 66 |
Issue | 1 |
Pagination | 97-104 |
Date Published | 2018 |
ISSN | 1875-8908 |
Abstract | BACKGROUND: To date, the therapeutic paradigm for Alzheimer's disease (AD) has focused 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. |
DOI | 10.3233/JAD-180619 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 30198872 |