Effect of canakinumab on frailty: A post hoc analysis of the CANTOS trial.

Autor: Orkaby AR; New England GRECC (Geriatric Research, Education, and Clinical Center), VA Boston Healthcare System, Boston, Massachusetts, USA.; Division of Aging, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Thomson A; Center for Cardiovascular Disease Prevention and Cardiovascular Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., MacFadyen J; Center for Cardiovascular Disease Prevention and Cardiovascular Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Besdine R; Alpert Medical School of Brown University, Providence, Rhode Island, USA., Forman DE; Section of Geriatric Cardiology, Department of Medicine (Divisions of Geriatrics and Cardiology), University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.; Geriatric Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA., Travison TG; Marcus Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, Massachusetts, USA., Ridker PM; Center for Cardiovascular Disease Prevention and Cardiovascular Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Jan; Vol. 23 (1), pp. e14029. Date of Electronic Publication: 2023 Nov 05.
DOI: 10.1111/acel.14029
Abstrakt: Although inflammation is strongly associated with frailty, whether medications that lower inflammation decrease frailty is unclear and randomized trial evidence is scant. We sought to test whether canakinumab, a therapeutic monoclonal antibody that inhibits IL-1β and reduces C-reactive protein (CRP), can lower frailty risk. This was a post hoc analysis of the Canakinumab ANti-inflammatory Thrombosis Outcome Study (CANTOS), a randomized double-blind placebo-controlled trial of 10,061 stable postmyocardial infarction patients randomized to subcutaneous canakinumab once every 3 months. Incident frailty was measured using a 34-item cumulative-deficit Frailty Index (FI). Time-to-event analysis using intent to treat. A total of 9942 CANTOS participants had data to calculate a baseline FI. Median age was 61 (IQR 54-68); 74% were male, 12% Asian, 3% Black, 80% White, and 16% Hispanic/Latino. At baseline, mean FI score was 0.12 and 13% were frail using a cutoff of 0.2. Over 5 years, 1080 participants (12.5%) became frail and mean FI scores increased to 0.14. There was no effect on frailty incidence according to randomization to any canakinumab dose versus placebo over time, HR 1.03 (0.91-1.17), p = 0.63. Results were similar using phenotypic frailty. Additionally, the primary findings of CANTOS in terms of canakinumab-associated cardiovascular event reduction were unchanged in analyses stratified by baseline frailty. In conclusion, among stable adult patients with atherosclerosis, random allocation to interleukin-1b inhibition with canakinumab versus placebo did not lower risk of incident frailty over 5 years. More randomized data are needed to understand the role of targeted anti-inflammatory medications for frailty prevention in older adults.
(© 2023 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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