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an affordable anti-inflammatory agent for atherosclerosis

Thompson, Peter L.a,b,c,d; Nidorf, S. Markb,d

doi: 10.1097/MOL.0000000000000552
THERAPY AND CLINICAL TRIALS: Edited by Erik S.G. Stroes and Gerald F. Watts

Purpose of review Inflammation has been shown to be central to the development and progression of atherosclerosis. Despite detailed understanding of its central role and the cellular dynamics, which contribute to atherosclerotic inflammation, there has been slow progress in finding suitable agents to treat it. The recent CANTOS trial showed that the interleukin-1β inhibitor canakinumab can improve outcomes after acute coronary syndromes. Being a monoclonal antibody, it is expensive and inconvenient to administer for long-term treatment. This review summarizes recent work in finding effective, affordable alternatives to canakinumab.

Recent findings Statin drugs have anti-inflammatory properties but separating their LDL lowering effect from their anti-inflammatory effect has been difficult. Drugs acting on targets outside of the interleukin-1β (IL-1β) pathway have been tested without finding a suitable candidate. Following the proof of principle provided by the success of canakinumab, other candidates targeting the IL-1β pathway are undergoing detailed evaluation. The most likely candidates are low-dose methotrexate and low-dose colchicine. The potential mechanisms and ongoing clinical trials are described.

Summary Targeting the IL-1β pathway has already been successful with canakinumab but its expense and inconvenience of administration may limit its widespread uptake for controlling inflammation in atherosclerosis. Low-dose methotrexate and low-dose colchicine are affordable and more accessible alternatives, currently undergoing detailed evaluation for safety and efficacy in large randomized controlled trials.

aHeart Research Institute, Sir Charles Gairdner Hospital

bHarry Perkins Institute of Medical Research

cSchool of Medicine and Pharmacology, University of Western Australia

dGenesisCare, Perth, Australia

Correspondence to Peter L. Thompson, MD, Heart Research Institute, Sir Charles Gairdner Hospital, Nedlands 6009, Perth, WA, Australia. E-mail:

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