The potential role of Colchicine in preventing coronary vascular disease in childhood\u2010onset lupus: a new view on an old drug

Mark Gorelik,Stacy P. Ardoin,Dori Abel

doi:10.1186/s12969-021-00504-6

Abstract

BackgroundPatients with systemic lupus erythematous have a significantly increased risk of cardiovascular disease, which is not fully explained by traditional cardiovascular disease risk factors. Despite increasing life expectancy in patients with systemic lupus erythematous, mortality due to cardiovascular disease, the major cause of death in these patients, has not changed. Children with lupus suffer from more aggressive disease compared to their adult counterparts, and there is a growing concern for their increased risk of cardiovascular disease as they age.Body:There is an unmet need for therapies to address the increased risk of cardiovascular disease in childhood-onset lupus. Colchicine has many anti-inflammatory and cardiovascular protective properties, including inhibition of IL-1β and IL-18 activity, key proinflammatory cytokines that are predictive of future adverse cardiovascular events. In the Colchicine Cardiovascular Outcomes Trial (COLCOT), colchicine was recently found to have significant benefit with minimal risk in adults with previous myocardial infarction for prevention of secondary vascular disease. While adult studies are promising, no studies have been conducted in pediatric patients to investigate colchicine’s potential for cardiovascular protection in children and adolescents with lupus.ConclusionsStudies investigating colchicine’s potential role for cardiovascular protection are needed in pediatric patients with systemic lupus erythematous.

Highlights

Role of inflammation in Atherosclerosis and cardiovascular disease (CVD) All three components of the immune system – innate, cellular, and humoral immunity – are involved in the development of atherosclerosis
Adults with history of childhood-onset systemic lupus erythematous (SLE) have a standardized mortality ratio of 2.5, with CVD the most common reported cause of death, and they experience these complications at an early age, with average age of first myocardial infarction (MI) as early as 32 [7, 9]
Elevated levels of autoantibodies, including anti-oxLDL antibodies, anti-phospholipid antibodies, anti-cardiolipin antibodies, anti-β2GP1 antibodies, and anti-HSP antibodies, which contribute to endothelial damage and interrupt normal anti-atherosclerotic defenses, have been associated with atherosclerosis and thrombosis, and autoantigens within vessel walls and cholesterol molecules play a role in inflammatory processes underlying atherogenesis [18]

Summary

Background

Due to advances in diagnosis and management of systemic lupus erythematous (SLE), patients are living longer. Adults with history of childhood-onset SLE have a standardized mortality ratio of 2.5, with CVD the most common reported cause of death, and they experience these complications at an early age, with average age of first MI as early as 32 [7, 9]. Both traditional Framingham CVD risk factors and SLE-specific risk factors, primarily related to the immune-mediated pathogenesis of the disease, make SLE itself a clear, independent risk factor for CVD [10]. This article will review the current knowledge and background in therapy regarding cardiac atherosclerosis and coronary artery disease in childhood-onset and adult lupus, and will conclude by proposing investigation on the use of colchicine for prevention of CVD in young patients with SLE

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