It's a warm summer evening in ancient Athens. Archimedes is sitting in the agora and notices redness, swelling and pain in his big toe after drinking a kylix of wine. He goes to the market and is given an herb by a local farmer. After taking the herb, his big toe starts to feel better. He runs through the streets crying "Eureka!".
Colchicine is an anti-inflammatory medication which is used to treat acute episodes of gout. It is derived from the plant Colchicum autumnaleor autumn crocus. It was in fact used in ancient Greece, but as a laxative. The ancient Egyptians used it to treat rheumatism. Colchicum plant extracts were used to treat gout starting about 550 AD. Benjamin Franklin, who suffered from gout, is credited with bringing Colchicum plants to the United States when he returned from Paris after completing his duties as French ambassador. Colchicine was first extracted in 1821 by French chemists and soon thereafter became a popular remedy for gout. It was approved for use in the US by the FDA in 1961. The anti-inflammatory effect of colchicine is very different from nonsteroidal anti-inflammatory (NSAID) medications and aspirin. For more than 50 years colchicine was used exclusively to treat gout. Over the past ten years it’s anti-inflammatory properties were found to be useful in heart disease. Even more recently, it has been used in COVID-19. So colchicine, an old drug, finds itself at the intersection of inflammation, heart disease and COVID-19. Here are some clinical scenarios where colchicine has found new uses.
Pericarditis is inflammation of the sac lining the heart (the pericardium). The most common cause of pericarditis is a virus, and symptoms are usually preceded by an upper respiratory infection, the flu or, recently, COVID-19. Chest pain is the main presenting symptom, often associated with changes on the EKG or fluid around the heart on echocardiogram. Acute episodes of pericarditis are treated with anti-inflammatory agents such as aspirin, NSAIDs, colchicine or steroids. Colchicine has been used since 1987 to treat acute pericarditis and recently it has been shown that colchicine combined with either an NSAID or aspirin was better for treatment than aspirin or NSAID alone. With the combination, symptoms usually resolve within 72 hours, but treatment should continue for three months to prevent repeat episodes. About 15 to 30% of patients will have recurrent episodes of pericarditis. As with acute bouts, colchicine plus either aspirin or an NSAID successfully treats recurrent pericarditis.
Coronary artery disease (CAD) or plaque in a heart artery can lead to a heart attack or chronic angina (chest pain). Low-grade inflammation within the walls of the heart arteries leads to plaque build up and blockage. Inflammation can also cause acute rupture of a plaque causing a heart attack. Previous research showed that a strong intravenous anti-inflammatory agent (a monoclonal antibody) improved outcomes for CAD patients but was expensive and had significant side effects. Would cheap, easily available colchicine be beneficial? Colchicine has been shown to reduce inflammation within the walls of arteries, so theoretically it should be helpful. Several studies examined the use of colchicine in chronic stable CAD patients and patients who had a recent heart attack. These studies show that colchicine consistently reduces the risk for cardiovascular outcomes (especially repeat heart stents). Therefore, it seems that colchicine can be added to the cardiac medication armamentarium.
COVID-19 is another inflammatory disease. In severe COVID-19, the immune system’s inflammatory response overtakes the body affecting the lungs, heart, and blood vessels especially hard. High dose, intravenous steroids are used to combat the inflammatory consequences of the disease. Given colchicine’s anti-inflammatory properties, can it be used to prevent serious complications in outpatients with mild COVID-19? Several trials are underway to answer the question, one of which was recently reported. The trial enrolled 4000 patients with a diagnosis of COVID-19 within the previous 24 hours. In addition, one high-risk characteristic was needed (older age, obesity, diabetes, hypertension or underlying heart or lung disease). Colchicine reduced hospitalizations, the need for a respirator and deaths. However, the trial was not peer-reviewed and with the sting of hydroxychloroquine fresh in mind, the data are being interpreted with caution. It is felt that colchicine may be beneficial, but that there is still insufficient evidence to use the medication. Fortunately, other trials are ongoing and may be able to provide yet another use for colchicine.
Currently, a massive amount of research is being conducted focusing on inflammation, it’s effects on the body and novel agents to treat it. Meanwhile, the tried and true drug colchicine, with known efficacy, few side effects, wide availability and low cost, may be an answer to treat inflammatory diseases both old and new.
