Colchicine - From rheumatology to the new kid on the block: Coronary syndromes and COVID-19

Abstract

Colchicine is an effective anti-inflammatory agent used to treat gout, coronary artery disease, viral pericarditis, and familial Mediterranean fever. It has been found to act by preventing the polymerization of the protein called tubulin, thus inhibiting inflammasome activation, proinflammatory chemokines, and cellular adhesion molecules. Accumulating evidence suggests that some patients with coronavirus disease 2019 (COVID-19) suffer from "cytokine storm" syndrome. The ideal anti-inflammatory in this setting would be one that is readily available, cheap, orally administered, with a good safety profile, well- tolerated, and that prevents or modulates inflammasome activation. The researchers selected colchicine for their study. This paper is a review of the literature describing the effects of colchicine, which is a drug that is being increasingly used, especially when standard therapy fails. Colchicine was shown to reduce inflammatory lung injury and respiratory failure by interfering with leukocyte activation and recruitment. In this publication, we try to systematically review the current data on new therapeutic options for colchicine. The article focuses on new data from clinical trials in COVID-19, rheumatic, cardiovascular, and other treatment such as familial Mediterranean fever, chronic urticaria, and PFAPA syndrome (periodic fever, aphthous, stomatitis, pharyngitis, and cervical adenitis). We also summarize new reports on the side effects, drug interactions, and safety of colchicine.

Keywords: COVID-19; cardiovascular diseases; colchicine; rheumatic diseases.

Figure 1

Mechanism of action of colchicine with regard to its potential role in the treatment of coronavirus disease 2019 (COVID-19) [–4]; TLR4 — toll-like receptor 4; RIG-I — retinoic acid-inducible gene I; NALP3 — NACHT, LRR, and PYD domains-containing protein 3; IL-1β — interleukin 1beta; IL-6 — interleukin 6; IL-18 — interleukin 18; IL-1R — interleukin-1 receptor; TNF-α — tumor necrosis factor alpha; VEGF — vascular endothelial growth factor.

Figure 2

Risk ratios of clinical outcomes with colchicine versus placebo. Based on [32]; RR — relative risk; CI — confidence interval; MACE — major adverse cardiac events; CV — cardiovascular; MI — myocardial infraction; NS — not significant.

Figure 3

The incidence and relative risk of adverse events in patients using colchicine compared to placebo and comparator drugs. Gastrointestinal included: diarrhea, nausea, vomiting, abdominal pain, loss of appetite, gas, constipation, tarry stools, and peptic ulcers; muscle included: myalgia, muscle cramps, elevated creatine phosphokinase and muscle weakness; infectious included: urinary tract infection, parotiditis, shingles, upper respiratory tract infection, nasopharyngitis and sinus congestion; liver included: increased liver enzymes, hepatitis, hepatotoxicity, and hepatic abnormalities; sensory included: dysesthesia in the legs and paresthesia; hematology included: anemia, bone marrow toxicity, leukopenia, and purpura. Based on [63]; CI — confidence interval.

Figure 4

Central illustration. Colchicine is obtained from Colchicum autumnale and is characterized by anti-inflammatory, immunomodulatory, and antimicrotubular properties. It also reduces uric acid levels. Colchicine is used in the treatment of rheumatic diseases, cardiovascular diseases, and recently also coronavirus disease 2019 (COVID-19).