Colchicine

Colchicine is an old drug known to interfere with microtubule polymerization, therefore affecting white blood cell diapedesis, endocytosis, and exocytosis. More recently, it has been shown to inhibit the NLRP3 inflammasome, perhaps through its effects on microtubule polymerization, and therefore inhibit inflammasome formation and subsequent IL-1 and IL-18 production. It has a narrow therapeutic window, with intolerance mainly due to GI side effects, and significant and potentially dangerous interactions with multiple medications, and is overall considered a weak anti-inflammatory medication. However, when used early in safe doses, it is an effective therapeutic in pericarditis, gout, familial mediteranean fever, behcet’s, and sweet syndrome. Likely its prophylactic and early use efficacy is related to its ability to prevent amplification of inflammatory pathways.

All interactions between colchicine and COVID19 are entirely theoretical and include: reduction of neutrophil recruitment, reduction of ACE2 expression and receptor mediated endocytosis (ACE2 identified as the receptor by which COVID19 enters cells), reduction of virus exit from cells, and inhibition of the NLRP3 inflammasome (the inflammasome which SARS-COV-1 activates).
There are several studies under way to evaluate the use of colchicine for patients with COVID19 however there is no data to date. At this time colchicine is NOT recommended outside of a clinical trial.

Given colchicine GI side effects and risk for unblinding, we recommend that randomized control trials consider use of safe placebo with similar side effect profile as done in the AMBER trial for patiromer (10.1016/S0140-6736(19)32135-X).