- The therapeutic use of colchicine is well-established in gout and familial Mediterranean fever.
- Its primary mechanism of action is the inhibition of microtubule polymerization. Other mechanisms of action are not fully understood.
- Colchicine interferes with several inflammatory pathways.
- Immunomodulatory and anti-inflammatory effects are partly through:
- Inhibition of NALP3 inflammasome responsible for caspase-1 activation that leads to subsequent IL1β and IL18 production, which are key mediators in an inflammatory cascade.
- Overtime, indications of colchicine have been extended to conditions such as pericarditis, Behçet syndrome, calcium pyrophosphate crystal arthritis (CPP) and more.1
How Could It Help Now?
- Evidence suggests that patients with severe COVID-19 might have a cytokine storm syndrome, a state of hyperinflammation with increased proinflammatory cytokines (IL2, IL7, IL10, GCSF, IP10, MCP1, MIP1A and TNFα among others).2,3
- In the current absence of effective treatments of COVID-19, immunomodulatory and anti-inflammatory effects of colchicine are interesting enough to generate a randomized controlled trial (COLCORONA) on its efficacy.4
These statements come from multiple sources in regard to colchicine. The explained background of colchicine comes from a literature review of a total of 381 articles from 2008 to June 2014. This review reports that further understanding of newly discovered mechanisms of action of colchicine underlying its therapeutic efficacy will lead it to new indications.1
According to a prospective observational study of 41 patients in China, COVID-19 can cause an acute respiratory distress syndrome and patients are likely admitted to intensive care. Patients admitted to an ICU had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A and TNFα compared with non-ICU patients. Evidence suggest that cytokines storm could be associated with disease severity.3
As of April 4 2020, COLCORONA is a recruiting phase 3, multi-center, randomized, double-blind, placebo-controlled multicenter study of 6000 patients evaluating the efficacy and safety of colchicine in adult patients with COVID-19. The primary endpoint will be the composite of death or the need for hospitalization due to COVID-19 infection after 30 days.4
- Leung Y, Hui L, Kraus V (June 26 2015). Colchicine — update on mechanisms of action and therapeutic uses. Semin Arthritis Rheum. https://doi.org/10.1016/j.semarthrit.2015.06.013
- Mehta P, McAuley DF, Brown M, et al (March 16 2020). COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. https://doi.org/10.1016/S0140-6736(20)30628-0
- Huang C, Wang Y, Li X, et al (February 15 2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. https://doi.org/10.1016/S0140-6736(20)30183-5
- Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) (COVID-19). Retrieved from https://clinicaltrials.gov/ct2/show/NCT04322682