Although colchicine first received approval from the US Food and Drug Administration in 2009, its modern use dates back two centuries. Indeed, papyri dating from 1500 BC describe the use of colchicine’s source plant—Colchicum autumnale—for pain and inflammation, making colchicine one of the world’s oldest anti-inflammatory therapeutics.35 Currently, colchicine is approved for treating and preventing acute gout and familial Mediterranean fever, and is used off label in Behçet’s disease, pericarditis and other inflammatory conditions.36
Colchicine trials in COVID-19
The recent open-label, multicentre Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial in the UK demonstrated a reduction in 28-day mortality with dexamethasone (n=2104) vs usual care (n=4321) in patients hospitalised with severe COVID-19.69 These data support the principle that an anti-inflammatory strategy in COVID-19 may be helpful. However, glucocorticoids such as dexamethasone have intrinsic immunosuppressive drawbacks that colchicine does not share.
Several early studies have evaluated the benefit of colchicine in COVID-19 patients. A retrospective single-centre study of 87 ICU patients with COVID-19 demonstrated a lower risk of death in patients on colchicine (adjusted HR 0.41, 95% CI 0.17 to 0.98).70 The Greek Effects of Colchicine in COVID-19 (GRECO-19) trial was the first prospective open-label randomised trial evaluating colchicine versus usual care in early hospitalised patients. This study of 105 patients found a significant reduction in the primary clinical outcome of a two-point deterioration on WHO disease severity scale.71 The authors additionally noted suppression of D-dimer levels in the colchicine vs control group.71 An Italian study compared 122 hospitalised patients who received colchicine plus standard-of-care (lopinavir/ritonavir, dexamethasone or hydroxychloroquine) with 140 hospitalised patients receiving standard-of-care alone. Colchicine had a significant mortality benefit (84% vs 64% survival) vs controls.72 A third prospective study randomised 38 hospitalised COVID-19 patients to colchicine or placebo in a double-blinded manner.73 Patients receiving colchicine had less need for supplemental oxygen at day 7 (6% vs 39%) and were more likely to be discharged at day 10 (94% vs 83%). Colchicine subjects also had greater reduction of CRP, and no increase in serious adverse events.73 Additional inpatient studies are ongoing (online supplemental table 2). Although the permitted use of other treatments could have biased the impact of colchicine in these studies, in the GRECO-19 trial no glucocorticoids were administered and other medications did not differ between the two groups; in the Italian study, there was no difference in outcomes among patients given colchicine who did or did not also receive dexamethasone.
Given its ease of use, tolerability and low cost, an argument for studying colchicine in the outpatient setting, to reduce hospitalisation and adverse outcomes, may be even more compelling. Unfortunately, data on the use of colchicine in the setting of outpatient COVID-19 cases are sparse. In a very small case series from Italy, nine outpatients with COVID-19 were administered colchicine, of whom only one subject was ultimately hospitalised. The hospitalised patient received 4 days of oxygen therapy and was discharged.74 Moreover, all patients experienced defervescence within 72 hours of colchicine initiation, suggesting an antipyretic effect. While these reports are insufficient to recommend colchicine for COVID-19 in clinical practice, they provide support for further study of colchicine in COVID-19, including in the outpatient setting. The ongoing ColCorona Trial (www.colcorona.net) is a large placebo-controlled trial of colchicine use within 2 days of COVID-19 diagnosis, regardless of symptoms, in patients with comorbidities that place patients at a higher risk of developing complications related to COVID-19 that may provide additional information.
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