Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study

Abstract

Actuality The course of the novel coronavirus disease (COVID-19) is unpredictable. It manifests in some cases as increasing inflammation to even the onset of a cytokine storm and irreversible progression of acute respiratory syndrome, which is associated with the risk of death in patients. Thus, proactive anti-inflammatory therapy remains an open serious question in patients with COVID-19 and pneumonia, who still have signs of inflammation on days 7–9 of the disease: elevated C-reactive protein (CRP)>60 mg/dL and at least two of the four clinical signs: fever >37.5°C; persistent cough; dyspnea (RR >20 brpm) and/or reduced oxygen blood saturation <94% when breathing atmospheric air. We designed the randomized trial: COLchicine versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients with COVID-19 (COLORIT). We present here data comparing patients who received colchicine with those who did not receive specific anti-inflammatory therapy. Results of the comparison of colchicine, ruxolitinib, and secukinumab will be presented later.Objective Compare efficacy and safety of colchicine compared to the management of patients with COVID-19 without specific anti-inflammatory therapy.Material and Methods Initially, 20 people were expected to be randomized in the control group. However, enrollment to the control group was discontinued subsequently after the inclusion of 5 patients due to the risk of severe deterioration in the absence of anti-inflammatory treatment. Therefore, 17 patients, who had not received anti-inflammatory therapy when treated in the MSU Medical Research and Educational Center before the study, were also included in the control group. The effects were assessed on day 12 after the inclusion or at discharge if it occurred earlier than on day 12. The primary endpoint was the changes in the SHOCS-COVID score, which includes the assessment of the patient’s clinical condition, CT score of the lung tissue damage, the severity of systemic inflammation (CRP changes), and the risk of thrombotic complications (D-dimer) [1].Results The median SHOCS score decreased from 8 to 2 (p = 0.017), i.e., from moderate to mild degree, in the colchicine group. The change in the SHOCS-COVID score was minimal and statistically insignificant in the control group. In patients with COVID-19 treated with colchicine, the CRP levels decreased rapidly and normalized (from 99.4 to 4.2 mg/dL, p<0.001). In the control group, the CRP levels decreased moderately and statistically insignificantly and achieved 22.8 mg/dL by the end of the follow-up period, which was still more than four times higher than normal. The most informative criterion for inflammation lymphocyte-to-C-reactive protein ratio (LCR) increased in the colchicine group by 393 versus 54 in the control group (p = 0.003). After treatment, it was 60.8 in the control group, which was less than 100 considered safe in terms of systemic inflammation progression. The difference from 427 in the colchicine group was highly significant (p = 0.003).The marked and rapid decrease in the inflammation factors was accompanied in the colchicine group by the reduced need for oxygen support from 14 (66.7%) to 2 (9.5%). In the control group, the number of patients without anti-inflammatory therapy requiring oxygen support remained unchanged at 50%. There was a trend to shorter hospital stays in the group of specific anti-inflammatory therapy up to 13 days compared to 17.5 days in the control group (p = 0.079). Moreover, two patients died in the control group, and there were no fatal cases in the colchicine group. In the colchicine group, one patient had deep vein thrombosis with D-dimer elevated to 5.99 µg/mL, which resolved before discharge.Conclusions Colchicine 1 mg for 1-3 days followed by 0.5 mg/day for 14 days is effective as a proactive anti-inflammatory therapy in hospitalized patients with COVID-19 and viral pneumonia. The management of such patients without proactive anti-inflammatory therapy is likely to be unreasonable and may worsen the course of COVID-19. However, the findings should be treated with caution, given the small size of the trial.

Efficacy and safety of colchicine in COVID-19: a meta-analysis of randomised controlled trials

“…All studies had used varying definitions of COVID-19 severity. The participants in treatment arms were comparable for the WHO clinical scale, 19 respiratory support, 20 Sequential Organ Failure Assessment Score, 21 National Early Warning Score 2, 24 symptomatic hospital and outpatient clinical score for COVID-19, 24 time from symptom to enrolment. 22 …”

Colchicine use in patients with COVID-19: a systematic review and meta-analysis

“…In this population, the primary endpoint did not reach statistical significance (OR=0.79, 0.61-1.03; p=0.08) (13). Other randomized controlled trials (RCT) and observational studies have also reported benefits for colchicine in COVID-19 (14)(15)(16)(17)(18)(20)(21). To our knowledge, only one prior meta-analysis has been conducted for colchicine in COVID-19 (22).…”

Colchicine use might be associated with lower mortality in COVID‐19 patients: A meta‐analysis

“…Hence, they were included in the quantitative analysis (Table 1 ). Three of the studies were randomized controlled trials 3 , 5 , 8 : one was quasi‐experimental, 9 and the remaining were observational. 2 , 6 , 10 , 11 , 12 The only included nonpeer‐reviewed publication by Tardif et al 8 accounted for the majority of included cases (4488 patients) and consisted of nonhospitalized patients.…”