Colchicine Abstracts 5 – Gout


The Use of Colchicine in Gout.
            (Finn, 1954) Download
Prof Cecil stated: “I do not know of any more dramatic treatment that to give a patient suffering from acute gout an intravenous injection of colchicine” along with sodium salicylate and iodine.

Intravenous colchicine in the management of gouty arthritis.
            (Graham and Roberts, 1953) Download
Many ancient remedies have survived the passage of centuries and still find their place in the modern pharmacopoeia. In most instances the secret of their action has come to light, and few, like coichicine, have defied the investigator for some 1,400 years.

The dissociation by colchicine of phagocytosis from increased oxygen consumption in human leukocytes.
            (Malawista and Bodel, 1967) Download
The effect of colchicine on the uptake of oxygen by human leukocytes during phagocytosis of live streptococci or of killed staphylococci was compared with the effect of colchicine on phagocytosis per se, measured in a sensitive bacterial system. The increase in oxygen consumption that normally accompanies phagocytosis was consistently diminished in leukocytes incubated with colchicine in concentrations as low as 2.5 x 10(-6) mole per L (1 mug per ml), and this inhibition was dosage dependent. Yet there was no evidence of decreased phagocytosis with concentrations of colchicine as high as 2.5 x 10(-4) mole per L (100 mug per ml). Furthermore, with measurements at 20, 40, and 60 minutes, the rate of phagocytosis was comparable with and without colchicine.A clue to the dissociation between oxygen consumption and phagocytosis was found in rapidly dried preparations of the incubated leukocytes. Ingested bacteria were present in both control and colchicine-treated granulocytes. In addition, control cells showed normal loss of granules (lysosomal particles) and prominent cytoplasmic vacuoles (digestive vacuoles). Colchicine-treated cells, however, showed less such degranulation and vacuolization. Measurements of granule-associated acid phosphatase activity after phagocytosis support the morphologic observations of less degranulation in colchicine-treated leukocytes. The muted metabolic and morpholgic response to phagocytosis in colchicine-treated cells may be important for the anti-inflammatory effect of colchicine in acute gouty arthritis. Colchicine may also find wider use in defining structure-function dependencies in metabolically stimulated cells.

Colchicine for acute gout.
            (van Echteld et al., 2014) Download
BACKGROUND:  This is an update of a Cochrane review first published in 2006. Gout is one of the most common rheumatic diseases worldwide. Despite the use of colchicine as one of the first-line therapies for the treatment of acute gout, evidence for its benefits and harms is relatively limited. OBJECTIVES:  To evaluate the benefits and harms of colchicine for the treatment of acute gout. SEARCH METHODS:  We searched the following electronic databases from inception to April 2014: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. We did not impose any date or language restrictions in the search. We also handsearched conference proceedings of the American College of Rheumatology and the European League against Rheumatism (2010 until 2013) and reference lists of identified studies. We searched the clinical trials register and the WHO trials register. SELECTION CRITERIA:  We considered published randomised controlled trials (RCTs) and controlled clinical trials (CCTs) evaluating colchicine therapy compared with another therapy (active or placebo) in acute gout. The primary benefit outcome of interest was pain, defined as a proportion with 50% or greater decrease in pain, and the primary harm outcome was study participants withdrawal due to adverse events. DATA COLLECTION AND ANALYSIS:  Two authors independently screened search results for relevant studies, extracted data into a standardised form and assessed the risk of bias of included studies. We pooled data if deemed to be sufficiently clinically homogeneous. We assessed the quality of the body of evidence for each outcome using the GRADE approach. MAIN RESULTS:  Two RCTs (124 participants) were included in this updated review, including one new RCT. We considered one trial to be at low risk of bias, while we considered the newly included trial to be at unclear risk of bias. Both trials included a placebo and a high-dose colchicine arm, although the colchicine regimens varied. In one trial 0.5 mg colchicine was given every two hours until there was either complete relief of symptoms or toxicity and the total doses were not specified. In the other trial a total of 4.8 mg colchicine was given over six hours. The newly identified trial also included a low-dose colchicine arm (total 1.8 mg over one hour).Based upon pooled data from two trials (124 participants), there is low-quality evidence that a greater proportion of people receiving high-dose colchicine experience a 50% or greater decrease in pain from baseline up to 32 to 36 hours compared with placebo (35/74 in the high-dose colchicine group versus 12/50 in the placebo group (risk ratio (RR) 2.16, 95% confidence interval (CI) 1.28 to 3.65), with a number needed to treat to benefit (NNTB) of 4 (95% CI 3 to 12). However, the total number of adverse events (diarrhoea, vomiting or nausea) is greater in those who receive high-dose colchicine versus placebo (62/74 in the high-dose colchicine group versus 11/50 in the placebo group (RR 3.81, 95% CI 2.28 to 6.38), with a number needed to treat to harm (NNTH) of 2 (95% CI 2 to 5). Only one trial included reduction of inflammation as part of a composite measure comprising pain, tenderness, swelling and erythema, each graded on a four-point scale (none 0 to severe 3) to derive a maximum score for any one joint of 12. They reported the proportion of people who achieved a 50% reduction in this composite score. Based upon one trial (43 participants), there was low-quality evidence that more people in the high-dose colchicine group had a 50% or greater decrease in composite score from baseline up to 32 to 36 hours than people in the placebo group (11/22 in the high-dose colchicine group versus 1/21 in the placebo group (RR 10.50, 95% CI 1.48 to 74.38) and 45% absolute difference).Based upon data from one trial (103 participants), there was low-quality evidence that low-dose colchicine is more efficacious than placebo with respect to the proportion of people who achieve a 50% or greater decrease in pain from baseline to 32 to 36 hours (low-dose colchicine 31/74 versus placebo 5/29 (RR 2.43, 95% CI 1.05 to 5.64)), with a NNTB of 5 (95% CI 2 to 20). There are no additional harms in terms of adverse events (diarrhoea, nausea or vomiting) with low-dose colchicine compared to placebo (19/74 and 6/29 respectively (RR 1.24, 95% CI 0.55 to 2.79)).Based upon data from one trial (126 participants), there is low-quality evidence that there are no additional benefits in terms of the proportion of people achieving 50% or greater decrease in pain from baseline up to 32 to 36 hours with high-dose colchicine compared to low-dose (19/52 and 31/74 respectively (RR 0.87, 95% CI 0.56 to 1.36). However, there were statistically significantly more adverse events in those who received high-dose colchicine (40/52 versus 19/74 in the low-dose group (RR 3.00, 95% CI 1.98 to 4.54)), with a NNTH of 2 (95% CI 2 to 3).No trials reported function of the target joint, patient-reported global assessment of treatment success, health-related quality of life or withdrawals due to adverse events. We identified no studies comparing colchicine to non-steroidal anti-inflammatory drugs (NSAIDs) or other active treatments such as glucocorticoids (by any route). AUTHORS' CONCLUSIONS:  Based upon only two published trials, there is low-quality evidence that low-dose colchicine is likely to be an effective treatment for acute gout. We downgraded the evidence because of a possible risk of selection and reporting biases and imprecision. Both high and low-dose colchicine improve pain when compared to placebo. While there is some uncertainty around the effect estimates, compared with placebo, high-dose but not low-dose colchicine appears to result in a statistically significantly greater number of adverse events. Therefore low-dose colchicine may be the preferred treatment option. There are no trials about the effect of colchicine in populations with comorbidities or in comparison with other commonly used treatments, such as NSAIDs and glucocorticoids.



Finn, N (1954), ‘The Use of Colchicine in Gout.’, Ann Rheum Dis, 13 (2), 163. PubMedID: 18623844
Graham, W and JB Roberts (1953), ‘Intravenous colchicine in the management of gouty arthritis.’, Ann Rheum Dis, 12 (1), 16-19. PubMedID: 13031443
Malawista, SE and PT Bodel (1967), ‘The dissociation by colchicine of phagocytosis from increased oxygen consumption in human leukocytes.’, J Clin Invest, 46 (5), 786-96. PubMedID: 6025483
van Echteld, I, et al. (2014), ‘Colchicine for acute gout.’, Cochrane Database Syst Rev, 8 CD006190. PubMedID: 25123076