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Fulltext The effect of colchicine on mortality outcome and duration of hospital stay in patients with COVID-19: A meta-analysis of randomized trials

Kow CS, Lee LH, Ramachandram DS, Hasan SS, Ming LC, Goh HP

Immun Inflamm Dis, 2022 Feb;10(2):255-264.
PMID: 34970856 DOI: 10.1002/iid3.562

BACKGROUND: Overactivation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome can lead to severe illness in patients with coronavirus disease-2019 (COVID-19). The NLRP3 inhibitor, colchicine, therefore, appears to be promising for the treatment of COVID-19.
AIMS: We aimed to perform a meta-analysis of randomized trials investigating the effect of colchicine in patients with COVID-19.
MATERIALS & METHODS: We systematically searched electronic databases and clinical trial registries (up to October 17, 2021) for eligible studies. The outcomes of interest were all-cause mortality and duration of hospital stay. Meta-analysis with the random-effects model was used to estimate the pooled odds ratio (OR) of mortality and 95% confidence interval (CI). The pooled standardized mean difference of duration of hospital stay with 95% CI between colchicine users and non-colchicine users was estimated using Cohen's d index.
RESULTS: The meta-analyses revealed no significant difference in the odds of mortality (pooled OR = 0.76; 95% CI: 0.53-1.07), but a significant reduction in the duration of hospital stay with the use of colchicine (pooled standardized mean difference = -0.59; 95% CI: -1.06 to -0.13).
DISCUSSION AND CONCLUSION: The ability of colchicine to reduce the length of stay in hospitalized patients with COVID-19 is consistent with its potential to prevent clinical deterioration via inhibition of NLRP3 inflammasome. Nevertheless, such beneficial effects of colchicine did not translate into mortality benefits in patients with COVID-19.

Matched MeSH terms: Colchicine/therapeutic use
The evidence from clinical trials on colchicine and corticosteroids' effect on COVID-19: a systematic review and meta-analysis

Bitar AN, Sulaiman SAS

Curr Med Res Opin, 2022 Dec;38(12):2097-2108.
PMID: 35819071 DOI: 10.1080/03007995.2022.2100654

OBJECTIVES: With no clear end for the outbreak, identifying the drugs that are effective in COVID-19's management is of utmost importance to reduce the impact on the general population and the healthcare systems.
METHODS: This is a systematic review and a meta-analysis evaluating the evidence from clinical trials on the effect of colchicine and corticosteroids against COVID-19. In this review, we have systematically searched five databases [(PubMed, Embase, clinicaltrials.gov, ICTRP, CINAHL (EBSCO)]. Cochrane's data extraction sheet was used to collect the required information, and RevMan-5.4.1 was used to conduct the meta-analysis and to assess the risk of bias. The review was registered in Prospero (CRD42022299718).
RESULTS: The total number of included studies was 17, with 18,956 participants; the majority were male 12,001. Out of which, 8772 participants were on colchicine, 569 took methylprednisolone, and 64 patients received prednisolone. The meta-analysis has shown that colchicine had no significant effect on reducing the mortality rate among COVID-19 patients [OR 0.98(95% CI 0.90-1.08), p = .70), I2:1%)], corticosteroids have significantly reduced the mortality rates [OR 0.55 (95% CI 0.33-0.91), p = .02, I2:40]. Colchicine did not reduce the incidence of ICU admissions [OR 0.74 (95% CI 0.39-1.40), p = .35, I2:0%], while steroidal drugs significantly reduced the ICU admissions [OR 0.42 (95% CI 0.23-0.78), p = .005, I2:0%]. Unlike steroidal drugs [OR 0.53 (95% CI 0.30-0.95), p = .03, I2:61%], colchicine failed to reduce the need for mechanical ventilation [OR 0.73 (95% CI 0.48-1.10), p = .13, I2:76%]. Steroidal drugs significantly reduced the duration of hospitalization among COVID-19 patients [OR -0.50 (95% CI -0.79-0.21), p = .0007, I2:36%].
CONCLUSIONS: The use of colchicine did not significantly reduce the mortality rate, ICU admissions, and mechanical ventilation among COVID-19 patients. Conversely, corticosteroids significantly reduced the mortality rate, ICU admissions, mechanical ventilation, and hospitalization duration among COVID-19 patients.

Matched MeSH terms: Colchicine/therapeutic use
Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial

Conen D, Popova E, Wang MK, Chan MTV, Landoni G, Reimer C, et al.

Am Heart J, 2023 May;259:87-96.
PMID: 36754105 DOI: 10.1016/j.ahj.2023.01.018

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery.
METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023.
CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Matched MeSH terms: Colchicine/therapeutic use
A survey on the management of gout in Malaysia

Yeap SS, Goh EM, Gun SC

Int J Rheum Dis, 2009 Dec;12(4):329-35.
PMID: 20374371 DOI: 10.1111/j.1756-185X.2009.01431.x

AIM: The aim of this study was to ascertain the management of gout by doctors in Malaysia.
METHODS: A cross-sectional questionnaire survey was carried out among doctors attending rheumatology post-graduate courses, where gout was not a lecture topic.
RESULTS: A total of 128 questionnaires were analyzed, of which the majority (67: 52.3%) were general practitioners. In the treatment of acute gout, 68.0% use non-selective non-steroidal anti-inflammatory drugs (NSAIDs), 53.9% use selective COX-2 inhibitors (coxibs), 66.4% use colchicine and 10.2% use allopurinol (ALLO). In the treatment of chronic gout, 36.7% use NSAIDs, 44.5% use coxibs, 19.5% use colchicine and 93% use ALLO. In both acute and chronic gout, corticosteroids (CS) are not used by over 90% of respondents. Fifty percent would stop ALLO during an acute attack. 95.3% do not start ALLO during an acute attack; 87.5% would start ALLO after the attack, with a median of 14 days afterwards. Once ALLO was started, 54.7% would continue indefinitely. Regarding target urate levels while on treatment, 10.9% would be satisfied with a high normal range, 21.9% middle of the range, 18.0% low normal range and 45.3% anywhere within the normal range. Fifteen percent would treat asymptomatic hyperuricemia.
CONCLUSIONS: In Malaysia, anti-inflammatory agents are most commonly used for the treatment of acute and chronic gout, with corticosteroid usage at a low level. However, there are areas of concern regarding the diagnosis of gout and the usage of ALLO which are not consistent with current guidelines

Matched MeSH terms: Colchicine/therapeutic use
Fulltext A rare cause of back pain and radiculopathy - spinal tophi: a case report

Wan SA, Teh CL, Jobli AT, Cheong YK, Chin WV, Tan BB

J Med Case Rep, 2019 Jan 08;13(1):8.
PMID: 30626451 DOI: 10.1186/s13256-018-1940-4

BACKGROUND: Gout is a monosodium urate deposition disease which is prevalent worldwide. The usual manifestations are crystal arthropathy and tophi deposition in the soft tissues. Spinal tophi may also occur and are rarely reported, resulting in various clinical manifestations such as back pain, spinal cord compression, radiculopathy, and even mimicking epidural abscess and spondylodiscitis.

CASE PRESENTATION: We report a case of a 42-year-old Chinese man with underlying gout who presented with back pain and radiculopathy. The diagnosis of spinal tophi was unsuspected and he was initially treated for epidural abscess and spondylodiscitis. He underwent a laminectomy and posterolateral fusion during which tophus material was discovered. He recovered and medications for gout were started.

CONCLUSION: Spinal tophi are rare. The diagnosis is difficult and spinal tophi may be mistaken for epidural abscess, spondylodiscitis, or neoplasm.

Matched MeSH terms: Colchicine/therapeutic use
Lower CYP2C9 activity in Turkish patients with Behçet's disease compared to healthy subjects: a down-regulation due to inflammation?

Goktaş MT, Hatta F, Karaca O, Kalkisim S, Kilic L, Akdogan A, et al.

Eur J Clin Pharmacol, 2015 Oct;71(10):1223-8.
PMID: 26233334 DOI: 10.1007/s00228-015-1899-7

BACKGROUND: We previously reported on a Swedish patient with Behçet's disease (BD) who was an ultra-rapid metaboliser of drugs catalysed by CYP2C9. Was this extreme metabolism caused by the disease?

AIM: This study aims to compare the genotype/phenotype of CYP2C9 in patients with BD and healthy subjects. As the occurrence of BD is high in Turkey, all subjects were recruited from this country.

METHODS: Genotyping of CYP2C9 was performed using standard PCR-RFLP and allele-specific PCR methods. Phenotyping of CYP2C9 was performed by administration of a 50-mg single oral dose of losartan and by calculating the urinary metabolic ratio (MR) of probe drug to its metabolite E-3174. Quantitation was performed by HPLC.

RESULTS: The frequency of CYP2C9*2 and *3 was not significantly different between the Behçet's disease patients (12.5 and 8.7%) and the healthy subjects (8.9 and 8.2%). The geometric mean losartan MR was higher in the 52 patients (1.75) than in the 96 healthy subjects (1.02) (p = 0.002; t-test). Within the genotypes *1/*1, there was a significant difference of MR between patients and healthy subjects (P = 0.006). All but three of the Behçet's disease patients were treated with colchicine. In nine subsequent patients, we found no significant effect of 2 weeks of treatment with colchicine on the CYP2C9 MR.

CONCLUSION: Contrary to expectation, the CYP2C9 activity was lower in Turkish BD patients compared to healthy subjects. As this seems not to be due to colchicine treatment, our hypothesis is that inflammation related to BD might have caused the down-regulation of the CYP2C9 activity due to immune cytokine reactions. The ultra-rapid metabolism of CYP2C9 substrate drugs in the Swedish patient was not due to her BD.

Matched MeSH terms: Colchicine/therapeutic use