The Evaluation of the Efficacy and Safety of Oral Colchicine in the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trails.

OBJECTIVE: To evaluate the efficacy and safety of oral colchicine in the treatment for knee OA. DESIGN: Meta-analysis. Data Sources. Embase, PubMed (MEDLINE), the Cochrane Library, and Web of Science from inception to December 12, 2021. Study Selection. RCTs comparing colchicine with placebo for knee OA were included. No language or date restrictions were applied. Two authors abstracted data and determined quality. Outcomes of interest included VAS-pain, WOMAC total index, and patient-reported adverse events. RESULTS: A total of five RCTs including 400 adult patients with OA met the inclusion criteria. The mean age of patients included was 56.05 years (range 21 to 79), and 80.87% were female. There was no difference in VAS-pain (MD -1.49; 95% CI -3.15, 0.17; p = 0.08) when compared colchicine group with placebo group. And there was no statistically difference in WOMAC total index (std. MD -0.13; 95% CI -0.64, 0.38; p = 0.61) and patient report adverse events (RR 1.23; 95% CI 0.72, 2.11; p = 0.46). CONCLUSION: Colchicine is not currently recommended as a treatment for knee OA but might have insignificant effect. The conclusion is limited due to the variation in assessment indicator among available data. Further RCTs with larger sample size and longer follow-up are needed to confirm the findings.

Colchicine Ameliorates 5-Fluorouracil-Induced Cardiotoxicity in Rats.

Background and Objective. 5-Fluorouracil is one of the most common chemotherapeutic agents used in the treatment of solid tumors. 5-Fluorouracil-associated cardiotoxicity is the second cause of cardiotoxicity induced by chemotherapeutic drugs after anthracyclines. Colchicine is a strong anti-inflammatory drug used to prevent and treat acute gout and treat familial Mediterranean fever. And also, its protective effects on cardiovascular disease have been reported in various studies. The current study is aimed at appraising the effect of colchicine on 5-fluorouracil-induced cardiotoxicity in rats. Methods. Twenty male Wistar rats were divided into four groups as follows: control, 5-fluorouracil, colchicine (5 mg/kg), and 5-fluorouracil+5 mg/kg colchicine. Cardiotoxicity was induced with an intraperitoneal injection of a single dose of 5-fluorouracil (100 mg/kg). The control group received normal saline, and the treatment groups received colchicine with an intraperitoneal injection for 14 days. Findings. 5-Fluorouracil resulted in significant cardiotoxicity represented by an increase in cardiac enzymes, malondialdehyde levels, cyclooxygenase-2 and tumor necrosis factor-alpha expression, cardiac enzymes, and histopathological degenerations. 5-Fluorouracil treatment also decreased body weight, total antioxidant capacity and catalase values, blood cells, and hemoglobin levels. In addition, 5-fluorouracil disrupted electrocardiographic parameters, including increased elevation in the ST segment and increased QRS duration. Treatment with colchicine reduced oxidative stress, cardiac enzymes, histopathological degenerations, and cyclooxygenase-2 expression in cardiac tissue, improved electrocardiographic disorders, and enhanced the number of blood cells and total antioxidant capacity levels. Moreover, body weight loss was hampered after treatment with colchicine. Our results demonstrated that treatment with colchicine significantly improved cardiotoxicity induced by 5-fluorouracil in rats.

Effect of colchicine on mortality in patients with COVID-19 - A systematic review and meta-analysis.

BACKGROUND AND AIM: This systematic review and meta-analysis aimed to evaluate the latest evidence on the association between colchicine and mortality in patients with COVID-19. METHODS: We performed a comprehensive literature search from the PubMed, Scopus, Embase, EuropePMC, and Clinicaltrials.gov up until 02 January 2022. We include randomized controlled trials (RCTs) and observational studies reporting colchicine use in patients with COVID-19 and mortality within 30 days. The intervention group was patients given colchicine during the course of treatment. The control group was patients given placebo or standard of care at the respective institutions. The outcome was mortality. The effect estimate was reported as risk ratio (RR). RESULTS: There were 12 studies comprising of 6953 patients included in this meta-analysis. Mortality rate was 0.18 [95%CI 0.10, 0.26] in the colchicine group and 0.26 [95%CI 0.15, 0.38] in the control group. Colchicine was associated with reduction in mortality (RR 0.66 [95%CI 0.53, 0.83], p < 0.001; I2: 42%). Sensitivity analysis using fixed-effect model (RR 0.73 [95%CI 0.63, 0.83], p < 0.001; I2: 42%. Subgroup analysis on the four RCTs showed non-significant result (RR 0.81 [95%CI 0.54, 1.20], p = 0.29; I2: 10%). Meta-regression showed that the association between colchicine and reduced mortality was not affected by age (p = 0.613) [Fig. 3], sex (p = 0.915), diabetes (p = 0.795), and hypertension (p = 0.403). CONCLUSION: Though the meta-analysis showed decreased mortality with colchicine in patients with COVID-19, the meta-analysis of randomized trials did not show any significant effect of colchicine on mortality.

The protective effects of S14G-humanin (HNG) against mono-sodium urate (MSU) crystals- induced gouty arthritis.

Gout is a common and complex form of arthritis that has brought great inconveniences to the normal lives of patients. It is reported that oxidative stress and nod-like receptor family protein 3 (NLRP3) inflammasome-mediated inflammatory reactions are involved in the pathogenesis of gout arthritis. S14G-humanin (S14G-HNG) is a modified peptide of HNG with higher inhibitory activity on the accumulation and deposition of Aß. Recently, S14G-HNG has been reported to exert great anti-inflammatory effects. The present study proposed to explore the possible therapeutic property of S14G-HNG against gout arthritis. An animal model was established by stimulation with mono-sodium urate (MSU) crystals, followed by treatment with colchicine and S14G-HNG, respectively. The elevated Gait score promoted synovitis score and activated myeloperoxidase (MPO) observed in MSU crystals-treated mice were significantly reversed by colchicine and S14G-HNG. Bone marrow-derived macrophages (BMDMs) were isolated from mice and stimulated with MSU crystals, followed by being treated with 25 and 50 µM S14G-HNG. The increased mitochondrial reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, upregulated NADPH oxidase-4 (NOX-4), activated NLRP3 inflammasome, and elevated production of inflammatory factors in MSU crystals-treated BMDMs were dramatically reversed by S14G-HNG, accompanied by the upregulation of sirtuin type-1 (SIRT1). Lastly, the protective effects of S14G-HNG against MSU crystals-induced NLRP3 inflammasome activation were significantly abolished by the knockdown of SIRT1. In conclusion, our data reveal that S14G-HNG could possess potential benefits against MSU crystals-induced gout arthritis, with colchicine displaying a better effect.

Consensus Statement Regarding the Efficacy and Safety of Long-Term Low-Dose Colchicine in Gout and Cardiovascular Disease.

Over the last decade, evidence has demonstrated that long-term, low-dose colchicine (0.5 mg daily) is effective for preventing gout flare and cardiovascular (CV) events in a wide range of patients. Given the potentially expanding use of colchicine in CV disease, we here review and update the biologic effects and safety of colchicine based on recent data gathered from bench and pharmacodynamic studies, clinical reports, controlled clinical trials, and meta-analyses, integrated with important studies over the last 50 years, to offer a consensus perspective by experts from multiple specialties familiar with colchicine's long-term use. We conclude that the clinical benefits of colchicine in gout and CV disease achieved at low dose do not sustain serum levels above the upper limit of safety when used in patients without advanced renal or liver disease or when used concomitantly with most medications. Further, data accrued over the last 50 years strongly suggest that the biologic effects of long-term colchicine do not increase the risk of cancer, sepsis, cytopenia, or myotoxicity.

A Proposed Approach for the Determination of the Bioequivalence Acceptance Range for Narrow Therapeutic Index Drugs in the European Union.

The current regulatory criterion for bioequivalence of narrow therapeutic index (NTI) drugs in the European Union requires that the 90% confidence interval for the ratio of the population geometric means of the test product compared with the reference for area under the plasma concentration-time curve (AUC), and in certain cases maximum plasma drug concentration (Cmax ), to be included within the tighter acceptance range of 90.00-111.11%. As a consequence, sponsors need to recruit a higher number of subjects to demonstrate bioequivalence and this may be seen as increasing the burden for the development of generics. This "one-size-fits-all" criterion is particularly questionable when the within-subject variability of the reference product is moderate to high. As an alternative, we propose a further refined statistical approach where the acceptance range is narrowed based on the within-subject variability of the reference product of the NTI drug, similar to the one used for widening the standard 80.00-125.00% acceptance range for highly variable drugs. The 80.00-125.00% acceptance range is narrowed, only if the within-subject variability is lower than 30%, down to the current NTI acceptance range of 90.00-111.11% when the within-subject variability is 13.93% or lower. Examples within the current European Medicines Agency list of NTI drugs show a considerable reduction in required sample size for drugs like tacrolimus and colchicine, where the predicted within-subject variability is 20-30%. In these cases, this approach is less sample size demanding without any expected increase in the therapeutic risks, since patients treated with reference products with moderate to high within-subject variability are frequently exposed to bioavailability differences larger than 10%.

Canakinumab is effective in patients with familial Mediterranean fever resistant and intolerant to the colchicine and/or anakinra treatment.

As an autosomal recessive autoinflammatory disease, treatment of Familial Mediterranean fever (FMF) has still gaps. Clinical studies are proving the safety and efficacy of colchicine in patients with FMF. However, there are very limited data on colchicine-resistant patients treated with canakinumab. This study presents the real-life experience of two rheumatology clinics choosing canakinumab in adult patients with FMF resistant to standard therapy. Treatment-resistant FMF patients with validated diagnoses enrolled from two rheumatology clinics. A special database was generated for the study and patients' demographic characteristics, FMF attack characteristics, adverse events seen during treatment, family history, MediterraneanFeVer (MEFV) mutations, and laboratory results recorded. Patients with missing dates were excluded from the analysis. PRAS score is used to assess the disease activity. A total of thirty colchicine and/or anakinra-resistant patients were enrolled to study. Twenty-one patients were female (70%) and the average disease duration was 21 years. The time from colchicine to anakinra was 4.27 years and the time to canakinumab was 1.52 years. Abdominal pain (100%), fever (93.3%), chest pain (56.7%) were the most prevailed findings. Morning stiffness, myalgia, low back pain, chest pain was the predominant musculoskeletal findings. Median colchicine dose was 2 mg/day (min-max 0.5-3 mg/day). The most common side effect during anakinra treatment, apart from treatment unresponsiveness, was injection site reactions. Before canakinumab treatment, the mean number of attacks was 8.3 in the 24 weeks, 4.33 in the third month of canakinumab treatment, and 1.56 at the last visit (p < 0.001). Also, the mean duration of attacks was 67.20 h before canakinumab treatment, this period decreased to 18.27 h after six months of canakinumab treatment (p < 0.001). Canakinumab is effective and tolerable to reduce attacks in resistant patients with FMF. Laboratory findings and clinical observation reveals that canakinumab can be another treatment option for colchicine and/or anakinra non-responders. Further studies with larger patients are required to validate recent findings with canakinumab.

Can we still consider treatment with colchicine effective in SARS-COV-2 infection? Systematic review, meta-analysis, and trial sequential analysis.

OBJECTIVE: To assess the effectiveness of colchicine, compared with standard of care, for reducing mortality, admission to intensive care, and use of mechanical ventilation. MATERIALS AND METHODS: We performed a systematic review, meta-analysis, and sequential trial analysis. The terms (SARS-CoV-2 OR COVID-19 OR coronavirus) AND (colchicine) were searched in MEDLINE, Scopus, Embase, Cochrane Central Register of Controlled Trials, and preprint repositories (February 2020 to April 2021, extended to June 2021). Risk of bias for randomised controlled trials and observational studies were assessed using the tools RoB 2.0 and ROBINS-I, respectively. We performed subgroup analyses based on study design and sensitivity analyses based on time of colchicine administration. RESULTS: We included six observational studies (1329 patients) and five clinical trials (16,048 patients). All studies but one were conducted in the hospital setting. Colchicine treatment was not associated with a significant decrease in mortality (RR 0.93, 95% CI 0.87 to 1; p=0.06, I2=72%) with a significant subgroup effect (p<0.001) depending on the design of the studies. The drug was effective in observational studies (RR 0.57, 95% CI 0.46 to 0.70, p<0.001, I2=50%) but not in clinical trials (RR 0.99, 95% CI 0.92 to 1.07, p=0.89, I2=21%). The effect of colchicine on intensive care admissions and the need for mechanical ventilation could not be confirmed. Trial sequential boundaries for cumulative meta-analyses of randomised controlled trials suggested no significant effect on mortality (p=0.182) beyond the optimal information size (13,107 patients). CONCLUSIONS: Our results suggest that colchicine treatment has no effect on mortality in hospitalised patients with SARS-CoV-2 infection, and that no further confirmatory clinical trials are needed owing to futility.

Perfil de efectividad y seguridad de la colchicina en pacientes con diagnóstico de COVID-19 en un área sanitaria / Efficacy and safety profile of colchsicine in patients diagnosed with COVID-19 in a healthcare area

Objetivo: describir la evolución y la seguridad de la utilización de colchicina en pacientes no ingresados con diagnóstico de COVID-19 leve-moderado en la Gerencia de Atención Integrada (GAI) de Albacete. Métodos: estudio observacional retrospectivo. De los 389 participantes incluidos en el primer reclutamiento, se seleccionaron 315 con datos válidos. La variable principal del estudio ha sido el fallecimiento o ingreso hospitalario en pacientes con diagnóstico de COVID-19 y tratamiento con colchicina. Se registraron variables sociodemográficas, clínicas y tratamientos y comorbilidades concomitantes. Resultados: fallecieron 6 (1,90%) pacientes y 49 (15,5%) requirieron ingreso hospitalario. A un 58,4% se les prescribió un antibiótico, siendo la azitromicina el más utilizado y el responsable en un 32,7% de las posibles interacciones. Un 34,5% y un 43% de pacientes recibieron heparinas de bajo peso molecular (HBPM) y corticosteroides respectivamente. En el 42,3% de pacientes no se tuvo en cuenta el valor del aclaramiento de creatinina al dosificar la colchicina. La edad elevada muestra una relación estadísticamente significativa con la gravedad de la clínica (68,5 versus 58,9) y con la variable recaída (ingreso + urgencias) (63,25 versus 58,54). Conclusiones: en nuestra muestra, la utilización de colchicina en pacientes ambulatorios no ha modificado el curso de la enfermedad en pacientes diagnosticados de COVID-19.(AU)

Objective: to describe the evolution and safety of the use of colchicine in outpatients with a diagnosis of mild-moderate COVID-19 in the Integrated Care Management of Albacete. Methods: retrospective observational study. Of the 389 participants included in the first recruitment, 315 subjects with valid data were selected. The main variable of the study has been death or hospital admission in patients diagnosed with COVID-19 and treatment with colchicine. Sociodemographic, clinical and treatment variables and concomitant comorbidities were recorded. Results: 6 (1.90%) patients died and 49 (15.5%) required hospital admission. 58.4% of the patients were prescribed an antibiotic, azithromycin being the most used and responsible for 32.7% of the interactions detected. 34.5% and 43% of the patients received LMWH and corticosteroids, respectively. In 42.3% of the patients, the value of creatinine clearance was not taken into account when dosing colchicine. High age shows a statistically significant relationship with the severity of the symptoms (68.5 vs 58.9) and with the variable relapse (admission + emergency room) (63.25 vs 58.54). Conclusions: in our sample, the use of colchicine in outpatients has not modified the course of the disease in patients diagnosed with COVID-19.(AU)

Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome.

BACKGROUND: Colchicine reduces risk of cardiovascular events in patients post-myocardial infarction and in patients with chronic coronary disease. It remains unclear whether this effect is related to the time of onset of treatment following an acute coronary syndrome (ACS). OBJECTIVES: This study investigates risk for major adverse cardiovascular events in relation to history and timing of prior ACS, to determine whether the benefits of colchicine are consistent independent of prior ACS status. METHODS: The LoDoCo2 (Low-Dose Colchicine 2) trial randomly allocated patients with chronic coronary disease to colchicine 0.5 mg once daily or placebo. The rate of the composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization was compared between patients with no prior, recent (6-24 months), remote (2-7 years), or very remote (>7 years) ACS; interaction between ACS status and colchicine treatment effect was assessed. RESULTS: In 5,522 randomized patients, risk of the primary endpoint was independent of prior ACS status. Colchicine consistently reduced the primary endpoint in patients with no prior ACS (incidence: 2.8 vs 3.4 events per 100 person-years; hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.52-1.27), recent ACS (incidence: 2.4 vs 3.3 events per 100 person-years; HR: 0.75; 95% CI: 0.51-1.10), remote ACS (incidence: 1.8 vs 3.2 events per 100 person-years, HR: 0.55; 95% CI: 0.37-0.82), and very remote ACS (incidence: 3.0 vs 4.3 events per 100 person-years, HR: 0.70; 95% CI: 0.51-0.96) (P for interaction = 0.59). CONCLUSIONS: The benefits of colchicine are consistent irrespective of history and timing of prior ACS. (The LoDoCo2 Trial: Low Dose Colchicine for secondary prevention of cardiovascular disease [LoDoCo2] ACTRN12614000093684).

Acute oral colchicine caused gastric mucosal injury and disturbance of associated microbiota in mice.

Colchicine (COL), an ancient and well-known drug, has been used in clinical practice for centuries. On the other hand, COL has also attracted extensive concerns for its potent toxic effects, especially gastrointestinal adverse reactions (nausea, vomiting, and diarrhea) before clinical symptoms relief. In this study, we used a rodent model to study the effects of COL on gastric mucosa and associated microbiota. The mice were exposed to various concentrations of COL (0.1, 0.5, and 2.5 mg kg-1 body weight per day) for 7 days, and the results showed that COL treatment caused severe gastric mucosal damage, accompanied by a significant decrease in gastric mucosal proinflammatory cytokines (IL-1ß, IL-6, and TNF-α). The 16S rRNA gene sequencing revealed that COL significantly perturbed the gastric microbiota composition and reduced the gastric microbiota diversity in mice. Also, we identified bacterial biomarkers associated with diarrhea, including phylum Firmicutes, class Bacilli, order Lactobacillales, family Lactobacillaceae, genu Lactobacillus, and genu Blautia, suggesting that COL-triggered adverse reactions are closely related to gastric microbial perturbations. Our findings open new paths for understanding the mechanism of COL-related adverse gastrointestinal reactions, broadening the scientific view on the interaction between drugs and host gastrointestinal microbiota.

Anti-inflammatory mechanisms and research progress of colchicine in atherosclerotic therapy.

Inflammatory responses play a vital role in the onset and development of atherosclerosis, and throughout the entire process of the chronic disease. The inflammatory responses in atherosclerosis are mainly mediated by the NLRP3 inflammasome and its downstream inflammatory factors. As a powerful anti-inflammatory medicine, colchicine has a history of more than 200 years in clinical application and is the first-choice treatment for immune diseases such as gout and familial Mediterranean fever. In atherosclerosis, colchicine can inhibit the assembly and activation of NLRP3 inflammasome via various mechanisms to effectively reduce the expression of inflammatory factors, thereby reducing the inflammation. Recent clinical trials show that a low dose of colchicine (0.5 mg per day) has a certain protective effect in stable angina patients or those with acute myocardial infarction after PCI. This article summarizes and discusses the mechanisms of colchicine in the treatment of atherosclerosis and the latest research progress.

Inflammation and Stroke Risk: A New Target for Prevention.

New therapeutic approaches are required for secondary prevention of residual vascular risk after stroke. Diverse sources of evidence support a causal role for inflammation in the pathogenesis of stroke. Randomized controlled trials of anti-inflammatory agents have reported benefit for secondary prevention in patients with coronary disease. We review the data from observational studies supporting a role for inflammation in pathogenesis of stroke, overview randomized controlled trials of anti-inflammatory therapy in cardiac disease and discuss the potential implications for stroke prevention therapy.

Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial.

BACKGROUND: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission. METHODS: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants. FINDINGS: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001). INTERPRETATION: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended. FUNDING: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.

Low-dose colchicine in type 2 diabetes with microalbuminuria: A double-blind randomized clinical trial.

BACKGROUND: Neutrophil-related chronic inflammation (NRCI) may contribute to the pathogenesis of diabetic kidney disease (DKD). We evaluated whether blocking NRCI with low-dose colchicine prevents DKD. METHODS: A double-blind, randomized, placebo-controlled study was conducted. A total of 160 patients with type 2 diabetes (T2D) and microalbuminuria (urinary albumin creatinine ratio [UACR] 30 to 300 mg/g Cr) who received angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) for at least 3 months were included. Subjects were 1:1 randomized to a placebo or colchicine group (0.5 mg/day). RESULTS: The primary end point was the incidence of overt nephropathy (UACR > 300 mg/g Cr). During the 36 months, 38 patients (51.4%) in colchicine group and 39 (54.1%) in the control group developed overt nephropathy (hazard ratio, 1.066; 95% confidence interval, 0.679-1.673; P = .78). Compared with placebo, colchicine modestly lowered levels of NRCI parameters (P values <.05 for high-sensitivity C-reactive protein, white blood cell counts, neutrophil counts, and neutrophil-to-lymphocyte ratio), whereas the changes of UACR and estimated glomerular filtration rate (eGFR) were similar between the two groups. There were no significant differences between the two groups in drug-related adverse events, including infection, gastrointestinal symptoms, and limb numbness. CONCLUSIONS: In patients with T2D with microalbuminuria, low-dose colchicine effectively and safely lowered NRCI but did not prevent the incidence of overt nephropathy.

Comparative efficacy of low-dose versus regular-dose colchicine to prevent flares in gout patients initiated on urate-lowering therapies.

OBJECTIVE: The objective of this study was to compare the prophylactic effect of regular-dose (RD, 1.2 mg/day) vs low-dose (LD, 0.6 mg/day) colchicine on gout flare when initiating urate-lowering therapy. METHODS: In this retrospective cohort study, we included gout patients who were initiated on either allopurinol or febuxostat, in combination with colchicine therapy and followed them up for 3 months. We analysed the rates of gout flare and adverse events according to the dose of colchicine. We performed the inverse probability of treatment weighting (IPTW) and weighted logistic regression analysis to assess the treatment effect. Analysis of gout flares and adverse events was performed on an intention-to-treat (ITT) and per-protocol (PP) basis. RESULTS: Of the total of 419 patients with gout, 177 patients (42.2%) received LD colchicine, whereas 242 patients (57.8%) received RD colchicine. Lower BMI and estimated glomerular filtration rate, and higher incidence of cardiovascular disease were seen in the LD group than in the RD group. In IPTW-adjusted analysis, events of gout flare were not significantly different between the LD and RD groups [ITT: 14.3% vs 11.3%; odds ratio (OR): 1.309, 95% CI: 0.668, 2.566, P = 0.432; PP: 15.3% vs 10.0%; OR: 1.623, 95% CI: 0.765, 3.443, P = 0.207]. However, LD colchicine was associated with a lower rate of adverse events than RD colchicine [ITT: 8.2% vs 17.9%; OR: 0.410, 95% CI: 0.217, 0.777; P < 0.05; PP: 8.4% vs 17.2%; OR: 0.442, 95% CI: 0.223, 0.878; P < 0.05]. CONCLUSION: Our data suggest that LD colchicine can adequately prevent gout flare with fewer adverse events compared with RD colchicine.

Potential of novel colchicine dosage schedule for the palliative treatment of advanced hepatocellular carcinoma.

Previous in vitro and in vivo experiments had demonstrated dose-dependent anti-cancer effects of clinical plasma colchicine concentrations on hepatocellular carcinoma (HCC) cells. This phase IIa trial was to evaluate the potential efficiency and safety of our novel colchicine dosage schedule for the palliative treatment of advanced HCC. The dosage schedule started from oral intake of 1 mg colchicine three times per day for 4 days and discontinuation in the following 3 days (one cycle). The treatment cycle was repeated and the dosage was adjusted ranging from 3 to 1.5 mg/day according to the condition of the participant. The control group was originated from chart review of 86 HCC patients treated by sorafenib for more than 2 months. Fifteen participants signed the inform consent. Two participants were excluded due to screening failure in one and less than four treatment cycles in another. For severe adverse events, the colchicine group demonstrated higher incidence of biliary tract obstruction (p = 0.0184) than the sorafenib group. Comparison grade 1 or 2 adverse events between two groups, the colchicine group had higher incidence of diarrhea (p = 0) and the sorafenib group had higher incidence of palmar-plantar erythrodysesthesia syndrome (p = 0.0045). There was no significant difference in mortality, median survival, and overall survival between two groups (all p > 0.2). In conclusion, our novel colchicine dosage schedule is clinically feasible and has the potential to be applied in the palliative treatment of advanced HCC especially based on the cost-effectiveness consideration.

Clinical features and outcomes of hospitalized COVID-19 patients in a low burden region.

Data on the clinical features and outcomes of COVID-19 patients from countries with low disease burden are rare. Greece, however, presented a low burden of COVID-19 disease during the first pandemic outbreak. This is a retrospective study of COVID-19 hospitalized patients in Greece. Clinical data were extracted from medical records using univariable and multivariable logistic regression analyses to assess the factors associated with Intensive Care Unit (ICU) admission and in-hospital death. Eighty-five patients were included in this study, 49 (57.7%) male with median (25th-75th) age 60 (49-72) years old. Sixty-one (72%) of them had at least one comorbidity with hypertension being the most common (45,6%). More than half (56%) had severe or critical disease, 20% required ICU care (14% received invasive ventilation) and 10.7% died. Solid tumor (p = 0.021) and NEWS score (p = 0.048), thrombocytopenia (p = 0.036) or involvement of all lung fields in chest x-ray (p = 0.002) on admission were independent risk factors for ICU admission. Immunosuppression (p = 0.032) and thrombocytopenia (p = 0.049) were independent predictors of death. Hospitalized COVID-19 patients in a European country with a low burden of the disease, in which hospital capacities had not been overwhelmed, had lower mortality rate compared to those reported for patients hospitalized in regions with a high burden of the disease.