Use Of Colchicine Research Articles

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

Background and aimThis systematic review and meta-analysis aimed to evaluate the latest evidence on the association between colchicine and mortality in patients with COVID-19. MethodsWe 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). ResultsThere 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). ConclusionThough 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.

Colchicine in Cardiovascular Disease: In-Depth Review.

Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.

Colchicine May Interfere With the Efficacy of the Adenoviral Vector-Based Vaccine for COVID-19.

Under the ongoing COVID-19 pandemic, vaccines have become the crucial players to reduce the spread of the infection. Among them, the ChAdOx1 nCoV-19 vaccine is an adenoviral vector vaccine with an overall efficacy of 70.4% in protection. The engineered adenovirus contains the SARS-CoV-2 spike protein gene and pushes its DNA into the vaccinated cell’s nucleus and subsequently, the spike protein can be made. During vaccination, the genome transition of adenovirus is influenced by the architecture and dynamics of the microtubule. Colchicine can alter microtubule dynamics by suppressing microtubule dynamics at lower concentrations and inducing depolymerization of microtubules at higher concentrations. Accordingly, the delivery of the genome to the vaccinated cell’s nucleus by the adenoviral vector could be hindered under the presence of colchicine. Nevertheless, colchicine is a common medication for gout therapy worldwide, and though not recommended by guidelines, colchicine has even been taken into consideration as a possible therapeutic option for COVID-19 infection. Given the above reasons and the worldwide use of colchicine, the impact of colchicine on the efficacy of the COVID-19 vaccine via adenoviral vector should be viewed cautiously.

Colchicine and the concepts of nephroprotection; a new feature of an old drug

Colchicine as an old drug and is usually the first choice of treatment for acute gout to reduce pain and inflammation. Colchicine seems to prevent various pro-inflammatory mechanisms, whereas it allows increasing concentration of anti-inflammatory molecules, which leads to clinical advantage in patients with gout. Colchicine is using generally as a treatment for acute gout however, it has also newly been revealed to have anti-fibrotic effects in different kinds of nephropathies such as polycystic kidney disease, diabetic nephropathy and amyloidosis. Extended use of colchicine is associated with nephrotoxicity depending on its dose, which results to impairment of renal function. Risk of colchicine therapy is accentuated in chronic kidney disease (CKD) patients; therefore, dose reduction is necessary dependent on CKD stage.

Colchicine for symptomatic coronary artery disease after percutaneous coronary intervention.

BackgroundPercutaneous coronary intervention (PCI), the preferred coronary reperfusion strategy, induces endothelial trauma which may mount an inflammatory response. This has been shown to increase the likelihood of further major adverse cardiovascular events (MACE). Colchicine, a cheap and widely used anti-inflammatory has shown promise in improving cardiovascular outcomes. We aimed to perform a systematic review and meta-analysis to study the effects of colchicine in patients with symptomatic coronary artery disease (CAD) who have undergone PCI.MethodWe systematically reviewed and meta-analysed 7 randomised controlled trials including a total of 6660 patients (colchicine group: 3347, control group: 3313; mean age=60.9±10). Six studies included participants who had a ≤13.5-day history of acute coronary syndrome (ACS). One study included patients with both ACS and chronic coronary syndrome. The follow-up of studies ranged from 3 days to 22.6 months.ResultsThe use of colchicine in patients who underwent PCI significantly reduced MACE outcomes (risk ratio 0.73 (95% CI 0.61 to 0.87); p=0.0003) with minimal heterogeneity across the analysis (I2=6%; P for Cochran Q=0.38). These results were driven mainly by the reduction in repeat vessel revascularisation, stroke and stent thrombosis. The number needed to treat to prevent one occurrence of MACE was 41.ConclusionColchicine significantly reduced the risk of MACE in patients with CAD who underwent PCI, mostly in the reduction of repeat vessel revascularisation, stroke and stent thrombosis. The efficacy of colchicine should be further studied by distinguishing its use alongside different stent types and dosing regimens.PROSPERO registration numberCRD42021245699.

Safety, Efficacy, and Drug Survival of Colchicine in Recurrent Aphthous Stomatitis in a Real-World Setting.

BackgroundRecurrent aphthous stomatitis (RAS) is a common disorder characterized by episodic ulcerations in the oral mucosa. Although colchicine has been a common systemic treatment for RAS, there is still considerable uncertainty regarding its efficacy and drug survival in this setting.ObjectiveWe aimed to study drug survival, efficacy, and safety of colchicine for the treatment of RAS, especially in the real clinical setting.MethodsBetween 2012 and 2016, 150 patients given colchicine for RAS were selected for a single-centre retrospective study of real-world efficacy and drug survival.ResultsAmong the 114 patients who qualified, 81.6% showed moderate or substantial responses (>25% improvement). Gastrointestinal complications (16.7%), neutropenia (3.5%), and liver enzyme elevation (4.4%) were reported within 2 weeks after initiating treatment. Delayed adverse manifestations were rare. One year after onset, colchicine use was sustained in roughly one-half (49.5%) of patients, whereas many (30.3%) had discontinued the drug, primarily due to lack of efficacy or adverse events. In Cox proportional hazard analysis, minor ulcers were identified as potential determinants of longer drug survival owing to less probability of non-efficacy. However, major ulcers had emerged as predictors of early discontinuation due to lack of efficacy.ConclusionIn patients with RAS, colchicine may be an effective and safe treatment amenable to long-term maintenance. Monitoring of adverse events within 2 weeks after initiating treatment is advisable to ensure safe administration.

Effect of Colchicine on Induction of Ploidy and Other Morphological Features of Different Crops: A Review

Colchicine is a mitotic inhibitor and it has been used for induction of tetraploids in different crops. Different concentration of colchicine has been used for different time period in vivo and in vitro. Colchicine is used for such purposes because rate of spontaneously doubling in most species is rare in tissue culture. Treatment of colchicine in in vitro culture plant tissues has been efficiently used to artificially produce polyploids in different plants. In different crops such as vegetables, fruits and flowers tetraploids produce variants with favourable horticultural characteristics like high yield, large fruit size and resistance to different environmental stresses. Tetraploids was induced in vivo by applying colchicine in an aqueous solution, lanolin paste, on apical shoot meristem of seedling and soaked seeds. Colchicine use has been found a very prosperous methodology for genome doubling in a lot of species.

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

BackgroundOveractivation 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.AimsWe aimed to perform a meta‐analysis of randomized trials investigating the effect of colchicine in patients with COVID‐19.Materials & MethodsWe 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.ResultsThe 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 ConclusionThe 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.

Usefulness of colchicine for Covid-19 myopericarditis in athletes. A case report and review of the literature

Cardiac injuries, specifically acute myocarditis, are a common complication of COVID-19. Recent studies in the literature have supported the beneficial and safe results of colchicine administration in the general population in cases of COVID-19 infection, especially in cases of myocardial injuries. However, the frequency of occurrence in athletes, its treatment, and management of these individuals concerning the return to competitive sports have not yet been clarified. The present case description is a novelty in that it refers to the onset of a mild form of acute myopericarditis secondary to COVID-19 infection in an athlete that was successfully treated as an outpatient with only colchicine. A 45-year-old marathon runner with no underlying health problems showed clinical symptoms of acute pericarditis and mild febrile infection. The biochemical tests were characterized by an increase in the level of troponin. MRI established the diagnosis of mild myopericarditis. In addition, he has been tested positive for COVID-19 by molecular/PCR test. The patient was treated with colchicine alone for three months. After that time, all the clinical and laboratory findings of myopericarditis were subsided. Six months after the onset of the disease, the athlete returned to full competitive action.

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

IntroductionColchicine may inhibit inflammasome signaling and reduce proinflammatory cytokines, a purported mechanism of COVID-19 pneumonia. The aim of this systematic review and meta-analysis is to report on the state of the current literature on the use of colchicine in COVID-19 and to investigate the reported clinical outcomes in COVID-19 patients by colchicine usage.MethodsThe literature was searched from January 2019 through January 28, 2021. References were screened to identify studies that reported the effect of colchicine usage on COVID-19 outcomes including mortality, intensive care unit (ICU) admissions, or mechanical ventilation. Studies were meta-analyzed for mortality by the subgroup of trial design (RCT vs observational) and ICU status. Studies reporting an risk ratio (RR), odds ratio (OR) and hazard ratio (HR) were analyzed separately.ResultsEight studies, reporting on 16,248 patients, were included in this review. The Recovery trial reported equivalent mortality between colchicine and non-colchicine users. Across the other studies, patients who received colchicine had a lower risk of mortality—HR of 0.25 (95% CI: 0.09, 0.66) and OR of 0.22 (95% CI: 0.09, 0.57). There was no statistical difference in risk of ICU admissions between patients with COVID-19 who received colchicine and those who did not–OR of 0.26 (95% CI: 0.06, 1.09).ConclusionColchicine may reduce the risk of mortality in individuals with COVID-19. Further prospective investigation may further determine the efficacy of colchicine as treatment in COVID-19 patients in various care settings of the disease, including post-hospitalization and long-term care.

The comparison of colchicine and standard treatment in COVID-19 patients: A mini review

Coronavirus disease 2019 (COVID-19) was declared a pandemic in March 2020. There are several drugs used at different stages of the disease, but none seem to be completely effective. In the absence of any known therapy, many drugs have been tested, including colchicine. Colchicine differs from these other therapies in having pleiotropic mechanism of action, being less potent on any single target, and being an oral agent. It is also a better option since colchicine is not immunosuppressive, is not known to increase risk of infection, and is inexpensive. The aim of this study was to provide evidence of the role of colchicine in improving clinical outcome and reducing death rate of COVID-19 patients through literature mini-review. A mini-review, composed of previous RCTs comparing the use of colchicine in COVID-19 with standard care or placebo under the keyword “COVID-19”, “COVID”, “coronavirus”, “SARS-CoV-2”, “coronavirus disease”, “Colchicine”, “CAS 64-86-8”, “standard treatment”, “standard care”, “standard of care”, “common treatment”, “placebo”, “clinical improvement”, and “clinical response”. The addition of colchicine to standard treatment can be beneficial in treating COVID-19. Studies included showed that colchicine has significantly improved time to clinical deterioration compared to the control group. Colchicine reduced the length of hospitalization and the need for supplemental oxygen therapy. One of the included studies mentioned that in outpatient settings, colchicine can prevent hospitalization and even death. Colchicine can improve the clinical outcome on CRP levels, the number of patients that need mechanical ventilation, and death rate in COVID-19 patients. The addition of colchicine to standard treatment should be considered to prevent clinical deterioration and death. Colchicine reduces the number of adverse effects in COVID-19 patients except for gastrointestinal adverse effects, especially diarrhea, which is consistently more common in the colchicine groups.

Effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir and combinations thereof in hospitalized patients with COVID-19: a pragmatic, open-label randomized trial.

SummaryBackgroundThe use of rosuvastatin plus colchicine and emtricitabine/tenofovir in hospitalized patients with SARS-CoV-2 disease (COVID-19) has not been assessed. The objective of this study was to assess the effectiveness and safety of rosuvastatin plus colchicine, emtricitabine/tenofovir, and their combined use in these patients.MethodsThis was a randomized, controlled, open-label, multicentre, parallel, pragmatic study conducted in six referral hospitals in Bogotá, Colombia. The study enrolled hospitalized patients over 18 years of age with a confirmed diagnosis of COVID-19 complicated with pneumonia, not on chronic treatment with the study medications, and with no contraindications for their use. Patients were assigned 1:1:1:1. 1) emtricitabine with tenofovir disoproxil fumarate (FTC/TDF, 200/300 mg given orally for 10 days); 2) colchicine plus rosuvastatin (COLCH+ROSU, 0.5 mg and 40 mg given orally for 14 days); 3) emtricitabine with tenofovir disoproxil plus colchicine and rosuvastatin at the same doses and for the same period of time (FTC/TDF+COLCH+ROSU); or 4) the Colombian consensus standard of care, including a corticosteroid (SOC). The primary endpoint was 28-day all-cause mortality. A modified intention-to-treat analysis was used together with a usefulness analysis to determine which could be the best treatment. The trial was registered at ClinicalTrials.gov: NCT04359095FindingsOut of 994 candidates considered between August 2020 and March 2021, 649 (65.3%) patients agreed to participate and were enrolled in this study; among them, 633 (97.5%) were included in the analysis. The mean age was 55.4 years (SD ± 12.8 years), and 428 (68%) were men; 28-day mortality was significantly lower in the FTC/TDF+COLCH+ROSUV group than in the SOC group, 10.7% (17/159) vs. 17.4% (28/161) (hazard ratio [HR] 0.53; 95% CI 0.29 to 0.96). Mortality in the FTC/TDF group was 13.8% (22/160, HR 0.68, 95% CI 0.39 to 1.20) and 14.4% in the COLCH+ROSU group (22/153) (HR 0.78, 95% CI 0.44 to 1.36). A lower need for invasive mechanical ventilation was observed in the FTC/TDF+COLCH+ROSUV group than in the SOC group (risk difference [RD] - 0.08, 95% CI 0.11 to 0.04). Three patients presented severe adverse events, one severe diarrhoea in the COLCH+ROSU and one in the FTC/TDF+COLCH+ROSU group and one general exanthema in the FTC/TDF group.InterpretationThe combined use of FTC/TDF+COLCH+ROSU reduces the risk of 28-day mortality and the need for invasive mechanical ventilation in hospitalized patients with pulmonary compromise from COVID-19. More randomized controlled trials are needed to compare the effectiveness and cost of treatment with this combination versus other drugs that have been shown to reduce mortality from SARS-CoV-2 infection and its usefulness in patients with chronic statin use.

Effect of colchicine, methotrexate, and hydroxychloroquine therapy on cardiovascular outcomes in patients with calcium pyrophosphate crystal deposition disease

Anti-inflammatory therapy, such as colchicine (COL), has been suggested to affect the incidence of cardiovascular events in patients with calcium pyrophosphate crystal deposition disease (CPPD).Objective: to study the effect of anti-inflammatory therapy with COL, hydroxychloroquine (HC), and methotrexate (MT) on cardiovascular outcomes in patients with CPPD.Patients and methods. The study included 305 patients with CPPD, the majority (62.30%) were women. The average follow-up period was 3.9±2.7 years. Among factors influencing cardiovascular outcome were considered: gender; age; smoking; alcohol intake &gt;20 conventional doses per week; arterial hypertension; a history of cardiovascular diseases (CVD), in particular ischemic heart disease, acute myocardial infarction, acute cerebrovascular accident, chronic heart failure &gt;III stage according to NYHA, as well as type 2 diabetes mellitus (DM); body mass index &gt;25 kg/m2 and &gt;30 kg/m2; cholesterol level (CHOL) &gt;5.1 mmol/l; glomerular filtration rate (GFR) &lt; 60 ml/min/1.73 m2; serum uric acid level &gt;360 μmol/l; hypercalcemia (serum calcium level &gt;2.62 mmol/L); CRP level &gt;2 mg/l; the presence of hyperparathyroidism (parathyroid hormone level &gt;65 pg/ml); CPPD phenotypes (asymptomatic, osteoarthritis with calcium pyrophosphate crystals, chronic arthritis, acute arthritis); intake of COL, HC, MT, glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs).Results and discussion. 264 patients were under dynamic observation. Any of the studied cardiovascular events were registered in 79 (29.9%) patients. During the observation period, 46 (17.4%) patients died, in 76.1% of cases the cause of death was CVD. Death from other causes was diagnosed in 11 (23.9%) patients. Non-fatal cardiovascular events were reported in 44 (16.7%) cases. The risk of cardiovascular events was higher in patients over 65 years of age (odds ratio, OR 5.97; 95% confidence interval, CI 3.33–10.71), with serum cholesterol levels ≥5.1 mmol/L (OR 1,95; 95% CI 1.04–3.65), GFR &lt;60 ml/min/1.73 m2 (OR 2.78; 95% CI 1.32–5.56), history of CVD (OR 2,32; 95% CI 1.22–4.44). COL therapy reduced the risk of cardiovascular events (OR 0.20; 95% CI 0.11–0.39).Conclusion. Poor CVD outcomes in CPPD are associated with age, hypercholesterolemia, chronic kidney disease, and a history of CVD. The use of COL, in contrast to MT and HC, was accompanied by a decrease in cardiovascular risk.

Colchicine for Patients With Coronary Artery Disease: A Systematic Review and Meta-analysis.

Several randomized controlled trials have studied the role of colchicine, a potent anti-inflammatory drug, to prevent adverse cardiovascular events in patients with coronary artery disease (CAD). In this meta-analysis, we aimed to determine the role of colchicine in patients with CAD in clinical outcomes and mortality. We searched PubMed, PubMed Central, Scopus, and Embase for randomized controlled trials/experimental studies evaluating the role of colchicine in patients with CAD. After assessing the eligibility for inclusion, risk-of-bias assessment, and data extraction from the included studies, a narrative synthesis was conducted. Of 17 studies included for the qualitative analysis, 11 studies reported that inflammatory markers such as C-reactive protein and cytokines were reduced in the colchicine group, suggesting an anti-inflammatory role of colchicine in CAD. Quantitative analysis with pooling of data from 9 studies using a fixed-effect model showed 28% lower odds of acute myocardial infarction [odds ratio (OR) 0.72, 95% CI 0.59-0.86; n = 11,712], 52% lower occurrence of stroke (OR 0.48, 95% CI 0.30-0.76), and 37% reduction in odds of coronary revascularization procedure in the colchicine group (OR 0.63, 95% CI 0.52-0.76; n= 11,258). However, the odds of gastrointestinal adverse events were 50% higher in the colchicine group (OR 1.50, 95% CI 1.01-2.23; n = 12,214). In conclusion, colchicine is associated with a lower risk of acute myocardial infarction, stroke, and coronary revascularization. However, there is some increased risk of gastrointestinal adverse events with the use of colchicine.

548 Colchicine in patients with coronary artery disease: a meta-analysis of randomized trials

Abstract Aims The aim of this study was to provide a systematic appraisal of the effects of colchicine treatment on cardiovascular outcomes, adverse events, and mortality in patients with coronary artery disease. Methods and results We performed a meta-analysis of randomized controlled trials (RCTs) that compared add-on colchicine to standard treatment vs. standard treatment in patients with coronary artery disease. Mixed-effects Poisson regression model with random intervention effects was used to estimate the pooled incidence rate ratios (IRR) with 95% confidence intervals (CI). The number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH) were calculated. Prespecified subgroup analyses according to colchicine dose (e.g. &amp;lt;1 mg/daily or ≥ 1 mg/daily) and the type of clinical syndrome [e.g. acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] were performed. Ten RCTs were identified, including 12 819 participants with a median follow-up of 6 months. Add-on colchicine, compared to standard treatment, was associated with a lower risk of major adverse cardiovascular events (IRR: 0.69, 95% CI: 0.60–0.79, NNTB = 28), myocardial infarction (IRR: 0.77, 95% CI: 0.64–0.93, NNTB = 95), and ischaemic stroke (IRR: 0.48, 95% CI: 0.30–0.76, NNTB = 155), while it was associated with a higher risk of gastrointestinal adverse events (IRR: 1.69, 95% CI: 1.12–2.54, NNTH = 10). Colchicine use did not affect all-cause death (IRR: 1.09, 95% CI: 0.85–1.40), or cardiovascular death (IRR: 0.75, 95% CI: 0.51–1.12), while it was associated with a higher risk of non-cardiovascular death (IRR: 1.45, 95% CI: 1.04–2.02, NNTH = 396). In the subgroup analysis of colchicine dose, a significant interaction was found with the risk of gastrointestinal adverse events (IRR: 1.03, 95% CI: 0.91–1.15, in patients receiving colchicine &amp;lt;1 mg/daily; IRR: 2.91, 95% CI: 1.91–4.44, in patients receiving colchicine ≥1 mg/daily, p for interaction &amp;lt;0.0001), while there was no evidence for a modification of treatment effect for the remaining endpoints. In the subgroup analysis of the clinical syndrome, there was little evidence for an interaction with the risk of myocardial infarction (IRR: 0.91, 95% CI: 0.71–1.18, in patients presenting with ACS; IRR: 0.65, 95% CI: 0.50–0.84, in patients presenting with CCS, p for interaction = 0.07), while there was no evidence for a modification of treatment effect for the remaining endpoints. Conclusions This meta-analysis of RCT provides evidence for a significant clinical benefit of add-on colchicine in terms of risk reduction of cardiovascular events in patients with coronary artery disease, that largely outweigh a potential harmful effect of colchicine on the risk of non-cardiovascular death. Colchicine is associated with a higher risk of gastrointestinal adverse effects that can be prevented by using a low-dose regimen (e.g. &amp;lt;1 mg daily).

Clinical significance of collchicine in pharmacotherapy of cardiovascular pathology in patients with hyperuricemia in rheumatic diseases

For a long time, there has been scientific debate about the appropriateness of prescribing drugs to lower the level of uric acid in patients without clinical manifestations of gout. Long-term hyperuricemia is known to be the cause of gout and gouty arthritis. However, an increased level of uric acid is often found in a number of other diseases (metabolic syndrome, kidney disease, cardiovascular disease, psoriasis). Clinical evidence suggests that uric acid-lowering therapy slows the progression of cardiovascular disease and chronic kidney disease. And, if in rheumatological practice this issue still remains a subject of discussion, then the cardiological community by 2019 has clearly defined the indications for starting urate-lowering therapy. The Consensus on the Management of Patients with Hyperuricemia and High Cardiovascular Risk strongly recommends that the practitioner prescribe drugs to control hyperuricemia in hypertensive patients. The need to control the level of uric acid is reflected in the relevant sections of the Clinical Guidelines for the Management of Patients with Arterial Hypertension, 2020. This article provides a review of the literature on the etiology, pathophysiology, pharmacotherapy of hyperuricemia in patients with cardiovascular and rheumatic diseases. A separate section is devoted to scientific studies of the effects of colchicine in advanced therapy for CVD and RD. A clinical case of observation of a patient with newly diagnosed psoriatic arthritis, hyperuricemia, high cardiovascular risk is presented. The peculiarity of this clinical case is the onset of the disease after orthopedic surgery on the knee joints, high comorbidity and poor tolerance of standard basic therapy. The use of colchicine stabilized the patient’s condition. Thus, in clinical practice, it is necessary to take into account the role of hyperuricemia in the pathogenesis of inflammation in cardiovascular pathology. Colchicine may be the drug of choice for patients with hyperuricemia at high cardiovascular risk.

ESCMID COVID-19 living guidelines: drug treatment and clinical management

ScopeIn January 2021, the ESCMID Executive Committee decided to launch a new initiative to develop ESCMID guidelines on several COVID-19-related issues, including treatment of COVID-19. MethodsAn ESCMID COVID-19 guidelines task force was established by the ESCMID Executive Committee. A small group was established, half appointed by the chair, and the remaining selected with an open call. Each panel met virtually once a week. For all decisions, a simple majority vote was used. A long list of clinical questions using the PICO (population, intervention, comparison, outcome) format was developed at the beginning of the process. For each PICO, two panel members performed a literature search with a third panellist involved in case of inconsistent results. Voting was based on the GRADE approach. Questions addressed by the guideline and recommendationsA synthesis of the available evidence and recommendations is provided for each of the 15 PICOs, which cover use of hydroxychloroquine, bamlanivimab alone or in combination with etesevimab, casirivimab combined with imdevimab, ivermectin, azithromycin and empirical antibiotics, colchicine, corticosteroids, convalescent plasma, favipiravir, remdesivir, tocilizumab and interferon β-1a, as well as the utility of antifungal prophylaxis and enoxaparin. In general, the panel recommended against the use of hydroxychloroquine, ivermectin, azithromycin, colchicine and interferon β-1a. Conditional recommendations were given for the use of monoclonal antibodies in high-risk outpatients with mild–moderate COVID-19, and remdesivir. There was insufficient evidence to make a recommendation for use of favipiravir and antifungal prophylaxis, and it was recommended that antibiotics should not be routinely prescribed in patients with COVID-19 unless bacterial coinfection or secondary infection is suspected or confirmed. Tocilizumab and corticosteroids were recommended for treatment of severe COVID-19 but not in outpatients with non-severe COVID-19. ScopeThe aim of the present guidance is to provide evidence-based recommendations for management of adults with coronavirus disease 2019 (COVID-19). More specifically, the goal is to aid clinicians managing patients with COVID-19 at various levels of severity including outpatients, hospitalized patients, and those admitted to intensive care unit. Considering the composition of the panel, mostly clinical microbiologists or infectious disease specialists with no pulmonology or intensive care background, we focus only on pharmacological treatment and do not give recommendations on oxygen supplement/support. Similarly, as no paediatricians were included in the panel; the recommendations are only for adult patients with COVID-19. Considering the current literature, no guidance was given for special populations such as the immunocompromised.

Colchicine, terug van nooit weggeweest

Colchicine: ancient and brand new Colchicine is an alkaloid initially extracted from an autumn crocus. Its use dates back to the 6th century BC, with the first indication being gout. In the last 50 years, further insights into its mechanism of action emerged along with an expansion of the number of indications. Colchicine inhibits the chemotaxis of leukocytes. Recently, it was discovered that in addition to its action on the microtubules, there is also an effect on the NLRP3 inflammasome. Colchicine has a narrow therapeutic index and caution is advised in patients with renal and hepatic failure. It’s a CYP3A4 and P-gp substrate. Therefore, concomitant use with CYP3A4 and P-gp inhibitors is contraindicated given the greatly increased risk of toxicity. Its most frequent side effect is diarrhea and severe intoxications can be lethal. The main rheumatologic indications are the treatment of gout in the acute phase, attack prevention and amyloidosis in familial Mediterranean fever, and ulcerations in Behçet’s disease. The cardiovascular use of colchicine in acute and relapsing/chronic pericarditis has been well established. Recent studies also show a beneficial effect in case of acute and chronic coronary artery disease. Additional studies for the implementation of colchicine for these indications are ongoing.

Pharmacologic treatment of acute and recurrent pericarditis: a systematic review and meta-analysis of controlled clinical trials.

Recurrence is the most frequent complication following acute pericarditis and may occur in 30% patients, rising to 50% in case of multiple recurrences, lack of colchicine treatment or use of glucocorticoids. Available treatments include aspirin or non-steroidal anti-inflammatory drugs (NSAIDs), colchicine, glucocorticoids, immunosuppressive agents, immunoglobulins, anti-interleukin-1 (IL-1) agents. This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to assess the efficacy of pharmacological treatments for acute and recurrent pericarditis. Bibliographic databases were searched (PubMed, MEDLINE, Embase, Scopus, and the Cochrane Library) using the terms "acute pericarditis" or "recurrent pericarditis" and "colchicine" or "NSAIDs" or "glucocorticoids" or "immunosuppressive agents" or "immunoglobulins" or "anti-IL1 agents." Random-effects meta-analysis was used to assess the risk of recurrent pericarditis. Publication bias was assessed using the Egger test, and meta-regression was performed to assess sources of heterogeneity. Eleven RCTs assessed the efficacy of pharmacological treatments for acute and recurrent pericarditis (colchicine and anti-interleukin-1 agents). Colchicine, assessed in nine RCTs, was effective in the reduction of recurrent pericarditis, compared with standard treatment (17% vs .34%, RR=0.50; 95% CI 0.42-0.60, P<0.001), without any differences according to clinical setting (i.e. acute pericarditis, recurrent pericarditis, post-pericardiotomy syndrome; P=0.58). Anti-interleukin-1 agents (anakinra, rilonacept), assessed in two RCT, were effective in the reduction of recurrences, compared with placebo (10% vs.78%, RR=0.14; 95% CI 0.05-0.35, P<0.001). A correct pharmacological management of pericarditis is key to prevent recurrences. Colchicine is the mainstay of treatment in acute and recurrent pericarditis, while anti-IL1 agents are a valuable option in case of recurrent pericarditis refractory to conventional drugs.

Colchicine treatment in COVID-19: the remaining unsolved question

Colchicine treatment in COVID-19: the remaining unsolved question