RESUMEN
Importance: Colchicine has many drug-drug interactions with commonly prescribed medications. Only pharmacokinetic studies have provided data on colchicine drug-drug interactions. Objective: To evaluate the clinical tolerability of colchicine according to the presence or absence of a drug-drug interaction. Design, Setting, and Participants: A secondary analysis of the COLCORONA trial was performed. The COLCORONA trial was a randomized, double-blind, placebo-controlled trial conducted in Brazil, Canada, Greece, South Africa, Spain, and the US between March 23, 2020, and January 20, 2021. The COLCORONA trial included ambulatory patients with COVID-19 with at least 1 high-risk characteristic and compared the effects of colchicine (0.5 mg twice daily for 3 days, then 0.5 mg daily thereafter) with placebo for 27 days. Data analysis was performed from February 24, 2023, to June 20, 2024. Exposure: In this secondary analysis, baseline medications that had interactions with colchicine were identified using a previously published expert classification. Main Outcomes and Measures: The primary outcome for this analysis was the composite of serious and nonserious treatment-related and treatment-unrelated gastrointestinal adverse events. The secondary outcomes were other adverse events and the composite of death or hospital admission due to COVID-19 infection. Logistic regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, heart failure, and myocardial infarction were assessed for effect modification of the association between the randomization arm and the outcomes of interest by drug-drug interaction status. Results: The cohort included 2205 participants in the colchicine arm and 2227 in the placebo arm (median age, 54 [IQR, 47-61] years; 2389 [54%] women). The most common colchicine drug-drug interactions were rosuvastatin (12%) and atorvastatin (10%). In fully adjusted models, the odds of any gastrointestinal adverse event were 1.80 (95% CI, 1.51-2.15) times higher in the colchicine arm than the placebo arm among people without a drug-drug interaction and 1.68 (95% CI, 1.24-2.26) times higher in the colchicine arm than the placebo arm among people with a drug-drug interaction (P = .69 for interaction). Drug-drug interaction status did not significantly modify the effect of colchicine on the composite of COVID-19 hospitalization or death (odds ratio, 0.91; 95% CI, 0.59-1.40 for drug-drug interaction and 0.84; 95% CI, 0.60-1.19 for no drug-drug interaction; P = .80 for interaction). Conclusions and Relevance: In this secondary analysis of the COLCORONA trial, operational classification of drug interactions system class 3 or 4 drug-drug interactions did not appear to significantly increase the risk of colchicine-related adverse effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04322682.
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COVID-19 , Colchicina , Interacciones Farmacológicas , SARS-CoV-2 , Humanos , Colchicina/efectos adversos , Colchicina/uso terapéutico , Colchicina/farmacocinética , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Anciano , Tratamiento Farmacológico de COVID-19 , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , PandemiasRESUMEN
OBJECTIVES: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3). DESIGN: Multicentre, double blind, randomised, placebo controlled trial. SETTING: 244 hospitals in China between 11 August 2022 and 13 April 2023. PARTICIPANTS: 8343 patients aged 40 years of age or older with a minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L were enrolled. INTERVENTIONS: Patients were randomly assigned 1:1 within 24 h of symptom onset to receive colchicine (0.5 mg twice daily on days 1-3, followed by 0.5 mg daily thereafter) or placebo for 90 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was any new stroke within 90 days after randomisation. The primary safety outcome was any serious adverse event during the treatment period. All efficacy and safety analyses were by intention to treat. RESULTS: 4176 patients were assigned to the colchicine group and 4167 were assigned to the placebo group. Stroke occurred within 90 days in 264 patients (6.3%) in the colchicine group and 270 patients (6.5%) in the placebo group (hazard ratio 0.98 (95% confidence interval 0.83 to 1.16); P=0.79). Any serious adverse event was observed in 91 (2.2%) patients in the colchicine group and 88 (2.1%) in the placebo group (P=0.83). CONCLUSIONS: The study did not provide evidence that low-dose colchicine could reduce the risk of subsequent stroke within 90 days as compared with placebo among patients with acute non-cardioembolic minor-to-moderate ischaemic stroke or transient ischaemic attack and a high sensitivity C-reactive protein ≥2 mg/L. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05439356.
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Colchicina , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Humanos , Colchicina/administración & dosificación , Colchicina/uso terapéutico , Colchicina/efectos adversos , Masculino , Femenino , Método Doble Ciego , Persona de Mediana Edad , Ataque Isquémico Transitorio/tratamiento farmacológico , Anciano , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Resultado del Tratamiento , China , Proteína C-Reactiva/análisis , AdultoRESUMEN
Colchicine is one of the oldest drugs in medicine. Traditionally used to treat and prevent gouty attacks, it has been introduced into cardiovascular medicine for the treatment and prevention of pericarditis, starting from the positive experience in the treatment and prevention of polyserositis in familial mediterranean fever. Colchicine is a lipophilic drug that enters the cells and is eliminated by glycoprotein P. As granulocytes are lacking in this protein, colchicine is able to concentrate in these cells, exerting a substantial anti-inflammatory action, even with low oral doses. As these cells may trigger acute cardiovascular events, colchicine has been shown to be efficacious and safe to prevent acute coronary syndromes and ischemic stroke with an efficacy comparable to more established treatments, such as antiplatelet agents and statins. On this basis, colchicine seems a promising, efficacious, well tolerated, and cheap option for the prevention of several cardiovascular events, and it may become an additional pillar in the pharmacologic treatment of cardiovascular diseases.
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Enfermedades Cardiovasculares , Colchicina , Colchicina/uso terapéutico , Colchicina/efectos adversos , Humanos , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Resultado del Tratamiento , Pericarditis/tratamiento farmacológicoRESUMEN
BACKGROUND: There is no known effective pharmacological therapy for long COVID, which is characterized by wide-ranging, multisystemic, fluctuating, or relapsing symptoms in a large proportion of survivors of acute COVID. This randomized controlled trial aims to assess the safety and efficacy of an anti-inflammatory agent colchicine, to reduce symptoms among those at high risk of developing long COVID. METHODS: This multi-centre, parallel arm, 1:1 individual randomized, placebo-controlled, double-blind superiority trial will enrol 350 individuals with persistent post-COVID symptoms. Participants will be randomized to either colchicine 0.5 mg once daily (< 70 kg) or twice daily (≥ 70 kg) or matched placebo for 26 weeks and will be followed up until 52 weeks after randomization. The primary trial objective is to demonstrate the superiority of colchicine over a placebo in improving distance walked in 6 min at 52 weeks from baseline. The secondary objectives are to assess the efficacy of colchicine compared to placebo with respect to lung function, inflammatory markers, constitutional symptoms, and mental health state. In a sub-sample of 100 participants, cardiac biomarkers of myocardial injury and myocardial oedema using MRI will be compared. DISCUSSION: Persistent inflammatory response following SARS-CoV-19 is one of the postulated pathophysiological mechanisms of long COVID. Colchicine, a low-cost anti-inflammatory agent, acts via multiple inflammatory pathways and has an established safety profile. This trial will generate evidence for an important health priority that can rapidly translate into practice. TRIAL REGISTRATION: This clinical trial has been registered prospectively on www. CLINICALTRIALS: gov with registration CTRI/2021/11/038234 dated November 24, 2021.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Colchicina , Humanos , Colchicina/uso terapéutico , Colchicina/efectos adversos , Método Doble Ciego , COVID-19/complicaciones , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Antiinflamatorios/uso terapéutico , Antiinflamatorios/efectos adversos , Inflamación/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , AdultoRESUMEN
BACKGROUND: Recent findings suggest a link between gout and the development of dementia. Early treatment with colchicine is recommended as a first-line therapy for gout flares. Animal studies demonstrate that colchicine could induce cognitive impairment. This cohort study aimed to investigate the association between colchicine use and the risk of developing dementia. METHODS: In this nationwide cohort study, we performed comparative analysis on 6147 patients ≥40 years, with gout and colchicine new users against 6147 controls to assess subsequent dementia risk. The colchicine group and the control group (urate lowering therapy group) were matched on the bases of age, sex, index year, and comorbidities. All participants were followed for up to 14 years for a diagnosis of dementia considering medical records were retrospectively checked over this period. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Sensitivity analyses were performed to validate our findings. RESULTS: The adjusted hazard ratio (aHR) of dementia for colchicine users was 1.45 (95% CI = 1.05, 1.99) relative to comparison group after adjusting for sex, age, and comorbidities. Sensitivity analysis aiming to minimize underdiagnosed occult dementia at the time of index year yielded consistent positive association. In higher accumulative dose colchicine group (cumulative defined daily dose [cDDD] >30), the aHR of dementia risk for colchicine users was 1.42 (95% CI = 1.03, 1.97) compared with nonusers. For those duration of colchicine use >30 days, the aHR was 1.53 (95% CI = 1.01-2.32) compared to the nonuser group. CONCLUSIONS: A significant risk of dementia was observed in this study in patients with gout using colchicine at higher cDDD and for a longer period. Further research is needed to elucidate the relationship between colchicine, gout, and dementia.
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Colchicina , Demencia , Supresores de la Gota , Gota , Humanos , Colchicina/efectos adversos , Colchicina/uso terapéutico , Gota/epidemiología , Gota/tratamiento farmacológico , Demencia/epidemiología , Demencia/inducido químicamente , Demencia/diagnóstico , Femenino , Masculino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Supresores de la Gota/efectos adversos , Factores de Riesgo , Medición de Riesgo , Factores de Tiempo , Taiwán/epidemiología , Adulto , Anciano de 80 o más Años , Bases de Datos FactualesRESUMEN
In the last century, there has been more than enough research that proved the association of high lipid and glucose levels with cardiovascular disease, thus establishing the current well-known traditional cardiovascular risk factors such as dyslipidemia, diabetes, and metabolic syndrome. Hence, these cardiovascular risk factors are target therapy for glucose and lipid-lowering agents to prevent adverse cardiovascular events. However, despite controlling the lipid and glucose levels, some studies demonstrated the subclinical atherosclerosis suggesting that these cardiovascular risk factors alone cannot account for the entire atherosclerosis burden. In the last years, large-scale clinical trials demonstrated the operation of the inflammatory pathway in atherosclerotic cardiovascular disease (ASCVD) by the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. In this regard, some studies that use antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, have been shown to reduce the risk of adverse cardiovascular events in patients with previous coronary artery disease. In this regard, the U.S. Food and Drug Administration (FDA) approved the use of colchicine 0.5 mg once daily for reducing cardiovascular events in patients who have established ASCVD and high residual systemic inflammation. Therefore, measuring the systemic inflammation can improve the cardiovascular risk assessment and identify the subsets of patients that will benefit from anti-cytokine therapy after diagnosis of ASCVD or after myocardial revascularization.
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Antiinflamatorios , Biomarcadores , Glucemia , Citocinas , Factores de Riesgo de Enfermedad Cardiaca , Mediadores de Inflamación , Inflamación , Triglicéridos , Humanos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/efectos adversos , Aterosclerosis/inmunología , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/sangre , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/inmunología , Colchicina/uso terapéutico , Colchicina/efectos adversos , Citocinas/sangre , Citocinas/metabolismo , Inflamación/inmunología , Inflamación/tratamiento farmacológico , Inflamación/sangre , Mediadores de Inflamación/sangre , Mediadores de Inflamación/metabolismo , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
OBJECTIVES: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies. METHODS: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. RESULTS: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. CONCLUSION: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.
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Anticuerpos Monoclonales Humanizados , Colchicina , Resistencia a Medicamentos , Fiebre Mediterránea Familiar , Humanos , Fiebre Mediterránea Familiar/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Niño , Masculino , Femenino , Estudios Retrospectivos , Colchicina/uso terapéutico , Colchicina/administración & dosificación , Colchicina/efectos adversos , Adolescente , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/inmunología , Resultado del Tratamiento , Preescolar , Israel , Esquema de MedicaciónRESUMEN
Low-dose colchicine (0.5â mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed in clinical practice. In this State-of-the-Art Review, data were collated from contemporary systemic reviews of case reports, drug registries, and placebo-controlled trials that assessed specific issues of safety related to the continuous use of colchicine in a range of clinical settings to inform physicians, pharmacists, and patients of the absolute risks of continuous use of low-dose colchicine, including among individuals taking statin therapy. Based upon these collective data, it is concluded that aside mild diarrhoea on initiation of colchicine that typically subsides in the vast majority of patients within a week of therapy, continuous use of low-dose colchicine is well tolerated and very safe. It does not affect renal, liver, or cognitive function, has no adverse effects on bleeding, wound healing, fertility, or pregnancy, and does not increase risks of cancer, serious infection, or cause-specific mortality. When appropriately prescribed to patients without significant renal or hepatic impairment, reports of myelosuppression, myotoxicity, and serious drug-drug interactions are rare and no more frequent than placebo, including in patients taking statin therapy. Physicians, pharmacists, and patients can be reassured that in the absence of significant renal or hepatic impairment continuous use of low-dose colchicine can be used safely in patients with atherosclerosis for the purpose of reducing cardiovascular risk.
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Colchicina , Colchicina/administración & dosificación , Colchicina/efectos adversos , Humanos , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Interacciones Farmacológicas , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéuticoRESUMEN
BACKGROUND: Atrial fibrillation (AF), the most common arrhythmia, is closely related to inflammation. Colchicine has the potent anti-inflammatory effects. Several randomized clinical trials (RCTs) have evaluated the efficacy and safety of colchicine in the prevention of AF but the results are inconsistent. OBJECTIVE: The purpose of our study was to evaluate the impact of colchicine on AF. METHOD AND RESULTS: PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov were searched for related studies until Jan 8, 2024. A total of 17 studies including 16,238 participants were included. Compared to the placebo group, there were fewer incidences of AF in the colchicine group (RR: 0.75, 95%CI: 0.68-0.83, P < 0.001). The incidence of overall adverse events and overall gastrointestinal intolerance did not differ significantly between the two groups. However, diarrhea, nausea, and discontinuation occurred more frequently in patients treated with colchicine. CONCLUSION: Colchicine can prevent patients from the incidence of AF, regardless of the mean age of patients, type of atrial fibrillation, maintenance dose, duration of colchicine use, cumulative daily dose, and follow-up time with more diarrhea, nausea and discontinuation. These adverse events can be avoided by low doses (0.5 mg once daily) and long period time of colchicine use.
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Fibrilación Atrial , Colchicina , Ensayos Clínicos Controlados Aleatorios como Asunto , Colchicina/uso terapéutico , Colchicina/efectos adversos , Fibrilación Atrial/prevención & control , Fibrilación Atrial/tratamiento farmacológico , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: 5-Fluorouracil (5-FU) is a first-line drug to treat cutaneous field cancerization (CFC). There are few clinical trials with topical colchicine (COL). OBJECTIVE: To evaluate the effectiveness of 0.5% COL cream versus 5% 5-FU cream in the treatment of CFC. METHOD: This was a randomized, open, self-controlled clinical trial. Forty-five patients (90 forearms), with three to ten actinic keratoses (AK) on each forearm, used 0.5% COL cream 2×/day for seven days on one forearm, and 5% 5-FU cream 2× /day, for 21 days, on the other forearm. The dosages were defined based on previous clinical trials for each drug. Adverse effects were evaluated after 14 days and outcomes after 90 days of inclusion. The primary outcome was complete AK clearance and the secondary outcomes were: partial clearance (≥50%), reduction in AK count, assessment of the Forearm Photoaging Scale (FPS), AK Severity Score (AKSS), and adverse effects. RESULTS: After 90 days, there was complete clearance of AK in 37% (95% CI 24%-49%) and partial clearance in 85% (95% CI 76%-93%) of the forearms treated with 5-FU,versus 17% (95% CI 7%-27%) and 78% (95% CI 66%-88%) for COL (p > 0.07). There was a percentage reduction of 75% in the AK count of the forearms treated with 5-FU (95% CI 66%-83%) and 64% in those treated with COL (95% CI 55%-72%). Regarding FPS and AKSS, there was improvement in both groups, with no difference regarding FPS (p = 0.654), and 5-FU superiority for AKSS (p = 0.012). STUDY LIMITATIONS: Single-center study. CONCLUSIONS: 5-FU and COL are effective for treating CFC, with neither showing superiority regarding the reduction in AK counts.
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Colchicina , Fluorouracilo , Queratosis Actínica , Crema para la Piel , Humanos , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Colchicina/administración & dosificación , Colchicina/efectos adversos , Colchicina/uso terapéutico , Queratosis Actínica/tratamiento farmacológico , Masculino , Femenino , Anciano , Resultado del Tratamiento , Persona de Mediana Edad , Crema para la Piel/administración & dosificación , Anciano de 80 o más Años , Administración Cutánea , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Índice de Severidad de la Enfermedad , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Factores de TiempoRESUMEN
BACKGROUND: To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. STUDY DESIGN: This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2-5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. STATISTICAL ANALYSIS PLAN: N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0-10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients' global assessment of treatment success are secondary outcomes. DISCUSSION: The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).
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Artritis Gotosa , Gota , Humanos , Artritis Gotosa/tratamiento farmacológico , Colchicina/efectos adversos , Gota/diagnóstico , Gota/tratamiento farmacológico , Dolor , Prednisolona/efectos adversos , Atención Primaria de Salud , Estudios Prospectivos , Resultado del Tratamiento , Masculino , FemeninoRESUMEN
BACKGROUND: Treatment with antiviral drugs for non-severe, early time from onset, adult outpatients with Coronavirus Disease 2019 (COVID-19) had not been established in 2021. However, some new variants of SARS-CoV-2 had caused rapid exacerbation and hospitalization among non-elderly outpatients with COVID-19, contributing to widespread crises within healthcare systems. METHODS: From July to October 2021, we urgently assessed a therapeutic program using oral colchicine (1.0 mg loading dose, followed approximately half a day later by 0.5 mg twice daily for 5 days, and then 0.5 mg once daily for 4 days) and low-dose aspirin (100 mg once daily for 10 days), for non-elderly, non-severe, early time from onset, adult outpatients with COVID-19. To verify its effectiveness, we set loxoprofen as a control arm, and com parison of these two arms was performed. The primary outcomes were hospitalization, criticality, and death rates. RESULTS: Thirty-eight patients (23 receiving colchicine and low-dose aspirin [CA]; 15 receiving loxoprofen [LO]) were evaluated. Hospitalization rate was lower in the CA group (1/23; 4.3%) than in the LO group (2/15; 13.3%); however, no significant difference was found between the two groups (p=0.34). No critical cases, deaths, or severe adverse events were found in either group. CONCLUSIONS: Our CA regimen did not show superiority over LO treatment. However, our clinical experience should be recorded as part of community health care activities carried out in Kurume City against the unprece dented COVID-19 pandemic.
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Aspirina , Tratamiento Farmacológico de COVID-19 , COVID-19 , Colchicina , Humanos , Colchicina/administración & dosificación , Colchicina/efectos adversos , Colchicina/uso terapéutico , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Aspirina/efectos adversos , Masculino , Femenino , Japón/epidemiología , Persona de Mediana Edad , Adulto , COVID-19/epidemiología , Administración Oral , Quimioterapia Combinada , Hospitalización , SARS-CoV-2 , Resultado del Tratamiento , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Pacientes Ambulatorios , FenilpropionatosRESUMEN
Colchicine-an anti-inflammatory alkaloid-has assumed an important role in the management of cardiovascular inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in high doses for the treatment of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine effectively treats acute gout attacks, lowers the risk of recurrent pericarditis, and can add to secondary prevention of major adverse cardiovascular events. As the first Food and Drug Administration-approved targeted anti-inflammatory cardiovascular therapy, colchicine currently has a unique role in the management of atherosclerotic cardiovascular disease. The safe use of colchicine requires careful monitoring for drug-drug interactions, changes in kidney and liver function, and counseling regarding gastrointestinal upset. Future research should elucidate the mechanisms of anti-inflammatory effects of colchicine relevant to atherosclerosis, the potential role of colchicine in primary prevention, in other cardiometabolic conditions, colchicine's safety in cardiovascular patients, and opportunities for individualizing colchicine therapy using clinical and molecular diagnostics.
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Enfermedades Cardiovasculares , Colchicina , Humanos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/efectos adversos , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Colchicina/uso terapéutico , Colchicina/efectos adversos , Interacciones Farmacológicas , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Resultado del TratamientoRESUMEN
Background: Colchicine has shown potential cardioprotective effects owing to its broad anti-inflammatory properties. We performed a meta-analysis to assess its safety and efficacy in secondary prevention in patients with established coronary artery disease (CAD). Methods: We searched Ovid Healthstar, MEDLINE, and Embase (inception to May 2022) for randomized controlled trials (RCTs) evaluating the cardiovascular effects of colchicine compared with placebo or usual care in patients with CAD. Study-level data on efficacy and safety outcomes were pooled using the Peto method. The primary outcome was the composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke. Results: A total of 8 RCTs were included with a follow-up duration of ≥1 month, comprising a total of 12,151 patients. Compared with placebo or usual care, colchicine was associated with a significant risk reduction in the primary outcome (odds ratio (OR) 0.70, 95% CI 0.60 to 0.83, P < 0.0001; I2 = 52%). Risks of MI (OR 0.75, 95% CI 0.62 to 0.91, P = 0.003; I2 = 33%), stroke (OR 0.47, 95% CI 0.30 to 0.74, P = 0.001; I2 = 0%), and unplanned coronary revascularization (OR 0.67, 95% CI 0.55 to 0.82, P = 0.0001; I2 = 58%) were all reduced in the colchicine group. Rates of CV and all-cause mortality did not differ between the two groups, but there was an increase in noncardiac deaths with colchicine (OR 1.54, 95% CI 1.10 to 2.15, P = 0.01; I2 = 51%). The occurrence of all other adverse events was similar between the two groups, including GI reactions (OR 1.06, 95% CI 0.94 to 1.20, P = 0.35; I2 = 42%) and infections (OR 1.04, 95% CI 0.84 to 1.28, P = 0.74; I2 = 53%). Conclusions: Colchicine therapy may reduce the risk of future cardiovascular events in patients with established CAD; however, there remains a concern about non-CV mortality. Further trials are underway that will shed light on non-CV mortality and colchicine NCT03048825, and NCT02898610.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Enfermedades Cardiovasculares/prevención & control , Colchicina/efectos adversos , Prevención Secundaria , Ensayos Clínicos Controlados Aleatorios como Asunto , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología , Enfermedad de la Arteria Coronaria/tratamiento farmacológicoRESUMEN
AIM: Anakinra, an anti IL-1 agent targeting IL-1 alfa and beta, is available for the treatment of recurrent pericarditis in cases with corticosteroid dependence and colchicine resistance after failure of conventional therapies. However, it is unclear if the combination with colchicine, a non-specific inhibitor of the inflammasome targeting the same inflammatory pathway of IL-1, could provide additional benefit to prevent further recurrences. The aim of the present observational study is to assess whether the addition of colchicine on top of anakinra could prolong the time to first recurrence and prevent recurrences better than anakinra alone. METHODS: International, all-comers, multicentre, retrospective observational cohort study analysing all consecutive patients treated with anakinra for corticosteroid-dependent and colchicine-resistant recurrent pericarditis. The efficacy endpoint was recurrence rate and the time to the first recurrence. RESULTS: A total of 256 patients (mean age 45.0±15.4 years, 65.6% females, 80.9% with idiopathic/viral aetiology) were included. 64 (25.0%) were treated with anakinra as monotherapy while 192 (75.0%) with both anakinra and colchicine. After a follow-up of 12 months, 56 (21.9%) patients had recurrences. Patients treated with colchicine added to anakinra had a lower incidence of recurrences (respectively, 18.8% vs 31.3%; p=0.036) and a longer event-free survival (p=0.025). In multivariable analysis, colchicine use prevented recurrences (HR 0.52, 95% CI 0.29 to 0.91; p=0.021). CONCLUSIONS: The addition of colchicine on top of anakinra treatment could be helpful to reduce recurrences and prolong the recurrence-free survival.
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Proteína Antagonista del Receptor de Interleucina 1 , Pericarditis , Femenino , Humanos , Adulto , Persona de Mediana Edad , Masculino , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Estudios Retrospectivos , Colchicina/efectos adversos , Corticoesteroides , Pericarditis/diagnóstico , Pericarditis/tratamiento farmacológico , Pericarditis/inducido químicamente , Interleucina-1RESUMEN
INTRODUCTION: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) is the most common periodic fever condition in children. There is no consensus on treatment to prevent attacks and reduce their frequency. In this study, we aimed to evaluate the effectiveness of colchicine treatment in PFAPA syndrome. In addition, we described the demographic and clinical features of PFAPA patients. MATERIALS AND METHODS: We retrospectively analyzed 58 PFAPA patients who were started on colchicine treatment between January 2017 and January 2022. Demographic data, clinical features, laboratory tests, genetic analysis of MEditerranean FeVer (MEFV) mutations, and autoinflammatory disease activity index (AIDAI) scores of all patients were evaluated. In addition, patients were divided into two groups according to MEFV variants and compared. RESULTS: Attack frequency, duration, and AIDAI scores decreased in all patients after colchicine treatment. Duration of follow-up was 13.53±6.65 months. The median±IQR age at diagnosis was 3.2 (2-5) years. Thirty three (56.9%) patients had heterozygous mutations of MEFV. The most common MEFV variants were M694V (63.6%). There was no significant difference between the two groups in terms of colchicine responses. CONCLUSION: Colchicine treatment is effective and safe in patients with PFAPA who have frequent attacks. No association was established between the presence of heterozygous mutations of MEFV and colchicine response.
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Colchicina , Linfadenitis , Faringitis , Pirina , Estomatitis Aftosa , Humanos , Colchicina/uso terapéutico , Colchicina/efectos adversos , Estomatitis Aftosa/tratamiento farmacológico , Estomatitis Aftosa/genética , Masculino , Linfadenitis/tratamiento farmacológico , Linfadenitis/genética , Faringitis/tratamiento farmacológico , Faringitis/genética , Femenino , Preescolar , Estudios Retrospectivos , Pirina/genética , Síndrome , Niño , Fiebre/tratamiento farmacológico , Mutación , Resultado del Tratamiento , Fiebre Mediterránea Familiar/tratamiento farmacológico , Fiebre Mediterránea Familiar/genética , Fiebre Mediterránea Familiar/diagnósticoRESUMEN
OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis. METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively. CONCLUSION: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.
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Supresores de la Gota , Gota , Metaanálisis en Red , Brote de los Síntomas , Ácido Úrico , Humanos , Gota/tratamiento farmacológico , Gota/sangre , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Supresores de la Gota/administración & dosificación , Ácido Úrico/sangre , Medición de Riesgo , Colchicina/uso terapéutico , Colchicina/efectos adversos , Colchicina/administración & dosificación , Febuxostat/uso terapéutico , Febuxostat/administración & dosificación , Febuxostat/efectos adversos , Resultado del Tratamiento , Factores de Riesgo , Quimioterapia Combinada , Proteínas Recombinantes de FusiónRESUMEN
OBJECTIVE: In the COVERT-MI randomised placebo-controlled trial, oral administration of high-dose colchicine at the time of reperfusion and for 5 days in acute ST-elevated myocardial infarction did not reduce infarct size but was associated with a significant increase in left ventricular thrombus (LVT) in comparison to placebo. We aimed to assess the 1-year clinical outcomes of the study population. METHODS: This study is a follow-up analysis of the COVERT-MI study on prespecified secondary clinical endpoints at 1 year. The primary endpoint of this study was a composite of major adverse cardiovascular events (MACEs), including all-cause death, acute coronary syndromes, heart failure events, ischaemic strokes, sustained ventricular arrhythmias and acute kidney injury at 1-year follow-up. The quality of life (QOL) and the drug therapy prescription were also assessed. RESULTS: At 1 year, 192 patients (101 patients in the colchicine group, 91 in the placebo group) were followed up. Seventy-six (39.6%) MACEs were reported in the study population. There was no significant difference regarding the number of MACEs between groups: 36 (35.6%) in the colchicine group and 40 (44.1%) in the placebo group (p=0.3). There were no differences in the occurrence of ischaemic strokes between the colchicine group and the control group (3 (3%) vs 2 (2.2%), respectively, p=0.99). There was a trend towards fewer heart failure events in the colchicine group compared with the placebo group (12 (11.9%) vs 18 (19.8%), p=0.20). There was no significant difference in QOL scores at 1 year (75.8±15.7 vs 72.7±16.2 respectively, p=0.18). CONCLUSIONS: There was no significant difference between the colchicine and placebo groups at 1 year regarding MACEs, especially concerning deaths or ischaemic strokes. No excess of ischaemic adverse events was observed despite the initial increase in LVT in the colchicine group. TRIAL REGISTRATION NUMBER: NCT0315681.
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Insuficiencia Cardíaca , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Humanos , Colchicina/efectos adversos , Estudios de Seguimiento , Calidad de Vida , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
OBJECTIVE: Clinical trials have evaluated the efficacy and safety of colchicine only in simple pericarditis, excluding cases of concomitant myocarditis. The aim of this paper is to evaluate the efficacy and safety of colchicine for the treatment of the first attack of acute pericarditis with concomitant myocardial involvement. METHODS: Double-centre retrospective cohort study analysing consecutive patients admitted for first attack of pericarditis with myocarditis and treated with or without colchicine. The primary efficacy end point was the time to the first recurrence. Propensity score matching was used to generate two groups of patients with similar baseline characteristics. Colchicine-associated side effects were analysed as safety end-point. RESULTS: A total of 175 patients (mean age 46.2±20.1 years, 25.1% females, 88.6% with idiopathic/viral aetiology) were included. Seventy-nine (45.1%) patients were treated with colchicine. After a median follow-up of 25.3 (IQR 8.3-45.6) months, 58 (33.1%) patients had recurrences. The propensity score generated two groups of 73 patients with similar baseline characteristics but the use of colchicine. Patients treated with colchicine had a lower incidence of recurrences (respectively, 19.2% vs 43.8%; p=0.001) and a longer event-free survival (p=0.005). In multivariable analysis, women (HR 1.97, 95% CI 1.04 to 3.73; p=0.037) and corticosteroid use (HR 2.27, 95% CI 1.15 to 4.47; p=0.018) were independent risk factors for recurrences. Colchicine-associated side effects were mild and occurred in 3 (1.7%) patients. CONCLUSION: In patients with first attack of pericarditis associated with myocardial involvement, colchicine was safe and efficacious for the reduction of recurrences.