A Meta-Analysis Evaluating the Colchicine Therapy in Patients With Coronary Artery Disease

Background: Evidence from recent studies has shown the benefits of colchicine for patients with coronary artery disease. The aim was to assess the effect of colchicine treatment on cardiovascular events, with an estimation of the risk of discontinuation and net clinical benefit.Methods and Results: Fourteen trials with a total of 13,186 patients were selected through a systematic search. Colchicine therapy significantly reduced the relative risk of primary endpoint by about 30% [RR 0.70 (95%CI:0.56–0.88)]. Compared with placebo, colchicine significantly reduced the risk of ischemia-driven revascularization [RR 0.57 (95%CI 0.41–0.80)], ischemia-driven revascularization and resuscitation [RR 0.50 (95%CI 0.34–0.73)], myocardial infarction [RR 0.73 (95%CI 0.57–0.95)], and stroke [RR 0.49 (95%CI 0.30–0.7)]. Patients treated with colchicine in comparison with placebo have a significant increase in the risk of treatment cessation (RR 1.60 95%CI 1.06–2.42). However, in the analysis which excluded studies without placebo, the relative risk of discontinuation was smaller (RR 1.34 95%CI 0.97–1.84) and in the three largest studies, the risk of discontinuation was lower and insignificant [RR 1.26 (95%CI 0.87–1.83)]. The net clinical benefit was 17.8/1,000 patients (p < 0.001).Conclusion: In coronary artery disease, low-dose colchicine significantly reduces the risk of the primary composite endpoint by about 30%. The drug should be considered as part of the preventive treatment in patients with good tolerance.

Colchicine may Induce Isolated and Reversible Oculomotor Neuropathy

Background: Colchicine is a medication described by a complex constellation of side effects. Case presentation: We report the case of an 80s- 80-year-old subject, treated with colchicine, who developed a left monolateral ptosis with horizontal diplopia after treatment with oral colchicine. Two months later, he underwent a clinical follow-up and complete recovery of the previous third cranial nerve deficit was reported at neurological examination. A few months later, colchicine therapy was reported with a reappearance of the same ocular deficit. Conclusion: Our report suggests that patients receiving colchicine should be followed prudently and, a possible iatrogenic origin of an isolated ocular cranial neuropathy must be taken into account, especially when other potential etiological entities are excluded by the instrumental and laboratory clinical investigations.

Colchicine for acute arthritis attacks prevention in patients with gout during urate-lowering therapy (results of a pilot study)

Objective: to investigate the efficacy and safety of low-dose colchicine in patients with gout receiving urate-lowering therapy (ULT).Patients and methods. A single-center prospective study included 113 patients with gout. The main group consisted of 92 patients who were prescribed colchicine 0.5 mg/day combined with ULT (allopurinol or febuxostat), control group – 21 patients with contraindications to colchicine therapy who received only ULT. Patient data were entered into individual registration cards at the first visit, as well as on the 90th and 180th day after the start of drug intake. The presence of arthritis attacks was recorded by doctor or patient using a validated questionnaire. We compared the mean frequency of arthritis attacks in the groups, their duration and maximum pain intensity according to the visual analogue scale (VAS). Laboratory tests included: complete blood count test, general urinary test, uric acid (UA), blood glucose, alanine aminotransferase, aspartate aminotransferase, creatinine, serum creatine phosphokinase.Results and discussion. Patients who did not receive prophylactic anti-inflammatory therapy had significantly longer duration of the disease and higher number of affected joints. For 6 months of follow-up, there were no arthritis attacks in 54% of patients who were prescribed colchicine, and only in 19% of patients who did not use prophylactic anti-inflammatory therapy (p=0.004). The duration of arthritis attacks and the intensity of pain according to the VAS were also statistically significantly lower in the colchicine group (p<0.031 and p<0.01, respectively). Due to the development of adverse events, related to colchicine therapy, only 3 were excluded from the study. The mean serum UA level by the end of the study in colchicine group did not differ from that in the control group.Conclusion. Administration of colchicine, 0.5 mg/dai for 6 months after initiation of ULT is safe and can reduce the frequency and severity of arthritis attacks.

Discontinuation of colchicine therapy in children with Familial Mediterranean Fever

Objective Colchicine has been considered a life-long therapy for Familial Mediterranean fever (FMF). Recent studies describe patients who discontinued colchicine, but data pertaining to predictors of success were not provided. The aims of our study are to describe a cohort of pediatric patients with FMF who discontinued colchicine therapy, and to identify factors predicting successful termination of colchicine. Methods This study describes a cohort of pediatric patients with FMF who discontinued colchicine therapy following a relatively prolonged attack-free period (≥6 month), and identifies factors predicting successful termination. Data collected included demographic, clinical, and laboratory characteristics of children diagnosed with FMF < 16 years who underwent a trial of colchicine discontinuation. Data from patients who successfully ceased colchicine therapy were compared to that of patients who relapsed. Results Of 571 patients with FMF, 59 (10.3%) discontinued colchicine therapy. The average attack-free period before enrollment was 1.4±0.97 years. Follow-up after ceasing colchicine was 5.0±3.05 years during which time 11 (20%) patients had an attack. The most common symptoms were fever (92%) and abdominal pain (84.6%). For those failing discontinuation, colchicine was restarted within 1.3 years (range: 0.3-5.0; median 0.7 years). A longer attack-free period prior to colchicine discontinuation predicted success. Myalgia and arthritis prior to colchicine cessation were more common among children who required renewal of colchicine. Conclusion Cessation of colchicine therapy should be considered following prolonged remission in a select group of patients. Patients with arthritis or myalgia are more likely to have an attack after ceasing colchicine therapy.

Hemophagocytic syndrome after recovery from SARS-Cov-2 infection: a Case Report

Background Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory disease, whose diagnosis is based on the HLH-2004 criteria. In secondary forms of HLH (sHLH), the primary goal is treating the triggering factors such as SARS-CoV-2-19 infection. The link between the cytokine storm related to SARS-CoV-2-19infection and development of sHLH has already been reported since the onset of pandemic (1), but little is known about clinical manifestations of HLH which develop after patient’s recovery from SARS-CoV-2-19 infection. Case presentation A 56-year-old caucasian female was diagnosed with sHLH according to HLH-2004 criteria, after recovery from a mild symptomatic SARS-CoV-2-19 infection and received immunosuppressive treatment (high-dose steroids, IVIG, low dose Ruxolitinib and Etoposide. Antiviral (acyclovir), antibiotic (sulfamethoxazole / trimethoprim) and heparin prophylaxes were administered. Colchicine therapy was added considering the pericarditis. Improvement in patient symptoms and normalization of blood count as well as fibrinogen and ferritin values was observed.Conclusion Our report suggests that HLH-like syndrome might be secondary to SARS CoV-2-19 infection, even after the patient completely recovered from the mildly symptomatic viral infection. In addition, we underline the treatment with low dose ruxolitinib plus etoposide as a potential choice for SARS-CoV-2-19 related HLH.

Familial Mediterranean Fever (FMF) and Pregnancy: Literature Review

В обзоре обобщается текущая информация о влиянии семейной средиземноморской лихорадки (ССЛ) и ее лечения на исходы беременности, анализируется вопрос гипотетической тератогенности колхицина. В случае резистентности/непереносимости колхицина обсуждается возможность использования других лекарственных средств во время беременности, в том числе, генно-инженерных биологических препаратов, среди которых при ССЛ наиболее предпочтительны ингибиторы интерлейкина 1. Представлена эволюция взглядов на необходимость проведения пренатальной диагностики хромосомных аномалий плода пациенткам с ССЛ, получающим колхицин во время зачатия и беременности, а также в тех случаях, когда колхицинотерапия проводилась мужьям во время зачатия их женами. Акцент сделан на аспектах безопасности терапии, основные положения которых представлены в клинических рекомендациях по лечению ССЛ Европейской антиревматической лиги (EULAR,2016). Согласно этим рекомендациям, прием колхицина не должен быть прекращен во время зачатия, беременности или лактации; имеющаяся на сегодняшний день доказательная база не подтверждает необходимость выполнения амниоцентеза. The review summarizes current information on the impact of FMF and its treatment on pregnancy outcomes, and analyses the hypothetical teratogenicity of colchicine. In the case of colchicine resistance/intolerability, the possibility of using other drugs during pregnancy, including genetically engineered biological drugs, among which interleukin 1 inhibitors are preferred for FMF. An evolutionary view is presented on the need for amniocentesis in FMF patients receiving colchicine during conception and pregnancy, as well as in cases where colchicine therapy was performed to husbands during conception with their wives. Emphasis is placed on the safety aspects of therapy, the main provisions of which are presented in the clinical recommendations for the treatment of FMF of the European Anti-Rheumatic League (EULAR, 2016). According to these recommendations, colchicine should not be discontinued during conception, pregnancy or lactation; today’s evidence does not support amniocentesis.

Role of colchicine in stroke prevention: an updated meta-analysis

Background Colchicine is a microtubule inhibitor with anti-inflammatory proprieties. As the body and quality of evidence regarding the efficacy of colchicine for cardiovascular prevention is controversial, the aims of this study was to evaluate the effect of colchicine therapy on vascular events. Methods A meta-analysis was performed of randomized controlled clinical trials of colchicine on high cardiovascular risk populations, reporting data from stroke, myocardial infarction, cardiovascular mortality and all-cause mortality, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A random-effects meta-analysis model was then applied. Results Nine eligible trials of colchicine therapy, involving a total of 6630 patients, were considered eligible for analysis (3359 subjects were allocated to receive colchicine while 3271 subjects were allocated to the respective control arms). The stroke incidence was lower in the colchicine group compared with placebo arm (OR, 0.33; 95% CI, 0.15–0.70; six studies evaluated). We did not find a significant reduction in the incidence of myocardial infarction, cardiovascular mortality or all-cause mortality. Conclusion Our data suggest that in a population with high cardiovascular risk, the use of colchicine results in significantly reduction on stroke risk. Colchicine is an accessible drug that could be successfully utilized for the prevention of atherosclerotic cerebrovascular disease. The tolerability and benefits should be confirmed in ongoing clinical trials. Forest Plot Primary endpoint Funding Acknowledgement Type of funding source: None