Factors Associated With Successful Withdrawal of Biologic Agents in Children With Colchicine-Resistant Familial Mediterranean Fever.

BACKGROUND: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%-10% of patients may respond inadequately to colchicine, and anti-interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy. METHODS: Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment. RESULTS: In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidities were found to be statistically more frequent in the group whose biological therapy could not be discontinued ( p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively). CONCLUSIONS: Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients.

Drug-Drug Interactions and the Clinical Tolerability of Colchicine Among Patients With COVID-19: A Secondary Analysis of the COLCORONA Randomized Clinical Trial.

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.

Anti-inflammatory effect of colchicine on organ damage during the perioperative period of cardiac surgery: a study protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial.

INTRODUCTION: The systemic inflammatory response syndrome during the perioperative period of cardiac surgery can lead to serious postoperative complications and significantly increase the hospital mortality rate. Colchicine, a widely used traditional anti-inflammatory drug, has good clinical value in cardiovascular anti-inflammatory therapy. Our preliminary single-centre study had confirmed the protective value of colchicine in patients undergoing cardiac surgery with cardiopulmonary bypass. For this multicentre investigation, we aim to further validate the anti-inflammatory and organ-protective effects of low-dose colchicine during the perioperative period in a low-risk population. METHODS AND ANALYSIS: This study is a multicentre, randomised, double-blind, placebo-controlled clinical trial. A total of 768 patients undergoing elective cardiac surgery will be enrolled from eight heart centres in China. The participants will be randomly assigned to two groups: the colchicine group will receive low-dose colchicine (0.5 mg once-a-day dosing regimen (QD) orally for 3 days before the surgery and 0.5 mg dosing frequency of every other day (QOD) continuously for 10 days after the surgery), whereas the placebo group will be given starch tablets for the same time and dosage. Primary endpoints are the occurrence of postoperative inflammatory diseases, including postoperative atrial fibrillation, acute respiratory distress syndrome, preoperative myocardial injury and post-pericardiotomy syndrome. Secondary endpoints included laboratory tests on postoperative days 1, 3, 5, 7 and 10, intensive care unit data, APACHE II score, Murray lung injury score, medication-related gastrointestinal reactions, 30-day and 90-day all-cause mortality, surgical data, chest radiograph on postoperative days 1, 2 and 3, and chest CT within 14 days after surgery. ETHICS AND DISSEMINATION: This research has received approval from the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number 2023-366-01). The study findings will be made available by publishing them in an open access journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT06118034).

Differential diagnosis of pseudogout of the lumbar spine.

This case report details a rare instance of calcium pyrophosphate dihydrate crystal deposition disease (CPPD), commonly known as pseudogout, affecting the lumbar spine. A man in his mid-50s of age presented with severe low-back pain and fever, initially suspected as a spinal infection. Elevated erythrocyte sedimentation rate and leucocytosis were observed, while the initial imaging showed only lumbar spondylosis with arthritic changes in the right L4-L5 facet joint. However, an MRI revealed a cystic lesion at the right L5-S1 facet joint without signs of spondylodiscitis. Ultrasound-guided needle aspiration and synovial fluid analysis, including polarised light microscopy, identified calcium pyrophosphate crystals. Treatment with intravenous pain management was initially ineffective. Confirmation of CPPD led to successful treatment with oral colchicine, resulting in rapid pain alleviation and fever reduction. The patient reported significant improvement at a 2-week follow-up. This case emphasises the importance of thorough investigation in differentiating common symptoms and avoiding unnecessary treatments, highlighting the role of histological examination in diagnosing rare conditions like spinal CPPD.

E148Q variant: a familial Mediterranean fever-causing mutation or a sequence variant?

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease, linked to mutations in the MEFV gene. The p.E148Q variant, found on exon 2, has an uncertain role in FMF, with debates on whether it is a benign polymorphism or a pathogenic mutation. This study aimed to assess the clinical characteristics and severity of FMF in patients homozygous for the p.E148Q variant and to evaluate the impact of the p.V726A variant in these patients. This retrospective cohort study analyzed data from electronic medical records at Carmel Medical Center, Israel. Patients who underwent genetic testing for FMF from November 2004 to December 2019 and had p.E148Q/p.E148Q or p.E148Q/p.E148Q + p.V726A variants were included. Disease severity was assessed using the Tel Hashomer Key to Severity Score. Statistical analyses compared clinical characteristics and severity between genotype groups. The study included 61 FMF patients, with 24 (39%) having p.E148Q/p.E148Q and 37 (61%) having p.E148Q/p.E148Q + p.V726A variants. The majority (72%) were Druze. Most patients (65.5%) exhibited mild disease, while 31.1% had moderate disease, with no cases of severe disease. Colchicine treatment significantly reduced CRP levels in all patients. CONCLUSION: These findings suggest that the p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity, supporting its pathogenic role in particular ethnicity. These results contribute to understanding the clinical significance of the p.E148Q variant and considering the patient's need for Colchicine treatment. WHAT IS KNOWN: • The role of the p.E148Q variant in FMF is debated, with questions about whether it is a benign polymorphism or a pathogenic mutation. • The prevalence of MEFV variants can vary significantly among different ethnic groups. WHAT IS NEW: • The p.E148Q variant has clinical significance in particular ethnicities, as supported by a significant reduction in CRP levels following colchicine treatment. • The p.E148Q variant, whether alone or with p.V726A, generally results in mild to moderate FMF severity.

Effects of Colchicine on Major Adverse Limb and Cardiovascular Events in Patients With Peripheral Artery Disease.

OBJECTIVE: To assess the effects of colchicine, which has been shown to reduce the risks of coronary artery disease but scarcely studied in peripheral artery disease (PAD), on major adverse limb events (MALE) in patients with PAD. METHODS: This is a retrospective study based on a nationwide database. Patients who were diagnosed with PAD between 2010 and 2020 and prescribed with colchicine after the diagnosis of PAD were identified. Patients were then categorized into the colchicine or the control group according to drug use. Propensity score matching was performed to mitigate selection bias. Risks of MALE (including lower limb revascularization and nontraumatic amputation) and major adverse cardiovascular events were compared between the two groups. RESULTS: After patient selection and propensity score matching, there were 60,219 patients in both colchicine and control groups. After a mean follow-up of 4.5 years, the risk of MALE was significantly lower in the colchicine group compared with control (subdistribution HR, 0.75; 95% CI, 0.71 to 0.80), as were the incidence of both components of MALE, lower limb revascularization and major amputations. Colchicine treatment was also associated with lower risk of cardiovascular death. The lower risk of MALE observed with colchicine therapy was accentuated in the subgroup of patients receiving concomitant urate-lowering medications. CONCLUSION: In patients diagnosed with PAD, the use of colchicine is associated with lower risks of MALE and cardiovascular death. Anti-inflammatory therapy with colchicine may provide benefits in vascular beds beyond the coronary arteries.

Recurrent pericarditis and interleukin (IL)-1 inhibitors.

Recurrent pericarditis (RP) is defined by the European Society of Cardiology (ESC) as an instance of acute pericarditis (AP) that occurs at least 4-6 weeks after the resolution of a previous episode of the same ailment. To mitigate the risk of RP, it is advised to administer accurate and prolonged pharmacological treatment for both the initial AP and subsequent RP. ESC guidelines recommend commencing treatment for any single episode of AP, including those that contribute to RP, with non-steroidal anti-inflammatory drugs (NSAIDs) in conjunction with colchicine for several months, often followed by gradual tapering. If there is an inadequate response, corticosteroids (CS) may be introduced cautiously. However, in a minority of cases, even when NSAIDs, colchicine, and CS are administered together at the highest recommended dosages, they may prove ineffective. In such instances, treatment with immunosuppressive drugs or biologics is advised. Among biologics, interleukin (IL)-1 inhibitors have been extensively studied, although certain gaps remain. This narrative review delves into the rationale for employing IL-1 inhibitors and presents findings from existing studies regarding their efficacy, tolerability, and safety. Analysis of the literature indicates that there is currently insufficient data to ascertain the true therapeutic role of IL-1 inhibitors in managing and preventing RP. However, theoretically, drugs targeting both IL-1α and IL-1ß may offer superior efficacy compared to those solely targeting IL-1ß due to the significant involvement of both cytokines in inflammation. Further research is warranted to determine the comparative effectiveness of IL-1α and IL-1ß inhibitors.

Clinical Associations of E148Q Heterozygosity: What to Expect From E148Q?

OBJECTIVE: The exact effects of MEFV variants on inflammation are still under investigation, and reports on variants of unknown significance, particularly the E148Q variant, have been conflicting. Therefore, this study aims to investigate patients exhibiting E148Q heterozygosity, focusing on diagnoses and disease courses to assist physicians in interpreting the variant. METHODS: Data of pediatric patients presenting to the Pediatric Rheumatology clinic between November 2016 and September 2023, exhibiting only E148Q heterozygosity in MEFV gene analysis, were extracted. Patients who were lost before 9 months of follow-up have been excluded to ensure the completion of initial diagnostic tests and evaluations. RESULTS: Among the 119 patients with E148Q variant, the diagnoses were as follows: healthy, 51.3%; IgA vasculitis, 10.1%; Familial Mediterranean Fever (FMF), 7.6%; Periodic fever, Aphtous stomatitis, Pharyngitis, Adenitis (PFAPA), 6.7%; and other diagnoses, 19.3%. IgA vasculitis patients experienced articular, gastrointestinal, and renal involvement at rates of 91.7%, 58.3%, and 16.7%, respectively. Complete response, partial response, and no response to colchicine were 37.5%, 12.5%, and 50%, respectively, in PFAPA patients. All FMF patients responded to colchicine treatment resulting in reduced mean FMF episode counts in 6 months from 3.22 ± 0.92 to 0.56 ± 0.52. CONCLUSIONS: The E148Q variant may amplify inflammation and modify disease courses. Patients with the E148Q variant experiencing typical FMF episodes should receive colchicine, but clinicians should exercise caution regarding alternative diagnoses. Additionally, the E148Q variant may increase acute phase reactants and disease severity in IgA vasculitis. However, to reach definitive conclusions on its treatment-modifying role in PFAPA, universal diagnosis and treatment response criteria should be adopted.

Challenging chest pain: salmonella myopericarditis.

Salmonella infections have been associated with cardiovascular complications, including myocarditis and myopericarditis. This presentation of Salmonella myopericarditis highlights key clinical features to aid in diagnosis and the importance of prompt treatment with antibiotics, colchicine and non-steroidal anti-inflammatory drugs (NSAIDs).

[Challenges in diagnosing familial Mediterranean fever: exploring atypical clinical features. Clinical case].

This clinical case series presents descriptions of 3 patients with familial Mediterranean fever (FMF) who have atypical manifestations and abnormal inheritance mechanisms in terms of Gregor Mendel's laws. Although molecular genetic testing can help with disease diagnosis, it is not always conclusive. The primary need for genetic testing in atypical cases is to explain the mechanism of inflammation and to select the optimal therapy. These clinical observations demonstrate the changes in the spectrum of phenotypic manifestations of FMF in the context of the widespread introduction of molecular genetic methods.

Adult-Onset PFAPA Syndrome: Successful Management with Colchicine.

BACKGROUND Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory fever syndrome primarily seen in children under age 5 years, and its etiology is unknown. Most cases are resolved by the age of 10 years, and it is rare in adults. PFAPA is characterized by recurrent episodes of fever associated with pharyngitis, stomatitis, and cervical adenitis, although not all clinical features are present at initial evaluation. Diagnosis is made clinically, as there are no specific biomarkers available. Treatment includes prednisone, colchicine, interleukin-1 blockers, and tonsillectomy. We report a case of adult-onset PFAPA syndrome that responded to colchicine. CASE REPORT A 22-year-old woman presented to the Rheumatology Clinic for evaluation of recurrent fevers associated with sore throat and enlarged painful cervical lymph nodes. She was symptom-free between the episodes. Workup for infectious causes and autoinflammatory/autoimmune diseases was unremarkable. Various differential diagnoses were considered, due to her unusual presentation. After all were ruled out, PFAPA was diagnosed based on her symptoms, and she started steroids, to which she had a dramatic response and resolution of symptoms. She was then transitioned to oral colchicine, which significantly decreased flare frequency. CONCLUSIONS Being aware of PFAPA syndrome in adults is vital. A timely diagnosis can significantly improve a patient's quality of life. This case highlights the importance of considering PFAPA syndrome in the differential diagnosis of periodic febrile illnesses in adults and the role of Colchicine as prophylaxis. Larger studies are needed to understand etiopathogenesis better and develop other effective therapeutics.

Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial.

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low-Dose Colchicine 2) studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] µm versus 87.2 [95% CI, 69.9 to 104.5] µm; difference, 34.2 [95% CI, 9.7 to 58.6] µm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.

Exploring factors for predicting colchicine responsiveness in children with PFAPA.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) are the most common autoinflammatory syndromes in children. This study aimed to evaluate the clinical and laboratory parameters that may predict colchicine responsiveness.This retrospective, multicenter, cross-sectional study involved nine pediatric rheumatology centers from our country., The patients diagnosed with PFAPA were compared on the basis of their responses to colchicine. In the 806 (42.3% female 57.7% male) patients, the most common clinical findings were fever (100%), exudative tonsillitis (86.5%), pharyngitis (80.9%), and aphthous stomatitis (50.5%). The mean attack frequency was 13.5 ± 6.8 attacks per year lasting for a mean of 3.9 ± 1.1 days. Colchicine treatment was attempted in 519 (64.4%) patients, with 419 (80.7%) showing a favorable response. In patients who underwent MEFV gene analysis (70.8%), the most common variant was M694V heterozygous (16.8%). The presence of pharyngitis (p = 0.03, 95% CI 0.885 to 0.994), the presence of arthralgia (p = 0.04, 95% CI 0.169 to 0.958), and having more frequent attacks (p = 0.001, 95% CI 0.028 to 0.748) were found to be associated with colchicine unresponsiveness, whereas the carriage of the M694V variant (p = 0.001, 95% CI 0.065 to 0.242) was associated with colchicine responsiveness. CONCLUSION: This study identified the presence of pharyngitis, arthralgia, and increased attack frequency in patients with PFAPA as factors predicting colchicine unresponsiveness, whereas the carriage of the M694V variant emerged as a predictor of colchicine responsiveness. Predicting colchicine response at disease onset may facilitate a more effective management of PFAPA. WHAT IS KNOWN: • Colchicine treatment can be used in the prophylaxis of PFAPA disease. • Having the MEFV variant is the most commonly known factor in predicting response to colchicine. WHAT IS NEW: • The presence of pharyngitis or arthralgia, and more frequent attacks in PFAPA disease were found to be independently associated with colchicine unresponsiveness. • Carrying the M694V variant was identified as the sole factor predicting colchicine responsiveness.

Gout: A Rapid Review of Presentation, Diagnosis and Management.

Gout is inflammatory arthritis caused by monosodium urate crystal deposition in articular and non-articular structures. Acute gout flares are often monoarticular/polyarticular involving lower extremity joints characteristically involving 1st metatarsophalangeal joint. However, gout flares can also be polyarticular, involving upper extremity joints, especially in patients with multiple comorbidities and contraindications to urate-lowering therapies (ULT). Risk factors exacerbating gout flares include obesity, high alcohol and purine-rich food consumption, and the use of diuretics. Diagnosis requires synovial fluid analysis with direct visualization of monosodium urate crystals. Acute flares are managed with steroids, non-steroidal anti-inflammatory drugs, or colchicine. Long-term management includes lifestyle modifications including a heavy emphasis on weight loss, avoidance of alcohol, purine-rich foods, and diuretics. ULT is indicated in patients with 2 or more gout flares/year, tophi, or radiographic evidence of gouty arthropathy. Although allopurinol is the first-line ULT agent, it does carry a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and patients harboring the HLA-B*5801 allele. Other ULT agents include febuxostat and probenecid. ULT is usually titrated to achieve goal serum uric acid (SUA) levels below 6 mg/dL. However, in patients with tophi, a lower SUA target of less than 5 mg/dL should be implemented for prompt urate crystal dissolution.

Effect of colchicine on progression of known coronary atherosclerosis in patients with STable CoROnary artery disease CoMpared to placebo (EKSTROM) trial-rationale and design.

BACKGROUND: Cardiovascular disease is the major cause of mortality in the United States. Despite lifestyle modification and traditional risk factor control residual inflammatory risk remains an untreated concern. Colchicine is an oral, medication that has been used for gout, mediterranean fever and pericarditis for decades. In recent trials, colchicine has been shown to reduce major adverse cardiovascular events, however the mechanism of benefit remains unclear. The objective of the randomized, double-blind, placebo controlled EKSTROM trial is to evaluate the effects of colchicine 0.5mg/day on atherosclerotic plaque. METHODS: Eighty-four participants will be enrolled after obtaining informed consent and followed for 12 months. Eligible patients will be randomly assigned to colchicine 0.5mg/day or placebo in a 1:1 fashion as add-on to their standard of care. All participants will undergo coronary computed tomography angiography (CCTA) at baseline and at 12 months. RESULTS: As of November 2023, the study is 100% enrolled with an expected end of study by the second quarter of 2024. The primary endpoint is change in low attenuation plaque volume as measured by CCTA. Secondary endpoints include change in volume of different plaque types (including total atheroma volume, noncalcified plaque volume, dense calcified plaque volume, remodeling index), change in inflammatory markers (IL-6, IL-1ß, IL-18, hs-CRP), change in pericoronary adipose tissue attenuation, change in epicardial adipose tissue volume and attenuation and change in brachial flow mediated dilation. CONCLUSION: EKSTROM is the first randomized study to assess the effects of colchicine on plaque progression, pericoronary and epicardial fat. EKSTROM will provide important information on the mechanistic effects of colchicine on the cardiovascular system. TRIAL REGISTRATION: Registry: clinicaltrials.gov, Registration Number: NCT06342609 url: https://www. CLINICALTRIALS: gov/study/NCT06342609?term=EKSTROM&rank=1.

Colchicine for the treatment of the spectrum of cardiovascular diseases: current evidence and ongoing perspectives.

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.

Colchicine to reduce coronavirus disease-19-related inflammation and cardiovascular complications in high-risk patients post-acute infection with SARS-COV-2-a study protocol for a randomized controlled trial.

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.