Colchicine Therapy Research Articles

Efficacy and safety of anti-interleukin-1 in children with colchicine-resistant familial Mediterranean fever.

The aim of this study was to evaluate the efficacy and safety of anti-interleukin-1 (IL-1) therapies in colchicine-resistant pediatric patients with familial Mediterranean fever (FMF). In this study, we retrospectively evaluated 656 children with FMF and 27 patients who had been treated with anti-IL-1 therapies (anakinra/canakinumab) . Clinical and laboratory features, MEFV gene mutations, treatment responses were investigated. Twenty of the patients were treated with anakinra (the treatment of 6 patients who initially used anakinra was switched to canakinumab in the follow-up period), and 13 patients were treated with canakinumab. Clinical symptom and severity scores decreased in all patients A decrease in acute phase reactants was also observed in patients. A total of 18 (66%) patients had a M694V homozygous mutation, while 24 (89%) patients had a M694V mutation, at least in one allele. FMF patients with colchicine resistance may progress to amyloidosis. IL-1 antagonist treatment could be used safely with a favorable outcome in pediatric patients with FMF resistance to colchicine therapy and/or who have renal amyloidosis.

269 EFFECTS OF COLCHICINE TREATMENT AFTER MYOCARDIAL INFARCTION ON TOP OF STANDARD THERAPY: EVIDENCE FROM A PRECLINICAL STUDY

Abstract Background An intense inflammatory and fibrotic response after myocardial infarction (MI) may lead to scar expansion and left ventricular (LV) remodeling, increasing the risk for ventricular arrhythmias and heart failure. Colchicine is an anti-inflammatory drug that has been reported to improve the outcome of patients with MI; its effects on LV remodeling have not been specifically investigated. We aimed to characterize the effects of the anti-inflammatory drug colchicine in an animal model of reperfused MI. Methods In 4-month-old pigs, MI was induced by occluding the LAD artery through an angioplasty balloon for 90 minutes. Pigs surviving MI induction were randomized in a 1:1 fashion to 2 arms: The pigs underwent a first CMR scan 72 hours after MI induction, and another CMR at day 30. The pigs were then sacrificed the day after the second CMR. The primary efficacy endpoint was LGE mass (as a percentage of LV mass). Results The infarcted area at 72 hours (expressed as absolute mass or as a percentage of the LV mass) and the changes over 1 month did not differ significantly between pigs on colchicine plus standard therapy vs. those on standard therapy alone. When assessing the extent of fibrosis on the explanted hearts (as a percentage of the tissue sample areas) there was a trend toward a lower extent of myocardial fibrosis in pigs on colchicine plus standard therapy (p=0.091). The percent differences in LV volumes, ejection fraction and mass across the two CMR scans did not reach statistical difference. Conclusions The results from a pig model of reperfused MI suggest that colchicine has no additional effects to standard MI therapy on MI size and LV remodeling.

A Typical Case of Familial Mediterranean fever in a War Survivor with Post-Traumatic Stress Disorder of Caucasian Descent Treated with Standard Colchicine Therapy

Objective: A rare case of FMF with atypical presentation of fever attacks lasting 7 days predominantly evident after the war has been described. Usually, the FMF bouts last for 3-4 days but the unusual presentation of our patient led to the initial misdiagnosis of PTSD (Post traumatic stress disorder). Patient and Method: A case of a 38-year-old former Armenian soldier who participated in a 44-day long war with Azerbaijan showing symptoms of recurrent fever, thoracic and abdominal pain predominant only on the left hypochondriac, lumbar and inguinal region. The changes in the laboratory examination were not significant. A wide range of diagnostic tests like X-Ray, CT, and MRI performed all of which were inconclusive. Result: The diagnosis was confirmed after 5 years by positive molecular genetic testing for the MEFV gene. The patient was given colchicine 1 mg/kg/day which reduced the severity and frequency of attacks. Conclusion: The atypical presentation of FMF with prolonged fever lasting up to 7 days, no familial history, post-war trauma, and pain only on the left side led to the differential diagnosis excluding FMF.FMF was suspected when his blood analysis showed acute phase reactants returned to normal after the 7-day attack period. He was started on colchicine therapy and showed a positive response which led to the diagnosis of FMF. The positive MEFV genetic testing confirmed the diagnosis. Clinicians should not exclude the possibility of FMF in patients who do not show the classic fever attack period of 3 to 4 days.

Colchicine for prevention of post-operative atrial fibrillation: Meta-analysis of randomized controlled trials.

This study intended to assess the efficacy of colchicine for prevention of post-operative atrial fibrillation (AF). Post-operative AF is a common complication of surgery operations. Inflammation plays a crucial role in the pathogenesis of post-operative AF. Colchicine, a potent anti-inflammatory drug, may have a role in mitigating the incidence of post-operative AF. We searched Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Database of Chinese sci-tech periodicals (COVIP), and Wanfang Database for randomized controlled trials (RCTs) comparing colchicine versus placebo, or usual care for prevention of post-operative AF. The main outcome was the occurrence of AF post operation, which includes cardiac surgery, lung surgery, or pulmonary vein isolation. The estimated risk ratio (RR) for the occurrence of post-operative AF was evaluated using a random-effects model. The safety end point was the development of any side effects. A total of 12 RCTs with 2274 patients were eventually included in this meta-analysis, where 1141 patients received colchicine and 1133 patients received placebo or usual care. Perioperative colchicine treatment was related to a decreased incidence of post-operative AF (RR: 0.65; 95% confidence interval [CI]: 0.56 to 0.75, p<0.001). Although the incidence of gastrointestinal side effects was increased with colchicine therapy when compared to placebo (RR = 2.49, 95% CI 1.85 to 3.34, p < 0.001), the incidence of major adverse events was not increased (RR = 0.86, 95% CI 0.46 to 1.60, p = 0.64). In conclusion, the results of our meta-analysis suggest that colchicine treatment could lower the incidence of post-operative AF. Further studies are needed to determine the optimal colchicine treatment regime to minimize the incidence of adverse events.

Colchicine for Prevention of Post-Cardiac Surgery and Post-Pulmonary Vein Isolation Atrial Fibrillation: A Meta-Analysis.

Post-cardiac procedure atrial fibrillation (PCP-AF) is a significant medical problem. Inflammation is one of the key factors in the pathogenesis of PCP-AF. As a classical anti-inflammatory drug, colchicine may prevent the occurrence of PCP-AF. This meta-analysis of 12 randomized controlled trials (RCTs) analyzed the feasibility and safety of colchicine for the prevention of PCP-AF. PubMed, EMBASE, Web of Science, the Cochrane Library, and Google Scholar were retrieved for RCTs on the efficacy of colchicine in preventing atrial fibrillation. The primary endpoint was the diagnosis of PCP-AF, which includes cardiac surgery or pulmonary vein isolation. Evaluation was performed with estimated odds ratios (OR) and 95% confidence intervals (CI). In this meta-analysis, 12 RCTs were selected and a total of 2297 patients were included. Colchicine therapy was associated with a reduced incidence of PCP-AF both in post-cardiac surgery (OR: 0.62; 95% CI: 0.49-0.78, p 0.0001, = 0%), and in post-pulmonary vein isolation (OR: 0.43; 95% CI: 0.30-0.62, p 0.0001, = 0%). Colchicine therapy was associated with increased side effects (OR: 2.81; 95% CI: 1.96-4.03, p 0.00001, = 26%). Colchicine can effectively prevent post-cardiac operative atrial fibrillation and relapse of atrial fibrillation after pulmonary vein isolation (PVI). However, colchicine can also increase the incidence of side effects, mainly gastrointestinal adverse events. More studies are needed to find a more appropriate treatment dose and time.

Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial

COVID-19 disease is accompanied by a dysregulated immune response and hypercoagulability. The Anti-Coronavirus Therapies (ACT) inpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with the combination of rivaroxaban and aspirin for prevention of disease progression in patients hospitalised with COVID-19. The ACT inpatient, open-label, 2 × 2 factorial, randomised, controlled trial was done at 62 clinical centres in 11 countries. Patients aged at least 18 years with symptomatic, laboratory confirmed COVID-19 who were within 72 h of hospitalisation or worsening clinically if already hospitalised were randomly assigned (1:1) to receive colchicine 1·2 mg followed by 0·6 mg 2 h later and then 0·6 mg twice daily for 28 days versus usual care; and in a second (1:1) randomisation, to the combination of rivaroxaban 2·5 mg twice daily plus aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome, assessed at 45 days in the intention-to-treat population, for the colchicine randomisation was the composite of the need for high-flow oxygen, mechanical ventilation, or death; and for the rivaroxaban plus aspirin randomisation was the composite of major thrombosis (myocardial infarction, stroke, acute limb ischaemia, or pulmonary embolism), the need for high-flow oxygen, mechanical ventilation, or death. The trial is registered at www. gov, NCT04324463 and is ongoing. Between Oct 2, 2020, and Feb 10, 2022, at 62 sites in 11 countries, 2749 patients were randomly assigned to colchicine or control and the combination of rivaroxaban and aspirin or to the control. 2611 patients were included in the analysis of colchicine (n=1304) versus control (n=1307); 2119 patients were included in the analysis of rivaroxaban and aspirin (n=1063) versus control (n=1056). Follow-up was more than 98% complete. Overall, 368 (28·2%) of 1304 patients allocated to colchicine and 356 (27·2%) of 1307 allocated to control had a primary outcome (hazard ratio [HR] 1·04, 95% CI 0·90-1·21, p=0·58); and 281 (26·4%) of 1063 patients allocated to the combination of rivaroxaban and aspirin and 300 (28·4%) of 1056 allocated to control had a primary outcome (HR 0·92, 95% CI 0·78-1·09, p=0·32). Results were consistent in subgroups defined by vaccination status, disease severity at baseline, and timing of randomisation in relation to onset of symptoms. There was no increase in the number of patients who had at least one serious adverse event for colchicine versus control groups (87 [6·7%] of 1304 vs 90 [6·9%] of 1307) or with rivaroxaban and aspirin versus control groups (85 [8·0%] vs 91 [8·6%]). Among patients assigned to colchicine, 8 (0·61%) had adverse events that led to discontinuation of study drug, mostly gastrointestinal in nature. 17 (1·6%) patients assigned to the combination of rivaroxaban and aspirin had bleeding compared with seven (0·66%) of those allocated to control (p=0·042); the number of serious bleeding events was two (0·19%) versus six (0·57%), respectively (p=0·18). No patients assigned to rivaroxaban and aspirin had serious adverse events that led to discontinuation of study drug. Among patients hospitalised with COVID-19, neither colchicine nor the combination of rivaroxaban and aspirin prevent disease progression or death. Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, Thistledown Foundation. For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial

The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed health-care systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19. The ACT outpatient, open-label, 2 × 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0·6 mg twice daily for 3 days and then 0·6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing. Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0·1%) of 3881 for major thrombosis, 123 (3·2%) of 3881 for hospitalisation, and 23 (0·6%) of 3881 for death; 66 (3·4%) of 1939 patients allocated to colchicine and 65 (3·3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1·02, 95% CI 0·72-1·43, p=0·93); and 59 (3·0%) of 1945 of patients allocated to aspirin and 73 (3·8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0·80, 95% CI 0·57-1·13, p=0·21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1·8%] of 1939 vs 27 [1·4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1·6%] vs 31 [1·6%]) and none that led to discontinuation of study interventions. The results provide no support for the use of colchicine or aspirin to prevent disease progression or death in outpatients with COVID-19. Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, and Thistledown Foundation. For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

Individual lifetime benefit from low-dose colchicine in chronic coronary artery disease patients

Abstract Background Low-dose colchicine reduces the risk of cardiovascular events in patients with chronic coronary artery disease (CAD), but the absolute benefit may vary between patients. Individual benefit from preventive therapies can be estimated using the guideline-recommended SMART-REACH model. Purpose This study aimed to assess the range of individual absolute 10-year and lifetime benefit from low-dose colchicine according to patient risk profile. Methods The SMART-REACH model was combined with the relative treatment effect of low-dose colchicine, and applied to all participants from the LoDoCo2 trial (n=5,522), and patients with chronic CAD from the UCC-SMART cohort (n=5,308). Individual treatment benefit was expressed as (i) 10-year absolute risk reductions (ARRs) for myocardial infarction, ischemic stroke, or cardiovascular death (MACE), and (ii) life-years gained free of MACE. Predictions were also performed for MACE plus ischemia-driven coronary revascularization (MACE+), through development of a new competing risk-adjusted lifetime prediction model in data from the REACH registry (n=14,522). Low-dose colchicine was compared to alternative intensive prevention goals, i.e. low density lipoprotein-cholesterol (LDL-c) reduction to &amp;lt;1.4 mmol/L, and systolic blood pressure (SBP) reduction to &amp;lt;130 mmHg. Results Median individual 10-year ARR for MACE from low-dose colchicine therapy was 4.6% (interquartile range [IQR] 3.6–6.0%), and median gain in life expectancy free of MACE was 2.0 (IQR 1.6–2.5) years. Median 10-year ARR for MACE+ was 8.6% (IQR 7.6–9.8%), and median gain in MACE+-free life expectancy was 3.4 (IQR 2.6–4.2) years. For intensified LDL-c and SBP reduction respectively, median 10-year ARRs were 3.0% (IQR 1.5–5.1%) and 1.7% (IQR 0.0–5.7%) for MACE, and 5.2% (IQR 2.5–8.7%) and 2.9% (IQR 0.0–9.5%) for MACE+. Median life-years gained from LDL-c and SBP reduction were 1.2 (IQR 0.6–2.1) and 0.7 (IQR 0.0–2.3) years free of MACE, and 1.8 (IQR 0.8–3.3) and 0.9 (IQR 0.0–3.4) years free of MACE+. Conclusion The individual absolute benefit from low-dose colchicine varies between patients. In an era where lipid- and blood pressure-lowering therapies are already routinely used, the benefits of low-dose colchicine are expected to be of at least similar magnitude to those of intensified LDL-c and SBP reduction in patients with chronic CAD. Funding Acknowledgement Type of funding sources: None.

Features predicting colchicine efficacy in treatment of children with undefined systemic autoinflammatory disease: A retrospective cohort study

Patients with undefined systemic autoinflammatory diseases (uSAIDs) are challenging to manage, as there are no guidelines or recommendations for targeted therapy. We aimed to evaluate the efficacy of empiric treatment with colchicine in our single-center uSAID population in the United States, as well as the patient characteristics associated with the most robust colchicine response. Children with uSAID 18 years old at initial evaluation during 2000-2019 were included if they received 3 months of colchicine therapy. Data on demographics, clinical features, laboratory/ genetic studies, and treatment responses were collected. Most statistics were based on chi-square analyses for categorical data. Complete response to colchicine was defined as resolution of episodes or the presence of minor residual symptoms that did not require any further therapy. A partial response was defined as a decrease in the frequency, severity, or length of episodes but still necessitating additional therapy. Patients were considered nonresponders if they did not experience any improvement with colchicine at target therapeutic dosing. We identified 133 children diagnosed with uSAID who met our inclusion criteria. The median time to starting empiric colchicine was 5 months from the diagnosis of autoinflammatory disease. 92.5% (n = 123) of patients had a beneficial response to colchicine, including 46.6% (n = 62) partial responders and 45.9% (n = 61) complete responders. The presence of a nonurticarial rash was associated with an incomplete colchicine response (29.2% (n = 21) vs 13.1% (n = 8), P = .025). The presence of a heterozygous MEFV mutation in patients who did not fit Familial Mediterranean Fever diagnostic criteria (n = 25) appeared to be associated with a greater likelihood of complete colchicine response, although this was not statistically significant (62.5% (n = 14) vs 42.6% (n =11), P = .08). In MEFV mutation-negative patients, a nonurticarial rash was even more strongly associated with incomplete colchicine response, with an OR of 27.53 (CI [1.59-477], P = .023). The presence of oral ulcers also corresponded to incomplete colchicine response, although this did not reach clinical significance (38.9% (n = 28) vs 24.6% (n = 15), P = .08). There was no significant association between episode duration or frequency and colchicine response. Colchicine leads to clinical benefits in most children with uSAID. We, thus, recommend an early trial of colchicine in newly diagnosed patients with uSAID.

Preventie van het postpericardiotomiesyndroom na cardiale heelkunde: wie heeft baat bij profylaxe?

Who should need colchicine for prevention of the postpericardiotomy syndrome? The post-cardiac pericardiotomy syndrome (PPS) is a probably immune-mediated inflammatory process as a reaction on cardiac tissue damage. It is a major cause of pericarditis after cardiac surgery, myocardial infarction or chest trauma, as well as less invasive surgery such as ablations or pacemaker lead insertions. It occurs in up to 29% of all patients following cardiac surgery. PPS is associated with a prolonged hospitalization, readmissions, the need for invasive interventions and a higher mortality rate, especially in case of invasive cardiac surgery. Colchicine prevents PPS at the cost of adverse events. Identification of patients prone to PPS is important to make an adequate prophylactic administration of colchicine possible. The aim of the study was to evaluate the risk factors for developing PPS after cardiac surgery. By reviewing the literature, multiple possible risk factors were identified: patient-related factors, environment-related factors, peri- and postoperative biochemical determinants, and procedure-related factors. A prospective indexation of all these risk factors as well as awareness for PPS can help the clinician to better identify these high-risk groups and optimally use prophylactic colchicine therapy for PPS prevention.

IL-1 inhibition in familial Mediterranean fever: clinical outcomes and expectations.

Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease, characterised by recurrent episodes of fever and serositis. Since 1972, colchicine is the drug of choice for FMF. It is effective in preventing the attacks and withholding amyloidosis in most patients with FMF. Colchicine blood and tissue levels are regulated by a glycoprotein pump (GLP) and by Cytochrome P450 3A4 (CYP450 3A4). It is secreted through the bile system and the kidneys. Over the years several problems have been raised following the use of colchicine in FMF. These include potential side effects (particularly gastrointestinal), non-compliance, inefficacy due to drug resistance, many drug-drug interactions and high risk for intoxication due to a narrow therapeutic range. In addition, colchicine does not prevent protracted febrile myalgia or exertional leg pain. Based upon our current understanding of the pathogenesis of FMF, it seems that anti-interleukin-1 (anti-IL-1) agents can solve many of the aforementioned problems related to colchicine therapy. The gastrointestinal side effects of colchicine are extremely uncommon with anti-IL-1 biologics. Drug-drug interactions are also unlikely, and their therapeutic window is not narrow. The once daily injection of anakinra, the once weekly injection of rilonacept, and the once monthly injection of canakinumab result in a better compliance to therapy. Nevertheless, there are no controlled trials showing the efficacy of anti-IL-1 agents in preventing amyloidosis or their safety in pregnancy. Therefore, it is still needed to give IL-1 blockers with concomitant colchicine in its tolerable dose effective in preventing amyloidosis (1.5 mg daily in adult).

Colchicine for the Treatment of Cardiac Injury in Hospitalized Patients With Coronavirus Disease-19.

IntroductionThe impact of colchicine on hospitalized patients with Coronavirus disease-19 (COVID-19) related cardiac injury is unknown.Materials and MethodsIn this multicenter randomized controlled open-label clinical trial, we randomized hospitalized adult patients with documented COVID-19 and evidence of cardiac injury in a 1:1 ratio to either colchicine 0.6 mg po twice daily for 30 days plus standard of care or standard of care alone. Cardiac injury was defined as elevated cardiac biomarkers, new arrhythmia, new/worsened left ventricular dysfunction, or new pericardial effusion. The primary endpoint was the composite of all-cause mortality, need for mechanical ventilation, or need for mechanical circulatory support (MCS) at 90 days. Key secondary endpoints included the individual components of the primary endpoint and change in and at least 2-grade reduction in the World Health Organization (WHO) Ordinal Scale at 30 days. The trial is registered with clinicaltrials.gov (NCT04355143).ResultsWe enrolled 93 patients, 48 patients in the colchicine arm and 45 in the control arm. There was no significant difference in the primary outcome between the colchicine and control arms (19 vs. 15%, p = 0.78), nor in the individual components of all-cause mortality (17 vs. 15%, p = 1.0) and need for mechanical ventilation (8 vs. 5%, p = 0.68); no patients in either group required MCS. The change in (−1.8 ± 2.4 vs. −1.2 ± 2.0, p = 0.12) and at least 2-grade reduction (75 vs. 75%, p = 1.0) in the WHO ordinal scale was also similar between groups.ConclusionPatients hospitalized with COVID-19 and evidence of cardiac injury did not benefit from colchicine therapy.

Cardiac repolarization abnormalities in children with familial Mediterranean fever

BackgroundFamilial Mediterranean fever (FMF) is an autoinflammatory disease that can have conduction disturbances and cardiac rhythm disorders as manifestations of cardiac involvement. The aim of the study is to assess the susceptibility of children with FMF to cardiac repolarization abnormalities and therefore arrhythmia in children with FMF.MethodsA cross sectional study conducted on 60 children had FMF and 40 age and sex matched healthy controls. Cardiac repolarization markers, cardiac dimensions and functions were assessed by electrocardiogram (ECG) and conventional echocardiography in patients and controls.ResultsThe mean ± SD age of the patients was 10.43 ± 3.472 years, corrected QT (QTc) and the ratio of peak to end T wave (Tpe) over QTc interval (Tpe /QTc) increased significantly in FMF patients more than healthy control (p value 0.023 and 0.022 respectively). P wave dispersion (Pd) was significantly higher in FMF patients with amyloidosis (p value 0.030). No significant difference was found in cardiac dimensions and functions between the two groups. We found a statistically negative correlation between Pd and age of patients at time of study, age of disease onset and age at diagnosis. On the other hand, we found a statistically significant positive correlation between Pd with number of attacks per year and disease severity score. Furthermore, Tpe/QTc ratio correlated with FMF 50 score, QTc correlated with 24 hours proteinuria. QT, JT intervals correlated with fibrinogen.ConclusionsFMF Patients may have increased risk of arrhythmia and should be monitored on regular basis. Compliance to colchicine therapy and better disease control might play a role in decreasing this risk.

Strong association between acute phase reactants (high-sensitivity C-reactive protein and erythrocyte sedimentation rate) and the familial Mediterranean fever (FMF) in patients but not with the MEFV genotype

Background and objectiveFMF (Familial Mediterranean fever) is an autoinflammatory hereditary disease with autosomal-recessive mode of inheritance.The main objective of our research was to establish if there is a link between acute phase reactants (APRs) (i.e. hs-CRP and ESR) and FMF in patients compared to controls at the time of diagnosis and before starting colchicine therapy. We also tried to find out if there is an association between the MEFV gene genotypes in FMF patients and APRs (ESR and hs-CRP). Moreover, we tried to find if there is a link between M694V genotypes and the hs-CRP and ESR levels. ResultsThis study was achieved on 101 FMF patients (group I), as well as 107 healthy individuals (group II). hs-CRP values ranged from 0.02 to 104 mg/L and from 0.1 to 5.29 mg/L in groups I and II, respectively. Mean hs-CRP was 7.97 ± 18.58 and 1.23 ± 1.58 mg/L in groups I and II, respectively. The p-value is 0.000243 which strongly indicates a significant difference between both groups. ESR values ranged between 1 and 75 mm in 1 h in group I and between 0.1 and 3.6 mm in one hour in group II. Mean ESR was 17.25 ± 19.40 and 1.31 ± 1.21 mm in one hour in group I and II, respectively. The p-value is <0.00001 which indicates a significant difference between both groups. However, our study did not indicate any link between genotypes of MEFV mutations and hs-CRP levels and ESR in our patients, in addition to the lack of a strong link between the M694V mutation and hs-CRP levels and ESR. ConclusionOur data show the significance of hs-CRP levels and ESR in patients with FMF when diagnosing the disease, before starting the colchicine treatment and in attack-free periods, which may give us an impression about the disease severity.

Sheppard Siegal Syndrome (Familial Mediterranean fever): The Value of Serum Amyloid a in the Diagnosis and Treatment Decision

Background: Sheppard Siegal syndrome was first described in 1945 by Sheppard Siegal. He described in details an extraordinary syndrome that was often undiagnosed because it was not clearly understood. The syndrome described by Siegal is characterized by recurrent attacks of fever, and commonly begins during childhood, and may begin as early as seven months. Attacks of the syndrome usually last two to three days and, often recur every few weeks. Siegal emphasized that progressive renal disease in the form of amyloidosis or chronic glomerulonephritis is the most serious organ involvement. Four mutations in the MEFV gene have been reported to account for 86% of the mutations causing Sheppard Siegal syndrome. Colchicine has been used for the treatment and prevention amyloidosis. Patients and methods: The father of a 3.5-year Iraqi boy (Born on the 19th of March, 2018) of Kurdish origin living in Dubai consulted us during September, 2021 about the appropriate treatment of his son who was experiencing recurrent attacks of high fever over about one year. He consulted us after consulting few physicians in Dubai who were prescribing oral and injectable acetaminophen for the symptomatic control of fever during the attacks. The case was studied and an evidenced-based recommendation is presented in this paper. Results: The attacks of fever were persisting for few days and were not generally associated with mo other significant symptoms other than the general ill health and tiredness that can be associate with fevers of various etiologies. Between the attacks, the boy was in good health and had normal activity. The father was unaware of a similar illness in their relatives. Serum amyloid A (EIA) was performed during the last attack of fever during August, 2021, and was very high (517mg/L), as the normal level is less than 6.40517mg/L. Analysis of regions of the MEFV gene showed no pathogenic variants were detected. Conclusion: We have recommended monitoring serum amyloid A during attack free periods, and initiate colchicine therapy if serum amyloid A was found high to prevent the development of amyloidosis according to the evidence provided by Berkun et al (2007).

The effect of colchicine treatment on complete blood cell count-based parameters in patients with Behçet's disease

Aim: Behçet's disease (BD) is a systemic disease, with still unknown etiology and pathogenesis and varying disease presentations, characterized by recurrent oral aphthae, followed by genital ulcers, arthritis, variable skin and ocular lesions, gastrointestinal and central nervous system involvement, as well as, vascular disease. Colchicine is one of the oldest remedies still in use today. The study aimed to investigate the effect of colchicine on levels of the complete blood cell count-based parameters in BD.&#x0D; Material and Method: A total of 117 (participants 60 healthy control and 57 patients with BD) were recruited from the rheumatology department in a single-center case-control study. The laboratory data were obtained from the electronic registration database. Laboratory findings of patients and healthy controls were evaluated. In addition, patients with BD were evaluated for these parameters before colchicine therapy and after 3-month from the beginning of colchicine treatment.&#x0D; Results: The levels of inflammatory markers such as neutrophil count, neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and systemic immune-inflammation index (SII), significantly higher than the control group before treatment, decreased to similar levels with the control group in the third month of colchicine use. However, red blood cell distribution width (RDW), mean platelet volume (MPV), and plateletcrit (PCT) were still statistically significantly different from the control group in BD patients.&#x0D; Conclusion: SII, CRP, ESR, and NLR are useful parameters to evaluate the colchicine response of patients with mucocutaneous BD.

Predictive risk factors for hospitalization and response to colchicine in patients with COVID-19

ObjectiveA predictive model for hospitalization due to COVID-19 or death was developed in the placebo group (N=2,084) from a large clinical trial of colchicine in COVID-19 patients (N = 4,159). ResultsThe 7 variables retained in the predictive model were age, gender, body-mass index, history of respiratory disease, use of diabetes drugs, use of anticoagulants, and use of oral steroids at the time of randomization. An optimal threshold value identified from the predictive model was used to classify high-risk patients (those with a predicted probability above the optimal threshold) and low-risk patients (those with a predicted probability below the optimal threshold). The number needed to treat to prevent 1 hospitalization or death with colchicine treatment decreased from 71 in the whole study population (N = 4,159) to 29 in the high-risk subgroup (N=1,692). ConclusionThis model could serve to identify high-risk subjects who will particularly benefit from early colchicine therapy.

Real-life data on tapering or discontinuation of canakinumab therapy in patients with familial Mediterranean fever.

This study aimed to investigate the disease characteristics of familial Mediterranean fever (FMF) patients undergoing dose optimisation and discontinuation of canakinumab therapy. A total of 61 patients diagnosed with FMF and using canakinumab for the resistant disease were enrolled on this retrospective study. Patients’ characteristics, disease activity, treatment response, dose optimisation, dose intervals, attack-free periods, drug-free periods and side effects were noted. Dose intervals were extended in patients who achieved remission without being bound by any protocol at the discretion of the rheumatology physician who followed up with the patients in the outpatient clinic. The drug was discontinued in some patients whose dose intervals were 2 months or longer and remained in remission for 6 months or longer. A total of 57 patients (56% female, median age 32.4 years) were included. The mean attack frequency before canakinumab was 3.4/6 months, while it was 1.2 at the last post-treatment visit (p < 0.001). The median duration of canakinumab use was 46 months. After the first 6 months, the dosing interval was extended in 22 patients, and then treatment was discontinued in 12 of them who did not have an attack in the last 6 months. Three of the 12 patients whose treatment was discontinued started monthly treatment again after their attacks recurred. In the remaining ten patients, dose intervals were extended to 8–12 weeks after 6 months of monthly treatment. Nine patients are still being followed up without attacks and receive only colchicine therapy. Canakinumab is a safe and effective treatment, dose intervals may be extended, and follow-up without medication may be possible for eligible patients. However, there is a need for a consensus on dose optimisation or tapering.

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.

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.