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עמוד בית
Tue, 04.10.22

Search results


March 2022
Ortal Tuvali MD, Gal Sella MD, Dan Haberman MD, Valeri Cuciuc MD, and Jacob George MD

The pathogenesis of atherosclerosis is multifactorial, mainly driven by complex inflammatory processes. Colchicine is an anti-inflammatory drug used in a variety of clinical settings. The purpose of this review is to evaluate the role of colchicine in atherosclerotic vascular disease and more specifically, its promising impact on the outcome of patients with stable and acute coronary syndrome and to review its effect in patients undergoing angioplasty. A literature review was performed using the search terms colchicine, coronary heart disease, or acute coronary syndrome, stable coronary disease. We accessed PubMed, Google scholar, and the Cochrane Library databases to search for studies. Patients with chronic coronary disease may benefit from treatment with low dose colchicine to reduce the occurrence of a cardiovascular event. Among patients with a recent myocardial infarction, colchicine treatment was associated with reduced ischemic cardiovascular events, although without a meaningful difference in mortality. Colchicine was found to be a promising agent that can be potentially integrated into the armamentarium of treatments for patients with atherosclerotic coronary disease pending careful patient selection

February 2020
Lev Freidkin MD, Uri Landes MD, Nili Schamroth Pravda MD, Dan Aravot MD, Ran Kornowski MD, Zaza Iakobishvili MD and Aviv Mager MD

Background: Post-pericardiotomy syndrome (PPS) is a major cause of pericarditis, yet data on the risk of recurrence are limited, and the impact of steroids and colchicine in this context is unknown.

Objectives: To examine the effect of prednisone and colchicine on the rate of recurrence of PPS.

Methods: Medical files of patients diagnosed with PPS were reviewed to extract demographic, echocardiographic, X-ray imaging, and follow-up data.

Results: The study comprised 132 patients (57% men), aged 27–86 years. Medical treatment included prednisone in 80 patients, non-steroidal anti-inflammatory agents in 41 patients, colchicine monotherapy in 2 patients, and no anti-inflammatory therapy in 9 patients. Fifty-nine patients were given colchicine for prevention of recurrence. The patients were followed for 5–110 months (median 64 months). Recurrent episodes occurred in 15 patients (11.4%), 10 patients had a single episode, 4 patients had two episodes, and one patient had three episodes. The rate of recurrence was lower in patients receiving colchicine compared to patients who did not (8.5% vs. 13.7%), and in patients not receiving vs. receiving prednisone (7.7% vs. 13.8%) but the differences were non-significant. Twenty-three patients died and there were no recurrence-related deaths.

Conclusions: The rate of recurrence after PPS is low and multiple recurrences are rare. The survival of patients with recurrent PPS is excellent. Prednisone pre-treatment was associated with a numerically higher rate of recurrence and colchicine treatment with a numerically lower rate, but the differences were non-significant.

June 2015
Naomi Nussinovitch MD PhD, Konstantin Esev MD, Merav Lidar MD, Udi Nussinovitch MD PhD and Avi Livneh MD

Abstract

Background: The relationship between autonomic nervous system (ANS) dysfunction and familial Mediterranean fever (FMF) is controversial. We recently reported normal heart rate variability (HRV), suggestive of normal ANS, in patients with uncomplicated FMF.

Objectives: To evaluate ANS function in colchicine non-responders by using the HRV tool.

Methods: The study group comprised 24 FMF patients suffering from recurrent FMF attacks despite treatment with a maximal colchicine dose. Electrocardiogram was measured under strict conditions and HRV parameters were calculated. Results were compared with age- and gender-matched unaffected controls.

Results: No statistically significant difference was found between the groups in any of the HRV parameters: maximal RR, minimal RR and average RR intervals, standard deviation of RR interval, square root of the mean squared differences of successive RR intervals, HRV triangular index, NN50, pNN50, and power spectral analysis parameters.

Conclusions: Although a small difference in HRV parameters in the current study cannot be entirely excluded, FMF patients in whom colchicine did not provide adequate symptomatic relief and who did not develop amyloidosis appear to have normal HRV parameters suggestive of normal ANS function, compared with healthy adults. 

March 2015
Philip J. Hashkes MD MSc and Bin Huang PhD

Abstract

Background: The familial Mediterranean fever 50 score (FMF50) score was recently devised to define response to treatment and as an outcome measure for clinical trials of FMF.

Objectives: To examine the performance of the FMF50 score in a previously published trial of rilonacept for patients whose FMF was resistant or intolerant to colchicine.

Methods: We reanalyzed the data from our controlled trial of rilonacept vs. placebo in 14 patients with colchicine-resistant or intolerant FMF using the FMF50 score as the primary outcome. The FMF50 score required improvement by ≥ 50 in five of six criteria (attack frequency, attack duration, global patient assessment, global physician assessment, frequency of attacks with arthritis, and levels of acute-phase reactants without worsening of the sixth criterion).

Results: In the original trial rilonacept was considered effective according to the primary outcome measure (differences in the attack frequency) with eight analyzable patients considered responders and four as non-responders. According to the FMF50 score, only two participants would have been considered responders to rilonacept, and one to placebo. Only two participants had ≥ 50% differences between rilonacept and placebo in five criteria. The major explanation for non-response to treatment was that with rilonacept the duration of attack decreased by ≥ 50% in only 2 participants and 5 participants had no attacks of arthritis either during screening (before randomization) or during treatment with rilonacept.

Conclusions: The proposed FMF50 score did not differentiate well between responders and non-responders compared to the a priori defined primary outcome measure in this successful controlled study. 

May 2014
Ilan Ben-Zvi MD and Avi Livneh MD
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease characterized by spontaneous short attacks of fever, elevated acute-phase reactants, and serositis. Approximately 5%–10% of FMF patients do not respond to colchicine treatment and another 5% are intolerant to colchicine because of side effects. Recently, following the discovery of the inflammasome and recognition of the importance of interleukin-1β (IL-1β) as the major cytokine involved in the pathogenesis of FMF, IL-1β blockade has been suggested and tried sporadically to treat FMF, with good results. To date, case reports and small case series involving colchicine-resistant FMF patients and showing high efficacy of IL-1β blockade have been reported. At the Israel Center for FMF at the Sheba Medical Center the first double-blind randomized placebo-controlled trial of anakinra in FMF patients who are resistant or intolerant to colchicines is underway. In this report we discuss the mechanism of colchicine resistance in FMF patients, the data in the literature on IL1β blockade in these patients, and the anakinra trial inclusion criteria and study protocol.

April 2012
I. Ben-Zvi, I. Danilesko, G. Yahalom, O. Kukuy, R. Rahamimov, A. Livneh and S. Kivity

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation in some patients.

Objectives: To assess demographic, clinical and genetic risk factors for the development of FMF amyloidosis in a subset of kidney-transplanted patients and to evaluate the impact of transplantation on the FMF course.

Methods: Demographic, clinical and genetic data were abstracted from the files, interviews and examinations of 16 kidney-transplanted FMF amyloidosis patients and compared with the data of 18 FMF patients without amyloidosis.

Results: Age at disease onset and clinical severity of the FMF amyloidosis patients prior to transplantation were similar to FMF patients without amyloidosis. Compliance with colchicine treatment, however, was much lower (50% vs. 98 %). Post-transplantation, FMF amyloidosis patients experienced fewer of the typical serosal attacks than did their counterparts (mean 2214 days since last attack vs. 143 days). Patients with FMF amyloidosis carried only M694V mutations in the FMF gene, while FMF without amyloidosis featured other mutations as well.

Conclusions: Compliance with treatment and genetic makeup but not severity of FMF constitutes major risk factors for the development of amyloidosis in FMF. Transplantation seems to prevent FMF attacks. The protective role of immunosuppressive therapy cannot be excluded.

 

April 2011
S. Kivity, I. Danilesko, I. Ben-Zvi, B. Gilburd, O.L. Kukuy, R. Rahamimov and A. Livneh

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation. Since amyloidosis is prompted by high serum amyloid A (SAA) levels, increased SAA is expected to persist after transplantation. However, no data are available to confirm such an assumption.

 Objectives: To determine SAA levels in kidney-transplanted FMF-amyloidosis patients and evaluate risk factors for the expected high SAA levels in this patient group.

Methods: SAA, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were obtained from 16 kidney-transplanted FMF-amyloidosis patients, 18 FMF patients without amyloidosis and 20 kidney-transplanted patients with non-inflammatory underlying disease. Demographic, clinical and genetic risk factors evaluation was based on data extracted from files, interviews and examination of the patients.

Results: SAA level in FMF patients who underwent kidney transplantation due to amyloidosis was elevated with a mean of 21.1 ± 11.8 mg/L (normal ≤ 10 mg/L). It was comparable to that of transplanted patients with non-inflammatory disorders, but tended to be higher than in FMF patients without amyloidosis (7.38 ± 6.36, P = 0.08). Possible risk factors for the elevated SAA levels in kidney transplant patients that were excluded were ethnic origin, MEFV mutations, gender, age and disease duration.

Conclusions: Kidney-transplanted patients with FMF-amyloidosis and with other non-FMF causes displayed mildly elevated SAA levels, possibly resulting from exposure to foreign tissue rather than from various FMF-related factors. 

 

January 2008
G. Markel, M. Imazio, A. Brucato and Y. Adler


The most troublesome complication of acute pericarditis is recurrent episodes of pericardial inflammation, which occur in 15–32% of cases. It was recently found that viral infection has a major role, but in many cases the cause is unknown. The optimal method for prevention has not been fully established; accepted modalities include non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents, and pericardiectomy. Based on the proven efficacy of colchicine in familial Mediterranean fever, several small and large-scale international clinical trials have shown the beneficial effect of colchicine therapy in preventing recurrent pericarditis. Indeed, colchicines-treated patients consistently display significantly fewer recurrences, longer symptom-free periods, and even when attacks occur they are weaker and shorter in nature. It was also found that pretreatment with corticosteroids substantially attenuates the efficacy of colchicine, as evidenced by significantly more recurrences and longer therapy periods. Colchicine is a safe and effective modality for the treatment and prevention of recurrent pericarditis, especially as an adjunct to other modalities, since it provides a sustained benefit superior to all current modalities. The safety profile seems superior to other drugs such as corticosteroids and immunosuppressive drugs.

July 2006
A. Leibovitz, M. Lidar, Y,. Baumoehl, A. Livneh and R. Segal

Backgound: Colchicine is widely used for treating gout and familial Mediterranean fever. However, studies in animal models have reported ill effects of colchicine on the central nervous system, including cognitive function.

Objectives: To evaluate the cognitive status of elderly FMF[1] patients on long-term colchicine treatment.

Methods: The study group consisted of 55 FMF patients aged 74 ± 5, attending an FMF outpatient clinic and receiving colchicine treatment for 25.1 ± 8.9 years. The Mini-Mental State Examination was used for cognitive evaluation. Patients' scores were compared with accepted age- and education-adjusted cutoff scores, population-based norms, and scores of a matched control group of 56 subjects.

Results: Individually, all colchicine-treated FMF patients scored well above the age- and education-corrected cutoff scores. Overall, there was a large difference, 5.0 ± 1.6, from the expected cutoff points, in favor of the study group scores (P < 0.001). The individual scores of the control group were also above the cutoff points, however with a lower but still statistically significant difference (3.71 ± 1.15 points, P < 0.001). Compared to population-based norms adjusted by age and education, the study group had significantly higher mean MMSE[2] scores (27.2 ± 2.2 vs. 25.5 ± 2.4, P < 0.001). The control group’s scores were also somewhat higher than expected, but not significantly so.

Conclusions: Our results do not support the view that prolonged colchicine treatment may be associated with cognitive impairment. On the contrary, it is possible that long-term colchicine treatment may even confer protection against cognitive decline in patients with FMF.


 





[1] FMF = familial Mediterranean fever

[2] MMSE = Mini-Mental State Examination


T. Hershcovici, T. Chajek-Shaul, T. Hasin, S. Aamar, N. Hiller, D. Prus and H. Peleg
January 2005
I. Dudkiewicz, I. Cohen, S. Horowitz, S. Regev, M. Perelman, A. Chechik, P. Langevitz, S. Strasburg, A. Livneh and M. Salai

Background: Heterotopic ossification is a common complication of hip surgery and musculoskeletal or brain traumas.

Objectives: To confirm by in vivo study that colchicine inhibits osteoblast cell proliferation with marked decrease in tissue mineralization.

Methods: Heterotopic ossification was induced in three groups of New Zealand white rabbits (females, 6 months old, weight 3–3.5 kg) by injecting 2 ml bone marrow drawn from the iliac crest into their right thigh muscle. To prevent heterotopic ossification, colchicine (0.25 mg/day) was administered orally for 4 weeks to two groups of adult rabbits: group A (preload group) – 1 week preceding bone marrow injection; group B – on day of injection; and group C – control group.

Results: After 4 weeks the rabbits were evaluated by radiographs and ultrasound for evidence of heterotopic ossification. At the end of the study histologic samples were taken from all the thighs. Imaging and histologic studies showed, with statistical significance, almost complete prevention of heterotopic ossification formation in group A (preload) and a marked decrease in group B, when compared with the controls in whom large new bone had formed at the injection site. These results indicated the inhibitory effects of colchicine on a bone-forming process in soft tissue such as heterotopic ossification.

Conclusions: The role of colchicine in preventing heterotopic ossification in other bone-forming conditions, such as hip arthroplasty or pelvic trauma, and after brain trauma, remains to be evaluated in a clinical setting.

 
 

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