Colchicine in the treatment of AA and AL amyloidosis

doi:10.1016/S0049-0172(05)80042-3

Seminars in Arthritis and Rheumatism

Volume 23, Issue 3, December 1993, Pages 206-214

https://doi.org/10.1016/S0049-0172(05)80042-3 Get rights and content

Colchicine is an effective medication in the prevention and treatment of amyloidosis of familial Mediterranean fever. Its therapeutic effect depends on the stage of renal disease and the drug dose. To evaluate colchicine effect in AA amyloidosis of other diseases and in primary AL amyloidosis; the literature was reviewed. Findings were that (1) the effect of colchicine in reactive amyloidosis has not been methodically studied, but anecdotal reports suggest it may be beneficial; and (2) the results of studies and case reports on the effect of colchicine in primary amyloidosis are conflicting. Because a therapeutic effect of colchicine in primary and reactive amyloidosis has been shown in sporadic cases, a prospective, controlled, multicenter study assessing the effect of colchicine in all types of amyloidosis appears to be justified. Until such a study is available, the addition of colchicine in an appropriate dose to any therapeutic regimen of patients with AA or AL amyloidosis should be considered.

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Straightforward one-step approach towards novel derivatives of 9-oxo-5,6,7,9-tetrahydrobenzo[9,10]heptaleno[3,2-b]furan-12-yl)acetic acid based on the multicomponent reaction of colchiceine, arylglyoxals and Meldrum's acid
2021, Tetrahedron Letters
A straightforward one-pot approach was developed for the synthesis of substituted colchicine derivatives based on the telescoped multicomponent reaction of colchiceine, arylglyoxals and Meldrum’s acid. Regiospecific formation of the 6,7-dihydrobenzo[9,10]heptaleno[3,2-b]furan-9(5H)-one moiety is a distinctive feature of the protocol. Advantages of this method include the use of readily accessible starting materials, process simplicity and easy isolation of the target products. The structure of one of the furotropolone derivatives was confirmed by 2D NMR-spectroscopy.
Age dependent safety and efficacy of colchicine treatment for familial mediterranean fever in children
2019, Seminars in Arthritis and Rheumatism
Citation Excerpt :
Nearly 75% of patients show almost full remission and 20%, partial remission. Studies in children reported improved quality of life, low morbidity, and normal growth, development, and life expectancy [7–11]. Colchicine has an excellent long-term safety profile in the adult [7,9] and pediatric populations [8,10], but numerous adverse events and lower therapeutic threshold may limit its use [12].
Objective: Colchicine has been found to be highly effective for the treatment of familial Mediterranean fever (FMF). However, it is FDA-approved only for children older than 4 years owing to the lack of studies in younger children. Our tertiary pediatric rheumatology department routinely uses colchicine even in very young children with FMF. The aim of the study was to evaluate its safety and efficacy in children with FMF <4 years old.
Methods: The departmental database was searched for all children diagnosed with FMF between 2010–2018. Those who started treatment with colchicine before age 4 years were identified and matched by MEFV variant to children who started treatment at age 4–8 years. Drug efficacy was assessed by the improvement in the frequency and duration of attacks. Adverse events were assessed according to the Rheumatology Common Toxicity Criteria ver. 2.0.
Results: The cohort included 89 patients with FMF: 41 first treated before age 4 years, and 48 first treated at age 4–8 years. Rates of complete response to colchicine were 61% in the younger group and 60.4% in the older group, Corresponding rates of partial remission were 24.4% and 29.2% (p = 0.77). The most frequent adverse event was diarrhea, with a prevalence of 24.4% in the younger group and22. 9% in the older group respectively (p = 0.87). There were no significant between-group differences in other adverse events.
Conclusion: Colchicine is equally effective and safe for use in patients with FMF under 4 years old, with no difference in response from older pediatric patients.
Familial Mediterranean Fever
2019, Presse Medicale
Citation Excerpt :
No opportunistic infections, tuberculosis or death was observed but 3 serious infections were reported in two crFMF patients. Regular colchicine intake after the development of amyloidosis is effective if the creatinine level is below 1.5 mg/dL, and colchicine dose is 1.5–2 mg/day [164], but the expected benefit is limited in patients with nephrotic range proteinuria and impaired renal function [130,165,166]. Colchicine is recommended also after renal transplantation [167].
Familial Mediterranean Fever (FMF) is the oldest and the most frequent of all described hereditary periodic fever syndromes. The populations originating from Mediterranean basin carry the highest risk for FMF however it is being increasingly recognized in many parts of the world. It is an autoinflammatory disease with an autosomal recessive transmission. In the majority of the patients it is related with mutations in the MEFV gene that encodes a protein named pyrin. This protein has been shown to act as a regulator of inflammation mediated by IL-1β, which plays a major role in the pathogenesis of FMF. Approximately one-third of the patients have either a single or no mutation which raise questions about its mode of inheritance. FMF is a clinical diagnosis and characterized by self-limited bouts of fever and serositis. The main long-term complication of the disease is AA amyloidosis. The mainstay of treatment is life-long colchicine given daily to prevent the recurrence of febrile attacks and the development of amyloidosis. Patients with insufficient response to colchicine may be treated with anti IL-1 agents.
Cochlear involvement in Familial Mediterranean Fever: A new feature of an old disease
2012, International Journal of Pediatric Otorhinolaryngology
Citation Excerpt :
The disease duration also has similar effect on cochlea which was not surprising, since complications of the disease are seen more frequently as the disease progresses. Another issue to discuss is the colchicine use; colchicine prevents the development of amyloidosis or may reverse amyloidosis and, as well, reduces hypercoagulability in FMF [25,26]. In our series 16 of 34 FMF children were on colchicine treatment already, and the others were newly diagnosed patients not using colchicine.
In this study we first aimed to assess the cochlear functions in children with Familial Mediterranean Fever. The second aim was to investigate the correlation between the hearing levels and some clinical features of Familial Mediterranean Fever including the duration of the disease, age at onset, genetic analysis and colchicine use.
Thirty-four children with Familial Mediterranean Fever and 27 age matched children were included in the study. Following otologic examination, all children underwent audiometric evaluation, including Pure Tone Average measurements and Distortion Product Otoaoustic Emission testing. Audiological results of the two groups were compared and correlation between the audiologic status and clinical parameters of the disease like the duration of disease, age at onset, mutations and colchicine treatment were studied.
Pure tone audiometry hearing levels were within normal levels in both groups. Hearing thresholds of Familial Mediterranean Fever patients were found to be increased at frequencies 8000, 10,000, 12,500 and 16,000 (p < 0.05). In otoacoustic emission evaluation, distortion products and signal–noise ratio of FMF children were lower in the tested frequencies, from 1400 Hz to 4000 Hz (p < 0.05). Interaction of the disease duration and age of disease onset was found to predict hearing levels, distortion products and signal–noise ratios of children with Familial Mediterranean Fever (F value = 2.034; p = 0.033).
To our knowledge this is the first study demonstrating cochlear involvement in children with Familial Mediterranean Fever which showed increased hearing thresholds at higher frequencies in audiometry together with decreased distortion products and signal–noise ratios demonstrated by distortion product otoacoustic emission testing. Similar studies must be carried out on adult patients to see if a clinical hearing impairment develops. The possible mechanisms that cause cochlear involvement and the effect of colchicine treatment on cochlear functions must be enlightened.
Chapter 1 Amyloidosis
2009, Advances in Clinical Chemistry
Citation Excerpt :
Control of the underlining inflammatory disease is of the utmost importance as has been clearly demonstrated by the relationship of SAA levels to survival [95, 142]. In the case of familial Mediterranean fever, colchicine is of known benefit with significant reduction of the clinical symptoms of the disease as well as stabilization and improvement of the kidney disease [143]. It is unclear whether colchicine is beneficial in other inflammatory conditions.
Amyloidosis: Diagnosis and management
2005, Clinical Lymphoma and Myeloma
Amyloidosis is a rare plasma cell proliferative disorder. The annual incidence in Olmsted County, Minnesota, is 8 in 1,000,000 patients. This is a difficult disorder to diagnose, because the symptoms at presentation are vague and include dyspnea, paresthesias, edema, weight loss, and fatigue. The clinical syndromes at the time of presentation include nephrotic-range proteinuria with or without renal failure, cardiomyopathy, “atypical multiple myeloma,” hepatomegaly, and autonomic or peripheral neuropathy. The serum immunoglobulin free light chain assay has been an important step forward in classifying systemic amyloidosis as an immunoglobulin light chain form and in monitoring therapy. Recently, the importance of serum cardiac biomarkers in assessing outcome has been recognized. New therapies developed over the past 5 years include high-dose chemotherapy with stem cell reconstitution, combinations of alkylating agents with dexamethasone, and, most recently, thalidomide.

View all citing articles on Scopus

¹: From the Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

²: Avi Livneh, MD: Senior Physician, Department of Medicine, Sheba Medical Center, Lecturer, Sackler School of Medicine

³: Deborah Zemer, MD: Senior Physician, Department of Medicine, Sheba Medical Center, Senior Lecturer, Sackler School of Medicine

⁴: Pnina Langevitz, MD: Senior Physician, Department of Medicine, Sheba Medical Lecturer, Sackler School of Medicine

⁵: Joshua Shemer, MD: Senior Physician, Department of Medicine, Sheba Medical Center, Senior Lecturer, Sackler School of Medicine

⁶: Ezra Sohar, MD: Emeritus Professor of Medicine, Sackler School of Medicine

⁷: Mordechai Pras, MD: Head, Department of Medicine F, Sheba Medical Center, Professor of Medicine, Sackler School of Medicine.

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Colchicine in the treatment of AA and AL amyloidosis

Semin Arthritis Rheum

Am J Med

Am J Med

Kidney Int

Am J Med

Am J Med

Gastroenterology

Gastroenterology

Am J Med

Am J Med

Blood

Am J Med

Fertil Steril

Am J Med

Mayo Clin Proc

Amyloidosis: Review of 236 cases

Medicine

Ueber den gang der amyloiden degeneration

Virchows Arch Pathol Anat

Chemical and clinical classification of amyloidosis 1985

Scand J Immunol

Clinical-pathologic differentiation of common amyloid syndromes

Medicine

Amyloidosis

Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever

N Engl J Med

The role of amyloidosis in familial Mediterranean fever. A population study

Israel J Med Sci

The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils

J Clin Invest

Amyloidosis as the sole manifestation of familial Mediterranean fever (FMF). Further evidence of its genetic nature

Ann Intern Med

Amyloidosis in familial Mediterranean fever. An independent genetically determined character

Arch Intern Med

Colchicine for familial Mediterranean fever

N Engl J Med

A controlled trial of colchicine in preventing attacks of familial Mediterranean fever

N Engl J Med

Colchicine therapy for familial mediterranean fever. A double-blind trial

N Engl J Med

Colchicine therapy for nephrotic syndrome due to familial Mediterranean fever

Can Med Assoc J

Prolonged colchicine treatment in four patients with amyloidosis

Ann Intern Med

Secondary systemic amyloidosis: Response and survival in 64 patients

Medicine

La Colchicine peut-elle guerir l'amylose renale de la maladie periodique?

Presse Med

Familial Mediterranean fever in the colchicine era. The fate of one family

Am J Med Genet

Reversal of the nephrotic syndrome by colchicine in amyloidosis of familial Mediterranean fever

Ann Intern Med

Fever of unknown origin and colchicine sensitive amyloidosis: Familial Mediterranean fever?

Dtsch Med Wochenschr

Regression of nephrotic syndrome in amyloidosis secondary to familial Mediterranean fever during maintenance therapy using colchicine

Med Clin Barc

Efficacy of colchicine therapy in patients with periodic disease and amyloidosis according to repeated biopsies of the rectal mucosa

Ter Arkh

Colchicine prevents kidney transplant amyloidosis in familial Mediterranean fever

Nephron