Colchicine intolerance in FMF patients and primary obstacles for optimal dosing

Colchicine intolerance in FMF patients and primary obstacles for optimal dosing

Background/aim: Colchicine is the mainstay of treatment in FMF. However, in daily practice it is not easy to maintain effective colchicine doses in a substantial number of patients due to its side effects. In this study, we aimed to investigate prevalence and risk factors for colchicine side effects that limit optimal drug dosing and cause permanent discontinuation. Materials and methods: All patients were recruited from “FMF in Central Anatolia” (FiCA) cohort, 915 adults with a minimum followup time of 6 months during which they had obeyed all treatment instructions. Demographic and anthropometric data, FMF disease characteristics, disease severity, complications, and treatment features were recorded on a web-based registry. Prevalence of colchicine intolerance and characteristics of intolerant patients were analyzed. Results: Effective colchicine doses cannot be maintained in 172 (18.7%) subjects. Main side effects that limit optimal dosing were as follows: diarrhea in 99 (10.8%), elevation in transaminases in 54 (5.9%), leukopenia in 10 (%1.1), renal impairment in 14 (1.3%), myopathy in five (0.5%), and allergic skin reaction in two. Colchicine had to be permanently ceased in 18 (2%) patients because of serious toxicity. Male sex and obesity were found to be associated with liver toxicity, and having a normal body weight was associated with diarrhea. Chronic inflammation and proteinuria were more common in colchicine-intolerant patients, and they had reported more frequent attacks compared to those tolerating optimal doses. Conclusion: Colchicine intolerance is an important problem in daily clinical practice, mainly due to diarrhea and liver toxicity. Suboptimal colchicine dosing is associated with complications.

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  • 1. Sönmez HE, Batu ED, Özen S. Familial Mediterranean fever: current perspectives. Journal of Inflammation Research 2016; 9: 13-20 doi: 10.2147/JIR.S91352
  • 2. Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E et al. EULAR recommendations for the management of familial Mediterranean fever. Annals of the Rheumatic Diseases 2016; 75 (4): 644-651. doi: 10.1136/annrheumdis-2015-208690
  • 3. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O et al. Familial Mediterranean fever (FMF) in Turkey: Results of a nationwide multicenter study. Medicine 2005; 84 (1): 1-11. doi: 10.1097/01.md0000152370.846280
  • 4. Zemer D, Revach M, Pras M, Modan B, Schor S et al. A controlled trial of colchicine in preventing attacks of familial Mediterranean fever. New England Journal of Medicine 1974; 291 (18): 932-934. doi: 10.1056/NEJM197410312911803
  • 5. Dinarello CA,Wolfe S, Goldfinger SE, Dale DC, Alling DW, et al. Colchicine therapy for familial Mediterranean fever: a double-blind trial. New England Journal of Medicine 1974; 291 (18): 934-937. doi: 10.1056/NEJM197410312911804
  • 6. Zemer D, Pras M, Sohar E , Modan M, Cabili S et al. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. New England Journal of Medicine 1986; 314 (16): 1001-1005. doi: 10.1056/NEJM/198604173141601
  • 7. Kasifoglu T, Bilge SY, Sari İ, Solmaz D, Senel S et al. Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: A multicentre study. Rheumatology 2013; 53(4):741-745. doi: 10.1093/rheumatology/ket400
  • 8. Slobodnick A, Shah B, Pillinger M.H, Krasnokutsky S. Colchicine: old and new. The American Journal of Medicine 2015; 128 (5): 461-470. doi: 10.1016/j.amjmed.2014.12.010
  • 9. Kuncl RW, Duncan G. Chronic human colchicine myopathy and neuropathy. New England Journal of Medicine 1988; 45 (3): 245-246 .doi: 10.1056/NEJM198706183162502
  • 10. Oh DH, Chan SQ, Wilson AM. Myopathy and possible intestinal dysfunction in a patient treated with colchicine and simvastatin. The Medical Journal of Australia 2012; 197 (6): 332-333. doi: 10.5694/mja12.10333
  • 11. Tufan A, Dede D, Cavus S, Altintas ND, Iskit AB et al. Rhabdomyolysis in a patient treated with colchicine and atorvastatin. Ann Pharmacotherapy 2006; 40 (7-8): 1466-9.doi: 10.1345/aph.1H064
  • 12. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheumatism 1997; 40 (10): 1879-85.doi: 10.1002/ art.1780401023
  • 13. Demirkaya E, Acikel C, Hashkes P, Gattorno M, Gul A et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Annals of Rheumatic Disease 2016; 75 (6): 1051-6.doi: 10.1136/ annrheumdis-2015-208671
  • 14. Ter Haar NM, Annink K V, Al-Mayouf SM, Amaryan G, Anton J et al. Development of the autoinflammatory disease damage index (ADDI). Annals of Rheumatic Disease 2017; 76 (5): 821- 830 doi: 10.1136/annrheumdis-2016-210092
  • 15. Rosenson RS, Baker Steven K, Jacobson TA, Kopecky SL, Parker BA et al. An assessment by the statin muscle safety task force: 2014 update. Journal of Clinical Lipidology 2014; 8 (3): S58-S71. doi: 10.1016/j.jacl.2014.03.004
  • 16. Organisation, W.H., WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 1999: Cambridge University Press.
  • 17. Varan O, Kucuk H , Babaoglu H, Tecer D, Atas N et al. Chronic inflammation in adult familial Mediterranean fever patients: underlying causes and association with amyloidosis. Scandivaian Journal of Rheumatology 2019; 48 (4): 315-319 doi: 10.1080/03009742.2108.1558282
  • 18. Ben-Zvi I, Livneh A. Chronic inflammation in FMF: Markers, risk factors, outcomes and therapy. Nature Reviews Rheumatology 2011; 7 (2): 105 doi: 10.1038/nrrheum.2010.181
  • 19. Korkmaz C, Özdogan H, Kasapçopur Ö, Yazici H et al. Acute phase response in familial Mediterranean fever. Annals of the Rheumatic Diseases 2002; 61 (1): 79-81 doi: 10.1136/ard.61.1.79
  • 20. Vermeire E, Hearnshaw H, Van Royen P, Denekens J et al. Patient adherence to treatment: Three decades of research. A comprehensive review. Journal of Clinical Pharmacy and Therapeutics 2001; 26 (5): 331-342 doi: 10.1046/j.1365- 2710.2001.00363
  • 21. Karaaslan Y, Dogan Į, Omma A, Sandikci S Can et al. Compliance to colchicine treatment and disease activity in Familial Mediterranean Fever (FMF) patients in Middle/ Black Sea Region of Turkey (in Çorum region). Pediatric Rheumatology 2015; 13 (1): 81. doi: 10.1186/1546-0096-13-S1- P81
  • 22. Ben-Chetrit E., Aamar S. About colchicine compliance, resistance and virulence. Clinical and Experimental Rheumatology 2009; 27 (2 Suppl 53): S1.
  • 23. Ozen S, Kone-Paut I, Gul A. Colchicine resistance and intolerance in familial mediterranean fever: Definition, causes, and alternative treatments. Seminars in Arthritis and Rheumatism 2017; 47 (1): 115-120.doi: 10.1016/j.semarthrit.2017.03.006
  • 24. Minetti EE, Minetti L. Multiple organ failure in a kidney transplant patient receiving both colchicine and cyclosporine. Journal of Nephrology 2003; 16 (3): 421-425.
  • 25. Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E. Acute colchicine intoxication—possible role of erythromycin administration. The Journal of Rheumatology 1992; 19 (3): 494- 496.
  • 26. Ehrenfeld M, Levy M, Sharon P, Rachmilewitz D, Eliakim M et al. Gastrointestinal effects of long-term colchicine therapy in patients with recurrent polyserositis (familial Mediterranean fever). Digestive Diseases and Sciences 1982; 27 (8): 723-727. doi: 10.1007/bf01393768
  • 27. Portincasa P. Colchicine, biologic agents and more for the treatment of familial mediterranean fever. The old, the new, and the rare. Current Medicinal Chemistry 2016; 23 (1): 60-86. doi: 10.2174/09298673236615111712706
  • 28. Finkelstein Y, Aks S E, Hutson J R, Juurlink D N, Nguyen P et al. Colchicine poisoning: the dark side of an ancient drug. Clinical Toxicology (Phila) 201; 48 (5): 407-14 doi: 10.3109/15563650.2010.495348
  • 29. Wolbold R, Klein K, Burk O, Nussler A K, Neuhaus P et al. Sex is a major determinant of CYP3A4 expression in human liver. Hepatology 2003; 38 (4): 978-88 doi: 10.1053/jhep.2003.50393
  • 30. Bremner WJ, Paulsen CA. Colchicine and testicular function in man. New England Journal of Medicine 1976; 294 (25): 1384-1385.
  • 31. Ehrenfeld M, Levy M, Margalioth EJ, Eliakim M. The effects of long‐term colchicine therapy on male fertility in patients with familial Mediterranean fever. Andrologia 1986; 18 (4): 420-426 doi: 10.1111/j.1439-0272ç1986.tb01801
  • 32. Ben-Chetrit A, Ben-Chetrit E, Nitzan R, Ron M. Colchicine inhibits spermatozoal motility in vitro. International Journal of Fertility and Menopausal Studies 1993; 38 (5):301- 304
  • 33. Merlin HE. Azoospermia caused by colchicine—a case report. Fertility and Sterility 1972; 23 (3):180-181 doi: 10.1016/s0015- 0282(16)38823-9
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