Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever--a randomized controlled noninferiority trial

Adem Polat, Cengizhan Acikel, Betul Sozeri, Ismail Dursun, Ozgur Kasapcopur, Nesrin Gulez, Dogan Simsek, Mehmet Saldir, Ipek Dokurel, Hakan Poyrazoglu, Sevcan Bakkaloglu, Ali Delibas, Zelal Ekinci, Nuray A Ayaz, Yasar Kandur, Harun Peru, Yasemin G Kurt, Safiye R Polat, Erbil Unsal, Balahan Makay, Faysal Gok, Seza Ozen, Erkan Demirkaya, FMF Arthritis Vasculitis and Orphan Disease Research in Pediatric Rheumatology (FAVOR), Adem Polat, Cengizhan Acikel, Betul Sozeri, Ismail Dursun, Ozgur Kasapcopur, Nesrin Gulez, Dogan Simsek, Mehmet Saldir, Ipek Dokurel, Hakan Poyrazoglu, Sevcan Bakkaloglu, Ali Delibas, Zelal Ekinci, Nuray A Ayaz, Yasar Kandur, Harun Peru, Yasemin G Kurt, Safiye R Polat, Erbil Unsal, Balahan Makay, Faysal Gok, Seza Ozen, Erkan Demirkaya, FMF Arthritis Vasculitis and Orphan Disease Research in Pediatric Rheumatology (FAVOR)

Abstract

Background: In this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF).

Methods: In this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement.

Results: A total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group.

Conclusions: Using colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage.

Trial registration id: ClinicalTrials.gov identifier NCT02602028 . Registered 5 November 2015.

Keywords: Colchicine; Dosage schema; Familial Mediterranean fever; Pediatric.

Figures

Fig. 1
Fig. 1
Flowchart of the patients through the study. A total of 92 patients were eligible for the study. Two of the patients were excluded due to having additional rheumatologic diseases. After randomization, three patients in the once-daily dosage group and five patients in the twice-daily dosage group were lost to follow-up. In the twice-daily dosage group, three patients refused treatment

References

    1. Onen F. Familial Mediterranean fever. Rheumatol Int. 2006;26:489–496. doi: 10.1007/s00296-005-0074-3.
    1. Simon A, van der Meer JW, Drenth JP. Familial Mediterranean fever—a not so unusual cause of abdominal pain. Best Pract Res Clin Gastroenterol. 2005;19:199–213. doi: 10.1016/j.bpg.2004.11.009.
    1. Gedalia A, Adar A, Gorodischer R. Familial Mediterranean fever in children. J Rheumatol Suppl. 1992;35:1–9.
    1. Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet. 1998;351:659–664. doi: 10.1016/S0140-6736(97)09408-7.
    1. Girre C, Thomas G, Scherrmann J, Crouzette J, Fournier P. Model‐independent pharmacokinetics of colchicine after oral administration to healthy volunteers. Fundam Clin Pharmacol. 1989;3:537–543. doi: 10.1111/j.1472-8206.1989.tb00688.x.
    1. Thomas G, Girre C, Scherrmann J, Francheteau P, Steimer J. Zero-order absorption and linear disposition of oral colchicine in healthy volunteers. Eur J Clin Pharmacol. 1989;37:79–84.
    1. Chappey ON, Niel E, Wautier JL, Hung PP, Dervichian M, Cattan D, et al. Colchicine disposition in human leukocytes after single and multiple oral administration. Clin Pharmacol Ther. 1993;54:360–367. doi: 10.1038/clpt.1993.161.
    1. Chappey O, Niel E, Dervichian M, Wautier J, Scherrmann J, Cattan D. Colchicine concentration in leukocytes of patients with familial Mediterranean fever. Br J Clin Pharmacol. 1994;38:87–89. doi: 10.1111/j.1365-2125.1994.tb04328.x.
    1. Niel E, Scherrmann JM. Colchicine today. Joint Bone Spine. 2006;73:672–678. doi: 10.1016/j.jbspin.2006.03.006.
    1. Goldfinger SE. Colchicine for familial Mediterranean fever. N Engl J Med. 1972;287:1302.
    1. Goldstein RC, Schwabe AD. Prophylactic colchicine therapy in familial Mediterranean fever: a controlled, double-blind study. Ann Intern Med. 1974;81:792–794. doi: 10.7326/0003-4819-81-6-792.
    1. Rigante D, La Torraca I, Avallone L, Pugliese A, Gaspari S, Stabile A. The pharmacologic basis of treatment with colchicine in children with familial Mediterranean fever. Eur Rev Med Pharmacol Sci. 2006;10:173–178.
    1. Ozen S, Demirkaya E, Erer B, Livneh A, Ben-Chetrit E, Giancane G, et al. EULAR recommendations for the management of familial Mediterranean fever. Ann Rheum Dis. 2016;75:644–651. doi: 10.1136/annrheumdis-2015-208690.
    1. Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med. 1990;150:1881–1884. doi: 10.1001/archinte.1990.00390200073014.
    1. Knieper A, Klotsche J, Föll D, Wittkowski H, Lainka E, Kallinich T. Colchicine therapy in children with FMF. Pediatr Rheumatol Online J. 2015;13(1):O44. doi: 10.1186/1546-0096-13-S1-O44.
    1. Schulz KF, Altman DG, Moher D, the CONSORT Group CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8:18. doi: 10.1186/1741-7015-8-18.
    1. Yalçınkaya F, Özen S, Özçakar ZB, Aktay N, Çakar N, Düzova A, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology. 2009;48:395–398. doi: 10.1093/rheumatology/ken509.
    1. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997;40:1879–1885. doi: 10.1002/art.1780401023.
    1. Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T. Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis. 2009;68:246–248. doi: 10.1136/ard.2008.092031.
    1. Kallinich T, Haffner D, Niehues T, Huss K, Lainka E, Neudorf U, et al. Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics. 2007;119:474–483. doi: 10.1542/peds.2006-1434.
    1. Duzova A, Bakkaloglu A, Besbas N, Topaloglu R, Ozen S, Ozaltin F, et al. Role of A-SAA in monitoring subclinical inflammation and in colchicine dosage in familial Mediterranean fever. Clin Exp Rheumatol. 2003;21:509–514.
    1. Blackwelder WC. “Proving the null hypothesis” in clinical trials. Control Clin Trials. 1982;3(4):345–353. doi: 10.1016/0197-2456(82)90024-1.
    1. Dinarello CA, Wolff SM, Goldfinger SE, Dale DC, Alling DW. Colchicine therapy for familial Mediterranean fever: a double-blind trial. N Engl J Med. 1974;291:934–937. doi: 10.1056/NEJM197410312911804.
    1. Amaryan G, Astvatsatryan V, Gabrielyan E, Panossian A, Panosyan V, Wikman G. Double-blind, placebo-controlled, randomized, pilot clinical trial of ImmunoGuard – a standardized fixed combination of Andrographis paniculata Nees, with Eleutherococcus senticosus Maxim., Schizandra chinensis Bail. and Glycyrrhiza glabra L. extracts in patients with familial Mediterranean fever. Phytomedicine. 2003;10:271–285. doi: 10.1078/094471103322004767.
    1. Wright DG, Wolff SM, Fauci AS, Alling DW. Efficacy of intermittent colchicine therapy in familial Mediterranean fever. Ann Intern Med. 1977;86:162–165. doi: 10.7326/0003-4819-86-2-162.
    1. Mor A, Shinar Y, Zaks N, Langevitz P, Chetrit A, Shtrasburg S, et al. Evaluation of disease severity in familial Mediterranean fever. Semin Arthritis Rheum. 2005;35:57–64. doi: 10.1016/j.semarthrit.2005.02.002.
    1. Lachmann H, Şengül B, Yavuzşen T, Booth D, Booth S, Bybee A, et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology. 2006;45:746–750. doi: 10.1093/rheumatology/kei279.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel