Iranian Journal of Pediatrics

Published by: Kowsar
Uncorrected Proof scheduled for 29 (4)

The Effect of Canakinumab Treatment on the Inflammatory Markers in Children with Colchicine-Resistant Familial Mediterranean Fever

Fatma Yazılıtaş ORCID 1 , * , Semanur Özdel ORCID 1 , Doğan Şimşek ORCID 1 , Esra Bağlan ORCID 1 and Mehmet Bülbül ORCID 1
Authors Information
1 Ankara Dr. Sami Ulus Maternity and Children Hospital Pediatric Nephrology and Rheumatology Department, Ankara, Turkey
Article information
  • Iranian Journal of Pediatrics: In Press (In Press); e84652
  • Published Online: August 10, 2019
  • Article Type: Research Article
  • Received: September 26, 2018
  • Revised: March 7, 2019
  • Accepted: March 27, 2019
  • DOI: 10.5812/ijp.84652

How to Cite: Yazılıtaş F, Özdel S, Şimşek D, Bağlan E, Bülbül M. The Effect of Canakinumab Treatment on the Inflammatory Markers in Children with Colchicine-Resistant Familial Mediterranean Fever, Iran J Pediatr. Online ahead of Print ; In Press(In Press):e84652. doi: 10.5812/ijp.84652.

Copyright © 2019, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Background
2. Objectives
3. Methods
4. Results
5. Discussion
  • 1. Ozen S, Bilginer Y. A clinical guide to autoinflammatory diseases: Familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol. 2014;10(3):135-47. doi: 10.1038/nrrheum.2013.174. [PubMed: 24247370].
  • 2. Chae JJ, Wood G, Richard K, Jaffe H, Colburn NT, Masters SL, et al. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood. 2008;112(5):1794-803. doi: 10.1182/blood-2008-01-134932. [PubMed: 18577712]. [PubMed Central: PMC2518886].
  • 3. Grattagliano I, Bonfrate L, Ruggiero V, Scaccianoce G, Palasciano G, Portincasa P. Novel therapeutics for the treatment of familial Mediterranean fever: From colchicine to biologics. Clin Pharmacol Ther. 2014;95(1):89-97. doi: 10.1038/clpt.2013.148. [PubMed: 23867542].
  • 4. Uslu AU, Deveci K, Korkmaz S, Aydin B, Senel S, Sancakdar E, et al. Is neutrophil/lymphocyte ratio associated with subclinical inflammation and amyloidosis in patients with familial Mediterranean fever? Biomed Res Int. 2013;2013:185317. doi: 10.1155/2013/185317. [PubMed: 23865042]. [PubMed Central: PMC3705820].
  • 5. Bilginer Y, Akpolat T, Ozen S. Renal amyloidosis in children. Pediatr Nephrol. 2011;26(8):1215-27. doi: 10.1007/s00467-011-1797-x. [PubMed: 21360109]. [PubMed Central: PMC3119800].
  • 6. Haviv R, Hashkes PJ. Canakinumab investigated for treating familial Mediterranean fever. Expert Opin Biol Ther. 2016;16(11):1425-34. doi: 10.1080/14712598.2016.1233963. [PubMed: 27603969].
  • 7. Balta S, Celik T, Mikhailidis DP, Ozturk C, Demirkol S, Aparci M, et al. The relation between atherosclerosis and the neutrophil-lymphocyte ratio. Clin Appl Thromb Hemost. 2016;22(5):405-11. doi: 10.1177/1076029615569568. [PubMed: 25667237].
  • 8. Templeton AJ, Ace O, McNamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: A systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1204-12. doi: 10.1158/1055-9965.EPI-14-0146. [PubMed: 24793958].
  • 9. Uluca U, Ece A, Sen V, Karabel D, Yel S, Gunes A, et al. Usefulness of mean platelet volume and neutrophil-to-lymphocyte ratio for evaluation of children with Familial Mediterranean fever. Med Sci Monit. 2014;20:1578-82. doi: 10.12659/MSM.892139. [PubMed: 25189760]. [PubMed Central: PMC4165509].
  • 10. Ozen S, Kone-Paut I, Gul A. Colchicine resistance and intolerance in familial mediterranean fever: Definition, causes, and alternative treatments. Semin Arthritis Rheum. 2017;47(1):115-20. doi: 10.1016/j.semarthrit.2017.03.006. [PubMed: 28413100].
  • 11. Yildirim K, Uzkeser H, Keles M, Karatay S, Kiziltunc A, Kaya MD, et al. Relationship between serum interleukin-1beta levels and acute phase response proteins in patients with familial Mediterranean fever. Biochem Med (Zagreb). 2012;22(1):109-13. doi: 10.11613/BM.2012.012. [PubMed: 22384525]. [PubMed Central: PMC4062326].
  • 12. Molad Y, Fridenberg A, Bloch K, Langevitz P, Mukamel M, Sulkes J, et al. Neutrophil adhesion molecule expression in familial Mediterranean fever: Discordance between the intravascular regulation of beta2 integrin and L-selectin expression in acute attack. J Investig Med. 2004;52(1):58-61. doi: 10.1136/jim-52-01-28. [PubMed: 14989371].
  • 13. Ahsen A, Ulu MS, Yuksel S, Demir K, Uysal M, Erdogan M, et al. As a new inflammatory marker for familial Mediterranean fever: Neutrophil-to-lymphocyte ratio. Inflammation. 2013;36(6):1357-62. doi: 10.1007/s10753-013-9675-2. [PubMed: 23794006].
  • 14. Ben-Chetrit E, Levy M. Colchicine: 1998 update. Semin Arthritis Rheum. 1998;28(1):48-59. doi: 10.1016/S0049-0172(98)80028-0. [PubMed: 9726336].
  • 15. Ozer S, Yilmaz R, Sonmezgoz E, Karaaslan E, Taskin S, Butun I, et al. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever. Med Sci Monit. 2015;21:298-303. doi: 10.12659/MSM.892289. [PubMed: 25615955]. [PubMed Central: PMC4315639].
  • 16. Basaran O, Uncu N, Celikel BA, Aydin F, Cakar N. Assessment of neutrophil to lymphocyte ratio and mean platelet volume in pediatric familial Mediterranean fever patients. J Res Med Sci. 2017;22:35. doi: 10.4103/1735-1995.202140. [PubMed: 28461821]. [PubMed Central: PMC5390538].
  • 17. Celikbilek M, Dogan S, Akyol L, Borekci E, Zararsiz G, Kozan M, et al. Neutrophil-lymphocyte ratio in patients with familial Mediterranean fever. J Clin Lab Anal. 2015;29(1):80-3. doi: 10.1002/jcla.21732. [PubMed: 24687426].
  • 18. Ben-Zvi I, Livneh A. Chronic inflammation in FMF: Markers, risk factors, outcomes and therapy. Nat Rev Rheumatol. 2011;7(2):105-12. doi: 10.1038/nrrheum.2010.181. [PubMed: 21060333].
  • 19. Esmon CT. Inflammation and thrombosis. J Thromb Haemost. 2003;1(7):1343-8. doi: 10.1046/j.1538-7836.2003.00261.x. [PubMed: 12871267].
  • 20. Yang M, Li K, Chui CM, Yuen PM, Chan PK, Chuen CK, et al. Expression of interleukin (IL) 1 type I and type II receptors in megakaryocytic cells and enhancing effects of IL-1beta on megakaryocytopoiesis and NF-E2 expression. Br J Haematol. 2000;111(1):371-80. doi: 10.1046/j.1365-2141.2000.02340.x. [PubMed: 11091227].
  • 21. Chuen CK, Li K, Yang M, Fok TF, Li CK, Chui CM, et al. Interleukin-1beta up-regulates the expression of thrombopoietin and transcription factors c-Jun, c-Fos, GATA-1, and NF-E2 in megakaryocytic cells. J Lab Clin Med. 2004;143(2):75-88. doi: 10.1016/j.lab.2003.09.006. [PubMed: 14966463].
  • 22. La Regina M, Orlandini F, Manna R. Autoinflammatory diseases: A possible cause of thrombosis? Thromb J. 2015;13:19. doi: 10.1186/s12959-015-0049-x. [PubMed: 25969671]. [PubMed Central: PMC4428094].
  • 23. Nakai S, Aihara K, Hirai Y. Interleukin-1 potentiates granulopoiesis and thrombopoiesis by producing hematopoietic factors in vivo. Life Sci. 1989;45(7):585-91. doi: 10.1016/0024-3205(89)90043-x. [PubMed: 2671565].
  • 24. Jagroop IA, Clatworthy I, Lewin J, Mikhailidis DP. Shape change in human platelets: Measurement with a channelyzer and visualisation by electron microscopy. Platelets. 2000;11(1):28-32. doi: 10.1080/09537100075760. [PubMed: 10938878].
  • 25. Thompson CB. From precursor to product: How do megakaryocytes produce platelets? Prog Clin Biol Res. 1986;215:361-71. [PubMed: 3523524].
  • 26. Aksu K, Donmez A, Keser G. Inflammation-induced thrombosis: Mechanisms, disease associations and management. Curr Pharm Des. 2012;18(11):1478-93. doi: 10.2174/138161212799504731. [PubMed: 22364132].
  • 27. Gasparyan AY, Ayvazyan L, Mikhailidis DP, Kitas GD. Mean platelet volume: A link between thrombosis and inflammation? Curr Pharm Des. 2011;17(1):47-58. doi: 10.2174/138161211795049804. [PubMed: 21247392].
  • 28. Demirel A, Celkan T, Kasapcopur O, Bilgen H, Ozkan A, Apak H, et al. Is Familial Mediterranean Fever a thrombotic disease or not? Eur J Pediatr. 2008;167(3):279-85. doi: 10.1007/s00431-007-0475-2. [PubMed: 17436016].
  • 29. Uluca U, Demir F, Ece A, Sen V, Gunes A, Aktar F, et al. Assessment of epicardial adipose tissue thickness and the mean platelet volume in children with familial Mediterranean fever. Ital J Pediatr. 2015;41:15. doi: 10.1186/s13052-015-0120-z. [PubMed: 25887962]. [PubMed Central: PMC4348162].
  • 30. Sahin S, Senel S, Ataseven H, Yalcin I. Does mean platelet volume influence the attack or attack-free period in the patients with Familial Mediterranean fever? Platelets. 2013;24(4):320-3. doi: 10.3109/09537104.2012.697591. [PubMed: 22720903].
  • 31. Arica S, Ozer C, Arica V, Karakus A, Celik T, Gunesacar R. Evaluation of the mean platelet volume in children with familial Mediterranean fever. Rheumatol Int. 2012;32(11):3559-63. doi: 10.1007/s00296-011-2251-x. [PubMed: 22086472].
  • 32. Dursun I, Gok F, Babacan O, Sarı E, Sakallıoglu O. Are mean platelet volume and splenomegaly subclinical inflammatory marker in children with familial mediterranean fever? Health. 2010;2(7):692-5. doi: 10.4236/health.2010.27105.
  • 33. Karakurt Ariturk O, Ureten K, Sari M, Yazihan N, Ermis E, Erguder I. Relationship of paraoxonase-1, malondialdehyde and mean platelet volume with markers of atherosclerosis in familial Mediterranean fever: An observational study. Anadolu Kardiyol Derg. 2013;13(4):357-62. doi: 10.5152/akd.2013.103. [PubMed: 23531873].
  • 34. Makay B, Turkyilmaz Z, Unsal E. Mean platelet volume in children with familial Mediterranean fever. Clin Rheumatol. 2009;28(8):975-8. doi: 10.1007/s10067-009-1148-5. [PubMed: 19283330].
  • 35. Sakalli H, Kal O. Mean platelet volume as a potential predictor of proteinuria and amyloidosis in familial Mediterranean fever. Clin Rheumatol. 2013;32(8):1185-90. doi: 10.1007/s10067-013-2257-8. [PubMed: 23592230].

Featured Image:

Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments