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Anti-TNF agents in familial Mediterranean fever: report of three cases and review of the literature

  • Case Report
  • Published:
Modern Rheumatology

Abstract

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent fever, peritonitis/pleuritis, or arthritis attacks. Patients may have FMF-associated mutations of pyrin. The role of biologics such as anti-tumor necrosis factor (TNF) agents (infliximab, etanercept, adalimumab, golimumab) and anakinra, canakinumab, or rilonacept in the treatment of FMF needs to be clarified. Herein we present reports of three patients (all were positive for HLA B27) with typical spondylitis associated with FMF who were successfully managed with anti-TNF agents, along with a literature review. The patients were a 37-year-old man with concomitant Crohn’s disease and amyloidosis who was treated with infliximab (INF, 5 mg/kg for 3 years) and switched to adalimumab (ADA), and two female patients (a 24-year-old and a 31-year-old) with FMF who developed severe spondylitis and who were also treated with ADA. Anti-TNF agents can control FMF attacks quite effectively and they reveal a promising role in the treatment of FMF-associated amyloidosis and spondylitis.

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References

  1. Grateau G, Duruoz MT. Autoinflammatory conditions: when to suspect? How to treat? Best Pract Res Clin Rheumatol. 2010;24:401–11.

    Article  PubMed  Google Scholar 

  2. Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet. 1998;351:659–64.

    Article  PubMed  CAS  Google Scholar 

  3. Berkun Y, Ben-Chetrit E, Klar A. Peritoneal adhesions and intestinal obstructions in patients with familial Mediterranean fever—are they more frequent? Semin Arthritis Rheum. 2007;36:316–21.

    Article  PubMed  Google Scholar 

  4. Brik R, Shinawi M, Kasinetz L, Gershoni-Baruch R. The musculoskeletal manifestations of familial Mediterranean fever in children genetically diagnosed with the disease. Arthritis Rheum. 2001;44:1416–9.

    Article  PubMed  CAS  Google Scholar 

  5. Younes M, Kahn MF, Meyer O. Hip involvement in patients with familial Mediterranean fever. A review of ten cases. Joint Bone Spine. 2002;69:560–5.

    Article  PubMed  Google Scholar 

  6. Incel NA, Saracoglu M, Erdem HR. Seronegative spondyloarthropathy of familial Mediterranean fever. Rheumatol Int. 2003;23:41–3.

    PubMed  Google Scholar 

  7. Kaushik P, el-Sobkie NI, Shehab D, Malaviya AN. Familial Mediterranean fever with HLA B-27 positive ankylosing spondylitis in a young Armenian man. Clin Exp Rheumatol. 1999;17:387–8.

    PubMed  CAS  Google Scholar 

  8. Livneh A, Langevitz P, Zemer D, et al. The changing face of familial Mediterranean fever. Semin Arthritis Rheum. 1996;26:612–27.

    Article  PubMed  CAS  Google Scholar 

  9. Cerquaglia C, Diaco M, Nucera G, La Regina M, Montalto M, Manna R. Pharmacological and clinical basis of treatment of familial Mediterranean fever (FMF) with colchicine or analogues: an update. Curr Drug Targets Inflamm Allergy. 2005;4:117–24.

    Article  PubMed  CAS  Google Scholar 

  10. Metyas S, Arkfeld DG, Forrester DM, Ehresmann GR. Infliximab treatment of familial Mediterranean fever and its effect on secondary AA amyloidosis. J Clin Rheumatol. 2004;10:134–7.

    Article  PubMed  Google Scholar 

  11. Daysal S, Akcil G, Goker B, Haznedaroglu S, Ercan N, Ozturk MA. Infliximab therapy in a patient with familial Mediterranean fever and chronic hip arthritis. Arthritis Rheum. 2005;53:146–7.

    Article  PubMed  Google Scholar 

  12. Yuksel S, Yalcinkaya F, Acar B, Ozcakar ZB, Ozturk B, Ekim M. Clinical improvement with infliximab in a child with amyloidosis secondary to familial Mediterranean fever. Rheumatology (Oxford). 2006;45:1307–8.

    Article  CAS  Google Scholar 

  13. Sakallioglu O, Duzova A, Ozen S. Etanercept in the treatment of arthritis in a patient with familial Mediterranean fever. Clin Exp Rheumatol. 2006;24:435–7.

    PubMed  CAS  Google Scholar 

  14. Ozgocmen S, Ozcakar L, Ardicoglu O, Kocakoc E, Kaya A, Kiris A. Familial Mediterranean fever responds well to infliximab: single case experience. Clin Rheumatol. 2006;25:83–7.

    Article  PubMed  Google Scholar 

  15. Seyahi E, Ozdogan H, Celik S, Ugurlu S, Yazici H. Treatment options in colchicine resistant familial Mediterranean fever patients: thalidomide and etanercept as adjunctive agents. Clin Exp Rheumatol. 2006;24:S99–103.

    PubMed  CAS  Google Scholar 

  16. Mor A, Pillinger MH, Kishimoto M, Abeles AM, Livneh A. Familial Mediterranean fever successfully treated with etanercept. J Clin Rheumatol. 2007;13:38–40.

    Article  PubMed  Google Scholar 

  17. Bodur H, Seckin U, Eser F, Ergul G, Seckin S. Coexistence of familial Mediterranean fever and psoriasis in a patient with seronegative spondyloarthropathy. Rheumatol Int. 2008;29:107–10.

    Article  PubMed  Google Scholar 

  18. Kaya S, Kaptanoglu E, Elden H, Hizmetli S. Coexistence of familial Mediterranean fever and juvenile idiopathic arthritis with osteoporosis successfully treated with etanercept. Intern Med. 2010;49:619–22.

    Article  PubMed  Google Scholar 

  19. Nakamura A, Matsuda M, Tazawa K, Shimojima Y, Ikeda S. Successful treatment with infliximab and low-dose methotrexate in a Japanese patient with familial Mediterranean fever. Intern Med. 2007;46:1247–9.

    Article  PubMed  Google Scholar 

  20. Bilginer Y, Ayaz NA, Ozen S. Anti-IL-1 treatment for secondary amyloidosis in an adolescent with FMF and Behcet’s disease. Clin Rheumatol. 2010;29:209–10.

    Article  PubMed  Google Scholar 

  21. Alpay N, Sumnu A, Caliskan Y, Yazici H, Turkmen A, Gul A. Efficacy of anakinra treatment in a patient with colchicine-resistant familial Mediterranean fever. Rheumatol Int. 2010.

  22. Garcia-Gonzalez A, Weisman MH. The arthritis of familial Mediterranean fever. Semin Arthritis Rheum. 1992;22:139–50.

    Article  PubMed  CAS  Google Scholar 

  23. Goldfinger SE. Colchicine for familial Mediterranean fever. N Engl J Med. 1972;287:1302.

    PubMed  CAS  Google Scholar 

  24. Zemer D, Pras M, Sohar E, Modan M, Cabili S, Gafni J. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med. 1986;314:1001–5.

    Article  PubMed  CAS  Google Scholar 

  25. Ben-Chetrit E, Ozdogan H. Non-response to colchicine in FMF—definition, causes and suggested solutions. Clin Exp Rheumatol. 2008;26:S49–51.

    PubMed  CAS  Google Scholar 

  26. Lidar M, Scherrmann JM, Shinar Y, et al. Colchicine nonresponsiveness in familial Mediterranean fever: clinical, genetic, pharmacokinetic, and socioeconomic characterization. Semin Arthritis Rheum. 2004;33:273–82.

    Article  PubMed  CAS  Google Scholar 

  27. Tufan A, Babaoglu MO, Akdogan A, et al. Association of drug transporter gene ABCB1 (MDR1) 3435C to T polymorphism with colchicine response in familial Mediterranean fever. J Rheumatol. 2007;34:1540–4.

    PubMed  CAS  Google Scholar 

  28. Silva LC, Ortigosa LC, Benard G. Anti-TNF-alpha agents in the treatment of immune-mediated inflammatory diseases: mechanisms of action and pitfalls. Immunotherapy. 2010;2:817–33.

    Article  PubMed  CAS  Google Scholar 

  29. Baykal Y, Saglam K, Yilmaz MI, Taslipinar A, Akinci SB, Inal A. Serum sIL-2r, IL-6, IL-10 and TNF-alpha level in familial Mediterranean fever patients. Clin Rheumatol. 2003;22:99–101.

    Article  PubMed  CAS  Google Scholar 

  30. Gang N, Drenth JP, Langevitz P, et al. Activation of the cytokine network in familial Mediterranean fever. J Rheumatol. 1999;26:890–7.

    PubMed  CAS  Google Scholar 

  31. Yilmaz E, Balci B, Kutlay S, et al. Analysis of the modifying effects of SAA1, SAA2 and TNF-alpha gene polymorphisms on development of amyloidosis in FMF patients. Turk J Pediatr. 2003;45:198–202.

    PubMed  Google Scholar 

  32. Celebi Kobak A, Kobak S, Kabasakal Y, Akarca US. Tumor necrosis factor-alpha gene promoter polymorphism in patients with familial Mediterranean fever. Clin Rheumatol. 2007;26:908–10.

    Article  PubMed  Google Scholar 

  33. Haddad JJ. The role of inflammatory cytokines and NF-kappaB/MAPK signaling pathways in the evolution of familial Mediterranean fever: current clinical perspectives and potential therapeutic approaches. Cell Immunol. 2009;260:6–13.

    Article  PubMed  CAS  Google Scholar 

  34. Papin S, Cazeneuve C, Duquesnoy P, Jeru I, Sahali D, Amselem S. The tumor necrosis factor alpha-dependent activation of the human mediterranean fever (MEFV) promoter is mediated by a synergistic interaction between C/EBP beta and NF kappaB p65. J Biol Chem. 2003;278:48839–47.

    Article  PubMed  CAS  Google Scholar 

  35. Ryan JG, Masters SL, Booty MG, et al. Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein. Ann Rheum Dis. 2010;69:1383–8.

    Article  PubMed  CAS  Google Scholar 

  36. Kasifoglu T, Calisir C, Cansu DU, Korkmaz C. The frequency of sacroiliitis in familial Mediterranean fever and the role of HLA-B27 and MEFV mutations in the development of sacroiliitis. Clin Rheumatol. 2009;28:41–6.

    Article  PubMed  Google Scholar 

  37. Cinar M, Dinc A, Simsek I, et al. The rate and significance of Mediterranean fever gene mutations in patients with ankylosing spondylitis: a three-month, longitudinal clinical study. Rheumatol Int. 2008;29:37–42.

    Article  PubMed  Google Scholar 

  38. Chae JJ, Wood G, Richard K, et al. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-kappaB through its N-terminal fragment. Blood. 2008;112:1794–803.

    Article  PubMed  CAS  Google Scholar 

  39. Roldan R, Ruiz AM, Miranda MD, Collantes E. Anakinra: new therapeutic approach in children with familial Mediterranean fever resistant to colchicine. Joint Bone Spine. 2008;75:504–5.

    Article  PubMed  Google Scholar 

  40. Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002;20:S1–13.

    PubMed  CAS  Google Scholar 

  41. Calligaris L, Marchetti F, Tommasini A, Ventura A. The efficacy of anakinra in an adolescent with colchicine-resistant familial Mediterranean fever. Eur J Pediatr. 2008;167:695–6.

    Article  PubMed  Google Scholar 

  42. Gattringer R, Lagler H, Gattringer KB, et al. Anakinra in two adolescent female patients suffering from colchicine-resistant familial Mediterranean fever: effective but risky. Eur J Clin Invest. 2007;37:912–4.

    Article  PubMed  CAS  Google Scholar 

  43. Kuijk LM, Govers AM, Frenkel J, Hofhuis WJ. Effective treatment of a colchicine-resistant familial Mediterranean fever patient with anakinra. Ann Rheum Dis. 2007;66:1545–6.

    Article  PubMed  Google Scholar 

  44. Hennig S, Bayegan K, Uffmann M, Thalhammer F, Winkler S. Pneumonia in a patient with familial Mediterranean fever successfully treated with anakinra–case report and review. Rheumatol Int. 2010.

  45. Moser C, Pohl G, Haslinger I, et al. Successful treatment of familial Mediterranean fever with anakinra and outcome after renal transplantation. Nephrol Dial Transplant. 2009;24:676–8.

    Article  PubMed  CAS  Google Scholar 

  46. Meinzer U, Quartier P, Alexandra JF, Hentgen V, Retornaz F, Kone-Paut I. Interleukin-1 targeting drugs in familial Mediterranean fever: a case series and a review of the literature. Semin Arthritis Rheum. 2011.

  47. Mitroulis I, Skendros P, Oikonomou A, Tzioufas AG, Ritis K. The efficacy of canakinumab in the treatment of a patient with familial Mediterranean fever and longstanding destructive arthritis. Ann Rheum Dis. 2011. doi:10.1136/ard.2010.146878.

  48. Hoffman HM, Throne ML, Amar NJ, et al. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58:2443–52.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Salih Ozgocmen.

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Ozgocmen, S., Akgul, O. Anti-TNF agents in familial Mediterranean fever: report of three cases and review of the literature. Mod Rheumatol 21, 684–690 (2011). https://doi.org/10.1007/s10165-011-0463-2

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  • DOI: https://doi.org/10.1007/s10165-011-0463-2

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