Clinical Rheumatology

, Volume 31, Issue 3, pp 569–574 | Cite as

Successful treatment of adult-onset Still’s disease with tocilizumab monotherapy: two case reports and literature review

  • Ryota Sakai
  • Hayato Nagasawa
  • Eiko Nishi
  • Ayumi Okuyama
  • Hirofumi Takei
  • Takahiko Kurasawa
  • Tsuneo Kondo
  • Koji Nishimura
  • Yuichiro Shirai
  • Tatsuya Ito
  • Hideto Kameda
  • Tsutomu Takeuchi
  • Koichi Amano
Case Based Review

Abstract

Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease of unknown etiology. Recently, it has been reported that quite a few cases of refractory AOSD were successfully treated with tocilizumab (TCZ) and corticosteroids were withdrawn in some of these patients. We report two AOSD patients who were treated successfully with TCZ monotherapy; thus, avoiding corticosteroid treatment. Because both of the patients refused to take corticosteroids, we planned to treat them with 8 mg/kg of TCZ monotherapy at weeks 0, 2, 6 and subsequently every 4 weeks. The efficacy of TCZ was assessed by patients’ clinical symptoms such as fever, arthralgia, skin eruptions, and laboratory markers such as serum levels of CRP, ferritin, and IL-6. We also reviewed 14 previous case reports including 30 cases who had been treated with TCZ for AOSD. Our patients responded rapidly and have been maintained in clinical remission without corticosteroid treatment. In the literature review, concomitant corticosteroid treatment described in 13 cases was successfully tapered in 7 and discontinued in 6 cases. TCZ monotherapy can be a candidate for the first-line therapy for some AOSD patients.

Keywords

Adult-onset Still’s disease Interleukin-6 Monotherapy Tocilizumab 

References

  1. 1.
    Bywaters EGL (1971) Still’s disease in the adult. Ann Rheum Dis 30:121–133PubMedCrossRefGoogle Scholar
  2. 2.
    Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y et al (1992) Preliminary criteria for classification of adult-onset Still’s disease. J Rheumatol 19:424–430PubMedGoogle Scholar
  3. 3.
    Bagnari V, Colina M, Ciancio G, Govoni M, Trotta F (2010) Adult-onset Still’s disease. Rheumatol Int 30:855–862PubMedCrossRefGoogle Scholar
  4. 4.
    Hoshino T, Ohta A, Yang D, Kawamoto M, Kikuchi M et al (1998) Elevated serum interleukin 6, interferon-gamma, and tumor necrosis factor-alpha levels in patients with adult Still’s disease. J Rheumatol 25:396–398PubMedGoogle Scholar
  5. 5.
    Efthimiou P, Kontzias A, Ward CM, Ogden NS (2007) Adult-onset Still’s disease: can recent advances in our understanding of its pathogenesis lead to targeted therapy? Nat Clin Pract Rheumatol 3:328–335PubMedCrossRefGoogle Scholar
  6. 6.
    Fautrel B, Sibilia J, Mariette X, Combe B, Club Rhumatismes et Inflammation (2005) Tumour necrosis factor alpha blocking agents in refractory adult Still’s disease: an observational study of 20 cases. Ann Rheum Dis 64:262–266PubMedCrossRefGoogle Scholar
  7. 7.
    Kraetsch HG, Antoni C, Kalden JR, Manger B (2001) Successful treatment of a small cohort of patients with adult-onset of Still's disease with infliximab: first experiences. Ann Rheum Dis 60(suppl 3):iii55–iii57PubMedGoogle Scholar
  8. 8.
    Fitzgerald AA, Leclercq SA, Yan A, Homik JE, Dinarello CA (2005) Rapid responses to anakinra in patients with refractory adult-onset Still’s disease. Arthritis Rheum 52:1794–1803PubMedCrossRefGoogle Scholar
  9. 9.
    Naumann L, Feist E, Natusch A, Langen S, Klause A et al (2010) IL-1-receptor antagonist anakinra provides long-lasting efficacy in the treatment of refractory adult-onset Still’s disease. Ann Rheum Dis 69:466–467PubMedCrossRefGoogle Scholar
  10. 10.
    Iwamoto M, Nara H, Hirata D, Minota S, Nishimoto N et al (2002) Humanized monoclonal anti-interleukin-6 receptor antibody for treatment of intractable adult-onset Still’s disease. Arthritis Rheum 46:3388–3389PubMedCrossRefGoogle Scholar
  11. 11.
    De Bandt M, Saint-Marcoux B (2009) Tocilizumab for multirefractory adult-onset Still’s disease. Ann Rheum Dis 68:153–154PubMedCrossRefGoogle Scholar
  12. 12.
    Nakahara H, Mima T, Yoshio-Hoshino N, Matsushita M, Hashimoto J et al (2009) A case report of a patient with refractory adult-onset Still’s disease who was successfully treated with tocilizumab over 6 years. Mod Rheumatol 19:69–72PubMedCrossRefGoogle Scholar
  13. 13.
    Matsumoto K, Nagashima T, Takatori S, Kawahara Y, Yagi M et al (2009) Glucocorticoid and cyclosporine refractory adult-onset Still’s disease successfully treated with tocilizumab. Clin Rheumatol 28:485–487PubMedCrossRefGoogle Scholar
  14. 14.
    Perdan-Pirkmajer K, Praprotnik S, Tomšič M (2010) A case of refractory adult-onset Still’s disease successfully controlled with tocilizumab and a review of the literature. Clin Rheumatol 29:1465–1467PubMedCrossRefGoogle Scholar
  15. 15.
    Naniwa T, Ito R, Watanabe M, Hayami Y, Maeda S, et al. (2010) Case report: successful use of short-term add-on tocilizumab for multirefractory systemic flare of adult-onset Still’s disease. Clin Rheumatol. doi:10.1007/s10067-010-1562-8
  16. 16.
    Sumida K, Ubara Y, Hoshino J, Suwabe T, Hiramatsu R et al (2010) Etanercept-refractory adult-onset Still’s disease with thrombotic thrombocytopenic purpura successfully treated with tocilizumab. Clin Rheumatol 29:1191–1194PubMedCrossRefGoogle Scholar
  17. 17.
    Yoshimura M, Makiyama J, Koga T, Miyashita T, Izumi Y et al (2010) Successful treatment with tocilizumab in a patient with refractory adult-onset Still’s disease (AOSD). Clin Exp Rheumatol 28:141–142PubMedGoogle Scholar
  18. 18.
    Rech J, Ronneberger M, Englbrecht M, Finzel S, Katzenbeisser J et al (2011) Successful treatment of adult-onset Still’s disease refractory to TNF and IL-1 blockade by IL-6 receptor blockade. Ann Rheum Dis 70:390–392PubMedCrossRefGoogle Scholar
  19. 19.
    Kishida D, Okuda Y, Onishi M, Takebayashi M, Matoba K et al (2011) Successful tocilizumab treatment in a patient with adult-onset Still’s disease complicated by chronic active hepatitis B and amyloid A amyloidosis. Mod Rheumatol 21:215–218PubMedCrossRefGoogle Scholar
  20. 20.
    Thonhofer R, Hiller M, Just H, Trummer M, Siegel C, et al. (2011) Treatment of refractory adult-onset still’s disease with tocilizumab: report of two cases and review of the literature. Rheumatol Int 31:1653–1656Google Scholar
  21. 21.
    Kobayashi M, Takahashi Y, Yamashita H, Kaneko H, Mimori A (2011) Benefit and a possible risk of tocilizumab therapy for adult-onset Still’s disease accompanied by macrophage-activation syndrome. Mod Rheumatol 21:92–96PubMedCrossRefGoogle Scholar
  22. 22.
    Puéchal X, DeBandt M, Berthelot JM, Breban M, Dubost JJ, Club Rhumatismes Et Inflammation et al (2011) Tocilizumab in refractory adult Still’s disease. Arthritis Care Res 63:155–159CrossRefGoogle Scholar
  23. 23.
    Sabnis GR, Gokhale YA, Kulkarni UP (2011) Tocilizumab in refractory adult-onset Still’s disease with aseptic meningitis—efficacy of interleukin-6 blockade and review of the literature. Semin Arthritis Rheum 40:365–368PubMedCrossRefGoogle Scholar
  24. 24.
    Aydintug AO, D’Cruz D, Cervera R, Khamashta MA, Hughes GR (1992) Low dose methotrexate treatment in adult Still’s disease. J Rheumatol 19:431–435PubMedGoogle Scholar
  25. 25.
    Fujii T, Akizuki M, Kameda H, Matsumura M, Hirakata M et al (1997) Methotrexate treatment in patients with adult-onset Still’s disease—retrospective study of 13 Japanese cases. Ann Rheum Dis 56:144–148PubMedCrossRefGoogle Scholar
  26. 26.
    Kalliolias GD, Georgiou PE, Antonopoulos IA, Andonopoulos AP, Liossis SN (2007) Anakinra treatment in patients with adult-onset Still’s disease is fast, effective, safe and steroid sparing: experience from an uncontrolled trial. Ann Rheum Dis 66:842–843PubMedCrossRefGoogle Scholar
  27. 27.
    Chen DY, Lan JL, Lin FJ, Hsieh TY et al (2004) Proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult-onset Still’s disease. J Rheumatol 31:2189–2198PubMedGoogle Scholar
  28. 28.
    Kawaguchi Y, Terajima H, Harigai M, Hara M, Kamatani N (2001) Interleukin-18 as a novel diagnostic marker and indicator of disease severity in adult-onset Still’s disease. Arthritis Rheum 44:1716–1717PubMedCrossRefGoogle Scholar
  29. 29.
    Kawashima M, Yamamura M, Taniai M, Yamauchi H, Tanimoto T et al (2001) Levels of interleukin-18 and its binding inhibitors in the blood circulation of patients with adult-onset Still’s disease. Arthritis Rheum 44:550–560PubMedCrossRefGoogle Scholar
  30. 30.
    Yokota S, Imagawa T, Takei S, Murata T, Tomiita M et al (2011) Guidance on using tocilizumab for juvenile idiopathic arthritis. Mod Rheumatol 21:563–571Google Scholar
  31. 31.
    Kaneko K, Kaburaki M, Muraoka S, Tanaka N, Yamamoto T et al (2010) Exacerbation of adult-onset Still’s disease, possibly related to elevation of serum tumor necrosis factor-alpha after etanercept administration. Int J Rheum Dis 13:e67–e69PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2011

Authors and Affiliations

  • Ryota Sakai
    • 1
  • Hayato Nagasawa
    • 1
  • Eiko Nishi
    • 1
  • Ayumi Okuyama
    • 1
  • Hirofumi Takei
    • 1
  • Takahiko Kurasawa
    • 1
  • Tsuneo Kondo
    • 1
  • Koji Nishimura
    • 1
  • Yuichiro Shirai
    • 1
  • Tatsuya Ito
    • 3
  • Hideto Kameda
    • 2
  • Tsutomu Takeuchi
    • 1
    • 2
  • Koichi Amano
    • 1
  1. 1.Department of Rheumatology and Clinical Immunology, Saitama Medical CenterSaitama Medical UniversityKawagoeJapan
  2. 2.Division of Rheumatology, Department of Internal Medicine, School of MedicineKeio UniversityTokyoJapan
  3. 3.Department of Internal MedicineSaitama Yorii HospitalYoriiJapan

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