Skip to main content

Advertisement

SpringerLink
Log in

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

  • Case Based Review
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

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that quite a few cases of refractory AOSD were successfully treated with tocilizumab (TCZ) and corticosteroids were withdrawn in some of these patients.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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bywaters EGL (1971) Still’s disease in the adult. Ann Rheum Dis 30:121–133

    Article  PubMed  CAS  Google Scholar 

  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 19:424–430

    PubMed  CAS  Google Scholar 

  3. Bagnari V, Colina M, Ciancio G, Govoni M, Trotta F (2010) Adult-onset Still’s disease. Rheumatol Int 30:855–862

    Article  PubMed  CAS  Google Scholar 

  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 25:396–398

    PubMed  CAS  Google Scholar 

  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 3:328–335

    Article  PubMed  CAS  Google Scholar 

  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 64:262–266

    Article  PubMed  CAS  Google Scholar 

  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–iii57

    PubMed  CAS  Google Scholar 

  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 52:1794–1803

    Article  PubMed  CAS  Google Scholar 

  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 69:466–467

    Article  PubMed  CAS  Google Scholar 

  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 46:3388–3389

    Article  PubMed  CAS  Google Scholar 

  11. De Bandt M, Saint-Marcoux B (2009) Tocilizumab for multirefractory adult-onset Still’s disease. Ann Rheum Dis 68:153–154

    Article  PubMed  Google Scholar 

  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 19:69–72

    Article  PubMed  Google Scholar 

  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 28:485–487

    Article  PubMed  Google Scholar 

  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 29:1465–1467

    Article  PubMed  Google Scholar 

  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. 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 29:1191–1194

    Article  PubMed  Google Scholar 

  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 28:141–142

    PubMed  CAS  Google Scholar 

  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 70:390–392

    Article  PubMed  Google Scholar 

  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 21:215–218

    Article  PubMed  Google Scholar 

  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 31:1653–1656

    Google Scholar 

  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 21:92–96

    Article  PubMed  Google Scholar 

  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 63:155–159

    Article  Google Scholar 

  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 40:365–368

    Article  PubMed  CAS  Google Scholar 

  24. Aydintug AO, D’Cruz D, Cervera R, Khamashta MA, Hughes GR (1992) Low dose methotrexate treatment in adult Still’s disease. J Rheumatol 19:431–435

    PubMed  CAS  Google Scholar 

  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 56:144–148

    Article  PubMed  CAS  Google Scholar 

  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 66:842–843

    Article  PubMed  CAS  Google Scholar 

  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 31:2189–2198

    PubMed  CAS  Google Scholar 

  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 44:1716–1717

    Article  PubMed  CAS  Google Scholar 

  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 44:550–560

    Article  PubMed  CAS  Google Scholar 

  30. Yokota S, Imagawa T, Takei S, Murata T, Tomiita M et al (2011) Guidance on using tocilizumab for juvenile idiopathic arthritis. Mod Rheumatol 21:563–571

    Google Scholar 

  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–e69

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

H.K. has received honoraria from Mitsubishi-Tanabe Pharma, Pfizer, Abbott, Eisai Pharma, and Bristol-Myers KK. T.T. has received research support and consulting or lecture fees from Chugai Pharma. K.A. received research grants from Tanabe-Mitsubishi, Astellas, and Chugai pharmaceutical companies. The other authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Rheumatology and Clinical Immunology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, 350-8550, Japan

    Ryota Sakai, Hayato Nagasawa, Eiko Nishi, Ayumi Okuyama, Hirofumi Takei, Takahiko Kurasawa, Tsuneo Kondo, Koji Nishimura, Yuichiro Shirai, Tsutomu Takeuchi & Koichi Amano

  2. Division of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan

    Hideto Kameda & Tsutomu Takeuchi

  3. Department of Internal Medicine, Saitama Yorii Hospital, Yorii, Japan

    Tatsuya Ito

Authors
  1. Ryota Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hayato Nagasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eiko Nishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayumi Okuyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hirofumi Takei
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takahiko Kurasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tsuneo Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Koji Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuichiro Shirai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tatsuya Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hideto Kameda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Tsutomu Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Koichi Amano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ryota Sakai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sakai, R., Nagasawa, H., Nishi, E. et al. Successful treatment of adult-onset Still’s disease with tocilizumab monotherapy: two case reports and literature review. Clin Rheumatol 31, 569–574 (2012). https://doi.org/10.1007/s10067-011-1917-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-011-1917-9

Keywords

Search

Navigation