Advertisement

Clinical Rheumatology

, Volume 33, Issue 1, pp 49–55 | Cite as

Tocilizumab for the treatment of adult-onset Still’s disease: results from a case series

  • Paola CiprianiEmail author
  • Piero Ruscitti
  • Francesco Carubbi
  • Ilenia Pantano
  • Vasiliki Liakouli
  • Onorina Berardicurti
  • Roberto Giacomelli
Original Article

Abstract

Adult-onset Still’s disease (AOSD) is a chronic inflammatory disease of unknown etiology which commonly affects young adults. Treatment of AOSD patients includes nonsteroidal anti-inflammatory drugs, corticosteroids, and DMARDs. Interleukin (IL)-6 blockade is an attractive therapeutic option for AOSD because this cytokine contributes to the pathogenesis of major AOSD symptoms. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that blocks the effects of IL-6. Preliminary results of TCZ in AOSD have been promising. Here, we reported our experience evaluating both the safety and the efficacy of 12 months therapy with TCZ in 11 patients with AOSD refractory to corticosteroids and MTX therapy, followed for 18 months, including the first 12 months of active treatment and the last 6 months to evaluate the activity of the disease when the treatment was discontinued. The main outcome measures were the European League Against Rheumatism (EULAR) improvement criteria and improvement of systemic symptoms at the 3, 6, 12, and 18-months follow-up periods. Our patients rapidly responded and experienced a sustained clinical remission over time during active treatment. Disease Activity Score 28 decreased from 5.62 (3.75–8.28) [median (range)] at baseline to 1.61(0.49–3.5) at month 12. EULAR remission was achieved in 81.82 % at 12 months. Tender joint and swollen joint counts displayed a progressive reduction during active therapy study period. During treatment, we observed a resolution of fever in our AOSD patient. In conclusion, TCZ might represent a suitable option for the therapy of refractory AOSD patients.

Keywords

Adult-onset Still’s disease First line therapy Interleukin-6 Tocilizumab 

Notes

Acknowledgments

The authors thank Mrs. Federica Sensini for her technical assistance.

Disclosures

None.

References

  1. 1.
    Bywaters EG (1971) Still’s disease in the adult. Ann Rheum Dis 30:121–133PubMedCrossRefGoogle Scholar
  2. 2.
    Cabane J, Michon A, Ziza JM, Bourgeois P, Bletry O, Godeau P, Kahn MF (1990) Comparison of long-term evolution of adult onset and juvenile onset Still’s disease, both followed up for more than10 years. Ann Rheum Dis 49:283–285PubMedCrossRefGoogle Scholar
  3. 3.
    Kong XD, Xu D, Zhang W, Zhao Y, Zeng X, Zhang F (2010) Clinical features and prognosis in adult-onset Still’s disease: a study of 104 cases. Clin Rheumatol 29:1015–1019PubMedCrossRefGoogle Scholar
  4. 4.
    Efthimiou P, Paik PK, Bielory L (2006) Diagnosis and management of adult onset Still’s disease. Ann Rheum Dis 65(5):564–572PubMedCrossRefGoogle Scholar
  5. 5.
    Choi JH, Suh CH, Lee YM, Kim SS, Nahm DH, Park HS (2003) Serum cytokine profiles in patients with adult onset Still’s disease. J Rheumatol 30:2422–2427PubMedGoogle Scholar
  6. 6.
    Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H et al (1992) Preliminary criteria for classification of adult Still’s disease. J Rheumatol 19:424–430PubMedGoogle Scholar
  7. 7.
    Fautrel B, Zing E, Golmard JL, Le Moel G, Bissery A, Rioux C, Rozenberg S, Piette JC, Bourgeois (2002) Proposal for a new set of classification criteria for adult-onset still disease. Med (Baltimore) 8:194–200CrossRefGoogle Scholar
  8. 8.
    Fautrel B (2008) Adult-onset Still disease. Best Pract Res 22(5):773–792CrossRefGoogle Scholar
  9. 9.
    Pouchot J, Arlet JB (2012) Biological treatment in adult-onset Still’s disease. Best Pract Res Clin Rheumatol 26:477–487. doi: 10.1016/j.berh.2012.07.002 PubMedCrossRefGoogle Scholar
  10. 10.
    Husni ME, Maier AL, Mease PJ, Overman SS, Fraser P, Gravallese EM, Weinblatt ME (2002) Etanercept in the treatment of adult patients with Still’s disease. Arthritis Rheum 46:1171–1176PubMedCrossRefGoogle Scholar
  11. 11.
    Fautrel B, Sibilia J, Mariette X, Combe B, the Club Rheumatisms et Inflammation (2005) Tumour necrosis factor _ blocking agents in refractory adult Still’s disease: an observational study of 20 cases. Ann Rheum Dis 64:262–266PubMedCrossRefGoogle Scholar
  12. 12.
    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
  13. 13.
    Lequerre T, Quartier P, Rosellini D, Alaoui F, De Bandt M, Mejjad O, Kone-Paut I, Michel M, Dernis E, Khellaf M, Limal N, Job-Deslandre C, Fautrel B, Le Loët X, Sibilia J, Société Francophone pour la Rhumatologie et les Maladies Inflammatoires en Pédiatrie (SOFREMIP), Club Rhumatismes et Inflammation (CRI) (2008) Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still’s disease: preliminary experience in France. Ann Rheum Dis 67:302–308PubMedCrossRefGoogle Scholar
  14. 14.
    de Boysson H, Février J, Nicolle A, Auzary C, Geffray L (2013) Tocilizumab in the treatment of the adult-onset Still’s disease: current clinical evidence. Clin Rheumatol 32:141–147. doi: 10.1007/s10067-012-2105-2, Epub 2012 Oct 30PubMedCrossRefGoogle Scholar
  15. 15.
    Nakahara H, Mima T, Yoshio-Hoshino N, Matsushita M, Hashimoto J, Nishimoto N (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 19:69–72PubMedGoogle Scholar
  16. 16.
    Matsumoto K, Nagashima T, Takatori S, Kawahara Y, Yagi M, Iwamoto M, Okazaki H, Minota S (2009) Glucocorticoid and cyclosporine refractory adult onset Still’s disease successfully treated with tocilizumab. Clin Rheumatol 28:485–487PubMedCrossRefGoogle Scholar
  17. 17.
    Sumida K, Ubara Y, Hoshino J, Suwabe T, Hiramatsu R, Hasegawa E, Hayami N, Yamanouchi M, Sawa N, Takemoto F, Takaichi K (2010) Etanercept-refractory adult-onset Still’s disease with thrombotic thrombocytopenic purpura successfully treated with tocilizumab. Clin Rheumatol 29:1191–1194PubMedCrossRefGoogle Scholar
  18. 18.
    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
  19. 19.
    Puéchal X, DeBandt M, Berthelot JM, Breban M, Dubost JJ, Fain O, Kahn JE, Lequen L, Longy-Boursier M, Perdriger A, Schaeverbeke T, Toussirot E, Sibilia J, Club Rhumatismes Et Inflammation (2011) Tocilizumab in refractory adult Still’s disease. Arthritis Care Res (Hoboken) 63:155–159CrossRefGoogle Scholar
  20. 20.
    Prakken B, Albani S, Martini A (2011) Juvenile idiopathic arthritis. Lancet 377:2138–2149PubMedCrossRefGoogle Scholar
  21. 21.
    Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, Iwata N, Umebayashi H, Murata T, Miyoshi M, Tomiita M, Nishimoto N, Kishimoto T (2008) Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomized, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 371:998–1006PubMedCrossRefGoogle Scholar
  22. 22.
    De Benedetti F, Brunner H, Ruperto N, Calvo N, Cuttica I, Malattia R et al (2010) Tocilizumab in patients with systemic juvenile idiopathic arthritis: efficacy data from the placebo controlled 12-week part of the phase 3 TENDER trial. Arthritis Rheum 62(suppl 10):1434Google Scholar
  23. 23.
    Van Gestel AM, Haagsma CJ, van Riel PL (1998) Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum 41:1845–1850PubMedCrossRefGoogle Scholar
  24. 24.
    Suematsu R, Ohta A, Matsuura E, Takahashi H, Fujii T, Horiuchi T, Minota S, Ishigatsubo Y, Ota T, Takei S, Soejima S, Inoue H, Koarada S, Tada Y, Nagasawa K (2012) Therapeutic response of patients with adult Still’s disease to biologic agents: multicenter results in Japan. Mod Rheumatol 22:712–719. doi: 10.1007/s10165-011-0569-6 PubMedGoogle Scholar
  25. 25.
    Nishimoto N, Hashimoto J, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, Murata N, van der Heijde D, Kishimoto T (2007) Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI): evidence of clinical and radiographic benefit from an x-ray reader-blinded randomised controlled trial of tocilizumab. Ann Rheum Dis 66:1162–1167PubMedCrossRefGoogle Scholar
  26. 26.
    Inaba Y, Ozawa R, Imagawa T, Mori M, Hara Y, Miyamae T, Aoki C, Saito T, Yokota S (2011) Radiographic improvement of damaged large joints in children with systemic juvenile idiopathic arthritis following tocilizumab treatment. Ann Rheum Dis 70:1693–1695PubMedCrossRefGoogle Scholar
  27. 27.
    Strand V, Burmester GR, Ogale S, Devenport J, John A, Emery P (2012) Improvements in health-related quality of life after treatment with tocilizumabin patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study. Rheumatol (Oxford) 51(10):1860–1869CrossRefGoogle Scholar
  28. 28.
    Fautrel B, Le Moel G, Saint-Marcoux B, Taupin P, Vignes S, Rozenberg S, Koeger AC, Meyer O, Guillevin L, Piette JC, Bourgeois P (2001) Diagnostic value of ferritin and glycosylated ferritin in adult onset Still’s disease. J Rheumatol 28:322–329PubMedGoogle Scholar
  29. 29.
    Van Reeth C, Le Moel G, Lasne Y, Revenant MC, Agneray J, Kahn MF, Bourgeois P (1994) Serum ferritin and isoferritins are tools for diagnosis of active adult Still’s disease. J Rheumatol 21:890–895PubMedGoogle Scholar
  30. 30.
    Akritidis N, Giannakakis I, Giouglis T (1996) Ferritin levels and response to treatment in patients with adult Still’s disease. J Rheumatol 23:201–202PubMedGoogle Scholar
  31. 31.
    Garnero P, Thompson E, Woodworth T, Smolen JS (2010) Rapid and sustained improvement in bone and cartilage turnover markers with the anti-interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone. Arthritis Rheumatol 62:33–43CrossRefGoogle Scholar
  32. 32.
    Udoetuk JD, Dai Y, Ying GS, Daniel E, Gangaputra S, Rosenbaum JT, Suhler EB, Thorne JE, Foster CS, Jabs DA, Levy-Clarke GA, Nussenblatt RB, Kempen JH (2012) Risk of corticosteroid-induced hyperglycemia requiring medical therapy among patients with inflammatory eye diseases. Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study Research Group. Ophthalmology 119(8):1569–1574PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Rech J, Ronneberger M, Englbrecht M, Finzel S, Katzenbeisser J, Manger K, Manger B, Schett G (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
  34. 34.
    Naniwa T, Ito R, Watanabe M, Hayami Y, Maeda S, Sasaki K, Iwagaitsu S (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 PubMedGoogle Scholar
  35. 35.
    Sakai R, Nagasawa H, Nishi E, Okuyama A, Takei H, Kurasawa T, Kondo T, Nishimura K, Shirai Y, Ito T, Kameda H, Takeuchi T, Amano K (2012) Successful treatment of adult-onset Still’s disease with tocilizumab monotherapy: two case reports and literature review. Clin Rheumatol 31:569–574PubMedCrossRefGoogle Scholar
  36. 36.
    De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A, PRINTO, PRCSG (2012) Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 20(367):2385–2395CrossRefGoogle Scholar
  37. 37.
    Dougados M, Kissel K, Sheeran T, Tak PP, Conaghan PG, Mola EM, Schett G, Amital H, Navarro-Sarabia F, Hou A, Bernasconi C, Huizinga TW (2013) Adding tocilizumab or switching to tocilizumab monotherapy in methotrexate inadequate responders: 24-week symptomatic and structural results of a 2-year randomised controlled strategy trial in rheumatoid arthritis (ACT-RAY). Ann Rheum Dis 72:43–50PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Mavragani CP, Spyridakis EG, Koutsilieris M (2012) Adult-onset Still’s disease: from pathophysiology to targeted therapies. Int J Inflamm 2012:879020. doi: 10.1155/2012/879020 CrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2013

Authors and Affiliations

  • Paola Cipriani
    • 1
    Email author
  • Piero Ruscitti
    • 1
  • Francesco Carubbi
    • 1
  • Ilenia Pantano
    • 1
  • Vasiliki Liakouli
    • 1
  • Onorina Berardicurti
    • 1
  • Roberto Giacomelli
    • 1
  1. 1.Department of Biotechnological and Applied Clinical Science, Rheumatology Unit, School of MedicineUniversity of L’AquilaL’AquilaItaly

Personalised recommendations