Abstract
Background
Treatment of systemic-onset juvenile idiopathic arthritis (So-JIA) is challenging, and the efficacy of injectable recombinant human tumor necrosis factor type 1 receptor-antibody fusion protein (etanercept) on So-JIA has been controversial.
Methods
We retrospectively studied 12 patients with refractory systemic juvenile arthritis treated with etanercept at our hospital in the past 5 years. The 12 patients were divided into a corticosteroid-dependent group (n=7) and an ineffective group (n=5) on the basis of their responses to treatment before the administration of etanercept. Etanercept was added to the treatment without substantially changing the original regimens in general, and doses, and signs of efficacy including alleviation or resolution of symptoms such as high fever, inflammatory arthropathy, eruption rash, hydrohymenitis, as well as changes in the levels of laboratory inflammatory markers such as the white blood cell count, erythrocyte sedimentation rate, levels of C-reactive protein and serum ferritin were recorded.
Results
Etanercept was withdrawn after the first dose from one patient in the corticosteroid-dependent group because of a systemic allergic rash, and was also withdrawn from one patient in the ineffective group after 2 months of treatment owing to inefficacy; the remaining 10 patients completed the entire treatment protocol, at which point etanercept was discontinued. At that time, clinical symptoms and laboratory inflammatory markers of the remaining patients were within the normal range and the mean dose of prednisone was 0.18 mg/kg per day, an 81% decrease from the mean dose at baseline. At present, the corticosteroid has been discontinued and only methotrexate maintenance treatment is used in 3 patients; the other 7 patients are treated with prednisone and methotrexate maintenance therapy. All of the 10 patients are in a medicated remission with no recurrence.
Conclusions
In the treatment of patients with refractory So-JIA, the principles of individual therapy and combinations of drugs should be followed. Etanercept is an important and valid candidate for use in such combined treatment strategies.
Similar content being viewed by others
References
Cassidy JT, Petty RE. Textbook of pediatric rheumatology, 5th ed. Philadelphia: Saunders, 2005.
Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet 2007;369:767–778.
Lomater C, Gerloni V, Gattinara M, Mazzotti J, Cimaz R, Fantini F. Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol 2000;27:491–496.
Kahn P. Juvenile idiopathic arthritis—current and future therapies. Bull NYU Hosp Jt Dis 2009;67:291–302.
DeWitt EM, Kimura Y, Beukelman T, Nigrovic PA, Onel K, Prahalad S, et al. Consensus treatment plans for newonset systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2012;64:1001–1010.
Wallace CA, Sherry DD. Trial of intravenous pulse cyclophosphamide and methylprednisolone in the treatment of severe systemic-onset juvenile rheumatoid arthritis. Arthritis Rheum 1997;40:1852–1855.
Gerloni V, Cimaz R, Gattinara M, Arnoldi C, Pontikaki I, Fantini F. Efficacy and safety profile of cyclosporin A in the treatment of juvenile chronic (idiopathic) arthritis. Results of a 10-year prospective study. Rheumatology (Oxford) 2001;40:907–913.
Wulffraat NM, Sanders LA, Kuis W. Autologous hemopoietic stem-cell transplantation for children with refractory autoimmune disease. Curr Rheumatol Rep 2000;2:316–323.
Adams A, Lehman TJ. Update on the pathogenesis and treatment of systemic onset juvenile rheumatoid arthritis. Curr Opin Rheumatol 2005;17:612–616.
Quartier P, Taupin P, Bourdeaut F, Lemelle I, Pillet P, Bost M, et al. Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. Arthritis Rheum 2003;48:1093–1101.
Katsicas MM, Russo RA. Use of infliximab in patients with systemic juvenile idiopathic arthritis refractory to etanercept. Clin Exp Rheumatol 2005;23:545–548.
Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med 2005;201:1479–1486.
Quartier P, Allantaz F, Cimaz R, Pillet P, Messiaen C, Bardin C, et al. A multicentre, randomised, double-blind, placebocontrolled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011;70:747–754.
Verbsky JW, White AJ. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J Rheumatol 2004;31:2071–2075.
Horneff G, Schmeling H, Biedermann T, Foeldvari I, Ganser G, Girschick HJ, et al. The German etanercept registry for treatment of juvenile idiopathic arthritis. Ann Rheum Dis 2004;63:1638–1644.
Yokota S, Imagawa T, Mori M, Miyamae T, Takei S, Iwata N, et al. Longterm safety and effectiveness of the anti-interleukin 6 receptor monoclonal antibody tocilizumab in patients with systemic juvenile idiopathic arthritis in Japan. J Rheumatol 2014;41:759–767.
Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, et al. Efficacy and safety of tocilizumab in patients with systemiconset juvenile idiopathic arthritis: a randomised, doubleblind, placebo-controlled, withdrawal phase III trial. Lancet 2008;371:998–1006.
De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, et al. Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012;367:2385–2395.
Wallace CA, Ruperto N, Giannini E, Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology International Trials Organization, Pediatric Rheumatology Collaborative Study Group. Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis. J Rheumatol 2004;31:2290–2294.
Kimura Y, Pinho P, Walco G, Higgins G, Hummell D, Szer I, et al. Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis. J Rheumatol 2005;32:935–942.
Minden K, Niewerth M, Listing J, Biedermann T, Bollow M, Schöntube M, et al. Long-term outcome in patients with juvenile idiopathic arthritis. Arthritis Rheum 2002;46:2392–2401.
Oen K, Malleson PN, Cabral DA, Rosenberg AM, Petty RE, Cheang M. Disease course and outcome of juvenile rheumatoid arthritis in a multicenter cohort. J Rheumatol 2002;29:1989–1999.
Ramanan AV, Schneider R. Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis. J Rheumatol 2003;30:401–403.
Murdaca G, Spanò F, Contatore M, Guastalla A, Magnani O, Puppo F. Efficacy and safety of etanercept in chronic immunemediated disease. Expert Opin Drug Saf 2014;13:649–661.
Murdaca G, Colombo BM, Cagnati P, Gulli R, Spanò F, Puppo F. Update upon efficacy and safety of TNF-α inhibitors. Expert Opin Drug Saf 2012;11:1–5.
Murdaca G, Spanò F, Puppo F. Selective TNF-a inhibitorinduced injection site reactions. Expert Opin Drug Saf 2013;12:187–193.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hu, X., Yuan, F., Zhang, J. et al. Effect of etanercept on refractory systemic-onset juvenile idiopathic arthritis. World J Pediatr 12, 96–102 (2016). https://doi.org/10.1007/s12519-015-0009-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12519-015-0009-3