Biologic agents for the treatment of juvenile rheumatoid arthritis: current status.
Biologic therapies, primarily anticytokine therapies, are being increasingly used in patients with juvenile rheumatoid arthritis (JRA). Levels of a variety of proinflammatory cytokines have been shown to be elevated in the peripheral blood and synovial fluid and tissue in children with JRA. In a blinded, randomized, controlled trial in children with severe, long-standing, polyarticular-course JRA not responsive to standard therapies, etanercept showed a statistically significantly greater response rate than placebo. Approximately 75% of these children responded to etanercept. Etanercept has been efficacious in 50-60% of children with active systemic JRA in open clinical trials with acceptable tolerance. Adverse events seen in children treated with etanercept have been similar in type and frequency to those reported in adults. Infliximab has been studied in several open clinical trials in both polyarticular and systemic JRA and found to, overall, have demonstrated efficacy in approximately 60% of patients. Approximately 3-5% of patients have demonstrated infusion reactions or frank allergic reactions and 9% developed new autoantibodies. Anakinra has been studied in children with polyarticular JRA. Approximately 65% of patients developed injection-site reactions and 68% demonstrated a response to the medication. Anakinra may have increased efficacy in systemic JRA. Interleukin (IL)-6 is highly related to the systemic disease manifestations in systemic JRA and two patients treated with a monoclonal antibody to the IL-6 receptor have demonstrated significant improvement with prolonged clinical control with continued treatment. A particular pediatric concern is the effect of immunosuppressive biologics in children who are exposed to or develop varicella. These children should be treated, both in terms of prophylaxis and aggressive antivaricella treatment, as for other immunosuppressed children. Anticytokine biologics have demonstrated great promise in the treatment of JRA and a variety of other pediatric rheumatic diseases, although at this time the randomized, placebo-controlled data are limited only to etanercept in children with polyarticular JRA. Randomized trials are ongoing to better define both the efficacy and safety of these novel treatments for children with JRA and other rheumatic diseases.
Carrasco
Ruy
R
Levinson Chair of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. Daniel.Lovell@cchmc.org
Smith
Judith A
JA
Lovell
Daniel
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D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001171:Arthritis, Juvenile / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D001691:Biological Therapy / Q000379:methods* / Q000639:trends*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004334:Drug Administration Schedule; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D000069285:Infliximab; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D000068800:Etanercept; D007074:Immunoglobulin G; D000069285:Infliximab; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; C502936:tocilizumab