Biologic therapies for juvenile arthritis.
A group of therapies with exciting potential has emerged for children and young people with severe juvenile idiopathic arthritis (JIA) uncontrolled by conventional disease modifying drugs. Theoretical understanding from molecular biologic research has identified specific targets within pathophysiological pathways that control rheumatoid arthritis (RA) and JIA. This review identifies the pathways of autoimmunity to begin to show how biologic agents have been produced to replicate, mimic, or block culpable molecules and so promote or inhibit cellular activity or proliferation. Of these agents, cytokine antagonists have shown greatest promise, and early clinical studies of tumour necrosis factor (TNF) blockade have identified dramatic clinical benefit in many children with JIA. However, as will also be discussed, overlap of pathways within a complex immune system makes clinical response unpredictable and raises additional ethical and administrative concerns.
Wilkinson
N
N
Department of Rheumatology, Great Ormond Street Hospital, London, UK. petherton@clara.co.uk
Jackson
G
G
Gardner-Medwin
J
J
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000276:immunology / Q000628:therapy*; D015551:Autoimmunity / Q000276:immunology; D001691:Biological Therapy / Q000379:methods*; D002648:Child; D016207:Cytokines / Q000627:therapeutic use; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D007378:Interleukins / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000941:ethics; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007378:Interleukins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept