Clinical research helps elucidate the role of tumor necrosis factor-alpha in the pathogenesis of T1-mediated immune disorders: use of targeted immunotherapeutics as pathogenic probes.
Psoriasis is a life-disabling disorder in which 8-10% of patients aged 18-54 actively contemplate suicide because of their disease. Owing to the toxicity and/or inconvenience of current, FDA-approved treatments far moderate-to-severe psoriasis, they are generally used intermittently so that patients experience cycles of remission-flare-remission-flare, etc. The challenge to drug development for moderate-to-severe psoriasis is to provide safe and effective long-term management. Immunobiologics offer the hope for safe, long-term control of psoriasis because they lack targeted organ toxicity. Thus the treatment paradigm may shift from one of intermittent treatment limited by toxicity with resultant flares of disease, to one similar to that seen in diabetes or hypertension in which disease is controlled continuously. Additionally, immunobiologics may alter the natural history of psoriasis. Etanercept, which targets TNF-alpha, controls signs and symptoms and halts joint destruction in patients with psoriatic arthritis. The long-lived remissions observed after cessation of alefacept or infliximab (anti-TNF-alpha monoclonal antibody) treatment lead this author to speculate that these immunobiologics may actually alter the natural history of the cutaneous manifestations of psoriasis.
Gottlieb
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Clinical Research Center, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08901-0019, USA. gottliab@umdnj.edu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D000068800:Etanercept; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology*; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D000069285:Infliximab; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept