Tumour necrosis factor-alpha blockade: a new era for effective management of rheumatoid arthritis.
Tumour necrosis factor (TNF)-alpha inhibitors have emerged as a new treatment option for rheumatoid arthritis (RA). The scientific rationale for targeting TNF-alpha in RA derives from extensive work in the laboratory, showing the importance of this pro-inflammatory cytokine as a mediator of joint inflammation. Proof of principle has now been firmly established in clinical trials where TNF-alpha inhibitors have been shown to decrease the signs and symptoms of joint inflammation and slow radiological progression of joint damage. Presently, the two TNF-alpha inhibitors available for use in RA are etanercept and infliximab. Etanercept is a soluble TNF receptor: Fc fusion protein that competes with the endogenous TNF receptors for TNF-alpha binding. Infliximab is a chimeric anti-TNF-alpha monoclonal antibody, which also binds with high affinity to soluble TNF-alpha. Etanercept and infliximab will be rapidly incorporated into current treatment paradigms, which call for early and intensive treatment of RA using disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, sulfasalazine and hydroxychloroquine. A major drawback to the widespread use of these biologics is their high costs. Some patients with limited financial means may be denied access to these effective anti-inflammatory agents. Moreover, long-term experience with TNF-alpha inhibitor therapy has been limited and concerns linger about the possibility that etanercept and infliximab may cause unforeseen side effects or increase the risk for opportunistic infection. Despite these caveats, TNF-alpha inhibitors represent a major advance for the treatment of RA and will likely spawn new indications for anti-TNF-alpha therapy and the development of novel therapeutic compounds with similar biological activity.
Division of Rheumatology, Allergy and Clinical Immunology, Department of Medicine, Duke University Medical Centre, Durham, NC 27710, USA.
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept