Safety and efficacy of disease-modifying anti-rheumatic agents: focus on the benefits and risks of etanercept.
The traditional approach to the treatment of rheumatoid arthritis (RA) has been the use of nonsteroidal anti-inflammatory drugs usually in combination with a disease-modifying antirheumatic drug (DMARD) such as hydroxychloroquine, gold, sulfasalazine, methotrexate, leflunomide or cyclosporin. Each of these DMARDs has its own distinct toxicities but has also been shown to be effective in reducing signs and symptoms of disease and to some extent, reduce radiological progression. Within the past 10 years, the combination of several traditional DMARDs has been shown to have increased efficacy over monotherapy without a significant increase in toxicity in a majority of studies. Recently, the US Food and Drug Administration has approved infliximab, a chimeric monoclonal antibody to tumour necrosis factor (TNF)-alpha in combination with methotrexate, for the treatment of signs and symptoms of RA, delay of radiological progression of disease and improvement of physical function while anakinra, an interleukin-1 receptor antagonist, has been approved for the treatment of the signs and symptoms of RA either as monotherapy or in combination with methotrexate. Etanercept is the first biological response modifier approved for use in RA in the US. Double-blind, randomised controlled studies have shown etanercept to be effective therapy in patients with RA who have had inadequate response to DMARDs, in combination with methotrexate, and as early monotherapy. Similar results were seen in juvenile and psoriatic arthritis in DMARD nonresponders. Open-label studies have shown efficacy in adult Still's disease, ankylosing spondylitis, progressive systemic sclerosis, Wegener's granulomatosis and chronic uveitis. Safety issues are a concern because of the ubiquitous role of TNF. To date the only consistent adverse event seen with etanercept has been injection site reactions. Infections occur at the same rate and with the same frequency as the placebo population. There should be caution, however, with using etanercept in patients with a serious infection, or recurrent infections or patients with untreated or latent tuberculosis. As of yet there has not been seen an increase of malignancies. Rare neurological and haematological events have been noted. Etanercept has been a significant addition to the armamentarium of medications for the treatment of RA, juvenile and psoriatic arthritis. Preliminary data show that it may be well tolerated and effective in other rheumatic diseases in which there is over production of TNFalpha.
Fleischmann
Roy
R
Radiant Research-Dallas, Dallas, Texas 75235, USA. royfleischmann@radiantresearch.com
Iqbal
Imran
I
Nandeshwar
Pallavi
P
Quiceno
Andres
A
D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D001171:Arthritis, Juvenile / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D007375:Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept