Etanercept (Enbrel, Immunex Corporation, Seattle, Washington, USA) is a new biological disease-modifying antirheumatic drug (DMARD) for the treatment of active rheumatoid arthritis (RA). It is one of two TNF-alpha blockers to be licensed for the treatment of active RA and is classified as a recombinant human soluble TNF receptor. The drug competitively inhibits the binding of TNF to cell surface receptors and thus renders TNF biologically inactive. In doing so, etanercept inhibits the pro-inflammatory effects of TNF and results in a reduction of joint inflammation in patients with RA. Etanercept has shown a statistically significant reduction in swollen and inflamed joint counts, biochemical markers such as erythrocyte sedimentation rate and C-reactive protein and shown significant improvements in quality of life measures (HAQ and global assessment scores) in all studies. In early disease, etanercept has shown a reduction in joint space narrowing equal to methotrexate (MTX) and a reduction in the appearance of new erosions significantly better than MTX after 1 year of treatment. Etanercept has a rapid onset of action which is significantly faster than standard DMARDs. Etanercept was well-tolerated in clinical trials. The commonest side effects were injection site reactions and upper respiratory tract infections. Etanercept therapy has resulted in serious infections in some patients and should be used with caution in any patient with a history of recurring infections or with disease states that may predispose to infections. In summary, etanercept is an effective and well-tolerated agent that is a significant breakthrough in the treatment of this disabling condition.

Leflunomide (Arava(trade mark), Hoescht Marion Roussel, now Aventis Pharma) is a new, oral disease modifying antirheumatic drug (DMARD) for the treatment of active rheumatoid arthritis (RA). It is a novel isoxazole derivative, which has shown both anti-inflammatory and immunomodulatory properties. Leflunomide primarily acts by inhibiting the de novo synthesis of pyrimidine nucleotides (and consequently DNA and RNA) in immune response cells, particularly activated T-cells. It also inhibits tyrosine kinases, with a subsequent reduction in the pro-inflammatory cytokines, TNF and IL-1. Leflunomide is significantly more effective than placebo and equivalent to sulfasalazine and methotrexate in short-term (26 - 52 week) studies, as measured by American College of Rheumatology (ACR) criteria. It has shown significant improvements in functional disability and health related quality of life and has consistently been shown to slow radiographic progression of RA. Leflunomide has a rapid onset of action (within 4 weeks) which is significantly faster than placebo and sulfasalazine. Leflunomide was well-tolerated in clinical trials with no serious adverse effects occurring. The most common side effects were gastrointestinal disturbances, reversible alopecia, rash, hypertension and abnormal liver function tests. Most of these were mild to moderate and resolved without any complications. In summary leflunomide is an effective and well-tolerated DMARD that is a welcome addition to the currently available DMARDs for the treatment of this disabling condition.

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