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Osteoarthritis (OA) is the most common form of arthritis and one of the leading causes of disability worldwide. The incidence of OA increases with age, and as longevity increases, it will cause a significant socioeconomic burden. No disease-modifying therapy is available for OA. Recent research has highlighted the role of inflammation in the progression of OA. Interleukin-1 appears to have a significant role in disease progression. Since the interleukin-1 receptor antagonist (IL-1Ra) anakinra has been used successfully in the treatment of the inflammation and bone destruction of rheumatoid arthritis, some have suggested that it may be able to retard the disease progression of OA. This article reviews the data on the use of anakinra in OA treatment.

The treatment of rheumatoid arthritis (RA) has changed dramatically over the past 15 years with the realisation that earlier, aggressive therapy limits progression. There is evidence that biological response modifiers (BRMs), which target specific cytokines such as TNF-alpha and IL-1, are more effective than traditional disease-modifying antirheumatic drugs (DMARDs), especially in combination with methotrexate. Four therapies are approved for use in RA; three target TNF-alpha (etanercept [Enbrel, Amgen Inc.], infliximab [Remicade, Centocor Inc.], and adalimumab [Humira, Abbott]), and one targets IL-1 (anakinra [Kineret, Amgen Inc.]). It is clear from both the clinical trials and postmarketing reports that all four agents have a different safety profile compared with traditional DMARDs. There are several areas of concern with the use of the BRMs, which include serious and opportunistic infections, malignancy/lymphoma, congestive heart failure, demyelination, injection/infusion reactions, development of autoantibodies and lupus-like disease. It is important to be fully aware of the safety profile and differences between BRMs in order to use them appropriately.

Anakinra (Amgen, Inc.) is a specific receptor antagonist of IL-1 that differs from naturally occurring IL-1 receptor antagonist by the presence of a methionine group. Anakinra has been shown to be of benefit in patients with active rheumatoid arthritis, either when given alone or in combination with methotrexate, as assessed by improvement in clinical signs and symptoms, decreased radiographic progression and improvement in patient function, pain and fatigue, although it appears to be effective in fewer patients than anti-TNF agents. It has a favourable safety profile as demonstrated in clinical trials. The physician and patient must be cognizant of serious infectious episodes. Many of the rare side effects seen with TNF blockers, such as tuberculosis, other opportunistic infections, worsening of congestive heart failure and the development of demyelinating disease, have not been seen in patients treated with anakinra. Anakinra should not be given in combination with anti-TNF agents.

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.

Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is commonly in a patient's twenties or thirties, they usually persist for the duration of the patient's life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Older patients with any of these three diseases are more likely to have more severe disease with significant functional decline. They are also more likely to have co-morbid diseases and use concomitant medications than patients who are younger. In patients with RA, AS or PsA, the introduction of anti-tumour necrosis factor (TNF)-α therapies such as etanercept, infliximab and adalimumab has had a significant impact in ameliorating the signs and symptoms of disease, improving patient function and inhibiting radiographic progression. Anti-TNFα therapies now have well recognised safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients =65 years of age. This review explores the information currently available regarding patients aged =65 years treated with anti-TNFα therapies for RA, AS or PsA, focusing on etanercept in RA because of a lack of data for other therapies and conditions. The analyses conducted show that there is similar efficacy in the treatment of RA in patients <65 years old and those =65 years of age. Although there are some differences in the adverse events noted in these two age groups, it appears as though treatment of patients =65 years of age, compared with age-matched controls, is not dissimilar to treatment of patients <65 years of age compared with their age-matched controls. Only by understanding the risks and benefits of therapy in the older age group can a true risk : benefit profile for etanercept, and ultimately other anti-TNFα therapies, be determined by the practising physician and the patient. [ABSTRACT FROM AUTHOR]