Management Of Rheumatoid Arth... Health Article

Determining The Best Time To Introduce Anti-tnf Therapy

Tumour necrosis factor (TNF) is a key cytokine in RA inflammation and damage. Over the past five years drugs that block this cytokine (adalimumab, etanercept and infliximab) have been introduced into clinical practice. Two of the drugs (adalimumab and etanercept) are subcutaneous injections and can be self-administered (see Figure 1). Infliximab is given intravenously every 8 weeks after initial induction. These drugs have made a huge difference to the management of many patients with active disease that has failed to respond to conventional treatments ( Table 4). It is estimated that up to 5% of all RA patients may require such therapy.

In the UK, anti-TNF therapies are restricted to patients with ongoing active disease who have failed to respond to at least two conventional DMARDs, where one is methotrexate. At first, clinicians approached these drugs cautiously, and because of financial restrictions on their use, tended to use them when many other DMARDs had failed. However, the success of patients on these therapies, and the fact that they are well tolerated by most, has led clinicians to use them earlier in the course of the disease, so that more patients are now receiving them before irreversible joint damage had occurred. Clinicians are informed by the national database for biologic therapies and new therapeutic regimes continue to be developed.

Deciding On When To Reduce Treatment In Responders

Ongoing patient monitoring provides a means of ensuring both safety and efficacy of treatment, with the opportunity to escalate therapy when the response to treatment is suboptimal. However, it may also be possible to cut back on treatment when patients are doing well. The main priority is to eradicate oral steroids for patients in whom these have been introduced. Patients who are doing well may also be able to stop NSAIDs. In a patient in remission, it may be tempting to stop DMARDs. Whether this is wise is difficult to judge as there is evidence of ongoing erosive damage in many patients who otherwise appear to be in remission. Therefore if a patient tolerates their DMARD well, they might, in discussion with their clinician, elect to remain on the drug, in the lowest dose that maintains remission. Because for each individual patient the correct approach is unknown, therapeutic tactics are open to informed negotiation. Relapse after stopping DMARD therapy is common and recommencement of DMARDs in such patients does not guarantee further remission.

The Future Management Of Ra

It is the hope of all RA patients and their carers that the exciting progress in this disease will continue, particularly in the following areas.

• Improved diagnostic tests for early RA with more specific blood tests (such as antibodies like anti-CCP), and greater access to imaging modalities such as ultrasound and MRI.

• Prognostic tests will improve, so that different regimes can be tailored to individual patients depending on these tests. Patients who are destined to do badly will be spotted early and treated aggressively with confidence. Pharmacogenetics and other investigations such as cytokine profiles will assist in regimes that patients can tolerate and benefit from.

• Analgesics and NSAIDs will improve for control of symptoms, and will have reassuring data on long-term safety, not only on the gastrointestinal tract, but also addressing recent concerns over cardiovascular risks.

• The health economic arguments for using anti-TNF and new emerging biological drugs will have reached a point where it is cost effective to broaden the eligibility criteria for these drugs, and use them earlier in the disease course. It may be determined that the ability to stay in work and avoid orthopaedic interventions has been improved by these drugs.

• Other new biological drugs, such as rituximab (a B cell depleter), and other cytokine blockers, will appear in well established regimes for RA.

• Remission will not only be an aspiration, but the chief objective in the management of RA.

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