Abstract and Introduction
Abstract
The efficacy of anti-tumour necrosis factor (anti-TNFα) therapy with infliximab and adalimumab in moderate to severe Crohn's disease has now been proved. This article reviews the evidence supporting best practice with these agents in the light of recent National Institute for Health and Clinical Excellence guidance. Recent studies point to greater efficacy when these drugs are used early in the disease, particularly when mucosal healing can be achieved. For infliximab, the combination with immunomodulator drugs appears to afford greater efficacy, but possibly at the expense of the risk of rare but serious side effects. Patients should be selected carefully for treatment based on prognostic factors predicting aggressive disease, on the one hand, and comorbid factors that might predict side effects, on the other. Multiple drug combinations should be avoided where possible. Finally, a minority of patients in stable remission with complete mucosal healing may be selected for anti-TNFα drug withdrawal.
Introduction
Since the initial reports of anti-tumour necrosis factor (anti-TNFα) antibody treatment for Crohn's disease in 1997 the use of both infliximab and adalimumab has become widespread, yet variable, in Europe and the Western world. Adalimumab and infliximab are both monoclonal antibodies that have a high affinity for TNFα. Infliximab is a chimeric human-murine antibody delivered intravenously according to body weight (usually 5 mg/kg), whereas adalimumab is a recombinant human antibody that is delivered subcutaneously and is not weight related (usually 40 mg every other week).
National Institute for Health and Clinical Excellence (NICE) guidance was published in 2010 and both drugs are now recommended as treatment options for severe active Crohn's disease which has not responded to conventional treatment (including immunosuppressive and/or corticosteroid treatments). It is recommended that treatment should normally be started with the less expensive drug, though this is not as straightforward as simply a measure of body weight and should include consideration of the cost of dose escalation and drug administration, and the guidance also allows for individual preference to be considered in drug choice. Infliximab is recommended as the preferred treatment for people with active fistulising Crohn's disease and for paediatric disease. NICE also recommends that patients should have their disease reassessed 12 months after the start of treatment to determine whether ongoing treatment is still clinically appropriate. Despite this clear guidance, questions of when and in whom to start treatment, whether immunomodulators (IMs) should be co-prescribed, what to do if response is lost and how to assess when treatment can be withdrawn remain uncertain. In this article we review the evidence that helps answer some of these key clinical questions