Infliximab treatment for Crohn's disease
- Pharmacy Department, Queen's Building, Bristol Royal Infirmary, Bristol BS2 8HW, UK
- Dr Conroy
- Received 27 September 2000
- Accepted 18 December 2000
Background
Crohn's disease is a lifelong inflammatory disorder characterised by the presence of inflammatory ulcerative lesions in the gastrointestinal tract.1 Lesions most commonly involve the large and small bowel, giving rise to symptoms of abdominal pain, weight loss, gastrointestinal haemorrhage, and fistula formation.2 The disease may present at any age, however the second and third decades of life represent the peak ages of diagnosis.3 Although the pathophysiology of Crohn's disease is unknown, a number of possible aetiologies have been reported. These include the interaction of environmental,4 5 infectious,6-8genetic,9 10 or immunological3 factors. To date, treatment has been geared towards symptomatic relief of disease exacerbations via pharmacological interventions such as aminosalicylates, corticosteroids, immunosuppressive agents, antibiotics, and nutritional therapy. Surgery is indicated in those patients who have failed to respond to medical management, or to correct intestinal obstruction or abscesses. This can be up to 50% of sufferers.1 Surgical intervention is by no means curative, with inflammatory episodes recurring in ≥80% of patients after intestinal resection.11
The advent of a therapy that can potentially restore immunological imbalance, modify the disease, and prolong remission in Crohn's disease patients, has thus been eagerly awaited.
Cytokine targeted treatment
The inflammatory response in Crohn's disease is regulated by intercellular mediators known as cytokines.12 The major contributing factor to chronic local inflammation in Crohn's disease is local mucosal overproduction of proinflammatory cytokines to anti-inflammatory cytokines.13 Tumour necrosis factor-α (TNF-α) is one of several proinflammatory mediators, which has a central role in chronic inflammatory conditions, such as Crohn's disease, rheumatoid arthritis, and other granulomatous diseases. There are currently two anti-TNF antibodies under clinical evaluation, infliximab and CDP571.14 Infliximab (Remicade, Schering Plough, UK) is a chimeric monoclonal antibody to TNF-α, developed as a therapeutic agent for TNF-α mediated diseases. Infliximab …
