[TNF-alpha inhibitors in inflammatory bowel disease].
Inflammatory bowel disease (IBD) is a chronic immunoinflammatory response to an stimulus that activates a chain of cellular mediators causing intestinal damage. One of the most well recognized proinflammatory mediators involved in the pathogenesis of IBD is tumor necrosis factor alpha (TNFalpha). The treatment of IBD has advanced in parallel to the improvement of the knowledge of its physiopathology, leading to the development of biological therapies. An example of this kind of treatment is the use of substances that antagonize TNFalpha, such as monoclonal antibodies infliximab, adalimumab, natalizumab, etanercept or onercept, with infliximab being the unique approved for use in IBD. Several studies have demonstrated that inhibition of TNFalpha is useful in the treatment of Crohn's disease (CD). In CD, infliximab induces the remission of relapses which are refractory to the conventional treatment, prevents more relapses and induces a closure of enterocutaneous and perianal fistula that do not respond to first line treatment. However, infliximab is not useful in ulcerative colitis. Infliximab treatment has some drawbacks, such as the development of anti-infliximab antibodies, which cause a loss of efficacy of the treatment and hypersensitivity reactions. Other reported adverse effects of infliximab are the development of autoimmunity, such as that related with antinuclear or anti-DNA antibodies, or the reactivation of infections such as tuberculosis. In fact, a screening for tuberculosis is necessary before administration of infliximab. To reduce the adverse effects due to infliximab immunogenicity, several trials with humanized or completely human agents, such as adalimumab or onercept, are under way. Until the precise stimulus that triggers IBD is identified, biological therapies have a great future and the selective antagonism of TNFalpha is already a reality.
Casellas i Jordà
Francesc
F
Servei de Digestiu, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab