Anti-tumour necrosis factor therapy in Crohn’s disease: where are we now?
- Department of Experimental Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; S.J.vanDeventer@amc.uva.nl
Controlled trials have confirmed the efficacy of two tumour necrosis factor α (TNF-α) antibodies in active Crohn’s disease.1–4 In responding patients, the therapeutic effects qualitatively differ from those observed with standard therapy, including corticosteroids and immunosuppressives, and complete clinical remission can be induced in about one third of patients that did not respond to standard treatment. More than 140 000 patients have been treated with infliximab, and in large centres the reported efficacy in Crohn’s disease is comparable with data reported in controlled clinical trials. Few would disagree that anti-TNF-α therapy is an important therapeutic addition in the treatment of patients with active Crohn’s disease. On the other hand, toxicities related to TNF-α neutralising therapies have emerged. Of 147 000 infliximab treated patients, 70 developed tuberculosis, and 12 subsequently died (four as a direct result of tuberculosis).5
The importance of TNF-α for the host defence against Mycobacterium tuberculosis,6Listeria monocytogene, and other intracellular pathogens is long known, and it should come as no surprise that neutralisation of TNF-α predisposes to (reactivation of) tuberculosis. Indeed, tuberculosis has been reported in etanercept (a TNF receptor II fusion protein) and D2E7 (a human anti-TNF-α antibody) treated patients. In the majority of cases, tuberculosis following treatment with …