Expert opinion on investigational drugs vol:9 issue:1 pages:103-11
The current treatment of Crohn's disease is limited by a lack of long-term efficacy of corticosteroid therapy and the associated side effects. Biological treatment strategies aimed at neutralising immune responses, offer new opportunities for the management of chronic inflammatory disorders. In Crohn's disease, anti-TNF agents have taken the lead in development of immune-modulating drugs since TNF is known to be a pivotal cytokine in this illness. Different strategies have been explored aimed at inhibiting TNF but at present, the majority of clinical data have been obtained with monoclonal antihuman TNF antibodies. The chimeric anti-TNF IgG1 antibody infliximab (cA2, Remicade, Centocor) has been proven, in multiple clinical trials, to be an effective and well tolerated therapy for the management of acute Crohn's disease and recently this compound has obtained FDA and European Medicines Evaluation Agency approval. Although there are some concerns about immunogenicity of the anti-TNF antibody resulting in the formation of human antichimeric antibodies (HACA) as well as lymphoproliferative disorders, the clinical benefit in the treatment of refractory Crohn's disease is a major therapeutic breakthrough. Further studies will be needed to establish the role and optimal dosing scheme of anti-TNF antibodies in maintenance of remission, monitor safety in the long run and to evaluate the effectiveness of alternative anti-TNF agents such as the TNF receptor/Fc fusion protein etanercept (Enbrel, Immunex) and TNF synthesis inhibitor thalidomide.