Biological Therapies For Inflammatory Bowel Disease: Research DrivesClinics

Silvio      Danese; Stefano      Semeraro; Alessandro      Armuzzi; Alfredo      Papa; Antonio      Gasbarrini

Abstract

The better understanding of the mechanisms of inflammatory bowel disease has driven our progress intothe development of new biological therapies targeting specific molecules. Anti-TNFα biologic compounds have shown great efficacy particularly in Crohns disease. Infliximab (an IgG1 mouse/human chimeric monoclonal anti-TNFα antibody fragment) is the most efficacious compound in inductionand maintenance therapy of active and fistulizing Crohns disease, being at present the only biological compoundapproved for therapy, but with the limit of the immunogenicity; CDP-571 (a humanized anti-TNFα antibody) andCDP-870 (a PEGylated anti-TNFα antibody) are less immunogenic, showed some efficacy in induction therapy inCrohn ’ s disease but a rapid loss of response in maintenance therapy. Etanercept and onercept (soluble humanrecombinant TNFα receptors fusion proteins) seem not to be efficacious in Crohns disease demonstrating noclass-effect for anti-TNFα compounds. In preliminary study, adalimumab (an IgG1 humanized monoclonal anti-TNFα antibody) offers good perspective of efficacy and safety also in infliximab-resistant or allergic patients.Inhibition of lymphocyte trafficking to the gut, through anti-adhesion molecules specific therapies (natalizumab,MLN-02, alicaforsen), has shown promising results: unfortunately, natalizumab, the most effective drug of thisclass, has recently been suspected to favour serious neurological complications. Other biologic therapies are underevaluation but at present seem to be less promising than infliximab; they consist of antiinflammatory cytokines,inhibitors of proinflammatory cytokines, hormones and growth factors: anti-IL12-antibody, interferonα,interferonβ,G-CSF, GM-CSF, EGF, growth hormone, anti-interferonγ, anti-IL-18, anti-IL-2-receptor and anti-CD3 antibodies. The evaluation of other biological drugs has been suspended for severe side effects as happened foranti-CD40L antibody causing thromboembolism and anti-CD4 antibody causing ly.mphopenia. Other compoundsas IL-10 and IL-11 have been proven to be ineffective even if an oral formulation of IL-11 is under evaluation.Among the MAP kinases inhibitors BIRB-796 and RDP58 showed to be ineffective while CNI-1493 is underevaluation. The effort in identifying specific patients features predicting therapy response and the possible combination ofdifferent biological therapies represent undoubtedly a very promising perspective. Aim of this article is to reviewthe biological compounds and their efficacy in IBD.

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