Biological therapies for inflammatory bowel disease

Research drives clinics

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

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The better understanding of the mechanisms of inflammatory bowel disease has driven our progress into the development of new biological therapies targeting specific molecules. Anti-TNF-α biologic compounds have shown great efficacy particularly in Crohn's disease. Infliximab (an IgG1 mouse/human chimeric monoclonal anti-TNF-α antibody fragment) is the most efficacious compound in induction and maintenance therapy of active and fistulizing Crohn's disease, being at present the only biological compound approved for therapy, but with the limit of the immunogenicity; CDP-571 (a humanized anti-TNF-α antibody) and CDP-870 (a PEGylated anti-TNF-α antibody) are less immunogenic, showed some efficacy in induction therapy in Crohn's disease but a rapid loss of response in maintenance therapy. Etanercept and onercept (soluble human recombinant TNF-α receptors fusion proteins) seem not to be efficacious in Crohn's disease demonstrating no class-effect for anti-TNF-α compounds. In preliminary study, adalimumab (an IgG1 humanized monoclonal anti-TNF-α 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 this class, has recently been suspected to favour serious neurological complications. Other biologic therapies are under evaluation but at present seem to be less promising than infliximab; they consist of antiinflammatory cytokines, inhibitors of proinflammatory cytokines, hormones and growth factors: anti-IL 12-antibody, interferon-α, interferon-β, G-CSF, GM-CSF, EGF, growth hormone, anti-interferon-γ, 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 for anti-CD40L antibody causing thromboembolism and anti-CD4 antibody causing ly.mphopenia. Other compounds as 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 under evaluation. The effort in identifying specific patients features predicting therapy response and the possible combination of different biological therapies represent undoubtedly a very promising perspective. Aim of this article is to review the biological compounds and their efficacy in IBD.

Original languageEnglish
Pages (from-to)771-784
Number of pages14
JournalMini-Reviews in Medicinal Chemistry
Volume6
Issue number7
DOIs
Publication statusPublished - Jul 2006

Fingerprint

Biological Therapy
Inflammatory Bowel Diseases
Anti-Idiotypic Antibodies
Antibodies
Crohn Disease
Research
Interferons
Interleukin-11
Granulocyte-Macrophage Colony-Stimulating Factor
Therapeutics
Immunoglobulin G
Monoclonal Antibodies
Cytokines
Antibodies, Monoclonal, Humanized
Immunoglobulin Fragments
CD40 Ligand
Interleukin-18
Molecules
Lymphocytes
Tumor Necrosis Factor Receptors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Chemistry(all)
  • Pharmacology

Cite this

Biological therapies for inflammatory bowel disease : Research drives clinics. / Danese, Silvio; Semeraro, Stefano; Armuzzi, Alessandro; Papa, Alfredo; Gasbarrini, Antonio.

In: Mini-Reviews in Medicinal Chemistry, Vol. 6, No. 7, 07.2006, p. 771-784.

Research output: Contribution to journalArticle

Danese, Silvio ; Semeraro, Stefano ; Armuzzi, Alessandro ; Papa, Alfredo ; Gasbarrini, Antonio. / Biological therapies for inflammatory bowel disease : Research drives clinics. In: Mini-Reviews in Medicinal Chemistry. 2006 ; Vol. 6, No. 7. pp. 771-784.
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