Details

Autor(en) / Beteiligte

• Levin, Alon D.
• Wildenberg, Manon E.
• van den Brink, Gijs R.

Titel

Mechanism of Action of Anti-TNF Therapy in Inflammatory Bowel Disease

Ist Teil von

• Journal of Crohn's and colitis, 2016-08, Vol.10 (8), p.989-997

Ort / Verlag

UK: Oxford University Press

Erscheinungsjahr

2016

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Several anti-tumour necrosis factor [TNF] blocking strategies have been evaluated in patients with Crohn’s disease. Compounds that have been tested included the full monoclonal IgG1 antibodies infliximab and adalimumab, the pegylated anti-TNF F[ab’]2 fragment certolizumab, an IgG4 anti-TNF CDP571 with reduced affinity for the Fc receptor, the soluble TNF receptor I onercept, and the TNF receptor II-Fc fusion protein etanercept. The endpoints of these studies suggest that not all methods of blocking TNF are equal. Here we will review the differences in the clinical, biochemical, and endoscopic endpoints of the major clinical studies. Collectively the data suggest that only IgG1 monoclonal antibodies have the ability to induce complete clinical, biochemical, and endoscopic remission. We discuss the potential multiple modes of action that may contribute to the response to full IgG1 anti-TNFs, focusing on the rapid induction of lamina propria T cell apoptosis and Fc receptor-dependent induction of M2-type wound-healing macrophages. We discuss how novel insights into the mechanism of action of anti-TNFs in Crohn’s disease may contribute to the development of novel anti-TNFs with improved efficacy.