TNF inhibitors - Mechanisms of action, approved and off-label indications.

Tumor necrosis factor inhibitors (TNFi) belong to the group of biologic drugs, holding presently top positions on lists of most profitable products for pharmaceutical companies. Although current indications for TNFi include only selected diseases with an established role of immune dysfunction in their pathogenesis, studies on new indications are being carried out all over the world. The most important aspect of TNFi therapy is a targeted therapeutic approach, allowing to avoid a wide range of side effects associated with treatment with nonspecific immunosuppressive agents. Results of the trials on TNFi in the approved indications are widely accessible and analyzed elsewhere, both in primary publications as well as in systematic reviews and meta-analyses. Here we aim to discuss their mechanisms of action, and approved, as well as off-label indications of TNFi. In addition, we present comprehensive evidence on TNFi in treatment of rheumatoid arthritis (RA); the first authorized and probably most extensively developed indication for the majority of TNFi.