[Non-cytokine therapeutic targets]

The arrival of anti-TNF-α to the clinic has been the most successful example of translational research. However, clinical experience has shown that these compounds do not induce clinical remission in half of rheumatoid arthritis (RA) patients. Recently, new biological drugs against non-cytokine targets have been available for RA patients. These compounds deplete B cells or interfere with the activation of T cells and have also shown effectiveness in controlling signs, symptoms and structural damage progression in RA. Second generation B-cell depletion therapies are progressing in the pipeline of several pharmaceutical companies. These compounds will likely improve the immunogenicity and formulation of rituximab, but it is improbable that they will improve the remission rate achieved by the anti-TNF-α δρυγσ. Currently, regulation of signal transduction has evolved into an important field of drug research, and small molecule inhibitors for a number of pathways are tested as new anti-inflammatory agents. For rheumatic diseases, specific Jak3 and Syk inhibitors are, so far, the most successful compounds representing a significant advance over p38 mitogen-activated protein kinase (MAPK) inhibitors.