Rheumatoid arthritis (RA) and
juvenile idiopathic arthritis (JIA) are heterogeneous
autoimmune diseases characterized by chronic joint
inflammation.
Methotrexate is used as the gold standard to treat
rheumatoid arthritis, yet there are many patients in whom the disease cannot be controlled or who experience unacceptable intolerance. Most of the biologics currently used are effective, but mostly if combined with
methotrexate. Long-term possible side effects, such as impaired host defense mechanisms against
infection and
lymphoma, are distinct disadvantages and a major concern of anticytokine
therapies. Parenteral administration is a problem, particularly in children. Thus, there is a need to explore new treatment options. Here we review the properties of
histone deacetylase inhibitors (HDACi) as they apply to
rheumatoid arthritis by looking at effects on
cytokine production, T-cell differentiation and the function of macrophages, dendritic cells, osteoblasts, osteoclasts and synovial fibroblasts. We also review the safety and efficacy of
givinostat (
ITF 2357) in the treatment of systemic onset
juvenile idiopathic arthritis (SOJIA) and its influence on the
cytokine networks in SOJIA.
Givinostat is an orally active HDACi which was given to children with SOJIA. After 12 wk of treatment, there were significant benefits, particularly in reducing the
pain and arthritic component of the disease and decreasing the neutrophilia.
CD40L, IL-1α and IFNγ in whole blood lysates decreased at wks 2 and 4 compared with baseline levels. The clinical data are consistent with those from animal models of
rheumatoid arthritis and suggest that trials with HDACi are promising as a safe oral alternative to anticytokines and
methotrexate.