Novel glucocorticoids: where are we now and where do we want to go?

Glucocorticoid (GC) therapy is widely accepted as effective treatment for many inflammatory conditions. However, the potential of GC to produce adverse effects may prompt both patients and prescribing doctors to take a critical view on these important drugs. The increasing awareness of potential side effects suggests that the improvement of the benefit:risk ratio represents both a current need and an ongoing challenge. The developing and detailed knowledge on mechanisms of GC action has resulted in exploration of numerous approaches to optimise treatments with these important drugs. Most advanced is a chronotherapeutic formulation of prednisone (termed modified- or delayed-release prednisone) that has been recently approved in many European and other countries, and very recently also in the United States. Another interesting example is the development of selective GC receptor (GR) agonists, with clinical studies being currently underway. The development of so called liposomal GC is ongoing. However, another approach, the synergistic combination of prednisolone and dipyridamole, has been recently discontinued because a phase 2b study with the treatment in patients with rheumatoid arthritis showed a statistically significant improvement in disease activity score measured in 28 joints (DAS28) compared with placebo, but not compared with prednisolone alone. Other interesting developments and promising concepts include the development of nitrosteroids, targeting the membrane-bound GR and the use of extracts of the medicinal plant Tripterygium wilfordii Hook F.