Psoriasis and
psoriatic arthritis are common clinical conditions that negatively impact health-related quality of life and are linked to serious medical comorbidities. Disease mechanisms involve local and systemic chronic inflammatory processes. Available
biologic therapies specifically target single inflammatory mediators, such as
tumor necrosis factor-α (TNF-α), in the context of a larger inflammatory signaling cascade. To interrupt this pathological cascade earlier in the response or further upstream, and return pro-inflammatory and anti-inflammatory signaling to a homeostatic balance, the use of a phosphodiesterase4 (
PDE4) inhibitor has been explored. PDE4 is the major
enzyme class responsible for the hydrolysis of cyclic
adenosine monophosphate (cAMP), an intracellular second messenger that controls a network of pro-inflammatory and anti-inflammatory mediators. With PDE4 inhibition, and the resulting increases in cAMP levels in immune and non-immune cell types, expression of a network of pro-inflammatory and anti-inflammatory mediators can be modulated.
Apremilast is an orally available targeted
PDE4 inhibitor that modulates a wide array of inflammatory mediators involved in
psoriasis and
psoriatic arthritis, including decreases in the expression of
inducible nitric oxide synthase, TNF-α, and
interleukin (IL)-23 and increases
IL-10. In phase II studies of subjects with
psoriasis and
psoriatic arthritis,
apremilast reversed features of the inflammatory pathophysiology in skin and joints and significantly reduces clinical symptoms. The use of an oral targeted
PDE4 inhibitor for chronic inflammatory diseases, like
psoriasis and
psoriatic arthritis, represents a novel treatment approach that does not target any single mediator, but rather focuses on restoring a balance of pro-inflammatory and anti-inflammatory signals.