A Comprehensive Monograph on Apremilast (Otezla®): Pharmacology, Clinical Efficacy, and Therapeutic Positioning

Executive Summary

Apremilast, marketed under the brand name Otezla®, is a first-in-class, orally administered small-molecule inhibitor of the enzyme phosphodiesterase 4 (PDE4). Its development and approval marked a significant advancement in the treatment of chronic inflammatory diseases, offering a novel non-biologic, systemic option for patients. The drug's primary mechanism of action involves the intracellular inhibition of PDE4, which leads to an increase in cyclic adenosine monophosphate (cAMP) levels within inflammatory cells. This elevation in cAMP modulates the expression of a wide network of inflammatory mediators, resulting in the down-regulation of pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-17 (IL-17), and IL-23, and the up-regulation of the anti-inflammatory cytokine IL-10.

Apremilast holds regulatory approvals in major global markets, including the United States and the European Union, for several indications. These include the treatment of moderate-to-severe plaque psoriasis in adults and pediatric patients, active psoriatic arthritis in adults, and oral ulcers associated with Behçet's disease in adults. Its efficacy profile is characterized by a statistically significant, albeit modest, improvement over placebo. This positions Apremilast as a valuable therapeutic option, particularly for patients who prefer an oral treatment, are averse to injections, or for whom biologic therapies are contraindicated or have failed.