At Last? Apremilast

In late September 2014, the US Food and Drug Administration approved the medication apremilast for treatment of moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy. It was previously approved for psoriatic arthritis in March 2014. Its mechanism includes selective inhibition of phosphodiesterase 4, resulting in increased intracellular cyclic adenosine monophosphate levels, indirectly mediating production of inflammatory mediators in many cell types, namely decreasing tumor necrosis factor α and IL-23 and increasing IL-10. Orally dosed at 30 mg twice daily, safety and efficacy was determined via 2 multicenter, randomized, double-blind, placebo-controlled trials—ESTEEM 1 and ESTEEM 2 (N=1257)—that highlighted a PASI-75 (psoriasis area severity index) in 30% of patients in the first 4 months and up to 88% of patients with PASI-75 in the first year (J Am Acad Dermatol. 2014;70(suppl 1):AB164). Additionally, according to results presented at a recent European Academy of Dermatology and Venereology meeting in early October 2014, pruritus and difficult areas such as the scalp, palmoplantar area, and nails showed significant improvement at week 16 (P<.0001). The most common side effects were diarrhea, nausea, upper respiratory infection, and headache, which occurred most often in the first 2 weeks of therapy. The medication does not require routine laboratory monitoring; however, because weight loss is possible, it is recommended that weight should be periodically checked. There are no contraindications aside from hypersensitivity to the drug itself, and caution should be taken in patients with unstable depression, suicidal ideation, or severe renal impairment. It is pregnancy category C.

What’s the issue?

Because it is administered orally; is dually indicated for plaque psoriasis and psoriatic arthritis; and does not require laboratory monitoring, alcohol consumption restrictions, category X classification, or immunosuppressive infection or cancer risk, the window-shopping appeal of this drug seems attractive compared to the veteran and contemporary pharmaceutical army of psoriasis therapy. However, based on the ESTEEM studies, meager apremilast PASI scores are not blowing us away like those of biologic medications. At a time when the evolution of medications for psoriasis seems like a revolving door for new products highlighting new mechanisms in new pathways in even newer cells in relationship to inflammation, how will this drug fit in?

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