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Psoriatic Arthritis Drug Apremilast (Otezla) Approved for Treatment of Plaque Psoriasis

Efficacy demonstrated in phase III trials

The FDA has approved apremilast (Otezla, Celgene Corp.), an oral, selective inhibitor of phosphodiesterase 4 (PDE4), for the treatment of patients with moderate-to-severe plaque psoriasis for whom phototherapy or systemic therapy is appropriate.

Apremilast is the first and only PDE4 inhibitor indicated for the treatment of plaque psoriasis. It was approved in March 2014 for use in adults with active psoriatic arthritis.

The expanded labeling for apremilast is based primarily on safety and efficacy results from two randomized, double-blind, placebo-controlled studies (ESTEEM 1 and ESTEEM 2) conducted in adult patients with moderate-to-severe plaque psoriasis, i.e., body surface area (BSA) involvement of 10% or greater; a static Physician Global Assessment (sPGA) score of 3 or greater (moderate or severe disease); a Psoriasis Area and Severity Index (PASI) score of 12 or greater; and candidates for phototherapy or systemic therapy.

The ESTEEM trials were pivotal, phase III, randomized, placebo-controlled studies that evaluated apremilast in patients who had moderate-to-severe plaque psoriasis for at least 12 months prior to screening and who were candidates for phototherapy and/or systemic therapy.

Approximately 1,250 patients were randomly assigned to receive either apremilast 30 mg twice daily or placebo (after an initial 5-day titration period) for the first 16 weeks, followed by a maintenance phase from weeks 16 to 32, during which placebo-treated patients were switched to apremilast 30 mg twice daily through week 32, and a randomized withdrawal phase for responders from week 32 to week 52, based on their initial apremilast randomization and PASI-75 response (i.e., a 75% reduction in the PASI score).

In the ESTEEM trials, treatment with apremilast resulted in significant and clinically meaningful improvements in plaque psoriasis, as measured by PASI scores at week 16. Clinical improvement, as measured by sPGA scores of "clear" to "almost clear," were also demonstrated in both studies.

The safety of apremilast was assessed in 1,426 patients from three clinical trials. Adverse events associated with apremilast included diarrhea, nausea, upper respiratory tract infection, tension headache, and headache.

Apremilast is an oral small-molecule PDE4 inhibitor that specifically targets cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which is thought to modulate indirectly the production of inflammatory mediators. The specific mechanism(s) by which apremilast exerts its therapeutic action in patients with psoriasis or psoriatic arthritis is not well defined.

Source: Celgene; September 23, 2014.

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