Product Spotlight: Otezla® (apremilast)

Celgene Corporation’s Otezla® (apremilast) was approved by the FDA on September 23, 2014, for the treatment of patients with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Apremilast is the first and only phosphodieterase 4 (PDE4) inhibitor approved for the treatment of plaque psoriasis. The PDE4 inhibitor was first FDA-approved on March 21, 2014, for the treatment of adult patients with active psoriatic arthritis (PsA).

Apremilast is an oral small-molecule inhibitor of PDE4 specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels, which is thought to indirectly modulate the production of inflammatory mediators. The specific mechanism(s) by which apremilast exerts its therapeutic action in patients with psoriasis or PsA is not well-defined, according to a Celgene news release announcing the drug’s approval.

To reduce the risk of gastrointestinal symptoms associated with initial therapy, clinicians should titrate to the recommended dose of 30 mg twice daily according to the following schedule:

    • Day 1: 10 mg in the morning
    • Day 2: 10 mg in the morning and 10 mg in the evening
    • Day 3: 10 mg in the morning and 20 mg in the evening
    • Day 4: 20 mg in the morning and 20 mg in the evening
    • Day 5: 20 mg in the morning and 30 mg in the evening
    • Day 6 and thereafter: 30 mg twice daily

For patients with severe renal impairment (creatinine clearance [CrCl] <30 mL/min estimated by Cockcroft–Gault equation), the apremilast dosage should be reduced to 30 mg once daily. For initial dosage titration in this group, it is recommended that apremilast be titrated using only the morning schedule outlined above and the evening doses be skipped. Apremilast can be administered without regard to meals.

The FDA approved apremilast based primarily on the efficacy and safety results from 2 multicenter, randomized, double-blind, placebo-controlled, phase 3 clinical trials conducted in adult patients with moderate-to-severe plaque psoriasis. The trials showed that apremilast resulted in significant and clinically meaningful improvements in plaque psoriasis at week 16 as measured by Psoriasis Area Severity Index (PASI) scores. Clinical improvement as measured by static Physician Global Assessment (sPGA) scores of clear to almost clear were also demonstrated in both studies.

Psoriasis is an immune-mediated, noncontagious chronic inflammatory skin disorder of unknown cause. It is a chronic recurring condition, which varies in severity from minor localized patches to complete body coverage. Plaque psoriasis is the most common form of psoriasis, affecting about 90% of individuals. Plaque psoriasis appears as raised, red patches covered by silvery-white scales. These patches or plaques most often appear on the scalp, knees, elbows, and lower back. Psoriasis occurs nearly equally in men and women, according to the National Psoriasis Foundation. An estimated 125 million people worldwide have this skin disease, with as many as 7.5 million individuals in the United States living with the condition each day.