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In September, FDA approved Apremilast (Otezla; Celgene) for treatment of moderate-to-severe plaque psoriasis in patients who are candidates for phototherapy or systemic therapy. Apremilast was first approved by FDA for treatment of adults with active psoriatic arthritis in March 2014. The first of a new class of drug therapy for these conditions, apremilast is a phosphodiesterase 4 (PDE4) inhibitor. It reduces the inflammatory processes associated with these conditions, resulting in symptom improvement. For patients with moderate-to-severe plaque psoriasis, apremilast offers a new oral option for treatment.
Apremilast was approved for treatment of moderate-to-severe plaque psoriasis on the basis of two randomized, double-blind, placebo-controlled trials (ESTEEM 1 and 2). Participants were at least 18 years of age with moderate-to-severe plaque psoriasis and were were candidates for phototherapy or systemic therapy.
In both studies, participants were randomized to receive either apremilast 30 mg twice daily or placebo for 16 weeks. The primary endpoint in both studies was the proportion of participants achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI-75). At week 16, 5% of participants taking placebo achieved PASI-75 in each trial compared to 33% (ESTEEM-1) and 28% (ESTEEM-2) of participants taking apremilast. The static Physician Global Assessment (sPGA) scores of “clear” or “almost clear” were assessed as a secondary endpoint.
Both studies demonstrated greater achievement of significantly improved sPGA scores with apremilast use at 16 weeks compared to placebo (21.7% vs. 3.9% in ESTEEM-1; 20.4% vs. 4.4% in ESTEEM-2). Study findings were deemed significant and clinically meaningful improvements in plaque psoriasis. While apremilast provides a therapeutic option for treatment of psoriasis, its efficacy has not been studied in comparison with other approved treatment options.
Apremilast was well tolerated in clinical trials. The most common adverse effects observed in the ESTEEM trials include diarrhea, nausea, headache, and upper respiratory infections. Nausea generally resolved within one month of use. The discontinuation rates resulting from adverse reaction for participants taking apremilast was 6.1% compared to 4.1% of participants taking placebo in studies.
In trials, apremilast is associated with an increase in depressed mood in some patients. A careful consideration of the risks and benefits of apremilast therapy should be performed before initiation of treatment in patients with a history of depression or suicidal thoughts or behaviors. Patients and caregivers should be advised to contact their healthcare provider immediately should changes in mood, worsening depression, or suicidal thoughts occur in patients taking apremilast.
Significant weight reduction has also been associated with apremilast use. Discontinuation of apremilast should be considered with any unexplained or clinically significant weight loss. Patients taking apremilast should be advised to monitor their weight regularly.
Apremilast should be initiated with a 10-mg morning dose and titrated up over six days to 30 mg twice daily. The drug is available in a two-week starter blister pack to simplify the dosing schedule for the patient. Tablets should not be crushed or split. A maximum daily dose of 30 mg should be used for patients with severe renal impairment (creatinine clearance <30 mL/min). Co-administration of apremilast with strong CYP450 inducers may result in reduced apremilast efficacy and should therefore be avoided. Apremilast may be taken without regard to food.
Kathryn Wheeleris associate clinical professor, Pharmacy Practice, University of Connecticut, School of Pharmacy, Storrs, Conn.