Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)

• Published in: Journal of the American Academy of Dermatology Vol. 73; no. 1; pp. 37 - 49
• Main Authors: Papp, Kim, Reich, Kristian, Leonardi, Craig L., Kircik, Leon, Chimenti, Sergio, Langley, Richard G.B., Hu, ChiaChi, Stevens, Randall M., Day, Robert M., Gordon, Kenneth B., Korman, Neil J., Griffiths, Christopher E.M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: Administration, Oral; apremilast; clinical trial; Dermatology; Double-Blind Method; ESTEEM; Female; Humans; Male; Middle Aged; phosphodiesterase 4 inhibitor; Phosphodiesterase 4 Inhibitors - administration & dosage; psoriasis; Psoriasis - drug therapy; Severity of Illness Index; Thalidomide - administration & dosage; Thalidomide - analogs & derivatives; treatment; clinical trial; treatment; FDA; PASI; sPGA; IL; AE; PDE4; apremilast; ESTEEM; Th; PASI-75; psoriasis; SAE; phosphodiesterase 4 inhibitor; static Physician Global Assessment; Psoriasis Area and Severity Index; phosphodiesterase 4; serious adverse event; interleukin; Food and Drug Administration; T helper; Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis; adverse event; 75% or greater reduction from baseline Psoriasis Area and Severity Index score
• ISSN: 0190-9622; 1097-6787; 1097-6787
• DOI: 10.1016/j.jaad.2015.03.049

Apremilast works intracellularly to regulate inflammatory mediators. ESTEEM 1 evaluated efficacy/safety of apremilast at 30 mg twice a day for moderate to severe plaque psoriasis. This phase III, multicenter, double-blind, placebo-controlled study randomized adults (2:1) to apremilast or placebo. At week 16, the placebo group switched to apremilast through week 32, followed by a randomized treatment withdrawal phase to week 52. Binary end points were analyzed using χ2 test; continuous end points used analysis of covariance. In all, 844 patients were randomized (n = 282, placebo; n = 562, apremilast). At week 16, significantly more patients taking apremilast achieved 75% or greater reduction from baseline Psoriasis Area and Severity Index score (PASI-75) (33.1%) versus placebo (5.3%, P < .0001; primary end point). Most (61.0%) patients rerandomized to apremilast at week 32 achieved PASI-75 at week 52 versus 11.7% rerandomized to placebo. Of patients rerandomized to apremilast at week 32, mean percentage change from baseline PASI score was −88% to −81% (weeks 32-52). During the placebo-controlled period, 55.7% and 69.3% of patients randomized to placebo and apremilast, respectively, had 1 or more adverse events. Most adverse events were mild/moderate in severity. No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period. Data were limited to 52 weeks and may not generalize to nonplaque psoriasis. Apremilast was effective in moderate to severe plaque psoriasis.