title: Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial.
abstract: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, works intracellularly within immune cells to regulate inflammatory mediators. This phase 2b randomized, placebo-controlled study evaluated efficacy and safety of apremilast among Japanese patients with moderate to severe plaque psoriasis. In total, 254 patients were randomized to placebo, apremilast 20 mg b.i.d. (apremilast 20) or apremilast 30 mg b.i.d. (apremilast 30) through week 16; thereafter, all placebo patients were re-randomized to apremilast 20 or 30 through week 68. Efficacy assessments included achievement of 75% or more reduction from baseline in Psoriasis Area and Severity Index score (PASI-75; primary) and achievement of static Physician Global Assessment (sPGA; secondary) score of 0 (clear) or 1 (minimal) at week 16. Safety was assessed through week 68. At week 16, PASI-75 response rates were 7.1% (placebo), 23.5% (apremilast 20; P = 0.0032 vs placebo) and 28.2% (apremilast 30; P = 0.0003 vs placebo); sPGA response rates (score of 0 or 1) were 8.8% (placebo), 23.9% (apremilast 20; P = 0.0165 vs placebo) and 29.6% (apremilast 30; P = 0.0020 vs placebo). Responses were maintained with apremilast through week 68. Most common adverse events (AEs) with placebo, apremilast 20 and apremilast 30 (0-16 weeks) were nasopharyngitis (8.3%, 11.8%, 11.8%), diarrhea (1.2%, 8.2%, 9.4%), and abdominal discomfort (1.2%, 1.2%, 7.1%), respectively. Exposure-adjusted incidence of these AEs did not increase with continued apremilast treatment (up to 68 weeks). Apremilast demonstrated efficacy and safety in Japanese patients with moderate to severe plaque psoriasis through 68 weeks that was generally consistent with prior studies.
authors.affiliation: Jichi Medical University, Shimotsuke, Japan.
authors.forename: Mamitaro
authors.initials: M
authors.lastname: Ohtsuki
authors.affiliation: Tokyo Medical University, Tokyo, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Okubo
authors.affiliation: Jichi Medical University, Shimotsuke, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Komine
authors.affiliation: Fukuoka University, Fukuoka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Imafuku
authors.affiliation: Celgene Corporation, Summit, New Jersey, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Day
authors.affiliation: Celgene Corporation, Summit, New Jersey, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Celgene Corporation, Summit, New Jersey, USA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Petric
authors.affiliation: Celgene Corporation, Summit, New Jersey, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Maroli
authors.affiliation: Kojinkai Sapporo Skin Clinic, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nemoto
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan; D008297:Male; D008875:Middle Aged; D009304:Nasopharyngitis / Q000139:chemically induced / Q000453:epidemiology; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D058988:Phosphodiesterase 4 Inhibitors; D010919:Placebos; D013792:Thalidomide; C505730:apremilast
keywords: Psoriasis Area and Severity Index; apremilast; phosphodiesterase 4; phosphodiesterase 4 inhibitor; psoriasis