title: Treatment of psoriatic arthritis in a phase 3 randomised, placebo-controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor.
abstract: OBJECTIVE
  Apremilast, an oral phosphodiesterase 4 inhibitor, regulates inflammatory mediators. Psoriatic Arthritis Long-term Assessment of Clinical Efficacy 1 (PALACE 1) compared apremilast with placebo in patients with active psoriatic arthritis despite prior traditional disease-modifying antirheumatic drug (DMARD) and/or biologic therapy.
  
  
  METHODS
  In the 24-week, placebo-controlled phase of PALACE 1, patients (N=504) were randomised (1:1:1) to placebo, apremilast 20 mg twice a day (BID) or apremilast 30 mg BID. At week 16, patients without ≥20% reduction in swollen and tender joint counts were required to be re-randomised equally to either apremilast dose if initially randomised to placebo or remained on their initial apremilast dose. Patients on background concurrent DMARDs continued stable doses (methotrexate, leflunomide and/or sulfasalazine). Primary outcome was the proportion of patients achieving 20% improvement in modified American College of Rheumatology response criteria (ACR20) at week 16.
  
  
  RESULTS
  At week 16, significantly more apremilast 20 mg BID (31%) and 30 mg BID (40%) patients achieved ACR20 versus placebo (19%) (p<0.001). Significant improvements in key secondary measures (physical function, psoriasis) were evident with both apremilast doses versus placebo. Across outcome measures, the 30-mg group generally had higher and more consistent response rates, although statistical comparison was not conducted. The most common adverse events were gastrointestinal and generally occurred early, were self-limiting and infrequently led to discontinuation. No imbalance in major adverse cardiac events, serious or opportunistic infections, malignancies or laboratory abnormalities was observed.
  
  
  CONCLUSIONS
  Apremilast was effective in the treatment of psoriatic arthritis, improving signs and symptoms and physical function. Apremilast demonstrated an acceptable safety profile and was generally well tolerated.
  
  
  BACKGROUND
  NCT01172938.
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California at San Diego, , La Jolla, California, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: Adewale O
authors.initials: AO
authors.lastname: Adebajo
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wollenhaupt
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
authors.forename: Eric
authors.initials: E
authors.lastname: Lespessailles
authors.forename: Stephen
authors.initials: S
authors.lastname: Hall
authors.forename: Marla
authors.initials: M
authors.lastname: Hochfeld
authors.forename: ChiaChi
authors.initials: C
authors.lastname: Hu
authors.forename: Douglas
authors.initials: D
authors.lastname: Hough
authors.forename: Randall M
authors.initials: RM
authors.lastname: Stevens
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage*; D011565:Psoriasis / Q000188:drug therapy; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D058988:Phosphodiesterase 4 Inhibitors; D013792:Thalidomide; C505730:apremilast; D008727:Methotrexate
keywords: Psoriatic Arthritis; Spondyloarthritis; Treatment