title: Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial.
abstract: BACKGROUND
  Since some patients with psoriatic arthritis do not respond to typical drug treatments, alternatives are needed. Findings suggest that interleukins 12 and 23 might affect clinical symptoms and pathological joint changes of psoriatic arthritis. Ustekinumab is a human monoclonal antibody that inhibits receptor-binding of these cytokines. We aimed to assess the efficacy and safety of ustekinumab for psoriatic arthritis in this phase II study.
  
  
  METHODS
  We undertook a double-blind, randomised, placebo-controlled, crossover study at 24 sites in North America and Europe. Patients with active psoriatic arthritis were randomly allocated via interactive voice response system to either ustekinumab (90 mg or 63 mg) every week for 4 weeks (weeks 0-3) followed by placebo at weeks 12 and 16 (n=76; Group 1) or placebo (weeks 0-3) and ustekinumab (63 mg) at weeks 12 and 16 (n=70; Group 2). The first 12 weeks of the study were placebo-controlled. Masking was maintained to week 16, and patients were followed up to week 36 [corrected]. The primary endpoint was ACR20 response at week 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00267956.
  
  
  RESULTS
  At week 12, 32 (42%) patients in Group 1 and ten (14%) in Group 2 achieved the primary endpoint (difference 28% [95% CI 14.0-41.6]; p=0.0002). Of 124 (85%) participants with psoriasis affecting 3% or more body surface area, 33 of 63 (52%) in Group 1 and three of 55 (5%) in Group 2 had a 75% or greater improvement in psoriasis area and severity index score at week 12 (47% [33.2-60.6]; p<0.0001). During the placebo-controlled period (weeks 0-12), adverse events arose in 46 (61%) patients in Group 1 and 44 (63%) in Group 2; serious adverse events were recorded in three (4%) Group 2 patients (none in Group 1).
  
  
  CONCLUSIONS
  Ustekinumab significantly reduced signs and symptoms of psoriatic arthritis and diminished skin lesions compared with placebo, and the drug was well tolerated. Larger and longer term studies are needed to further characterise ustekinumab efficacy and safety for treatment of psoriatic arthritis.
authors.affiliation: Tufts Medical Center, Boston, MA, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Gottlieb
authors.forename: Alan
authors.initials: A
authors.lastname: Menter
authors.forename: Alan
authors.initials: A
authors.lastname: Mendelsohn
authors.forename: Yaung-Kaung
authors.initials: YK
authors.lastname: Shen
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Cynthia
authors.initials: C
authors.lastname: Guzzo
authors.forename: Scott
authors.initials: S
authors.lastname: Fretzin
authors.forename: Rod
authors.initials: R
authors.lastname: Kunynetz
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015535:Arthritis, Psoriatic / Q000145:classification / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D023381:Endpoint Determination / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069549:Ustekinumab