title: Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2).
abstract: BACKGROUND
  Ustekinumab, a human monoclonal antibody against interleukins 12 and 23, has shown therapeutic potential for psoriasis. This study assessed the efficacy and safety of ustekinumab in psoriasis patients and assessed dosing intensification in partial responders.
  
  
  METHODS
  In this multicentre, phase III, double-blind, placebo-controlled study, 1230 patients with moderate-to-severe psoriasis (defined by a psoriasis area and severity index [PASI] score > or =12, and at least 10% total body surface area involvement) were randomly assigned to receive ustekinumab 45 mg (n=409) or 90 mg (n=411) at weeks 0 and 4, then every 12 weeks, or placebo (n=410). Partial responders (ie, patients achieving > or =50% but <75% improvement from baseline in PASI) were re-randomised at week 28 to continue dosing every 12 weeks or escalate to dosing every 8 weeks. Both randomisations were done with a minimisation method via a centralised interactive voice response. The primary endpoint was the proportion of patients achieving at least 75% improvement in PASI (PASI 75) at week 12. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00307437.
  
  
  RESULTS
  All randomised patients were included in the efficacy analysis. 273 (66.7%) patients receiving ustekinumab 45 mg, 311 (75.7%) receiving ustekinumab 90 mg, and 15 (3.7%) receiving placebo achieved the primary endpoint (difference in response rate 63.1%, 95% CI 58.2-68.0, p<0.0001 for the 45 mg group vs placebo and 72.0%, 67.5-76.5, p<0.0001 for the 90 mg group vs placebo). More partial responders at week 28 who received ustekinumab 90 mg every 8 weeks achieved PASI 75 at week 52 than did those who continued to receive the same dose every 12 weeks (22 [68.8%] vs 11 [33.3%]; difference in response rate 35.4%, 95% CI 12.7-58.1, p=0.004). There was no such response to changes in dosing intensity in partial responders treated with ustekinumab 45 mg. During the placebo-controlled phase, 217 (53.1%) patients in the 45 mg group, 197 (47.9%) in the 90 mg group, and 204 (49.8%) in the placebo group experienced adverse events; serious adverse events were seen in eight (2.0%) patients in the 45 mg group, five (1.2%) in the 90 mg group, and eight (2.0%) in the placebo group.
  
  
  CONCLUSIONS
  Although treatment with ustekinumab every 12 weeks is effective for most patients with moderate-to-severe psoriasis, intensification of dosing to once every 8 weeks with ustekinumab 90 mg might be necessary to elicit a full response in patients who only partially respond to the initial regimen.
authors.affiliation: Probity Medical Research, Waterloo and University of Western Ontario, London, ON, Canada. kapapp@probitymedical.com
authors.forename: Kim A
authors.initials: KA
authors.lastname: Papp
authors.forename: Richard G
authors.initials: RG
authors.lastname: Langley
authors.forename: Mark
authors.initials: M
authors.lastname: Lebwohl
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Krueger
authors.forename: Philippe
authors.initials: P
authors.lastname: Szapary
authors.forename: Newman
authors.initials: N
authors.lastname: Yeilding
authors.forename: Cynthia
authors.initials: C
authors.lastname: Guzzo
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Hsu
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Dooley
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D007641:Keratolytic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000145:classification / Q000188:drug therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D053759:Interleukin-23; D007641:Keratolytic Agents; D018664:Interleukin-12