title: A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis.
abstract: BACKGROUND
  Little is known about the effect of specific anti-interleukin-23 therapy, as compared with established anti-tumor necrosis factor therapies, for the treatment of moderate-to-severe plaque psoriasis.
  
  
  METHODS
  In a 52-week, phase 2, dose-ranging, randomized, double-blind, placebo-controlled, active-comparator trial, we compared guselkumab (CNTO 1959), an anti-interleukin-23 monoclonal antibody, with adalimumab in patients with moderate-to-severe plaque psoriasis. A total of 293 patients were randomly assigned to receive guselkumab (5 mg at weeks 0 and 4 and every 12 weeks thereafter, 15 mg every 8 weeks, 50 mg at weeks 0 and 4 and every 12 weeks thereafter, 100 mg every 8 weeks, or 200 mg at weeks 0 and 4 and every 12 weeks thereafter) through week 40, placebo, or adalimumab (standard dosage for psoriasis). At week 16, patients in the placebo group crossed over to receive guselkumab at a dose of 100 mg every 8 weeks. The primary end point was the proportion of patients with a Physician's Global Assessment (PGA) score of 0 (indicating cleared psoriasis) or 1 (indicating minimal psoriasis) at week 16.
  
  
  RESULTS
  At week 16, the proportion of patients with a PGA score of 0 or 1 was significantly higher in each guselkumab group than in the placebo group: 34% in the 5-mg group, 61% in the 15-mg group, 79% in the 50-mg group, 86% in the 100-mg group, and 83% in the 200-mg group, as compared with 7% in the placebo group (P≤0.002 for all comparisons). Moreover, the proportion was significantly higher in the 50-mg, 100-mg, and 200-mg guselkumab groups than in the adalimumab group (58%) (P<0.05 for all comparisons). At week 16, the proportion of patients with at least a 75% improvement in Psoriasis Area and Severity Index scores was significantly higher in each guselkumab group than in the placebo group (P<0.001 for all comparisons). At week 40, the proportion of patients with a PGA score of 0 or 1 remained significantly higher in the 50-mg, 100-mg, and 200-mg guselkumab groups than in the adalimumab group (71%, 77%, and 81%, respectively, vs. 49%) (P<0.05 for all comparisons). Between week 0 and week 16, infections were observed in 20% of the patients in the guselkumab groups, 12% in the adalimumab group, and 14% in the placebo group.
  
  
  CONCLUSIONS
  The results of this phase 2 trial suggest that guselkumab may be an effective therapy for plaque psoriasis and that control of psoriasis can be achieved with specific anti-interleukin-23 therapy. (Funded by Janssen Research and Development; X-PLORE ClinicalTrials.gov number, NCT01483599.).
authors.affiliation: From the Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago (K.B.G.); the Department of Dermatology, University of Utah School of Medicine, Salt Lake City (K.C.D.); Innovaderm Research, Montreal (R.B.); the Department of Dermatology, Ludwig-Maximilians-Universität München, Munich (J.C.P.), and the Dermatologikum Hamburg, Hamburg (K.R.) - both in Germany; and Janssen Research and Development, Spring House (Y.W., S.L., Y.-K.S., P.S., B.R.), and the Department of Dermatology, University of Pennsylvania, Philadelphia (B.R.) - both in Pennsylvania.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Gordon
authors.forename: Kristina Callis
authors.initials: KC
authors.lastname: Duffin
authors.forename: Robert
authors.initials: R
authors.lastname: Bissonnette
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Prinz
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Wasfi
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Yaung-Kaung
authors.initials: YK
authors.lastname: Shen
authors.forename: Philippe
authors.initials: P
authors.lastname: Szapary
authors.forename: Bruce
authors.initials: B
authors.lastname: Randazzo
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D053759:Interleukin-23 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha; C000588857:guselkumab; D000068879:Adalimumab