A Phase 2 Trial of Guselkumab versus Adalimumab for Plaque Psoriasis

作者：Gordon, Kenneth B.; Duffin, Kristina Callis; Bissonnette, Robert; Prinz, Joerg C.; Wasfi, Yasmine; Li, Shu; Shen, Yaung-Kaung; Szapary, Philippe; Randazzo, Bruce; Reich, Kristian^*

来源：New England Journal of Medicine, 2015, 373(2): 136-144.

DOI：10.1056/NEJMoa1501646

• TO-SEVERE PSORIASIS
• INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY
• LONG-TERM EFFICACY
• DOUBLE-BLIND
• FOLLOW-UP
• USTEKINUMAB
• MODERATE
• SAFETY
• THERAPY
• CELLS

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.

• 出版日期2015-7-9
• 单位西北大学