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: Kenneth B Gordon, Kristina Callis Duffin, Robert Bissonnette, Jörg C Prinz, Yasmine Wasfi, Shu Li, Yaung-Kaung Shen, Philippe Szapary, Bruce Randazzo, Kristian Reich
• Journal: The New England journal of medicine (N Engl J Med) Vol. 373 Issue 2 Pg. 136-44 (Jul 09 2015) ISSN: 1533-4406 [Electronic] United States
• PMID: 26154787 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Interleukin-23
• Tumor Necrosis Factor-alpha
• guselkumab
• Adalimumab

Topics

• Adalimumab
• Adult
• Anti-Inflammatory Agents (administration & dosage, adverse effects)
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Injections, Subcutaneous
• Interleukin-23 (antagonists & inhibitors)
• Male
• Middle Aged
• Psoriasis (drug therapy, pathology)
• Severity of Illness Index
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)