A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis.

Abstract

BACKGROUND:

Skin-infiltrating lymphocytes expressing type 1 cytokines have been linked to the pathophysiology of psoriasis. We evaluated the safety and efficacy of a human interleukin-12/23 monoclonal antibody in treating psoriasis.

METHODS:

In this double-blind, placebo-controlled trial, 320 patients with moderate-to-severe plaque psoriasis underwent randomization to treatment with the interleukin-12/23 monoclonal antibody (one 45-mg dose, one 90-mg dose, four weekly 45-mg doses, or four weekly 90-mg doses) or placebo; 64 patients were randomly assigned to each group. Patients assigned to the interleukin-12/23 monoclonal antibody received one additional dose at week 16 if needed. Patients assigned to placebo crossed over to receive one 90-mg dose of interleukin-12/23 monoclonal antibody at week 20.

RESULTS:

There was at least 75% improvement in the psoriasis area-and-severity index at week 12 (the primary end point) in 52% of patients who received 45 mg of the interleukin-12/23 monoclonal antibody, in 59% of those who received 90 mg, in 67% of those who received four weekly 45-mg doses, and in 81% of those who received four weekly 90-mg doses, as compared with 2% of those who received placebo (P<0.001 for each comparison), and there was at least 90% improvement in 23%, 30%, 44%, and 52%, respectively, of patients who received the monoclonal antibody as compared with 2% of patients who received placebo (P<0.001 for each comparison). Adverse events occurred in 79% of patients treated with the interleukin-12/23 monoclonal antibody as compared with 72% of patients in the placebo group (P=0.19). Serious adverse events occurred in 4% of patients who received the monoclonal antibody and in 1% of those who received placebo (P=0.69).

CONCLUSIONS:

This study demonstrates the therapeutic efficacy of an interleukin-12/23 monoclonal antibody in psoriasis and provides further evidence of a role of the interleukin-12/23 p40 cytokines in the pathophysiology of psoriasis. Larger studies are needed to determine whether serious adverse events might limit the clinical usefulness of this new therapeutic target. (ClinicalTrials.gov number, NCT00320216 [ClinicalTrials.gov].).

• Authors: Gerald G Krueger, Richard G Langley, Craig Leonardi, Newman Yeilding, Cynthia Guzzo, Yuhua Wang, Lisa T Dooley, Mark Lebwohl, CNTO 1275 Psoriasis Study Group
• Journal: The New England journal of medicine (N Engl J Med) Vol. 356 Issue 6 Pg. 580-92 (Feb 08 2007) ISSN: 1533-4406 [Electronic] United States
• PMID: 17287478 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 Massachusetts Medical Society.

Chemical References

• Antibodies, Monoclonal
• Immunologic Factors
• Interleukin-23
• Interleukin-12

Topics

• Adult
• Antibodies, Monoclonal (administration & dosage, adverse effects, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Immunologic Factors (therapeutic use)
• Interleukin-12 (immunology)
• Interleukin-23 (immunology)
• Male
• Middle Aged
• Psoriasis (drug therapy, immunology)
• Treatment Outcome