A Human Interleukin-12/23 Monoclonal Antibody for the Treatment of Psoriasis

TLDR

Skin‑infiltrating lymphocytes expressing type‑1 cytokines are linked to psoriasis pathophysiology. The study aimed to evaluate the safety and efficacy of a human interleukin‑12/23 monoclonal antibody for psoriasis and to determine whether larger trials are needed to assess serious adverse events. In a double‑blind, placebo‑controlled trial of 320 patients, participants were randomized to single or multiple doses of the IL‑12/23 monoclonal antibody or placebo, with an optional week‑16 dose for the antibody groups and a week‑20 crossover for placebo recipients. The antibody produced dose‑dependent PASI responses, with 81% of patients receiving four weekly 90‑mg doses achieving ≥75% improvement versus 2% of placebo, and serious adverse events were low and similar between groups (4% vs 1%). ClinicalTrials.gov identifier: NCT00320216.

Abstract

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.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.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).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]. ).