Wirksamkeit und Sicherheit des humanen monoklonalen Interleukin-12/23-Antikörpers Ustekinumab bei Patienten mit Psoriasis: Ergebnisse der randomisierten, doppel-blinden, plazebokontrollierten Phase-III-Studien PHOENIX 1 und PHOENIX 2

Abstract

Interleukin-12 and Interleukin-23 play important roles in the pathophysiology of psoriasis. The human monoclonal antibody ustekinumab binds to the p40 subunit which is present in both cytokines thereby blocking the binding of the cytokines to their respective receptors. The two randomised, double-blind, placebo-controlled phase-III-trials PHOENIX 1 and PHOENIX 2 assessed the efficacy and safety of 45 mg and 90 mg s. c. ustekinumab in almost 2000 patients with moderate-to-severe psoriasis. Both studies had a placebo-controlled first part with ustekinumab injections at weeks 0 and 4. At week 12 67 % and 72 % of patients treated with ustekinumab 45 or 90 mg respectively achieved an at least 75 % improvement of their psoriasis area and severity index (PASI 75) compared to 4 % of patients treated with placebo. The reduction of skin symptoms was associated with a significant improvement of patients’ quality of life. At week 12 55 % and 71 % of patients receiving 45 mg and 90 mg of ustekinumab, respectively, reported a dermatology life quality index (DLQI) of ‘0’ or ‘1’ consistent with a high quality of life unaffected by psoriasis (placebo 4 %). The existing data of longterm ustekinumab therapy with injections every 12 weeks document maintenance of good clinical efficacy in the majority of patients for up to 76 weeks. Ustekinumab showed a favourable safety profile and good tolerability during induction and maintenance therapy. The frequency of adverse events, serious adverse events and adverse events leading to study termination were similar among patients treated with ustekinumab and those treated with placebo. These data suggest that ustekinumab is an effective and safe new option for the treatment of patients with moderate-to-severe psoriasis