Ustekinumab (Stelara): First-in-class human monoclonal antibody approved for treatment of moderate-to-severe plaque psoriasis

November 1, 2009

New biologic: Ustekinumab (Stelara) was approved on September 25, 2009, for the treatment of adult patients aged 18 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Ustekinumab is a human interleukin (IL)-12 and IL-23 antagonist. Ustekinumab was approved on September 25, 2009, for the treatment of adult patients aged 18 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. Ustekinumab is administered as a subcutaneous injection given at weeks 0 and 4, followed by every-12-week or quarterly dosing.

Efficacy. The clinical development program for ustekinumab included more than 2,200 patients, with two pivotal phase 3 trials serving as the primary basis for FDA approval. The trials showed that the majority of patients with moderate to severe plaque psoriasis who received ustekinumab sustained, clinically significant improvement in their disease severity. At week 12, the primary endpoint of both studies, at least two thirds of patients who received just two doses of ustekinumab, 45 mg or 90 mg, respectively, at weeks 0 and 4, achieved 75% improvement on the Psoriasis Activity and Severity Index (PASI), compared with 3% to 4% of patients receiving placebo (P<.001). An additional phase 3 study evaluated the safety and efficacy of ustekinumab compared with etanercept in 903 patients with plaque psoriasis (etanercept=347, ustekinumab 45 mg=209, ustekinumab 90 mg=347). Patients were randomly assigned to receive ustekinumab 45 mg or 90 mg doses at weeks 0 and 4, while the etanercept group received twice-weekly doses of 50 mg over 12 weeks. The primary endpoint of the study was the proportion of patients who achieved a PASI at week 12. Study results showed that 68% and 74% of patients receiving ustekinumab 45 mg or ustekinumab 90 mg, respectively, at weeks 0 and 4 achieved PASI 75 compared with 57% of patients receiving twice-weekly doses of etanercept 50 mg over 12 weeks (P=.012 for ustekinumab 45 mg; P<.001 for ustekinumab 90 mg each, each compared with etanercept).

Safety. Ustekinumab should not be given to patients with any clinically important active infection. Ustekinumab is an immunosuppressant and may heighten the risk for serious infections and malignancy. Patients should be evaluated for tuberculosis infection prior to initiating treatment with ustekinumab.