An Update on the Long-Term Safety Experience of Ustekinumab: Results From the Psoriasis Clinical Development Program With up to Four Years of Follow-Up

March 2012 | Volume 11 | Issue 3 | Original Article | 300 | Copyright © March 2012

Background: The efficacy and safety profile of ustekinumab with up to three years of exposure suggested a favorable benefit-risk profile in patients with moderate to severe psoriasis.
Objective: To evaluate the safety of ustekinumab in patients with moderate to severe psoriasis treated for up to four years.
Methods: Safety data were pooled across four Phase II/III randomized controlled trials. Rates over time and cumulative rates of adverse events (AEs), AEs leading to treatment discontinuation, serious adverse events (SAEs), serious infections, malignancies, and major adverse cardiovascular events (MACE) (i.e., cardiovascular death, myocardial infarction [MI], or stroke as adjudicated by an independent panel of academic cardiologists) were evaluated. Observed rates of AEs of interest were compared with those expected in the general (malignancies, MI, and stroke) and psoriasis (serious infections, MI, and stroke) populations.
Results: Overall, 3,117 patients were followed for up to four years (6,791 patient-years). Rates of AEs, AEs leading to treatment discontinuation, and SAEs remained stable over time, whereas cumulative rates were generally comparable between patients who received 45 mg and 90 mg of ustekinumab. The rates of AEs of interest also remained stable over time, and cumulative rates per 100 patient-years were 0.80 and 1.32 (serious infections), 0.70 and 0.53 (nonmelanoma skin cancer), 0.63 and 0.61 (other malignancies), and 0.56 and 0.46 (MACE) in patients treated with 45 mg and 90 mg, respectively. Rates of AEs of interest were consistent with those in the general and psoriasis populations.
Conclusion: The safety profile of long-term ustekinumab treatment with up to four years of continuous use remains consistent with previous reports, with no evidence of cumulative toxicity.

J Drugs Dermatol. 2012;11(3):300-312


Moderate to severe psoriasis, an immune-mediated disease with debilitating physical and psychological effects, often requires long-term therapy with systemic agents.1 Chronic therapy with conventional systemic agents may be limited by cumulative organ toxicity,2 thereby restricting their long-term usefulness. Cumulative end-organ toxicities have not been associated with biologic agents, making them potentially suitable for chronic use. However, the safety of long-term maintenance treatment with biologic agents for psoriasis is not yet fully understood and warrants additional study.3
Ustekinumab (Stelara®, Janssen Biotech, Inc., Malvern, PA) is a human monoclonal antibody with a novel mechanism that selectively targets the shared p40 subunit of interleukin (IL)-12 and IL-23 and, therefore, inhibits binding to their receptors.4 Data from four randomized trials (i.e., one placebo-controlled Phase II study, one comparator-controlled Phase III study [ACCEPT], and two pivotal Phase III studies [PHOENIX 1 and 2]),5-8 demonstrated that ustekinumab is highly efficacious, with a favorable benefit-risk profile for up to three years of treatment.9-12 When final data from the long-term extensions of the PHOENIX 1 and 2 trials become