GOTHENBURG, SWEDEN – Long-term risks of malignancies, serious infections, and cardiovascular events in ustekinumab-treated psoriasis patients was found to be what is expected in the general U.S. population, according to a 3-year safety analysis of the major randomized clinical trials of the biologic agent.
Placebo-treated control groups were utilized during the first 12 weeks of the phase III PHOENIX I and II trials and not at all in the phase III Active Comparator Psoriasis Trial (ACCEPT). For the safety analysis based on 3 years of follow-up – for purposes of comparison – risk estimates for the general U.S. population were derived from the National Institute of Health’s Surveillance, Epidemiology and End Results (SEER) database and MarketScan Research Data, Dr. Kenneth B. Gordon explained at the annual congress of the European Academy of Dermatology and Venereology.
The 3-year safety analysis included 3,117 psoriasis patients treated with ustekinumab (Stelara) at 45 mg or 90 mg per dose based on body weight, in accordance with the product labeling. Among this group were 1,247 patients who received the interleukin-12 and -23 inhibitor for at least 2 years, noted Dr. Gordon, a dermatologist at the University of Chicago.
The cumulative incidence of nonmelanoma skin cancer through year 3 in the 3,117 psoriasis patients was 0.64 cases per 100 patient-years in patients on ustekinumab 45 mg and 0.77 per 100 patient-years in those on ustekinumab 90 mg. During the 12-week controlled period of the studies, the incidence in placebo-treated patients was 1.13 cases per 100 patient-years.
Rates of other malignancies, including melanoma and lymphoma, through 3 years were 0.69 and 0.46 cases per 100 patient-years in patients on ustekinumab 45 and 90 mg, respectively. These rates were consistent with those expected in the U.S. general population based upon SEER data. Rates of malignancies other than nonmelanoma skin cancer were also comparable to those reported in a large population of psoriasis patients treated with systemic agents in the U.K. General Practice Research Database, where the incidence was 0.58 cases per 100 patient-years (J. Invest. Dermatol. 2009;129:2604-12).
The rate of serious infections through 3 years was 0.82 per 100 patient-years in psoriasis patients on ustekinumab 45 mg and 1.5 per 100 patient-years in those on the higher dose, for a combined event rate of 1.19 per 100 patient-years. This compared favorably to the expected rate of 1.51 per 100 patient-years in psoriasis patients with nonbiologic systemic agents derived from the MarketScan database, Dr. Gordon said.
The combined rate of cardiovascular death, MI, or stroke through 3 years in ustekinumab-treated psoriasis patients was 0.41 per 100 patient-years in those on the lower dose and 0.35 per 100 patient-years in those receiving 90 mg. These rates were lower, albeit not significantly so, than rates expected in the general population using data from the Framingham Heart Study and in psoriasis patients using the U.K. General Practice Research Database.
Rates of malignancies, serious infections, and cardiovascular events in ustekinumab-treated patients remained stable over time without any indication of cumulative toxicity. Another safety analysis is planned when participants in the phase III trials reach the 5-year follow-up mark.
The study was funded by Centocor. Dr. Gordon disclosed that he serves as a consultant to the company.