LAS VEGAS – Cardiovascular event rates in patients treated with ustekinumab have been found to remain stable over time, according to 5-year follow-up data from the manufacturer.
"The overall safety profile of ustekinumab [Stelara] remained stable in adults with moderate to severe plaque psoriasis receiving up to 5 years of ustekinumab treatment," noted the manufacturer of Stelara, Janssen Pharmaceuticals, in a statement. "There was no dose-response or cumulative effect of increasing duration of exposure to ustekinumab on the rates of overall and targeted adverse events after up to 5 years of treatment."
Craig Leonardi
The cardiovascular safety of the plaque psoriasis treatment has been a concern because early testing detected a slightly higher incidence of events in patients treated with ustekinumab, compared with placebo.
But among 3,117 patients – 838 of whom were on the biologic for 5 years – and after a cumulative total of 8,998 patient-years, the rate of major adverse cardiovascular events (MACEs) held largely steady at 0.47 per 100 patient-years at year 1, 0.44 at year 5, and comparable numbers in between. The data were pooled from one phase II and three phase III trials, with MACE defined as stroke, myocardial infarction, or cardiovascular death.
The MACE rate at 5-year follow-up was 0.56 per 100 patient-years (95% confidence interval, 0.35-0.85) among patients receiving the 45-mg dose of the injectable and 0.36 per 100 patient-years (95% CI, 0.22-0.57) in patients receiving 90 mg.
In comparable 4-year follow-up data, researchers found that MACE and other serious adverse event rates among ustekinumab users "were consistent with those in the general and psoriasis populations" (J. Drugs Dermatol. 2012;11:300-12).
"The cardiovascular events over time seem to be stable," said Dr. Craig Leonardi, of the dermatology department at St. Louis University, who summarized the 5-year findings during a talk about the drug.
Even so, Dr. Leonardi, who presented the study results at a seminar sponsored by Skin Disease Education Foundation (SDEF), said that he remains concerned, noting that follow-up studies select for patients who do well on a drug and have minimal adverse events.
It’s possible that patients susceptible to MACEs – those with preexisting cardiac risk factors or, perhaps, an as-yet unrecognized genetic predisposition – dropped out early due to angina or other problems.
Dr. Leonardi also noted a recent meta-analysis that found a higher risk of MACEs in patients treated with ustekinumab or briakinumab – another interleukin-12/23 antibody no longer under development – compared with those on placebo (J. Eur. Acad. Dermatol. Venereol. 2012 March 8 [doi: 10.1111/j.1468-3083.2012.04500]).
It followed an earlier meta-analysis, conducted by Dr. Leonardi and his colleagues, of 22 trials that found 10 MACEs among 3,179 patients on ustekinumab or briakinumab but none among 1,474 placebo patients (JAMA 2011;306:864-71). Even though the results were not statistically significant, "there was a trend, and we are concerned about it. It seems to correspond to peak levels of the drug. We are awaiting further analysis," Dr. Leonardi said.
There’s "no question [ustekinumab] is a high-performance drug with a durable response," but in the meantime, "I am putting all my ustekinumab patients on aspirin, 81 mg/day," he said.
Patients with multiple cardiovascular risk factors should start with a tumor necrosis factor antagonist instead, according to Dr. Leonardi. "These are drugs with proven cardiovascular friendliness," he added. It is also probably wise to start out with the lower 45-mg dose of ustekinumab when initiating treatment.
Dr. Leonardi is a consultant, investigator, and speaker for Abbott, Amgen, and other companies. SDEF and this news organization are owned by Frontline Medical Communications.