Cardiovascular Events Similar Between Ustekinumab, Placebo

New Orleans—Patients taking ustekinumab for ≤3 years had similar rates of serious and nonserious cardiovascular (CV) events compared with a placebo group, according to a pooled analysis of phase 2 and 3 trials. Kenneth B. Gordon, MD, medical director at the NorthShore University Health System in Chicago, Illinois, the study’s lead author, presented the findings during a poster presentation at the AAD meeting. The poster was titled Effect of Ustekinumab on Cardiovascular Events: Results from Pooled Phase 2 & 3 Trials. Psoriasis, a chronic inflammatory skin disease, is the most common immune-mediated inflammatory condition in the United States and affects 2% to 3% of the world’s population. Some studies have shown that patients with psoriasis may be at increased risk for myocardial infarction, stroke, CV death, and mortality. However, Dr. Gordon said other studies have not indicated these risks exist. In this analysis, the authors were interested in determining the effect that ustekinumab has on atherosclerotic CV disease and the drug’s CV safety. Ustekinumab, a biologic agent, is a human monoclonal antibody approved by the US Food and Drug Administration to treat psoriasis. The researchers analyzed a phase 2 trial (C0379T04) as well as three phase 3 trials: PHOENIX 1 (a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of CNTO 1275 in the treatment of patients with moderate-to-severe plaque-type psoriasis followed by long-term extension), PHOENIX 2, and ACCEPT (Active Comparator [CNTO1275/ Enbrel] Psoriasis Trial). The CV adverse events included cerebrovascular events through week 12, which was the placebo-controlled period, the researchers said. The authors performed an analysis of 3117 patients in May 2009 that included 4782 patient-years of follow-up. The group had 1247 patients treated for ≥2 years, and the study had a median follow-up period of 1.7 years. The patients in the 4 trials had similar baseline demographic information. Risk factors for CV included that approximately 80% of patients were obese, approximately 60% had a history of smoking, approximately 25% had hypertension, approximately 15% had hyperlipidemia, and approximately 10% had diabetes. In an analysis of the phase 3 trials at baseline, the authors found that 58.6% of patients had ≥2 CV risk factors, and 28.8% had ≥3. They considered risk factors as males ≥45 years of age, females ≥66 years of age, diabetes, hypertension, fasting high-density lipoprotein cholesterol <40 mg/dL, current smoking, and family history of early coronary artery disease. Through 12 weeks, 4.5% of patients in the placebo group had ≥2 serious or nonserious CV events compared with 4.0% of the ustekinumab group. In addition, 0.1% of patients in the placebo group had a serious CV event compared with 0.4% in the ustekinumab group. Hypertension was the only adverse event occurring in ≥1.0% of both groups (1.5% for patients taking placebo and 1.3% for patients taking ustekinumab). The authors also evaluated major adverse cardiac events (MACEs) such as CV death, nonfatal myocardial infarction, and nonfatal stroke. During the placebo-controlled period, the MACE rate was 1.23 events per 100 patient-years. Through 3 years of follow-up, 21 patients treated with ustekinumab had a MACE. The authors indicated there was a difference in MACE between the groups during the placebo-controlled period of the phase 2 trial, but the difference did not exist in the phase 3 trials.