Adverse effects were dose-dependent. Adverse events that occurred in 5% or more of patients included headache, nausea, diarrhea, and upper respiratory tract infections. These typically occurred early in the course of treatment.
Serious adverse events included one myocardial infarction and one case of prostate cancer in the 30-mg BID group. But there was also a prostate cancer and a sudden death among the placebo recipients. "We really don’t have enough patients to look at adverse effects," Dr. Gordon said.
• Tofacitinib: This oral Janus kinase inhibitor demonstrated dose-dependent efficacy, with 67% of patients randomized at 15 mg twice a day achieving PASI 75 and "clear" or "almost clear." The phase II, 12-week, double-blind, placebo-controlled trial enrolled 197 patients with moderate to severe plaque psoriasis.
Concomitant overall decreases in hemoglobin and neutrophil counts from baseline were also dose-dependent. The finding did not specify the proportion of patients who had the decreases or the individual degree of change. "If everyone had a small change, it’s not going to bother me too much. But, if 10% of patients had a big change, it’s a really important finding. Those are the questions we need to ask," Dr. Gordon said.
Dr. Gordon said that so far the phase II safety data for the agents are encouraging, but enthusiasm should still be tempered. "When multiple drugs with the same mechanism have [similar] results, you start to feel more confident. But still, we need to see larger studies."
"It’s really an exciting time for new psoriatic therapies based on a better understanding of psoriasis pathophysiology."
Dr. Leonardi’s presentation focused on anti-IL 12/23 inhibitor treatment; he noted that the recently-approved monoclonal antibody ustekinumab binds to the same shared p40 subunit of IL-12 and IL-23 as briakinumab, the agent that was withdrawn from development in phase III. "There are more similarities than differences" between the two agents, he commented.
He and his colleagues recently conducted a meta-analysis of 22 randomized controlled clinical trials of biologic therapies comprising 10,183 patients with chronic plaque psoriasis, in which 10 of 3,179 patients receiving either ustekinumab or briakinumab experienced a MACE, compared with 0 events in 1,474 patients receiving placebo, for a MACE rate of 1.33 per 100 patient-years.
In contrast, no difference was seen among patients in the anti-TNF-alpha trials, with only 1 of 3,858 patients receiving anti-TNF-alpha agents experiencing a MACE, compared with 1 of 1,812 patients receiving placebo (JAMA 2011;306:864-71).
Although the difference for the anti-IL 12/23 agents was not statistically significant, the data set was not large enough to detect rare events. "This is a class effect in my mind," Dr. Leonardi said, adding that he uses ustekinumab as a second-line agent, after the TNF antagonists.
"It’s important to remember that all new drugs are ‘new’ ... We will learn more and more about these drugs as time goes on," he said.
Dr. Gordon disclosed that he has received research support or honoraria as a consultant from Abbott, Amgen, Centocor, Eli Lilly, Merck, Novartis, and Pfizer. Dr. Leonardi disclosed that he has had financial relationships with 23 companies that are involved in psoriasis treatment development, including Abbott and Centocor.
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