The positive results have led to the initiation of two pivotal phase III trials: the multicenter ESTEEM 1 and ESTEEM 2 safety and efficacy studies comprising, respectively, 825 patients and 405 patients with moderate to severe plaque psoriasis. Primary outcome data from both studies will be available in the summer of 2011.
Topical Niacin/Calcipotriene
The nonsteroidal topical options for psoriasis will likely be expanded further by the addition of topical niacin (nicotinamide) to standard treatment with the synthetic vitamin D derivative calcipotriene, according to Dr. Gottlieb.
A recent 168-patient multicenter, double-blind, randomized trial reported that 50% of patients randomized to combination therapy with 0.005% calcipotriene and 1.4% nicotinamide achieved symptom clearance or near clearance, compared with 18.8% of patients randomized to placebo, 25% of patients treated with nicotinamide alone, and 31.5% of patients treated with calcipotriene alone.
The findings suggest that the combination therapy "may prove effective as an alternative therapeutic option to calcipotriene monotherapy and may provide an attractive option for patients seeking an effective corticosteroid-sparing topical psoriatic agent," the investigators wrote (J. Am. Acad. Dermatol. 2010;63:775-81).
In the midst of all of the new developments, it is important to note that tumor necrosis factor (TNF) antagonists continue to perform well, Dr. Leonardi stressed. "Given that the class is now 12 years old and includes 2 million patients, we are unlikely to learn of major safety risks at this point, and registry data support the notion that TNF blockade is cardioprotective in [rheumatoid arthritis], in distinction to the IL 12/23 blockers, where the MACE issue is unresolved," he said. "At this point, it is important for dermatologists to remember that the IL-12/23 drugs, in particular, are new, and since they are psoriasis specific, there are no other disease states where they were previously used."
Until the new drugs are in widespread use, "they should be used with caution," Dr. Leonardi continued. "The last psoriasis-specific biologic we used was Raptiva, which was voluntarily removed from the market by Genentech after 3 patients were identified with a rare and fatal central nervous system infection. At the time these patients were identified, the drug had been on the market for 5 years and had been used in 23,000 patients."
[Topical Tar Making a Comeback in Psoriasis]
What this means in clinical practice is that ustekinumab or briakinumab may be reasonable options for patients with a history of failure of TNF antagonists or a history of central or peripheral demyelination, but until longer-term safety data are available, it should not be the first choice in the majority of treatment-naive patients, said Dr. Leonardi.
Dr. Leonardi is a consultant, investigator, and/or on the speakers bureau of Amgen, Abbott, Celgene, Centocor, Genentech, Incyte, Novartis Pfizer, and several other pharmaceutical companies.
Dr. Gottlieb has current consulting/advisory board agreements with Abbott, Amgen, Celgene, Incyte, and numerous other pharmaceutical companies.