HOUSTON, June 18 -- Psoriasis patients who had extended exposure to high-dose etanercept (Enbrel) responded well without increased infections or other serious adverse effects, researchers here reported.
Exposure-adjusted event rates for serious noninfectious adverse events and infection rates for up to 96 weeks of etanercept treatment were similar to those for placebo, reported Stephen Tyring, M.D., Ph.D., of the University of Texas here, and colleagues, in the June issue of the Archives of Dermatology.
In a phase III, randomized, double-blind trial with an open-label extension, 618 adults with moderate to severe plaque psoriasis were studied at 39 centers in the U.S. and Canada from May 23, 2003 through June 22, 2005.
Three hundred and seven patients were randomized to placebo treatment for the first 12 weeks, and 311 were given twice-weekly subcutaneous injections of 50 mg of etanercept.
Beginning with week 13, all patients, 591 at that point, were given etanercept. During the open-label part of the study, assessments were done every 12 weeks. Patients given etanercept from the start took the drug for up to 96 weeks.
Of the total patient population, 67.6% were men, 89.2% were white, and the mean age was 45.7. On average, the duration of psoriasis was 19.9 years, with 27.2% of the body surface affected.
There were antibodies to etanercept, determined to be non-neutralizing, in 18.3% of patients, but they had no apparent effect on safety or efficacy, the researchers reported.
Patients responded within two weeks to etanercept, with statistically significant differences between the treated and placebo groups at week 12 in the Psoriasis Area and Severity Index, the researchers reported.
However, at week 24, after 12 weeks of open-label etanercept treatment, the patients in the original placebo group caught up to the etanercept patients with comparable clinical benefits, the researchers reported.
After 96 weeks of therapy, 51.1 % of the original etanercept-treated patients and 51.6% of those given placebo for the first 12 weeks had improvements from baseline of at least 75%.
The exposure-adjusted event rates of noninfectious adverse events for placebo and etanercept exposures were 418.8 and 158.0 per 100 patient-years, respectively.
The rates for serious noninfectious events per 100 patient-years were 6.1 for placebo exposure and 7.7 for etanercept patients.
The most frequently observed noninfectious adverse events per 100 patient-years for placebo and etanercept included headache (36.4 versus 9.2 events), injection-site hemorrhage (24.3 versus 5.8). arthralgia (19.7 versus 4.8), and back pain (4.6 versus 5.2).
The most common serious noninfectious adverse events reported for etanercept treatment were myocardial infarction, basal cell carcinoma, and depression. None of these was reported after placebo exposure.
The exposure-adjusted event rates for serious infections were similar for the placebo and etanercept treated patients (1.5 and 1.2 events per 100 patient-years), the researchers reported.
Serious events, such as gangrene, viral meningitis, diverticulitis, infectious enteritis, gastroenteritis, and localized staphylococcal infection were each reported in one patient. However, viral meningitis was the only serious infections considered possibly related to the drug, the researchers said.
Extended exposure to etanercept was generally well tolerated. However, interpretation of the safety data was limited by the open-label nature of the study and the fact that the total number of exposure years for placebo was much lower than that for etanercept, the researchers noted.
Exposure-adjusted rates of noninfectious and infectious adverse events were similar for the two drug-treated groups at week 12 and 96, indicating that extended exposure to etanercept did not increase the drug's toxicity. In addition, the researchers said, the safety profile observed in this study is consistent with results previously reported for the lower dose of twice weekly 25 mg.
Although loss of efficacy during long-term therapy was observed in a small subset, most patients maintained their high response for up to 96 weeks. This loss may have been due to a variety of reasons, the researchers said, including non-compliance with taking the drug, from weeks 48 to 96, inherent limitations in the assessments of the psoriasis-severity scores, and psoriaisis-specific factors that decrease TNF dependency of the disease in patients with TNF antagonists, the researchers said.
"This study represents, to our knowledge, the longest continuous exposure of patients with psoriasis to 50 mg of etanercept twice weekly and provides further insights into the safety and efficacy of high-dose etanercept therapy for the management of moderate to severe psoriasis," Dr. Tyring and his colleagues concluded.
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