Extending Higher Dosage of Etanercept Found Safe : Some prescribers may keep patients on a regimen in order to maintain insurance coverage of the drug.

CHICAGO — Maintaining patients with moderate to severe psoriasis on a higher than recommended dose of etanercept is safe, according to new long-term multicenter phase III data.

Although the recommended dosing in the United States is for 3 months of 50 mg etanercept twice weekly, followed by a reduction to a maintenance dose of 50 mg per week, the current analysis evaluated 50 mg twice weekly through 48 weeks.

The study reflects the off-label use of etanercept (Enbrel) at the higher dose to tackle new lesions that develop in about half of patients and to maintain continuous insurance coverage.

“The most difficult thing is to justify to the insurance company that you need to put a patient back on 100 mg a week,” lead author Stephen Tyring, M.D., told this newspaper. “They won't pay for the 100 mg beyond the 3 months if you reduce it. If you just keep them on 100 mg, often they don't notice.”

This scenario has left physicians facing the most important question, which is whether the higher extended dosing is safe.

The safety is definitely indistinguishable from placebo, and there were twice as many patients as controls, said Dr. Tyring, who presented the data in a poster at the American Academy of Dermatology's Academy 2005 meeting.

The study randomized 307 patients to placebo and 311 patients to etanercept 50 mg twice weekly for 12 weeks.

A total of 599 patients continued in the ongoing open-label phase of the study in which patients continued on treatment or were switched from placebo to etanercept 50 mg twice weekly.

Analysis through week 48 showed there were no deaths and no cases of opportunistic infections, tuberculosis, demyelinating diseases, hematologic events, or congestive heart failure.

Dr. Tyring and colleagues at the University of Texas, Houston, perform chest x-rays and purified protein derivative TB skin tests as standard of care. But not all sites screened for TB, nor did they perform MRIs.

There have not been enough cases of multiple sclerosis in psoriasis patients using biologic therapies to determine if there is a cause-and-effect relationship or if it is just background, Dr. Tyring said.

For the time being, he does not treat psoriasis patients with etanercept if they have multiple sclerosis or if they have close family members who have multiple sclerosis.

There was one case of lymphoma in the study. Dr. Tyring said it was probably background, and noted that some studies put the risk of lymphoma in psoriasis patients as at least twice that of healthy controls.

In the double-blind period, nine patients discontinued because of an adverse event; 13 additional patients have since discontinued because of an adverse event.

Finally, the data showed that there was no diminished treatment effect from baseline, which has been a problem with some psoriasis treatments.

At week 48, dermatologists accessed about 55% of patients as clear or almost clear, whereas 65% of patients made the same assessment.

The study was funded by Immunex Corp., a subsidiary of Wyeth Research and Amgen Inc., which markets etanercept.

Dr. Tyring did not disclose any financial relationship to any of the three companies.