(San Francisco, CA) - Tumor-necrosis factor-a (TNF-a) inhibitors marketed for use in rheumatoid arthritis have shown promise in the treatment of psoriatic arthritis, and have now shown a benefit in patients who have the skin disorder psoriasis without any arthritis symptoms. New data from the second phase of the clinical trials in psoriasis with infliximab (Remicade, Centocor) and etanercept (Enbrel, Amgen) were reported at the American Academy of Dermatology meeting.

The trials were conducted in patients with moderate to severe psoriasis, who constitute about one third of the total psoriasis patient population. Until recently, this patient population has not been well served with therapies. Earlier this year, alefacept (Amevive, Biogen) was the first biologic drug for psoriasis, and another biologic specifically developed for use in psoriasis, efalizumab (Raptiva, Genentech, Xoma, Sereno), is awaiting approval in both Europe and the U.S.

From the results reported so far, the responses in patients with TNF-a inhibitors appears to be a little better than those reported for the new biological therapies specifically developed for psoriasis. Among results previously reported, alefacept reduced symptoms by at least 75% in 21% of patients after three months therapy, while efalizumab had that effect in 29% of patients after three months.

Dr. Kenneth Gordon (Loyola University, Chicago, IL) reported that after 10 weeks of infliximab therapy, 88% of the patients with psoriasis on the highest dose (5 mg/kg) and 72% of the patients on the lower dose (3 mg/kg) achieved at least a 75% improvement in their symptoms.

With etanercept, at least a 75% improvement in symptoms was seen in 49% of patients on the higher dose (50 mg twice weekly) and in 34% patients on the lower dose (25 mg twice weekly, the dose commonly used in rheumatoid arthritis) after three months of therapy. These responses rose to nearly 60% and 44% after six months of treatment, noted Dr. Alice Gottlieb from the Robert Wood Johnson School, New Brunswick, NJ.

In Dr. Gerald Kruger's (dermatologist, Salt Lake City, UT) opinion, the new biologic therapies have shown to dramatically improve psoriasis, and they are revolutionizing its treatment. "Much as when antibiotics and topical steroids were introduced to treat skin diseases, these biologics may become the treatment of choice, especially for patients in whom current therapies are no longer effective or cause unacceptable side effects," he said. He notes that the biologic drugs are expensive and may prohibit some patients from receiving the medications, Dr. Krueger believes that "these treatments are a positive step forward in treating this skin disease because they maintain long-term remission while improving the patients' quality of life."

Dr. Kruger explains that psoriasis originates in the immune system and there are many current therapies that target the immune system. But the TNF-a medications target only the specific immune responses that are involved, not the entire immune system, thereby creating fewer side effects for the patient and less damage to the immune system as a whole.

In psoriasis, T-cell activation is thought to be the key immune system trigger, and the T-cells then release cytokines (among which is TNF-a) that provoke the skin cells to reproduce and mature at an accelerated rated. The biologic Alefacept works by destroying the activated T-cells that in turn stops the early cycle of psoriasis, while efalizumab interferes with the migration of T-cells to the skin and their activation in tissue. Infliximab and etanercept both work by inhibiting TNF-a, one of the main cytokines released by activated T-cells. A third TNF-a inhibitor, adalimumab (Humira, Abbott) recently launched for rheumatoid arthritis, is also being investigated for psoriasis and psoriatic arthritis.