SAN ANTONIO—Biologics that block inflammatory cytokine activity, inhibit T-cell activation, reduce pathogenic T-cells, or shift a TH1 immune response toward a greater TH2-type response offer new strategies for bringing psoriasis under control, according to Jeffrey M. Weinberg, MD. Assistant clinical professor of medicine at Columbia University College of Physicians and Surgeons in New York City, Dr. Weinberg presented an overview of these advances at the American Academy of Dermatology 66th annual meeting.¹

"These therapies offer successful therapy of psoriasis, with a lack of organ toxicity seen with traditional systemic therapies such as methotrexate and cyclosporine," Dr. Weinberg said. "Limitations of the current data include the lack of direct head-to-head comparisons with traditional agents and the absence of pharmacoeconomic evaluations of these agents, especially given the expected high costs of treatment."

Dr. Weinberg also pointed out that psoriasis patients taking these agents necessitate long-term monitoring because of the associated potential risk for infection or malignancy.

Cooling inflammatory cytokines

Infliximab (Remicade®), etanercept (Enbrel®), and adalimumab (Humira®) are all effective in severe plaque psoriasis, Dr. Weinberg said. Infliximab is approved for Crohn's disease, psoriasis, psoriatic arthritis, and rheumatoid arthritis. Etanercept is approved for rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, psoriasis, and psoriatic arthritis. Adalimumab is approved for psoriatic arthritis and has completed phase III clinical trials for treatment of psoriasis, Dr. Weinberg noted. All three drugs have notably efficacy in psoriasis, with most studies showing dramatic improvements in symptoms and quality of life.

"The TNF inhibitors share a number of common safety issue and concerns. These include infection, risk of lymphoma, demyelinating disease, heart failure, and drug-induced lupus," Dr. Weinberg continued. However, he noted that the main infection concern is reactivation of latent tuberculosis and that increased risk of serious infection has not been observed in most studies. Demyelinating disease, heart failure, and drug-induced lupus are rare occurrences, but Dr. Weinberg warned that etanercept, infliximab, and adalimumab should be avoided in patients with a history of any central nervous system demyelinating disorder, and that these drugs should be used "with caution" in patients with a family history of these disorders.

Inhibiting T-cell activation

Efalizumab (Raptiva®) blocks T-cell adhesion, which interferes with T-cell activation, with migration into skin, and with cytotoxic T-cell function. "Recently, a phase III trial with subcutaneous efalizumab showed promising results in treatment of moderate-to-severe plaque psoriasis," Dr. Weinberg said. Efalizumab does not deplete T-cells, and the blockade it produces is reversible.

However, concerns remain about rebound of disease (defined as a worsening of psoriasis to 125% of the baseline or as the appearance of psoriasis variants such as erythrodermic or pustular psoriasis) after discontinuation of therapy.

Reducing pathogenic T-cells

Alefacept binds to CD2 on memory-effector T-cells (which infiltrate psoriatic plaques), inhibits their activation, and reduces their numbers. Dr. Weinberg said that clinical trials have shown that psoriasis patients treated with alefacept have reduced numbers of CD45RO+ memory T-cells, and that this reduction correlates with improvement in psoriasis.

"To date, no clinically significant signs of immunosuppression or opportunistic infections have been observed, and no increase in malignancy has been observed. In the United States, weekly monitoring of T-cells is recommended in patients treated with alefacept," Dr. Weinberg said.

He concluded, "Biologic therapy research continues to make great strides in the treatment of psoriasis. With continued progress at this rate, it is possible that one or more of these pharmacologic agents will become major therapeutic options for psoriasis."


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