New biologic therapeutics for psoriasis management

British Columbia - A plethora of new agents are available to treat psoriasis. The new generation of therapies includes the biologics that appear to be effective and have an acceptable safety profile, according to Aditya K. Gupta, M.D., Ph.D., F.R.C.P.C., of the division of dermatology, department of medicine at University of Toronto, Canada.

"New research into possible treatment options has been inspired by advances in our understanding of the pathophysiology of psoriasis and the implication of immunological events in its pathogenesis," Dr. Gupta explained at the Canadian Dermatology Association meeting. "This has resulted in the development of drugs that target the cells responsible for the inflammatory nature of psoriasis, such as T-lymphocytes and cytokines."

BiologicsBiologic therapeutics are primarily fusion proteins, cytokines, fusion toxins or antibodies. These immunotherapeutic approaches either target T-cells or modulate cytokines.

The biologics can be categorized by their method of action: mechanism 1 (inhibition/elimination of activated T-cells); mechanism 2 (inhibition of T-cell activation); mechanism 3 (induction of immune deviation); and mechanism 4 (inhibition of cytokines).

"Efalizumab (Raptiva, Genentech), etanercept (Enbrel, Amgen/Wyeth), alefacept (Amevive, Biogen), and infliximab (Remicade, Centocor) are the biologics furthest along in clinical testing for moderate to severe psoriasis," Dr. Gupta reports.

Alefacept, efalizumab and etanercept have been approved for use in plaque psoriasis in the United States and are currently being tested in Canada. Infliximab is in phase 3 testing in both the United States and Canada, and is currently only approved for rheumatoid arthritis and active Crohn's disease in the United States.

ConsiderationsRecombinant DNA technology allows the molecules to be humanized, thereby reducing the potential for immune responses against the biologic medications.

Also, these systemic biologics are administered by injection and infusion.

"Frequently, patients using alefacept, efalizumab or etanercept can be taught to self-inject, which increases the convenience of the therapy to the patient," Dr. Gupta says, adding that injections may be less time-consuming and more effective than a topical agent for some cases of psoriasis. He points out that while injections may be associated with more adverse events, safety of the biologic regimens has been good, overall.

Infliximab is administered as a two-hour infusion, which may not be as convenient as an injection. However, its efficacy and improvement of quality of life make it a potentially useful alternative to conventional therapies, notes Dr. Gupta.

Dr. Gupta recommends that physicians look at the clinical trial activity profiles of the biologics when selecting one over another.

For example, in a patient with acute erythrodermic psoriasis, infliximab may be a consideration. Also, patients on alefacept therapy may have longer remissions compared to some other agents.

Top fourAlefacept is a dimeric fusion protein. The CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) is linked to human IgG1. The biologic binds lymphocyte antigen CD2 preventing activation of T-cells (mechanism 1) and reducing CD2+ T-cell count (mechanism 2). Administration is 7.5 mg once weekly as an IV bolus, or 15 mg once weekly as an IM injection, for 12 weeks.

Efalizumab is a recombinant humanized monoclonal antibody IgG1-kappa, which binds human CD11a. Efalizumab inhibits stimulation of T-cells and T-cell migration into the skin (mechanism 2). Administration is a single 0.7 mg/kg conditioning dose, followed by weekly SC dose of 1 mg/kg. Single doses should not exceed 200 mg, he notes.

Etanercept is a dimeric fusion protein consisting of p75 tumor necrosis factor receptor linked to the IgG1 antibody. The biologic blocks TNF and prevents TNF-generated inflammatory response (mechanism 4). The treatment regimen is 50 mg/week given twice weekly (three to four days apart) for three months. This is followed by a reduction to maintenance dose of 50 mg/week.

"Safety and efficacy is not established bey-ond 12 months of treatment," Dr. Gupta says.