A surge in biologics

Key Points

Hawaii - Approximately 4.5 million adults in the United States have psoriasis, of which 1.5 million have a moderate-to-severe form. Furthermore, 260,000 new cases are diagnosed annually. Psoriatic arthritis (PsA), which causes functional impairment and a significantly diminished quality of life, occurs in up to 35 percent of psoriasis patients. According to one expert, early treatment of psoriasis may prevent the development of PsA.

"The traditional topical therapies, as well as systemic therapies, have served well in the fight to control psoriasis and acute psoriatic flares, but the new biologics are potentially able to give patients long-term relief from the disease," says Alice B. Gottlieb, M.D., Ph.D., Harvey B. Ansell Professor and chairman, department of dermatology, Tufts University School of Medicine and Tufts-New England Medical Center, Boston.

"Furthermore," she adds, "it is imaginable that the early treatment of psoriasis may possibly prevent psoriatic arthritis."

Dr. Gottlieb says etanercept (Enbrel, Amgen/Wyeth) is indicated by the Food and Drug Administration (FDA) as therapy for moderate-to-severe psoriasis and for PsA. The drug is a synthetic protein that works by binding and blocking tumor necrosis factor (TNF) alpha, a protein responsible for promoting inflammation. It has also been used as an adjunct in patients who do not respond to methotrexate alone. It is under a phase 3 trial in children with psoriasis.

Infliximab (Remicade, Centocor) is another injectable antibody that also works by blocking TNF-alpha. The FDA has approved this drug for severe cases of psoriasis and for PsA.

"It is indicated for chronic severe plaque psoriasis in patients who are candidates for systemic therapies and for whom other systemic treatments are medically less appropriate. It is important that patients be closely monitored and have regular follow-up visits with a physician," Dr. Gottlieb says.

Infliximab binds to TNF-alpha with high specificity, affinity and avidity. It has been shown to significantly decrease signs and symptoms, as well as X-ray progression, of patients with PsA. It has also been found to improve physical function. Dosing regimens include 5 mg/kg/infusion at baseline, week two, week six, and then every eight weeks.

Certolizumab pegol is a new biologic (not FDA-approved) derived from a fragment of a humanized anti-TNF monoclonal antibody. The molecule has no Fc region, meaning that, in vitro, it does not mediate cell lysis. Recent studies have shown that 74.6 percent of psoriasis patients who were administered 400 mg of certolizumab pegol at baseline and during the treatment course were reduced to 200 mg received a PASI 75 at week 12. Dr. Gottlieb says that 82.8 percent of another group who were administered 400 mg of the drug throughout the treatment course reached PASI 75 at week 12.

Phosphodiesterase Type IV (PDE4) Inhibitor: CC 10004 is a new experimental drug with anti-inflammatory activities given in patients with severe plaque-type psoriasis. The therapeutic regimen is 20 mg/day.

"This new compound is given orally and has shown very encouraging results in the phase 2 psoriasis trials, so far. In the 19-patient study from baseline to day 29, 15.8 percent of patients achieved a PASI greater than 50, 47.4 percent improved sPGA and 52.6 percent reduced BSA after only one month of low-dose therapy. The only adverse events observed were headache and nausea, and no clinically significant changes were noted in laboratory values," Dr. Gottlieb says.

She says that CC-10004 inhibits TNF, IL-8, IL-12, iNOS, IL-2 and IFN gamma, and increases IL-10 production in vitro. Also, oral PDE4 inhibitor increases cAMP in monocytes, T cells and neutrophils. The primary endpoint in the study was to reduce the epidermal skin thickness from baseline to day 29. Eight (53.3 percent) of the 15 patients who completed the study demonstrated greater than 20 percent reduction in epidermal thickness.