The investigational drug infliximab may provide a rapid and high degree of clinical benefit in patients with moderate- to-severe psoriasis, according to research published by the University of Medicine and Dentistry of New Jersey (UMDNJ) in the 09 June 2001, issue of The Lancet. Approximately a quarter of the seven million Americans with psoriasis suffer from moderate- to-severe disease, which can be both physically and emotionally debilitating.

"The high degree of efficacy and rapid response seen in patients treated with infliximab far exceeded our expectations," said Alice Gottlieb, M.D., Ph.D., principal investigator and professor of medicine at UMDNJ-Robert Wood Johnson Medical School. "Infliximab is able to clear psoriasis in a high proportion of patients in a manner comparable to cyclosporine." Psoriasis is a chronic skin disease that generally appears as patches of raised red skin covered by a flaky white buildup. Although the exact cause is unknown, psoriasis is believed to be related to signals sent by the body's immune system, accelerating the growth cycle of skin cells causing them to pile up on the surface when the body can't shed them fast enough. The findings of this investigator-initiated Phase II study suggest that a key inflammatory mediator called tumor necrosis alpha (TNF-alpha), plays a pivotal role in the maintenance of psoriasis. Infliximab (also known as REMICADE(R)) is a monoclonal antibody that specifically targets and irreversibly binds to TNF-alpha. Researchers believe that blocking TNF-alpha activity will reduce inflammation in psoriasis.

"Since the realization that the T-cell plays an important role in psoriasis there's been a resurgence in drug research," said Dr. Gottlieb. "The publication of these data in The Lancet underscores the level of unmet need for psoriasis patients and the importance of educating physicians about the potential benefits of novel therapies in development."

Moderate- to-severe psoriasis is defined as involving 5 percent or more of the body surface. Although these patients are typically treated with systemic immunosuppressants, such as cyclosporine, long-term exposure can cause toxic side effects such as hypertension and irreversible renal insufficiency.

Study Overview

The study was a 10-week, phase II, investigator-initiated, double-blind, placebo-controlled, clinical trial performed at the Clinical Research Center. Thirty-three patients, ages 18 to 75, with moderate-to-severe psoriasis over five percent of their body or more were enrolled and randomized to receive an infusion of infliximab -- 5 or 10 mg/kg -- or placebo. Infusions were given to all patients at baseline and at Weeks 2 and 6 of the trial.

The primary endpoint of the study, the Physician's Global Assessment (PGA), was evaluated at Week 10. A treatment response was defined by a PGA rating of good (50-74 percent clearing with moderate improvement), excellent (75-99 percent clearing with marked improvement) or clears (100 percent clearing). Non-responders were those with a fair (25-49 percent clearing with slight improvement) or poor (0-24 percent clearing with little or no change) PGA rating.

The data showed that 82 and 91 percent of patients taking 5 mg/kg and 10 mg/kg of infliximab respectively, achieved the primary endpoint of a good, excellent or clear PGA rating at Week 10 versus 18 percent of patients on placebo. All responders in the infliximab 5 mg/kg group and 64 percent in the 10 mg/kg group were rated either excellent or clear on the PGA.

Disease severity was also assessed using the Psoriasis Area Severity Index (PASI). According to this secondary endpoint, 82 and 73 percent of patients in the infliximab 5 mg/kg and 10 mg/kg treatment groups, respectively, experienced a 75 percent improvement compared to 18 percent of patients receiving placebo.

In this study, infliximab was generally well tolerated. Three patients withdrew from the study and were considered non-responders, one from each treatment group (the 5 mg/kg patient at Week 2, secondary to a mild rash; the 10 mg/kg patient due to worsening psoriasis and the placebo patient due to lack of improvement in disease).

Infliximab is currently indicated for the treatment of Crohn's disease and rheumatoid arthritis. Because it suppresses part of the immune response, infliximab may increase the risks of serious infections, including sepsis and tuberculosis. These infections may be life threatening. There are also reports of serious infusion reactions with hives, difficulty breathing, and low blood pressure. In rare cases, people with de-myelinating disease who were treated with infliximab have seen their symptoms intensify. In clinical studies, some people experienced the following side effects: upper respiratory infections, headache, cough, nausea, sinusitis or mild reactions to the infusion such as rash or itchy skin. In the present study, mild headache was the only side effect seen with a higher incidence among infliximab-treated patients compared to those treated with placebo.