Infliximab (RemicadeR) monotherapy shows rapid onset of action and sustained efficacy as both induction and maintenance therapy for patients with moderate-to-severe skin and nail psoriasis, according to results of a multicenter Phase III study published in the October 15 issue of The Lancet.¹

The study showed, in fact, that the majority of patients receiving infliximab achieved psoriasis area and severity index (PASI) 75 and PASI 90 improvements for up to 1 year, according to researchers led by Kristian Reich, MD, a professor of dermatology at Georg-August University in Göttingen, Germany. At week 50, 61% and 45% of infliximab-treated patients reached PASI 75 and PASI 90, respectively, researchers found.

The EXPRESS study, the first multicenter trial of infliximab in patients with moderate-to-severe plaque psoriasis, showed that the agent has a rapid onset of action, with 80% of infliximab patients achieving a PASI 75, and  57% at least a  PASI 90, by week 10, compared with 3% and 1% in the placebo group, respectively (P <.0001). At week 24, 82% and 58% of infliximab patients maintained a PASI 75 and PASI 90, respectively, versus 4% and 1% of placebo patients (P <.0001).

Nail psoriasis, a manifestation of plaque psoriasis that is often resistant to treatment, improved significantly in patients taking infliximab, compared with their control counterparts. By week 24, patients who received infliximab experienced a 56.3% decrease in nail psoriasis severity index (NAPSI) (P <.0001), a response that was maintained throughout the duration of the trial.

"Infliximab monotherapy is highly effective in the treatment of skin and nail disease in patients with moderate-to-severe psoriases, with a rapid onset of action and a sustained effect in most patients," the researchers conclude.

Biologics are "most important development" in psoriasis in decades

Michael P. Schön, MD, of the Rudolf Virchow Centre, DFG Research Centre for Experimental Biomedicine, and the department of dermatology at the University of Würzburg, Germany, tells CIAOMed that biologics represent a new generation of psoriasis therapies. "As a class, they are probably the most important development in the field of psoriasis treatment over the last two decades," he says.

Dr. Schön explained that [biologics] have advantages over other available therapies. "Systemic treatment of psoriasis is often limited by the long-term toxicity and unwanted side effects of the traditional drugs," he says. "In addition, quality of life of many patients is impaired by the inconvenient application of some of the traditional treatments, including regimens involving UV-irradiation and time needed to apply topicals. In this light, the advent of the biologicals bears the potential to improve the quality of life for many patients."

New study provides insight on potential response parameters

Maintenance of the therapeutic response appeared to be related to the achievement of stable serum infliximab concentrations, levels that were more common in patients who tested negative for infliximab antibodies than in antibody-positive patients, the study showed. These findings "provide insights into the potential parameters that affect the long-term clinical response," the researchers point out.

In the phase III, multicenter, double-blind trial, 378 patients with moderate-to-severe plaque psoriasis were allocated in a 4:1 ratio to receive infusions of infliximab 5 mg/kg or placebo at weeks 0, 2, and 6, then every 8 weeks to week 46. At week 24, placebo-treated patients crossed over to infliximab treatment. Skin and nail signs of psoriasis were assessed via PASI and NAPSI, respectively. The primary endpoint, analyzed on an intention-to-treat basis, was the proportion of patients achieving at least a 75% improvement in PASI from baseline to week 10.

Benefits justify risks

When asked by CIAOMed whether the benefits of biologics justify their risks in psoriasis, Dr. Schön, who wrote an editorial accompanying the new study,²  says that "given that the traditional systemic treatments are associated with considerable long-term risks, I believe that the risks associated with biologicals indeed justify the benefits in many patients with moderate-to-severe psoriasis." He conceded, however, that the high cost of these drugs may be a problem in many countries.

"Each of these novel drugs has its strengths and weaknesses," Dr. Schön explains. For example, "infliximab shows the best response rates, but is associated with a higher risk of infections and has to be administered intravenously. Efalizumab (Raptiva®) shows the lowest rate of unwanted side effects, but there is a rather high proportion of patients who do not respond sufficiently to treatment with efalizumab."

Moreover, Dr. Schoen says, both infliximab and etanercept are efficacious in psoriatic arthritis, while efalizumab is not. "As both efalizumab and etanercept (Enbrel®) are administered subcutaneously, patients can self-administer the drugs, [but] this is not possible with infliximab," he says.

References

1. Reich K, Nestle FO, Papp K, et al. Infliximab induction and maintenance therapy for moderate-to-severe psoriasis: a phase III, multicentre, double-blind trial. Lancet. 2005;366:1367-1374.

2. Schöen MP. Advances in psoriasis treatment. Lancet. 2005;366:1333-1355.