BACKGROUND:Effective, rapid-acting, safe therapies are needed for the long-term treatment of psoriasis.OBJECTIVE:We sought to evaluate infliximab monotherapy in maintaining clinical benefit in psoriasis.METHODS:A total of 33 patients received 3 doses of 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6 (double-blind phase). During the open-label phase (weeks 10-26), responding patients were evaluated for relapse (loss of at least half of the improvement in the Psoriasis Area Severity Index score at week 10) and retreated with open-label infliximab (5 or 10 mg/kg) as needed. Placebo nonresponders were treated with an induction regimen of infliximab (5 or 10 mg/kg) and followed up through week 26.RESULTS:In all, 29 patients received either 5 or 10 mg/kg of infliximab in the open-label extension. At week 26, psoriasis area severity index response was maintained in 40% and 73% of patients receiving 5 and 10 mg/kg of infliximab, respectively.CONCLUSION:Infliximab produced a rapid, effective, and sustainable (through week 26) effect in patients with moderate to severe psoriasis.

Objective: Infliximab monotherapy provided a rapid and high degree of clinical benefit in patients with moderate to severe psoriasis in a previously conducted trial. Herein we describe the pharmacodynamic and pharmacokinetic results observed in this clinical trial. Methods: Patients with psoriasis received 5 or 10 mg/kg of infliximab or placebo at weeks 0, 2, and 6. Immunohistochemical analysis of lesional (weeks 0, 2, 10) and nonlesional (week 0) biopsies was conducted. Median infliximab half-life and peak serum concentrations over time were calculated. Results: Infliximab immunotherapy resulted in rapid and dramatic decreases in epidermal inflammation and normalization of keratinocyte differentiation in psoriatic plaques; these changes preceded maximal clinical response. Infliximab concentrations were maintained above the detection limit (0.1 mg/mL) in the majority of patients through week 14. Conclusion: The clinical and immunohistologic data demonstrate a pivotal role for tumor necrosis factor-α in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-α. (J Am Acad Dermatol 2003;48:68-75.)

The Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA) are commonly used, but fail to measure quality of life and the patient's perception of well-being. In response to these limitations, the National Psoriasis Foundation (NPF) Medical Advisory Board has developed the NPF Psoriasis Score (NPF-PS). This article evaluates the degree of concordance between NPF-PS, PASI, and PGA scores via an investigator-initiated, single-center, double-blind, placebo-controlled study of thirty-three patients with moderate to severe plaque psoriasis. Our results indicated that NPF-PS was strongly correlated with PASI and PGA in this study, while better reflecting patient perception. This is the first report of a double-blind placebo-controlled study demonstrating this concordance.

Pathologic T-cell activation is implicated in psoriasis progression. CD80, a costimulatory molecule involved in T-cell activation, likely plays a key role. IDEC-114, an IgG(1) anti-CD80 antibody, was evaluated for safety, pharmacokinetics, and preliminary clinical activity in this open-label, single-dose, dose-escalating study in patients with moderate to severe chronic plaque psoriasis. Twenty-four patients received IDEC-114 (0.05 mg/kg, 0.25 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg, or 15 mg/kg). Psoriasis Area and Severity Index, Physician's Global Psoriasis Assessment, and Psoriasis Severity Scale scores improved in the highest-dose groups. Average plaque thickness and plaque CD3+ and CD8+ T-cell counts decreased in the 10 mg/kg dose group. Adverse events were primarily mild, transient, constitutional symptoms; the most common related events were mild asthenia (29% of patients), chills (25%), and headache (21%). The serum half-life of IDEC-114 was approximately 13 days. A single dose of IDEC-114 appears to be safe and well tolerated and has promising clinical activity in psoriasis.

Background: Although betamethasone valerate (BMV) foam, 0.12% (Luxiq, Connectics Corporation, Palo Alto, CA) is approved by the Food and Drug Administration for the treatment of corticosteroid-responsive scalp dermatoses, no data are available for its use on nonscalp psoriasis. Objective: We evaluated the safety and efficacy of BMV foam in treating psoriatic lesions at nonscalp sites. Methods: We conducted a randomized, double-blind, placebo-controlled, paired-comparison, split-body study of 40 patients with mild to moderate plaque-type psoriasis. Patients applied BMV foam and placebo foam twice daily for 12 weeks. Results: At the end of the treatment period, 70% of patients had greater than 50% improvement of lesions on their active foam-treated side compared with 24% of patients with similar improvement on their placebo foam-treated side. Adverse effects were limited to temporary stinging, burning, or itching in several patients. Three patients (7.5%) withdrew because of stinging or itching. Conclusions: The results indicate that BMV foam is effective against nonscalp psoriasis. Twice-daily applications are well tolerated, compliance exceeds 90%, cosmetic characteristics are acceptable, and the medication may reduce the need for multiple prescriptions.

Background Currently available treatments for moderate to severe psoriasis are either incompletely effective in some patients, or are associated with toxic effects. Since tumour necrosis factor alpha (TNF-alpha) is thought to have a role in the pathogenesis of psoriasis, we did a double-blind, randomised trial to assess the clinical benefit and safety of infliximab-a monoclonal antibody against TNF-alpha.Methods 33 patients with moderate to severe plaque psoriasis were randomly assigned intravenous placebo (n=11), infliximab 5 mg/kg (n=11), or infliximab 10 mg/kg (n=11) at weeks 0, 2, and 6. Patients were assessed at week 10 for the primary endpoint (score on the physician's global assessment [PGA]). Analysis was by intention to treat.Findings Of the 33 patients enrolled, three dropped out. Nine of 11 (82%) patients in the Infliximab 5 mg/kg group were responders (good, excellent, or clear rating on PGA), compared with two of 11 (18%) In the placebo group (difference 64% [95% CI 20-89], p=0.0089), and ten of 11 (91%) patients in the infliximab 10 mg/kg group were responders (difference from placebo 73% [30-94], p=0.0019). The median time to response was 4 weeks for patients in both infliximab groups. There were no serious adverse events, and infliximab was well tolerated.Interpretation In this controlled trial, patients receiving the anti-TNF-alpha agent infliximab as monotherapy experienced a high degree of clinical benefit and rapid time to response In the treatment of moderate to severe plaque psoriasis compared with patients who received placebo. These findings suggest that TNF-alpha has a pivotal role in the pathogenesis of psoriasis.