Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis.

BACKGROUND: Reduction in lesional, activated T cells induces improvement in psoriatic plaques. Galiximab (IDEC-114), an IgG(1) anti-CD80 antibody, binds to CD80, a costimulatory molecule involved in T-cell activation. OBJECTIVE: A Phase I/II, multidose, multischedule, dose-finding study of galiximab to evaluate safety, pharmacokinetics, and clinical activity was conducted in 35 patients with moderate to severe plaque psoriasis. METHODS: Seven cohorts of five patients received galiximab intravenously on three different schedules at different dose levels. RESULTS: Adverse events (AEs) commonly occurred as mild and self-limiting. Improvements were observed in most cohorts without evidence of a dose response in Psoriasis Area and Severity Index (50% or greater reduction in PASI score in 40% of patients), Physician's Global Psoriasis Assessment (PGA rating of Good or above in 57% of patients), and Psoriasis Severity Scale (PSS, baseline mean of 7.6 decreased by Study Day 127 to 5.0). An association was observed between reduction in CD3(+) cell count in histologic studies and reduction in PASI score. No antibodies to galiximab were detected. CONCLUSION: Galiximab appears to be safe and well tolerated with preliminary evidence of clinical and histologic response.

Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-alpha monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris.

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-alpha in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-alpha.

Clinical and histologic response to single-dose treatment of moderate to severe psoriasis with an anti-CD80 monoclonal antibody.

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.