Pharmacodynamic and pharmacokinetic response to anti-tumor necrosis factor-⍺ monoclonal antibody (infliximab) treatment of moderate to severe psoriasis vulgaris - 29/08/11
Abstract |
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-⍺ in the pathogenesis of psoriasis and support further development of drugs targeting tumor necrosis factor-⍺. (J Am Acad Dermatol 2003;48:68-75.)
Le texte complet de cet article est disponible en PDF.Abbreviations : CSF, ICAM, IL, NFκB, PASI, PGA, RA, TNF-⍺
Plan
Funding sources: Supported in part by Centocor Inc, a COSAT grant from the Johnson and Johnson Focused Giving Program, general support of the Clinical Research Center by Merck Inc, and a grant from the Dr David Ju Foundation. |
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Conflict of interest: None. |
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Reprint requests: Alice B. Gottlieb, MD, PhD, the Clinical Research Center, UMDNJ-Robert Wood Johnson Medical School, 51 French St, New Brunswick, NJ 08901-0019. E-mail: gottliab@umdnj.edu. |
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0190-9622/2003/$30.00 + 0 |
Vol 48 - N° 1
P. 68-75 - janvier 2003 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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