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

• Published in: Journal of the American Academy of Dermatology Vol. 48; no. 1; pp. 68 - 75
• Main Authors: Gottlieb, Alice B., Masuda, Salman, Ramamurthi, Rallapalli, Abdulghani, Ahsan, Romano, Pat, Chaudhari, Umesh, Dooley, Lisa T., Fasanmade, Adedigbo A., Wagner, Carrie L.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.01.2003; Elsevier
• Subjects: Adolescent; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Dermatologic Agents - administration & dosage; Dermatologic Agents - therapeutic use; Dermatology; Humans; Immunohistochemistry; Infliximab; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Psoriasis - drug therapy; Psoriasis - immunology; Psoriasis - metabolism; Psoriasis - pathology; Psoriasis. Parapsoriasis. Lichen; Skin, nail, hair, dermoskeleton; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - metabolism; PASI; IL; ICAM; NFκB; TNF-α; CSF; PGA; RA; Human; Skin disease; Chemotherapy; Treatment; Infliximab; Psoriasis; Immunotherapy; Cytokine; Anticytokine; Monoclonal antibody; Pharmacokinetics; Tumor necrosis factor α
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1067/mjd.2003.10

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.)