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.


CONCLUSIONS
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.
Gottlieb
Alice B
AB
Clinical Research Center, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901-0019, USA. gottliab@umdnj.edu
Masud
Salman
S
Ramamurthi
Rallapalli
R
Abdulghani
Ahsan
A
Romano
Pat
P
Chaudhari
Umesh
U
Dooley
Lisa T
LT
Fasanmade
Adedigbo A
AA
Wagner
Carrie L
CL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D000069285:Infliximab; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D003879:Dermatologic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab