T-cell modulation for the treatment of chronic plaque psoriasis with efalizumab (Raptiva): mechanisms of action.
Psoriasis is a chronic, incurable, auto-immune disorder with cutaneous manifestations. New evidence on the central role of the immune system in the pathogenesis of psoriasis increasingly provides insight into pathogenic steps that can be modulated to provide disease control. Numerous biological therapies are in various stages of clinical development, with expectation of providing enhanced safety and efficacy over currently available psoriasis therapies. Efalizumab, a recombinant humanized monoclonal IgG1 antibody, is a novel targeted T-cell modulator that inhibits multiple steps in the immune cascade that result in the production and maintenance of psoriatic plaques, including initial T-cell activation and T-cell trafficking into sites of inflammation, including psoriatic skin, with subsequent reactivation in these sites. This article reviews the pharmacodynamic, pharmacokinetic and clinical effects observed during phase I, II and III efalizumab trials in patients with moderate to severe chronic plaque psoriasis.
Jullien
D
D
Department of Dermatology and INSERM U346, Hôpital Edouard Herriot, Lyon, France. denis.jullien@chu-lyon.fr
Prinz
J C
JC
Langley
R G B
RG
Caro
I
I
Dummer
W
W
Joshi
A
A
Dedrick
R
R
Natta
P
P
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D006801:Humans; D011565:Psoriasis / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C472181:efalizumab