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Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis - 05/09/11

Doi : 10.1016/S0190-9622(00)90214-7 
Alice Gottlieb, MD, PhDa, James G. Krueger, MD, PhDb, Ross Bright, MDc, Mark Ling, MDd, Mark Lebwohl, MDe, Sewon Kang, MDf, Steve Feldman, MDg, Mary Spellman, MDh, Knut Wittkowski, DSc, PhDb, Hans D. Ochs, MDi, Paula Jardieu j, Robert Bauer k, Mark White j, Russell Dedrick, PhDk, Marvin Garovoy, MDk
New Brunswick, NewJersey; New York NewYork; Palo Alto, San Diego, South San Francisco, and Berkeley, California; Atlanta, Georgia; Ann Arbor, Michigan; Chapel Hill, North Carolina; and Seattle, Washington 
From the Clinical Research Center, University of Medicine and Dentistry of New Jersey—Robert Wood Johnson Medical School, New Brunswicka; The Rockefeller University New Yorkb; the Psoriasis Research Institute, Palo Altoc; Emory University, Atlantad; Mount Sinai Medical Center, New Yorke; the University of Michigan, Ann Arborf; the University of North Carolina, Chapel Hillg; VRG Inc, San Diegoh; the University of Washington, Seattlei; Genentech, South San Francisco,j and XOMA (US) LLC, Berkeley.k 

Abstract

Background: CD11a/CD18 comprise subunits of leukocyte function associated antigen (LFA-1), a T-cell surface molecule important in T-cell activation, T-cell emigration into skin, and cytotoxic T-cell function. Objective: We explored the immunobiologic and clinical effects of treating moderate to severe psoriasis vulgaris with a single dose of humanized monoclonal antibody against CD11a (hu1124). Methods: This was an open label study with a single dose of hu1124 at doses of 0.03 to 10 mg/kg. Clinical (Psoriasis Area and Severity Index [PASI]) and immunohistologic parameters (epidermal thickness, epidermal and dermal T-cell numbers, and keratinocyte intercellular adhesion molecule 1 [ICAM-1] expression) were followed. Results: Treatment with hu1124, at doses higher than 1.0 mg/kg (group III), completely blocks CD11a staining for at least 14 days in both blood and psoriatic plaques. At 0.3 to 1.0 mg/kg, T-cell CD11a staining was completely blocked; however, blockade lasted less than 2 weeks (group II). Only partial saturation of either blood or plaque cellular CD11a was observed at doses of hu1124 between 0.01 and 0.1 mg/kg (group I). This pharmacodynamic response was accompanied by decreased numbers of epidermal and dermal CD3+ T cells, decreased keratinocyte and blood vessel expression of ICAM-1, and epidermal thinning. Statistically significant drops in PASI compared with baseline were observed in group II patients at weeks 3 and 4 and in group III patients at weeks 2 through 10. No significant drop in PASI score was observed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and included mild chills, abdominal discomfort, headache, and fever. At a single dose of 0.6 mg/kg or higher, headache was the most common dose-limiting toxicity observed. Conclusion: Targeting CD11a may improve psoriasis by inhibiting T-cell activation, T-cell emigration into the skin, and cytotoxic T-cell function. (J Am Acad Dermatol 2000;42:428-35.)

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 Supported in part by XOMA (US) LCC, Johnson and Johnson Focused Giving Program (to A. B. G.). J. G. K. is supported in part by grant No. AI/AR39214 from the National Institutes of Health.
 Reprint requests: Alice Gottlieb, MD, PhD, WH Conzen Chair in Clinical Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place, New Brunswick, NJ 08903.


© 2000  American Academy of Dermatology, Inc. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 42 - N° 3

P. 428-435 - mars 2000 Retour au numéro
Article précédent Article précédent
  • Patterns of remission in pemphigus vulgaris
  • Andrew Herbst, Jean-Claude Bystryn
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  • Rate of body dysmorphic disorder in dermatology patients
  • Katharine A. Phillips, Raymond G. Dufresne, Caroline S. Wilkel, Carmela C. Vittorio

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