Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial.
BACKGROUND
Skin-homing, memory T lymphocytes play an important role in the pathogenesis of psoriasis by interacting with the vascular addressin, E-selectin and trafficking into lesional skin. Thus an attractive option for targeted therapy of the disease would be blockade of skin-homing T cells with an antibody directed at E-selectin.


OBJECTIVE
We performed a multicentre, randomized, placebo-controlled trial to investigate the clinical efficacy and side-effect profile of a humanized monoclonal antibody to E-selectin, CDP850, in the treatment of moderate to severe chronic plaque psoriasis.


METHODS
Patients with moderate/severe chronic plaque psoriasis were selected for study. Nine male subjects (mean age 37 years, range 25-47) were given 20 mg kg-1 CDP850 intravenously as a single dose and four subjects (three males, one female; mean age 40 years, range 23-50) received placebo infusion. Clinical response to treatment was assessed using the psoriasis area and severity index (PASI). Skin biopsies were taken for immunohistochemical analysis at the baseline, pretreatment, visit and also at day 2 and weeks 1 and 4 postinfusion.


RESULTS
The treatment was well-tolerated with a minimal side-effect profile. Plasma E-selectin levels were significantly decreased in those subjects who received CDP850 compared with those who had placebo for the entire study period. At the end of study (8 weeks postinfusion), there was no significant reduction in PASI from baseline for either the CDP850 or placebo-treated groups. Immunohistochemical analysis of biopsies taken from lesional psoriatic skin showed that 2 days after dosing with CDP850, staining for E-selectin was decreased, although not absent, on dermal vascular endothelial cells when compared with baseline (P < 0.01). This decrease in E-selectin expression was maintained 4 weeks after infusion (P < 0.05). It was not, however, accompanied by a significant reduction in numbers of neutrophils or lymphocytes in the dermis. There was a statistically significant increase in CD1a-positive epidermal Langerhans cells compared with pre-dose levels at week 1 (P < 0.05).


CONCLUSIONS
This clinicopathological study shows that anti-E-selectin (CDP850), although a well-tolerated, logical and safe therapy, does not appear to possess a therapeutic role in the treatment of chronic plaque psoriasis.
Bhushan
M
M
The Dermatology Centre, Irving Building, University of Manchester, Hope Hospital, Salford, Manchester M6 8HD, UK.
Bleiker
T O
TO
Ballsdon
A E
AE
Allen
M H
MH
Sopwith
M
M
Robinson
M K
MK
Clarke
C
C
Weller
R P J B
RP
Graham-Brown
R A C
RA
Keefe
M
M
Barker
J N W N
JN
Griffiths
C E M
CE
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002908:Chronic Disease; D004311:Double-Blind Method; D019040:E-Selectin / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D019040:E-Selectin