Explorative immunohistochemical study to evaluate the addition of a topical corticosteroid in the early phase of alefacept treatment for psoriasis.
The aim of this study was to explore the additional effect of betamethasone dipropionate cream in the early phase of an intramuscular (IM) alefacept course, on plaque severity and on modulating T-cell subsets, cells expressing NK-receptors, epidermal proliferation and keratinocyte differentiation in lesional psoriatic skin. Therefore, sixteen patients with moderate-to-severe chronic plaque psoriasis received 15 mg alefacept IM for 12 weeks, followed by a 12-week follow-up period. The first 4 weeks, patients were randomized 1:1 to either betamethasone dipropionate, or the vehicle cream, once daily. Plaque severity (SUM) was assessed and serial biopsies were immunohistochemically stained for T-cell subsets (CD3, CD4, CD8, CD45RO, CD45RA, CD2, CD25, GITR), cells expressing NK-receptors (CD94 and CD161), epidermal proliferation (Ki67) and differentiation (K10), which were quantified using manual and digital image analysis. Alefacept monotherapy resulted in statistically significant improvement in plaque severity. Subsequently, immunohistochemical assessments on T-cell subsets, epidermal proliferation (Ki67) and keratinization (K10) revealed marked time-related improvements with respect to the mentioned parameters, without significant differences between both treatment regimens. Alefacept monotherapy induces improvement of plaque severity, which is accompanied by a reduction in activated (CD2+, CD25+, CD45RO+) dermal CD4+ and activated epidermal CD8+ T cells, epidermal proliferation and differentiation. Once daily treatment with betamethasone dipropionate cream during the first 4 weeks of an intramuscular alefacept course did not provide substantial additional clinical and immunohistochemical improvement.
Bovenschen
H J
HJ
Department of Dermatology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen, 6500 HB, The Netherlands. j.bovenschen@derma.umcn.nl
Gerritsen
W J
WJ
van Rens
D W A
DW
Seyger
M M B
MM
de Jong
E M G J
EM
van de Kerkhof
P C M
PC
D000287:Administration, Topical; D000328:Adult; D000077944:Alefacept; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004817:Epidermis / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D015603:Keratinocytes / Q000187:drug effects; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D003879:Dermatologic Agents; D011993:Recombinant Fusion Proteins; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D000077944:Alefacept