A phase II multicenter clinical trial of systemic bexarotene in psoriasis.
BACKGROUND
Bexarotene, a novel and unique synthetic P, RXR-selective retinoid, is available as a treatment for cutaneous T-cell lymphoma. In psoriasis, a common retinoid-sensitive disease, no data are available on bexarotene treatment.


OBJECTIVE
In this phase II study we investigated the safety, tolerability, and effectiveness of bexarotene in psoriasis at doses of 0.5 to 3.0 mg/kg/day.


METHODS
Fifty patients with moderate to severe plaque-type psoriasis were treated with bexarotene in 4 sequential dose-defined panels of 12-13 patients at doses of 1.0, 2.0, 0.5, and 3.0 mg/kg/day for 12-24 weeks. Patients were monitored for safety and clinical efficacy.


RESULTS
No serious adverse events related to the drug occurred. Bexarotene was well tolerated in most patients. Most frequently observed adverse events related to bexarotene were hypertriglyceridaemia (56%) and a decrease in free T4 serum levels (54%). Significant improvement of psoriasis after bexarotene at all doses was confirmed by a modified psoriasis area and severity index (mPASI), plaque elevation (PEL), and physician's global assessment (PGA). Overall response rates (> or =50% improvement) for mPASI, PEL, and PGA were 22%, 52%, and 36%, respectively. No significant dose-response effect was established for these parameters.


CONCLUSIONS
The present study indicates an anti-psoriatic effect of bexarotene. Further studies are necessary to assess the optimal dose and the potential for bexarotene as a new therapy for psoriasis.
Department of Dermatology at the University Medical Center, Nijmegen, The Netherlands.
Jürgen V
JV
Smit
Manon E J
ME
Franssen
Elke M G J
EM
de Jong
Julien
J
Lambert
Diane I
DI
Roseeuw
Jozef
J
De Weert
Richard C
RC
Yocum
Victor J
VJ
Stevens
P C M
PC
van De Kerkhof
D000328:Adult; D000077610:Bexarotene; D015704:CD4 Antigens / Q000097:blood / Q000187:drug effects; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced; D008297:Male; D011565:Psoriasis / Q000188:drug therapy*; D011788:Quality of Life; D055502:Secondary Prevention; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D015704:CD4 Antigens; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene