Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding trial.
BACKGROUND
There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis.


OBJECTIVE
Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis.


METHODS
A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks.


METHODS
The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations.


RESULTS
The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen.


CONCLUSIONS
Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.
Gottlieb
A B
AB
UMDNJ-Robert Wood Johnson Medica School, New Brunswick, NJ, USA. gottliab@umdnj.edu
Griffiths
C E M
CE
Ho
V C
VC
Lahfa
M
M
Mrowietz
U
U
Murrell
D F
DF
Ortonne
J-P
JP
Todd
G
G
Cherill
R
R
Marks
I
I
Emady-Azar
S
S
Paul
C F
CF
D015746:Abdominal Pain / Q000139:chemically induced; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced; D013223:Statistics as Topic; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D001786:Blood Glucose; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D016559:Tacrolimus