Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability.
OBJECTIVE
To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM).


METHODS
In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse.


RESULTS
The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups.


CONCLUSIONS
If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.
Zachariae
H
H
Abrams
B
B
Bleehen
S S
SS
Bräutigam
M
M
Burrows
D
D
Ettelt
M J
MJ
Fry
L
L
Happle
R
R
Haustein
U F
UF
Ganslandt
J
J
Jung
E G
EG
Knop
J
J
Kühne
K H
KH
Mellein
B
B
Mørk
N J
NJ
Rogers
S
S
Schmidt
A G
AG
Schopf
R E
RE
Sumner
M
M
Taube
K M
KM
Weidinger
G
G
Wurdel
C
C
Zahn
E
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000139:chemically induced; D002626:Chemistry, Pharmaceutical; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004655:Emulsions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007669:Kidney Calculi / Q000139:chemically induced / Q000150:complications; D007866:Leg / Q000473:pathology; D008297:Male; D008595:Menorrhagia / Q000139:chemically induced; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000150:complications; D011565:Psoriasis / Q000188:drug therapy*; D016896:Treatment Outcome
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine