Microemulsion formulation of cyclosporin (Sandimmun Neoral) vs Sandimmun: comparative safety, tolerability and efficacy in severe active rheumatoid arthritis. On behalf of the OLR 302 Study Group.
OBJECTIVE
To compare the safety, tolerability and efficacy of the new oral microemulsion formulation of cyclosporin A (CyA; Sandimmun Neoral) and the original CyA formulation (Sandimmun), in patients with severe active rheumatoid arthritis (RA), over a 12-month period.


METHODS
In this double-blind, multicentre study, patients were randomized to treatment with Neoral or Sandimmun, starting with 2.5 mg/kg/day, with dose adjustments after 4 weeks. Primary efficacy criteria included patients' assessment of disease activity. Pharmacokinetic and safety assessments were performed at regular intervals.


RESULTS
Compared with Sandimmun, Neoral showed a consistent trend towards greater clinical efficacy from week 12 onwards, including a significant difference in patients' assessment of disease activity at the study end-points. A significantly lower increase in dose from baseline was observed with Neoral at week 24. Pharmacokinetic assessments at week 24 showed increased absorption and decreased variability with Neoral. No differences in safety were found between treatment groups.


CONCLUSIONS
These observations indicate that Neoral is as safe and at least as effective as Sandimmun and have important implications for patient management given the increasing role for CyA in the treatment of severe, active RA.
Yocum
D E
DE
Arizona Arthritis Center, University of Arizona, Tucson, Arizona, USA.
Allard
S
S
Cohen
S B
SB
Emery
P
P
Flipo
R M
RM
Goobar
J
J
Jayawardena
S
S
Job-Deslandre
C
C
Jubb
R W
RW
Krüger
K
K
Lopes Vaz
A
A
Manger
B
B
Mur
E
E
Nygaard
H
H
Weiner
S M
SM
Rainer
F
F
Sack
M R
MR
Schiff
M H
MH
Schnitzer
T J
TJ
Trigg
L B
LB
Whatmough
I
I
Schmidt
A G
AG
D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004655:Emulsions; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D017060:Patient Satisfaction; D011446:Prospective Studies; D012449:Safety; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D004655:Emulsions; D016572:Cyclosporine; D003404:Creatinine