The BILAG multi-centre open randomized controlled trial comparing ciclosporin vs azathioprine in patients with severe SLE.
OBJECTIVE
To determine whether low-dose ciclosporin was a more effective corticosteroid-sparing agent than AZA in patients with SLE.


METHODS
Patients with SLE requiring a change or initiation of a corticosteroid-sparing agent and who were taking > or =15 mg of prednisolone/day were randomized to receive either ciclosporin or AZA during this 12-month open-label multi-centre trial. There were strict guidelines for the reduction of prednisolone. The primary outcome was the absolute mean change in prednisolone.


RESULTS
Eighty-nine patients were randomized. Using an intention-to-treat analysis, the absolute mean change in prednisolone dose between baseline and 12 months, adjusted for baseline prednisolone dose, was 9.0 mg for ciclosporin (95% CI 7.2, 10.8) and 10.7 mg for AZA (95% CI 8.8, 12.7). The difference in the change between treatment groups was -1.7 mg (95% CI -4.4, 0.9; P = 0.2). No significant differences were detected for the secondary outcomes: change in disease activity [classic British Isles Lupus Assessment Group (BILAG) index], number of flares, development of new damage or change in quality of life. A similar number of patients in each arm stopped the study drugs due to adverse events and ineffectiveness. No patient developed severe hypertension or a persistent rise in creatinine. One patient in the ciclosporin arm developed a significant increase in proteinuria due to disease activity.


CONCLUSIONS
Both drugs were effective corticosteroid-sparing agents. Ciclosporin was not a more effective corticosteroid-sparing agent. Ciclosporin may be considered in patients who are unable to tolerate AZA. Patients on ciclosporin require close monitoring of blood pressure and creatinine.


BACKGROUND
Current Controlled Trials, http://www.controlled-trials.com/, ISRCTN35919612.
Griffiths
Bridget
B
Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK. bridget.griffiths@nuth.nhs.uk
Emery
Paul
P
Ryan
Vicky
V
Isenberg
David
D
Akil
Mohammed
M
Thompson
Robert
R
Maddison
Peter
P
Griffiths
Ian D
ID
Lorenzi
Alice
A
Miles
Sarah
S
Situnayake
Deva
D
Teh
Lee Suan
LS
Plant
Mike
M
Hallengren
Christina
C
Nived
Ola
O
Sturfelt
Gunnar
G
Chakravarty
Kuntal
K
Tait
Tim
T
Gordon
Caroline
C
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage*; D013223:Statistics as Topic; D013548:Sweden; D016896:Treatment Outcome; D006113:United Kingdom
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D001379:Azathioprine