A randomized controlled trial of tacrolimus versus cyclosporine after lung transplantation.
BACKGROUND
The optimal maintenance immunosuppressive regimen after lung transplantation is uncertain.


METHODS
We conducted a randomized controlled trial of tacrolimus versus cyclosporine in combination with azathioprine and prednisone after lung transplantation. Ninety adults were randomized to tacrolimus (n = 44) or cyclosporine (n = 46). The primary end point was a composite of a cumulative acute rejection A score of 3 or higher, a cumulative lymphocytic bronchitis B score of 4 or higher, or the onset of bronchiolitis obliterans syndrome (BOS) stage 0-p.


RESULTS
Recipients randomized to cyclosporine were significantly more likely to develop the primary end point than those randomized to tacrolimus. During the study period, the primary end point developed in 39 of 46 cyclosporine subjects compared with 24 of 44 tacrolimus subjects (p = 0.002); acute rejection or lymphocytic bronchitis end points developed in 29 of 46 cyclosporine subjects compared with 18 of 44 tacrolimus subjects (p = 0.036). Furthermore, BOS stage 0-p was more likely to develop in the cyclosporine group than in the tacrolimus group, but this was not statistically significant (log-rank p = 0.1). In addition, there was a trend to a higher incidence of diabetes among those in the tacrolimus group, but there was no significant difference in graft survival or the total number of infections, or in the incidence of hypertension, chronic kidney disease, or cancer between the 2 groups.


CONCLUSIONS
Tacrolimus is associated with a lower burden of acute rejection and lymphocytic bronchitis and a trend to a greater freedom from BOS stage 0-p than cyclosporine after lung transplantation.
Hachem
Ramsey R
RR
Division of Pulmonary & Critical Care, Washington University School of Medicine, St. Louis, Missouri 63110, USA. rhachem@im.wustl.edu
Yusen
Roger D
RD
Chakinala
Murali M
MM
Meyers
Bryan F
BF
Lynch
John P
JP
Aloush
Aviva A
AA
Patterson
G Alexander
GA
Trulock
Elbert P
EP
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D001989:Bronchiolitis Obliterans / Q000209:etiology; D001991:Bronchitis / Q000209:etiology; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000139:chemically induced; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D016559:Tacrolimus