Reduced risk of cytomegalovirus infection in solid organ transplant recipients treated with sirolimus: a pooled analysis of clinical trials.
BACKGROUND
Cytomegalovirus (CMV) is an opportunistic infection that causes substantial morbidity and mortality in transplant recipients. This pooled analysis of Wyeth clinical trials explored the incidence of CMV infection in solid organ transplant recipients treated with sirolimus versus comparator immunosuppressant drugs.


METHODS
Wyeth-conducted, multicenter, randomized, comparative trials with at least one non-sirolimus-containing arm and at least 6 months' complete data were included. Cases of CMV were investigator-identified. The occurrence of CMV in sirolimus-treated patients was assessed versus all other comparator agents, versus antimetabolite agents, and versus calcineurin inhibitors.


RESULTS
Nine trials in recipients of renal, liver, and cardiac transplants met the inclusion criteria; eight enrolled de novo allograft recipients, and one was a conversion trial. The primary pooled analysis revealed an odd ratio for CMV infection of 0.64 (95% confidence interval [CI] 0.42 to 1.0, P = .047) on sirolimus versus comparator immunosuppressant drugs. The subanalysis of sirolimus versus antimetabolites showed an odds ratio for CMV of 0.39 (95% CI 0.19 to 0.81, P = .012), and for sirolimus versus calcineurin inhibitors the odds ratio was 0.58 (95% CI 0.34 to 1.01, P = .054).


CONCLUSIONS
This pooled analysis demonstrated a reduced risk of CMV infection among sirolimus-treated patients as compared to those receiving alternative forms of immunosuppression in Wyeth-sponsored clinical trials in solid organ transplantation. This risk reduction persisted in subgroup analyses stratified by class of comparator treatment.
Demopoulos
L
L
Global Safety Surveillance, Epidemiology, and Labeling & Clinical Research and Development, Wyeth Research, Collegeville, Pennsylvania 19426, USA. demopol@wyeth.com
Polinsky
M
M
Steele
G
G
Mines
D
D
Blum
M
M
Caulfield
M
M
Adamkovic
A
A
Liu
Q
Q
Harler
M B
MB
Hahn
C
C
Singh
A
A
D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000517:prevention & control; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology; D015337:Multicenter Studies as Topic; D016377:Organ Transplantation / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D020123:Sirolimus