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Clin Transplant. 2019 Feb;33(2):e13470. doi: 10.1111/ctr.13470. Epub 2019 Jan 20.

Longitudinal immunosuppression data can minimize misclassification bias in solid organ transplantation cohorts.

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Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia.
Sydney School of Public Health, University of Sydney, Sydney, New South Wales, Australia.
Centre for Transplant and Renal Research, Westmead Hospital, Sydney, New South Wales, Australia.
The Centenary Research Institute, Australian National Liver Transplant Unit Royal Prince Alfred Hospital and University of Sydney, Sydney, New South Wales, Australia.
St Vincent's Hospital, Sydney, New South Wales, Australia.
The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.



Most cohort studies investigating the effect of immunosuppression on transplant outcomes use drugs at first hospital discharge. We evaluated the extent of drug exposure misclassification and its impact on outcome prediction.


We retrospectively collected longitudinal immunosuppression data, at discharge and at 1, 5, 10, and 15 years after transplantation, and outcomes for solid organ transplant recipients 1984-2006 (n = 3133). We compared the risk of death from exposure to individual immunosuppressive drugs (cyclosporine, tacrolimus, azathioprine, and mycophenolate) and dual therapies, as defined by discharge only vs longitudinal immunosuppression data, using adjusted Cox proportional hazards models.


During a median follow-up of 5.2 years, immunosuppressive drugs were altered for 947 (30%) recipients and 955 recipients died. Longitudinal receipt of cyclosporine and azathioprine were associated with an increased risk (HR 1.41, 95% CI 1.07-1.89, and HR 1.34, 95% CI 1.00-1.80), and mycophenolate with a reduced risk (HR 0.35, 0.16-0.78), of death. Recipients on mycophenolate and tacrolimus dual therapy had a lower risk of death compared to those on azathioprine and cyclosporine dual therapy (HR 0.30, 0.10-0.93). The increased risk of death associated with the receipt of cyclosporine or azathioprine was not shown in the analyses based on drugs allocated at discharge, and all of the associations between immunosuppressive regimens and death were strengthened in the analyses based on longitudinal immunosuppression data.


Cohort findings based on immunosuppressive drugs allocated at discharge should be interpreted with caution due to potential exposure misclassification. The use of granular, longitudinal data on immunosuppressive regimens could improve prediction.


cohort; immunosuppression; longitudinal; misclassification; prediction; transplantation


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