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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/ctr.13470
Journal or Publication Title: Clinical Transplantation
Volume: 33
Number: 2
Page Range: e13470
Date: 2019
Divisions: Liver Injury and Cancer
Depositing User: General Admin
Identification Number: 10.1111/ctr.13470
ISSN: 09020063
Date Deposited: 17 Dec 2020 02:48
Abstract:

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: cohort; immunosuppression; longitudinal; misclassification; prediction; transplantation.

© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Creators:
Creators
Email
Laaksonen, Maarit A.
UNSPECIFIED
Webster, Angela C.
UNSPECIFIED
McCaughan, Geoff W.
UNSPECIFIED
Keogh, Anne M.
UNSPECIFIED
Grulich, Andrew E.
UNSPECIFIED
Vajdic, Claire M.
UNSPECIFIED
Last Modified: 17 Dec 2020 02:48
URI: https://eprints.centenary.org.au/id/eprint/287

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