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Randomized Controlled Trial
. 2025 Apr 28:38:14189.
doi: 10.3389/ti.2025.14189. eCollection 2025.

Tremors and Health-Related Quality of Life in Liver Transplant Recipients: Post-hoc Analysis of a Multicenter, Randomized, Controlled Trial Comparing a Life Cycle Pharma-Tacrolimus Regimen and Extended-Release Tacrolimus Regimen

M B Mulder  1   2 , J J Busschbach  3 , B van Hoek  4 , W G Polak  2   5 , I P J Alwayn  6 , B C M de Winter  1   2 , S Darwish Murad  2   7 , E Verhey-Hart  2   7 , L Elshove  2   7 , N S Erler  8   9 , D A Hesselink  2   10 , C M den Hoed  2   7 , H J Metselaar  2   7
Affiliations
Randomized Controlled Trial

Tremors and Health-Related Quality of Life in Liver Transplant Recipients: Post-hoc Analysis of a Multicenter, Randomized, Controlled Trial Comparing a Life Cycle Pharma-Tacrolimus Regimen and Extended-Release Tacrolimus Regimen

M B Mulder et al. Transpl Int. .

Abstract

We investigated whether life cycle pharma (LCP)-tacrolimus compared to extended-release (ER)-tacrolimus results in a difference in severity of tremors and HRQoL. In this multi-center, open-label, randomized, controlled trial, 108 patients were randomized in a 1:1 ratio to either LCP-tacrolimus regimen or ER-tacrolimus regimen after transplantation. HRQoL was assessed with the EQ-5D-5L and SF-36 questionnaire (two generic HRQoL instruments) and the quality of life in essential tremor (QUEST) questionnaire (domain specific HRQoL instrument). The EQ-5D-5L scores were translated to the societal values. We examined the HRQoL over the course of the study by fitting generalized mixed effect models. In total, 105 patients were included, 53 to the LCP- and 52 to the ER-tacrolimus regimen. Baseline questionnaires were available for every LT recipient. At 12 months 25% [10/40], 95% confidence interval (CI) 14.2%-40.2% of the LT recipients in the LCP-tacrolimus regimen group experienced tremors compared to 30.4% [14/46], 95%-CI 19.1%-44.8% of the LT recipients in the ER-tacrolimus regimen group; risk difference: 0.054; 95%-CI -0.151-0.249; p = 0.63. No statistically significant differences in HRQoL were seen between the two regimens. We could not demonstrate differences in the HRQoL or occurrence of tremors between LCP-tacrolimus and ER-tacrolimus regimens.

Keywords: healthrelated quality of life; immunosuppressive therapy; liver transplantation; tacrolimus; tremors.

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Conflict of interest statement

MM has received lecture fees and consulting fees from Chiesi Pharma and grant support from Astellas Pharma. MM does not have employment or stock ownership at any of these companies, and neither does he have patents or patent applications. DH has received lecture fees and consulting fees from Astellas Pharma, Astra Zeneca, Chiesi Pharma, Medincell, Novartis Pharma, Sangamo Therapeutics and Vifor Pharma. He has received grant support from Astellas Pharma, Bristol-Myers Squibb and Chiesi Pharma (paid to his institution). DH does not have employment or stock ownership at any of these companies, and neither does he have patents or patent applications. CH has received lecture fees and consulting fees from Chiesi Pharma, Takeda, Novartis Pharma, Abacus medical and travel grants from Orphalan. CH does not have employment or stock ownership at any of these companies, and neither does she have patents or patent applications. HM has received lecture fees from Astellas Pharma and received grant support from Astellas Pharma, Novartis Pharma and Chiesi Pharma. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Enrollment, randomization, and follow-up.
FIGURE 2
FIGURE 2
Proportion of LT recipients experiencing tremors during follow-up. The proportion of LT recipients with 95%-CI experiencing tremors during follow-up. At 12 months 25% [10/40], 95% confidence interval (CI) 14.2%–40.2% of the LT recipients in the LCP-tacrolimus group versus 30.4% [14/46], 95%CI 19.1%–44.8% of the LT recipients in the ER-tacrolimus group experienced tremors; risk difference: 0.054; 95%CI -0.151–0.249; p = 0.63.
FIGURE 3
FIGURE 3
EQ-VAS score and EQ-5D-5L scores on the dimensions translated to the societal values. (A) Patient’s self-rated QoL (EQ-VAS) Group-wise mean EQ-VAS with 95%-confidence interval (CI) during the course of the study represented as solid lines. The dashed lines and shaded areas indicate the expected values and corresponding 95%-CI from the generalized mixed effect model (assuming the median or reference value for the continuous or categorical covariates, respectively: tacrolimus trough concentrations, kidney function, hemoglobin, recipient age and sex, primary disease, diabetes mellitus and hypertension pretransplantation as well as the interaction between visit and the study group). Dotted black line indicates the mean self-reported EQ-VAS score by the general Dutch population [15]. (B) EQ-5D-5L scores translated to the values given by the general public to the health states. Group-wise mean of the societal values of the EQ-5D-5L health states with 95%-confidence interval (CI) during the course of the study represented as solid lines. The dashed lines and shaded areas indicate the expected values and corresponding 95%-CI from the generalized mixed effect model (assuming the median or reference value for the continuous or categorical covariates, respectively tacrolimus trough concentrations, kidney function, hemoglobin, recipient age and sex, primary disease, diabetes mellitus and hypertension pretransplantation as well as the interaction between visit and the study group). Dotted black line indicates the mean EQ-5D-5L score given by the general Dutch population to the health states. [15]. Abbreviations: QoL, quality of life; VAS, visual analogue scale.
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