Longitudinal changes in laboratory parameters and QTc during isavuconazole therapy in Japanese patients with hematologic malignancies

Figures

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  Fig 1. Longitudinal distribution of treatment status. Stacked bar chart showing the proportions of the three treatment groups (ATO alone, ATO-ISCZ, and ATO-other antifungals) among 17 patients over the course of arsenic trioxide therapy. The numbers below the x-axis indicate the total number of patients e.valuated at each time point. Abbreviations: ATO, arsenic trioxide; ISCZ, isavuconazole.

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  Fig 2. Longitudinal trajectories of clinical laboratory parameters during isavuconazole therapy. The solid lines represent the estimated marginal means derived from linear mixed-effects models, with shaded areas indicating 95% confidence intervals. Linear mixed-eTheffects modeling revealed no evidence of a unidirectional and clinically meaningful deterioration over time in any of the evaluated parameters, including hepatic markers (AST, ALT, T-Bil, γ-GTP, ALP, LDH), renal function (Cre), or electrolytes (Na, K, CL). The dashed red lines represent the baseline value (zero change), and scatter plots show individual data points for the 45 patients.

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  Fig 3. Individual longitudinal changes in QTcB and QTcF intervals under ATO-containing regimens. Longitudinal changes from baseline in (a) QTcB and (b) QTcF intervals are shown for individual patients, stratified by treatment group: ATO, ATO-ISCZ and ATO-other antifungals. Each line represents an individual patient’s trajectory. The red dashed lines indicate baseline (zero change).

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  Fig 4. Predicted trajectories of QTcB and QTcF intervals based on non-linear mixed-effects modeling. Estimated marginal means for (a) absolute QTcB values and (b) absolute QTcF values over time, modeled using restricted cubic splines with four knots to account for non-linear dynamics. Predicted values are adjusted for baseline levels. Patients are stratified into three treatment groups: ATO alone (red lines), ATO-ISCZ (green lines), and ATO-other antifungal agents (blue lines). Shaded areas represent 95% confidence intervals.