Pharmacodynamic analysis of hypertension caused by lenvatinib using real‐world postmarketing surveillance data

Figures

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  Figure 1. Overview of the study population of lenvatinib‐treated patients with unresectable thyroid cancer. Of the initial patient population (n = 584), a total of 480 patients were eligible for pharmacodynamic analysis. BP, blood pressure; BW, body weight

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  Figure 2. Visual predictive check of observed and model‐predicted change in dBP after exposure to lenvatinib. Purple dots represent individually observed dBP. Blue shades represent predicted dBP. Each shade is the 95% CI of the 5th, 50th, and 95th percentile lines. Black line represents observed dBP of the 5th, 50th, and 95th percentiles. CI, confidence interval; dBP, diastolic blood pressure

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  Figure 3. Histogram plot of the direct hypotensive effect of ACEi/ARB or CCB (480 patients). The histogram plot: demonstrates the antihypertensive effect of ACEi/ARB or CCB. The antihypertensive effect was calculated using a post‐hoc estimate in 480 patients. ACEi/ARB, angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker; CCB, calcium channel blocker

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  Figure 4. Graphical image of change in the dosing regimen and antihypertensive treatment during 16 weeks of therapy and simulated change in dBP from baseline over 16 weeks for different regimens (1000 simulations). The figure corresponds to the simulated data shown in Table 3. (a) Each black arrow (↑) represents the initiation of treatment with ACEi/ARB or CCB at week 2 and dose reduction at week 6 and week 12. Blue shade represents the use of ACEi/ARB or CCB from week 2. Orange dashed line represents the lenvatinib dosing regimen of 24 → 20→14 mg/day; each change in dose performed at week 6 and week 12. Black line represents the lenvatinib dosing regimen of 20 → 14→10 mg/day; each change in dose was performed at week 6 and week 12. Purple dot and dashed line represent the lenvatinib dosing regimen of 14 → 10→8 mg/day; each change in dose was performed at week 6 and week 12. (b) Change in dBP according to dose change in a patient with baseline dBP of 60 mmHg. (c) Change in dBP according to dose change in a patient with baseline dBP of 90 mmHg. Black line represents the 25th percentile. Purple line represents the 50th percentile. Orange line represents the 75th percentile. Black dotted line…