Girardin François R, Nicolet Anna, Bestard Oriol, Lefaucheur Carmen, Budde Klemens, Halleck Fabian, Brouard Sophie, Giral Magali, Gourraud Pierre-Antoine, Horcholle Béatrice, Villard Jean, Marti Joachim, Loupy Alexandre
Division of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital, Faculty of Medicine, University of Lausanne, Lausanne, Switzerland.
Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Clinical Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.
Front Pharmacol. 2023 Apr 27;14:1040584. doi: 10.3389/fphar.2023.1040584. eCollection 2023.
Patient-Reported Outcomes (PRO) integrate a wide range of holistic dimensions that arenot captured within clinical outcomes. Particularly, from induction treatment to maintenance therapy, patient quality-of-life (QoL) of kidney transplant recipients have been sparsely investigated in international settings. In a prospective, multi-centric cohort study, including nine transplant centers in four countries, we explored the QoL during the year following transplantation using validated elicitation instruments (EQ-5D-3L index with VAS) in a population of kidney transplant patients receiving immunosuppressive therapies. Calcineurin inhibitors (tacrolimus and ciclosporin), IMPD inhibitor (mycophenolate mofetil), and mTOR inhibitors (everolimus and sirolimus) were the standard-of-care (SOC) medications, together with tapering glucocorticoid therapy. We used EQ-5D and VAS data as QoL measures alongside descriptive statistics at inclusion, per country and hospital center. We computed the proportions of patients with different immunosuppressive therapy patterns, and using bivariate and multivariate analyses, assessed the variations of EQ-5D and VAS between baseline (i.e., inclusion Month 0) and follow up visits (Month 12). Among 542 kidney transplant patients included and followed from November 2018 to June 2021, 491 filled at least one QoL questionnaire at least at baseline (Month 0). The majority of patients in all countries received tacrolimus and mycophenolate mofetil, ranging from 90.0% in Switzerland and Spain to 95.8% in Germany. At M12, a significant proportion of patients switched immunosuppressive drugs, with proportion varying from 20% in Germany to 40% in Spain and Switzerland. At visit M12, patients who kept SOC therapy had higher EQ-5D (by 8 percentage points, < 0.05) and VAS (by 4 percentage points, < 0.1) scores than switchers. VAS scores were generally lower than EQ-5D (mean 0.68 [0.5-0.8] vs. 0.85 [0.8-1]). Although overall a positive trend in QoL was observed, the formal analyses did not show any significant improvements in EQ-5D scores or VAS. Only when the effect of a therapy use was separated from the effect of switching, the VAS score was significantly worse for switchers during the follow up period, irrespective of the therapy type. If adjusted for patient characteristics and medical history (e.g., gender, BMI, eGRF, history of diabetes), VAS and EQ-5D delivered sound PRO measures for QoL assessments during the year following renal transplantation.
患者报告结局（PRO）整合了一系列临床结局未涵盖的整体维度。特别是，从诱导治疗到维持治疗，肾移植受者的患者生活质量（QoL）在国际环境中鲜有研究。在一项前瞻性、多中心队列研究中，该研究涵盖四个国家的九个移植中心，我们使用经过验证的测评工具（带有视觉模拟评分法的EQ-5D-3L指数），对接受免疫抑制治疗的肾移植患者群体在移植后一年的生活质量进行了探究。钙调神经磷酸酶抑制剂（他克莫司和环孢素）、肌苷单磷酸脱氢酶（IMPD）抑制剂（霉酚酸酯）和哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂（依维莫司和西罗莫司）是标准治疗（SOC）药物，同时还有逐渐减量的糖皮质激素治疗。我们将EQ-5D和视觉模拟评分法（VAS）数据用作生活质量指标，并在纳入研究时、按国家和医院中心进行描述性统计。我们计算了采用不同免疫抑制治疗模式的患者比例，并通过双变量和多变量分析，评估了EQ-5D和VAS在基线（即纳入研究的第0个月）和随访（第12个月）之间的变化。在2018年11月至公元2021年6月期间纳入并随访的542例肾移植患者中，491例至少在基线（第0个月）填写了至少一份生活质量问卷。所有国家的大多数患者都接受了他克莫司和霉酚酸酯治疗，比例从瑞士和西班牙的90.0%到德国的95.8%不等。在第12个月时，相当一部分患者更换了免疫抑制药物，比例从德国的20%到西班牙和瑞士的40%不等。在第12个月的随访中，维持标准治疗的患者的EQ-5D评分（高8个百分点，<0.05）和VAS评分（高4个百分点，<0.1）高于更换药物的患者。VAS评分总体上低于EQ-5D评分（平均0.68[0.5 - 0.8]对0.85[0.8 - 1]）。尽管总体上观察到生活质量呈积极趋势，但正式分析并未显示EQ-5D评分或VAS有任何显著改善。只有当治疗使用的效果与更换药物的效果分开时，随访期间更换药物的患者的VAS评分明显更差，无论治疗类型如何。如果对患者特征和病史（如性别、体重指数、估算肾小球滤过率、糖尿病史）进行调整，VAS和EQ-5D为肾移植后一年的生活质量评估提供了可靠的患者报告结局指标。
