Objective

To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers.

Methods

Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings.

Results

Fifteen cases of adults with PKU (eight males, seven females), representing a spectrum of age (18 to 53 years), previous PKU care, comorbidities, and socioeconomic situations were reviewed and discussed. Full extended case reports are included in the Supplement. The cases showed that treating patients with a daily injectable can be challenging due to a patient's financial problems, treatment challenges, and neuropsychological and psychiatric comorbidities, which can be identified before starting pegvaliase, but do not prohibit successful treatment. The authors agreed that patient education on adverse events (AEs), time to efficacy, dietary changes, and food preparation is an ongoing process that should start prior to initiating pegvaliase treatment. Treatment goals and planned dietary changes once efficacy is reached should be defined prior to treatment initiation and re-evaluated throughout the course of therapy. Each patient's titration schedule and dietary adjustments are unique, depending on occurrence of AEs and individual goals of treatment. Despite the AE profile of pegvaliase, all but two patients remained motivated to continue treatment and achieved efficacy (except one patient in whom titration was still ongoing). AEs occurring early in the treatment pathway may require prolongation of the titration phase and/or concomitant medication use, but do not seem indicative of future tolerability or eventual efficacy. Close follow-up of patients during titration and maintenance to help with dietary changes is important.

Conclusion

This case series provides real-world experience on the use of pegvaliase. Until data from registries and independent research become available, the data presented herein can support appropriate management of patients receiving pegvaliase in clinical practice.

中文翻译：

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聚乙二醇化酶在苯丙酮尿症治疗中的应用：美国诊所早期经验的病例系列

客观的

根据美国医疗保健提供者的初步经验，展示一个案例系列，说明 pegvaliase 在现实世界中的使用。

方法

自 FDA 批准（2018 年 5 月）以来的两年多时间里，来自美国 14 个中心的 16 家医疗保健提供者在使用 pegvaliase 治疗苯丙酮尿症 (PKU) 患者方面拥有丰富的临床经验，提供的案例证明了他们最初使用 pegvaliase 治疗患者的经验中的重要教训. 在现场和虚拟会议中讨论了每个案例的主要经验教训和要点。

结果

回顾和讨论了 15 例 PKU 成人患者（8 名男性，7 名女性），代表不同的年龄范围（18 至 53 岁）、以前的 PKU 护理、合并症和社会经济状况。完整的扩展病例报告包含在补编中。这些案例表明，由于患者的经济问题、治疗挑战以及神经心理和精神合并症，可以在开始 pegvaliase 之前确定这些问题，但不妨碍成功的治疗，因此使用每日注射剂治疗患者可能具有挑战性。作者一致认为，关于不良事件 (AE)、疗效时间、饮食变化和食物准备的患者教育是一个持续的过程，应在开始 pegvaliase 治疗之前开始。一旦达到疗效，治疗目标和计划的饮食变化应在治疗开始前确定，并在整个治疗过程中重新评估。每个患者的滴定计划和饮食调整都是独一无二的，具体取决于 AE 的发生和个人治疗目标。尽管有 pegvaliase 的 AE 特征，但除两名患者外，所有患者仍然有继续治疗的动力并取得了疗效（除了一名仍在进行滴定的患者）。在治疗途径早期发生的 AE 可能需要延长滴定阶段和/或伴随药物使用，但似乎并不表示未来的耐受性或最终疗效。在滴定和维持期间密切随访患者以帮助改变饮食是很重要的。

结论

本案例系列提供了使用 pegvaliase 的真实经验。在获得来自注册和独立研究的数据之前，本文提供的数据可以支持在临床实践中对接受 pegvaliase 的患者进行适当管理。