Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre+ (MUMC+), P. Debyelaan 25, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
Kleijnen Systematic Reviews Ltd, York, UK.
Pharmacoeconomics. 2022 May;40(5):509-518. doi: 10.1007/s40273-021-01098-3. Epub 2021 Oct 19.
The National Institute for Health and Care Excellence (NICE) invited the manufacturer (Kyowa Kirin) of mogamulizumab (Poteligeo), as part of the single technology appraisal process, to submit evidence for its clinical and cost-effectiveness for previously treated mycosis fungoides (MF) and Sézary syndrome (SS). Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre, was commissioned to act as the independent evidence review group (ERG). This paper summarises the company submission (CS), presents the ERG's critical review of the clinical and cost-effectiveness evidence in the CS, highlights the key methodological considerations and describes the development of the NICE guidance by the Appraisal Committee. Based on a systematic literature review, one randomised controlled trial, MAVORIC, was identified showing favourable results in patients with MF and SS. However, MAVORIC compared mogamulizumab to vorinostat, which is not standard care in the NHS, and there is uncertainty due to the study design, specifically crossover of patients. Based on a "naïve comparison of results from the vorinostat arm of the MAVORIC study and the physician's choice arm (methotrexate or bexarotene i.e. United Kingdom [UK] standard treatments) of the ALCANZA study as well as comparison to Phase II bexarotene data", the company considered vorinostat to be "a reasonable proxy for current standard of care in the NHS". The ERG considered, based on the limited data available, that the comparability of vorinostat (MAVORIC) and physician's choice (ALCANZA) could not be established. In response to the Appraisal Consultation Document, the company provided an unanchored matched adjusted indirect comparison (MAIC) of mogamulizumab with UK standard care by analysing Hospital Episode Statistics (HES) data. However, given the high risk of bias of an unanchored MAIC, these results needed to be regarded with a considerable degree of caution. The economic analysis suffered from uncertainty because there was no trial evidence on the comparator in the England and Wales National Health Service (NHS), and it was unclear to what extent the trial (MAVORIC) comparator (vorinostat) was comparable to standard care, referred to as established clinical management (ECM) in the NHS. The evidence for overall survival had not reached maturity and was confounded by treatment switching, for which different crossover adjustment methods produced large variations in life years. Caregiver utilities were applied in the analysis, but there was a lack of guidance on their application and whether these were indicated in this appraisal. After consultation, the company updated the economic analysis with the MAIC. Incremental cost-effectiveness ratios comparing mogamulizumab against ECM were (depending on whether the HES or MAVORIC comparison were used) £31,030 or £32,634 per quality-adjusted life years (QALYs) gained according to the company's base case and £38,274 or £80,555 per QALY gained according to the ERG's base case. NICE did not recommend mogamulizumab for treating MF or SS in adults who have had at least one previous systemic treatment. This decision was subsequently appealed, and an appeal decision has been reached.
国家卫生与保健卓越研究所（NICE）邀请 mogamulizumab（Poteligeo）的制造商（协和麒麟），作为单一技术评估过程的一部分，提交其在先前治疗蕈样真菌病（MF）和塞扎里综合征（SS）方面的临床和成本效益的证据。Kleijnen 系统评价有限公司与马斯特里赫特大学医学中心合作，被委托作为独立的证据审查小组（ERG）。本文总结了公司提交的材料（CS），展示了 ERG 对 CS 中临床和成本效益证据的关键审查，强调了关键的方法学考虑因素，并描述了评估委员会制定 NICE 指南的过程。基于系统文献回顾，确定了一项随机对照试验 MAVORIC，显示 MF 和 SS 患者的结果有利。然而，MAJORIC 将 mogamulizumab 与 vorinostat 进行了比较，而 vorinostat 并非英国国民保健署（NHS）的标准治疗方法，并且由于研究设计，特别是患者的交叉，存在不确定性。基于“从 MAVORIC 研究的 vorinostat 臂和 ALCANZA 研究的医生选择臂（即甲氨蝶呤或贝沙罗汀，即英国标准治疗）的结果进行的天真比较，以及与 II 期贝沙罗汀数据的比较”，公司认为 vorinostat 是“NHS 中当前标准治疗的合理代表”。ERG 认为，根据现有有限的数据，vorinostat（MAVORIC）和医生选择（ALCANZA）之间的可比性无法建立。针对评估咨询文件，公司通过分析医院住院统计数据（HES）提供了 mogamulizumab 与英国标准护理的无锚匹配调整间接比较（MAIC）。然而，由于无锚 MAIC 的高度偏倚风险，这些结果需要非常谨慎地对待。由于英格兰和威尔士国民保健署（NHS）中没有关于对照的试验证据，并且不清楚试验（MAVORIC）对照（vorinostat）与标准护理的可比性，因此经济分析存在不确定性，NHS 中的标准护理被称为既定临床管理（ECM）。总体生存的证据尚未成熟，并且受到治疗转换的影响，不同的交叉调整方法会导致生命年数的大幅变化。在分析中应用了护理人员效用，但缺乏关于其应用的指导以及在该评估中是否需要这些指导的信息。在磋商后，公司根据 MAIC 更新了经济分析。与 ECM 相比，mogamulizumab 的增量成本效益比（取决于使用 HES 或 MAVORIC 比较）分别为每增加一个质量调整生命年（QALY）31030 英镑或 32634 英镑，而根据公司的基本情况，每增加一个 QALY 则为 38274 英镑或 80555 英镑。NICE 不建议将 mogamulizumab 用于治疗至少接受过一次先前全身治疗的成年人的 MF 或 SS。这一决定随后被上诉，现已做出上诉决定。
