IMS Health Consulting, Vilvoorde, Belgium.
Pharmacoeconomics. 2010;28(12):1129-46. doi: 10.2165/11584920-000000000-00000.
Knee cartilage lesions increase the risk of developing osteoarthritis (OA), and may eventually result in a total knee replacement (TKR). There is currently no consensus on the optimal treatment of cartilage lesions. ChondroCelect® (CC) is a cell-based therapy approved for use in autologous chondrocytes implantation (ACI) to treat symptomatic cartilage defects of the femoral condyle. Its capacity to safely restore good-quality cartilage was demonstrated in a randomized controlled trial (RCT) versus the surgical procedure microfracture (MFX).
This study investigated the cost utility of CC used in ACI compared with MFX to treat symptomatic knee cartilage lesions in Belgium.
A decision tree model comparing CC with MFX over a 40-year horizon was developed in TreeAge Pro™. The key timepoints of the model were (i) clinical assessment 5 years after initial intervention (success or no success, with or without re-operation); (ii) development of OA at 15 years (yes/no); (iii) need for TKR at 20 years (yes/no); and (iv) need for prosthesis revision at 35 years (yes/no). Clinical data provided by the RCT of CC versus MFX were the clinical success (response) rate based on the Knee injury and Osteoarthritis Outcome Score (KOOS) at 36 months (82.9% vs 62.0%; p = 0.048) and the proportion of good structural repair/presence of hyaline cartilage based on International Cartilage Repair Society (ICRS II) visual item at 12 months (44.9% vs 23.2%; p = 0.023). Utility scores by surgery outcome were derived from the SF-36 questionnaire responses collected in the RCT. Conservative assumptions related to the incidences of OA, TKR and prosthesis revision relied on a literature search. A patient chart review (n = 82) provided follow-up costs by surgery outcome. National tariffs were applied to direct medical resources used (healthcare payer perspective, year 2008 costs). Annual discounting was applied to costs (3%) and effects (1.5%) as recommended by the Belgian pharmacoeconomic guidelines.
The incremental cost per QALY gained for CC compared with MFX was €16,229, with a difference in costs of €20,802 and 1.282 QALYs gained. Sensitivity analyses indicated that the key model drivers were the proportion of patients with hyaline cartilage and the correlation between hyaline cartilage formation and later avoidance of OA. Probabilistic sensitivity analyses showed robustness of the results, with 80% of the simulations below the usual UK National Institute for Health and Clinical Excellence (NICE) threshold of €22,000 per QALY.
Assuming a good correlation between high-quality cartilage repair and avoidance of OA at a later stage, the benefits of the cell therapy CC over MFX in terms of QALYs gained and OA-related costs avoided appear real. Further research is required to explore long-term effects of cartilage repair and reduce uncertainty on quality of life of patients with OA before and after joint replacement.
膝关节软骨损伤会增加发生骨关节炎（OA）的风险，并最终导致全膝关节置换（TKR）。目前对于软骨损伤的最佳治疗方法尚无共识。ChondroCelect®（CC）是一种细胞基疗法，已获得批准用于自体软骨细胞植入（ACI）以治疗股骨髁的有症状软骨缺陷。在一项随机对照试验（RCT）中，它在安全性和恢复高质量软骨方面优于微骨折（MFX）。
本研究调查了在比利时，使用 CC 进行 ACI 与 MFX 治疗有症状的膝关节软骨病变的成本效用。
在 TreeAge Pro™中开发了一个比较 CC 与 MFX 的决策树模型，该模型的关键时间点为：（i）初次干预后 5 年的临床评估（成功或不成功，是否需要再次手术）；（ii）15 年时发生 OA（是/否）；（iii）20 年时需要 TKR（是/否）；（iv）35 年时需要进行假体翻修（是/否）。CC 与 MFX 的 RCT 提供了临床数据，包括基于膝关节损伤和骨关节炎结果评分（KOOS）的临床成功率（反应率）（36 个月时为 82.9% vs 62.0%；p = 0.048）和基于国际软骨修复协会（ICRS II）视觉项目的高质量结构修复/透明软骨存在率（12 个月时为 44.9% vs 23.2%；p = 0.023）。基于 SF-36 问卷调查的手术结果得出效用评分。与 OA、TKR 和假体翻修发生率相关的保守假设是基于文献检索得出的。对 82 例患者进行病历回顾，按手术结果提供随访成本。直接医疗资源的使用采用国家关税（医保支付方视角，2008 年成本）。根据比利时药物经济学指南的建议，对成本（3%）和效果（1.5%）进行了年度贴现。
与 MFX 相比，CC 的增量成本每增加一个质量调整生命年（QALY）为 16,229 欧元，成本差异为 20,802 欧元，QALY 增加 1.282。敏感性分析表明，模型的关键驱动因素是透明软骨患者的比例，以及透明软骨形成与后期避免 OA 之间的相关性。概率敏感性分析表明，结果稳健，80%的模拟结果低于英国国家卫生与临床优化研究所（NICE）通常的 22,000 欧元/QALY 阈值。
假设高质量软骨修复与后期避免 OA 之间有很好的相关性，那么细胞疗法 CC 在获得 QALYs 和避免 OA 相关成本方面优于 MFX。需要进一步研究以探索软骨修复的长期效果，并降低对接受关节置换手术前后 OA 患者生活质量的不确定性。
