Datalytics Pty Ltd, Bruce, ACT, Australia.
Pharmacoeconomics. 2014 Feb;32(2):193-207. doi: 10.1007/s40273-013-0125-7.
The efficacy and safety of adding rituximab to fludarabine and cyclophosphamide (R-FC) for the treatment of chronic lymphocytic leukaemia (CLL) has been demonstrated in two randomised trials: CLL-8 was conducted in previously untreated patients, and REACH was conducted in previously treated patients. In both trials, progression-free survival was increased in the R-FC treatment groups compared with the FC treatment groups. In CLL-8, overall survival was also significantly increased.
To develop an economic model to assess the cost effectiveness, from the Australian healthcare perspective, of rituximab when used as a treatment for both previously untreated and relapsed/refractory CLL.
A Markov model with three health states (unprogressed, progressed and death) was developed to extrapolate the trial results over a 15-year time horizon. A treatment algorithm was developed with Australian haematologists to inform the treatments to be modelled. The base-case compares up to three courses of six cycles of R-FC ('first-line' treatment) followed by three courses of post-progression salvage ('Salvage') treatment (including rituximab) with three courses of FC followed by three courses of Salvage treatment (excluding rituximab). Subsequent treatments are incorporated into the model by repeating the unprogressed and progressed health states for each treatment. Time-dependent transition probabilities for the model were estimated from an analysis of individual patient data from CLL-8 and REACH. Comparisons of the hazard rates for the CLL-8 and REACH trials enabled an assessment of the impact on the transitions of receiving the same regimen as the first or second treatment, and hence inform assumptions regarding transitions for third and subsequent treatments. Costs applied in the model were based on published Australian prices in 2009.
The model predicts patients receive an average of approximately two courses of treatment, and the addition of rituximab results in an incremental gain of 0.94 quality-adjusted life-years (QALYs). The incremental cost associated with the addition of rituximab is A$40,268, and hence the cost per QALY gained (QALYG) is A$42,906.
Rituximab, in combination with chemotherapy, when used multiple times throughout the treatment algorithm, appears to be cost effective for CLL from the Australian healthcare perspective, with a cost/QALYG within the range generally accepted as providing value.
在两项随机试验中，已经证明在氟达拉滨和环磷酰胺（R-FC）治疗基础上添加利妥昔单抗治疗慢性淋巴细胞白血病（CLL）的疗效和安全性：CLL-8 试验在未经治疗的患者中进行，而 REACH 试验在已治疗的患者中进行。在这两项试验中，与 FC 治疗组相比，R-FC 治疗组的无进展生存期增加。在 CLL-8 中，总生存期也显著增加。
从澳大利亚医疗保健的角度出发，建立一种经济模型来评估利妥昔单抗作为治疗初治和复发/难治性 CLL 的成本效益。
采用具有三个健康状态（无进展、进展和死亡）的 Markov 模型来推断试验结果在 15 年时间范围内的情况。根据澳大利亚血液学家的建议制定了治疗方案，以告知模型中所使用的治疗方法。基本情况比较了最多三个疗程六周期的 R-FC（“一线”治疗），随后是三个疗程的进展后挽救治疗（包括利妥昔单抗），以及三个疗程的 FC 治疗，随后是三个疗程的挽救治疗（不包括利妥昔单抗）。通过重复每个治疗的无进展和进展健康状态，将后续治疗纳入模型。模型中时间依赖性转移概率是根据 CLL-8 和 REACH 的个体患者数据的分析来估计的。对 CLL-8 和 REACH 试验的风险率进行比较，可以评估接受与第一或第二治疗相同方案对转移的影响，从而为第三及后续治疗的转移假设提供信息。模型中应用的成本基于 2009 年澳大利亚公布的价格。
模型预测患者平均接受大约两个疗程的治疗，添加利妥昔单抗可获得 0.94 个质量调整生命年（QALY）的增量获益。添加利妥昔单抗的增量成本为 40268 澳元，因此每获得一个 QALY 的增量成本（QALYG）为 42906 澳元。
从澳大利亚医疗保健的角度来看，利妥昔单抗联合化疗，在治疗方案的多个阶段多次使用，似乎具有成本效益，其成本/QALY 在普遍被认为具有价值的范围内。
