Montgomery Stephen M, Kusel Jeanette, Nicholas Richard, Adlard Nicholas
a Costello Medical Consulting Ltd , Cambridge , UK.
b Imperial College Healthcare NHS Trust, Charing Cross Hospital , London , UK.
J Med Econ. 2017 Sep;20(9):962-973. doi: 10.1080/13696998.2017.1345748. Epub 2017 Jul 11.
Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis.
A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs.
Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient.
When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of confidential PAS discount.
接受疾病修正疗法（DMTs）治疗的复发缓解型多发性硬化症（RRMS）患者若仍有疾病活动，可考虑升级疗法，如芬戈莫德，或考虑使用阿仑单抗。以往的经济学模型采用马尔可夫模型；应用另一种技术，即离散事件模拟（DES）建模，可将再治疗和长期不良事件（AEs）纳入分析。
采用DES对阿仑单抗复发触发的再治疗以及纳入超出先前1年马尔可夫周期的AEs持续质量调整生命年（QALY）递减效应进行建模。由于英国国家医疗服务体系（NHS）中芬戈莫德的价格因患者保密获取计划（PAS）而未知，因此测试了各种可能的折扣。测试阿仑单抗再治疗假设与芬戈莫德可能折扣之间的相互作用，以确定哪种DMT导致更低的终身成本。终身QALY结果来自建模的治疗效果以及短期和长期AEs。
芬戈莫德PAS折扣和阿仑单抗再治疗率的大多数排列组合导致芬戈莫德的成本低于阿仑单抗。当因复发而接受阿仑单抗再治疗的患者百分比接近治疗期间复发患者的100%时，芬戈莫德成本更低所需的折扣降至5%以下。仅考虑治疗效果时，发现阿仑单抗每位患者产生的QALY多0.2；纳入长达1年的AEs后，这一优势降至仅每位患者0.14 QALY。对具有终身QALY递减的AEs进行建模发现，两种DMT产生的QALY非常相似，差异仅为每位患者0.04 QALY。
当模型纳入阿仑单抗再治疗和长期AE递减时，发现假设仅应用适度水平的保密PAS折扣，与阿仑单抗相比，芬戈莫德具有成本效益。
