Fischer K, Lewandowski D, Janssen M P
Julius Center for Health Sciences and Primary care, University Medical Center Utrecht, Utrecht, The Netherlands.
Van Creveldkliniek, University Medical Center Utrecht, Utrecht, The Netherlands.
Haemophilia. 2016 Sep;22(5):e375-82. doi: 10.1111/hae.13019. Epub 2016 Jun 28.
Lifelong prophylactic replacement therapy with clotting factor concentrates is recommended for severe haemophilia. The prophylactic dose determines both clinical outcome and treatment cost. In the absence of clinical studies, computer simulation was used to explore lifelong effects and clotting factor consumption for various prophylactic dose levels, and optimize strategies for switching between prophylactic and on-demand treatment.
Individual patients' lifetime joint bleeds, radiological arthropathy (Pettersson score, 0-78) and consumption were simulated for each treatment strategy. Treatment effectiveness (expressed as % of patients maintaining a lifetime Pettersson score ≤14) and clotting factor consumption were modelled for lifelong prophylaxis at dose levels 1000-4500 IU kg(-1) year(-1) , for on-demand treatment and for switching strategies. Treatment efficiency (consumption per unit of effectiveness) was used to compare strategies.
Compared to lifelong on-demand treatment, lifelong prophylaxis at 1000 IU kg(-1) year(-1) increased effectiveness from 21 to 36%, at an additional consumption of 0.9 × 10(6) IU kg(-1) . For lifelong prophylaxis, each additional 1000 IU kg(-1) year(-1) resulted in a proportional increase in consumption by ±5 × 10(6) IU kg(-1) but a less than proportional reduction in arthropathy by ±50%; consequently, increasing consumption progressively diminished treatment efficiency. Switching strategies slightly reduce effectiveness and consumption. Optimum switching criteria were similar across prophylactic dose levels.
According to the simulation model, low-dose prophylaxis (1000 IU kg(-1) year(-1) ) improved outcome at a limited increase in consumption compared to on-demand treatment. Increasing prophylactic dose further improved health outcomes, but at decreasing efficiency. Optimal prophylactic dose should therefore be selected balancing acceptable health impact and available budget.
对于重度血友病患者，建议采用凝血因子浓缩物进行终身预防性替代治疗。预防剂量决定了临床疗效和治疗成本。在缺乏临床研究的情况下，利用计算机模拟来探究不同预防剂量水平的终身影响和凝血因子消耗情况，并优化预防治疗和按需治疗之间的转换策略。
针对每种治疗策略，模拟个体患者的终身关节出血、放射学关节病（Pettersson评分，0 - 78）和消耗量。对剂量水平为1000 - 4500 IU kg⁻¹ 年⁻¹ 的终身预防治疗、按需治疗以及转换策略，模拟治疗效果（以终身Pettersson评分≤14的患者百分比表示）和凝血因子消耗情况。采用治疗效率（每单位疗效的消耗量）来比较不同策略。
与终身按需治疗相比，1000 IU kg⁻¹ 年⁻¹ 的终身预防治疗使疗效从21%提高到36%，额外消耗量为0.9×10⁶ IU kg⁻¹ 。对于终身预防治疗，每增加1000 IU kg⁻¹ 年⁻¹ ，消耗量相应增加±5×10⁶ IU kg⁻¹ ，但关节病的减少幅度小于相应比例，约为±50%；因此，随着消耗量的增加，治疗效率逐渐降低。转换策略可略微降低疗效和消耗量。不同预防剂量水平的最佳转换标准相似。
根据模拟模型，与按需治疗相比，低剂量预防治疗（1000 IU kg⁻¹ 年⁻¹ ）在消耗量有限增加的情况下改善了治疗效果。增加预防剂量可进一步改善健康结局，但效率降低。因此，应在可接受的健康影响和可用预算之间进行平衡，选择最佳预防剂量。
