Boonen A, van der Heijde D, Severens J L, Boendermaker A, Landewé R, Braun J, Brandt J, Sieper J, van der Linden Sj
Department of Internal Medicine, Division of Rheumatology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, Netherlands.
Ann Rheum Dis. 2006 Feb;65(2):201-8. doi: 10.1136/ard.2004.032565. Epub 2005 Jul 13.
To estimate the incremental cost-utility of etanercept and infliximab compared with usual care in active ankylosing spondylitis.
A Markov model over five years with cycle times of three months was computed. Patients included all had active disease, defined as Bath ankylosing spondylitis disease activity index (BASDAI) >or=4 and could reach low disease activity, defined as BASDAI <4. Non-response to tumour necrosis factor alpha (TNFalpha) inhibitors was always followed by cessation of treatment. Response to TNFalpha inhibitors could be followed at any time by either relapse to BASDAI >or=4, leading to cessation of treatment, or toxicity, leading to cessation of treatment if major. Probabilities for efficacy, relapse, and toxicity were derived from two European randomised controlled trials. Utilities and costs assigned to the BASDAI disease states were derived from a two year observational Dutch cohort. In sensitivity analyses probabilities of effectiveness, toxicity, costs, and utilities were varied.
Over five years the total quality adjusted life years varied from 2.57 to 2.89 for usual care, compared with 3.13 to 3.42 and 3.07 to 3.35 for etanercept or infliximab. Cumulative costs were between 49,555 to 69,982 for usual care compared with 59,574 to 91,183 or 28,3330 to 106,775 for etanercept and infliximab. This resulted in incremental cost-utility ratios varying between 42,914 and 123,761 per QALY for etanercept compared with usual care and 67,207 to 237,010 for infliximab. The model was sensitive to drug prices.
Etanercept and infliximab have large clinical effects in ankylosing spondylitis. The present model suggests the high drug costs restricts efficient use in all patients who have a BASDAI >4. The validity of the model is limited by insufficient insight in the natural course of the disease and long term effectiveness and toxicity of TNFalpha inhibitors.
评估与常规治疗相比,依那西普和英夫利昔单抗用于活动性强直性脊柱炎的增量成本效益。
构建一个为期五年、周期为三个月的马尔可夫模型。纳入的患者均患有活动性疾病,定义为巴斯强直性脊柱炎疾病活动指数(BASDAI)≥4,且能够达到低疾病活动度,定义为BASDAI<4。对肿瘤坏死因子α(TNFα)抑制剂无反应者始终停止治疗。对TNFα抑制剂有反应者在任何时候都可能出现复发至BASDAI≥4(导致停止治疗)或出现毒性反应(如为重度则导致停止治疗)。疗效、复发和毒性的概率来自两项欧洲随机对照试验。分配给BASDAI疾病状态的效用值和成本来自一项为期两年的荷兰观察性队列研究。在敏感性分析中,改变了有效性、毒性、成本和效用的概率。
在五年期间,常规治疗的总质量调整生命年为2.57至2.89,依那西普或英夫利昔单抗则为3.13至3.42以及3.07至3.35。常规治疗的累积成本在49,555至69,982之间,依那西普和英夫利昔单抗则为59,574至91,183或28,3330至106,775。这导致依那西普与常规治疗相比的增量成本效益比在每质量调整生命年42,914至123,761之间,英夫利昔单抗则为67,207至237,010。该模型对药物价格敏感。
依那西普和英夫利昔单抗在强直性脊柱炎中具有显著临床效果。当前模型表明,高昂的药物成本限制了对所有BASDAI>4患者的有效应用。该模型的有效性因对疾病自然病程以及TNFα抑制剂的长期有效性和毒性了解不足而受到限制。