Pharmerit North America, LLC Bethesda, MD, USA.
J Med Econ. 2012;15(6):1054-63. doi: 10.3111/13696998.2012.692341. Epub 2012 Jun 11.
To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients.
Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review.
The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p=0.26 vs etanercept; p=0.86 vs adalimumab), adalimumab (p=0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p<0.001 vs etanercept; p=0.18 vs adalimumab), 0.63 for adalimumab (p=0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France).
Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.
评估接受抗肿瘤坏死因子（anti-TNF）治疗的强直性脊柱炎（AS）患者同时发生关节外表现（EAM）的比率，并检查法国和德国 AS 患者葡萄膜炎和炎症性肠病（IBD）的经济负担。
在 PubMed/Medline（2000 年 1 月至 2011 年 8 月）中确定了接受英夫利昔单抗、依那西普或阿达木单抗治疗的 AS 患者的葡萄膜炎和 IBD 之前的分析。补充分析纳入了最近的阿达木单抗临床试验数据（ATLAS[NCT00085644]和 RHAPSODY[NCT00478660]）。对于与 EAMs 相关的资源利用/成本，搜索范围扩大到了一般脊柱关节炎（SpA）疾病（即 AS、反应性关节炎或银屑病关节炎、银屑病脊柱炎、IBD 和未分化 SpA）。根据对法国和德国临床医生的访谈和文献回顾，估计了与 AS 相关的葡萄膜炎和 IBD 相关的直接和间接年度成本。
两项荟萃分析和补充阿达木单抗临床试验中接受抗 TNF 治疗的患者的前葡萄膜炎（AU）发作的平均合并率为 4.9/100 患者年（PYs）。AU 发生率（每 100-PYs）分别为 3.4、3.7 和 5.7 为英夫利昔单抗（p=0.26 与依那西普；p=0.86 与阿达木单抗），阿达木单抗（p=0.033 与依那西普；p=0.18 与阿达木单抗）和依那西普。IBD 发作（每 100-PYs）分别为英夫利昔单抗 0.2（p<0.001 与依那西普；p=0.18 与阿达木单抗），阿达木单抗 0.63（p=0.009 与依那西普）和依那西普 2.2。未发现评估 AS 患者 EAM 相关资源利用或成本的研究。IBD 治疗相关的直接医疗费用在德国为 483 欧元，在法国为 6443 欧元。临床医生估计的与 AS 相关的葡萄膜炎直接医疗费用在德国为 1410 欧元，在法国为 1812 欧元。
临床数据综合分析表明，阿达木单抗与依那西普相比，AU 发作率显著降低，阿达木单抗和英夫利昔单抗与依那西普相比，IBD 发生率显著降低。经济分析表明，法国和德国因 AS 而继发的 AU 和 IBD 发作会产生大量成本。未来对抗 TNF 药物的经济评估应纳入 EAMs 和随后的治疗成本。限制包括随机、安慰剂对照临床试验数据的可用性有限、纳入开放标签研究的数据、缺乏真实世界（即非试验基础）EAM 率以及缺乏 EAM 特异性直接和间接成本，无法与本文中呈现的结果进行比较。
