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生物疗法治疗斑块状银屑病患者的累积临床获益成本:系统评价。

Cost per cumulative clinical benefit of biologic therapies for patients with plaque psoriasis: a systematic review.

机构信息

Oregon Medical Research Center, Portland, OR.

Eli Lilly and Company, Indianapolis, IN, and University of Cincinnati, Cincinnati, OH.

出版信息

J Manag Care Spec Pharm. 2021 Jan;27(1):84-94. doi: 10.18553/jmcp.2021.27.1.084.

Abstract

Measuring cumulative clinical treatment benefit over time captures speed and magnitude of effects. Assessing the cost of biologics relative to their cumulative clinical benefits versus a single time point represents an alternative to evaluate the value of a given biologic used to treat psoriasis. To compare cumulative benefit and cost per cumulative benefit of biologics in treatment of moderate to severe psoriasis from a network meta-analysis (NMA). Biologics included in the analysis were ixekizumab, adalimumab, guselkumab, ustekinumab, secukinumab, risankizumab, and certolizumab pegol. Psoriasis Area and Severity Index (PASI) responses over the initial 16-week treatment period were obtained from 31 articles. Cumulative benefits for PASI 75, PASI 90, and PASI 100 responses were measured as area under the curve (AUC) using the trapezoidal method. Bayesian-based NMA modeled percent maximum AUC through week 16 (%Max_AUC). The AUC estimates over 16 weeks were converted to total skin clearance threshold days achieved for PASI 75, PASI 90, and PASI 100 with each biologic. Cost per cumulative benefit was estimated by multiplying number of doses (per FDA label) by nationally representative discounted wholesale acquisition costs (WACs) for 16 weeks of treatment divided by %Max_AUC. The primary cost analysis used WACs, including week 16 doses. Co-primary cost analysis used discounted WACs, including week 16 doses. Sensitivity analysis was conducted using WACs and discounted WACs, excluding doses administered at week 16. Among biologics with available week 16 AUC data for PASI 90 and PASI 100, cumulative benefits over the initial 16-week treatment period ranged from 20.2% (certolizumab pegol) to 47.0% (ixekizumab) for PASI 90 and from 7.4% (adalimumab) to 22.2% (ixekizumab) for PASI 100. The total number of estimated PASI 90 and PASI 100 days achieved over the first 16 weeks of treatment was highest with ixekizumab (53 days and 25 days, respectively). In the primary analysis, guselkumab had the lowest cost per cumulative benefit (95% credible interval [CrI]; $99,742 [$89,941-$111,653]), followed by ixekizumab ($108,906 [$95,928-$126,093]) and adalimumab ($111,233 [$97,549-$129,022]) for PASI 90, and ixekizumab had the lowest cost per cumulative benefit ($230,884 [$191,611-$291,115]), followed by secukinumab ($238,945 [$204,029-$288,072]) and risankizumab ($279,968 [$250,683-$316,872]) for PASI 100 responses. In the co-primary analysis, ixekizumab had the lowest discounted cost per AUC (95% CrI; $60,988 [$53,719-$70,612]), followed by guselkumab ($66,827 [$60,260-$74,807]) and secukinumab ($69,622 [$61,783-$79,786]) for PASI 90, and ixekizumab had the lowest cost per cumulative benefit ($129,295 [$107,302-$163,024]), followed by secukinumab ($148,146 [$126,498-$178,605]) and guselkumab ($188,190 [$166,791-$215,969]) for PASI 100 responses. Among biologics studied, ixekizumab demonstrated the greatest cumulative clinical benefit, maintaining the lowest cost per cumulative benefit for PASI 100 responses and lowest discounted cost per cumulative benefit for PASI 90 and PASI 100 responses for moderate to severe psoriasis over the initial 16-week treatment period. This study was funded by Eli Lilly and Company (Indianapolis, IN). Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Ortho, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma and as a paid speaker for AbbVie. Burge, Zhu, Malatestinic, Brnabic, Guo, and Janardhanan are employees and shareholder of Eli Lilly and Company.

摘要

评估生物制剂相对于其在单一时间点的累积临床获益的成本,代表了评估用于治疗银屑病的特定生物制剂价值的一种替代方法。本网络荟萃分析(NMA)旨在比较生物制剂在中重度银屑病治疗中的累积获益和成本效益。纳入分析的生物制剂包括依奇珠单抗、阿达木单抗、古塞库单抗、乌司奴单抗、司库奇尤单抗、瑞莎珠单抗和certolizumab pegol。从 31 篇文章中获得了初始 16 周治疗期间的银屑病面积和严重程度指数(PASI)反应。PASI 75、PASI 90 和 PASI 100 反应的累积获益通过使用梯形法计算曲线下面积(AUC)。基于贝叶斯的 NMA 通过第 16 周的最大 AUC(%Max_AUC)来模拟百分率 AUC。在 16 周内的 AUC 估计值被转换为在每个生物制剂中实现 PASI 75、PASI 90 和 PASI 100 总皮肤清除阈值的天数。通过将剂量(按 FDA 标签)乘以国家代表性的折扣批发收购成本(WAC),并除以%Max_AUC,计算出每累积获益的成本。主要成本分析使用了 WAC,包括第 16 周的剂量。共同主要成本分析使用了折扣后的 WAC,包括第 16 周的剂量。敏感性分析使用了 WAC 和折扣后的 WAC,排除了第 16 周给药的剂量。在具有可用的 PASI 90 和 PASI 100 周 16 AUC 数据的生物制剂中,初始 16 周治疗期间的累积获益从 PASI 90 的 20.2%(certolizumab pegol)到 47.0%(依奇珠单抗)不等,PASI 100 的 7.4%(阿达木单抗)到 22.2%(依奇珠单抗)不等。使用依奇珠单抗治疗,在第 16 周治疗的前 16 周内,估计 PASI 90 和 PASI 100 的天数最高,分别为 53 天和 25 天。在主要分析中,古塞库单抗的每累积获益成本最低(95%可信区间[CrI];$99742[$89941-$111653]),其次是依奇珠单抗($108906 [$95928-$126093])和阿达木单抗($111233 [$97549-$129022]),用于治疗 PASI 90,而依奇珠单抗的每累积获益成本最低($230884 [$191611-$29115]),其次是司库奇尤单抗($238945 [$204029-$288072])和瑞莎珠单抗($279968 [$250683-$316872]),用于治疗 PASI 100。在共同主要分析中,依奇珠单抗的折扣后每 AUC 成本最低(95% CrI;$60988 [$53719-$70612]),其次是古塞库单抗($66827 [$60260-$74807])和司库奇尤单抗($69622 [$61783-$79786]),用于治疗 PASI 90,而依奇珠单抗的每累积获益成本最低($129295 [$107302-$163024]),其次是司库奇尤单抗($148146 [$126498-$178605])和古塞库单抗($188190 [$166791-$215969]),用于治疗 PASI 100。在研究的生物制剂中,依奇珠单抗显示出最大的累积临床获益,在初始 16 周治疗期间,PASI 100 反应的成本效益最高,PASI 90 和 PASI 100 反应的折扣后每累积获益成本最低。本研究由礼来公司(印第安纳波利斯,IN)资助。Blauvelt 曾担任 AbbVie、Aclaris、Almirall、Arena、Athenex、Boehringer Ingelheim、Bristol-Myers Squibb、Dermavant、Dermira、Eli Lilly and Company、Forte、Galderma、Incyte、Janssen、Leo、Novartis、Orth o、Pfizer、Rapt、Regeneron、Sandoz、Sanofi Genzyme、Sun Pharma 和 UCB Pharma 的科学顾问和/或临床研究研究员,并为 AbbVie、Aclaris、Almirall、Arena、Athenex、Boehringer Ingelheim、Bristol-Myers Squibb、Dermavant、Dermira、Eli Lilly and Company、Forte、Galderma、Incyte、Janssen、Leo、Novartis、Orth o、Pfizer、Rapt、Regeneron、Sandoz、Sanofi Genzyme、Sun Pharma 和 UCB Pharma 做过付费演讲。Burge、Zhu、Malatestinic、Brnabic、Guo 和 Janardhanan 是礼来公司的员工和股东。

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