H. P. Acthar gel, or repository corticotropin (rACTH), was approved by the US Food and Drug Administration (FDA) in 1952 and currently is indicated for the treatment of infantile spasms, exacerbations of multiple sclerosis, and, nebulously, “rheumatic; collagen; dermatologic; allergic states; ophthalmic; respiratory; and edematous state.”1 The unremarkable history of this little-known drug is in contrast to its astounding rise in price, detailed in this issue of JAMA Internal Medicine, by Hartung and colleagues.2 The authors found that the price of the drug to Medicare increased almost overnight from $1650 to over $24 000 per 5-mL vial when it was acquired by Questcor in 2001 and continued to rise. It was acquired by Mallinkrodt in 2014, who increased the price yet again. It is currently $34 034 per 5 mL vial. Remarkably, Medicare spent $1.3 billion dollars on Achthar gel between 2011 and 2015.2 Although the usual stated reason (if there is one) for the high prices of drugs is high research and development costs, or life-saving qualities of the drug, neither of these explain the high price for Achthar gel. The strongest data for rACTH are for infantile spasms, which include randomized clinical trials performed in the 1980s.3 However, in adult medicine, it is being prescribed primarily by rheumatologists, neurologists, and nephrologists despite the lack of evidence for its efficacy in any adult conditions. Indeed, the only available data applicable to these 3 specialties come from case series and “prospective cohort studies” focusing on low vs high dosages, not placebo comparisons, of rACTH gel. There are fewer than 30 small and underpowered studies, all with less than 50 patients, investigating the efficacy of rACTH for conditions such as sarcoidosis, systemic lupus erythematosus, nephrotic syndrome, and multiple sclerosis. Even a “multicenter” study included only 44 patients.4 In addition, for nearly all of these studies, multiple authors have conflicts of interest owing to ties with the manufacturer of Acthar gel,5-7 and some of these studies are supported by grants from Mallinckrodt (née Questcor).8-10 The FDA does not consider cost in the approval process and often approves drugs that lack comparative effectiveness data.11 Medicare routinely pays for all FDA-approved drugs and has no authority to negotiate drug prices. The case of Achthar gel illustrates the problems of this system, compounded when many physicians prescribe an expensive drug that has weak to no effectiveness data despite the availability of a less costly and effective alternative (corticosteroids). Hartung et al2 allude to “high-pressure sales tactics” from representatives of QuestCor or Mallinckrodt Pharmaceuticals. The lack of high-quality evidence supporting Achthar gel’s benefit in a variety of conditions, along with the unconscionable price increase by the manufacturer, should give pause to all practitioners. Not only should clinicians consider the lack of evidence supporting the efficacy of rACTH, but its story should cause us to reexamine and strengthen our standards for FDA approval, Medicare and private insurance coverage, and professional use patterns.

中文翻译：

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旧药的新（非常高）价格

HP Acthar 凝胶或促肾上腺皮质激素 (rACTH) 于 1952 年获得美国食品和药物管理局 (FDA) 的批准，目前适用于治疗婴儿痉挛症、多发性硬化症的恶化以及模糊的“风湿性；胶原; 皮肤科；过敏状态；眼科；呼吸; 和水肿状态。”1 这种鲜为人知的药物平淡无奇的历史与其惊人的价格上涨形成鲜明对比，Hartung 及其同事在本期 JAMA Internal Medicine 中对此进行了详细介绍。2 作者发现，这种药物的价格高达在 2001 年被 Questcor 收购时，Medicare 几乎在一夜之间从每 5 毫升小瓶的 1650 美元增加到超过 24000 美元，并继续上涨。它于 2014 年被 Mallinkrodt 收购，后者再次提高了价格。目前每 5 毫升小瓶售价 34 034 美元。值得注意的是，Medicare 花了 1 美元。2011 年至 2015 年间，Achthar 凝胶的价格为 30 亿美元。2 尽管通常所说的药物价格高的原因（如果有的话）是高研发成本或药物的救命品质，但这些都不能解释高价格用于 Achthar 凝胶。rACTH 最强的数据是婴儿痉挛症，其中包括 1980 年代进行的随机临床试验。 3 然而，在成人医学中，尽管缺乏证据证明其对任何成人有效，但它主要由风湿病学家、神经病学家和肾病学家开处方使适应。实际上，适用于这 3 个专业的唯一可用数据来自病例系列和“前瞻性队列研究”，这些研究侧重于 rACTH 凝胶的低剂量与高剂量，而不是安慰剂比较。有不到 30 项小型和动力不足的研究，所有研究都少于 50 名患者，研究 rACTH 对结节病、系统性红斑狼疮、肾病综合征和多发性硬化症等疾病的疗效。即使是“多中心”研究也仅包括 44 名患者。 4 此外，对于几乎所有这些研究，多位作者由于与 Acthar 凝胶制造商的关系而存在利益冲突，5-7 并且其中一些研究得到了资助来自 Mallinckrodt (née Questcor)。8-10 FDA 在批准过程中不考虑成本，并且经常批准缺乏比较有效性数据的药物。11 Medicare 通常为所有 FDA 批准的药物支付费用，并且无权协商药物价格。Achthar凝胶的案例说明了这个系统的问题，当许多医生开出一种昂贵的药物时，尽管有一种成本较低且有效的替代品（皮质类固醇），但其有效性数据很弱甚至没有，这种情况更加复杂。Hartung 等人 2 暗指来自 QuestCor 或 Mallinckrodt Pharmaceuticals 代表的“高压销售策略”。缺乏支持 Achthar 凝胶在各种条件下有益的高质量证据，以及制造商不合理的价格上涨，应该让所有从业者停下来。临床医生不仅应该考虑缺乏支持 rACTH 疗效的证据，而且它的故事应该促使我们重新审视和加强我们对 FDA 批准、医疗保险和私人保险范围以及专业使用模式的标准。Hartung 等人 2 暗指来自 QuestCor 或 Mallinckrodt Pharmaceuticals 代表的“高压销售策略”。缺乏支持 Achthar 凝胶在各种条件下有益的高质量证据，以及制造商不合理的价格上涨，应该让所有从业者停下来。临床医生不仅应该考虑缺乏支持 rACTH 疗效的证据，而且它的故事应该促使我们重新审视和加强我们对 FDA 批准、医疗保险和私人保险范围以及专业使用模式的标准。Hartung 等人 2 暗指来自 QuestCor 或 Mallinckrodt Pharmaceuticals 代表的“高压销售策略”。缺乏支持 Achthar 凝胶在各种条件下有益的高质量证据，以及制造商不合理的价格上涨，应该让所有从业者停下来。临床医生不仅应该考虑缺乏支持 rACTH 疗效的证据，而且它的故事应该促使我们重新审视和加强我们对 FDA 批准、医疗保险和私人保险范围以及专业使用模式的标准。