Sickle cell disease (SCD)** For this study, individuals with SCD were identified as children in the National Health Interview Survey (NHIS) whose parental guardian confirmed that “a doctor or other health professional has ever told the parents their child has sickle cell anemia.”
is one of the most common inherited blood disorders in the United States (US), found in nearly 1/3000 Americans¹ and disproportionately affecting Black (1/365 births) and Hispanic (1/16300) populations.¹

Clinical manifestations start in early childhood, including severe episodic and chronic pain, multisystem organ failure, stroke, and life-threatening infections. In addition, patients experience lower academic achievement compared to healthy individuals with similar demographic characteristics, have lower chances of meaningful employment in adulthood, face trouble in attention and concentration, score lower on measures of intelligence,² have increased school absences, and are more likely to repeat grades.³ For children with SCD in households below the federal poverty line (FPL) or with parents without higher education, disease impacts are exacerbated.

While newborn screening programs, penicillin prophylaxis and modest improvements in treatment options have enabled individuals with SCD to live into adulthood, current life expectancy (LE) estimates vary but are not beyond the fifth decade.⁴

SCD also perpetuates existing disparities in health and wealth between Blacks, other minority groups, and non-Hispanic Whites. In an environment where Black Americans disproportionately experience poorer health, educational, and economic outcomes compared to other groups, Black Americans with SCD and their families are left further behind. A recent report by the National Academy of Sciences, Engineering, and Medicine reviewed research on economic disparities, finding higher unemployment rates attributable to lower educational attainment, cognitive impairment, and high treatment burden for those living with SCD, compared to matched controls.² Additionally, children with SCD reported delays in accessing care, a reality consistent across the entire SCD population.

Despite all this, the economic impact of SCD for Black Americans remains poorly understood. A previous cohort simulation model estimated projected lifetime income for individuals with SCD to be $695 000 less than that of matched individuals without SCD, due to differences in LE alone.⁵ However, no studies to date have considered or modeled new earnings trajectories of SCD patients if cured from disease or assessed how changes in earnings would reduce income disparities,†† Throughout this paper, cure is used to describe hypothetical future genetic therapy; no cure is used to describe currently available therapies. The authors acknowledge there is no universal definition of a cure, and that “cure” may mean something different to everyone. For purposes of this model, cure is defined as stoppage of the active manifestation of disease, and based on age of treatment, a potential offsetting of the downstream impact on lifelong disease-related comorbidity.
both of which seem meaningful and timely in anticipation of new curative-intent treatments in this setting.

To quantify effects of a cure on annual income and future earnings, we use a cohort-based microsimulation model to project lifetime earnings trajectories at different points along the life course among individuals with imputed SCD, pre- and post-cure. Additional detail on the study methodology is available in the Supporting Information S1 to this article.

In our model, a cured individual experienced increased productivity and a new earnings trajectory, due to absence of SCD-related health crises and hospitalizations along with increased LE and increased opportunity to pursue education.

Among a nationally representative sample of 6352 weighted individuals (SCD: 3176, Non-SCD: 3176) from the 1997 Child Development Supplement to the Panel Survey on Income Dynamics, we found substantial gaps in earnings between individuals with SCD and comparable individuals without SCD. As shown in Figure 1A, individuals with SCD earn between 42% and 46% less annually than the healthy comparison group. NPV of lifetime earnings of the SCD cohort is 59%–66% lower, and undiscounted lifetime income is 69%–75% lower, compared to matched controls.

Introducing a cure partially closes this SCD earnings gap, though some issues may remain due to disease-related morbidity. For individuals cured before high school, annual earnings are projected to be only 8% lower than those of the healthy comparison group, equaling a 58.6% increase in annual earnings from pre- to post-cure. Additionally, NPV of lifetime earnings and undiscounted lifetime income are projected to be 7% and 5% lower than those of non-SCD individuals, translating into increases of 126.8% and 206.5%, respectively. Similarly, for individuals receiving the cure during/after high school, when educational and career pathways are likely at least partially formed, annual earnings are projected to be 22% lower than those of the healthy comparison group, while NPV of lifetime earnings and undiscounted lifetime income are both projected to be 22% lower than those of non-SCD individuals. This means following cure, annual earnings are projected to increase by 44.4%, while NPV of lifetime earnings and undiscounted lifetime income are projected to increase by 136.4% and 212.0%, respectively (Figure 1A).

Additional sensitivity analyses are presented in the Supporting Information S1, but results were directionally consistent across model scenarios.

Model results were then applied to projected income and poverty effects of curing SCD for Black Americans specifically, as they make up the predominant share of the US SCD population.

If a cure were applied today across the Black American population with SCD, annual median income is projected to increase from $25 442 to $38 618 compared to the $45 438 median income of the general Black Americans population. This increase in annual earnings could have substantial effects on poverty rates among a marginalized segment of the US population. The share of Black Americans with SCD earning annual income below FPL would decline from 28.6% (n = 23 137) to 23.4% (n = 18 917), moving the SCD population closer to the 20.8% share of the overall Black American population in poverty. While not an end goal, this reflects a meaningful reduction (~20%) in earning inequities between individuals with SCD and matched controls. Over a lifetime, effects of curing SCD are even more pronounced: post-cure, NPV of lifetime earnings of Black Americans with SCD is projected to increase by $341 929 (from $660 266 to $1 002 195, compared to $1 179 172 for Black Americans generally), while undiscounted lifetime earnings would increase by $1 269 413 (from $661 507 to $1 930 920, compared to $2271900) (Figure 1B).

Racial disparities in health, education and wealth are endemic to the United States and are exacerbated for minority groups with severe conditions such as SCD. While our study focused on disparities of Blacks with SCD compared to Black America, we acknowledge equal disparity is by no means the goal. Curing SCD to support economic transformation of persons affected is one of many opportunities to reduce disparities within the Black population, thereby facilitating a more equitable society across demographic lines.

As modeled, a cure would offer immediate improvement in health with downstream improvements in the ability for children to pursue an education similar to their peers, yielding lifelong income benefits. It is also possible benefits of a cure may have generational impact: Lifelong benefits for an individual may help future generations close income gaps, although this has not been formally explored here.

This study focused on quantifying economic benefits of a cure on annual income and future earnings of individuals with SCD. Our study confirmed what is already known: individuals with SCD have lower income trajectories compared to similar individuals without SCD, lower annual earnings, and lower lifetime earnings. These differences are due not only to fewer earning years,⁵ but are very likely the result of disease impact on education and employment preferences and pathways.^{1, 6} Our study further shows curing SCD significantly reduces income inequality, leading to greater individual earnings and by extension, societal spillover benefits including diminished reliance on government programs.

Our results expand upon Lubeck et al., who explored associations between SCD and productivity from a lifetime societal perspective and showed projected lifetime income for individuals with SCD was $1 227 000 vs. $1 922 000 for matched individuals without SCD.⁵ This $695 000 income loss was attributed to the 22-year difference in LE between cohorts.⁵ Our study is directionally consistent with this study, yet offers important extensions such as modeling annual earnings trajectories and career pathways specific to curing SCD versus prolonged disease management.

To our knowledge, our study is the first to model SCD patients to new trajectories following cure, adding important context on the value of innovative therapies for broader societal disparities. The full value of a cure for SCD is not limited to therapeutic effect. Instead, evaluating benefits of a potential cure requires consideration of elements beyond traditional efficacy and productivity, such as spillover effect on education and earnings and resultant impact on equity.

Using SCD as an example, this study illustrates important potential for curative therapies to not only clinically-transform lives, but to offer broader, profound opportunities for patients and affected communities. Given our model only measures economic benefits related to annual and lifetime incomes and not other aspects such as societal benefits and caregiver burden, benefit of potential cures is likely underestimated. Developing novel curative therapies for SCD and enabling broad access offers significant opportunity to patients and opens-up meaningful and transformative pathways to reduce inequities tied to health and wealth.

镰状细胞病 (SCD)**在这项研究中，SCD 患者在全国健康访谈调查 (NHIS) 中被确定为儿童，其父母监护人确认“医生或其他健康专业人士曾告诉父母他们的孩子患有镰状细胞性贫血”。
是美国 (US) 最常见的遗传性血液疾病之一，在近 1/3000 的美国人中发现¹并且不成比例地影响黑人（1/365 出生）和西班牙裔（1/16300）人群。¹

临床表现始于儿童早期，包括严重的发作性和慢性疼痛、多系统器官衰竭、中风和危及生命的感染。此外，与具有相似人口特征的健康个体相比，患者的学业成绩较低，成年后有意义就业的机会较低，注意力和注意力不集中，智力指标得分较低，²缺课率增加，并且更有可能重复成绩。³对于在联邦贫困线 (FPL) 以下的家庭或父母未受过高等教育的患有 SCD 的儿童，疾病影响会加剧。

虽然新生儿筛查计划、青霉素预防和治疗方案的适度改进使 SCD 患者能够活到成年，但目前的预期寿命 (LE) 估计值各不相同，但并未超过 50 岁。⁴

SCD 还延续了黑人、其他少数群体和非西班牙裔白人之间在健康和财富方面的现有差距。在与其他群体相比，美国黑人的健康、教育和经济成果更加糟糕的环境中，患有 SCD 的美国黑人及其家人被远远抛在后面。美国国家科学、工程和医学研究院最近的一份报告回顾了关于经济差异的研究，发现与匹配的对照组相比，SCD 患者的受教育程度较低、认知障碍和治疗负担较高，失业率较高。²此外，患有 SCD 的儿童报告了在获得护理方面的延误，这一现实在整个 SCD 人群中都是一致的。

尽管如此，SCD 对美国黑人的经济影响仍然知之甚少。先前的队列模拟模型估计，仅由于 LE 的差异，SCD 个体的预计终生收入比没有 SCD 的匹配个体低 695 000 美元。⁵然而，迄今为止，没有研究考虑或模拟 SCD 患者在疾病治愈后的新收入轨迹或评估收入变化将如何减少收入差距，††在整篇论文中，治愈用于描述假设的未来基因治疗；没有治愈方法用于描述目前可用的疗法。作者承认，治愈没有普遍的定义，“治愈”可能对每个人都有不同的含义。就该模型而言，治愈被定义为疾病的积极表现的停止，并根据治疗年龄，潜在抵消下游对终生疾病相关合并症的影响。
在这种情况下，对于预期新的治疗性治疗而言，这两者似乎都是有意义且及时的。

为了量化治愈对年收入和未来收入的影响，我们使用基于队列的微观模拟模型来预测患有 SCD、治愈前和治愈后的个体在生命历程中不同点的终生收入轨迹。有关研究方法的更多详细信息，请参阅本文的支持信息 S1。

在我们的模型中，由于没有与 SCD 相关的健康危机和住院以及 LE 增加和接受教育的机会增加，治愈的个人经历了更高的生产力和新的收入轨迹。

在来自 1997 年收入动态小组调查的儿童发展补充资料的 6352 名加权个体（SCD：3176，非 SCD：3176）的全国代表性样本中，我们发现患有 SCD 的个体与没有 SCD 的可比个体之间的收入存在巨大差距。如图 1A 所示，SCD 患者的年收入比健康对照组低 42% 至 46%。与匹配的对照组相比，SCD 队列的终生收入 NPV 低 59%–66%，未贴现终生收入低 69%–75%。

尽管与疾病相关的发病率可能仍然存在一些问题，但引入治疗方法可以部分缩小这种 SCD 收入差距。对于高中前治愈的个体，预计年收入仅比健康对照组低 8%，相当于从治愈前到治愈后的年收入增加 58.6%。此外，终生收入和未贴现终生收入的净现值预计将比非 SCD 个人低 7% 和 5%，从而分别增加 126.8% 和 206.5%。同样，对于在高中期间/之后接受治疗的个人，当教育和职业道路可能至少部分形成时，预计年收入将比健康对照组低 22%，而终生收入和未贴现终生收入的 NPV 预计都比非 SCD 个人低 22%。这意味着治愈后，年收入预计将增长 44.4%，而终生收入的净现值和未贴现终生收入预计将分别增长 136.4% 和 212.0%（图 1A）。

支持信息 S1 中提供了额外的敏感性分析，但结果在模型场景中是方向一致的。

然后，模型结果被应用于治疗 SCD 对美国黑人的预计收入和贫困效应，因为他们占美国 SCD 人口的主要份额。

如果今天在患有 SCD 的美国黑人人群中应用治疗方法，那么与一般美国黑人人口的 45 438 美元中位数收入相比，预计年收入中位数将从 25 442 美元增加到 38 618 美元。这种年收入的增加可能会对美国边缘化人群的贫困率产生重大影响。SCD 年收入低于 FPL 的美国黑人比例将从 28.6% ( n  = 23 137) 下降到 23.4% ( n = 18 917），使 SCD 人口接近美国黑人贫困人口的 20.8%。虽然不是最终目标，但这反映了 SCD 和匹配控制个体之间的收入不平等显着减少（约 20%）。在一生中，治愈 SCD 的效果更加明显：治愈后，患有 SCD 的美国黑人终生收入的净现值预计将增加 341 929 美元（从 660 266 美元增加到 1 002 195 美元，而美国黑人为 1 179 172 美元一般而言），而未贴现的终生收入将增加 1 269 413 美元（从 661 507 美元增加到 1 930 920 美元，与 2271900 美元相比）（图 1B）。

健康、教育和财富方面的种族差异是美国特有的，对于患有 SCD 等严重疾病的少数群体来说，这种差异更加严重。虽然我们的研究侧重于与美国黑人相比 SCD 的黑人的差异，但我们承认平等的差异绝不是目标。治愈 SCD 以支持受影响人群的经济转型是减少黑人人口差距的众多机会之一，从而促进跨人口群体的更公平的社会。

如模型所示，治愈将立即改善健康状况，并在下游提高儿童接受与同龄人相似的教育的能力，从而产生终身收入收益。治愈的好处也可能对世代产生影响：个人的终身福利可能会帮助后代缩小收入差距，尽管这里尚未正式探讨这一点。

本研究的重点是量化治疗对 SCD 患者年收入和未来收入的经济效益。我们的研究证实了已知的情况：与没有 SCD 的类似个人相比，患有 SCD 的人的收入轨迹较低，年收入较低，终生收入较低。这些差异不仅是由于收入年限减少⁵ ，而且很可能是疾病对教育和就业偏好和途径的影响的结果。^{1, 6}我们的研究进一步表明，治愈 SCD 可显着减少收入不平等，从而提高个人收入，进而带来社会溢出效益，包括减少对政府计划的依赖。

我们的结果扩展了 Lubeck 等人，他们从终生社会的角度探讨了 SCD 与生产力之间的关联，并显示 SCD 患者的预计终生收入为 1 227 000 美元，而没有 SCD 的匹配个体的预计终生收入为 1 922 000 美元。⁵这 695 000 美元的收入损失归因于队列之间 22 年的 LE 差异。⁵我们的研究在方向上与本研究一致，但提供了重要的扩展，例如模拟年收入轨迹和特定于治愈 SCD 与长期疾病管理的职业路径。

据我们所知，我们的研究是第一个将 SCD 患者模拟到治愈后的新轨迹，为更广泛的社会差异的创新疗法的价值增加了​​重要背景。治愈 SCD 的全部价值不仅限于治疗效果。相反，评估潜在治愈的益处需要考虑传统功效和生产力之外的因素，例如对教育和收入的溢出效应以及由此产生的对公平的影响。

以 SCD 为例，这项研究说明了治愈性疗法的重要潜力，不仅可以在临床上改变生活，而且可以为患者和受影响的社区提供更广泛、更深刻的机会。鉴于我们的模型仅衡量与年收入和终生收入相关的经济利益，而不是社会福利和照顾者负担等其他方面，潜在治愈的好处可能被低估了。为 SCD 开发新的治疗方法并实现广泛的可及性为患者提供了重要的机会，并开辟了有意义和变革性的途径，以减少与健康和财富相关的不平等。