BACKGROUND Therapies that target the underlying defect in Cystic Fibrosis (CF) will likely impact the future characteristics of the CF population and healthcare utilization. The objectives of this study were to estimate the potential impact of elexacaftor/tezacaftor/ivacaftor on morbidity and mortality, and the impact of delayed access. METHOD A microsimulation transition model was applied to Canadian CF Registry data to forecast lung disease severity, pulmonary exacerbations, deaths and transplants to 2030 under three scenarios: 1) no availability of elexacaftor/tezacaftor/ivacaftor, 2) availability in 2021 ('early') or 3) availability in 2025 ('delayed'). Published Phase III data on treatment effects were used to estimate transition rates between disease severity states. RESULTS Under specific assumptions regarding disease state and treatment effect applied to the Canadian CF population it is projected that by 2030, early introduction of elexacaftor/tezacaftor/ivacaftor is expected to reduce the number of individuals with severe lung disease by 60% (95% CI 55.3; 63.9), increase the number of individuals with mild lung disease by 18% (95%CI 18.2; 19.0) and reduce the number of pulmonary exacerbations by 19% (95%CI 18.9; 19.5). Earlier introduction of elexacaftor/tezacaftor/ivacaftor could reduce deaths by 15% (95% 13.2; 18.4) and improve the median age of survival by 9.2 years (7.5; 10.8) over a 10-year period. The expected benefits of therapy are cumulative, therefore delayed access to elexacaftor/tezacaftor/ivacaftor will result in preventable health care utilization and deaths. CONCLUSIONS Delayed access to elexacaftor/tezacaftor/ivacaftor will have a negative impact on lung health and survival in the CF population.

中文翻译：

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预测延迟使用 elexacaftor/tezacaftor/ivacaftor 对囊性纤维化患者的影响

背景 针对囊性纤维化 (CF) 潜在缺陷的治疗可能会影响 CF 人群的未来特征和医疗保健利用。本研究的目的是估计 elexacaftor/tezacaftor/ivacaftor 对发病率和死亡率的潜在影响，以及延迟进入的影响。方法 将微观模拟过渡模型应用于加拿大 CF Registry 数据，以预测到 2030 年以下三种情况下的肺部疾病严重程度、肺部恶化、死亡和移植情况：1) elexacaftor/tezacaftor/ivacaftor 不可用，2) 2021 年可用（“早期” ) 或 3) 2025 年的可用性（“延迟”）。已发表的 III 期治疗效果数据用于估计疾病严重程度之间的转变率。结果 根据适用于加拿大 CF 人群的疾病状态和治疗效果的特定假设，预计到 2030 年，早期引入 elexacaftor/tezacaftor/ivacaftor 有望将患有严重肺部疾病的人数减少 60% (95% CI 55.3；63.9），将患有轻度肺部疾病的人数增加 18%（95%CI 18.2；19.0），将肺部恶化的人数减少 19%（95%CI 18.9；19.5）。早期引入 elexacaftor/tezacaftor/ivacaftor 可以在 10 年期间将死亡人数减少 15%（95% 13.2；18.4），并将中位生存年龄提高 9.2 岁（7.5；10.8）。治疗的预期益处是累积的，因此延迟使用 elexacaftor/tezacaftor/ivacaftor 将导致可预防的医疗保健利用和死亡。