Cardio-Oncology Research Unit, Cardiovascular Analytics Group, Hong Kong, China.
Department of Medical Oncology, University College London Hospitals NHS Foundation Trust, London, UK.
Cancer Med. 2023 Apr;12(7):8144-8153. doi: 10.1002/cam4.5616. Epub 2023 Jan 16.
Immune checkpoint inhibitors (ICIs) are increasingly established cancer therapeutics, but they are associated with new-onset diabetes mellitus (DM). Such risks have not been adequately quantified, and between-class and -sex differences remain unexplored.
This was a prospective cohort study of cancer patients receiving any ICI in Hong Kong between 2013 and 2021. Patients with known DM were excluded. Due to few patients using other ICIs, only programmed cell death 1 inhibitors (PD-1i) and programmed death ligand 1 inhibitors (PD-L1i) were compared, alongside between-sex comparison. When comparing PD-1i against PD-L1i, patients with the use of other ICIs or both PD-1i and PD-L1 were further excluded. Inverse probability treatment weighting (IPTW) was used to minimize between-group covariate imbalances.
Altogether, 3375 patients were analyzed (65.2% males, median age 62.2 [interquartile range 53.8-69.5] years old). Over a median follow-up of 1.0 [0.4-2.4] years, new-onset DM occurred in 457 patients (13.5%), with a 3-year risk of 14.5% [95% confidence interval 13.3%, 15.8%]. IPTW achieve acceptable covariate balance between sexes, and between PD-1i (N = 622) and PD-L1i (N = 2426) users. Males had significantly higher risk of new-onset DM (hazard ratio 1.35 [1.09, 1.67], p = 0.006), while PD-1i and PD-L1i users did not have significantly different risks (hazard ratio vs PD-L1i 0.81 [0.59, 1.11], p = 0.182). These were consistent in those with at least 1 year of follow-up, and on competing risk regression.
Users of ICI may have a substantial risk of new-onset DM, which may be higher in males but did not differ between PD-1i and PD-L1i.
免疫检查点抑制剂（ICIs）已成为癌症治疗的新兴方法，但它们与新发糖尿病（DM）有关。这些风险尚未得到充分量化，且不同类别和性别的差异仍未得到探索。
这是一项在香港进行的前瞻性队列研究，纳入了 2013 年至 2021 年间接受任何 ICI 治疗的癌症患者。排除已知患有 DM 的患者。由于使用其他 ICI 的患者较少，因此仅比较了程序性细胞死亡 1 抑制剂（PD-1i）和程序性死亡配体 1 抑制剂（PD-L1i），并进行了性别间比较。当比较 PD-1i 与 PD-L1i 时，排除了使用其他 ICI 或同时使用 PD-1i 和 PD-L1i 的患者。采用逆概率治疗加权（IPTW）来最小化组间协变量的不平衡。
共分析了 3375 例患者（65.2%为男性，中位年龄 62.2[四分位距 53.8-69.5]岁）。中位随访 1.0[0.4-2.4]年后，457 例患者（13.5%）新发 DM，3 年风险为 14.5%[95%置信区间 13.3%，15.8%]。IPTW 在性别间以及 PD-1i（N=622）和 PD-L1i（N=2426）使用者间实现了可接受的协变量平衡。男性新发 DM 的风险显著更高（风险比 1.35[1.09，1.67]，p=0.006），而 PD-1i 和 PD-L1i 使用者的风险无显著差异（与 PD-L1i 相比的风险比 0.81[0.59，1.11]，p=0.182）。这些结果在至少随访 1 年的患者和竞争风险回归中是一致的。
ICI 的使用者可能有发生新发 DM 的显著风险，且男性的风险可能更高，但 PD-1i 和 PD-L1i 之间无差异。
