Immune Checkpoint Inhibitor-related Type 1 Diabetes Incidence, Risk, and Survival Association

Overview

Journal J Diabetes Investig

Specialty Endocrinology

Date 2024 Nov 21

PMID 39569589

Authors

Fumika Kamitani

Yuichi Nishioka

Miyuki Koizumi

Hiroki Nakajima

Yukako Kurematsu

Sadanori Okada

Shinichiro Kubo

Tomoya Myojin

Tatsuya Noda

Tomoaki Imamura

Yutaka Takahashi

Affiliations

Soon will be listed here.

Abstract

Aim/introduction: Although immune checkpoint inhibitor-related type 1 diabetes mellitus (ICI-T1DM) is a rare condition, it is of significant concern globally. We aimed to elucidate the precise incidence, risk factors, and impact of ICI-T1DM on survival outcomes.

Materials And Methods: The study is a large retrospective cohort study, performed using the DeSC Japanese administrative claims database comprising 11 million patients. The database population is reportedly similar to the entire population of Japan. Patients administered ICI between 2014 and 2022 were enrolled in the study, including 21,121 patients. The risk factors for ICI-T1DM development and their characteristics were evaluated by logistic regression analysis. Development of a new irAE after the day following the first administration of ICI was set as the study outcome.

Results: ICI-T1DM was observed in 102 (0.48%) of the 21,121 patients after ICI initiation. PD-(L)1 and CTLA-4 combination therapy was associated with an increased risk of ICI-T1DM compared with PD-1 monotherapy (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.21-4.58; P = 0.01). Patients with a prior diagnosis of diabetes mellitus (OR, 1.59; 95% CI, 1.03-2.46; P = 0.04) or hypothyroidism (OR, 2.48; 95% CI, 1.39-4.43; P < 0.01) also exhibited an increased risk of ICI-T1DM. The Kaplan-Meier analysis revealed that patients with ICI-T1DM showed higher survival rates than those without (log-lank test, P < 0.01). Multivariable Cox regression analysis demonstrated that ICI-T1DM development was associated with lower mortality (hazard ratio, 0.60; 95% CI, 0.37-0.99; P = 0.04).

Conclusions: Collectively, the results of this study demonstrate the precise incidence and risk factors of ICI-T1DM. The development of ICI-T1DM, like other irAEs, is associated with higher survival rates.

References

Chen X, Affinati A, Lee Y, Turcu A, Henry N, Schiopu E . Immune Checkpoint Inhibitors and Risk of Type 1 Diabetes. Diabetes Care. 2022; 45(5):1170-1176. PMC: 9174959. DOI: 10.2337/dc21-2213. View

Okada A, Yasunaga H . Prevalence of Noncommunicable Diseases in Japan Using a Newly Developed Administrative Claims Database Covering Young, Middle-aged, and Elderly People. JMA J. 2022; 5(2):190-198. PMC: 9090547. DOI: 10.31662/jmaj.2021-0189. View

Cho Y, Jung C . Immune-Checkpoint Inhibitors-Induced Type 1 Diabetes Mellitus: From Its Molecular Mechanisms to Clinical Practice. Diabetes Metab J. 2023; 47(6):757-766. PMC: 10695719. DOI: 10.4093/dmj.2023.0072. View

Shankar B, Zhang J, Naqash A, Forde P, Feliciano J, Marrone K . Multisystem Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors for Treatment of Non-Small Cell Lung Cancer. JAMA Oncol. 2020; 6(12):1952-1956. PMC: 7596677. DOI: 10.1001/jamaoncol.2020.5012. View

Faje A, Sullivan R, Lawrence D, Tritos N, Fadden R, Klibanski A . Ipilimumab-induced hypophysitis: a detailed longitudinal analysis in a large cohort of patients with metastatic melanoma. J Clin Endocrinol Metab. 2014; 99(11):4078-85. DOI: 10.1210/jc.2014-2306. View

Chang L, Barroso-Sousa R, Tolaney S, Hodi F, Kaiser U, Min L . Endocrine Toxicity of Cancer Immunotherapy Targeting Immune Checkpoints. Endocr Rev. 2018; 40(1):17-65. PMC: 6270990. DOI: 10.1210/er.2018-00006. View

Postow M, Sidlow R, Hellmann M . Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018; 378(2):158-168. DOI: 10.1056/NEJMra1703481. View

Colli M, Hill J, Marroqui L, Chaffey J, Dos Santos R, Leete P . PDL1 is expressed in the islets of people with type 1 diabetes and is up-regulated by interferons-α and-γ via IRF1 induction. EBioMedicine. 2018; 36:367-375. PMC: 6197434. DOI: 10.1016/j.ebiom.2018.09.040. View

Steck A, Rewers M . Genetics of type 1 diabetes. Clin Chem. 2011; 57(2):176-85. PMC: 4874193. DOI: 10.1373/clinchem.2010.148221. View

10.

Inaba H, Kaido Y, Ito S, Hirobata T, Inoue G, Sugita T . Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors. Endocrinol Metab (Seoul). 2022; 37(1):84-95. PMC: 8901959. DOI: 10.3803/EnM.2021.1282. View

11.

Takahashi Y . Paraneoplastic autoimmune hypophysitis: a novel form of paraneoplastic endocrine syndrome. Endocr J. 2023; 70(6):559-565. DOI: 10.1507/endocrj.EJ23-0050. View

12.

Atkinson M, Eisenbarth G, Michels A . Type 1 diabetes. Lancet. 2013; 383(9911):69-82. PMC: 4380133. DOI: 10.1016/S0140-6736(13)60591-7. View

13.

Wang Y, Zhou S, Yang F, Qi X, Wang X, Guan X . Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis. JAMA Oncol. 2019; 5(7):1008-1019. PMC: 6487913. DOI: 10.1001/jamaoncol.2019.0393. View

14.

Tachibana M, Imagawa A . Type 1 diabetes related to immune checkpoint inhibitors. Best Pract Res Clin Endocrinol Metab. 2022; 36(3):101657. DOI: 10.1016/j.beem.2022.101657. View

15.

Inaba H, Morita S, Kosugi D, Asai Y, Kaido Y, Ito S . Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors. Front Immunol. 2023; 14:1165004. PMC: 10128036. DOI: 10.3389/fimmu.2023.1165004. View

16.

Kotwal A, Haddox C, Block M, Kudva Y . Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes. BMJ Open Diabetes Res Care. 2019; 7(1):e000591. PMC: 6398813. DOI: 10.1136/bmjdrc-2018-000591. View

17.

Quandt Z, Young A, Perdigoto A, Herold K, Anderson M . Autoimmune Endocrinopathies: An Emerging Complication of Immune Checkpoint Inhibitors. Annu Rev Med. 2020; 72:313-330. DOI: 10.1146/annurev-med-050219-034237. View

18.

Quan H, Li B, Couris C, Fushimi K, Graham P, Hider P . Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011; 173(6):676-82. DOI: 10.1093/aje/kwq433. View

19.

Nishioka Y, Noda T, Okada S, Myojin T, Kubo S, Higashino T . Incidence and seasonality of type 1 diabetes: a population-based 3-year cohort study using the National Database in Japan. BMJ Open Diabetes Res Care. 2020; 8(1). PMC: 7526280. DOI: 10.1136/bmjdrc-2020-001262. View

20.

Imagawa A, Hanafusa T . Fulminant Type 1 Diabetes-East and West. J Clin Endocrinol Metab. 2023; 108(12):e1473-e1478. DOI: 10.1210/clinem/dgad329. View