1. Characteristics of insulinopenic and non insulinopenic diabetes related to immune checkpoint inhibitors: A French pharmacovigilance study
- Author
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Marion Allouchery, Kevin Bihan, Bénédicte Lebrun-Vignes, Franck Rouby, Marie Bastin, Pirayeh Eftekhari, Marion Sassier, Fabrizio Andreelli, Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
medicine.medical_specialty ,Ipilimumab ,Type 2 diabetes ,Pembrolizumab ,030226 pharmacology & pharmacy ,03 medical and health sciences ,Pharmacovigilance ,0302 clinical medicine ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Pharmacology (medical) ,Immune Checkpoint Inhibitors ,ComputingMilieux_MISCELLANEOUS ,business.industry ,[SCCO.NEUR]Cognitive science/Neuroscience ,medicine.disease ,Ketoacidosis ,Nivolumab ,Diabetes Mellitus, Type 2 ,business ,Adverse drug reaction ,medicine.drug - Abstract
Summary Introduction Immune checkpoint inhibitor-induced diabetes mellitus (ICI-DM) is an immune-related adverse drug reaction (irADR). Hyperglycemia can be linked to endogenous insulin deficiency with ketoacidosis or associated with preserved beta-cell function. Objectives We aimed to identify the characteristics of both types of ICI-DM (type 1 and type 2 DM), to improve our understanding of this irADR and its management. Methods Data for ICI-DM recorded in the French Pharmacovigilance Database from 2015 to October 2019 were analyzed according to the French causality assessment. Results In total, 60 subjects were included. Anti-PD1/PDL1 pathway blockade therapy (nivolumab: 61.7% + 3.3% in association with ipilimumab pembrolizumab: 28.3%) was most frequently implicated in ICI-DM, but some reports involved anti-CTLA4 drug (ipilimumab: 6.7% + 3.3% in association with nivolumab). One third of reports occurred within one month of the initiation of immunotherapy. Decreased insulin secretion (defined by the presence of ketone bodies) were confirmed in 80% of reports. Among them, 54% of patients met the diagnostic criteria for fulminant diabetes. Overall, 17.7% of the reports had pre-existing type 2 diabetes T2D. Four deaths due to hyperglycemia were declared, with altered insulin secretion in only two of these reports. BMI was lower in the insulinopenic group (23.4 ± 0.7 vs. 27.9 ± 1.6, P = 0.004) and other irADRs were more frequently observed in patients with persistent insulin secretion (66.7 vs. 18.8%, P = 0.02). We found no difference in age, indication or cumulative ICI dose between the two groups (with and without insulinopenia). The presence of GAD antibodies was associated with a shorter time to diabetes onset (42.6 ± 6.1 vs. 208.1 ± 41.6 days, P = 0.029). Conclusions ICI-DM is a rare but serious irADR triggered by all classes of immunotherapy. The observation period for ICI-DM can be shortened for patients positive for anti-GAD antibodies. Endogenous insulin deficiency did not appear to be the only mechanism involved in ICI-DM, as beta-cell function was preserved in 20% of reports. Improvements in our understanding of this complication will be required for its prevention.
- Published
- 2021