| アブストラクト | 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. |
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| 投稿者 | Bastin, Marie; Allouchery, Marion; Sassier, Marion; Rouby, Franck; Eftekhari, Pirayeh; Lebrun-Vignes, Benedicte; Andreelli, Fabrizio; Bihan, Kevin |
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| 組織名 | Pitie Salpetriere Hospital, Diabetology Dpt, Sorbonne University, APHP, 75013;Paris, France.;Regional Pharmacovigilance Center, Department of clinical Pharmacology,;University of Poitiers, Poitiers University Hospital, 86073 Poitiers, France.;Regional Pharmacovigilance Center, Department of Pharmacology, Caen University;Hospital, 14000 Caen, France.;Regional Pharmacovigilance Center, Department of Pharmacology, Aix-Marseille;University Hospital, 13015 Marseille, France.;Regional Pharmacovigilance Center, Department of Pharmacology, Fernand-Widal;Hospital, 75010 Paris, France.;Regional Pharmacovigilance Center, Department of Pharmacology, Pitie-Salpetriere;Hospital, 47-83, boulevard de l'Hopital, 75013 Paris, France.;Hospital, 47-83, boulevard de l'Hopital, 75013 Paris, France. Electronic address:;kevin.bihan@aphp.fr. |
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