| アブストラクト | BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but may also trigger autoimmune adverse drug reactions (ADRs) referred to as immune-related adverse events (irAEs). Although endocrinopathies are among the most common form of irAEs, primary adrenal insufficiency (PAI) is infrequent and has only been published in case reports. The aim of this study was to identify and characterize the main features of PAI-irAE. MATERIALS AND METHODS: Suspected PAI-irAE cases were identified using VigiBase, the World Health Organization's pharmacovigilance database of individual case safety reports. RESULTS: From September 2, 2008, through October 5, 2018, a total of 50,108 ICI-associated ADRs were reported. Since 2008, there were 451 cases of PAI-irAE identified of which 45 were "definite PAI" and 406 "possible PAI." Patients were mainly male (58.1%) with a median age of 66 years (range, 30-95). Indications of ICI were predominantly for melanoma (41.2%) and lung cancer (28.6%). The majority of patients were treated with ICI monotherapy (nivolumab: 44.3%, pembrolizumab: 11.7%, ipilimumab: 23.6%), and 17.9% were treated with ICI combination therapy. These events occurred with a median time to onset of 120 days (range, 6-576). ICI-associated PAI was associated with significant morbidity (>/=90% severe) and mortality (7.3%). Fatality rates were similar in the subgroups of combination therapy versus monotherapy. There were no relevant differences in clinical or demographical characteristics and outcomes between "definite" versus "possible" PAI group. CONCLUSION: Our study represents the largest clinical description and characterization of PAI-irAE. Although ICI-associated PAI is a rare adverse event, early recognition is important to implement corticosteroid treatment. Further studies are required to elucidate risk factors and reversibility of this rare but severe irAE. Clinical trial identification number. NCT03492242 IMPLICATIONS FOR PRACTICE: Immune checkpoint inhibitor (ICI)-associated primary adrenal insufficiency (PAI) is a rare adverse event that is important to recognize because it may be severe and life-threatening, requiring emergent and often lifelong hormonal replacement therapy. Awareness regarding this ICI-related endocrinopathy is strongly encouraged among clinicians in addition to patient education about common PAI symptoms that should prompt urgent medical evaluation. In clinical practice, close monitoring and investigation for PAI is crucial to allow for early management and to further define the pathophysiology and prognosis of ICI-PAI. Corticotrophin (adrenocorticotrophic hormone) circulating level evaluation may be often lacking but should be considered as part of the diagnostic workup to differentiate PAI from secondary (central) adrenal insufficiency. |
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| ジャーナル名 | The oncologist |
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| 投稿日 | 2020/5/12 |
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| 投稿者 | Grouthier, Virginie; Lebrun-Vignes, Benedicte; Moey, Melissa; Johnson, Douglas B; Moslehi, Javid J; Salem, Joe-Elie; Bachelot, Anne |
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| 組織名 | Department of Endocrinology, Diabetes and Nutrition, University of Bordeaux, USN;Haut Leveque, Bordeaux, France.;Pharmacovigilance Unit, Department of Pharmacology, Unite de Cardio-Oncologie;Sorbonne Universite-Groupe de Recherche Clinique en Cardio-Oncologie;(UNICO-GRECO), INSERM Centre d'Investigation Clinique (CIC)-1901,;Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris (AP-HP), Paris,;France.;Equipe d'Accueil 7379 EpiDermE, Universite Paris-Est Creteil (UPEC), Paris,;Cardio-Oncology Program, Departments of Medicine and Pharmacology, Vanderbilt;University Medical Center, Nashville, Tennessee, USA.;Department of Endocrinology and Reproductive Medicine, Centre de Reference des;Maladies Endocriniennes Rares de la Croissance and Centre de Reference des;Pathologies Gynecologiques Rares, Institute of Cardiometabolism and Nutrition;(ICAN), Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris;(AP-HP), Paris, France. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/32390168/ |
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