| アブストラクト | INTRODUCTION: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Among them, ICIs-induced systemic sclerosis (SSc) is poorly known. METHODS: To better characterize this irAE, our comprehensive approach combined the description of ICIs-induced scleroderma cases, the systematic review of the literature and the analysis of VigiBase, the WHO pharmacovigilance database. RESULTS: We identified two cases with underlying limited cutaneous SSc who presented a dramatic increase in the skin thickening following pembrolizumab, associated with scleroderma renal crisis in one case. In the literature, four cases of scleroderma and four cases of morphea have been reported with pembrolizumab or nivolumab. None following ipilimumab, atezolizumab or durvalumab were retrieved. Skin changes appeared or worsened more quickly with pembrolizumab than nivolumab, and had different patterns between both drugs. Patients with generalized skin changes required high-dose prednisone to improve skin thickening. Among the 2527 scleroderma cases identified in VigiBase, 35 were associated with ICIs. Nivolumab and pembrolizumab showed a disproportionality in scleroderma reporting. No disproportionality was found for ipilimumab, atezolizumab or durvalumab. CONCLUSION: The risk of scleroderma or fibrosis extension in SSc patients should be considered when initiating anti-PD-1 agents. It suggests the role of PD-1/PD-L1 interaction in the pathophysiology of SSc. |
|---|
| 投稿者 | Terrier, Benjamin; Humbert, Sebastien; Preta, Laure-Helene; Delage, Laure; Razanamahery, Jerome; Laurent-Roussel, Sara; Mestiri, Raphaele; Beaudeau, Lauren; Legendre, Paul; Goupil, Francois; Hadjadj, Jerome; Stolzenberg, Marie-Claude; Treluyer, Jean-Marc; Westeel, Virginie; Valnet-Rabier, Marie-Blanche; Wislez, Marie; Mouthon, Luc; Chouchana, Laurent |
|---|
| 組織名 | Department of Internal Medicine, Cochin Hospital, Paris, France; National;Referral Centre for Systemic and Autoimmune Diseases, Hopital Cochin, Paris,;France; Universite Paris Descartes, Sorbonne Paris Cite, Paris, France.;Electronic address: benjamin.terrier@aphp.fr.;Department of Internal Medicine, CHU, Besancon, France.;Regional Center of Pharmacovigilance, Department of Pharmacology, Cochin;Hospital, Paris, France.;Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institue, Paris, France;;Checkpoint Immunology, Immunology and Inflammation Therapeutic Area, Sanofi,;Vitry, France.;Department of Pathology, Cochin Hospital, Paris, France.;Department of Internal Medicine, Cochin Hospital, Paris, France.;Department of Pulmonology, General Hospital, Le Mans, France.;Department of Internal Medicine, Cochin Hospital, Paris, France; Immunogenetics;of Pediatric Autoimmune Diseases, Imagine Institue, Paris, France; Checkpoint;Immunology, Immunology and Inflammation Therapeutic Area, Sanofi, Vitry, France.;Universite Paris Descartes, Sorbonne Paris Cite, Paris, France; Regional Center;of Pharmacovigilance, Department of Pharmacology, Cochin Hospital, Paris, France.;Department of Pulmonology, University Hospital Jean Minjoz, INSERM UMR 1098,;Universite de Bourgogne Franche Comte, Besancon, France.;Regional Center of Pharmacovigilance, Department of Pharmacology, CHU, Besancon,;France.;Universite Paris Descartes, Sorbonne Paris Cite, Paris, France; Department of;Pulmonology, Thoracic Oncology Unit, Cochin Hospital, Paris, France. |
|---|
