Benjamin Terrier1, Sébastien Humbert2, Laure-Hélène Preta3, Laure Delage4, Jérôme Razanamahery2, Sara Laurent-Roussel5, Raphaële Mestiri6, Lauren Beaudeau7, Paul Legendre6, François Goupil8, Jérôme Hadjadj9, Marie-Claude Stolzenberg4, Jean-Marc Treluyer10, Virginie Westeel11, Marie-Blanche Valnet-Rabier12, Marie Wislez13, Luc Mouthon6, Laurent Chouchana3. 1. Department of Internal Medicine, Cochin Hospital, Paris, France; National Referral Centre for Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. Electronic address: benjamin.terrier@aphp.fr. 2. Department of Internal Medicine, CHU, Besançon, France. 3. Regional Center of Pharmacovigilance, Department of Pharmacology, Cochin Hospital, Paris, France. 4. Immunogenetics of Pediatric Autoimmune Diseases, Imagine Institue, Paris, France; Checkpoint Immunology, Immunology and Inflammation Therapeutic Area, Sanofi, Vitry, France. 5. Department of Pathology, Cochin Hospital, Paris, France. 6. Department of Internal Medicine, Cochin Hospital, Paris, France; National Referral Centre for Systemic and Autoimmune Diseases, Hôpital Cochin, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 7. Department of Internal Medicine, Cochin Hospital, Paris, France. 8. Department of Pulmonology, General Hospital, Le Mans, France. 9. 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. 10. Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Regional Center of Pharmacovigilance, Department of Pharmacology, Cochin Hospital, Paris, France. 11. Department of Pulmonology, University Hospital Jean Minjoz, INSERM UMR 1098, Université de Bourgogne Franche Comté, Besançon, France. 12. Regional Center of Pharmacovigilance, Department of Pharmacology, CHU, Besançon, France. 13. Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Department of Pulmonology, Thoracic Oncology Unit, Cochin Hospital, Paris, France.
Abstract
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.
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.
Authors: José A Gómez-Puerta; David Lobo-Prat; Carolina Perez-García; Andrés Ponce; Beatriz Frade-Sosa; Ana Milena Millán Arciniegas; Fabiola Ojeda; Virginia Ruiz-Esquide; Hector Corominas Journal: Front Med (Lausanne) Date: 2022-06-15
Authors: Nicola Farina; Giovanni Benanti; Giacomo De Luca; Anna Palmisano; Giovanni Peretto; Sara Tomassetti; Veronica Giorgione; Ornella Forma; Antonio Esposito; Silvio Danese; Lorenzo Dagna; Marco Matucci-Cerinic; Corrado Campochiaro Journal: J Multidiscip Healthc Date: 2022-04-20
Authors: Brittany A Klein; Muhammad Ali Shazib; Alessandro Villa; Fábio de Abreu Alves; Piamkamon Vacharotayangul; Stephen Sonis; Stefano Fedele; Nathaniel S Treister Journal: Front Oral Health Date: 2022-08-11