Sébastien Le Burel1, Stéphane Champiat2, Christine Mateus3, Aurélien Marabelle2, Jean-Marie Michot4, Caroline Robert3, Rakiba Belkhir5, Jean-Charles Soria2, Salim Laghouati6, Anne-Laure Voisin6, Olivier Fain7, Arsène Mékinian7, Laetitia Coutte8, Tali-Anne Szwebel8, Laetitia Dunogeant9, Bertrand Lioger10, Cécile Luxembourger11, Xavier Mariette12, Olivier Lambotte13. 1. Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie Clinique, F-94275 Le Kremlin-Bicêtre, France. 2. Département D'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, F-94805 Villejuif, France; INSERM U981, F-94805 Villejuif, France. 3. Département de Dermatologie, Institut Gustave Roussy, F-94805 Villejuif, France. 4. Département D'Innovation Thérapeutique et des Essais Précoces (DITEP), Gustave Roussy, Université Paris Saclay, F-94805 Villejuif, France. 5. Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Service de Rhumatologie, F-94275 Le Kremlin-Bicêtre, France. 6. Unité Fonctionnelle de Pharmacovigilance, Institut Gustave Roussy, F-94805 Villejuif, France. 7. Assistance Publique - Hôpitaux de Paris, Hôpital Saint-Antoine, Service de Médecine Interne, DHU I2B, Université Paris 6, F-75012 Paris, France. 8. Assistance Publique - Hôpitaux de Paris, Hôpital Cochin, Service de Médecine Interne, F-75014 Paris, France. 9. Center Hospitalier Du Pays D'Aix, Service de Rhumatologie et Médecine Interne, F-13616 Aix en Provence, France. 10. CHRU de Tours, Hôpital Bretonneau, Service de Médecine Interne, F-37044 Tours, France. 11. CHU de Toulouse, Hôpital Pierre-Paul Ricquet, Center de Rhumatologie, F-31059 Toulouse, France. 12. Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Service de Rhumatologie, F-94275 Le Kremlin-Bicêtre, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, F-94276 Le Kremlin-Bicêtre, France; Université Paris Sud, UMR 1184, F-94276 Le Kremlin-Bicêtre, France. 13. Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Service de Médecine Interne et Immunologie Clinique, F-94275 Le Kremlin-Bicêtre, France; INSERM, U1184, Immunology of Viral Infections and Autoimmune Diseases, F-94276 Le Kremlin-Bicêtre, France; Université Paris Sud, UMR 1184, F-94276 Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, IDMIT, F-92265 Fontenay-aux-Roses, France. Electronic address: olivier.lambotte@aphp.fr.
Abstract
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)1 a French registry of grade ≥2 irAEs occurring in ICI-treated patients. The pathologies of interest were systemic autoimmune and inflammatory diseases, rheumatic diseases and immune cytopenia. RESULTS: Out of 908 patients treated with anti-Programmed cell Death 1 (PD1)/anti-Programmed cell Death-Ligand 1 (PD-L1) agents (together with an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) agent in 40 cases) between December 2012 and December 2016 at a single centre, 21 patients experienced systemic irAEs. The types and the prevalence of irAEs were as follows: immune thrombocytopenia (0.2%), Sjögren syndrome (0.3%), rheumatoid arthritis (0.2%), polymyalgia rheumatica (0.2%), psoriatic arthritis (0.2%), seronegative polyarthritis (0.7%) and sarcoidosis (0.2%). Patients with Sjögren syndrome or seronegative polyarthritis were more likely to have received combination therapy with ipilimumab (2.5% for both). We described these 21 cases, together with nine additional cases from five other centres. Most irAE were moderately severe (grade 2, 63%). The median time to onset was 57°days (interquartile range (IQR) 24-117). The ICI was withdrawn in 12 cases, 25 patients (83%) received corticosteroids, and five patients (17%) received immunosuppressant/immunomodulatory agents. The irAEs resolved fully or partially in 28 cases (93%). CONCLUSION: Although systemic, immunohaematological and rheumatic diseases are rarely associated with ICI use, the prevalence is higher when two ICIs are combined. Corticosteroids are often effective and may enable the continued administration of ICIs. Studies designed to identify at-risk patients are warranted.
AIM: The growing use of immune checkpoint inhibitors (ICIs) is associated with the occurrence of immune-related adverse events (irAEs). Few data are published on systemic, immunohaematological and rheumatic irAEs. In a pharmacovigilance database analysis, we screened for these irAEs and calculated their prevalence. PATIENTS AND METHODS: Participants were recruited via Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC)1 a French registry of grade ≥2 irAEs occurring in ICI-treated patients. The pathologies of interest were systemic autoimmune and inflammatory diseases, rheumatic diseases and immune cytopenia. RESULTS: Out of 908 patients treated with anti-Programmed cell Death 1 (PD1)/anti-Programmed cell Death-Ligand 1 (PD-L1) agents (together with an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) agent in 40 cases) between December 2012 and December 2016 at a single centre, 21 patients experienced systemic irAEs. The types and the prevalence of irAEs were as follows: immune thrombocytopenia (0.2%), Sjögren syndrome (0.3%), rheumatoid arthritis (0.2%), polymyalgia rheumatica (0.2%), psoriatic arthritis (0.2%), seronegative polyarthritis (0.7%) and sarcoidosis (0.2%). Patients with Sjögren syndrome or seronegative polyarthritis were more likely to have received combination therapy with ipilimumab (2.5% for both). We described these 21 cases, together with nine additional cases from five other centres. Most irAE were moderately severe (grade 2, 63%). The median time to onset was 57°days (interquartile range (IQR) 24-117). The ICI was withdrawn in 12 cases, 25 patients (83%) received corticosteroids, and five patients (17%) received immunosuppressant/immunomodulatory agents. The irAEs resolved fully or partially in 28 cases (93%). CONCLUSION: Although systemic, immunohaematological and rheumatic diseases are rarely associated with ICI use, the prevalence is higher when two ICIs are combined. Corticosteroids are often effective and may enable the continued administration of ICIs. Studies designed to identify at-risk patients are warranted.
Authors: Jiun-Ruey Hu; Roberta Florido; Evan J Lipson; Jarushka Naidoo; Reza Ardehali; Carlo G Tocchetti; Alexander R Lyon; Robert F Padera; Douglas B Johnson; Javid Moslehi Journal: Cardiovasc Res Date: 2019-04-15 Impact factor: 10.787
Authors: Laura C Cappelli; Julie R Brahmer; Patrick M Forde; Dung T Le; Evan J Lipson; Jarushka Naidoo; Lei Zheng; Clifton O Bingham; Ami A Shah Journal: Semin Arthritis Rheum Date: 2018-03-22 Impact factor: 5.532