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Musculoskeletal immune-related adverse events in 927 patients treated with immune checkpoint inhibitors for solid cancer
Affiliation:1. Department of Rheumatology, University Hospital of Marseille Sainte-Marguerite, Aix Marseille University, AP–HM, Marseille, France;2. Biostatistics department, Institut Paoli-Calmettes, Marseille, France;3. Oncology department, Institut Paoli-Calmettes, Marseille, France;1. Rheumatology department, Pitié Salpêtrière hospital, AP–HP, 75013 Paris, France;2. Sorbonne Université, Inserm UMRS 1136, Institut Pierre Louis d’Épidémiologie et de Santé Publique, 75013 Paris, France;1. Department of Rheumatology, Besançon University Medical Center, Besançon, France;2. Department of Pharmacovigilance, Besançon University Medical Center, Besançon, France;3. Department of Pharmacovigilance, Grenoble University Medical Center, Besançon, France;4. EA 4267 “PEPITE”, FHU Increase, Bourgogne-Franche Comte University, UFR SMP, Besançon, France;5. Department of Ophthalmology, Besançon University Medical Center, Besançon, France;6. Department of Rheumatology, Cochin University Hospital, Paris, France;7. EA 4266 “EPILAB”, Bourgogne-Franche Comte University, UFR SMP, Besançon, France;1. Service de radiologie ostéoarticulaire, hôpital Lariboisière, AP–HP Nord-université Paris Cité, 75010 Paris, France;2. Laboratoire B3OA, CNRS UMR 7052, Paris, France;3. Department of Medical Physics, hôpital Lariboisière, AP–HP Nord-université Paris Cité, Paris, France;1. Department of Development and Regeneration, Skeletal Biology and Engineering Research Centre, KU Leuven, Leuven, Belgium;2. Rheumatology, KU Leuven University Hospitals Leuven, Leuven, Belgium;1. Service de Médecine Interne and Inflammation-Immunopathology, Biotherapy Department (DMU 3iD), Sorbonne Université, Hôpital Saint-Antoine, AP–HP, 75012 Paris, France;2. Service de rhumatologie, Groupe Hospitalier Intercommunal Le Raincy Montfermeil, 93370 Montfermeil, France;3. Service de Médecine interne, Centre hospitalier de Melun, 77000 Melun, France;4. Unité Inserm 1136, faculté Pierre- et Marie-Curie, institut Pierre-Louis d’épidémiologie et de santé publique, site de l’hôpital Saint-Antoine, 75012 Paris, France
Abstract:ObjectiveThe prevalence of the musculoskeletal immune-related adverse events (irAEs) is probably underestimated, as most studies report only severe side effects. Our aim was to describe and characterize all musculoskeletal irAEs in a large cohort of patients treated with immune checkpoint inhibitors (ICI).MethodsWe conducted a retrospective study among patients who received ICI from 07/27/2014 to 05/08/2020 at the medical oncology department of the Institut Paoli-Calmettes, Marseille, France. All medical files were systemically reviewed by a rheumatologist who collected clinical features, time of occurrence, treatment regimen, irAEs management, course and outcomes. We also assessed tumor response 3 months after introduction of ICI, according to severity and treatments used to manage musculoskeletal irAEs.ResultsAmong 927 patients treated with ICI for a solid tumor, 118 patients (12.7%) presented a musculoskeletal irAE. Their median age was 66.5, 61% were male, and they mainly had a lung (57.6%) or urological cancer (27.1%). The most frequently involved ICI was an anti PD-1. Arthralgias and myalgias were the most frequent musculoskeletal irAEs (9.8%) and inflammatory rheumatic features were reported in 36 patients (3.9%) with elevated acute phase reactants and negative immunological markers. The median time of onset was 2 months (IC 95% 1.8; 2.7). Tumor response at 3 months did not differ according to musculoskeletal irAE severity, type of manifestation (arthralgias/myalgias versus inflammatory rheumatic features), pain patterns (mechanical versus inflammatory) or irAE treatments.ConclusionMusculoskeletal irAEs in this large cohort of patients treated with ICI were frequent (12.7%), mostly mild and well tolerated.
Keywords:Immune checkpoint inhibitors  Musculoskeletal immune-related adverse events  Non-inflammatory musculoskeletal irAEs  Pre-existing chronic inflammatory rheumatic diseases  Systemic glucocorticoids  Tumor response  ICI"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_sK4f6VfW7l"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  immune checkpoint inhibitors  IrAE(s)"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_HZ7qDKunAV"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  immune-related adverse event(s)  CTCAE"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_Wotbz11svw"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  common terminology criteria for adverse events  NSAIDS"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_nNNNP3s5bo"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  non-steroidal anti-inflammatory drugs  csDMARD(s)"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_y1qUXUK8Z6"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  conventional synthetic disease-modifying antirheumatic drug(s)  bDMARD(s)"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_fiK7EBCq0w"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  biological disease-modifying antirheumatic drug(s)  DMARD(s)"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_ZY3tDkF4ol"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  disease-modifying antirheumatic drug(s)  NA"  },{"  #name"  :"  keyword"  ,"  $"  :{"  id"  :"  pc_xAQAsyYXUx"  },"  $$"  :[{"  #name"  :"  text"  ,"  _"  :"  not applicable
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