title: Update on malignancies in children with juvenile idiopathic arthritis in the German BIKER Registry.
abstract: OBJECTIVE
  While tumour necrosis factor (TNF)-α-inhibitor treatment improved outcome of juvenile idiopathic arthritis (JIA) management markedly, concerns have been raised about an association of TNF-α-inhibitor treatment and an increased risk for malignancies especially lymphoma.
  
  
  METHODS
  Cases of suspected malignancies documented in the German Biker Registry are reviewed in detail.
  
  
  RESULTS
  Until Dec 31, 2015, 3695 JIA patients were prospectively followed with a total of more than 13,198 observation years. 12 cases of suspected malignancies, including 7 lymphoid neoplasms, have been reported in patients treated with methotrexate (MTX) , and /or TNF-α inhibitors. 11 patients had received MTX, two received cyclosporine A, single patients received sulfasalazine, azathioprine or leflunomide. 10 patients were exposed to biologics, 9 etanercept, two adalimumab, one infliximab and one case was consecutively treated with adalimumab, etanercept, infliximab and abatacept. A case of mild myelodysplasia, in which the patient recovered spontaneously, a case of lymphoproliferation without clonality and a case of cervical dysplasia were treated as suspected, but not confirmed malignancies. Cases in which a malignant disease was confirmed included two cases of Hodgkin's lymphoma, one case of non-Hodgkin's lymphoma, two cases of acute lymphatic leukaemia (ALL) and one patient with lymphoproliferative disorder, who recovered after discontinuation of immunosuppressive therapy. Single confirmed cases of thyroid carcinoma, yolk sac carcinoma and anaplastic ependymoma have also been described. One patient not exposed to biologics died of ALL, all other patients recovered.
  
  
  CONCLUSIONS
  In this large cohort of JIA patients, the occurrence of malignancies was higher than in the general population. Whether JIA patients had an increased risk for malignancies, either through their rheumatic disease, or through treatment remains in debate. Treatment with etanercept seems not to further increase the malignancy risk. Long-term observation of JIA patients treated with TNF-α inhibitors into adulthood remains an important task.
authors.affiliation: Centre for Paediatric Rheumatology, Department of Paediatrics, Asklepios Clinic Sankt Augustin, Germany. g.horneff@asklepios.com.
authors.forename: Gerd
authors.initials: G
authors.lastname: Horneff
authors.affiliation: Centre for Paediatric Rheumatology, Department of Paediatrics, Asklepios Clinic Sankt Augustin, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Klein
authors.affiliation: Department of Paediatric Oncology, Haematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Prasad T
authors.initials: PT
authors.lastname: Oommen
authors.affiliation: Olga Hospital, Stuttgart, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Hospach
authors.affiliation: Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.affiliation: Klinikum Mutterhaus der Borromäerinnen, Trier, Germany.
authors.forename: Isa
authors.initials: I
authors.lastname: Feddersen
authors.affiliation: Charité University Medicine and Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Minden
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008223:Lymphoma / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D012042:Registries; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha