title: Report on malignancies in the German juvenile idiopathic arthritis registry.
abstract: OBJECTIVE
  TNF inhibitors have markedly improved the therapeutic options for JIA patients. The report on malignancies observed in children exposed to TNF inhibitors flagged up questions about a potential increased risk especially for lymphoma.
  
  
  METHODS
  Cases with malignancies observed in the German registry have been reviewed to give detailed information on the patients' pretreatment and outcome.
  
  
  RESULTS
  From 2001 to 2009, five cases of malignancies were documented in the German JIA biologics registry actually covering 1260 patients, one of each non-Hodgkin's lymphoma, Hodgkin's lymphoma, thyroid carcinoma, yolk sac carcinoma and cervical dysplasia. All patients have been exposed to a number of cytotoxic drugs including MTX, LEF, AZA, CSA before institution of TNF-α blockers. The malignant diagnosis has been given after exposure to etanercept for 3 weeks up to >6 years. Two patients have also been exposed to adalimumab or infliximab. At occurrence of the malignancy, three patients were still on etanercept, four on MTX and one on infliximab. In three patients, the malignancy occurred at adulthood. All patients recovered.
  
  
  CONCLUSIONS
  While in some of the patients exposed to TNF inhibitors the exposure time was too short for a meaningful relationship, in others the extensive pretreatment may also be causative. Two lymphomas have been observed while other entities occurred only once. JIA patients exposed to biologics or cytotoxic drugs have to be followed carefully and long-term observation has to be continued in adulthood.
authors.affiliation: Department of Pediatrics, Asklepios Clinic Sankt Augustin, Arnold-Jannssen Str. 29, 53757 Sankt Augustin, Germany. g.horneff@asklepios.com
authors.forename: Gerd
authors.initials: G
authors.lastname: Horneff
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.forename: Kirsten
authors.initials: K
authors.lastname: Minden
authors.forename: Dagmar
authors.initials: D
authors.lastname: Moebius
authors.forename: Toni
authors.initials: T
authors.lastname: Hospach
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001171:Arthritis, Juvenile / Q000150:complications / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005858:Germany; D006801:Humans; D007223:Infant; D008223:Lymphoma / Q000139:chemically induced*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D009369:Neoplasms / Q000139:chemically induced* / Q000150:complications; D012042:Registries; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate