• Gerd Horneff, Ariane Klein, Prasad T Oommen, Anton Hospach, Ivan Foeldvari, Isa Feddersen, and Kirsten Minden.
• Centre for Paediatric Rheumatology, Department of Paediatrics, Asklepios Clinic Sankt Augustin, Germany. g.horneff@asklepios.com.
• Clin Exp Rheumatol. 2016 Nov 1; 34 (6): 1113-1120.

ObjectivesWhile 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.MethodsCases of suspected malignancies documented in the German Biker Registry are reviewed in detail.ResultsUntil 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.ConclusionsIn 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.

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