Background While TNFα-inhibitors improved outcome of JIA markedly, concerns have been raised about an increased risk for malignancies especially lymphoma, probably already due to the disease itself.
Methods The BIKER data base was used to identify cases of suspected and confirmed malignancies
Results Until 2015, 3695 pts treated with MTX and /or TNFα inhibitors were prospectively followed with 13198 observation years (OY). 12 cases of suspected malignancies, including 7 lymphoid neoplasms, have been reported. 11 pts had received MTX, 2 CSA, single patients received Sulfasalazine, Azathioprine or Leflunomide. 9 pts received Etanercept (ETA), 2 Adalimumab, and 1 case consecutively ETA, Infliximab and Abatacept. A case of myelodysplasia, with spontaneous recovery and a cervical dysplasia were labelled as suspected. Confirmed cases included 2 Hodgkin's lymphoma, 1 non-Hodgkin's lymphoma, 2 ALL and 2 lymphoproliferative disorders, who recovered after discontinuation of immunosuppressive therapy. Singular confirmed cases were thyroid carcinoma, yolk sac carcinoma, cervical dysplasia and anaplastic ependymoma. The total rate of malignancies observed in the registry (0.91/1000Y) exceeds the rate expected according to data of the German cancer registry (0.16/1000Y, p<0.001). The calculated risk-ratio in the MTX cohort (n=3: 1 lymphoma, 2 acute lymphatic leukaemias) was significantly increased for both all malignancies (RR 4.5; 95% CI1.5–14.0) and for haemato-lymphatic malignancies (RR 10.1; 95% CI 3.2–31.2). The risk ratio in the ETA cohort also was significantly increased (RR for all malignancies 8.1; 95% CI 4.2–15.5; RR for leukaemia/lymphoma 10.4 (3.9–27.7). No difference was found between the incidence rate of malignancies within the ETA cohort compared to the MTX cohort (p=0.39). Rates did not markedly differ if suspected malignancies (cervical dysplasia, myelodysplasia) were excluded. 6 of the 7 haemato-lymphatic malignancies occurred in ps <15 y of age. There was a higher rate within MTX (0.93/1000Y; 95%CI 0.30–2.89) than with ETA (0.56/1000Y; 95%CI 0.18–1.74). 4 of 5 solid tumours occurred after the age of 15, all in the ETA cohort. One patient never exposed to biologics but to MTX died of ALL, all other recovered.
Conclusions Malignancies were more frequent than expected. Whether the increased risk is through the rheumatic disease or through treatment remains unclear. Treatment with ETA seems not to further increase the malignancy risk. Long-term observation of JIA patients treated with TNFα inhibitors into adulthood remains an important challenge.
Disclosure of Interest None declared