Report on malignancies in the German juvenile idiopathic arthritis registry.

OBJECTIVES: 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. METHOD: 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. CONCLUSION: 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.

B cell depletion for autoimmune diseases in paediatric patients.

Data on B cell depletion therapy in severe autoimmune diseases in paediatric patients are very limited. We conducted a retrospective cohort study and recruited patients who were treated with rituximab (RTX) and followed up for at least 6 months through the German societies of paediatric rheumatology and nephrology. The aim was to describe the spectrum of autoimmune disorders for which RTX was used and to describe the applied therapeutic regimens, the observed efficacy, as well as potential immunological side effects. The need to develop standard treatment guidelines for future trials should be discussed. Sixty-five patients were included. Nineteen patients suffered from systemic lupus erythematosus, 13 from vasculitic disorders, 12 from hematological autoimmune diseases, 5 from mixed connective tissue disorders, 4 from juvenile idiopathic arthritis, and 9 had other autoimmune diseases. Adverse, infusion-related events were reported in 12/65 (18%) patients. Considering laboratory and clinical parameters, 13 patients (22%) were in complete remission, 31 (52%) were in partial remission, 6 (10%) were unchanged and 10 (17%) had progressed after 6 months. In 46% of the patients, the steroid dose could be more than halved. IgG, IgM and IgA decreased from normal levels prior to RTX therapy to below normal levels at 6 months in 2/22 (9%), 10/21 (48%), and 4/22 (18%) patients, respectively. Immunoglobulin deficiency or prolonged CD20 depletion was reported in eight patients after an observation period longer than 12 months. RTX therapy led to a perceivable reduction in disease activity. However, long-term immunological alterations may occur in more than 10% of the patients. Guidelines and protocols for off-label therapy are desirable to document reasonable follow-up data. Controlled prospective studies for RTX therapies in children with standardised therapeutic and diagnostic protocols are urgently needed.