Background/Purpose:  Some patients with juvenile dermatomyositis (JDM) have a disease course which is refractory to multiple drug treatments. There is evidence that prolonged disease activity is associated with increased mortality and morbidity. High levels of TNFα have been reported in JDM patients with a long disease course, suggesting it may play a significant role in refractory disease. There are no published clinical trials of this therapy but some are in progress. The aim of this study was to evaluate the efficacy and safety of anti-TNF treatment in UK JDM Cohort and Biomarker Study patients.

Methods:  Data were analysed from children who were recruited to the UK JDM Cohort and Biomarker Study, met Bohan-Peter criteria and were on anti-TNF treatment at the time of analysis, and had had at least 3 months of therapy. Childhood Myositis Assessment Scale (CMAS), Manual Muscle Testing (MMT8), muscle enzymes and physicians global assessment (PGA) were recorded. Skin disease was assessed using modified skin Disease activity score (DAS).

Results:  67 patients with JDM actively treated with anti-TNF agents were analyzed. 41 patients were female (61%). The median [IQR] age at disease onset was 5.2 [3.4-9.5] years and the median age at beginning of anti-TNF was 10.1 [6.5-14] years. The median disease duration at beginning of anti-TNF was 3.2 [1.8-5.3] years and the median duration on anti-TNF was of 2.55 [1.5-3.9] years. Muscle involvement significantly improved, with median [IQR] CMAS and MMT8 values at initiation of anti-TNF therapy of 45.50 [39.75-52.25] and 74 [59.5-79.5] respectively, and at current evaluation (or date of anti-TNF treatment completion) of 53 [50-53] and 79 [74.5­80] (p<0.0001 and p=0.0097; Mann Whitney test), respectively. For skin involvement the initial modified DAS was 4 [2-5] and final 1 [0-3] (p<0.0001; Mann Whitney test). Assessing global disease activity the initial PGA was 2.9 [1.3-4.3] and final 0.5 [0-1.45] (p<0.0001; Mann Whitney test). Sixteen patients (24%) switched their anti-TNF treatment. 62.5% of the switches were due to therapy failure, 25% due to adverse events and 12.5% for patient preference in subcutaneous administration. Of 31 adverse events registered (13.3 adverse events per 100 patient-years), 12 were considered severe. One patient died due to small bowel perforation (not felt to be related to the use of TNF antagonists). The remaining adverse reactions were not severe and 79% (n=15) of them were due to infections causes. In 5 of the mild to moderate adverse reactions the drug had to be discontinued and switched to another TNF antagonist, while in the remaining patients temporarily withholding the drug proved sufficient. No malignancies or tuberculosis were reported.

Conclusion:  This study is one of the largest to explore the efficacy and safety of TNF antagonist treatment in a large independent cohort of JDM patients. Both muscle and skin involvement appeared to improve after anti-TNF treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-tumour-necrosis-factor-antagonists-in-a-large-cohort-of-juvenile-dermatomyositis-patients/