EULAR 2016 | Daily Highlights

EFFICACY AND SAFETY OF TUMOUR NECROSIS FACTOR-?LFA ANTAGONISTS IN A LARGE COHORT OF JUVENILE DERMATOMYOSITIS PATIENTS

Abstract: OP0221
Authors: R. Campanilho-Marques^1,2,3,4,*, C. Deakin¹, S. Simou¹, L. R. Wedderburn^1,5, C. Pilkington² on behalf of Juvenile Dermatomyositis Research Group (JDRG)
Co Authors: ¹Infection, Inflammation and Rheumatology Section, UCL, Institute of Child Health, ²Rheumatology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom, ³Rheumatology, Instituto Português de Reumatologia, ⁴Rheumatology, Santa Maria Hospital, Lisbon, Portugal, ⁵Arthritis Research UK Centre for Adolescent Rheumatology, UCL, UCLH, GOSH NHS Trust, London, United Kingdom

Background
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 anti-TNF? 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.

Objectives
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
66 patients with JDM actively treated with anti-TNF agents were analyzed. 41 patients were female (62%). The current mean (±SD) age of these patients was 16.8±5.6 years old, the mean age at diagnosis was 7.31±4.04 years old and the mean disease duration was of 9.6±4.6. Mean disease duration at the beginning of anti-TNF treatment was 3.49±2.80 years and mean duration of anti-TNF therapy was of 2.76±2.09 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 [74.5-80] (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 21 adverse reactions registered, 7 were considered severe (anaphylactic reactions on infliximab infusion). 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 77% (n=10) of them were due to infections causes. In 4 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 tuberculosis case was registered.

Conclusions
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.

Disclosure of Interest
None declared

DOI: 10.1136/annrheumdis-2016-eular.5062

Comment:
There are almost no data available on the treatment of juvenile dermatomyositis patients. In addition, juvenile dermatomyositis is often severe and associated with increased morbidity and mortality. The current study included a remarkably high number of patients from an observational cohort and shows consistent improvements across different clinically relevant endpoints. These kinds of innovative study designs are important in particular for rare diseases, where classical randomized controlled trials are difficult to perform. At the same time, they have some inherited limitations: Due to the observational nature, there is a treatment by indication error, thus particular those patients are treated by the observing physicians that are more likely to respond to the selected therapy. The study also lacked a control group which is important to differentiate the results from the natural course of the disease. Finally, some of the changes appear to be rather small (e.g. MMT-8) and it needs further assessments whether they are clinically meaningful. It is also remarkable that the effects of the TNFa inhibitor Infliximab were mixed at best in refractory adult inflammatory myopathies with some patients sowing flares under treatment (Ann Rheum Dis. 2008 Dec;67(12):1670-7). Thus, these interesting findings in juvenile dermatomyositis patients need further assessments before it can be implemented in clinical practice as a routine treatment.

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