Stefania Simou

Muscle biopsy in combination with myositis-specific autoantibodies aids prediction of outcomes in juvenile dermatomyositis.

Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis‐specific autoantibodies (MSAs) have prognostic significance in juvenile DM.

Autoantibodies in juvenile-onset myositis: Their diagnostic value and associated clinical phenotype in a large UK cohort

Objectives Juvenile myositis is a rare and heterogeneous disease. Diagnosis is often difficult but early treatment is important in reducing the risk of associated morbidity and poor outcomes. Myositis specific autoantibodies have been described in both juvenile and adult patients with myositis and can be helpful in dividing patients into clinically homogenous groups. We aimed to explore the utility of myositis specific autoantibodies as diagnostic and prognostic biomarkers in patients with juvenile-onset disease. Methods Using radio-labelled immunoprecipitation and previously validated ELISAs we examined the presence of myositis specific autoantibodies in 380 patients with juvenile-onset myositis in addition to, 318 patients with juvenile idiopathic arthritis, 21 patients with juvenile-onset SLE, 27 patients with muscular dystrophies, and 48 healthy children. Results An autoantibody was identified in 60% of juvenile-onset myositis patients. Myositis specific autoantibodies (49% patients) were exclusively found in patients with myositis and with the exception of one case were mutually exclusive and not found in conjunction with another autoantibody. Autoantibody subtypes were associated with age at disease onset, key clinical disease features and treatment received. Conclusions In juvenile patients the identification of a myositis specific autoantibody is highly suggestive of myositis. Autoantibodies can be identified in the majority of affected children and provide useful prognostic information. There is evidence of a differential treatment approach and patients with anti-TIF1γ autoantibodies are significantly more likely to receive aggressive treatment with IV cyclophosphamide and/or biologic drugs, clear trends are also visible in other autoantibody subgroups.

Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients

Objective. We aimed to establish the prevalence and clinical associations of anti-HMG-CoA-reductase (anti-HMGCR) in a large UK cohort with juvenile myositis. Methods. There were 381 patients investigated for anti-HMGCR using ELISA. Results. Anti-HMGCR autoantibodies were detected in 4 patients (1%). These children had no or minimal rash and significant muscle disease. Muscle biopsies were considered distinctive, with widespread variation in fiber size, necrotic fibers, and chronic inflammatory cell infiltrates; all had prolonged elevation of creatine kinase and all ultimately received biologic therapies. Conclusion. Anti-HMGCR in UK children with myositis are associated with severe disease that is poorly responsive to standard treatment.

Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling

In patients with severe or refractory juvenile dermatomyositis (DM), second‐line treatments may be required. Cyclophosphamide (CYC) is used to treat some connective tissue diseases, but evidence of its efficacy in juvenile DM is limited. This study was undertaken to describe clinical improvement in juvenile DM patients treated with CYC and model the efficacy of CYC treatment compared to no CYC treatment.

OP0221 Efficacy and Safety of Tumour Necrosis Factor-Alpha Antagonists in A Large Cohort of Juvenile Dermatomyositis Patients

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-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. Objectives To evaluate the efficacy and safety of anti-TNFα 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