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Arthritis Rheumatol. 2018 May;70(5):785-793. doi: 10.1002/art.40418. Epub 2018 Mar 25.

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

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University College London Great Ormond Street Institute of Child Health, London, UK.
Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon Academic Medical Centre and Instituto Português de Reumatologia, Lisbon, Portugal.
University College London Great Ormond Street Institute of Child Health, Great Ormond Street Hospital for Children, NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children, NHS Foundation Trust, and Arthritis Research UK Centre for Adolescent Rheumatology at University College London, University College London Hospital, and Great Ormond Street Hospital, London, UK.
Hospital for Sick Children, Toronto, Ontario, Canada.
Great Ormond Street Hospital for Children, London, UK.



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.


Clinical data on skin, global, and muscle disease for patients recruited to the Juvenile DM Cohort and Biomarker Study were analyzed. Clinical improvement following CYC treatment was described using unadjusted analysis. Marginal structural models (MSMs) were used to model treatment efficacy and adjust for confounding by indication.


Compared to the start of CYC treatment, there were reductions at 6, 12, and 24 months in skin disease (P = 1.3 × 10-10 ), global disease (P = 2.4 × 10-8 ), and muscle disease (P = 8.0 × 10-10 ) for 56 patients treated with CYC in unadjusted analysis. Limited evidence suggested a reduction in glucocorticoid dose (P = 0.047) in patients treated with CYC. MSM analysis showed reduced global disease and skin disease in patients who started an ~6-month course of CYC treatment >12 months ago compared to patients never or not yet treated with CYC. In the treated patients, the modified skin Disease Activity Score for juvenile DM was 1.19 units lower (P = 0.0085) and the physician's global assessment was 0.66 units lower (P = 0.027). Minor adverse events were reported in 3 patients within 1 year of stopping CYC.


Our findings indicate that CYC is efficacious with no short-term side effects. Improvements in skin, global, and muscle disease were observed. Further studies are required to evaluate longer-term side effects.

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