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Cyclophosphamide (<jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content>) is used to treat some connective tissue diseases, but evidence of its efficacy in juvenile <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content> is limited. This study was undertaken to describe clinical improvement in juvenile <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content> patients treated with <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> and model the efficacy of <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> treatment compared to no <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical data on skin, global, and muscle disease for patients recruited to the Juvenile <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content> Cohort and Biomarker Study were analyzed. Clinical improvement following <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> treatment was described using unadjusted analysis. Marginal structural models (<jats:styled-content style=\"fixed-case\">MSM<\/jats:styled-content>s) were used to model treatment efficacy and adjust for confounding by indication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared to the start of <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> treatment, there were reductions at 6, 12, and 24 months in skin disease (<jats:italic>P<\/jats:italic> = 1.3 \u00d7 10<jats:sup>\u201010<\/jats:sup>), global disease (<jats:italic>P<\/jats:italic> = 2.4 \u00d7 10<jats:sup>\u20108<\/jats:sup>), and muscle disease (<jats:italic>P<\/jats:italic> = 8.0 \u00d7 10<jats:sup>\u201010<\/jats:sup>) for 56 patients treated with <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> in unadjusted analysis. Limited evidence suggested a reduction in glucocorticoid dose (<jats:italic>P<\/jats:italic> = 0.047) in patients treated with <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">MSM<\/jats:styled-content> analysis showed reduced global disease and skin disease in patients who started an ~6\u2010month course of <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> treatment &gt;12 months ago compared to patients never or not yet treated with <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content>. In the treated patients, the modified skin Disease Activity Score for juvenile <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content> was 1.19 units lower (<jats:italic>P<\/jats:italic> = 0.0085) and the physician's global assessment was 0.66 units lower (<jats:italic>P<\/jats:italic> = 0.027). Minor adverse events were reported in 3 patients within 1 year of stopping <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings indicate that <jats:styled-content style=\"fixed-case\">CYC<\/jats:styled-content> is efficacious with no short\u2010term side effects. Improvements in skin, global, and muscle disease were observed. Further studies are required to evaluate longer\u2010term side effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40418","type":"journal-article","created":{"date-parts":[[2018,1,17]],"date-time":"2018-01-17T19:06:42Z","timestamp":1516216002000},"page":"785-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile Dermatomyositis Shown by Marginal Structural Modeling"],"prefix":"10.1002","volume":"70","author":[{"given":"Claire T.","family":"Deakin","sequence":"first","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Campanilho\u2010Marques","sequence":"additional","affiliation":[{"name":"University College London Great Ormond Street Institute of Child Health London UK"},{"name":"Hospital de Santa Maria Centro 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