Background/Purpose:  Cyclophosphamide (CYC) has been used as a second-line agent in the treatment of severe or refractory JDM. The published literature on the efficacy of CYC in JDM is limited to a small number of case series and case reports. The aim of this study was to describe the efficacy and safety of CYC in a large national UK patient cohort with severe or refractory JDM.

Methods:  Patients treated with CYC met Bohan and Peter criteria and were recruited to the UK JDM Cohort and Biomarker Study (JDCBS). Patients received CYC at 500mg/m2 (max 500mg) every 2 weeks for first 3 doses and then 750mg/m2 (max 1.2g) every 3-4 weeks according to response for total 6-10 doses. Clinical data at baseline and 6, 12 and 24 months were recorded, including physician’s global assessment (PGA) to assess overall disease activity, modified disease activity score (mDAS) to assess skin disease, and Childhood Myositis Assessment Scale (CMAS) and Manual Muscle Testing (MMT8) to assess muscle weakness. Data are presented as median [interquartile range] and were analyzed using Friedman’s test for non-parametric repeated measures ANOVA, with post-hoc tests using the Wilcoxon signed rank test and Bonferroni adjustment.

Results:  Of 525 patients in the JDCBS 83 patients were treated with CYC, of whom 62.7% were female. Age at diagnosis was 6.2 [4.0-10.0] years and disease duration at CYC start was 45 [26-320] days. Total duration of disease was 8.6 [5.0-12.8] years. Patients who received CYC had more severe disease compared to patients who did not receive CYC, as assessed by PGA (p=3.60e-12), mDAS (p=0.00056), CMAS (p=1.98e-9) and MMT8 (p=6.21e-5). Overall, disease activity improved over the time-points analyzed, with improvements in PGA (p=5.5e-13), mDAS (p=4.98e-10), CMAS (p=4.08e-13) and MMT8 (p=1.33e-5). For all outcome measures, the 6, 12 and 24 month time-points differed significantly from baseline. PGA reduced from 6.9 [4.1-8.0] at baseline to 2.0 [1.0-3.1] at 6 months (p=3.61e-9), 0.8 [0.3-2.3] at 12 months (p=3.89e-8) and 0.9 [0.0-1.8] at 24 months (p=4.13e-9). mDAS decreased from 4 [2.5-5] at baseline to 3 [0-4] at 6 months (p=0.00099), 2 [0-4] at 12 months (p=2.99e-5) and 0 [0-3] at 24 months (p=1.00e-7). CMAS increased from 22 [6.75-38] at baseline to 45 [38.75-49.25] at 6 months (p=9.32e-8), 47 [44-52] at 12 months (p=1.32e-7) and 49 [45-53] at 24 (p=1.77e-7) months. MMT8 increased from 52 [30.25-62.75] at baseline to 78 [67-80] at 6 months (p=9.82e-5), 76 [70-79] at 12 months (p=9.49e-5) and 80 [73-80] at 24 months (p=4.29e-5). Finally, CYC appeared to be well-tolerated with no serious adverse events including infections reported during the study period.

Conclusion:  Significant improvement in both skin and muscle disease was observed in patients who received CYC at 6, 12 and 24 months after the onset of therapy. Ongoing analyses are exploring whether overall disease trajectories of patients treated with CYC differ from those of patients who were not treated with CYC.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/analysis-of-efficacy-and-safety-of-cyclophosphamide-in-juvenile-dermatomyositis-using-a-large-national-uk-cohort/