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

Claire T Deakin,Clarissa A Pilkington,Stefania Simou,Eleanor Pullenayegum,Raquel Campanilho-Marques,Elena Moraitis,Lucy R Wedderburn,Juvenile Dermatomyositis Research Group

doi:10.1002/art.40418

Claire T Deakin, Clarissa A Pilkington + Show 6 more

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https://doi.org/10.1002/art.40418

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Abstract

ObjectiveIn 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.MethodsClinical 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.ResultsCompared 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.ConclusionOur 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.

Highlights

Compared to the start of CYC treatment, there were reductions at 6, 12, and 24 months in skin disease (P = 1.3 3 10-10), global disease (P = 2.4 3 10-8), and muscle disease (P = 8.0 3 10-10) for 56 patients treated
Demographic, clinical, and serologic features of patients receiving CYC and those not receiving CYC. Both patients who received CYC and those who did not receive CYC were predominantly female, white, and diagnosed as having definite juvenile DM, and the 2 groups had an equivalent duration of follow-up (Table 1)
Skin disease activity at diagnosis was equivalent between the treatment groups, the patients treated with CYC had more global disease activity and muscle disease activity at diagnosis

Summary

Objective

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

Methods

Results

Conclusion

RESULTS

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