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.
Arthritis Rheumatol. 2018 May;70(5):785-793. doi: 10.1002/art.40418. Epub 2018 Mar 25.
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 ), global disease (P = 2.4 × 10 ), and muscle disease (P = 8.0 × 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.
对于严重或难治性幼年特发性皮肌炎（DM）患者，可能需要二线治疗。环磷酰胺（CYC）用于治疗某些结缔组织疾病，但在幼年 DM 中的疗效证据有限。本研究旨在描述接受 CYC 治疗的幼年 DM 患者的临床改善情况，并建立 CYC 治疗与不接受 CYC 治疗的疗效模型。
对参加幼年 DM 队列和生物标志物研究的患者的皮肤、整体和肌肉疾病的临床数据进行了分析。使用未调整分析描述 CYC 治疗后的临床改善情况。使用边际结构模型（MSM）对治疗效果进行建模，并调整指示性混杂因素。
与开始 CYC 治疗相比，56 例接受 CYC 治疗的患者在未调整分析中，皮肤疾病（P=1.3×10）、整体疾病（P=2.4×10）和肌肉疾病（P=8.0×10）在 6、12 和 24 个月时均有下降。有限的证据表明接受 CYC 治疗的患者糖皮质激素剂量减少（P=0.047）。MSM 分析显示，与从未接受过或尚未接受 CYC 治疗的患者相比，开始接受~6 个月 CYC 治疗且已过去>12 个月的患者整体疾病和皮肤疾病有所改善。在接受治疗的患者中，改良的幼年 DM 皮肤疾病活动评分降低了 1.19 分（P=0.0085），医生整体评估降低了 0.66 分（P=0.027）。3 例患者在停止 CYC 治疗后 1 年内报告了轻微不良反应。
我们的研究结果表明，CYC 有效且无短期副作用。观察到皮肤、整体和肌肉疾病的改善。需要进一步研究来评估长期副作用。
