Park Ryan, Nevskaya Tatiana, Baron Murray, Pope Janet E
Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
Division of Rheumatology, Department of Medicine, St. Joseph's Health Care, London, ON, Canada.
J Scleroderma Relat Disord. 2022 Feb;7(1):33-41. doi: 10.1177/23971983211000971. Epub 2021 Mar 29.
Immunosuppression remains the main treatment for progressing skin involvement, interstitial lung disease and inflammatory joint or muscle disease in systemic sclerosis. This study investigated the pattern and trends in immunosuppressive agents used in early systemic sclerosis (diagnosed before and after 2007) to determine whether the changes in the preferred type, timing and combination of immunosuppression took place over the past decade.
In total, 397 Canadian Scleroderma Research Group database patients (183 diffuse cutaneous systemic sclerosis and 214 limited cutaneous systemic sclerosis) who had baseline and follow-up visits within 3 years (mean: 1.8 ± 0.8) after disease onset were included: 82% females, age at diagnosis 53 ± 13 years. Bivariate, chi-square, analysis of variance and adjusted regression analyses were used.
In total, 115 diffuse cutaneous systemic sclerosis patients (63%) and 62 limited cutaneous systemic sclerosis (29%) received immunosuppressive drugs, most commonly methotrexate, followed by mycophenolate mofetil and cyclophosphamide. In diffuse cutaneous systemic sclerosis, immunosuppressants were prescribed after 2007 more often (74% vs 50%, = 0.001), especially methotrexate ( = 0.02) and mycophenolate mofetil ( = 0.04), and earlier (peak at 2 years after onset). Immunosuppressive therapy was associated with male gender, interstitial lung disease, anti-Scl70 positivity, ACA negativity and inflammatory joint disease in limited cutaneous systemic sclerosis and with ACA negativity and a higher modified Rodnan skin score in diffuse cutaneous systemic sclerosis. Multivariate regression analysis showed that the use of immunosuppressants after 2007 was predicted only by ACA negativity in limited cutaneous systemic sclerosis and by younger age in diffuse cutaneous systemic sclerosis.
Over the past decade, there has been a trend to prescribe immunosuppressants more often and earlier in diffuse cutaneous systemic sclerosis patients, regardless of modified Rodnan skin score. Methotrexate is being more frequently used, and mycophenolate mofetil has gained favour over cyclophosphamide. Autoantibody status was the most consistent predictor of immunosuppressive therapy.
免疫抑制仍然是系统性硬化症中进展性皮肤受累、间质性肺病以及炎性关节或肌肉疾病的主要治疗方法。本研究调查了早期系统性硬化症（2007年前后诊断）中使用免疫抑制剂的模式和趋势，以确定在过去十年中免疫抑制的首选类型、时机和联合使用是否发生了变化。
总共纳入了397名加拿大硬皮病研究组数据库中的患者（183例弥漫性皮肤系统性硬化症和214例局限性皮肤系统性硬化症），这些患者在疾病发作后3年内（平均：1.8±0.8）进行了基线和随访：82%为女性，诊断时年龄为53±13岁。使用了双变量分析、卡方检验、方差分析和调整后的回归分析。
总共115例弥漫性皮肤系统性硬化症患者（63%）和62例局限性皮肤系统性硬化症患者（29%）接受了免疫抑制药物治疗，最常用的是甲氨蝶呤，其次是霉酚酸酯和环磷酰胺。在弥漫性皮肤系统性硬化症中，2007年后更频繁地开具免疫抑制剂（74%对50%，P = 0.001），尤其是甲氨蝶呤（P = 0.02）和霉酚酸酯（P = 0.04），且更早开具（发病后2年达到峰值）。在局限性皮肤系统性硬化症中，免疫抑制治疗与男性、间质性肺病、抗Scl70阳性、抗着丝点抗体阴性和炎性关节疾病相关；在弥漫性皮肤系统性硬化症中，与抗着丝点抗体阴性和更高的改良Rodnan皮肤评分相关。多变量回归分析显示，在局限性皮肤系统性硬化症中，2007年后使用免疫抑制剂仅由抗着丝点抗体阴性预测；在弥漫性皮肤系统性硬化症中，由更年轻的年龄预测。
在过去十年中，无论改良Rodnan皮肤评分如何，弥漫性皮肤系统性硬化症患者中都存在更频繁、更早开具免疫抑制剂的趋势。甲氨蝶呤的使用更为频繁，霉酚酸酯比环磷酰胺更受青睐。自身抗体状态是免疫抑制治疗最一致的预测因素。
