Abstract：
This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.
The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.
Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.
This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.
The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.
Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.
This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.
摘要：
背景：这项研究检查了标准护理系统性红斑狼疮（SLE）药物与关键结局的关系，例如低疾病活动程度，耀斑,损害应计，和类固醇的节省，目前缺乏数据。
方法：亚太狼疮合作组织（APLC）前瞻性地在众多地点收集有关人口统计学和疾病特征的数据，药物使用,和狼疮的结果。使用倾向评分方法和面板逻辑回归模型，我们确定了狼疮药物和结局之间的关联.
结果：在1707名患者中，随访超过12,689次，中位时间为2.19年，1332例（78.03%）患者达到狼疮低疾病活动状态（LLDAS），976次（57.18%）经历过耀斑，在大多数就诊中，患者服用抗疟疾药(69.86%)或免疫抑制药(76.37%)。泼尼松龙,在所有器官结构域中使用羟氯喹和硫唑嘌呤的频率相似；甲氨蝶呤用于肌肉骨骼活动。各国之间的药物利用率存在差异，羟氯喹的频率较低，钙调磷酸酶抑制剂更常见，在日本使用。更多的患者服用来氟米特，甲氨蝶呤,氯喹/羟氯喹，硫唑嘌呤，和霉酚酸酯/霉酚酸服用≤7.5mg/天的泼尼松龙（相比于>7.5mg/天），表明类固醇保留作用。患者服用他克莫司的可能性更大（赔率比[95%置信区间]13.58[2.23-82.78]，p=0.005)以获得LLDAS。服用硫唑嘌呤的患者（OR0.67[0.53-0.86]，p=0.001）和甲氨蝶呤（OR0.68[0.47-0.98]，p=0.038）不太可能达到LLDAS。服用霉酚酸酯的患者不太可能出现耀斑（OR0.79[0.64-0.97]，p=0.025)。没有一种药物与损害累积的减少有关。
结论：这项研究表明，SLE治疗中最常用的标准治疗免疫抑制剂具有节省类固醇的益处，其中一些与获得LLDAS的可能性增加有关，或减少耀斑的发生率。它还强调了对狼疮有效治疗的未满足需求。
方法：亚太狼疮合作组织（APLC）前瞻性地在众多地点收集有关人口统计学和疾病特征的数据，药物使用,和狼疮的结果。使用倾向评分方法和面板逻辑回归模型，我们确定了狼疮药物和结局之间的关联.
结果：在1707名患者中，随访超过12,689次，中位时间为2.19年，1332例（78.03%）患者达到狼疮低疾病活动状态（LLDAS），976次（57.18%）经历过耀斑，在大多数就诊中，患者服用抗疟疾药(69.86%)或免疫抑制药(76.37%)。泼尼松龙,在所有器官结构域中使用羟氯喹和硫唑嘌呤的频率相似；甲氨蝶呤用于肌肉骨骼活动。各国之间的药物利用率存在差异，羟氯喹的频率较低，钙调磷酸酶抑制剂更常见，在日本使用。更多的患者服用来氟米特，甲氨蝶呤,氯喹/羟氯喹，硫唑嘌呤，和霉酚酸酯/霉酚酸服用≤7.5mg/天的泼尼松龙（相比于>7.5mg/天），表明类固醇保留作用。患者服用他克莫司的可能性更大（赔率比[95%置信区间]13.58[2.23-82.78]，p=0.005)以获得LLDAS。服用硫唑嘌呤的患者（OR0.67[0.53-0.86]，p=0.001）和甲氨蝶呤（OR0.68[0.47-0.98]，p=0.038）不太可能达到LLDAS。服用霉酚酸酯的患者不太可能出现耀斑（OR0.79[0.64-0.97]，p=0.025)。没有一种药物与损害累积的减少有关。
结论：这项研究表明，SLE治疗中最常用的标准治疗免疫抑制剂具有节省类固醇的益处，其中一些与获得LLDAS的可能性增加有关，或减少耀斑的发生率。它还强调了对狼疮有效治疗的未满足需求。
