OBJECTIVE T cells play a key role in the pathogenesis of early systemic sclerosis. This study was undertaken to assess the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc). METHODS In this 12-month, randomized, double-blind, placebo-controlled trial, participants were randomized 1:1 to receive either subcutaneous abatacept 125 mg or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at 6 months for worsening disease. The coprimary end points were change in the modified Rodnan skin thickness score (MRSS) compared to baseline and safety over 12 months. Differences in longitudinal outcomes were assessed according to treatment using linear mixed models, with outcomes censored after initiation of escape therapy. Skin tissue obtained from participants at baseline was classified into intrinsic gene expression subsets. RESULTS Among 88 participants, the adjusted mean change in the MRSS at 12 months was -6.24 units for those receiving abatacept and -4.49 units for those receiving placebo, with an adjusted mean treatment difference of -1.75 units (P = 0.28). Outcomes for 2 secondary measures (Health Assessment Questionnaire disability index and a composite measure) were clinically and statistically significantly better with abatacept. The proportion of subjects in whom escape therapy was needed was higher in the placebo group relative to the abatacept group (36% versus 16%). In the inflammatory and normal-like skin gene expression subsets, decline in the MRSS over 12 months was clinically and significantly greater in the abatacept group versus the placebo group (P < 0.001 and P = 0.03, respectively). In the abatacept group, adverse events occurred in 35 participants versus 40 participants in the placebo group, including 2 deaths and 1 death, respectively. CONCLUSION In this phase II trial, abatacept was well-tolerated, but change in the MRSS was not statistically significant. Secondary outcome measures, including gene expression subsets, showed evidence in support of abatacept. These data should be confirmed in a phase III trial.

中文翻译：

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阿巴西普治疗早期弥漫性皮肤系统性硬化症：II 期研究人员发起的、多中心、双盲、随机、安慰剂对照试验的结果。


目的 T细胞在早期系统性硬化症的发病机制中发挥着关键作用。本研究旨在评估阿巴西普治疗弥漫性皮肤系统性硬化症 (dcSSc) 患者的安全性和有效性。方法 在这项为期 12 个月的随机、双盲、安慰剂对照试验中，参与者以 1:1 的比例随机接受皮下注射阿巴西普 125 mg 或匹配的安慰剂，并按 dcSSc 持续时间分层。 6个月后，由于病情恶化，允许进行逃避治疗。共同主要终点是改良罗德南皮肤厚度评分 (MRSS) 与基线相比的变化以及 12 个月内的安全性。使用线性混合模型根据治疗评估纵向结果的差异，并在开始逃避治疗后对结果进行审查。在基线时从参与者获得的皮肤组织被分类为内在基因表达子集。结果 在 88 名参与者中，接受阿巴西普治疗的患者 12 个月时 MRSS 的调整后平均变化为 -6.24 单位，接受安慰剂的患者为 -4.49 单位，调整后平均治疗差异为 -1.75 单位（P = 0.28）。阿巴西普的 2 项次要指标（健康评估问卷残疾指数和综合指标）的结果在临床和统计学上均显着改善。安慰剂组中需要逃避治疗的受试者比例高于阿巴西普组（36% 比 16%）。在炎症和类正常皮肤基因表达子集中，阿巴西普组与安慰剂组相比，12 个月内 MRSS 的临床下降显着更大（分别为 P < 0.001 和 P = 0.03）。 在阿巴西普组中，有 35 名参与者发生不良事件，而安慰剂组有 40 名参与者发生不良事件，分别包括 2 例死亡和 1 例死亡。结论 在这项 II 期试验中，阿巴西普耐受性良好，但 MRSS 的变化没有统计学意义。次要结果指标，包括基因表达子集，显示了支持阿巴西普的证据。这些数据应在 III 期试验中得到证实。