University of Michigan Health, Ann Arbor.
Arizona Arthritis & Rheumatology Research, Phoenix.
Arthritis Rheumatol. 2022 Aug;74(8):1399-1408. doi: 10.1002/art.42133. Epub 2022 Jun 27.
Hand dysfunction is common in systemic sclerosis (SSc). We undertook this study to evaluate the capacity of autologous adipose-derived regenerative cells (ADRCs) to improve hand function in SSc patients.
The Scleroderma Treatment with Celution Processed Adipose Derived Regenerative Cells Trial was a prospective, randomized, double-blind trial of ADRCs, in which ADRCs were obtained from patients with SSc by small-volume adipose tissue harvest, and the fingers of each patient were injected with ADRCs. The primary end point was change in hand function at 24 and 48 weeks, assessed using the Cochin Hand Function Scale (CHFS). One of the secondary end points included the change in Health Assessment Questionnaire disability index (HAQ DI) at 48 weeks. Separate prespecified analyses were performed for patients with diffuse cutaneous SSc (dcSSc) and those with limited cutaneous SSc (lcSSc).
Eighty-eight patients were randomized to receive ADRCs (n = 48 [32 patients with dcSSc and 16 with lcSSc]) or placebo (n = 40 [19 patients with dcSSc and 21 with lcSSc]). Change in hand function according to CHFS score was numerically higher for the ADRC group compared to the placebo group but did not achieve statistical significance (mean ± SD improvement in the CHFS score at 48 weeks 11.0 ± 12.5 versus 8.9 ± 10.5; P = 0.299). For patients with dcSSc, the between-group difference in the CHFS at 48 weeks was 6.3 points (nominal P = 0.069). For the secondary end point, the dcSSc group exhibited a between-group difference of 0.17 points in the HAQ DI (nominal P = 0.044) at 48 weeks. Of the ADRC-treated patients with dcSSc, 52% reported improvement greater than the minimum clinically important difference for both CHFS and HAQ DI compared to 16% in the placebo group (nominal P = 0.016). Small-volume adipose tissue harvest and ADRC treatment were well tolerated.
While the primary end point of this trial was not achieved, efficacy trends were observed in patients with dcSSc. Adipose tissue harvest and ADRC injection were demonstrated to be feasible. Further clinical trials of this intervention in the setting of dcSSc are warranted.
手功能障碍在系统性硬化症（SSc）中较为常见。我们进行这项研究是为了评估自体脂肪来源的再生细胞（ADRCs）改善 SSc 患者手部功能的能力。
硬皮病治疗与细胞处理的脂肪衍生再生细胞试验（Scleroderma Treatment with Celution Processed Adipose Derived Regenerative Cells Trial）是一项前瞻性、随机、双盲的 ADRC 试验，从 SSc 患者中通过小体积脂肪组织采集获得 ADRC，然后将每个患者的手指注射 ADRC。主要终点是在 24 周和 48 周时使用科钦手功能量表（Cochin Hand Function Scale，CHFS）评估手部功能的变化。次要终点之一包括在 48 周时评估健康评估问卷残疾指数（Health Assessment Questionnaire disability index，HAQ DI）的变化。对弥漫性皮肤型 SSc（dcSSc）患者和局限性皮肤型 SSc（lcSSc）患者分别进行了预先指定的分析。
88 名患者被随机分配接受 ADRC（n=48 [32 名 dcSSc 患者和 16 名 lcSSc 患者]）或安慰剂（n=40 [19 名 dcSSc 患者和 21 名 lcSSc 患者]）。根据 CHFS 评分，ADRC 组的手部功能改善数值高于安慰剂组，但未达到统计学意义（48 周时 CHFS 评分的平均改善±标准差，ADRC 组为 11.0±12.5，安慰剂组为 8.9±10.5；P=0.299）。对于 dcSSc 患者，48 周时 CHFS 的组间差异为 6.3 分（名义 P=0.069）。次要终点方面，dcSSc 组在 48 周时 HAQ DI 的组间差异为 0.17 分（名义 P=0.044）。在接受 dcSSc 治疗的 ADRC 患者中，与安慰剂组的 16%相比，52%的患者报告 CHFS 和 HAQ DI 的改善大于最小临床重要差异（名义 P=0.016）。小体积脂肪组织采集和 ADRC 治疗耐受性良好。
虽然该试验的主要终点未达到，但在 dcSSc 患者中观察到了疗效趋势。证明了脂肪组织采集和 ADRC 注射是可行的。需要在 dcSSc 中进一步开展该干预措施的临床试验。
