University of Michigan, Ann Arbor.
Genentech, South San Francisco, California.
Arthritis Rheumatol. 2021 Jul;73(7):1301-1310. doi: 10.1002/art.41668. Epub 2021 May 25.
Tocilizumab (TCZ) has demonstrated lung function preservation in 2 randomized controlled trials in early systemic sclerosis (SSc). This effect has yet to be characterized in terms of radiographically evident quantitative lung involvement. We undertook this study to assess the impact of TCZ on lung function preservation in a post hoc analysis, stratifying treatment arms according to the degree of lung involvement.
The focuSSced trial was a phase III randomized placebo-controlled trial of TCZ in patients with SSc and progressive skin disease. Participants underwent baseline and serial spirometry along with high-resolution chest computed tomography at baseline and at week 48. Quantitative interstitial lung disease (QILD) and fibrosis scores were assessed by computer software. We classified QILD into the following categories of lung involvement: mild (>5-10%), moderate (>10-20%), and severe (>20%).
Of 210 participants recruited for the trial, 136 patients (65%) had ILD. The majority of these patients (77%) had moderate-to-severe involvement (defined as >10% lung involvement). The TCZ arm demonstrated preservation of forced vital capacity percent predicted (FVC%) over 48 weeks (least squares mean change in FVC% = -0.1) compared to placebo (-6.3%). For mild, moderate, and severe QILD, the mean ± SD change in FVC% in the TCZ arm at 48 weeks were -4.1 ± 2.5% (n = 11), 0.7 ± 1.9% (n =19), and 2.1 ± 1.6% (n = 26), respectively, and in the placebo group were -10.0 ± 2.6% (n = 11), -5.7 ± 1.6% (n = 26), and -6.7 ± 2.0% (n = 16), respectively. Similar treatment-related preservation findings were seen independent of fibrosis severity.
TCZ in early SSc-associated ILD with progressive skin disease stabilized FVC% over 48 weeks, independent of the extent of radiographically evident QILD.
托珠单抗（TCZ）在两项早期系统性硬皮病（SSc）的随机对照试验中显示出肺功能的保留作用。然而，在影像学上明显的定量肺受累方面，这种作用尚未得到描述。我们进行这项研究是为了在后分析中评估 TCZ 对肺功能保留的影响，根据肺受累程度对治疗臂进行分层。
focuSSced 试验是一项 III 期 TCZ 治疗 SSc 伴进行性皮肤疾病的随机安慰剂对照试验。参与者在基线和第 48 周进行了基线和连续肺活量测定以及高分辨率胸部计算机断层扫描。通过计算机软件评估定量间质性肺病（QILD）和纤维化评分。我们将 QILD 分为以下肺受累类别：轻度（>5-10%）、中度（>10-20%）和重度（>20%）。
在该试验招募的 210 名参与者中，有 136 名患者（65%）患有间质性肺病。这些患者中的大多数（77%）有中重度受累（定义为>10%的肺受累）。与安慰剂组（-6.3%）相比，TCZ 组在 48 周时用力肺活量百分比预测值（FVC%）保持不变（最小二乘均值变化 FVC%=-0.1%）。对于轻度、中度和重度 QILD，TCZ 组在第 48 周时 FVC%的平均±SD 变化分别为-4.1±2.5%（n=11）、0.7±1.9%（n=19）和 2.1±1.6%（n=26），而安慰剂组分别为-10.0±2.6%（n=11）、-5.7±1.6%（n=26）和-6.7±2.0%（n=16）。无论纤维化严重程度如何，都观察到了类似的与治疗相关的保留发现。
在早期与 SSc 相关的 ILD 伴进行性皮肤疾病中，TCZ 在 48 周内稳定了 FVC%，与影像学上明显的 QILD 程度无关。
