Safety and efficacy of namilumab for the treatment of chronic pulmonary sarcoidosis (RESOLVE-Lung): a randomised, double-blinded, multicentre, phase 2 study.

Namilumab, an investigational humanised monoclonal antibody inhibiting granulocyte-macrophage colony-stimulating factor, was hypothesised to downregulate the granulomatous response in pulmonary sarcoidosis.

Namilumab是一种正在研究中的人源化单克隆抗体，用于抑制粒细胞-巨噬细胞集落刺激因子，据推测能够下调肺结节病中的肉芽肿反应。

Methods

RESOLVE-Lung was a double-blind, placebo-controlledtrial in participants with chronic active pulmonary sarcoidosis on oral corticosteroids (OCS) and/or immunosuppressive therapies (IST).

RESOLVE-Lung 是一项双盲、安慰剂对照试验，针对正在接受口服皮质类固醇（OCS）和/或免疫抑制治疗（IST）的慢性活动性肺部肉芽肿病患者。

Participants were randomised (1:1) to receive 150 mg namilumab or placebo via subcutaneous injection every 4 weeks and were required to stop IST and/or taper OCS.

参与者按1:1的比例随机分配，每4周通过皮下注射接受150 mg的namilumab或安慰剂，并且需要停止使用IST和/或逐渐减少OCS。

End-points were assessed at week 26.

在第26周评估了研究终点。

The primary end-point was the proportion of participants with a rescue event, such as disease worsening necessitating treatment.

主要终点是参与者中需要治疗的疾病恶化等救援事件的比例。

Secondary end-points included safety, lung function assessments and corticosteroid burden.

次要终点包括安全性、肺功能评估和皮质类固醇负担。

The trial was registered at ClinicalTrials.gov (NCT05314517).

该试验已在ClinicalTrials.gov注册（NCT05314517）。

Results

Of 209 participants screened, 107 were randomised to receive namilumab (n=53) or placebo (n=54).

在筛选的209名参与者中，有107人被随机分配接受namilumab（n=53）或安慰剂（n=54）。

The proportion of participants with a rescue event was higher for the namilumab group (37.5%) compared with the placebo group (23.5%) (stratified difference 13.6 (90% CI -1.5-28.7) percentage points; p=0.12).

与安慰剂组（23.5%）相比，接受namilumab组的救援事件比例更高（37.5%）（分层差异13.6（90%置信区间-1.5-28.7）百分点；p=0.12）。

The least squares (LS) mean change from baseline in forced vital capacity % predicted was -3.3 (90% CI -5.1- -1.5) percentage points for namilumab and -2.9 (90% CI -4.5- -1.3) percentage points for placebo (LS mean difference -0.4 (90% CI -2.7-2.0) percentage points).

在基线时，使用最小二乘法（LS）计算的用力肺活量（FVC）%预测值的平均变化为：namilumab组为-3.3（90%置信区间-5.1至-1.5）个百分点，安慰剂组为-2.9（90%置信区间-4.5至-1.3）个百分点（LS平均差异为-0.4（90%置信区间-2.7至2.0）个百分点）。

The proportion of participants successfully achieving OCS taper was 53.3% for namilumab and 76.9% for placebo (difference -19.4 (90% CI -47.5-8.7) percentage points).

成功实现OCS减量的参与者比例为：namilumab组为53.3%，安慰剂组为76.9%（差异为-19.4（90%置信区间-47.5至8.7）个百分点）。

Treatment-emergent adverse events were reported in 94% in both groups, most being mild or moderate in severity.

两组中报告的治疗后不良事件发生率为94%，大多数为轻度或中度。

Conclusions

In participants with chronic active pulmonary sarcoidosis, namilumab did not provide clinical benefit.

在慢性活动性肺部肉芽肿病患者中，namilumab并未提供临床益处。