Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colorado, USA
Biostatistics and Bioinformatics, National Jewish Health, Denver, Colorado, USA.
Thorax. 2023 Nov;78(11):1097-1104. doi: 10.1136/thorax-2022-219795. Epub 2023 Apr 7.
Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients.
We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety.
After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference -0.76%, 95% CI -6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events.
The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP.
NCT02958917.
纤维化性过敏性肺炎（FHP）是一种具有高发病率和死亡率的不可逆肺疾病。我们旨在评估吡非尼酮在这类患者疾病进展中的安全性和疗效。
我们开展了一项单中心、随机、双盲、安慰剂对照试验，纳入纤维化性过敏性肺炎且病情进展的成年人患者。患者按照 2:1 的比例随机分组，分别接受口服吡非尼酮（2403 mg/天）或安慰剂治疗 52 周。主要终点为用力肺活量（FVC）预计值的绝对变化的平均值（%）。次要终点包括无进展生存期（PFS，FVC 和/或一氧化碳弥散量（DLCO）相对下降≥10%、急性呼吸恶化、6 分钟步行距离下降≥50m、免疫抑制药物的使用或停药、FVC 斜率和平均 DLCO%的变化、住院、肺纤维化的影像学进展以及安全性）。
在纳入 40 例患者后，因 COVID-19 大流行而中断了入组。第 52 周时，两组间 FVC%无显著差异（平均差值-0.76%，95%CI-6.34 至 4.82）。吡非尼酮可降低第 26 周时调整后的 FVC%的下降率，并改善 PFS（HR 0.26，95%CI 0.12 至 0.60）。其他次要终点的结果两组间无显著差异。吡非尼酮组无死亡事件，安慰剂组发生 1 例死亡（呼吸）。无治疗相关的严重不良事件发生。
该试验在主要终点方面的效力不足。吡非尼酮在 FHP 患者中是安全的，并改善了 PFS。
NCT02958917。
