Respiratory Research@Alfred, Central Clinical School, Monash University, Melbourne, Australia
Department of Respiratory and Sleep Medicine, Austin Health, Heidelberg, Australia.
Eur Respir J. 2023 May 5;61(5). doi: 10.1183/13993003.02163-2022. Print 2023 May.
Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria.
Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria.
Out of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation ( provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19-50%. Adding 6MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4-18% (n=12-61), respectively. Patients meeting the composite common criteria had less-rapid 1-year FVC decline than those who did not (-90 -103 mL, p=0.01). Definite IPF generally had more-rapid 1-year FVC decline compared to provisional IPF.
Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations.
特发性肺纤维化（IPF）的随机对照试验（RCT）的普遍性知之甚少。我们评估了 III 期 IPF RCT 的入选标准，以确定它们在临床登记中的代表性，并根据入选标准计算用力肺活量（FVC）的变化。
从文献检索中确定了 >60%的 IPF RCT 中常用的入选标准，并将其应用于前瞻性澳大利亚和加拿大登记处的 IPF 患者。还评估了 6 分钟步行距离（6MWD）和不同疾病进展前测量的其他预定标准。联合纵向生存模型用于比较根据个体和综合标准入选的 FVC 下降情况。
在 990 名 IPF 患者中，527 名（53%）在首次就诊时符合所有常见 RCT 入选标准，其中 343 名患者为明确的 IPF，184 名患者为放射学上可能的寻常间质性肺炎模式，无组织学证实（暂定 IPF）。尼达尼布和吡非尼酮里程碑 RCT 的合格患者比例为 19-50%。将 6MWD≥150m 和不同的疾病进展前测量添加到综合常见标准中，使符合入选标准的患者比例分别降至 52%（n=516）和 4-18%（n=12-61）。符合综合常见标准的患者 1 年 FVC 下降速度较慢，与不符合标准的患者相比（-90-103mL，p=0.01）。明确的 IPF 通常比暂定的 IPF 具有更快的 1 年 FVC 下降速度。
以前的 IPF RCT 的入选标准对临床 IPF 人群的普遍性有限，符合入选标准和不符合入选标准的人群的 FVC 下降速度不同。
