Kulkarni Tejaswini, Newton Chad A, Gupta Sachin, Samara Katerina, Bernstein Elana J
Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, 1900 University Blvd., THT 422, Birmingham, AL, 35294, USA.
University of Texas Southwestern, Medical Center, Dallas, TX, USA.
Pulm Ther. 2024 Sep;10(3):331-346. doi: 10.1007/s41030-024-00267-x. Epub 2024 Jul 29.
Clinical practice guidelines recommend autoimmune serological testing in patients newly diagnosed with interstitial lung disease of apparently unknown cause who may have idiopathic pulmonary fibrosis (IPF), in order to exclude connective tissue disease (CTD). Autoantibody positivity has been associated with unique patient profiles and prognosis in patients with IPF who otherwise lack a CTD diagnosis.
This post-hoc analysis of patients with IPF from the Phase III ASCEND trial (NCT01366209) evaluated the association of antinuclear antibodies (ANA), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) status with baseline disease characteristics, disease progression [percent predicted forced vital capacity (%FVC), forced vital capacity (FVC) volume and progression-free survival (PFS)], and treatment outcomes with pirfenidone and placebo (%FVC, FVC and PFS).
Of 555 participants, 244/514 (47.5%) were ANA positive (ANA+), 83/514 (16.1%) had high ANA+ (ANA titre ≥ 1:160 or positive nucleolar- or centromere-staining patterns), 60/555 (10.8%) were RF positive (RF+) and/or anti-CCP positive (anti-CCP+) and 270/514 (52.5%) were autoantibody negative (AAb-). Baseline demographics and characteristics were generally comparable between autoantibody subgroups. Although not statistically significant, more placebo-treated participants with ANA+ or high ANA+ had a decline from baseline to Week 52 of ≥ 10% in %FVC or death (48.7% and 55.9%, respectively) or in FVC volume or death (48.7% and 47.1%, respectively) compared with the AAb- group (%FVC or death: 42.0%; FVC volume or death: 42.0%). The RF+ and/or anti-CCP+ group was similar to AAb-. No differences were observed in PFS. A treatment benefit for pirfenidone versus placebo was observed regardless of autoantibody status [PFS: ANA+ HR (95% CI): 0.56 (0.37 to 0.86), P = 0.007; AAb- HR (95% CI): 0.50 (0.32 to 0.78), P = 0.002].
IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA.
ClinicalTrials.gov identifier, NCT01366209.
临床实践指南建议，对于新诊断为病因不明的间质性肺疾病且可能患有特发性肺纤维化（IPF）的患者，应进行自身免疫血清学检测，以排除结缔组织病（CTD）。自身抗体阳性与无CTD诊断的IPF患者的独特患者特征和预后相关。
这项对III期ASCEND试验（NCT01366209）中IPF患者的事后分析评估了抗核抗体（ANA）、类风湿因子（RF）和抗环瓜氨酸肽（抗CCP）状态与基线疾病特征、疾病进展[预计用力肺活量百分比（%FVC）、用力肺活量（FVC）体积和无进展生存期（PFS）]以及吡非尼酮和安慰剂治疗结果（%FVC、FVC和PFS）之间的关联。
在555名参与者中，244/514（47.5%）为ANA阳性（ANA+），83/514（16.1%）为高ANA+（ANA滴度≥1:160或阳性核仁或着丝粒染色模式），60/555（10.8%）为RF阳性（RF+）和/或抗CCP阳性（抗CCP+），270/514（52.5%）为自身抗体阴性（AAb-）。自身抗体亚组之间的基线人口统计学和特征总体上具有可比性。尽管无统计学意义，但与AAb-组相比，更多接受安慰剂治疗且ANA+或高ANA+的参与者从基线到第52周%FVC下降≥10%或死亡（分别为48.7%和55.9%），或FVC体积下降或死亡（分别为48.7%和47.1%）（%FVC或死亡：42.0%；FVC体积或死亡：42.0%）。RF+和/或抗CCP+组与AAb-组相似。PFS未观察到差异。无论自身抗体状态如何，均观察到吡非尼酮相对于安慰剂的治疗益处[PFS：ANA+ HR（95%CI）：0.56（0.37至0.86），P = 0.007；AAb- HR（95%CI）：0.50（0.32至0.78），P = 0.002]。
在ASCEND中，IPF病程不因自身抗体状态而异。无论ANA是否存在，吡非尼酮均具有治疗益处。
ClinicalTrials.gov标识符，NCT01366209。
