自身抗体对特发性肺纤维化患者预后的影响：III期ASCEND试验的事后分析

IF 2.3 Q2 RESPIRATORY SYSTEM Pulmonary Therapy Pub Date : 2024-09-01 Epub Date: 2024-07-29 DOI:10.1007/s41030-024-00267-x

Tejaswini Kulkarni, Chad A Newton, Sachin Gupta, Katerina Samara, Elana J Bernstein

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引用次数: 0

摘要

导言：临床实践指南建议对新诊断为原因不明的间质性肺病患者进行自身免疫血清检测，这些患者可能患有特发性肺纤维化（IPF），以排除结缔组织病（CTD）。自身抗体阳性与缺乏 CTD 诊断的 IPF 患者的独特病史和预后有关：本研究对 ASCEND III 期试验（NCT01366209）中的 IPF 患者进行了事后分析，评估了抗核抗体（ANA）、类风湿因子（RF）和抗环瓜氨酸肽（anti-CCP）状态与基线疾病特征的相关性、疾病进展[预测用力肺活量百分比 (%FVC)、用力肺活量 (FVC) 容积和无进展生存期 (PFS)]，以及吡非尼酮和安慰剂的治疗结果（预测用力肺活量百分比、用力肺活量容积和无进展生存期）之间的关系。结果：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或核极或中心粒染色模式阳性），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-）。不同自身抗体亚组的基线人口统计学特征和特性基本相当。虽然没有统计学意义，但与 AAb- 组相比，更多安慰剂治疗的 ANA+ 或高 ANA+ 参与者从基线到第 52 周的 FVC 或死亡百分比下降≥10%（分别为 48.7% 和 55.9%）或 FVC 容量或死亡百分比下降≥10%（分别为 48.7% 和 47.1%）（FVC 或死亡百分比：42.0%；FVC 容量或死亡百分比：42.0%）。RF+和/或抗CCP+组与AAb-组相似，在PFS方面未观察到差异。无论自身抗体状态如何，吡非尼酮与安慰剂相比均有治疗获益[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]：结论：在ASCEND研究中，IPF的病程并不因自身抗体状态而异。无论是否存在ANA，吡非尼酮都有治疗效果：试验注册：ClinicalTrials.gov标识符，NCT01366209。

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The Impact of Autoantibodies on Outcomes in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analyses of the Phase III ASCEND Trial.

Introduction: 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.

Methods: 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).

Results: 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].

Conclusion: IPF disease course did not differ by autoantibody status in ASCEND. Pirfenidone had a treatment benefit regardless of the presence of ANA.

Trial registration: ClinicalTrials.gov identifier, NCT01366209.

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来源期刊

Pulmonary Therapy Medicine-Pulmonary and Respiratory Medicine

CiteScore

5.20

自引率

3.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Pulmonary Therapy is an international, open access, peer-reviewed (single-blind), and rapid publication journal. The scope of the journal is broad and will consider all scientifically sound research from pre-clinical, clinical (all phases), observational, real-world, and health outcomes research around the use of pulmonary therapies, devices, and surgical techniques. Areas of focus include, but are not limited to: asthma; chronic obstructive pulmonary disease; idiopathic pulmonary fibrosis; pulmonary hypertension; cystic fibrosis; lung cancer; respiratory tract disorders; allergic rhinitis and other respiratory allergies; influenza, pneumococcal infection, respiratory syncytial virus and other respiratory infections; and inhalers and other device therapies. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/series, trial protocols and short communications such as commentaries and editorials. Pulmonary Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. Rapid Publication The journal’s publication timelines aim for a rapid peer review of 2 weeks. If an article is accepted it will be published 3–4 weeks from acceptance. The rapid timelines are achieved through the combination of a dedicated in-house editorial team, who manage article workflow, and an extensive Editorial and Advisory Board who assist with peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model this allows for the rapid, efficient communication of the latest research and reviews, fostering the advancement of pulmonary therapies. Open Access All articles published by Pulmonary Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning authors will always have an editorial contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE, GPP and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. Digital Features and Plain Language Summaries Pulmonary Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’. For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/ Publication Fees Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €4500/ $5100/ £3650. The journal will consider fee discounts and waivers for developing countries and this is decided on a case by case basis. 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Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed). Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors’ or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals. 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