Patients with High Baseline Neutrophil-to-Lymphocyte Ratio Exhibit Better Response to Filgotinib as Treatment for Rheumatoid Arthritis.

IF 2.9 3区医学 Q2 RHEUMATOLOGY

Rheumatology and Therapy Pub Date : 2024-10-01 Epub Date: 2024-07-10 DOI:10.1007/s40744-024-00695-w

Peter C Taylor, Bryan Downie, Ling Han, Rachael Hawtin, Angie Hertz, Robert J Moots, Tsutomu Takeuchi

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Abstract

Introduction: High baseline neutrophil-to-lymphocyte ratio (NLR) in rheumatoid arthritis (RA) has been associated with positive responses to biologic tumor necrosis factor inhibition and negative responses to conventional synthetic disease-modifying antirheumatic drug (csDMARD) triple therapy. Datasets from three randomized clinical trials in patients with RA were used to test the hypothesis that baseline NLR is associated with improved clinical response to filgotinib in methotrexate (MTX)-naïve or MTX-experienced RA populations.

Methods: Patients from FINCH 1 (inadequate response to MTX, MTX-IR; NCT02889796), FINCH 2 (inadequate response to biologic DMARDs; NCT02873936), and FINCH 3 (MTX-naïve; NCT02886728) were classified as baseline NLR-High or baseline NLR-Low based on a previously published cut point of 2.7. In total, 3365 patients were included across the three studies. Differences in clinical outcomes and patient-reported outcomes (PROs) were determined using linear-regression models.

Results: Control-arm patients (placebo + MTX/placebo + csDMARD) classified as NLR-High exhibited worse continuous clinical and PRO responses at week 12 across clinical trials compared to NLR-Low patients. In contrast, NLR-High patients who received FIL 200 mg + MTX/csDMARD exhibited consistently better responses after 12 weeks compared to NLR-Low patients across clinical trials, clinical endpoints, and PROs. These trends were most prominent among the MTX-IR population.

Conclusion: The 2.7 baseline NLR cut point could be used to enrich for patients most likely to benefit from the addition of filgotinib to background MTX/csDMARD. Use of baseline NLR as part of therapeutic decision-making would not require additional diagnostics and could contribute to improved outcomes for patients with RA.

Trial registration: Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728.

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基线中性粒细胞与淋巴细胞比率高的患者对菲戈替尼治疗类风湿性关节炎的反应更好

导言：类风湿性关节炎（RA）患者基线中性粒细胞与淋巴细胞比值（NLR）高与生物肿瘤坏死因子抑制剂的阳性反应和传统合成改善病情抗风湿药物（csDMARD）三联疗法的阴性反应有关。我们使用了三项针对RA患者的随机临床试验数据集，以检验基线NLR与甲氨蝶呤（MTX）无效或有MTX经验的RA人群对非格替尼临床反应的改善有关这一假设：FINCH 1（对MTX反应不足，MTX-IR；NCT02889796）、FINCH 2（对生物DMARDs反应不足；NCT02873936）和FINCH 3（MTX-naïve；NCT02886728）的患者根据之前公布的切点2.7分为基线NLR-高或基线NLR-低。三项研究共纳入 3365 例患者。采用线性回归模型确定了临床结果和患者报告结果（PROs）的差异：结果：与NLR-Low患者相比，被归类为NLR-High的对照组患者（安慰剂+MTX/安慰剂+csDMARD）在各临床试验的第12周表现出更差的连续临床和PRO反应。相比之下，接受 FIL 200 mg + MTX/csDMARD 治疗的 NLR 高患者与 NLR 低患者相比，在各临床试验、临床终点和 PROs 中，12 周后的反应持续较好。这些趋势在MTX-IR人群中最为突出：结论：基线NLR为2.7的切点可用于筛选最有可能从在MTX/csDMARD基础上加用filgotinib中获益的患者。使用基线NLR作为治疗决策的一部分不需要额外的诊断，并有助于改善RA患者的预后：试验注册：Clinicaltrials.gov：NCT02889796；NCT02873936；NCT02886728。

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来源期刊

Rheumatology and Therapy RHEUMATOLOGY-

CiteScore

6.00

自引率

5.30%

发文量

审稿时长

6 weeks

期刊介绍： Aims and Scope Rheumatology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of rheumatologic therapies. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. Areas of focus include, but are not limited to, rheumatoid arthritis, gout, gouty arthritis, psoriatic arthritis, osteoarthritis, juvenile idiopathic/rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, Pompe’s disease, inflammatory joint conditions, musculoskeletal conditions, systemic sclerosis, and fibromyalgia. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial protocols, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Rheumatology and 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 all scientifically and ethically sound research. Ethics and Disclosures The journal is a member of the Committee on Publication Ethics (COPE) and subscribes to its principles on how to deal with acts of misconduct thereby committing to investigate allegations of misconduct in order to ensure the integrity of research. Content in this journal is peer-reviewed (Single-blind). For more information on our publishing ethics policies, please see here: https://www.springer.com/gp/editorial-policies Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid 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 and efficient communication of the latest research and reviews, allowing the advancement of rheumatologic therapies. 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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: https://springerhealthcare.com/expertise/publishing-digital-features/ 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. Authors should disclose details of preprint posting during the submission process or at any other point during consideration in the journal. 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At least two extensive reviews are required to make the editorial decision. Where reviewer recommendations are conflicted, the editorial board will be contacted for further advice and a presiding decision. 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, and authors are welcome to make rebuttals against individual reviewer comments if appropriate. 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