Abstract：
BACKGROUND: 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.
CONCLUSIONS: 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.
BACKGROUND: Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728.
Rheumatoid arthritis is a disease that results in swollen and painful joints. There is currently no method to determine which treatment will work best for an individual patient. However, there may be identifying markers found in the blood that could indicate how a patient will respond to treatment. One of these possible markers is a ratio of two types of white blood cells, neutrophils and lymphocytes, which are part of the body’s immune system and help the body detect and fight infection and other diseases. This ratio is referred to as the neutrophil-to-lymphocyte ratio. The current study evaluated whether the neutrophil-to-lymphocyte ratio at the beginning of treatment was associated with rheumatoid arthritis treatment outcomes. Blood test results were used from 3365 patients receiving filgotinib (a medicine used to treat rheumatoid arthritis) or other therapies as part of the FINCH clinical trials. Patients were classified as having a high or low neutrophil-to-lymphocyte ratio at the start of treatment. Patients receiving filgotinib over 24 weeks who had a high neutrophil-to-lymphocyte ratio showed less disease activity than patients whose ratio was low. This study provides support for the use of the neutrophil-to-lymphocyte ratio as a way to help determine whether a patient would benefit from filgotinib as part of their rheumatoid arthritis treatment and may help improve rheumatoid arthritis treatment outcomes.
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.
CONCLUSIONS: 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.
BACKGROUND: Clinicaltrials.gov: NCT02889796; NCT02873936; NCT02886728.
Rheumatoid arthritis is a disease that results in swollen and painful joints. There is currently no method to determine which treatment will work best for an individual patient. However, there may be identifying markers found in the blood that could indicate how a patient will respond to treatment. One of these possible markers is a ratio of two types of white blood cells, neutrophils and lymphocytes, which are part of the body’s immune system and help the body detect and fight infection and other diseases. This ratio is referred to as the neutrophil-to-lymphocyte ratio. The current study evaluated whether the neutrophil-to-lymphocyte ratio at the beginning of treatment was associated with rheumatoid arthritis treatment outcomes. Blood test results were used from 3365 patients receiving filgotinib (a medicine used to treat rheumatoid arthritis) or other therapies as part of the FINCH clinical trials. Patients were classified as having a high or low neutrophil-to-lymphocyte ratio at the start of treatment. Patients receiving filgotinib over 24 weeks who had a high neutrophil-to-lymphocyte ratio showed less disease activity than patients whose ratio was low. This study provides support for the use of the neutrophil-to-lymphocyte ratio as a way to help determine whether a patient would benefit from filgotinib as part of their rheumatoid arthritis treatment and may help improve rheumatoid arthritis treatment outcomes.
摘要：
背景：类风湿关节炎（RA）的高基线中性粒细胞与淋巴细胞比率（NLR）与生物肿瘤坏死因子抑制的阳性反应和常规合成疾病缓解抗风湿药（csDMARD）三联疗法的阴性反应有关。来自三项RA患者的随机临床试验的数据集用于检验以下假设：基线NLR与甲氨蝶呤（MTX）初治或MTX经历过的RA人群中对菲尔戈替尼的临床反应改善有关。
方法：来自FINCH1的患者（对MTX的反应不足，MTX-IR;NCT02889796),FINCH2（对生物DMARDs反应不足；NCT02873936），和FINCH3(MTX-Naive;NCT02886728)被分类为基线NLR-高或基线NLR-低，基于先前公布的2.7分点。总的来说,在三项研究中纳入了3365名患者。使用线性回归模型确定临床结果和患者报告结果（PRO）的差异。
结果：与NLR-Low患者相比，在临床试验中，被分类为NLR-High的对照组患者（安慰剂+MTX/安慰剂+csDMARD）在第12周表现出更差的持续临床和PRO反应。相比之下,与临床试验中的NLR-Low患者相比，接受FIL200mgMTX/csDMARD的NLR-High患者在12周后表现出持续更好的反应。临床终点，和PROS。这些趋势在MTX-IR人群中最为突出。
结论：2.7基线NLR切点可用于富集最有可能从背景MTX/csDMARD中添加菲格替尼中受益的患者。使用基线NLR作为治疗决策的一部分不需要额外的诊断，并且可能有助于改善RA患者的预后。
背景：Clinicaltrials.gov：NCT02889796；NCT02873936；NCT02886728。
类风湿性关节炎是一种导致关节肿胀和疼痛的疾病。目前没有方法来确定哪种治疗对个体患者最有效。然而,在血液中可能有识别标记，可以指示患者对治疗的反应。这些可能的标记之一是两种白细胞的比例，中性粒细胞和淋巴细胞，它们是身体免疫系统的一部分，帮助身体检测和对抗感染和其他疾病。该比率被称为嗜中性粒细胞与淋巴细胞比率。本研究评估了治疗开始时的中性粒细胞与淋巴细胞比率是否与类风湿关节炎治疗结果相关。作为FINCH临床试验的一部分，使用了接受filgotinib（一种用于治疗类风湿性关节炎的药物）或其他疗法的3365名患者的血液检查结果。患者在治疗开始时被分类为中性粒细胞与淋巴细胞比率高或低。接受filgotinib超过24周的中性粒细胞与淋巴细胞比率高的患者比比率低的患者显示出更少的疾病活动。这项研究为使用中性粒细胞与淋巴细胞的比率提供了支持，以帮助确定患者是否会受益于filgotinib作为类风湿性关节炎治疗的一部分，并可能有助于改善类风湿性关节炎的治疗结果。
方法：来自FINCH1的患者（对MTX的反应不足，MTX-IR;NCT02889796),FINCH2（对生物DMARDs反应不足；NCT02873936），和FINCH3(MTX-Naive;NCT02886728)被分类为基线NLR-高或基线NLR-低，基于先前公布的2.7分点。总的来说,在三项研究中纳入了3365名患者。使用线性回归模型确定临床结果和患者报告结果（PRO）的差异。
结果：与NLR-Low患者相比，在临床试验中，被分类为NLR-High的对照组患者（安慰剂+MTX/安慰剂+csDMARD）在第12周表现出更差的持续临床和PRO反应。相比之下,与临床试验中的NLR-Low患者相比，接受FIL200mgMTX/csDMARD的NLR-High患者在12周后表现出持续更好的反应。临床终点，和PROS。这些趋势在MTX-IR人群中最为突出。
结论：2.7基线NLR切点可用于富集最有可能从背景MTX/csDMARD中添加菲格替尼中受益的患者。使用基线NLR作为治疗决策的一部分不需要额外的诊断，并且可能有助于改善RA患者的预后。
背景：Clinicaltrials.gov：NCT02889796；NCT02873936；NCT02886728。
类风湿性关节炎是一种导致关节肿胀和疼痛的疾病。目前没有方法来确定哪种治疗对个体患者最有效。然而,在血液中可能有识别标记，可以指示患者对治疗的反应。这些可能的标记之一是两种白细胞的比例，中性粒细胞和淋巴细胞，它们是身体免疫系统的一部分，帮助身体检测和对抗感染和其他疾病。该比率被称为嗜中性粒细胞与淋巴细胞比率。本研究评估了治疗开始时的中性粒细胞与淋巴细胞比率是否与类风湿关节炎治疗结果相关。作为FINCH临床试验的一部分，使用了接受filgotinib（一种用于治疗类风湿性关节炎的药物）或其他疗法的3365名患者的血液检查结果。患者在治疗开始时被分类为中性粒细胞与淋巴细胞比率高或低。接受filgotinib超过24周的中性粒细胞与淋巴细胞比率高的患者比比率低的患者显示出更少的疾病活动。这项研究为使用中性粒细胞与淋巴细胞的比率提供了支持，以帮助确定患者是否会受益于filgotinib作为类风湿性关节炎治疗的一部分，并可能有助于改善类风湿性关节炎的治疗结果。
