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. 2024 Oct;11(5):1383-1392.
doi: 10.1007/s40744-024-00695-w. Epub 2024 Jul 10.

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

Peter C Taylor  1 , Bryan Downie  2 , Ling Han  2 , Rachael Hawtin  2 , Angie Hertz  2 , Robert J Moots  3   4 , Tsutomu Takeuchi  5
Affiliations

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

Peter C Taylor et al. Rheumatol Ther. 2024 Oct.

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.

Keywords: Biomarker; Filgotinib; Janus kinase; Neutrophil-to-lymphocyte ratio; Rheumatoid arthritis.

Plain language summary

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.

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Conflict of interest statement

Peter C. Taylor has been a consultant for and/or has received grant/research support from: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos NV, Gilead Sciences, Inc., GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer, Sanofi, and UCB Pharma. Bryan Downie and Ling Han are employees of Gilead Sciences, Inc., and own stock in Gilead Sciences, Inc. Rachael Hawtin was an employee of Gilead Sciences, Inc., when this work was done and owns stock in Gilead Sciences, Inc. (current affiliation Ultragenyx Pharmaceutical Inc.). Angie Hertz was an employee of Gilead Sciences, Inc., when this work was done and owns stock in Gilead Sciences, Inc. (on sabbatical at the time of final submission). Robert J. Moots reports his institution receiving grants for research from Novartis; consulting fees paid to Rheum 4 Life, Ltd, by Chugai and Gilead Sciences, Inc.; honoraria or other payments to Rheum 4 Life, Ltd, from Amgen, Galapagos, Gilead Sciences, Inc., and Pfizer; support for attending meetings paid to Rheum 4 Life, Ltd, by Pfizer; and receipt of materials, drugs, medical writing support, or other services from Gilead Sciences, Inc. Tsutomu Takeuchi reports relationships with AbbVie, Astellas Pharma, Eisai, Eli Lilly Japan, Gilead Sciences, Inc., and Pfizer Japan Inc.

Figures

Fig. 1
Fig. 1
Changes from baseline in DAS28(CRP) over time in NLR-High vs NLR-Low subgroups by patient population and by treatment. Changes in DAS28(CRP) were estimated from the marginal means based on a fully adjusted mixed-effects model. Numbers and outlined circles show significant (P < 0.05) differences between NLR-High and NLR-Low patients within the treatment arm. csDMARD conventional synthetic disease-modifying antirheumatic drug, DAS28(CRP) Disease Activity Scale with 28 joints using C-reactive protein, MTX methotrexate, NLR neutrophil-to-lymphocyte ratio
Fig. 2
Fig. 2
DAS28(CRP) < 2.6 adjusted rate at week 12 (A); difference in number needed to treat to achieve DAS28(CRP) < 2.6 at week 12 (B). A Solid-colored bars represent patients in NLR-Low subgroup; striped bars represent patients in NLR-High subgroup. DAS28(CRP) < 2.6 rate estimated from the fully adjusted logistic regression model. P values show the comparison of DAS28(CRP) < 2.6 rates between NLR-Low and NLR-High patients. B Solid-colored bars represent patients in NLR-Low subgroup; striped bars represent patients in NLR-High subgroup. Number needed to treat reflects the number of patients one would need to treat with an investigational product to achieve a given clinical endpoint relative to the control arm. ADA adalimumab, csDMARD conventional synthetic disease-modifying antirheumatic drug, DAS28(CRP) Disease Activity Scale with 28 joints using C-reactive protein, FIL100 filgotinib 100 mg/day, FIL200 filgotinib 200 mg/day, mono monotherapy, MTX methotrexate, NLR neutrophil-to-lymphocyte ratio, PBO placebo
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References

    1. Villarino AV, Kanno Y, O’Shea JJ. Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol. 2017;18(4):374–84. - PMC - PubMed
    1. Chatzidionysiou K. Beyond methotrexate and biologics in RA—efficacy of JAK inhibitors and their place in the current treatment armamentarium. Mediterr J Rheumatol. 2020;31:120–8. - PMC - PubMed
    1. Tecchio C, Micheletti A, Cassatella MA. Neutrophil-derived cytokines: facts beyond expression. Front Immunol. 2014;5:508. - PMC - PubMed
    1. Wright HL, Lyon M, Chapman EA, Moots RJ, Edwards SW. Rheumatoid arthritis synovial fluid neutrophils drive inflammation through production of chemokines, reactive oxygen species, and neutrophil extracellular traps. Front Immunol. 2020;11: 584116. - PMC - PubMed
    1. Erre GL, Paliogiannis P, Castagna F, et al. Meta-analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio in rheumatoid arthritis. Eur J Clin Invest. 2019;49(1): e13037. - PubMed

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