Evidence map›Paper›PMID 37490202›Full record

ArticleRheumatology and therapy2023

Filgotinib Modulates Inflammation-Associated Peripheral Blood Protein Biomarkers in Adults with Active Rheumatoid Arthritis and Prior Inadequate Response to Methotrexate.

Yoshiya Tanaka, Peter C Taylor, Emon Elboudwarej, Angie Hertz, Xiaorong Shao, Vladislav A Malkov, Hironori Matsushima, Kahaku Emoto, Bryan Downie, Tsutomu Takeuchi

Erratum issued Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Rheumatology and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT02889796 (A Randomized, Double-blind, Placebo- and Active-controlled, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Filgotinib Administered for 52 Weeks in Combination With Methotrexate to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02889796 phase3completednot on this map

A Randomized, Double-blind, Placebo- and Active-controlled, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Filgotinib Administered for 52 Weeks in Combination With Methotrexate to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

TypeinterventionalSponsorGilead SciencesRan2016 to 2019Enrolled1,759ConditionsRheumatoid ArthritisArmsFilgotinib, Placebo to match filgotinib, Adalimumab, Placebo to match adalimumab, MTX
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Yoshiya Tanaka *The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1, Iseigaoka, Kitakyushu, 807-8555, Japan. tanaka@med.uoeh-u.ac.jp.ORCID http://orcid.org/0000-0002-0807-7139
Peter C Taylor *Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Headington, Oxford, OX3 7LD, UK. peter.taylor@kennedy.ox.ac.uk.ORCID http://orcid.org/0000-0001-7766-6167
Emon ElboudwarejGilead Sciences, Inc., Foster City, CA, USA.
Angie HertzGilead Sciences, Inc., Foster City, CA, USA.
Xiaorong ShaoGilead Sciences, Inc., Foster City, CA, USA.
Vladislav A MalkovGilead Sciences, Inc., Foster City, CA, USA.
Hironori MatsushimaGilead Sciences, Inc., Foster City, CA, USA.
Kahaku EmotoGilead Sciences, Inc., Foster City, CA, USA.
Bryan DownieGilead Sciences, Inc., Foster City, CA, USA.
Tsutomu TakeuchiDivision of Rheumatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Gilead Sciences (United States) · USKeio University · JPNuffield Orthopaedic Centre · GBUniversity of Occupational and Environmental Health Japan · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionOur aim was to evaluate protein biomarker changes related to the administration of filgotinib, a Janus kinase (JAK) 1 preferential inhibitor, in patients with moderately to severely active rheumatoid arthritis (RA) with inadequate response to methotrexate.

methodsPlasma and serum samples were collected from patients enrolled in FINCH 1 (NCT02889796), a Phase 3 trial. Patients with stable backgrounds of methotrexate were randomly assigned once-daily oral filgotinib 200 or 100 mg, subcutaneous adalimumab 40 mg every 2 weeks (W), or placebo. Up to 35 biomarkers were analyzed at baseline, W4, and W12 with enzyme-linked immunosorbent assays and chemiluminescence and electrochemiluminescence assays.

resultsAt baseline, four distinct biomarker clusters were identified. The strongest intragroup correlations were in bone-cartilage resorption/inflammation and JAK/signal transducer and activator of transcription (STAT) signaling activity. At baseline, significant positive correlations were identified for cytokines with patient-reported pain and with patient measures of fatigue. Filgotinib reduced levels of cytokines associated with inflammation and cell migration as early as W4 and through W12. Compared to adalimumab, filgotinib induced significant reductions in bone-related turnover biomarkers, N-telopeptide of type 1 collagen and C-telopeptide 1, as well as biomarkers associated with baseline disease activity. No baseline predictors of therapeutic response to filgotinib were identified.

conclusionsFilgotinib reduced peripheral protein biomarkers associated with JAK/STAT signaling, inflammatory signaling, immune cell migration, and bone resorption as soon as W4 in FINCH 1. Effects were dose-dependent and consistent with the clinical efficacy of filgotinib observed in FINCH 1. The changes in peripheral biomarkers associated with filgotinib treatment in methotrexate-experienced patients are consistent with changes observed in both methotrexate-naïve and biologic disease-modifying antirheumatic drug-experienced RA populations. These data demonstrate dose-dependent effects of preferential JAK1 inhibition by filgotinib on peripheral blood protein biomarkers in methotrexate-experienced patients with RA.

trial registrationClinicalTrials.gov, NCT02889796.

Indexed as

Biological therapyBiomarkerCytokinesInflammationMethotrexateRheumatoid factor

Identifiers

PMID37490202
PMCPMC10468462
OpenAlexW4385230442

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.