Evidence map›Paper›PMID 32646919›Full record

SynthesisThe European respiratory journal2021

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

Pierre-Antoine Juge, Joyce S Lee, Jessica Lau, Leticia Kawano-Dourado, Jorge Rojas Serrano, Marco Sebastiani, Gouri Koduri, Eric Matteson, Karina Bonfiglioli, Marcio Sawamura and 45 more

Open access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The European respiratory journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
108citing papers in PubMed, 10 pooled it
15.4field-weighted citation impact, top 1% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

108 citing papers in PubMed, 10 syntheses or guidelines pooled it, 230 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Guideline
  7. Guideline
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Article
  12. Lung disease in rheumatoid arthritis.Nature reviews. Rheumatology · 2026
    Review
  13. Review
  14. Review
  15. Interstitial lung disease in psoriasis: A systematic review and meta-analysis.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2026
    Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

48 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

55 authors at 17 institutions in 6 countries.

Pierre-Antoine JugeDept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.
Joyce S LeeDept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Jessica LauDivision of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
Leticia Kawano-DouradoPulmonary Division, Heart Institute (InCor) Medical School of the University of São Paulo, São Paulo, Brazil.ORCID 0000-0003-0784-1331
Jorge Rojas SerranoUnidad de Enfermedades del Intersticio Pulmonar y Reumatología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosió Villegas, Ciudad de México, México.
Marco SebastianiRheumatology Unit, Azienda Ospedaliera Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy.
Gouri KoduriRheumatology Dept, Southend University Hospital NHSFT, Southend-on-Sea, UK.
Eric MattesonDivision of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
Karina BonfiglioliDivision of Rheumatology, Medical School of the University of São Paulo, São Paulo, Brazil.
Marcio SawamuraDivision of Radiology, Medical School of the University of São Paulo, São Paulo, Brazil.
Ronaldo KairallaPulmonary Division, Heart Institute (InCor) Medical School of the University of São Paulo, São Paulo, Brazil.
Lorenzo CavagnaUniversity and IRCCS Policlinico S. Matteo Foundation of Pavia, Pavia, Italy.
Emanuele Bozzalla CassioneUniversity and IRCCS Policlinico S. Matteo Foundation of Pavia, Pavia, Italy.ORCID 0000-0001-6578-6938
Andreina ManfrediRheumatology Unit, Azienda Ospedaliera Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy.
Mayra MejiaUnidad de Enfermedades del Intersticio Pulmonar y Reumatología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosió Villegas, Ciudad de México, México.
Pedro Rodríguez-HenriquezDepartamento de Reumatologia, Hospital General Dr. Manuel Gea González, Ciudad de México, México.
Montserrat I González-PérezUnidad de Enfermedades del Intersticio Pulmonar y Reumatología, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosió Villegas, Ciudad de México, México.
Ramcés Falfán-ValenciaHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Ciudad de México, México.ORCID 0000-0001-6877-8124
Ivette Buendia-RoldánResearch Direction, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas, Ciudad de México, México.
Gloria Pérez-RubioHLA Laboratory, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Ciudad de México, México.
Esther EbsteinDept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.
Steven GazalDept of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Raphaël BorieDept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, INSERM UMR1152, DHU APOLLO, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.ORCID 0000-0002-9906-0024
Sébastien OttavianiDept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.
Caroline KannengiesserDept of Genetics, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.ORCID 0000-0003-2155-9383
Benoît WallaertCHRU de Lille, Service de Pneumologie et Immuno-Allergologie, Centre de compétence des maladies pulmonaires rares, FHU IMMINENT, Lille, France.
Yurdagul UzunhanDept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, Inserm 1272, Hôpital Avicenne, APHP, Université Paris 13, Bobigny, France.ORCID 0000-0002-1607-1407
Hilario NunesDept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, Inserm 1272, Hôpital Avicenne, APHP, Université Paris 13, Bobigny, France.
Dominique ValeyreDept of Pulmonology, Centre de Référence des Maladies Pulmonaires Rares, Inserm 1272, Hôpital Avicenne, APHP, Université Paris 13, Bobigny, France.
Nathalie Saidenberg-Kermanac'hDept of Rheumatology, Hôpital Avicenne, APHP, Bobigny, France.
Marie-Christophe BoissierDept of Rheumatology, Hôpital Avicenne, APHP, Bobigny, France.
Lidwine Wemeau-StervinouCHRU de Lille, Service de Pneumologie et Immuno-Allergologie, Centre de compétence des maladies pulmonaires rares, FHU IMMINENT, Lille, France.
René-Marc FlipoCHU de Lille, Service de Rhumatologie, Lille, France.
Sylvain Marchand-AdamDept of Pulmonology, CHRU Tours, Tours, France.
Pascal RichetteAP-HP, Hôpital Lariboisière, Service de Rhumatologie, DMU Locomotion, Université de Paris, Paris, France.
Yannick AllanoreAPHP, Hôpital Cochin, Service de Rhumatologie A, Université de Paris, Paris, France.
Claire DromerService de Pneumologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Marie-Elise TruchetetCHU de Bordeaux, Service de Rhumatologie, Bordeaux, France.
Christophe RichezCHU de Bordeaux, Service de Rhumatologie, Bordeaux, France.ORCID 0000-0002-3029-8739
Thierry SchaeverbekeCHU de Bordeaux, Service de Rhumatologie, Bordeaux, France.
Huguette LiotéAPHP, Hôpital Tenon, Service de Pneumologie, Paris, France.
Gabriel ThabutAPHP, Hôpital Bichat, INSERM 1152, Service de Pneumologie B, DHU FIRE, Université de Paris, Paris, France.
Kevin D DeaneDept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Joshua J SolomonDept of Medicine, National Jewish Health, Denver, CO, USA.
Tracy DoyleDept of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Jay H RyuDivision of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
Ivan RosasDept of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
V Michael HolersDept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Catherine BoileauDept of Genetics, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.ORCID 0000-0002-0371-7539
Marie-Pierre DebrayDept of Radiology, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.
Raphaël PorcherUniversité de Paris, CRESS, INSERM, INRA, Paris, France.ORCID 0000-0002-5277-4679
David A SchwartzDept of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Robert VassalloDivision of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
Bruno CrestaniDept of Genetics, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.
Philippe DieudéDept of Rheumatology, DMU Locomotion, INSERM UMR1152, Hôpital Bichat-Claude Bernard, APHP, Université de Paris, Paris, France.ORCID 0000-0002-4814-0307
Université Claude Bernard Lyon 1 · FRInserm · FRInstituto Nacional de Enfermedades Respiratorias · MXCentre Hospitalier Universitaire de Bordeaux · FRMayo Clinic · USUniversidade de São Paulo · BRUniversity of Colorado Denver · USCentre Hospitalier Universitaire de Lille · FRBrigham and Women's Hospital · USHôpital Avicenne · FRUniversity of Modena and Reggio Emilia · ITBroad Institute · USCentre Hospitalier Universitaire de Tours · FRHospital General Dr. Manuel Gea Gonzalez · MXNational Jewish Health · USSorbonne Université · FRSouthend University Hospital NHS Foundation Trust · GB

Funding

Mechanisms of Familial Pulmonary FibrosisP01HL092870 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLACKWELL, TIMOTHY S. · 2010 to 2020
$21.6M
MULTIDISCIPLINARY RESPIRATORY DISEASES RESEARCH TRAININGT32HL007085 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI ELLEN L BURNHAM, LISA A MAIER · 1985 to 2026
$21.6M
Role of Genetics in Idiopathic Pulmonary Fibrosis (IPF)R01HL097163 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI FINGERLIN, TASHA E., SCHWARTZ, DAVID ALBERT · 2009 to 2018
$16.4M
Preclinical Pulmonary Fibrosis, an opportune rare disease cohortUH3HL151865 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHWARTZ, DAVID ALBERT · 2022 to 2025
$4.3M
MUC5B, a novel therapeutic target for Idiopathic Pulmonary Fibrosis (IPF)UH2HL123442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHWARTZ, DAVID ALBERT · 2014 to 2015
$3.0M
Genes and Transcripts that Interact with MUC5B in Pulmonary FibrosisR01HL149836 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI CLOUTHIER, DAVID E., SCHWARTZ, DAVID ALBERT · 2020 to 2023
$3.0M
Preclinical Pulmonary Fibrosis, an opportune rare disease cohortUG3HL151865 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHWARTZ, DAVID ALBERT · 2020 to 2021
$1.7M
Functional Genetics in Idiopathic Pulmonary FibrosisR33HL120770 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI SCHWARTZ, DAVID ALBERT · 2016 to 2018
$1.6M
Clinical and Molecular Characteristics of Rheumatoid Arthritis-associated ILDK23HL119558 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DOYLE, TRACY JENNIFER · 2015 to 2018
$763k
Rheumatoid Arthritis Patients at Risk for Interstitial Lung DiseaseK23HL138131 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI LEE, JOYCE SUJIN · 2017 to 2019
$576k
BLRD VA I01 BX005295NHLBI NIH HHS K23 HL119558NHLBI NIH HHS K23 HL138131NHLBI NIH HHS P01 HL092870NHLBI NIH HHS R01 HL097163NHLBI NIH HHS R01 HL149836NHLBI NIH HHS R33 HL120770NHLBI NIH HHS T32 HL007085NHLBI NIH HHS UG3 HL151865NHLBI NIH HHS UH2 HL123442NHLBI NIH HHS UH3 HL151865
6 · The paper itself

Abstract

question addressed by the studyMethotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Fibrotic interstitial lung disease (ILD) is a common complication of RA. Whether MTX exposure increases the risk of ILD in patients with RA is disputed. We aimed to evaluate the association of prior MTX use with development of RA-ILD.

methodsThrough a case-control study design with discovery and international replication samples, we examined the association of MTX exposure with ILD in 410 patients with chronic fibrotic ILD associated with RA (RA-ILD) and 673 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques.

resultsAnalysis of the discovery sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted OR 0.46, 95% CI 0.24-0.90; p=0.022), which was confirmed in the replication samples (pooled adjusted OR 0.39, 95% CI 0.19-0.79; p=0.009). The combined estimate using both the derivation and validation samples revealed an adjusted OR of 0.43 (95% CI 0.26-0.69; p=0.0006). MTX ever-users were less frequent among patients with RA-ILD compared to those without ILD, irrespective of chest high-resolution computed tomography pattern. In patients with RA-ILD, ILD detection was significantly delayed in MTX ever-users compared to never-users (11.4±10.4 years and 4.0±7.4 years, respectively; p<0.001). ANSWER TO THE QUESTION: Our results suggest that MTX use is not associated with an increased risk of RA-ILD in patients with RA, and that ILD was detected later in MTX-treated patients.

Indexed as

Antirheumatic AgentsArthritis, RheumatoidLung Diseases, InterstitialCase-Control StudiesHumansMethotrexateAntirheumatic AgentsMethotrexate

Identifiers

PMID32646919
PMCPMC8212188
OpenAlexW3041647848

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.