TY - JOUR
T1 - Methotrexate and rheumatoid arthritis associated interstitial lung disease
AU - Juge, Pierre Antoine
AU - Lee, Joyce S.
AU - Lau, Jessica
AU - Kawano-Dourado, Leticia
AU - Serrano, Jorge Rojas
AU - Sebastiani, Marco
AU - Koduri, Gouri
AU - Matteson, Eric
AU - Bonfiglioli, Karina
AU - Sawamura, Marcio
AU - Kairalla, Ronaldo
AU - Cavagna, Lorenzo
AU - Cassione, Emanuele Bozzalla
AU - Manfredi, Andreina
AU - Mejia, Mayra
AU - Rodríguez-Henriquez, Pedro
AU - González-Pérez, Montserrat I.
AU - Falfán-Valencia, Ramcés
AU - Buendia-Roldán, Ivette
AU - Pérez-Rubio, Gloria
AU - Ebstein, Esther
AU - Gazal, Steven
AU - Borie, Raphaël
AU - Ottaviani, Sébastien
AU - Kannengiesser, Caroline
AU - Wallaert, Beno t.
AU - Uzunhan, Yurdagul
AU - Nunes, Hilario
AU - Valeyre, Dominique
AU - Saidenberg-Kermanac h, Nathalie
AU - Boissier, Marie Christophe
AU - Wemeau-Stervinou, Lidwine
AU - Flipo, René Marc
AU - Marchand-Adam, Sylvain
AU - Richette, Pascal
AU - Allanore, Yannick
AU - Dromer, Claire
AU - Truchetet, Marie Elise
AU - Richez, Christophe
AU - Schaeverbeke, Thierry
AU - Lioté, Huguette
AU - Thabut, Gabriel
AU - Deane, Kevin D.
AU - Solomon, Joshua J.
AU - Doyle, Tracy
AU - Ryu, Jay H.
AU - Rosas, Ivan
AU - Michael Holers, V.
AU - Boileau, Catherine
AU - Debray, Marie Pierre
AU - Porcher, Raphaël
AU - Schwartz, David A.
AU - Vassallo, Robert
AU - Crestani, Bruno
AU - Dieudé, Philippe
N1 - Funding Information:
Support statement: Supported by grants from Société Française de Rhumatologie, National Heart, Lung, and Blood Institute (K23-HL138131 and K23-HL119558). Funding information for this article has been deposited with the Crossref Funder Registry.
Funding Information:
Conflict of interest: P-A. Juge has nothing to disclose. J.S. Lee reports grants from NIH, personal fees for advisory board work from Genentech and Celgene, outside the submitted work. J. Lau has nothing to disclose. L. Kawano-Dourado has nothing to disclose. J. Rojas-Serrano has nothing to disclose. M. Sebastiani has nothing to disclose. G. Koduri has nothing to disclose. E. Matteson has nothing to disclose. K. Bonfiglioli has nothing to disclose. M. Sawamura has nothing to disclose. R. Kairalla has nothing to disclose. L. Cavagna has nothing to disclose. E. Bozzalla Cassione has nothing to disclose. A. Manfredi has nothing to disclose. M. Mejia has nothing to disclose. P. Rodríguez-Henriquez has nothing to disclose. M.I. González Pérez has nothing to disclose. R. Falfán-Valencia has nothing to disclose. I. Buendia-Roldán has nothing to disclose. G. Pérez-Rubio has nothing to disclose. E. Ebstein reports personal fees from Sanofi, outside the submitted work. S. Gazal has nothing to disclose. R. Borie reports grants and personal fees for lectures from Roche and Boehringer Ingelheim, outside the submitted work. S. Ottaviani has nothing to disclose. C. Kannengiesser has nothing to disclose. B. Wallaert reports grants and personal fees for advisory board work and meeting attendance from Boehringer Ingelheim and Roche, outside the submitted work. Y. Uzunhan reports personal fees from Roche and Boehringer Ingelheim, non-financial support from Oxyvie, outside the submitted work. H. Nunes has nothing to disclose. D. Valeyre reports personal fees for advisory board work from Roche and Boehringer Ingelheim, personal fees for lectures from AstraZeneca, outside the submitted work. N. Saidenberg-Kermanac’h has nothing to disclose. M-C. Boissier has nothing to disclose. L. Wemeau-Stervinou reports personal fees for lectures and travel support from Roche, personal fees for lectures and advisory board work, and travel support from Boehringer-Ingelheim, personal fees for lectures from Janssen-Cilag and Bristol-Myers-Squibb, outside the submitted work. R.M. Flipo reports grants and personal fees from Roche Chugai, Abbvie and Pfizer, personal fees from Bristol-Meyers Squibb, outside the submitted work. S. Marchand-Adam reports fees for research, lectures, meeting attendance, consultancy and advisory board work from Roche, Boehringer Ingelheim and Novartis, outside the submitted work. P. Richette reports personal fees from Ipsen/Menarini, AstraZeneca, Savient and Grünenthal, outside the submitted work. Y. Allanore reports personal fees from Actelion, Bayer, Bristol-Myers Squibb, Boehringer and Inventiva, grants from Sanofi and Roche, outside the submitted work. C. Dromer has nothing to disclose. M-E. Truchetet has nothing to disclose. C. Richez has nothing to disclose. T. Schaeverbeke has nothing to disclose. H. Lioté has nothing to disclose. G. Thabut reports personal fees from AstraZeneca, outside the submitted work. K.D. Deane has nothing to disclose. J. Solomon has nothing to disclose. T. Doyle has nothing to disclose. J.H. Ryu has nothing to disclose. I. Rosas reports personal fees for advisory board work from Genentech, Boehringer and Three Lakes Partners, outside the submitted work. V.M. Holers reports grants from NIH/NIAID (U01 Grant), during the conduct of the study. C. Boileau has nothing to disclose. M-P. Debray reports personal fees and non-financial support for travel to meetings from Boehringer Ingelheim and Roche, outside the submitted work. R. Porcher has nothing to disclose. D.A. Schwartz reports grants from NIH-NHLBI (P01 HL092870, R01 HL097163, R33 HL120770 and UH2 HL123442) and DOD Focused Program (W81XWH-17-1-0597), during the conduct of the study; personal fees for consultancy and advisory board work from NuMedii, Inc., and is an employee of Eleven P15, Inc., outside the submitted work; and has a patent Compositions and Methods of Treating or Preventing Fibrotic Diseases pending, a patent Biomarkers for the Diagnosis and Treatment of Fibrotic Lung Disease pending, and a patent Methods and Compositions for Risk Prediction, Diagnosis, Prognosis, and Treatment of Pulmonary Disorders issued. R. Vassallo reports grants from Pfizer, Bristol-Myers-Squibb and SunPharma, outside the submitted work. B. Crestani reports grants from Apellis and MedImmune, grants and personal fees for lectures from Boehringer Ingelheim and Roche, personal fees for lectures from AstraZeneca and Sanofi, outside the submitted work. P. Dieudé reports fees for consultancy from Pfizer, Abbvie and MSD, grants and personal fees for consultancy and lectures from Roche, Chugai and BMS, outside the submitted work.
Publisher Copyright:
© 2021 European Respiratory Society. All rights reserved.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - Question addressed by the study: Methotrexate (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. Methods: Through 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. Results: Analysis 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 highresolution 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.
AB - Question addressed by the study: Methotrexate (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. Methods: Through 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. Results: Analysis 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 highresolution 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.
UR - http://www.scopus.com/inward/record.url?scp=85091117988&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091117988&partnerID=8YFLogxK
U2 - 10.1183/13993003.00337-2020
DO - 10.1183/13993003.00337-2020
M3 - Article
C2 - 32646919
AN - SCOPUS:85091117988
VL - 57
JO - European Respiratory Journal
JF - European Respiratory Journal
SN - 0903-1936
IS - 2
M1 - 2000337
ER -