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; Ronaldo Kairalla; Lorenzo Cavagna; Emanuele Bozzalla Cassione; Andreina Manfredi; Mayra Mejia; Pedro Rodríguez-Henriquez; Montserrat I. González-Pérez; Ramcés Falfán-Valencia; Ivette Buendia-Roldán; Gloria Pérez-Rubio; Esther Ebstein; Steven Gazal; Raphaël Borie; Sébastien Ottaviani; Caroline Kannengiesser; Beno t. Wallaert; Yurdagul Uzunhan; Hilario Nunes; Dominique Valeyre; Nathalie Saidenberg-Kermanac h; Marie Christophe Boissier; Lidwine Wemeau-Stervinou; René Marc Flipo; Sylvain Marchand-Adam; Pascal Richette; Yannick Allanore; Claire Dromer; Marie Elise Truchetet; Christophe Richez; Thierry Schaeverbeke; Huguette Lioté; Gabriel Thabut; Kevin D. Deane; Joshua J. Solomon; Tracy Doyle; Jay H. Ryu; Ivan Rosas; V. Michael Holers; Catherine Boileau; Marie Pierre Debray; Raphaël Porcher; David A. Schwartz; Robert Vassallo; Bruno Crestani; Philippe Dieudé

doi:10.1183/13993003.00337-2020

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, Ronaldo Kairalla, Lorenzo Cavagna, Emanuele Bozzalla Cassione, Andreina Manfredi, Mayra Mejia, Pedro Rodríguez-Henriquez, Montserrat I. González-Pérez, Ramcés Falfán-Valencia, Ivette Buendia-Roldán, Gloria Pérez-RubioEsther Ebstein, Steven Gazal, Raphaël Borie, Sébastien Ottaviani, Caroline Kannengiesser, Beno t. Wallaert, Yurdagul Uzunhan, Hilario Nunes, Dominique Valeyre, Nathalie Saidenberg-Kermanac h, Marie Christophe Boissier, Lidwine Wemeau-Stervinou, René Marc Flipo, Sylvain Marchand-Adam, Pascal Richette, Yannick Allanore, Claire Dromer, Marie Elise Truchetet, Christophe Richez, Thierry Schaeverbeke, Huguette Lioté, Gabriel Thabut, Kevin D. Deane, Joshua J. Solomon, Tracy Doyle, Jay H. Ryu, Ivan Rosas, V. Michael Holers, Catherine Boileau, Marie Pierre Debray, Raphaël Porcher, David A. Schwartz, Robert Vassallo, Bruno Crestani, Philippe Dieudé

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English (US)
Article number	2000337
Journal	European Respiratory Journal
Volume	57
Issue number	2
DOIs	https://doi.org/10.1183/13993003.00337-2020
State	Published - Feb 1 2021

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1183/13993003.00337-2020

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Juge, P. A., Lee, J. S., Lau, J., Kawano-Dourado, L., Serrano, J. R., Sebastiani, M., Koduri, G., Matteson, E., Bonfiglioli, K., Sawamura, M., Kairalla, R., Cavagna, L., Cassione, E. B., Manfredi, A., Mejia, M., Rodríguez-Henriquez, P., González-Pérez, M. I., Falfán-Valencia, R., Buendia-Roldán, I., ... Dieudé, P. (2021). Methotrexate and rheumatoid arthritis associated interstitial lung disease. European Respiratory Journal, 57(2), Article 2000337. https://doi.org/10.1183/13993003.00337-2020

Juge, PA, Lee, JS, Lau, J, Kawano-Dourado, L, Serrano, JR, Sebastiani, M, Koduri, G, Matteson, E, Bonfiglioli, K, Sawamura, M, Kairalla, R, Cavagna, L, Cassione, EB, Manfredi, A, Mejia, M, Rodríguez-Henriquez, P, González-Pérez, MI, Falfán-Valencia, R, Buendia-Roldán, I, Pérez-Rubio, G, Ebstein, E, Gazal, S, Borie, R, Ottaviani, S, Kannengiesser, C, Wallaert, BT, Uzunhan, Y, Nunes, H, Valeyre, D, Saidenberg-Kermanac h, N, Boissier, MC, Wemeau-Stervinou, L, Flipo, RM, Marchand-Adam, S, Richette, P, Allanore, Y, Dromer, C, Truchetet, ME, Richez, C, Schaeverbeke, T, Lioté, H, Thabut, G, Deane, KD, Solomon, JJ, Doyle, T, Ryu, JH, Rosas, I, Michael Holers, V, Boileau, C, Debray, MP, Porcher, R, Schwartz, DA, Vassallo, R, Crestani, B & Dieudé, P 2021, 'Methotrexate and rheumatoid arthritis associated interstitial lung disease', European Respiratory Journal, vol. 57, no. 2, 2000337. https://doi.org/10.1183/13993003.00337-2020

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title = "Methotrexate and rheumatoid arthritis associated interstitial lung disease",

abstract = "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.",

author = "Juge, {Pierre Antoine} and Lee, {Joyce S.} and Jessica Lau and Leticia Kawano-Dourado and Serrano, {Jorge Rojas} and Marco Sebastiani and Gouri Koduri and Eric Matteson and Karina Bonfiglioli and Marcio Sawamura and Ronaldo Kairalla and Lorenzo Cavagna and Cassione, {Emanuele Bozzalla} and Andreina Manfredi and Mayra Mejia and Pedro Rodr{\'i}guez-Henriquez and Gonz{\'a}lez-P{\'e}rez, {Montserrat I.} and Ramc{\'e}s Falf{\'a}n-Valencia and Ivette Buendia-Rold{\'a}n and Gloria P{\'e}rez-Rubio and Esther Ebstein and Steven Gazal and Rapha{\"e}l Borie and S{\'e}bastien Ottaviani and Caroline Kannengiesser and Wallaert, {Beno t.} and Yurdagul Uzunhan and Hilario Nunes and Dominique Valeyre and {Saidenberg-Kermanac h}, Nathalie and Boissier, {Marie Christophe} and Lidwine Wemeau-Stervinou and Flipo, {Ren{\'e} Marc} and Sylvain Marchand-Adam and Pascal Richette and Yannick Allanore and Claire Dromer and Truchetet, {Marie Elise} and Christophe Richez and Thierry Schaeverbeke and Huguette Liot{\'e} and Gabriel Thabut and Deane, {Kevin D.} and Solomon, {Joshua J.} and Tracy Doyle and Ryu, {Jay H.} and Ivan Rosas and {Michael Holers}, V. and Catherine Boileau and Debray, {Marie Pierre} and Rapha{\"e}l Porcher and Schwartz, {David A.} and Robert Vassallo and Bruno Crestani and Philippe Dieud{\'e}",

year = "2021",

month = feb,

day = "1",

doi = "10.1183/13993003.00337-2020",

language = "English (US)",

volume = "57",

journal = "European Respiratory Journal",

issn = "0903-1936",

publisher = "European Respiratory Society",

number = "2",

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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

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.

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JO - European Respiratory Journal

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Methotrexate and rheumatoid arthritis associated interstitial lung disease

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