Dataset Information

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 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.

SUBMITTER: Juge PA

PROVIDER: S-EPMC8212188 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

Juge Pierre-Antoine PA Lee Joyce S JS Lau Jessica J Kawano-Dourado Leticia L Rojas Serrano Jorge J Sebastiani Marco M Koduri Gouri G Matteson Eric E Bonfiglioli Karina K Sawamura Marcio M Kairalla Ronaldo R Cavagna Lorenzo L Bozzalla Cassione Emanuele E Manfredi Andreina A Mejia Mayra M Rodríguez-Henriquez Pedro P González-Pérez Montserrat I MI Falfán-Valencia Ramcés R Buendia-Roldán Ivette I Pérez-Rubio Gloria G Ebstein Esther E Gazal Steven S Borie Raphaël R Ottaviani Sébastien S Kannengiesser Caroline C Wallaert Benoît B Uzunhan Yurdagul Y Nunes Hilario H Valeyre Dominique D Saidenberg-Kermanac'h Nathalie N Boissier Marie-Christophe MC Wemeau-Stervinou Lidwine L Flipo René-Marc RM Marchand-Adam Sylvain S Richette Pascal P Allanore Yannick Y Dromer Claire C Truchetet Marie-Elise ME Richez Christophe C Schaeverbeke Thierry T Lioté Huguette H Thabut Gabriel G Deane Kevin D KD Solomon Joshua J JJ Doyle Tracy T Ryu Jay H JH Rosas Ivan I Holers V Michael VM Boileau Catherine C Debray Marie-Pierre MP Porcher Raphaël R Schwartz David A DA Vassallo Robert R Crestani Bruno B Dieudé Philippe P

The European respiratory journal 20210211 2

<h4>Question addressed by the study</h4>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.<h4>Methods</h4>Through a case-control study design with discovery and international replication samples, we examined the association of MTX exp ...[more]

PMID: 32646919

Similar Datasets

Project description:Rheumatoid arthritis (RA) is a type of inflammatory arthritis that affects ~1% of the general population. Although arthritis is the cardinal symptom, many extra-articular manifestations can occur. Lung involvement and particularly interstitial lung disease (ILD) is among the most common. Although ILD can occur as part of the natural history of RA (RA-ILD), pulmonary fibrosis has been also linked with methotrexate (MTX); a condition also known as MTX-pneumonitis (M-pneu). This review aims to discuss epidemiological, diagnostic, imaging and histopathological features, risk factors, and treatment options in RA-ILD and M-pneu. M-pneu, usually has an acute/subacute course characterized by cough, dyspnea and fever. Several risk factors, including genetic and environmental factors have been suggested, but none have been validated. The diagnosis is based on clinical and radiologic findings which are mostly consistent with non-specific interstitial pneumonia (NSIP), more so than bronchiolitis obliterans organizing pneumonia (BOOP). Histological findings include interstitial infiltrates by lymphocytes, histiocytes, and eosinophils with or without non-caseating granulomas. Treatment requires immediate cessation of MTX and commencement of glucocorticoids. RA-ILD shares the same symptomatology with M-pneu. However, it usually has a more chronic course. RA-ILD occurs in about 3-5% of RA patients, although this percentage is significantly increased when radiologic criteria are used. Usual interstitial pneumonia (UIP) and NSIP are the most common radiologic patterns. Several risk factors have been identified for RA-ILD including smoking, male gender, and positivity for anti-citrullinated peptide antibodies and rheumatoid factor. Diagnosis is based on clinical and radiologic findings while pulmonary function tests may demonstrate a restrictive pattern. Although no clear guidelines exist for RA-ILD treatment, glucocorticoids and conventional disease modifying antirheumatic drugs (DMARDs) like MTX or leflunomide, as well as treatment with biologic DMARDs can be effective. There is limited evidence that rituximab, abatacept, and tocilizumab are better options compared to TNF-inhibitors.

Dataset Information

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

Question addressed by the study

Methods

Results

Answer to the question

Publications

Methotrexate and rheumatoid arthritis associated interstitial lung disease.

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