Journal Information
Vol. 18. Issue 7.
Pages 440-441 (August - September 2022)
Vol. 18. Issue 7.
Pages 440-441 (August - September 2022)
Letter to the Editor
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Answer to the Letter to the Editor: Methotrexate in interstitial lung disease associated with rheumatoid arthritis
Respuesta a la carta al editor: Metotrexato en la neumopatía intersticial asociada a la artritis reumatoide
Carmen Carrasco Cuberoa,
Corresponding author

Corresponding author.
, Eugenio Chamizo Carmonab
a Servicio de Reumatología, Hospital Universitario de Badajoz, Badajoz, Spain
b Servicio de Reumatología, Hospital General de Mérida, Mérida, Badajoz, Spain
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Dear Editor,

We appreciate the interest shown by Arboleya-Rodríguez1 in our original: “Systematic Review of the Impact of Drugs on Diffuse Interstitial Lung Disease Associated with Rheumatoid Arthritis (RA-DILD)”2 and his critical comment on one of the conclusions given in our article: “It is not necessary to discontinue methotrexate (MTX) in patients with RA-DILD, as there is evidence that it does not increase the incidence or exacerbations of DILD and improves survival”.

We did not include acute MTX pneumonitis (idiosyncratic hypersensitivity reaction) in our PICO question2. We believe that it cannot be claimed that RA-associated DILD predisposes to the development of acute MTX pneumonitis based on a single retrospective study conducted in the 1980s3. We emphasise the value of systematic reviews (SR) rather than individual studies to search for evidence that is useful for clinical practice. The evidence found in our SR2 indicates that MTX does not increase either the incidence or exacerbations of RA-DILD.

The aim of treatment should be to control RA without worsening the course of the DILD. When MTX is part of the treatment, the decision to continue or discontinue it should be tailored to the individual patient. However, there is growing evidence that rather than being discontinued, MTX has an important role to play in the treatment of patients with RA-DILD2,4–6.

Of the other two articles mentioned by Arboleya to advise discontinuing MTX in patients with RA and DILD, one is a retrospective study7, without a control group, of a single-centre case series that was included in our SR2, and our analysis can be found there. The other is the CIRT trial8 (published after our SR2), conducted in patients with cardiovascular disease and metabolic syndrome or diabetes to investigate the side effects of MTX versus placebo. Patients with systemic rheumatic diseases and/or interstitial lung disorders were excluded from this clinical trial. They found episodes consistent with acute pneumonitis in six of the 3291 patients allocated to MTX and one of the 2080 allocated to placebo (HR 6.94 [95% CI .85–56.0]), but in no case was this considered likely or definitive on adjudication. Therefore, no conclusions can be drawn from this study on the performance of MTX in RA-DILD.

In conclusion, we believe that it is very important to control the inflammatory activity of RA without worsening the progression of DILD. When these patients need biological therapy, abatacept or rituximab is preferable to anti-TNF (with more potential risk) or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), given the lack of evidence. Treatment should always be individualised. In this context, it does not seem necessary to discontinue MTX in patients with AR-DILD, as there is evidence that it increases neither the incidence nor exacerbations of RA-DILD and it improves survival.

L. Arboleya-Rodríguez, M. Arias-Gillén.
Metotrexato en la neumopatía intersticial asociada a la artritis reumatoide.
C. Carrasco Cubero, E. Chamizo Carmona, P. Vela Casasempere.
Revisión sistemática sobre el impacto de los fármacos en la enfermedad pulmonar intersticial difusa asociada a Artritis Reumatoide.
M.R. Golden, R.S. Katz, R.A. Balk, H.E. Golden.
The relationship of preexisting lung disease to the development of methotrexate pneumonitis in patients with rheumatoid arthritis.
J Rheumatol, 22 (1995), pp. 1043-1047
J. Rojas-Serrano, D. Herrera-Bringas, D.I. Pérez-Román, R. Pérez-Dorame, H. Mateos-Toledo, M. Mejía.
Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosis.
Clin Rheumatol, 36 (2017), pp. 1493-1500
C. Fernández-Díaz, S. Castañeda, R. Melero, R. Loricera, F. Ortiz-Sanjuán, A. Jun-Mas, et al.
Interstitial lung disease: national multicenter study of 263 patients.
Ann Rheum Dis, 79 (2020), pp. 968
S.A. Nokhatha, R. Harrington, R. Conway.
Is methotrexate contra-indicated in lung involvement of rheumatoid arthritis?.
T. Mochizuki, K. Ikari, K. Yano, M. Sato, K. Okazaki.
Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept.
Mod Rheumatol, 29 (2019), pp. 413-417
D. Solomon, R.J. Glynn, E. Karlson, F. Lu, C. Corrigan, J. Colls, et al.
Adverse effects of low-dose methotrexate: a randomized trial.
Ann Intern Med, 172 (2020), pp. 369-380

Please cite this article as: Carrasco Cubero C, Chamizo Carmona E. Respuesta a la carta al editor: Metotrexato en la neumopatía intersticial asociada a la artritis reumatoide. Reumatol Clin. 2022;18:440–441.

Copyright © 2020. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
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