Trial reportArthritis & rheumatology (Hoboken, N.J.)2020
Pulmonary Adverse Events in Patients Receiving Low-Dose Methotrexate in the Randomized, Double-Blind, Placebo-Controlled Cardiovascular Inflammation Reduction Trial.
Trial report in Arthritis & rheumatology (Hoboken, N.J.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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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.
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.
Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Disease-modifying antirheumatic drugs and risk of incident interstitial lung disease among patients with rheumatoid arthritis: A systematic review and meta-analysis.Seminars in arthritis and rheumatism · 2024Pooled it
- Does methotrexate cause progressive fibrotic interstitial lung disease? A systematic review.Rheumatology international · 2021Pooled it
- Agomelatine Alleviates Methotrexate-Induced Lung Injury by Concurrently Inhibiting CD45/CD68-Positive Immune Cell Infiltration and Modulating the BAX/BCL2 Apoptosis Pathway.Journal of applied toxicology : JAT · 2026Article
- Differential Protective Actions of Dulaglutide and Dexamethasone in Methotrexate Induced Pulmonary Fibrosis: Relationship with AMPK and Beclin-1 Levels.Biomedicines · 2026Article
- Low prevalence of methotrexate intolerance in rheumatoid arthritis: a South African study.Clinical rheumatology · 2025Article
- Methotrexate - Safe Backbone for the Treatment of Rheumatoid Arthritis.Current rheumatology reviews · 2025Review
- Treatment of rheumatoid arthritis-associated interstitial lung disease: An appraisal of the 2023 ACR/CHEST guideline.Current treatment options in rheumatology · 2024Article
- Screening, diagnosis, and monitoring of interstitial lung disease in autoimmune rheumatic diseases: A narrative review.Revista colombiana de reumatologia · 2024Article
- Article
- Low-Dose Methotrexate and Serious Adverse Events Among Older Adults With Chronic Kidney Disease.JAMA network open · 2023Article
- Article
- Prevalence, incidence and cause-specific mortality of rheumatoid arthritis-associated interstitial lung disease among older rheumatoid arthritis patients.Rheumatology (Oxford, England) · 2021Article
- Transcriptomic Analysis of the Mechanisms for Alleviating Psoriatic Dermatitis Using Taodan Granules in an Imiquimod-Induced Psoriasis-like Mouse Model.Frontiers in pharmacology · 2021Article
- A novel biomarker of MMP-cleaved prolargin is elevated in patients with psoriatic arthritis.Scientific reports · 2020Article
- Advances in the identification and management of progressive pulmonary fibrosis: perspective from Chinese experts.Therapeutic advances in respiratory diseaseReview
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7 authors at 1 institution in 1 country.
Funding
Abstract
objectiveWe previously reported that low-dose methotrexate (MTX) was associated with an increased risk of pulmonary adverse events (AEs) in a large randomized, placebo-controlled trial. Herein, we report details on the predictors and severity of pulmonary AEs.
methodsWe conducted a prespecified analysis of pulmonary AEs in the Cardiovascular Inflammation Reduction Trial. Adults with known cardiovascular disease and diabetes/metabolic syndrome were randomly allocated to receive low-dose MTX (target dose 15-20 mg/week) or placebo after a 6-8-week open-label run-in phase in which all patients received low-dose MTX. Individuals with systemic inflammatory diseases were excluded. Pulmonary AEs were adjudicated in a blinded manner. We described severe pulmonary AEs and examined associations of baseline characteristics with pulmonary AEs in patients receiving low-dose MTX.
resultsA total of 2,391 subjects were randomized to receive low-dose MTX and 2,395 to receive placebo. There were 13 severe pulmonary AEs (0.5%) and 7 cases of possible pneumonitis (0.3%) in the low-dose MTX group, compared to 8 (0.3%) and 1 (<0.1%), respectively, in the placebo group. Among those randomized to receive low-dose MTX, risk factors for any pulmonary AE included female sex (hazard ratio [HR] 1.69 versus male sex [95% confidence interval (95% CI) 1.16-2.45]), white race (HR 2.35 versus other race [95% CI 1.03-5.36]), and insulin use (HR 1.60 versus non-use [95% CI 1.11-2.30]). The only risk factor for severe pulmonary AEs was older age at baseline (HR 1.09 per year increase [95% CI 1.02-1.16]).
conclusionIn this large placebo-controlled trial, pulmonary AEs, including possible pneumonitis, were uncommon but were more likely to occur in those randomized to receive low-dose MTX. White race, older age, male sex, and insulin use were associated with an increased risk of pulmonary AEs in those receiving low-dose MTX.
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