Introduction
Rheumatoid Arthritis (RA) is an autoimmune disorder characterized by chronic inflammation, primarily affecting the joints but also potentially leading to a variety of systemic manifestations. Among such complications, Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD) is recognized as a significant cause of morbidity and mortality. With the advent of various disease-modifying antirheumatic drugs (DMARDs) such as Methotrexate (MTX), the treatment landscape for RA has considerably evolved. However, MTX’s link to ILD development remains the subject of investigation. A recent study published in the BMJ Open, which critically analyzed data from the Early Rheumatoid Arthritis Study (ERAS) and Early Rheumatoid Arthritis Network (ERAN) inception cohorts, sheds light on this association. This extensive analysis is poised to illuminate the intricacies of RA-ILD, its association with MTX, and the resulting clinical implications.
Elaborate Analysis of RA-ILD in Relation to MTX Treatment
The multifaceted study aimed to discern predictive factors for RA-ILD within two early RA inception cohorts, with a sharp focus on Methotrexate (MTX) exposure. The multicentre prospective early RA inception cohort studies—ERAS and ERAN—involved secondary care from ERAS’s nine centres and ERAN’s 23 centres across England, Wales, and Ireland. The study encompassed a pool of 2701 patients newly diagnosed with RA. The meticulous gathering of standardized data included demographics, drug therapies, and clinical outcomes, such as RA-ILD presence, collected at baseline, within 3-6 months, at 12 months, and yearly thereafter. The primary focus was on the associations between MTX exposure and RA-ILD diagnosis. Secondary outcomes included associations of demographic, comorbid, and RA-specific factors on RA-ILD diagnosis, along with the impact of MTX exposure on the timing of RA-ILD diagnosis.
Research Findings
In the dataset of 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX-exposed and 53 in 1114 (4.8%) non-MTX-exposed cases. The primary analysis, considering RA-ILD cases developing post-exposure to any conventional synthetic DMARDs (n=67), indicated that MTX exposure was not associated with a higher incidence of RA-ILD, boasting an odds ratio (OR) of 0.85 (95% CI 0.49 to 1.49, p=0.578). Additionally, there was a non-significant trend suggesting MTX might delay the ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). Intriguingly, expanded analyses that included RA-ILD cases present at RA diagnosis (n=92) asserted that MTX exposure corresponded to a significantly diminished risk of RA-ILD incidence (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and elongated the period to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other determinants independently linked with RA-ILD onset included higher age at RA initiation, past smoking habits, male gender, rheumatoid nodules, and protracted duration from initial RA symptom to first outpatient visit.
Interpretation and Implications
This composite study indicates that MTX treatment was not associated with an elevated risk of RA-ILD diagnosis. Contrarily, the evidence leans towards MTX potentially delaying the onset of ILD within the RA patient demographic. This revelation comes as a paramount finding in the clinical RA treatment domain, suggesting that MTX might not only be safe in terms of ILD risk but also potentially beneficial in postponing pulmonary complications, a substantial concern for RA patients.
DOI and References
DOI: 10.1136/bmjopen-2018-028466
References
1. Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960–77. DOI: 10.1136/annrheumdis-2016-210715
2. Sokka T, Kautiainen H, Toloza S, et al. QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries. Ann Rheum Dis 2007;66:1491–6. DOI: 10.1136/ard.2006.069252
3. Micha R, Imamura F, Wyler von Ballmoos M, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 2011;108:1362–70. DOI: 10.1016/j.amjcard.2011.06.054
4. Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis 2009;68:1100–4. DOI: 10.1136/ard.2008.093690
5. Iqbal K, Kelly C. Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review. Ther Adv Musculoskelet Dis 2015;7:247–67. DOI: 10.1177/1759720X15612250
Keywords
1. Methotrexate Rheumatoid Arthritis
2. Interstitial Lung Disease RA
3. MTX RA-ILD Incidence
4. ERAS ERAN study Rheumatology
5. DMARDs RA Pulmonary Risks
Conclusion
The study’s findings reiterate the complexity of RA-ILD pathogenesis and bilateral effects of treatment regimens. MTX’s role in the treatment of RA is reinforced by this research, underscoring its safety concerning pulmonary health in RA patients. As we continue to unravel the interplay between RA and its extra-articular manifestations, such research remains vital. These outcomes should be echoed throughout clinical practices and patient communications to ease concerns regarding MTX-related lung disease while maintaining vigilance for the minority who may be at risk. With these insights, the medical community takes a step forward in personalizing RA treatments for optimized patient outcomes.