{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T23:25:10Z","timestamp":1780529110502,"version":"3.54.1"},"reference-count":24,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Interstitial lung disease (ILD) is a prominent complication in the course of rheumatoid arthritis (RA), with a prevalence ranging from 5% to 60% and several phenotypes. The existing knowledge on the impact of different pharmacological interventions in individuals with rheumatoid arthritis-related interstitial lung disease (RA-ILD) is inconclusive, and this variable response to treatment highlights the need for a personalized approach to the management of RA-associated ILD. Therefore, we aimed to evaluate the therapeutic effect and safety of different pharmacological agents, including conventional synthetic DMARDs (Cs DMARDs), biologic DMARDs (bDMARDs), targeted synthetic DMARDs (Ts DMARDs), and antifibrotic agents, in patients with RA-ILD. Method: This systematic review and meta-analysis searched for available randomized controlled trials (RCTs) and prospective cohort studies. A search was performed in the PubMed, Google Scholar, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Eligible studies comprised those involving hospitalized patients diagnosed with RA-ILD, regardless of concomitant medications, who were of adult age (\u226518 years); the studies measured the effect of pharmacological interventions, including methotrexate, leflunomide, tumor necrosis factor inhibitors (anti-TNF), abatacept, rituximab, JAK inhibitors, and antifibrotic agents, compared to placebo or other therapies for RA. Results: Out of 446 studies from 2002 to 2024, only 16 were included in this systematic review, including 14 prospective cohort studies and 2 placebo-controlled studies. Unfortunately, no RCTs were found that address our research question. The most relevant studies (n = 4) were performed in different countries (mainly Spain and the UK), with sample sizes varying from 23 to 381 patients (total: 2199 patients). The current study reveals that non-anti-TNF biologics were associated with a decreased risk of radiologic progression, while advanced therapies improved disease-related outcomes in patients requiring oxygen therapy. Methotrexate and other DMARDs were found to have inconsistent effects on ILD progression and mortality. Conclusions: Our review supports the integration of personalized medicine into the management of RA-ILD. By considering patient-specific factors and therapeutic responses, clinicians can better tailor interventions. We confirmed the high methodological quality of the trials, yielding solid evidence for the clinical management of RA-ILD. This review adds to the existing literature by identifying nintedanib as a potential disease-modifying therapy with the potential to slow the progression of lung disease.<\/jats:p>","DOI":"10.3390\/jpm15060239","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T05:54:05Z","timestamp":1749448445000},"page":"239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of Pharmacological Treatments on Rheumatoid Arthritis-Associated Diffuse Interstitial Lung Disease: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Ariam A.","family":"Muarif","sequence":"first","affiliation":[{"name":"College of Medicine, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Algahtani","sequence":"additional","affiliation":[{"name":"College of Medicine, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujain H.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Jeddah, Jeddah 23218, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6874-5772","authenticated-orcid":false,"given":"Sarah S.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Jeddah, Jeddah 23218, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5255-5790","authenticated-orcid":false,"given":"Lama","family":"Al Nemer","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Vision Colleges, Riyadh 13226, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5496-5226","authenticated-orcid":false,"given":"Reman","family":"Alsaqrah","sequence":"additional","affiliation":[{"name":"College of Medicine, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4232-1732","authenticated-orcid":false,"given":"Yazeed","family":"Alsulami","sequence":"additional","affiliation":[{"name":"College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha","family":"Alsharif","sequence":"additional","affiliation":[{"name":"College of Medicine, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Alznbagi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Abdulaziz University, Rabigh 25732, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Aljehani","sequence":"additional","affiliation":[{"name":"College of Medicine, University of Jeddah, Jeddah 23218, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyad","family":"Alsaeedi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Abdulaziz University, Jeddah 80200, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultan","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"College of Medicine, King Abdulaziz University, Jeddah 80200, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taif A.","family":"Sayel","sequence":"additional","affiliation":[{"name":"College of Medicine, King Abdulaziz University, Jeddah 80200, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basma","family":"Al Ghamdi","sequence":"additional","affiliation":[{"name":"Pulmonology Division, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Al Bshabshe","sequence":"additional","affiliation":[{"name":"Adult Critical Care Division, College of Medicine, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e003789","DOI":"10.1136\/rmdopen-2023-003789","article-title":"Impact of DMARD treatment and systemic inflammation on all-cause mortality in patients with rheumatoid arthritis and interstitial lung disease: A cohort study from the German RABBIT register","volume":"10","author":"Rudi","year":"2024","journal-title":"RMD 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