{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:04:54Z","timestamp":1790949894338,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,10]],"date-time":"2023-12-10T00:00:00Z","timestamp":1702166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a common extra-articular clinical manifestation of rheumatoid arthritis (RA) that has negative impacts on morbidity and mortality. In addition, there has been no proven treatment for RA-ILD to date. Thus, we planned a meta-analysis of a literature search to confirm the clinical effects of antifibrotic agents in RA-ILD patients. Materials and Methods: We conducted the literature search in Ovid MEDLIVE\u00ae databases, Cochrane Library databases, EMBASE, and KoreaMed and identified references elucidating the role of nintedanib or pirfenidone in adult patients with RA-ILD. Among the identified studies, those with comparative interventions, complete results of clinical trials, and available full text were included in the analysis. The primary outcome was the effect of the antifibrotic agent on disease progression in RA-ILD patients assessed with a mean difference in the change of forced vital capacity (FVC) and the proportion of patients with an increase in percent predicted FVC of 10% or more over 52 weeks. Analysis for heterogeneity was assessed through I2 statistics. Meta-analysis with a fixed effect model was performed on changes in FVC. Results: A total of 153 articles were identified through database searches, of which 28 were excluded because of duplication. After additional screening, 109 studies were selected with full text and two articles qualified for analysis according to the set inclusion and exclusion criteria. As a result, two randomized controlled studies were selected, comparing nintedanib and pirfenidone to placebo, respectively. The meta-analysis revealed that antifibrotic agents showed a significant reduction in FVC decline compared to placebo in patients with RA-ILD (mean difference, 88.30; 95% CI, 37.10\u2013139.50). Additionally, there were significantly fewer patients experienced an increase in percent predicted FVC of 10% or more in the antifibrotic agent group compared to the placebo group (Odds ratio 0.42; 95% CI 0.19\u20130.95, p = 0.04). There was no significant heterogeneity between the two included studies (\u03c72 = 0.35, p = 0.0007, I2 = 0%). Conclusions: The meta-analysis suggests that nintedanib and pirfenidone may have clinical utility in reducing disease progression in patients with RA-ILD. Further research is needed to confirm the clinical benefits of antifibrotic agents in RA-ILD.<\/jats:p>","DOI":"10.3390\/life13122318","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T06:56:00Z","timestamp":1702277760000},"page":"2318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antifibrotic Agents in Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"13","author":[{"given":"Ji Hoon","family":"Jang","sequence":"first","affiliation":[{"name":"Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junghae","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0155-5473","authenticated-orcid":false,"given":"So Young","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae-Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-3810","authenticated-orcid":false,"given":"Ju Hyun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul 01757, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3140-3681","authenticated-orcid":false,"given":"Tae-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Hospital Pathology, Yeouido St. Mary\u2019s Hospital, The Catholic University of Korea, Seoul 07345, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-7025","authenticated-orcid":false,"given":"Joo Hun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Health Technology Assessment Research, National Evidence-Based Healthcare Collaborating Agency (NECA), Seoul 04933, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0932-2826","authenticated-orcid":false,"given":"Jae Ha","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_2","first-page":"286","article-title":"Extra-articular Manifestations in Rheumatoid Arthritis","volume":"5","author":"Cojocaru","year":"2010","journal-title":"Maedica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1055\/s-0039-1683995","article-title":"Pulmonary Complications of Rheumatoid Arthritis","volume":"40","author":"Farquhar","year":"2019","journal-title":"Semin. 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Care Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"360","DOI":"10.3899\/jrheum.171315","article-title":"Rheumatoid Arthritis-Interstitial Lung Disease in the United States: Prevalence, Incidence, and Healthcare Costs and Mortality","volume":"46","author":"Raimundo","year":"2019","journal-title":"J. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cassone, G., Manfredi, A., Vacchi, C., Luppi, F., Coppi, F., Salvarani, C., and Sebastiani, M. (2020). Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows. J. Clin. Med., 9.","DOI":"10.3390\/jcm9041082"},{"key":"ref_12","first-page":"155","article-title":"Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease","volume":"9","author":"Suda","year":"2015","journal-title":"Clin. Med. Insights Circ. Respir. Pulm. 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