{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:28:33Z","timestamp":1785932913618,"version":"3.56.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Interstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD) that manifests as several subtypes with significant differences in prognosis. It is necessary to evaluate the efficacy and safety of pirfenidone (PFD) combined with immunosuppressant (IS) in the treatment of CTD-ILD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 111 patients with CTD-ILD were enrolled, including those with systemic sclerosis (SSc), inflammatory myopathy (IIM), rheumatoid arthritis (RA), and other CTDs (such as systemic lupus erythematosus, primary Sjogren's syndrome, and undifferentiated CTD). After evaluation of the high-resolution computed tomography (HRCT), pulmonary function (PF), and basic disease activity, patients either were or were not prescribed PFD and were followed up regularly for 24 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After 24 weeks of treatment, predicted forced vital capacity (FVC%) in the SSc-PFD group had improved by 6.60%, whereas this value was 0.55% in patients with SSc-no-PFD. The elevation in FVC% was also significant in IIM-PFD over the IIM-no-PFD controls (7.50 vs. 1.00%). The predicted diffusing capacity for carbon monoxide (DLCo%) of RA-PFD was enhanced by 7.40%, whereas that of RA-no-PFD decreased by 5.50%. When performing a subtype analysis of HRCT images, the change in FVC% among patients with SSc with a tendency toward usual interstitial pneumonia (UIP) was higher in those given PFD (SSc-PFD-UIP) than the no-PFD group (8.05 vs. \u22123.20%). However, in IIM patients with a non-UIP tendency, PFD displayed better therapeutic effects than the control (10.50 vs. 1.00%). DLCo% improved significantly in patients with the PFD-treated RA-non-UIP subtype compared with the patients with no-PFD (10.40 vs. \u22124.45%). Dichotomizing the patients around a baseline FVC% or DLCo% value of 70%, the PFD arm had a more improved FVC% than the no-PFD arm within the high-baseline-FVC% subgroups of patients with SSc and IIM (6.60 vs. 0.10%, 6.30 vs. 1.10%). In patients with RA-PFD, DLCo% showed a significant increase in the subgroup with low baseline DLCo% compared to that in patients with RA-no-PFD (7.40 vs. \u22126.60%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The response of PF to PFD varied between CTD-ILD subsets. Patients with SSc and IIM showed obvious improvements in FVC%, especially patients with SSc-UIP and IIM-non-UIP. In RA, the subsets of patients with non-UIP and a lower baseline DLCo% most benefited from PFD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.871861","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T06:16:03Z","timestamp":1652336163000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["The Efficacy and Safety of Pirfenidone Combined With Immunosuppressant Therapy in Connective Tissue Disease-Associated Interstitial Lung Disease: A 24-Week Prospective Controlled Cohort Study"],"prefix":"10.3389","volume":"9","author":[{"given":"Jiaqi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2168","DOI":"10.3899\/jrheum.141182","article-title":"Connective tissue disease-associated interstitial lung diseases (Ctd-Ild)\u2014Report from Omeract Ctd-Ild working group","volume":"42","author":"Khanna","year":"2015","journal-title":"J Rheumatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1136\/annrheumdis-2020-217230","article-title":"Mechanisms of progressive fibrosis in connective tissue disease (Ctd)-associated interstitial lung diseases (Ilds)","volume":"80","author":"Spagnolo","year":"2021","journal-title":"Ann Rheum Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1177\/1479972310393758","article-title":"Review series: aspects of interstitial lung disease: connective tissue disease-associated interstitial lung disease: how does it differ from Ipf? How should the clinical approach differ?","volume":"8","author":"de Lauretis","year":"2011","journal-title":"Chron Respir Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.ccm.2019.05.010","article-title":"Imaging of the thoracic manifestations of connective tissue disease","volume":"40","author":"Elicker","year":"2019","journal-title":"Clin Chest Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"100311","DOI":"10.1016\/j.ejro.2020.100311","article-title":"Connective tissue disease-related interstitial lung disease (Ctd-Ild) and interstitial lung abnormality (Ila): evolving concept of ct findings, pathology and management","volume":"8","author":"Yoo","year":"2021","journal-title":"Eur J Radiol Open."},{"key":"B6","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1097\/TP.0b013e3182584879","article-title":"Inhibitory effects of pirfenidone on dendritic cells and lung allograft rejection","volume":"94","author":"Bizargity","year":"2012","journal-title":"Transplantation."},{"key":"B7","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1471-2466-12-24","article-title":"Pirfenidone inhibits Tgf-?1-induced over-expression of collagen type I and heat shock protein 47 in A549 cells","volume":"12","author":"Hisatomi","year":"2012","journal-title":"BMC Pulm Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e28134","DOI":"10.1371\/journal.pone.0028134","article-title":"In vitro effects of pirfenidone on cardiac fibroblasts: proliferation, myofibroblast differentiation, migration and cytokine secretion","volume":"6","author":"Shi","year":"2011","journal-title":"PLoS ONE."},{"key":"B9","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1097\/TP.0b013e3181ae3392","article-title":"Pirfenidone inhibits T-cell activation, proliferation, cytokine and chemokine production, and host alloresponses","volume":"88","author":"Visner","year":"2009","journal-title":"Transplantation."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1056\/NEJMoa1402582","article-title":"A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis","volume":"370","author":"King","year":"2014","journal-title":"N Engl J Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1016\/s0140-6736(11)60405-4","article-title":"Pirfenidone in patients with idiopathic pulmonary fibrosis (capacity): two randomised trials","volume":"377","author":"Noble","year":"2011","journal-title":"Lancet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1183\/09031936.00005209","article-title":"Pirfenidone in idiopathic pulmonary fibrosis","volume":"35","author":"Taniguchi","year":"2010","journal-title":"Eur Respir J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.3899\/jrheum.151322","article-title":"An open-label, phase ii study of the safety and tolerability of pirfenidone in patients with scleroderma-associated interstitial lung disease: the Lotuss trial","volume":"43","author":"Khanna","year":"2016","journal-title":"J Rheumatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"33226","DOI":"10.1038\/srep33226","article-title":"Pirfenidone in patients with rapidly progressive interstitial lung disease associated with clinically amyopathic dermatomyositis","volume":"6","author":"Li","year":"2016","journal-title":"Sci Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1002\/art.41752","article-title":"2021 American college of rheumatology guideline for the treatment of rheumatoid arthritis","volume":"73","author":"Fraenkel","year":"2021","journal-title":"Arthritis Rheumatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1002\/art.40320","article-title":"2017 European league against rheumatism\/American College of rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups","volume":"69","author":"Lundberg","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/annrheumdis-2016-210571","article-title":"2016 American College of Rheumatology\/European League against Rheumatism Classification Criteria for Primary Sjogren's Syndrome: a consensus and data-driven methodology involving three international patient cohorts","volume":"76","author":"Shiboski","year":"2017","journal-title":"Ann Rheum Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12890-021-01516-4","article-title":"Effectiveness of pirfenidone in idiopathic pulmonary fibrosis according to the autoantibody status: a retrospective cohort study","volume":"21","author":"Song","year":"2021","journal-title":"BMC Pulm Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1136\/annrheumdis-2013-204424","article-title":"2013 classification criteria for systemic sclerosis: An American College of Rheumatology\/European League against Rheumatism Collaborative Initiative","volume":"72","author":"van den Hoogen","year":"2013","journal-title":"Ann Rheum Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1849","DOI":"10.1148\/rg.2015140334","article-title":"American Thoracic Society-European Respiratory Society Classification of the idiopathic interstitial pneumonias: advances in knowledge since 2002","volume":"35","author":"Sverzellati","year":"2015","journal-title":"Radiographics."},{"key":"B21","article-title":"The role of comorbidities alongside patient and disease characteristics on long-term disease activity in Ra Using Uk inception cohort data","volume-title":"Rheumatology.","author":"Busby","year":"2022"},{"key":"B22","doi-asserted-by":"publisher","first-page":"628128","DOI":"10.3389\/fcell.2021.628128","article-title":"Aberrantly expressed galectin-9 is involved in the immunopathogenesis of anti-Mda5-positive dermatomyositis-associated interstitial lung disease","volume":"9","author":"Liang","year":"2021","journal-title":"Front Cell Dev Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"106125","DOI":"10.1016\/j.rmed.2020.106125","article-title":"The Potential utility of anterior upper lobe honeycomb-like lesion in interstitial lung disease associated with connective tissue disease","volume":"172","author":"Yamakawa","year":"2020","journal-title":"Respir Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.chest.2018.11.008","article-title":"Efficacy of pirfenidone in the context of multiple disease progression events in patients with idiopathic pulmonary fibrosis","volume":"155","author":"Nathan","year":"2019","journal-title":"Chest."},{"key":"B25","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/s2213-2600(19)30341-8","article-title":"Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial","volume":"8","author":"Maher","year":"2020","journal-title":"Lancet Respir Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1007\/s00296-020-04565-w","article-title":"Efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease-a randomised controlled trial","volume":"40","author":"Acharya","year":"2020","journal-title":"Rheumatol Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/s2213-2600(20)30554-3","article-title":"Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (relief): a double-blind, randomised, placebo-controlled, phase 2b trial","volume":"9","author":"Behr","year":"2021","journal-title":"Lancet Respir Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"560","DOI":"10.55563\/clinexprheumatol\/off5n7","article-title":"The Role of Pirfenidone in the Treatment of Interstitial Pneumonia with Autoimmune Features","volume":"40","author":"Chen","year":"2022","journal-title":"Clin Exp Rheumatol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/1465-9921-12-143","article-title":"Exploratory analysis of a phase Iii trial of pirfenidone identifies a subpopulation of patients with idiopathic pulmonary fibrosis as benefiting from treatment","volume":"12","author":"Arata","year":"2011","journal-title":"Respir Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e1600","DOI":"10.1097\/MD.0000000000001600","article-title":"Double-blind randomized trial of pirfenidone in Chinese idiopathic pulmonary fibrosis patients","volume":"94","author":"Huang","year":"2015","journal-title":"Medicine."},{"key":"B31","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00408-019-00276-7","article-title":"Clinical characteristics and natural history of autoimmune forms of interstitial lung disease: a single-center experience","volume":"197","author":"Chartrand","year":"2019","journal-title":"Lung."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1007\/s12325-019-01086-2","article-title":"The design and rationale of the trail1 trial: a randomized double-blind phase 2 clinical trial of pirfenidone in rheumatoid arthritis-associated interstitial lung disease","volume":"36","author":"Solomon","year":"2019","journal-title":"Adv Ther."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.871861\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T06:16:06Z","timestamp":1652336166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.871861\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,12]]},"references-count":32,"alternative-id":["10.3389\/fmed.2022.871861"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.871861","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,12]]},"article-number":"871861"}}