2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/2iy5wruuedsh6.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/00yc7rcvua6a7.js","/_next/static/immutable/chunks/37ktb71aq3480.js","/_next/static/immutable/chunks/2d50b-7eu4558.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/2d6noqpp6ehas.js","/_next/static/immutable/chunks/1sx186c93bpzg.js","/_next/static/immutable/chunks/3dc-1n866s65i.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2w1bvggzb0ga8.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T79b,Although post-COVID-19 interstitial lung abnormalities (ILAs) are common, the use of antifibrotic agents to prevent their onset and progression is controversial. We aimed to investigate the effectiveness and safety of pirfenidone to mitigate the onset and progression of ILAs in patients with severe COVID-19. We systematically searched literature published before July 21, 2025, from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biology Medicine, Weipu, and Wanfang databases, without language limitation. Randomized controlled trials and cohort studies that evaluated the effect of pirfenidone on COVID-19-induced ILAs were included. Risk of bias was determined using the Revised Cochrane Randomized Trial Risk Bias Tool Version 2 and the Newcastle-Ottawa Scale. The efficacy and safety of pirfenidone for ILAs in COVID-19 were analyzed by Review Manager 5.4 software. Eight studies were included, comprising 335 patients in pirfenidone treatment groups and 302 controls. Risk of bias ranged from low to moderate. Pirfenidone significantly decreased chest high-resolution CT (HRCT) scores during early- and late-stage COVID-19 and significantly improved forced expiratory volume in 1 s, especially in late-stage COVID-19. Pirfenidone treatment was associated with statistically nonsignificant trends toward improved forced vital capacity and decreased all-cause mortality. Furthermore, HRCT scores, pulmonary function, and inflammatory cytokine levels following pirfenidone treatment were superior to those obtained after glucocorticoid therapy. The incidence of gastrointestinal adverse events was higher in the pirfenidone than the control group, but no serious adverse events or fatalities occurred. Pirfenidone therapy may mitigate ILAs and preserve pulmonary function among survivors of COVID-19 pneumonia. Furthermore, pirfenidone exhibited acceptable safety and tolerability profiles.31:Ta01, Background Although post‐COVID‐19 interstitial lung abnormalities (ILAs) are common, the use of antifibrotic agents to prevent their onset and progression is controversial. We aimed to investigate the effectiveness and safety of pirfenidone to mitigate the onset and progression of ILAs in patients with severe COVID‐19. Methods We systematically searched literature published before July 21, 2025, from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biology Medicine, Weipu, and Wanfang databases, without language limitation. Randomized controlled trials and cohort studies that evaluated the effect of pirfenidone on COVID‐19–induced ILAs were included. Risk of bias was determined using the Revised Cochrane Randomized Trial Risk Bias Tool Version 2 and the Newcastle‐Ottawa Scale. The efficacy and safety of pirfenidone for ILAs in COVID‐19 were analyzed by Review Manager 5.4 software. Results Eight studies were included, comprising 335 patients in pirfenidone treatment groups and 302 controls. Risk of bias ranged from low to moderate. Pirfenidone significantly decreased chest high‐resolution CT (HRCT) scores during early‐ and late‐stage COVID‐19 and significantly improved forced expiratory volume in 1 s, especially in late‐stage COVID‐19. Pirfenidone treatment was associated with statistically nonsignificant trends toward improved forced vital capacity and decreased all‐cause mortality. Furthermore, HRCT scores, pulmonary function, and inflammatory cytokine levels following pirfenidone treatment were superior to those obtained after glucocorticoid therapy. The incidence of gastrointestinal adverse events was higher in the pirfenidone than the control group, but no serious adverse events or fatalities occurred. Conclusion Pirfenidone therapy may mitigate ILAs and preserve pulmonary function among survivors of COVID‐19 pneumonia. Furthermore, pirfenidone exhibited acceptable safety and tolerability profiles. 32:T83d,Background: Pulmonary fibrosis is a progressive and often irreversible condition that can develop following acute lung injury (ALI), particularly in patients requiring prolonged mechanical ventilation. Antifibrotic agents such as pirfenidone and nintedanib slow fibrosis progression in idiopathic pulmonary fibrosis, but their role in post-ALI fibrosis remains unclear. This meta-analysis aimed to evaluate the effects of antifibrotic therapy on mortality and secondary outcomes in patients with ALI. Methods: We searched Embase, PubMed, and Cochrane up to 17 March 2025 for randomized controlled trials and observational studies comparing antifibrotic therapy to standard care in patients with ALI. The primary outcome was all-cause mortality at the longest follow-up available. Secondary outcomes were length of hospital stay and radiological and functional findings. Results: We identified six studies (two randomized, two propensity matched and two case control studies) for a total of 697 COVID-19 patients and no study performed on non-COVID-19 patients. Antifibrotic therapy was associated with a significant reduction in all-cause mortality compared to the control group (16.1% vs. 23.9%, OR 0.61, 95% CI 0.40–0.93, p = 0.02, I2 = 40%). The number needed to treat to prevent one death was 13. There was no significant difference in length of hospital stay between the antifibrotic and control groups. Individual studies reported improvements in computed tomography severity scores and pulmonary function parameters in the antifibrotic group. Conclusions: This meta-analysis suggests that antifibrotic therapy might reduce mortality in patients with ALI. Improvements in radiological and functional outcomes indicate a potential role for antifibrotic agents in modifying disease progression. Further well-designed randomized controlled trials are necessary to confirm these results and determine the optimal use of antifibrotic therapy in post-ALI fibrosis. The PROSPERO Registration: The study protocol was prospectively registered in PROSPERO (registration number CRD420251001885).25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"pirfenidone: generic Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on pirfenidone (generic). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/generic/pirfenidone\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Generics\",\"item\":\"https://www.reachrx.ai/hub/tag/generic\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"pirfenidone\",\"item\":\"https://www.reachrx.ai/hub/tag/generic/pirfenidone\"}]}}"}}]],["$","$L2f",null,{"title":"pirfenidone: Research & Clinical Takeaways","description":"Explore research on pirfenidone (generic) — efficacy, safety, and comparative data.","papers":[{"doi":"10.1136/rmdopen-2026-006943","pmid":"42508943","title":"Characteristics and outcomes of anti-Ku antibody–associated interstitial lung disease: a retrospective study of 60 patients","journal_title":"RMD Open","journal_issn":"2056-5933","published_at":"2026-07-27T00:00:00.000Z","url":"https://doi.org/10.1136/rmdopen-2026-006943","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:18:05.680Z","updated_at":"2026-08-04T18:18:05.680Z","tags":[{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"condition","value":"Idiopathic Inflammatory Myopathy","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"condition","value":"Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"condition","value":"Pulmonary Fibrosis","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"condition","value":"Sjögren's Disease","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"condition","value":"Systemic Lupus Erythematosus","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"condition","value":"Systemic Sclerosis","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"generic","value":"azathioprine","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"generic","value":"methotrexate","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"generic","value":"mycophenolate mofetil","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"modality","value":"Antifibrotic Agent","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"modality","value":"Immunosuppressive Therapy","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"sample_size","value":"n=154","value_numeric":154},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"warning","value":"The ILD progression rate of 75% likely overestimates what would be found under strict 12-month ATS/ERS/JRS/ALAT criteria (only 6 patients met that stricter definition); direct comparison with other ILD cohorts using the standard definition should be made cautiously.","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"warning","value":"The parent cohort included a paediatric department (Hôpital Necker), but the reported median age of 56 years and ILD cohort demographics suggest predominant adult inclusion; age-group tagging reflects this, though a small number of younger patients may be included.","value_numeric":null},{"paper_doi":"10.1136/rmdopen-2026-006943","tag_type":"warning","value":"The study predates routine use of antifibrotic agents—only 3 patients received them—so conclusions about antifibrotic efficacy in this population cannot be drawn.","value_numeric":null}],"summaries":{"what_studied":"This retrospective, multicentre cohort study across 10 French university hospitals (2010–2025) described the characteristics and outcomes of ILD in 60 anti-Ku antibody–positive patients with systemic autoimmune diseases (from a parent cohort of 154), with a median follow-up of 6 years.","key_result":"ILD occurred in 39% (60/154) of anti-Ku–positive patients; 75% (45/60) progressed over a median of 4 years. Male sex was independently associated with faster progression (aHR 2.7; 95% CI 1.4–5.2). Baseline pulmonary fibrosis (present in 57%) independently predicted death (aHR 6.5; 95% CI 1.5–28.2). Inaugural ILD also worsened overall survival (aHR 3.1; 95% CI 1.3–7.3). The most common CT pattern was fibrotic NSIP (27%).","limitations":"- Retrospective design with non-uniform follow-up intervals; progression criteria were applied over the entire observation period rather than within the standard 12-month window, likely inflating the progressor rate compared to studies using strict ATS/ERS/JRS/ALAT criteria.\n- Not all anti-Ku–positive patients (17%) underwent chest CT, risking underestimation of true ILD prevalence.\n- Treatment heterogeneity and lack of longitudinal treatment-timing data precluded reliable adjustment for therapy as a time-dependent covariate.","practice_takeaway":"Screen every anti-Ku–positive patient for ILD at diagnosis and monitor regularly with PFTs and chest CT, as ILD is present in ~40% and progresses in ~75%. Male sex and baseline pulmonary fibrosis flag higher-risk patients who may benefit from earlier consideration of antifibrotic therapy."}},{"doi":"10.1183/16000617.0076-2026","pmid":"42419778","title":"Fibrotic chronic eosinophilic pneumonia: from inflammation to fibrosis and therapeutic implications","journal_title":"European Respiratory Review","journal_issn":"0905-9180","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1183/16000617.0076-2026","source_score":12,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:19.771Z","updated_at":"2026-07-14T13:24:19.771Z","tags":[{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"brand","value":"Fasenra","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"brand","value":"Nucala","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"condition","value":"Chronic Eosinophilic Pneumonia","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"condition","value":"Fibrotic Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"condition","value":"Hypereosinophilic Syndrome","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"benralizumab","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"mepolizumab","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"nerandomilast","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"reslizumab","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Antifibrotic Agent","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Anti-IL-5 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Anti-IL-5Rα Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"PDE-4B Inhibitor","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"No sample_size tag was assigned for the review overall, as it synthesises data across heterogeneous sources with varying N; the Mayo Clinic cohort (n=62) is the largest single cited dataset.","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"Pirfenidone has been associated with rare cases of eosinophilic pneumonia, a specific safety concern flagged for diseases already driven by eosinophilic inflammation.","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"The paper includes two congress abstracts (not peer-reviewed publications) as key clinical evidence for antifibrotic use in eosinophilic fibrotic lung disease — findings from these should be interpreted with extra caution.","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"The study design is a narrative review with no formal quality assessment or meta-analysis; conclusions on therapeutic efficacy are based on extrapolation and expert opinion.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluated the evidence for anti-IL-5/IL-5Rα monoclonal antibodies (mepolizumab, benralizumab, reslizumab) as glucocorticoid-sparing agents in chronic eosinophilic pneumonia (CEP), examined the emerging fibrotic CEP phenotype, and explored mechanistic links between eosinophilic inflammation and pulmonary fibrosis. It also assessed the potential role of antifibrotic agents (nintedanib, pirfenidone, nerandomilast) in progressive fibrotic CEP.","key_result":"A Mayo Clinic retrospective cohort (n=62) found fibrotic changes in 37% of CEP patients, with ~78% of fibrosis cases appearing within 2 years of diagnosis; 70% had non-UIP patterns. Anti-IL-5/IL-5Rα biologicals consistently reduced relapses and enabled glucocorticoid tapering in case series (largest n=10), but no study has specifically evaluated these agents in established fibrotic CEP. Only one published case of fibrotic CEP treated with mepolizumab showed disease stabilisation rather than fibrosis regression.","limitations":"- All evidence for anti-IL-5/IL-5Rα use in CEP comes from case reports and small series (max n=10 in a single study, 63 total reported cases in a 2024 scoping review), with likely publication bias toward positive outcomes.\n- No prospective or randomised trials exist for any therapy specifically in fibrotic CEP; antifibrotic trial data (INBUILD, FIBRONEER-ILD) included at most one CEP patient.\n- Mechanistic evidence linking eosinophils to lung fibrosis is largely from in vitro models and inference from asthma/IPF; direct causal evidence in human eosinophilic ILD is lacking.","practice_takeaway":"CEP should not be considered fully reversible — screen patients with worsening symptoms, declining lung function, or persistent HRCT changes for a fibrotic phenotype. In relapsing or glucocorticoid-dependent CEP, anti-IL-5/IL-5Rα biologicals are a reasonable steroid-sparing option; if progressive fibrosis develops, nintedanib may be added, though evidence remains limited to case reports."}},{"doi":"10.1038/s41584-026-01394-2","pmid":"42315602","title":"Lung disease in rheumatoid arthritis","journal_title":"Nature Reviews Rheumatology","journal_issn":"1759-4790","published_at":"2026-06-18T00:00:00.000Z","url":"https://doi.org/10.1038/s41584-026-01394-2","source_score":9,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-20T13:24:51.988Z","updated_at":"2026-06-20T13:24:51.988Z","tags":[{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"condition","value":"Bronchiectasis","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"condition","value":"Bronchiolitis","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"condition","value":"Chronic Obstructive Pulmonary Disease","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"condition","value":"Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"condition","value":"Lung Cancer","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"condition","value":"Rheumatoid Arthritis","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"generic","value":"baricitinib","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"generic","value":"brensocatib","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"generic","value":"methotrexate","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"generic","value":"tocilizumab","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"modality","value":"Antifibrotic","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"modality","value":"DPP-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"modality","value":"Immunosuppressant","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"warning","value":"Full text of the article was not accessible; summary and tags are derived from the abstract, key points, glossary, and reference list only — specific prevalence figures, hazard ratios, and detailed management algorithms could not be verified.","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"warning","value":"Study design is classified as 'Narrative Review' rather than 'Systematic Review' based on the absence of reported search methodology or PRISMA-style data synthesis.","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01394-2","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the review's synthesis of evolving screening and antifibrotic treatment recommendations, not a single landmark trial result.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluates the full spectrum of pulmonary manifestations in rheumatoid arthritis (RA), including ILD, COPD, bronchiectasis, bronchiolitis, pleural disease, and lung cancer, with a focus on pathophysiology, screening strategies, and management approaches.","key_result":"RA-ILD (especially usual interstitial pneumonia pattern) carries the worst prognosis among RA lung manifestations. Key risk factors for RA-ILD include male sex, older age, ACPA seropositivity, smoking, and high disease activity. Evidence-based treatments remain limited, but antifibrotics (nintedanib, pirfenidone) can be considered for progressive fibrotic phenotypes. COPD and bronchiectasis significantly raise infection risk and mortality in RA and are underrecognized.","limitations":"- Full text was not accessible; summary is based on the abstract, key points, and reference list only, limiting depth of evidence appraisal.\n- As a narrative review, it does not perform systematic pooled analysis, so estimates of effect size or prevalence are not consistently reported.\n- Evidence-based treatment recommendations for RA-ILD remain sparse, reflecting the limited RCT data in this population.","practice_takeaway":"Screen RA patients for ILD using HRCT when risk factors (male sex, older age, ACPA positivity, smoking, high disease activity) are present. For progressive fibrosing RA-ILD, consider antifibrotics (nintedanib or pirfenidone) alongside a multidisciplinary approach that includes smoking cessation, vaccinations, and pulmonary rehabilitation."}},{"doi":"10.1183/13993003.01557-2025","pmid":"42276742","title":"Progressive pulmonary fibrosis: a state-of-the-art review","journal_title":"European Respiratory Journal","journal_issn":"0903-1936","published_at":"2026-06-11T00:00:00.000Z","url":"https://doi.org/10.1183/13993003.01557-2025","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-23T13:25:18.949Z","updated_at":"2026-06-23T13:25:18.949Z","tags":[{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"brand","value":"Ofev","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"condition","value":"Fibrosing Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"condition","value":"Idiopathic Pulmonary Fibrosis","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"condition","value":"Progressive Pulmonary Fibrosis","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"generic","value":"nerandomilast","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"modality","value":"Antifibrotic Agent","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"modality","value":"Phosphodiesterase 4B Inhibitor","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"Nerandomilast is described as reducing disease progression in a 2025 trial but is not yet guideline-endorsed; regulatory approval status is not specified in the abstract.","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"Sample sizes of the individual trials referenced are not provided in the abstract.","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"Sex of the studied populations is not reported in the abstract, so a sex tag was omitted.","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"This is a narrative review; conclusions about treatment efficacy are drawn from summarized trial data rather than a pooled meta-analysis — individual trial effect sizes should be checked in primary sources.","value_numeric":null}],"summaries":{"what_studied":"This state-of-the-art review evaluates the diagnosis, disease course, and emerging treatment landscape of progressive pulmonary fibrosis (PPF) — a progressive fibrosing phenotype seen in non-IPF interstitial lung diseases — covering key trials through 2025.","key_result":"Nintedanib (a tyrosine kinase inhibitor) halved FVC decline over one year in a 2019 phase III trial and holds a conditional guideline recommendation for PPF (2022). In 2025, the PDE4B inhibitor nerandomilast further reduced disease progression in PPF. Smaller trials also suggest a benefit with pirfenidone.","limitations":"This is a narrative review, not a systematic review or meta-analysis, limiting strength of evidence synthesis. Many supporting trials are described as 'smaller,' and most treatments carry only conditional recommendations. The PPF concept itself is still being validated.","practice_takeaway":"Identify PPF early — worsening symptoms, declining FVC, and radiologic progression despite conventional therapy — and initiate antifibrotic therapy (nintedanib is guideline-supported; nerandomilast is emerging) promptly. Refer eligible patients for lung transplant evaluation as part of holistic care."}},{"doi":"10.1038/s41584-026-01386-2","pmid":"42215625","title":"The evolving comorbidity landscape of rheumatoid arthritis","journal_title":"Nature Reviews Rheumatology","journal_issn":"1759-4790","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1038/s41584-026-01386-2","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-03T13:44:29.779Z","updated_at":"2026-06-03T13:44:29.779Z","tags":[{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"condition","value":"Anxiety","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"condition","value":"Depression","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"condition","value":"Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"condition","value":"Malignancy","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"condition","value":"Osteoporosis","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"condition","value":"Rheumatoid Arthritis","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"generic","value":"methotrexate","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"generic","value":"tocilizumab","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"generic","value":"tofacitinib","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"modality","value":"Biologic DMARD","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"modality","value":"Disease-Modifying Antirheumatic Drug","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"modality","value":"Glucocorticoid","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"modality","value":"TNF Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"warning","value":"No sample size tag was applied as this is a review article without a single study population.","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the breadth of updated screening and DMARD-selection guidance synthesized in this review, but individual recommendations should be cross-checked against specific society guidelines cited within.","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01386-2","tag_type":"warning","value":"This is a narrative review — no pooled statistics or meta-analytic effect sizes are provided; clinical estimates cited are drawn from referenced primary studies.","value_numeric":null}],"summaries":{"what_studied":"This narrative review examines the evolving spectrum of comorbidities in rheumatoid arthritis (RA) over the past three decades, covering cardiovascular disease, interstitial lung disease (ILD), malignancy, infection, mental health disorders, osteoporosis, cerebrovascular disease, and dementia, with attention to how DMARD advances and treat-to-target strategies have shifted comorbidity patterns.","key_result":"Incidence of extra-articular manifestations, cardiovascular disease, and overall malignancy in RA is declining, while ILD, anxiety, and depression remain persistently high or are increasing despite therapeutic advances. DMARD choice — including the elevated cardiovascular risk signal with JAK inhibitors (vs. TNF inhibitors in ORAL Surveillance) and the enhanced cervical cancer screening needed for immunosuppressed patients — meaningfully shapes comorbidity risk.","limitations":"- Review covers literature from 2015–2025 only; older epidemiological trends may be underrepresented.\n- Causal relationships between specific DMARDs and comorbidity risk are largely observational; RCTs are limited.\n- The review does not provide pooled effect sizes or patient-level data for most comorbidities.","practice_takeaway":"Screen RA patients more aggressively for ILD, cardiovascular disease, and osteoporosis than the general population — especially those on glucocorticoids or DMARDs — and apply enhanced (more frequent) cervical cancer screening for all immunosuppressed patients. Prioritize treat-to-target strategies, as controlling RA inflammation is the single most important lever for reducing the overall comorbidity burden."}},{"doi":"10.1093/ajrccm/aamag249","pmid":"42155010","title":"Gut microbiota associate with disease severity and survival in idiopathic pulmonary fibrosis","journal_title":"American Journal of Respiratory and Critical Care Medicine","journal_issn":"1073-449X","published_at":"2026-05-19T00:00:00.000Z","url":"https://doi.org/10.1093/ajrccm/aamag249","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-12T13:24:32.159Z","updated_at":"2026-06-12T13:24:32.159Z","tags":[{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"brand","value":"Bactrim","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"condition","value":"Idiopathic Pulmonary Fibrosis","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"generic","value":"trimethoprim-sulfamethoxazole","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"modality","value":"Antibiotic","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"modality","value":"Antifibrotic","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"sample_size","value":"n=411","value_numeric":411},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"study_design","value":"Prospective Cohort Study (Secondary Analysis of RCT)","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"warning","value":"Co-trimoxazole is listed under the brand name 'Bactrim' for recognition; the generic used in the paper is 'co-trimoxazole' (trimethoprim-sulfamethoxazole).","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"warning","value":"Study design tag notes: this is a secondary/post-hoc analysis of an RCT cohort, not a primary RCT — level of evidence reflects the observational/exploratory nature of this analysis.","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag249","tag_type":"warning","value":"This is a post-hoc exploratory analysis of the CleanUP-IPF trial; findings are hypothesis-generating and should not be used to guide clinical decisions without further prospective validation.","value_numeric":null}],"summaries":{"what_studied":"This study examined associations between gut microbiota composition (via 16S rRNA and shotgun metagenomic sequencing of fecal swabs) and disease severity, lung transplant-free survival, and treatment heterogeneity in 411 IPF patients enrolled in the CleanUP-IPF trial.","key_result":"Higher abundance of *Lachnospiraceae* unclassified genus was linked to improved transplant-free survival in patients not on anti-microbials (HR 0.34, 95% CI 0.14–0.87, P=.02), but to worse survival in those receiving co-trimoxazole (HR 6.09, 95% CI 1.36–27.27, P=.02). Gut microbial diversity and composition also correlated significantly with impaired gas exchange (ppDLCO).","limitations":"- Exploratory post-hoc analysis limits causal inference and increases risk of false-positive findings.\n- Fecal swabs (vs. fresh stool) may yield lower-quality microbiome data.\n- Confounders such as PPI use, sex, and age influenced microbiota composition and may not be fully adjusted.","practice_takeaway":"Gut microbiota — particularly *Lachnospiraceae* abundance — may help predict survival and modulate response to co-trimoxazole or pirfenidone in IPF patients. These findings are hypothesis-generating; routine microbiome testing in IPF is not yet supported by this evidence alone."}},{"doi":"10.1155/carj/8812779","pmid":"41522210","title":"Efficacy and Safety of Pirfenidone for Mitigation of Interstitial Lung Abnormalities in COVID‐19 Patients: A Meta‐Analysis","journal_title":"Canadian Respiratory Journal","journal_issn":"1198-2241","published_at":"2026-01-12T00:00:00.000Z","url":"https://doi.org/10.1155/carj/8812779","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-14","doi":"10.1155/carj/8812779","days":"7","issn":"1198-2241","rank":"9","field":"Clinical Medicine","score":"2","category":"Respiratory System","categories":["Respiratory System"],"_categories":["Respiratory System"]},"pubmed":{"doi":"10.1155/carj/8812779","title":"Efficacy and Safety of Pirfenidone for Mitigation of Interstitial Lung Abnormalities in COVID-19 Patients: A Meta-Analysis.","journal":"Canadian respiratory journal","methods":"","results":"Eight studies were included, comprising 335 patients in pirfenidone treatment groups and 302 controls. Risk of bias ranged from low to moderate. Pirfenidone significantly decreased chest high-resolution CT (HRCT) scores during early- and late-stage COVID-19 and significantly improved forced expiratory volume in 1 s, especially in late-stage COVID-19. Pirfenidone treatment was associated with statistically nonsignificant trends toward improved forced vital capacity and decreased all-cause mortality. Furthermore, HRCT scores, pulmonary function, and inflammatory cytokine levels following pirfenidone treatment were superior to those obtained after glucocorticoid therapy. The incidence of gastrointestinal adverse events was higher in the pirfenidone than the control group, but no serious adverse events or fatalities occurred.","abstract":"$30","keywords":["COVID-19","glucocorticoid","interstitial lung abnormalities","pirfenidone"],"pubmed_id":"41522210","conclusions":"Pirfenidone therapy may mitigate ILAs and preserve pulmonary function among survivors of COVID-19 pneumonia. Furthermore, pirfenidone exhibited acceptable safety and tolerability profiles.","publication_date":"2026-01-12T00:00:00"},"crossref":{"DOI":"10.1155/carj/8812779","URL":"https://doi.org/10.1155/carj/8812779","ISSN":["1198-2241","1916-7245"],"link":[{"URL":"https://onlinelibrary.wiley.com/doi/pdf/10.1155/carj/8812779","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"1","score":1,"title":["Efficacy and Safety of Pirfenidone for Mitigation of Interstitial Lung Abnormalities in COVID‐19 Patients: A Meta‐Analysis"],"author":[{"given":"Ziyi","family":"Zhang","sequence":"first","affiliation":[]},{"given":"Xiang","family":"Fang","sequence":"additional","affiliation":[]},{"given":"Jinhui","family":"Gao","sequence":"additional","affiliation":[]},{"given":"Heming","family":"Sun","sequence":"additional","affiliation":[]},{"given":"Ting","family":"Xu","sequence":"additional","affiliation":[]},{"given":"Jiajia","family":"Wang","sequence":"additional","affiliation":[]}],"editor":[{"given":"Hongda","family":"Liu","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/501100014554","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100014554","name":"Hui-Chun Chin and Tsung-Dao Lee Chinese Undergraduate Research Endowment","award":["GSWS202206"],"award-info":[{"award-number":["GSWS202206"]}],"doi-asserted-by":"publisher"},{"id":[{"id":"10.13039/100017413","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/100017413","name":"Innovation 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Respiratory Journal"],"published-print":{"date-parts":[[2026,1]]},"reference-count":36,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,10]]},"references-count":36,"short-container-title":["Canadian Respiratory Journal"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1155/carj/8812779","is_oa":true,"title":"Efficacy and Safety of Pirfenidone for Mitigation of Interstitial Lung Abnormalities in COVID‐19 Patients: A Meta‐Analysis","updated":"2026-01-13T16:36:47+00:00","published_date":"2026-01-01","best_oa_location":{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1155/carj/8812779","pmh_id":null,"url_for_pdf":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1155/carj/8812779","url_for_landing_page":"https://doi.org/10.1155/carj/8812779"}}},"created_at":"2026-01-16T11:56:46.634Z","updated_at":"2026-01-16T11:56:46.634Z","tags":[{"paper_doi":"10.1155/carj/8812779","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"condition","value":"COVID-19","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"condition","value":"Interstitial Lung Abnormalities","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"modality","value":"Antifibrotic","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"sample_size","value":"n=637","value_numeric":637},{"paper_doi":"10.1155/carj/8812779","tag_type":"study_design","value":"Systematic Review and Meta-Analysis","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"warning","value":"Abstract does not provide numerical effect sizes or define early vs late-stage timing.","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"warning","value":"Design mixes randomized and cohort studies, which complicates classification and pooling.","value_numeric":null},{"paper_doi":"10.1155/carj/8812779","tag_type":"warning","value":"Safety outcomes are summarized without event counts; interpret tolerability comparisons cautiously.","value_numeric":null}],"summaries":{"what_studied":"Systematic review and meta-analysis of randomized trials and cohort studies assessing pirfenidone versus control or glucocorticoids to prevent or slow interstitial lung abnormalities in severe COVID-19; searches through July 21, 2025.","key_result":"Across eight studies (pirfenidone n=335; controls n=302), pirfenidone significantly reduced HRCT scores in early and late COVID-19 and improved FEV1 (especially late-stage); FVC and all-cause mortality showed nonsignificant trends toward benefit. Compared with glucocorticoids, pirfenidone yielded better HRCT, pulmonary function, and inflammatory cytokine profiles; gastrointestinal adverse events were more frequent with pirfenidone, with no serious adverse events or deaths reported.","limitations":"Only eight studies with mixed RCT and cohort designs and low-to-moderate risk of bias were included. Numerical effect sizes and timing details were not reported in the abstract, and benefits for FVC and mortality were not statistically significant.","practice_takeaway":"For COVID-19–related interstitial lung abnormalities, pirfenidone improved HRCT scores and FEV1 versus control and glucocorticoids, at the cost of more gastrointestinal side effects and no serious safety signals; effects on FVC and mortality were not significant."}},{"doi":"10.22514/sv.2025.163","pmid":null,"title":"Antifibrotic therapy in patients with acute lung injury: a systematic review and meta-analysis","journal_title":"Signa Vitae","journal_issn":"1334-5605","published_at":"2025-12-08T00:00:00.000Z","url":"https://doi.org/10.22514/sv.2025.163","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-12","doi":"10.22514/sv.2025.163","days":"30","issn":"1334-5605","rank":"4","field":"Clinical Medicine","score":"9","category":"Emergency Medicine","categories":["Emergency Medicine"],"_categories":["Emergency Medicine"]},"pubmed":null,"crossref":{"DOI":"10.22514/sv.2025.163","URL":"https://doi.org/10.22514/sv.2025.163","ISSN":["1334-5605","1845-206X"],"page":"4","type":"journal-article","issue":null,"score":1,"title":["Antifibrotic therapy in patients with acute lung injury: a systematic review and meta-analysis"],"author":[{"given":"Nora Di","family":"Tomasso","sequence":"first","affiliation":[]}],"issued":{"date-parts":[[2025,12,8]]},"member":"26027","prefix":"10.22514","source":"Crossref","volume":null,"created":{"date-time":"2025-10-28T09:15:29Z","timestamp":1761642929000,"date-parts":[[2025,10,28]]},"indexed":{"date-time":"2025-12-09T07:26:49Z","timestamp":1765265209051,"date-parts":[[2025,12,9]]},"subject":[],"abstract":"$32","relation":{},"resource":{"primary":{"URL":"https://www.signavitae.com/articles/10.22514/sv.2025.163"}},"subtitle":[],"deposited":{"date-time":"2025-12-09T07:22:12Z","timestamp":1765264932000,"date-parts":[[2025,12,9]]},"issn-type":[{"type":"print","value":"1334-5605"},{"type":"electronic","value":"1845-206X"}],"published":{"date-parts":[[2025,12,8]]},"publisher":"MRE Press","reference":null,"short-title":[],"content-domain":{"domain":[],"crossmark-restriction":false},"original-title":[],"container-title":["Signa Vitae"],"published-print":{"date-parts":[[2025,12,8]]},"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,12,8]]},"references-count":0,"short-container-title":["SV"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.22514/sv.2025.163","is_oa":true,"title":"Antifibrotic therapy in patients with acute lung injury: a systematic review and meta-analysis","updated":"2025-12-11T01:31:13+00:00","published_date":"2025-10-28","best_oa_location":{"url":"https://doi.org/10.22514/sv.2025.163","pmh_id":null,"url_for_pdf":null,"url_for_landing_page":"https://doi.org/10.22514/sv.2025.163"}}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-11T11:19:33.869Z","tags":[{"paper_doi":"10.22514/sv.2025.163","tag_type":"category","value":"Emergency Medicine","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"condition","value":"Acute Lung Injury","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"condition","value":"COVID-19","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"modality","value":"Antifibrotic","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"sample_size","value":"n=697","value_numeric":697},{"paper_doi":"10.22514/sv.2025.163","tag_type":"study_design","value":"Systematic Review and Meta-analysis","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"All included studies enrolled COVID-19 patients only; applicability to non-COVID ALI/ARDS is unclear.","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"All studies were rated high risk of bias and the GRADE certainty for mortality was low.","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"Designs were mixed (randomized and observational), and one study had imbalance in co-interventions (tocilizumab).","value_numeric":null},{"paper_doi":"10.22514/sv.2025.163","tag_type":"warning","value":"Radiologic and functional outcomes varied across studies and were not meta-analyzed.","value_numeric":null}],"summaries":{"what_studied":"Systematic review and meta-analysis of 6 studies (2 randomized, 2 propensity-matched, 2 case-control; total n=697) of antifibrotic therapy (pirfenidone or nintedanib) versus standard care in acute lung injury, all in COVID-19 patients, with searches through March 17, 2025. The primary outcome was all-cause mortality at the longest follow-up; secondary outcomes included length of stay and radiologic/functional measures.","key_result":"Across 4 studies reporting mortality (n=612), antifibrotics reduced deaths: 48/298 (16.1%) vs 75/314 (23.9%); OR 0.61 (95% CI 0.40–0.93), p=0.02; I2=40%; number needed to treat=13. Length of stay showed no difference (mean difference −0.98 days, 95% CI −7.36 to 5.39; p=0.57; I2=65%); individual studies reported improvements in CT scores, SpO2/FiO2, and spirometry with antifibrotics.","limitations":"All included studies were at high risk of bias, with mixed randomized and observational designs and low certainty of evidence for mortality. The evidence was limited to COVID-19 ALI, reducing generalizability to non-COVID ALI/ARDS. Radiologic and functional outcomes were heterogeneous and not pooled; one study had imbalance in tocilizumab use despite matching.","practice_takeaway":"In COVID-19–related acute lung injury, antifibrotic therapy was associated with lower mortality (NNT 13) but the certainty is low and all studies were high risk of bias; routine use should await well-designed randomized trials. No reduction in length of stay was seen; radiologic and functional improvements were reported only in individual small studies."}}],"initialOffset":8,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"generic","value":"pirfenidone"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Generics","href":"/hub/tag/generic"},{"name":"pirfenidone"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"generic","hub_tag_value":"pirfenidone"}}}]]

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