Thomas Barba1, Romain Fort1, Vincent Cottin2, Steeve Provencher3, Isabelle Durieu4, Sabine Jardel5, Arnaud Hot6, Quitterie Reynaud4, Jean-Christophe Lega7. 1. Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite F-69310, France; Univ Lyon, Claude Bernard University Lyon 1, France. 2. National Reference Centre for Rare Pulmonary Diseases, Department of Respiratory Medicine, Louis Pradel Hospital, Hospices Civils de Lyon, OrphaLung, UMR 754, Claude Bernard University Lyon 1, University of Lyon, France. 3. Institut universitaire de cardiologie et de pneumologie de Québec Research Center, Laval University, Quebec City, Canada. 4. Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite F-69310, France; Health Services and Performance Research EA7425, France. 5. Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite F-69310, France; UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, F-69003, France. 6. UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, F-69003, France. 7. Department of Internal and Vascular Medicine, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite F-69310, France; Department of Internal and Vascular Medicine, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon F-69003, France. Electronic address: jean-christophe.lega@chu-lyon.fr.
Abstract
OBJECTIVE: Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD. METHODS: Studies were selected from MEDLINE up to July 2017. Two investigators independently extracted data on study design, patient characteristics, clinical features, treatment, follow-up and outcomes. Global survival rates and objectively confirmed lung function improvements were extracted as the main outcome for rapidly progressive IIM-related ILD (RP-ILD) and chronic forms of ILD (C-ILD), respectively, and pooled using the weighted mean proportion with fixed or random-effects models in case of significant heterogeneity (I2 > 50%). RESULTS: Twenty-seven studies encompassing 553 patients (male: 30.5%, age: 53.5 ± 5.5 years) were included in the meta-analysis. Globally, retrieved studies were of limited methodological quality (no controlled studies and only 2 prospective studies). Dermatomyositis (40%) and anti-tRNA synthetase syndrome (45%) were the most represented IIM subtypes. In C-ILD, functional improvement rates were 89.2% (95%CI 82.5-93.6; 7 studies, n = 124) for corticosteroids alone, 80.7% (95%CI 49.6-94; 6 studies, n = 38) for cyclosporine A, 64.1% (95%CI 46.3-78.7; 4 studies, n = 32) for azathioprine, 86.2% (95%CI 61.5-96; 2 studies, n = 23) for tacrolimus, 56.4% (95%CI 44-68.0; 8 studies, n = 71) for cyclophosphamide, and 76.6% (95%CI 50.4-96.0; 2 studies, n = 20) for rituximab. In RP-ILD, survival rates at 3 months were 51.7% (95%CI 24.2-78.1; 2 studies, n = 11) for corticosteroids alone, 69.2% (95%CI 55.0-80.5; 8 studies, n = 146) for cyclosporine A and 72.4% (95%CI 6.4-99.0, 2 studies, n = 16) for cyclophosphamide. CONCLUSION: Despite aggressive immunosuppressive therapies, the short-term mortality of RP-ILD remains high. While immunosuppressive therapies are associated with significant functional improvements in most patients with C-ILD, substantial uncertainty remains about the best treatment strategy in the absence of good quality evidence.
OBJECTIVE:Interstitial lung disease (ILD) is the most severe complication of idiopathic inflammatory myositis (IIM), resulting in significant increase in morbidity and mortality and for which the best treatment remains controversial. We conducted a meta-analysis to evaluate the efficacy of therapies used for the management of IIM-related ILD. METHODS: Studies were selected from MEDLINE up to July 2017. Two investigators independently extracted data on study design, patient characteristics, clinical features, treatment, follow-up and outcomes. Global survival rates and objectively confirmed lung function improvements were extracted as the main outcome for rapidly progressive IIM-related ILD (RP-ILD) and chronic forms of ILD (C-ILD), respectively, and pooled using the weighted mean proportion with fixed or random-effects models in case of significant heterogeneity (I2 > 50%). RESULTS: Twenty-seven studies encompassing 553 patients (male: 30.5%, age: 53.5 ± 5.5 years) were included in the meta-analysis. Globally, retrieved studies were of limited methodological quality (no controlled studies and only 2 prospective studies). Dermatomyositis (40%) and anti-tRNA synthetase syndrome (45%) were the most represented IIM subtypes. In C-ILD, functional improvement rates were 89.2% (95%CI 82.5-93.6; 7 studies, n = 124) for corticosteroids alone, 80.7% (95%CI 49.6-94; 6 studies, n = 38) for cyclosporine A, 64.1% (95%CI 46.3-78.7; 4 studies, n = 32) for azathioprine, 86.2% (95%CI 61.5-96; 2 studies, n = 23) for tacrolimus, 56.4% (95%CI 44-68.0; 8 studies, n = 71) for cyclophosphamide, and 76.6% (95%CI 50.4-96.0; 2 studies, n = 20) for rituximab. In RP-ILD, survival rates at 3 months were 51.7% (95%CI 24.2-78.1; 2 studies, n = 11) for corticosteroids alone, 69.2% (95%CI 55.0-80.5; 8 studies, n = 146) for cyclosporine A and 72.4% (95%CI 6.4-99.0, 2 studies, n = 16) for cyclophosphamide. CONCLUSION: Despite aggressive immunosuppressive therapies, the short-term mortality of RP-ILD remains high. While immunosuppressive therapies are associated with significant functional improvements in most patients with C-ILD, substantial uncertainty remains about the best treatment strategy in the absence of good quality evidence.