A Systematic Review and Metaanalysis of Predictors of Mortality in Idiopathic Inflammatory Myopathy–Associated Interstitial Lung Disease

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Objective Idiopathic inflammatory myopathy (IIM)–associated interstitial lung disease (ILD) can range from rapidly progressive disease with high mortality to indolent disease with minimal morbidity. This systematic review and metaanalysis describe immunological, clinical, and radiographical predictors of mortality in IIM-ILD. Methods MEDLINE and Embase database searches were completed on October 18, 2021, to identify articles providing survival data according to baseline characteristics in patients with concurrent IIM and ILD. Prognostic factors common to more than 5 papers were included in the metaanalysis using a random-effects model to report odds ratios (ORs) for binary variables and Hedgesgfor continuous variables. Risk of bias was assessed using the Newcastle-Ottawa Scale score and the Egger test for publication bias. Results From 4433 articles, 62 papers were suitable for inclusion; among these studies, 38 different variables were considered. The OR for risk of death regarding the presence of anti–melanoma differentiation–associated protein 5 (MDA5) antibodies was 6.20 (95% CI 3.58-10.71), and anti–tRNA synthetase antibodies were found to be protective (OR 0.24, 95% CI 0.14-0.41). Neither antinuclear antibodies, anti–52-kDa Ro antigen antibodies, nor SSA significantly altered mortality, nor was MDA5 titer predictive. Examples of prognostic factors that are significantly associated with mortality in this study include the following: age; male sex; acute/subacute onset; clinically amyopathic dermatomyositis; dyspnea; ulceration; fever; raised C-reactive protein, ferritin, lactate dehydrogenase, alveolar to arterial O2(A-aO2) gradient, groundglass opacity on high-resolution computed tomography (HRCT), and overall HRCT score; and reduced albumin, lymphocytes, ratio of partial pressure of oxygen in the arterial blood to fraction of inspired oxygen (PF ratio), percentage predicted transfer factor for carbon monoxide, and percentage predicted forced vital capacity. Baseline surfactant protein-D and Krebs von den Lungen-6 levels were not predictors of mortality. Conclusion Many mortality risk factors were identified, though heterogeneity was high, with a low quality of evidence and a risk of publication bias. Studies regarding anti-MDA5 antibody–positive disease and and those from East Asia predominate, which could mask risk factors relevant to other IIM subgroups or populations.

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