Risk Prediction Modeling Based on a Combination of Initial Serum Biomarker Levels in Polymyositis/Dermatomyositis–Associated Interstitial Lung Disease

Abstract

and the Multicenter Retrospective Cohort of Japanese Patients with Myositis-Associated ILD (JAMI) Investigators Objective. To establish predictive models for mortality in patients with polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD) using a combination of initial serum biomarker levels. Methods. The Multicenter Retrospective Cohort of Japanese Patients with Myositis-Associated ILD (JAMI) database of 497 incident cases of PM/DM-ILD was used as a derivation cohort, and 111 cases were additionally collected as a validation cohort. Risk factors predictive of all-cause mortality were identified by univariate and multivariable Cox regression analyses using candidate serum biomarkers as explanatory variables. The predictive models for mortality were generated in patients with and those without anti-melanoma differentiation-associated gene 5 (MDA-5) antibody, using a combination of risk factors. Cumulative survival rates were assessed using Kaplan-Meier analysis, and were compared between subgroups using the Breslow test. Results. In the derivation cohort, C-reactive protein (CRP) and Krebs von den Lungen 6 (KL-6) levels were identified as independent risk factors for mortality in both anti-MDA-5-positive and anti-MDA-5-negative patients. We then developed a prediction model based on anti-MDA-5 antibody status, CRP level, and KL-6 level, termed the "MCK model," to identify patients at low (<15%), moderate (15-50%), or high (≥50%) risk of mortality, based on the number of risk factors. The MCK model successfully differentiated cumulative survival rates in anti-MDA-5-positive patients (P < 0.01 for low versus moderate risk and P = 0.03 for moderate versus high risk) and in anti-MDA-5-negative patients (P < 0.001 for low versus moderate risk). The utility of the MCK model was replicated in the validation cohort. Conclusion. Our findings indicate that an evidence-based risk prediction model using CRP and KL-6 levels combined with anti-MDA-5 antibody status might be useful for predicting prognosis in patients with PM/DM-ILD.

KL-6 as an Immunological Biomarker Predicts the Severity, Progression, Acute Exacerbation, and Poor Outcomes of Interstitial Lung Disease: A Systematic Review and Meta-Analysis

“…(AE-ILD: n = 112, Stable ILD: n = 298). Additionally, adjusted HR (95%CI) of estimating the mortality about ILD were collected from 10 studies ( 13 , 15 , 21 , 24 , 26 , 37 , 40 , 42 , 48 , 50 ), and also adjusted HR (95%CI) of estimating progression of ILD were collected from five studies ( 17 , 21 , 28 , 40 , 44 ).…”

Successful Treatment of Anti-MDA5 Antibody-Positive Dermatomyositis-Associated Rapidly Progressive-Interstitial Lung Disease by Plasma Exchange: Two Case Reports

“…In addition to these factors, the age, titer of anti-MDA5 antibody, C-reactive protein levels, and KL-6 levels have also been reported to be possible factors to predict the prognosis in patients with anti-MDA5 antibody-positive DM-associated RP-ILD. 16 , 17 By using these variables, the starting criteria of PE may be defined.…”

Low Circulating Monocytes Is in Parallel With Lymphopenia Which Predicts Poor Outcome in Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis-Associated Interstitial Lung Disease

“…As a rare but unique subtype of DM without fully understood pathogenesis and limited treatment choice, the mortality within 6 months due to RPILD remains high. Although multiple prognostic factors have been reported in different cohorts, including C-reactive protein (CRP) ( 2 ), Krebs von den Lungen-6 (KL-6) ( 3 , 4 ), serum ferritin (SF) ( 5 , 6 ), lactate dehydrogenase (LDH) ( 6 ), CD4+ CXCR4+ T cells ( 7 ), baseline forced vital capacity (FVC) ( 8 ), and radiographic features ( 9 ), some of the predictors are not universally accessible. Thus, simple but robust prognostic biomarkers are still in need in practice.…”