Initial predictors for short-term prognosis in anti-melanoma differentiation-associated protein-5 positive patients

Yang, Qihua; Li, Tianfang; Zhang, Xin; Lyu, Kunlong; Wu, Shuisheng; Chen, Yan; Liu, Shengyun; Yu, Zujiang

doi:10.21203/rs.3.rs-40977/v2

Cited by 6 publications

(13 citation statements)

References 23 publications

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“…Previous reports shows the correlation of high-level serum ferritin and KL-6 with poor prognosis in anti-MDA5-DM (2,4), whereas no signi cant difference was detected in our study. Bivariate correlation analysis reveals a close correlation of ferritin with LDH and albumin.…”

Section: Discussioncontrasting

confidence: 95%

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Efficacy and safety of a triple combination of glucocorticoids, tofacitinib and calcineurin inhibitors in anti-MDA5 positive dermatomyositis

Liu

Zhang

Guan

et al. 2022

Preprint

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Objectives. To explore the risk factors of early death in dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 (anti-MDA5) antibody (anti-MDA5-DM). To determine the optimal initial treatment regimen for patients with anti-MDA5-DM.Methods. Patients with newly onset anti-MDA5-DM from June 2018 to October 2021 in our center were retrospectively reviewed for 6 months. Patients were divided into five groups based on initial treatments. The major outcome was mortality in 6 months. Secondary outcomes included changing therapy, low-dose-glucocorticoid maintenance, remission and severe infection.Results. A total of 214 patients were included in the study. Five patients (2.34%) were lost to follow-up during 6 months, 63 patients (30.14%) died, 52 patients (24.88%) experienced serious infection, 112 patients (53.59%) achieved remission, and 86 patients (41.15%) were maintained with low-dose glucocorticoids. Age over 50 years, skin ulcer, lactate dehydrogenase (LDH) > 350 U/L, C reactive protein (CRP) > 5mg/L, anti-Ro52 antibody, higher ground-glass opacity (GGO) score, and pulse glucocorticoid at baseline were independent risk factors of mortality in the first 6 months of disease courses. Conversely, arthritis and prophylactic use of compound sulfamethoxazole (SMZ Co) were independent protective factors. Patients initially treated with a triple combination of high-dose glucocorticoid (GC), tofacitinib and high-dose calcineurin inhibitors (CNIs) had the lowest risk of mortality within 6 months, and were more likely to achieve remission under the maintenance of low-dose-glucocorticoids.Conclusion. A triple combination of high-dose GC, tofacitinib and high-dose CNIs is an effective and safe treatment regimen for newly onset anti-MDA5-DM.

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Section: Discussioncontrasting

confidence: 95%

“…Interstitial lung disease (ILD) is a major cause of death in patients with DM. When rapidly progressive ILD (RPILD) occurs, the mortality rate is signi cantly increased (1)(2)(3)(4)(5). Although not completely understood, data suggest that the pathogenesis of ILD in anti-MDA5-DM may be different from other types of DM(6).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of a triple combination of glucocorticoids, tofacitinib and calcineurin inhibitors in anti-MDA5 positive dermatomyositis

Liu

Zhang

Guan

et al. 2022

Preprint

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“…Interestingly, another case-control research reported that an elevated serum KL-6 was with negative correlation with FVC% and forced expiratory volume in the first second (FEV1%) (r = −0.93, r = −0.91, respectively) (12). On the other hand, a recent study reported the HRCT ground-glass opacity (GGO) score ≥4 (HR 4.8; 95% CI, 1.3-17.9), KL-6 >1,600 U/ml (HR 3.7; 95% CI, 1.5-9.1) were identified as independent predictors for progressive ILD (48). To some extent, the elevated KL-6 concentrations may have consistency with the progressive lesion of HRCT under the inflammatory storm.…”

Section: Discussionmentioning

confidence: 99%

“…(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).…”

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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

et al. 2021

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ObjectInterstitial lung disease (ILD) is a specific form of chronic fibrosing interstitial pneumonia with various etiology. The severity and progression of ILD usually predict the poor outcomes of ILD. Otherwise, Krebs von den Lungen-6 (KL-6) is a potential immunological biomarker reflecting the severity and progression of ILD. This meta-analysis is to clarify the predictive value of elevated KL-6 levels in ILD.MethodEBSCO, PubMed, and Cochrane were systematically searched for articles exploring the prognosis of ILD published between January 1980 and April 2021. The Weighted Mean Difference (WMD) and 95% Confidence Interval (CI) were computed as the effect sizes for comparisons between groups. For the relationship between adverse outcome and elevated KL-6 concentration, Hazard Ratio (HR), and its 95%CI were used to estimate the risk factor of ILD.ResultOur result showed that ILD patients in severe and progressive groups had higher KL-6 levels, and the KL-6 level of patients in the severe ILD was 703.41 (U/ml) than in mild ILD. The KL-6 level in progressive ILD group was 325.98 (U/ml) higher than that in the non-progressive ILD group. Secondly, the KL-6 level of patients in acute exacerbation (AE) of ILD was 545.44 (U/ml) higher than stable ILD. Lastly, the higher KL-6 level in ILD patients predicted poor outcomes. The KL-6 level in death of ILD was 383.53 (U/ml) higher than in survivors of ILD. The pooled HR (95%CI) about elevated KL-6 level predicting the mortality of ILD was 2.05 (1.50–2.78), and the HR (95%CI) for progression of ILD was 1.98 (1.07–3.67).ConclusionThe elevated KL-6 level indicated more severe, more progressive, and predicted the higher mortality and poor outcomes of ILD.

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Roles of biomarkers in anti‐MDA5‐positive dermatomyositis, associated interstitial lung disease, and rapidly progressive interstitial lung disease

Liu

Cheng

et al. 2022

Clinical Laboratory Analysis

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Background: Anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (MDA5 + DM) is significantly associated with interstitial lung disease (ILD), especially rapidly progressive ILD (RPILD) due to poor prognosis, resulting in high mortality rates. However, the pathogenic mechanism of MDA5 + DM-RPILD is unclear. Although some MDA5 + DM patients have a chronic course of ILD, many do not develop RPILD. Therefore, the related biomarkers for the early diagnosis, disease activity monitoring, and prediction of the outcome of RPILD in MDA5 + DM patients should be identified. Blood-based biomarkers are minimally invasive and can be easily detected. Methods:Recent relative studies related to blood biomarkers in PubMed were reviewed.Results: An increasing number of studies have demonstrated that dysregulated expression of blood biomarkers related to ILD such as ferritin, Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D), and cytokines, and some tumor markers in MDA5 + DM may provide information in disease presence, activity, treatment response, and prognosis. These studies have highlighted the great potentials of blood biomarker values for MDA5 + DM-ILD and MDA5 + DM-RPILD. This review provides an overview of recent studies related to blood biomarkers, besides highlighted protein biomarkers, including antibody (anti-MDA5 IgG subclasses and anti-Ro52 antibody), genetic (exosomal microRNAs and neutrophil extracellular traps related to cell-free DNA), and immune cellular biomarkers in MDA5 + DM, MDA5 + DM-ILD, and MDA5 + DM-RPILD patients, hopefully elucidating the pathogenesis of MDA5 + DM-ILD and providing information on the early diagnosis, disease activity monitoring, and prediction of the outcome of the ILD, especially RPILD. Conclusions: Therefore, this review may provide insight to guide treatment decisions for MDA5 + DM-RPILD patients and improve outcomes.

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Initial predictors for short-term prognosis in anti-melanoma differentiation-associated protein-5 positive patients

Cited by 6 publications

References 23 publications

Efficacy and safety of a triple combination of glucocorticoids, tofacitinib and calcineurin inhibitors in anti-MDA5 positive dermatomyositis

Efficacy and safety of a triple combination of glucocorticoids, tofacitinib and calcineurin inhibitors in anti-MDA5 positive dermatomyositis

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

Roles of biomarkers in anti‐MDA5‐positive dermatomyositis, associated interstitial lung disease, and rapidly progressive interstitial lung disease

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