Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis

Kurasawa, Kazuhiro; Arai, Satoko; Namiki, Y; Tanaka, Ayae; Takamura, Yuta; Owada, Takayoshi; Arima, Masafumi; Maezawa, Reika

doi:10.1093/rheumatology/key188

Cited by 237 publications

(171 citation statements)

References 12 publications

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“…Our study has revealed a high prevalence of ILD inanti-MDA5 positive patients, consistentwith previous studies in Europeans and Japanese [2,20]. The short-term mortality rate of anti-MDA5 positive patients was especially high within the rst 6-12 months [5,9,13]. Based on these ndings, we set to analyze the rst six months living situation and identify the predictive factors for death in anti-MDA5 positive patients.…”

Section: Discussionsupporting

confidence: 89%

“…Of note, in the studycontaining all types of myositis, anti-MDA5 has such a strong association with poor prognosis, that it dominates the analysis and makes other potential poor prognostic factors even tendto be a protective factor [11]. While in the subgroup of anti-MDA5 positive patients, the reported risk factors varied in different reports, possibly due to small sample size [5,9,13].…”

Section: Risk Factors Predicting Poor Prognosis Have Been Establishedmentioning

confidence: 97%

“…Since then, a lot of studies have veri edthe association between anti-MDA5 and CADM [2,3]. Accumulating evidences have demonstrated that patients with anti-MDA5 often have a high mortality rate caused byrapidly progressive interstitial lung disease (RP-ILD) [2][3][4][5][6]. While immunosuppressive treatment has improved the outcome of anti-MDA5 positive patients [7,8], therestill were patients failing to respond and dying of respiratory failure shortly after the diagnosis was established.…”

Section: Introductionmentioning

confidence: 99%

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Initial Predictors for Short-termprognosisin Anti-melanoma Differentiation-associated Protein-5 Positive Patients

Yang

Zhang

et al. 2020

Preprint

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Background: Anti-melanoma differentiation-associated protein-5 (anti-MDA5) positive patients are characterized by the high mortality rate caused by interstitial lung disease (ILD). We conducted a retrospective study to summarize the clinical features and identify the initial predictors for death in anti-MDA5 positive patients.Methods:We designed a retrospective cohort of anti-MDA5 positive patients.The demographic and clinical data recorded on first admission, as well as the outcomes during the first six months follow-up were collected. Risk factors for death were identified using multivariate analyses.Results: A total of 90 anti-MDA5 positive patients were included in this study. Eighty-one (90%) patients presentedILD on admission and 35(38.9%) patients developed rapidly progressive ILD (RP-ILD) subsequently.During the first six months of follow-up, 22 (24.4%) patients died of respiratory failure at an average time of 6.6 ± 5.9 weeks.Univariate analysis identified several factors associated with death, including demographic, clinical, laboratory and image variables. Multivariate analysis showed that total CT GGO score≥4(HR 4.8, 95%CI 1.3-17.9,P=0.020), KL-6>1600U/ml (HR3.7, 95%CI 1.5-9.1, P=0.004) and CRP>5.8mg/L (HR3.7, 95%CI 1.0-12.8, P=0.044) were poor prognostic risk factors, however initial combined treatment(HR 0.3, 95%CI 0.1-0.8, P=0.019) predicted good prognosis in anti-MDA5 positive patients.Conclusion: Anti-MDA5 positive patients demonstrated a high prevalence of ILD on admission, leading to a high short-term mortality rate. Higher total GGO score, higher levels of initial KL-6 and CRP predict poor outcome in anti-MDA5 positive patients. However, in tial intensive treatment may improve the prognosis.

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Section: Discussionsupporting

confidence: 89%

Section: Risk Factors Predicting Poor Prognosis Have Been Establishedmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Initial Predictors for Short-termprognosisin Anti-melanoma Differentiation-associated Protein-5 Positive Patients

Yang

Zhang

et al. 2020

Preprint

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“…On the faith of a small case series of four patients, basiliximab, a monoclonal antibody targeting CD25+ activated T cells, could improve patients' survival (105). Similarly, JAK-inhibitors (in this case tofacitinib), which blocks interferon pathways and other proinflammatory cytokine pathways, has shown a promising survival rate improvement (17,106).…”

Section: Biologicsmentioning

confidence: 99%

Inflammatory Myopathy-Related Interstitial Lung Disease: From Pathophysiology to Treatment

Hervier

Uzunhan

2020

Front. Med.

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Inflammatory myopathies (IM) are auto-immune connective tissue diseases characterized by muscle involvement and by extramuscular manifestations. As such, pulmonary manifestations, which mainly include interstitial lung disease (ILD), often darken two out of four distinct IM, namely dermatomyositis and overlapping myositis. Being the initiation site of the disease and being the leading cause of morbidity and mortality, ILD is of major importance in this context. ILD has a heterogeneous expression among the patients, with various onset mode, various radiological pattern, various severity and finally with different prognoses, which are particularly difficult to predict at the time of IM diagnosis. Therefore, ILD is a challenging issue. Treatments are based on steroids and immunosuppressive or targeted therapies. Their respective place is yet poorly codified however and remains often based on clinician expertise. Dedicated clinical trials are lacking to date and are also difficult to build, due to difficulty of constituting large and homogeneous patient groups and to rigorously evaluate disease outcomes. Indeed, pulmonary function tests alone are being regularly defeated in IM, in which respiratory muscles are often involved. Composite scores, bringing together several lung parameters, should thus be developed and validated in the future, to better assess the disease response to treatment. This review aims to describe the current knowledge of IM immuno-pathogenesis, the clinical features associated with IM related-ILD, focusing of both severity and prognosis, and the actual therapeutic approaches.

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“…Of note, in the study containing all types of myositis, anti-MDA5 has such a strong association with poor prognosis, that it dominates the analysis and makes other potential poor prognostic factors even tend to be a protective factor [11]. While in the subgroup of anti-MDA5 positive patients, the reported risk factors varied in different reports, possibly due to small sample size [5,9,13].…”

Section: Risk Factors Predicting Poor Prognosis Have Been Establishedmentioning

confidence: 97%

Initial Predictors for Short-Term Prognosis in Anti-Melanoma Differentiation-Associated Protein-5 Positive Patients

Yang

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Anti-melanoma differentiation-associated protein-5 (anti-MDA5) positive patients are characterized by the high mortality rate caused by interstitial lung disease (ILD). We conducted a retrospective study to summarize the clinical features and identify the initial predictors for death in anti-MDA5 positive patients.Methods: We designed a retrospective cohort of anti-MDA5 positive patients. The demographic and clinical data recorded on first admission, as well as the outcomes during the first six months follow-up, were collected. Predictors of rapidly progressive ILD (RPILD) and poor outcomes were calculated using logistic regression models and Cox proportional hazard regression models, respectively.Results: A total of 90 anti-MDA5 positive patients were included in this study. Eighty-one (90%) patients presented ILD on admission and 35 (38.9%) patients developed RPILD subsequently. During the first six months of follow-up, 22 (24.4%) patients died of respiratory failure at an average time of 6.6 ± 5.9 weeks. Factors including disease duration < 2 months (OR 6.1, 95% CI 1.7-22.4, P = 0.007), serum ferritin ≥ 1500 ng/ml (OR 12.3, 95% CI 3.1-49.6, P <0.001), CRP≥13mg/L (OR 4.6, 95% CI 1.3-16.9, P = 0.021) and total GGO score≥4 (OR 6.3, 95% CI 1.8-21.9, P = 0.003), were identified as independent predictors for RPILD. Cox regression model showed that total CT GGO score ≥ 4 (HR 4.8, 95% CI 1.3-17.9, P = 0.020), KL-6 > 1600 U/ml (HR 3.7, 95% CI 1.5-9.1, P = 0.004) and CRP > 5.8 mg/L (HR 3.7, 95% CI 1.0-12.8, P = 0.044) were poor prognostic risk factors, however initial combined treatment (HR 0.3, 95% CI 0.1-0.8, P = 0.019) predicted good prognosis in anti-MDA5 positive patients.Conclusion: Anti-MDA5 positive patients demonstrated a high prevalence of ILD on admission, leading to a high short-term mortality rate. Higher total GGO score, higher levels of initial KL-6 and CRP predict poor outcome in anti-MDA5 positive patients. However, initial intensive treatment may improve the prognosis.

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Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis

Abstract: Combination therapy with TOF might have the potential to control refractory anti-MDA5 Ab+ DM-ILD.

Cited by 237 publications

References 12 publications

Initial Predictors for Short-termprognosisin Anti-melanoma Differentiation-associated Protein-5 Positive Patients

Initial Predictors for Short-termprognosisin Anti-melanoma Differentiation-associated Protein-5 Positive Patients

Inflammatory Myopathy-Related Interstitial Lung Disease: From Pathophysiology to Treatment

Initial Predictors for Short-Term Prognosis in Anti-Melanoma Differentiation-Associated Protein-5 Positive Patients

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