scholarly journals Role of antifibrotics in the management of idiopathic inflammatory myopathy associated interstitial lung disease

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110609
Author(s):  
Erin M. Wilfong ◽  
Rohit Aggarwal
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
The United States ◽  
Inflammatory Myopathies ◽  
Mortality And Morbidity ◽  
Randomized Controlled ◽  
Fda Approval

The antifibrotic therapies nintedanib and pirfenidone were first approved by the United States for the treatment of idiopathic pulmonary fibrosis in 2014. In 2020, nintedanib received U.S. Food and Drug Administration (FDA) approval for the treatment of all progressive fibrosing interstitial lung disease (ILD). Given that a major cause of mortality and morbidity in the idiopathic inflammatory myopathies (IIM) is progressive interstitial lung disease and respiratory failure, antifibrotic therapies may be useful as adjuvant to traditional immunosuppression. However, randomized controlled trials of antifibrotic therapies in IIM are lacking. The purpose of this review is to (1) summarize the mechanism of action of nintedanib and pirfenidone in ILD with possible role in IIM-ILD, (2) review the clinical data supporting their use in interstitial lung disease in general, and more specifically in connective tissue disease associated ILD, and (3) discuss the evidence and remaining challenges for using antifibrotic therapies in IIM-ILD.

SAT0288 CHARACTERIZATION OF ANTI-AMINOACYL TRNA SYNTHETASE AUTOANTIBODIES IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1088.1-1089
Author(s):  
C. Preger ◽  
A. Notarnicola ◽  
C. Hellström ◽  
E. Wigren ◽  
C. Cerqueira ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Clinical Manifestations ◽  
Trna Synthetase ◽  
University Hospital ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Research Support ◽  
Mortality And Morbidity

Background:Idiopathic inflammatory myopathies (IIM) are rare chronic inflammatory diseases associated with high mortality and morbidity [1]. One sub-group of IIM, anti-synthetase syndrome (ASS), is characterized by the presence of autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS), together with specific clinical manifestations such as myositis, interstitial lung disease (ILD), arthritis, mechanic’s hand, Raynaud’s syndrome and fever [2]. The most common anti-aaRS autoantibody, anti-Jo1 targeting histidyl tRNA synthetase (HisRS), is present in up to 20-30% of patients with IIM, and up to 90% of patients with myositis and ILD [3, 4]. Besides Jo1, there are today seven other identified autoantigens within the aaRS family.Objectives:A large part of patients with IIM, including individuals with clinical manifestations indicating ASS, test seronegative to all known myositis specific autoantibodies. However, these patients could potentially harbor autoantibodies against targets not tested for in clinic. In this study, we aimed at extending the detection of autoantibodies by including all cytoplasmic aaRS in the analysis of patients with IIM. We hypothesized the existence of new potential autoantigens within this protein family.Methods:The presence of anti-aaRS autoantibodies was determined using a multiplex suspension bead array assay on 242 IIM patients from the Karolinska University Hospital myositis cohort. A panel of 186 recombinant constructs, representing 57 proteins that included full-length or partial sequence overlaps between constructs of all cytoplasmic aaRS as well as other myositis related proteins, were coupled to magnetic color-coded beads and each plasma sample was tested against the complete antigen panel.Results:By the use of this multiplex method we identified patients with autoantibodies against many of the tested aaRS. Autoantibodies binding to HisRS have previously been shown to bind with higher reactivity to the WHEP domain of HisRS and this was also confirmed in this study. We confirmed reactivity against three of the other aaRS tested for in the clinic (PL-12, PL-7, and EJ). In addition, we identified patients positive for anti-Zo, -KS and -HA, autoantibodies usually not screened for in routine. Finally, our data indicates that there are autoantibodies binding to other aaRS than the previously known eight autoantigens, which will be presented.Conclusion:In this study, we could detect autoantibodies in plasma from patients with IIM, both against the most common aaRS autoantigens, but also against other aaRS that are usually not tested for in clinic. We conclude that it is important to continue the studies of anti-aaRS autoantibodies, and their correlation to clinical manifestations, and in the long run also include more aaRS autoantigens in clinical practice.References:[1]Dobloug, G.C., et al., Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study. Ann Rheum Dis, 2018. 77(1): p. 40-47.[2]Barsotti, S. and I.E. Lundberg, Myositis an evolving spectrum of disease. Immunol Med, 2018. 41(2): p. 46-54.[3]Vencovsky, J., H. Alexanderson, and I.E. Lundberg, Idiopathic Inflammatory Myopathies. Rheum Dis Clin North Am, 2019. 45(4): p. 569-581.[4]Richards, T.J., et al., Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum, 2009. 60(7): p. 2183-92.Disclosure of Interests:Charlotta Preger: None declared, Antonella Notarnicola: None declared, Cecilia Hellström: None declared, Edvard Wigren: None declared, Catia Cerqueira: None declared, Peter Nilsson: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Helena Persson: None declared, Susanne Gräslund: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,

scholarly journals Series of clinical cases of patients with idiopathic inflammatory myopathy and interstitial lung disease from the registry of idiopathic inflammatory myopathies of the Argentine Society of Rheumatology

2020 ◽  
pp. 12-17
Author(s):  
Y.M. Ponce ◽  
M.M. Zalazar ◽  
A.D. García Coello ◽  
O.L. Rillo
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Clinical Manifestations ◽  
Idiopathic Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Disease Prognosis ◽  
Immune Mediated ◽  
Necrotizing Myositis

Idiopathic Inflammatory Myopathies (MII) are a heterogeneous group of diseases characterized by muscle weakness and inflammation underlying muscle biopsy. The main organs affected are muscle, skin and the lung can also be affected. They are distinguished within clinical subtypes such as Polymyositis (PM), Dermatomyositis (DM), DM with the variant Clinically Amiopathic Dermatomyositis (DMCA), the Syndrome Antisynthetase (SAS), Immune-mediated Necrotizing Myositis, Body Myositis Inclusion (MCI) and Neoplasia-Associated Myositis. The presence of certain specific and associated antibodies predisposes to the development of clinical manifestations, determining the disease prognosis. 4 patients from the Registry of MII of the Argentine Society of Rheumatology (SAR) are presented with these characteristics: one patient with PM and anti Jo-1 positive and three patients with DM (one with DMCA and anti-RO 52 and two patients with anti-PL7 and anti-TI-F1γ respectively).

scholarly journals The lungs were on fire: a pilot study of 18F-FDG PET/CT in idiopathic-inflammatory-myopathy-related interstitial lung disease

2021 ◽  
Author(s):  
Junyu Liang ◽  
Heng Cao ◽  
Yinuo Liu ◽  
Bingjue Ye ◽  
Yiduo Sun ◽  
...  
Keyword(s):  
Lymph Node ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Ct Scan ◽  
Mediastinal Lymph Node ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Pet Ct ◽  
Bilateral Lung ◽  
Pet Ct Scan

Abstract Background: Interstitial lung disease (ILD) and its rapid progression (RP) were main contributors to unfavorable outcome of idiopathic inflammatory myopathy (IIM) patients. This study aimed at identifying the clinical value of PET/CT scan in IIM-ILD patients as well as constructing a predicting model for RP-ILD.Methods: Adult IIM-ILD patients who were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine (FAHZJU) from Jannuary 1st 2017 to December 31st 2020 were reviewed. PET/CT scan as well as other factors of patients who met the inclusion and exclusion criteria were collected and analyzed.Results: A total of 61 IIM-ILD patients were finally enrolled into this study. Twenty-one patients (34.4%) developed RP-ILD and 24 patients (39.3%) died in follow-up. After false discovery rate (FDR) correction, percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P=0.014), bilateral lung mean standard uptake value (SUVmean, P=0.014) and abnormal mediastinal lymph node (P=0.045) were significantly different in comparison between RP-ILD and non-RP-ILD groups. A “DLM” model was hereby established by including the above three values to predict RP-ILD with a cutoff value of ≥2 and an area under the curve (AUC) of 0.905. Higher bilateral lung SUVmean (P=0.019) and spleen SUVmean (P=0.011) were observed in IIM-ILD patients who died within three months, and a moderate correlation was recognized between the two values. Conclusions: Elevated bilateral lung SUVmean and abnormal mediastinal lymph node were associated with RP-ILD in IIM-ILD patients. The “DLM” model was valuable in predicting RP-ILD and demanded further evaluation.

scholarly journals Risk factors associated with Pneumocystis jirovecii pneumonia in juvenile myositis in North America

Rheumatology ◽  
2020 ◽  
Author(s):  
Sara E Sabbagh ◽  
Jessica Neely ◽  
Albert Chow ◽  
Marietta DeGuzman ◽  
Jamie Lai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Immunosuppressive Therapy ◽  
Inflammatory Myopathy ◽  
Severe Infection ◽  
Idiopathic Inflammatory Myopathy ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
The Usa

Abstract Objectives Pneumocystis jirovecii pneumonia (PJP) is associated with significant morbidity and mortality in adult myositis patients; however, there are few studies examining PJP in juvenile myositis [juvenile idiopathic inflammatory myopathy (JIIM)]. The purpose of this study was to determine the risk factors and clinical phenotypes associated with PJP in JIIM. Methods An research electronic data capture (REDCap) questionnaire regarding myositis features, disease course, medications and PJP infection characteristics was completed by treating physicians for 13 JIIM patients who developed PJP (PJP+) from the USA and Canada. Myositis features and medications were compared with 147 JIIM patients without PJP (PJP–) from similar geographic regions who enrolled in National Institutes of Health natural history studies. Results PJP+ patients were more often of Asian ancestry than PJP– patients [odds ratio (OR) 8.7; 95% CI 1.3, 57.9]. Anti- melanoma differentiation associated protein 5 (MDA5) autoantibodies (OR 12.5; 95% CI 3.0, 52.4), digital infarcts (OR 43.8; 95% CI 4.2, 460.2), skin ulcerations (OR 12.0; 95% CI 3.5, 41.2) and interstitial lung disease (OR 10.6; 95% CI 2.1, 53.9) were more frequent in PJP+ patients. Before PJP diagnosis, patients more frequently received pulse steroids, rituximab and more immunosuppressive therapy compared with PJP– patients. Seven PJP+ patients were admitted to the intensive care unit and four patients died due to PJP or its complications. Conclusions PJP is a severe infection in JIIM that can be associated with mortality. Having PJP was associated with more immunosuppressive therapy, anti-MDA5 autoantibodies, Asian race and certain clinical features, including digital infarcts, cutaneous ulcerations and interstitial lung disease. Prophylaxis for PJP should be considered in juvenile myositis patients with these features.

Prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease: a retrospective study of 679 adult cases

Rheumatology ◽  
2020 ◽  
Author(s):  
Shan Li ◽  
Yuxin Sun ◽  
Chi Shao ◽  
Hui Huang ◽  
Qian Wang ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Retrospective Study ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Mortality Rates ◽  
Trna Synthetase ◽  
Significant Difference ◽  
All Cause Mortality

Abstract Objectives Few studies have investigated the prognostic factors for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) across different clinical/serological phenotypes. Methods We conducted a retrospective analysis of patients diagnosed with IIM between January 2012 and December 2017. Results Of the 760 IIM cases registered, 679 adult cases were included in this study. ILD was present in 508 cases, and the presence of ILD in the clinically amyopathic DM, DM and PM groups was 92.7, 73.6 and 55.1%, respectively (P < 0.01). The prevalence of ILD in the anti-synthetase antibody (ASA)+-IIM group was higher than that in ASA–-IIM group (95.2 vs 72.4%, P < 0.01); no such difference was found between the anti-histidyl-tRNA synthetase (Jo-1)+-IIM and Jo-1–ASA+-IIM groups (93.0 vs 98.5%, P > 0.05). The prevalence of ILD in the melanoma differentiation-associated protein-5 (MDA-5)+-IIM group was higher than that in MDA-5–-IIM group (97.8 vs 72.1%, P < 0.01). Among adults with IIM, men with concurrent ILD, who were older than 50 years, were most likely to die. No significant difference was found in the all-cause mortality rates between DM-ILD and clinically amyopathic DM-ILD groups (33.3 vs 23%, P > 0.05), although both were higher than that in PM group (13.2%, P = 0.01 and P < 0.05, respectively). No difference was found in the all-cause mortality rates between MDA5–ASA–-IM-ILD and MDA5–ASA+-IM-ILD groups (17.2 vs 12.8%, P > 0.05), and both were lower than that in MDA5+ASA–-IM-ILD group (33.7%, P < 0.05). Conclusion The prevalence of ILD in IIM and the prognosis of IIM-ILD patients may vary depending on the statuses of the ASA and MDA-5 antibodies.

scholarly journals Anti-MDA5 juvenile idiopathic inflammatory myopathy: a specific subgroup defined by differentially enhanced interferon-α signalling

Rheumatology ◽  
2019 ◽  
Vol 59 (8) ◽  
pp. 1927-1937 ◽  
Author(s):  
Isabelle Melki ◽  
Hervé Devilliers ◽  
Cyril Gitiaux ◽  
Vincent Bondet ◽  
Darragh Duffy ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Interferon Α ◽  
Type I ◽  
Group 2 ◽  
Skin Ulcerations ◽  
Overlap Myositis ◽  
Group 1

Abstract Objectives JDM and juvenile overlap myositis represent heterogeneous subtypes of juvenile idiopathic inflammatory myopathy (JIIM). Chronic evolution can occur in up to 60% of cases, and morbidity/mortality is substantial. We aimed to describe the clinical, biological, histological and type I IFN status in JIIM associated with anti-melanoma differentiation-associated protein 5 (anti-MDA5) autoantibodies at presentation (group 1) in comparison with other JIIM (group 2). Methods This was a retrospective and prospective study of patients with JIIM ascertained from three French paediatric rheumatology reference centres between 2013 and 2019. Muscle biopsies were reviewed. Type I interferon pathway activity was assessed by dosage of IFNα serum protein and the expression of IFN-stimulated genes. Results Sixty-four patients were included, 13 in group 1 (54% JDM and 46% juvenile overlap myositis) and 51 in group 2 (76% JDM and 24% juvenile overlap myositis). Group 1 patients demonstrated more arthritis, skin ulcerations, lupus features and interstitial lung disease, and a milder muscular involvement. Serum IFNα levels were higher in group 1 than 2, and decreased after treatment or improvement in both groups. Outcome was similar in both groups. Unconventional treatment (more than two lines) was required in order to achieve remission, especially when skin ulceration was reported. Conclusion This study indicates a higher frequency of arthritis, skin ulcerations and interstitial lung disease, but milder muscular involvement, in JIIM with positive anti-MDA5 autoantibodies compared with other JIIM. Our data support an important role of systemic IFNα in disease pathology, particularly in the anti-MDA5 auto-antibody-positive subgroup. In severe and refractory forms of JIIM, IFNα may represent a therapeutic target.

Mortality factors in idiopathic inflammatory myopathy: focusing on malignancy and interstitial lung disease

2013 ◽  
Vol 23 (3) ◽  
pp. 503-508 ◽  
Author(s):  
Jin-Hyun Woo ◽  
Yun Jung Kim ◽  
Jin Ju Kim ◽  
Chan-Bum Choi ◽  
Yoon-Kyoung Sung ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Mortality Factors

scholarly journals Cyclophosphamide Versus Obinutuzumab for the Treatment of Anti-MDA5 Positive Inflammatory Myopathy with Interstitial Lung Disease: A Study Protocol and Literature Review

2019 ◽  
Vol 19 (02) ◽  
pp. 53-58
Author(s):  
Ho So ◽  
Chi Chiu Mok
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Primary Outcome ◽  
Treatment Guidelines ◽  
Controlled Trial ◽  
Treatment Options ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
High Dose ◽  
Multicenter Randomized Controlled Trial

In patients with idiopathic inflammatory myopathy, the presence of the melanoma differentiation-associated gene 5 (MDA5) antibody carries an extremely poor prognosis as a result of the associated interstitial lung disease (ILD) that is often rapidly progressive and refractory to therapies. Management of anti-MDA5 associated ILD is a challenging task as there is a paucity of clinical data and treatment guidelines in the literature. We hereby describe a proposed protocol for a multicenter randomized controlled trial to compare the efficacy of intravenous cyclophosphamide and obinutuzumab in combination with high-dose glucocorticoids and tacrolimus in terms of mortality at six months (primary outcome). The epidemiology, pathogenesis and treatment options of anti-MDA5 associated ILD are briefly reviewed.

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