scholarly journals Real-world Experience of Nintedanib Therapy in Idiopathic-inflammatory-myopathy-related Interstitial Lung Disease: Efficacy and Tolerability

2020 ◽  
Author(s):  
Junyu Liang ◽  
Heng Cao ◽  
Yang Yang ◽  
Yini Ke ◽  
Chuanyin Sun ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Interstitial Lung Disease ◽  
Propensity Score ◽  
Disease Activity ◽  
Lung Disease ◽  
Real World ◽  
Dosage Reduction ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Therapy Discontinuation

Abstract Background Interstitial lung disease (ILD) is a common and frequently fatal extra-muscular complication in patients with idiopathic inflammatory myopathy (IIM), and is refractory to the conventional immunosuppressive medications. Nintedanib has previously been proven to be effective and tolerable in idiopathic pulmonary fibrosis, systemic-sclerosis-related ILD, etc. However, the efficacy and safety of nintedanib in idiopathic-inflammatory-myopathy-related ILD (IIM-ILD) remain unknown. The purpose of this study was to initially explore the efficacy and tolerability of nintedanib in IIM-ILD patients. Methods A real-world analysis was conducted to explore the efficacy and tolerability of nintedanib in IIM-ILD patients who regularly received outpatient visit or hospitalization from January 2018 to October 2019 in one medical center. The primary end point was occurrence of rapid progression of interstitial lung disease (RP-ILD) in the follow-up. And time to death from any cause, complication of pulmonary infection and difference in immunosuppressive regimen were taken as secondary end points in this study. Adverse events were descriptively recorded. Results 22 patients receiving nintedanib therapy and 82 patients under conventional medications were included. After propensity score matching, the primary comparison revealed that better survival (P = 0.036) and prominently less RP-ILD (P = 0.031) in patients with nintedanib therapy. Logistic regression analysis identified that disease activity (P = 0.032), anti-PM-Scl75 antibody (P = 0.027) and nintedanib therapy (P = 0.023, OR value = 0.063) were significantly correlated with RP-ILD. Cox proportional hazards regression analysis demonstrated that disease activity (P = 0.007), anti-MDA5 antibody (P = 0.004) and nintedanib therapy (P = 0.027, HR value = 0.190) were significantly associated with survival of IIM-ILD patients. Similar results can also be seen in analyses before propensity score matching. In the 22 patients with nintedanib therapy, diarrhea was the most common adverse event (54.5%) and hepatic insufficiency contributed to most dosage reduction (50%) or therapy discontinuation (50%). Conclusion Nintedanib therapy might reduce incidence of RP-ILD and improve survival in IIM-ILD patients. Anti-PM-Scl75 and anti-MDA5 antibodies could predict RP-ILD and survival respectively. In addition to the most frequent diarrhea, hepatic insufficiency was closely related to dosage reduction or therapy discontinuation. Trial registration: ISRCTN.com, ISRCTN 10507540. Retrospectively registered.

scholarly journals Efficacy and Tolerability of Nintedanib in Idiopathic-Inflammatory-Myopathy-Related Interstitial Lung Disease: A Pilot Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Junyu Liang ◽  
Heng Cao ◽  
Yang Yang ◽  
Yini Ke ◽  
Ye Yu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Interstitial Lung Disease ◽  
Propensity Score ◽  
Lung Disease ◽  
Propensity Score Matching ◽  
Dosage Reduction ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Regression Analyses ◽  
Therapy Discontinuation

Objectives: To initially clarify the efficacy and tolerability of nintedanib in patients with idiopathic-inflammatory-myopathy-related interstitial lung disease (IIM-ILD).Methods: A retrospective, real-world analysis was conducted in IIM-ILD patients who regularly received outpatient visit or hospitalization from January 2018 to March 2020 in three centers. And the patients were divided into two groups depending on presence or absence of nintedanib therapy. Comparisons, Kaplan-Meier survival analysis and propensity score matching were made to identify difference in time to death from any cause, incidence of rapidly progressive interstitial lung disease (RP-ILD) and comorbidity of pulmonary infection between the two groups. The following logistic regression analyses and Cox proportional-hazard regression analyses were used to verify the therapeutic value of nintedanib as well as clinical significance of other factors. Adverse events were descriptively recorded.Results: Thirty-six patients receiving nintedanib therapy and 115 patients without use of nintedanib were included. Before and after propensity score matching, the primary comparisons revealed better survival (P = 0.015, P = 0016, respectively) and lower incidence of RP-ILD (P = 0.017, P = 0.014, respectively) in patients with nintedanib therapy. Logistic regression analysis identified that disease activity (P < 0.001), percent-predicted diffusing capacity of the lung for carbon monoxide (DLCO%, P = 0.036), nintedanib therapy (P = 0.004, OR value = 0.072) and amyopathic dermatomyositis (ADM, P = 0.012) were significantly correlated with RP-ILD. Cox proportional hazards regression analysis suggested that disease activity (P < 0.001), anti-MDA5 antibody (P < 0.001) and nintedanib therapy (P = 0.013, HR value=0.268) were significantly associated with survival of IIM-ILD patients. Similar results can also be seen in analyses after propensity score matching. In the 36 patients with nintedanib therapy, diarrhea was the most common adverse event (44.4%) and hepatic insufficiency contributed to most dosage reduction (44.4% of nine patients) or therapy discontinuation (60.0% of five patients).Conclusions: Nintedanib was found to reduce incidence of RP-ILD and improve survival in IIM-ILD patients in a real-world setting. Anti-MDA5 antibody could be taken as a risk factor for unfavorable outcome. ADM was significantly correlated with occurrence of RP-ILD. In addition to the most frequent diarrhea, hepatic insufficiency was closely related to dosage reduction or therapy discontinuation.

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.

scholarly journals Coexistence of Axial Spondyloarthritis and Idiopathic Inflammatory Myopathy

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Yongpeng Ge ◽  
Linrong He
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Skin Rash ◽  
Axial Spondyloarthritis ◽  
Age Of Onset ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Hla B27 ◽  
Laboratory Features ◽  
Friendship Hospital

Both axial spondyloarthritis (axSpA) and idiopathic inflammatory myopathy (IIM) are infrequent, and their coexistence is even rarer; there are a few reported cases in the literature. The aim of this study was to assess their association and clinical and laboratory features in our patients. The clinical data of patients with axSpA and IIM diagnosed in China-Japan Friendship Hospital from July 2015 to February 2019 were retrospectively analyzed. This study included 7 patients with axSpA who met the IIM criteria, including 3 males and 4 females. The age of onset was 16 to 39 years. Four patients were HLA-B27 positive, and three were negative. All patients were first diagnosed as axSpA, and then IIM was detected after 0.5–20 years (mean ± SD, 9.9 ± 5.0 years). After being diagnosed to have axSpA and IIM, those patients were given prednisone and immunosuppressant drugs, and their symptoms gradually improved. Our study provides further evidence of the coexistence of IIM with axSpA. In patients with axSpA who have skin rash, interstitial lung disease (ILD), myalgia, or muscle weakness, we should suspect that they may have IIM.

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