Treatment of systemic sclerosis associated fibrotic manifestations: Current options and future directions

Daoussis, Dimitrios; Liossis, S.-N.

doi:10.31138/mjr.30.1.33

Cited by 15 publications

(5 citation statements)

References 31 publications

(29 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Uncontrolled fibrosis can impair organ function to the point of failure and even death (Varga and Abraham, 2007). Current treatments for SSc are limited with variable clinical response (Allanore et al, 2016;Kowal-Bielecka et al, 2017;Varga et al, 2017), and emerging therapeutics target fundamental fibrotic processes associated with SSc (Daoussis and Liossis, 2019). Metalloproteinases and their regulators play pivotal roles in mediating fibrosis, making them attractive therapeutic targets in SSc.…”

Section: Introductionmentioning

confidence: 99%

Distinct Metalloproteinase Expression and Functions in Systemic Sclerosis and Fibrosis: What We Know and the Potential for Intervention

2021

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a chronic debilitating idiopathic disorder, characterized by deposition of excessive extracellular matrix (ECM) proteins such as collagen which leads to fibrosis of the skin and other internal organs. During normal tissue repair and remodeling, the accumulation and turnover of ECM proteins are tightly regulated by the interaction of matrix metalloproteinases (MMPs) and endogenous tissue inhibitors of metalloproteinases (TIMPs). SSc is associated with dysregulation of the activity of these proteolytic and inhibitory proteins within the tissue microenvironment, tipping the balance toward fibrosis. The resultant ECM accumulation further perpetuates tissue stiffness and decreased function, contributing to poor clinical outcomes. Understanding the expression and function of these endogenous enzymes and inhibitors within specific tissues is therefore critical to the development of therapies for SSc. This brief review describes recent advances in our understanding of the functions and mechanisms of ECM remodeling by metalloproteinases and their inhibitors in the skin and lungs affected in SSc. It highlights recent progress on potential candidates for intervention and therapeutic approaches for treating SSc fibrosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Distinct Metalloproteinase Expression and Functions in Systemic Sclerosis and Fibrosis: What We Know and the Potential for Intervention

2021

View full text Add to dashboard Cite

show abstract

“…Recent studies evaluated the FDA-approved tyrosine kinase inhibitor, nintedanib, as well as tocilizumab to address pulmonary function decline with ILD [ 9 , 14 ]. Methotrexate was found to improve skin findings, with little to no effect on other organ manifestations such as ILD [ 15 , 16 ]. Hemopoietic stem-cell transplantation was also studied in severe SSc patients, showing improvement in skin and pulmonary function [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Respiratory Failure in Patients Hospitalized With Systemic Sclerosis: An Analysis of the National Inpatient Sample

Trang¹,

Kambhatla²,

Manadan³

2023

Cureus

View full text Add to dashboard Cite

BackgroundSystemic sclerosis (SSc) patients are at high risk for respiratory failure due to the progression of their disease. Investigating factors predictive of impending respiratory failure in this patient population can be used to improve hospital outcomes. Here, we investigate risk factors associated with developing respiratory failure in patients hospitalized with a diagnosis of SSc in the United States using a large, multi-year, populationbased dataset. MethodologyThis retrospective study was conducted on SSc hospitalizations from 2016 to 2019 with and without a principal diagnosis of respiratory failure from the United States National Inpatient Sample database. A multivariate logistic regression analysis was performed to calculate adjusted odds ratios (OR adj ) for respiratory failure. ResultsThere were 3,930 SSc hospitalizations with a principal diagnosis of respiratory failure and 94,910 SSc hospitalizations without a diagnosis of respiratory failure. Among SSc hospitalizations, multivariable analysis showed that the following were associated with a principal diagnosis of respiratory failure: Charlson comorbidity index (OR adj = 1.05), heart failure (OR adj = 1.81), interstitial lung disease (ILD) (OR adj = 3.62), pneumonia (OR adj = 3.40), pulmonary hypertension (OR adj = 3.59), and smoking (OR adj = 1.42). ConclusionsThis analysis represents the largest sample to date in assessing risk factors for respiratory failure among SSc inpatients. Charlson comorbidity index, heart failure, ILD, pulmonary hypertension, smoking, and pneumonia were associated with higher odds of inpatient respiratory failure. Patients with respiratory failure had higher in-hospital mortality compared to those without it. Outpatient optimization and inpatient recognition of these risk factors can lead to improved hospitalization outcomes for SSc patients.

show abstract

“…As expected, the most common concomitant medications were corticosteroids (prednisolone < 7.5 mg/day) and MMF. Fewer patients were treated with biologic drugs such as tocilizumab, abatacept, and rituximab, as indicated by recent studies [ 51 , 52 , 53 , 54 ]. Data from the SENSCIS trial strongly suggest that the co-administration of immunosuppressive drugs and nintedanib may provide the greatest efficacy in slowing FVC decline in SSc-ILD patients.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Nintedanib in Patients with Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD): A Real-World Single Center Experience

et al. 2023

View full text Add to dashboard Cite

Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. The aim of this study was to assess the effectiveness and safety of nintedanib in CTD-ILD patients in a real-world data setting. A single-center, retrospective, and descriptive analysis of CTD-ILD patients treated with nintedanib from June 2019 to November 2022 was performed. The assessment of nintedanib treatment’s efficacy was judged solely on the evolution of pulmonary function tests (PFTs), which were evaluated before and after treatment. Twenty-one patients (67% females, median age 64 years (IQR = 9) with CTD-ILD (systemic sclerosis n = 9, rheumatoid arthritis n = 5, dermatomyositis n = 4, juvenile rheumatoid arthritis n = 1, undifferentiated CTD n = 1, interstitial pneumonia with autoimmune features n = 1), 18 of whom were on concomitant immunosuppressives, had a median follow-up period of 10 months (IQR = 5). PFTs before and after treatment did not significantly differ. The mean FVC% difference was +0.9 (sd = 7.6) and the mean DLco% difference was +3.4 (sd = 12.6), suggesting numerical improvement of PFTs. The average percentage change was −0.3% and +7.6% for FVC% and DLco%, respectively, indicating stabilization of lung function. Our real-world data across a broad spectrum of CTD-ILD suggest that nintedanib could be beneficial in combination with immunosuppressives in slowing the rate of lung function decline.

show abstract

Treatment of systemic sclerosis associated fibrotic manifestations: Current options and future directions

Cited by 15 publications

References 31 publications

Distinct Metalloproteinase Expression and Functions in Systemic Sclerosis and Fibrosis: What We Know and the Potential for Intervention

Distinct Metalloproteinase Expression and Functions in Systemic Sclerosis and Fibrosis: What We Know and the Potential for Intervention

Risk Factors for Respiratory Failure in Patients Hospitalized With Systemic Sclerosis: An Analysis of the National Inpatient Sample

Efficacy and Safety of Nintedanib in Patients with Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD): A Real-World Single Center Experience

Contact Info

Product

Resources

About