Antifibrotic drugs in connective tissue disease-related interstitial lung disease (CTD-ILD): from mechanistic insights to therapeutic applications

Erre, Gian Luca; Sebastiani, Marco; Manfredi, Andreina; Gerratana, Elisabetta; Atzeni, Fabiola; Passiu, Giuseppe; Mangoni, Arduino A.

doi:10.7573/dic.2020-8-6

Cited by 8 publications

(8 citation statements)

References 98 publications

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“…CTD-ILD with the PF-ILD phenotype and SSc-ILD patients who still exhibit disease progression after being treated with MMF or CYC may benefit from the addition of nintedanib to standard treatment ( 212 , 240 , 241 ). Although a pilot study has shown that administration of pirfenidone was associated with a reduction in dyspnea and an increase in vital capacity in SSc-ILD ( 242 ), other studies have not demonstrated a significant effect of pirfenidone ( 243 ), and therefore, the evidence for pirfenidone in these groups is less convincing ( 244 ). Other treatments include IVIG, plasmapheresis ( 245 ), and anti-reflux drugs.…”

Section: Assessment and Treatment Of Ctd-ildmentioning

confidence: 99%

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

et al. 2021

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Connective tissue disease (CTD) related interstitial lung disease (CTD-ILD) is one of the leading causes of morbidity and mortality of CTD. Clinically, CTD-ILD is highly heterogenous and involves rheumatic immunity and multiple manifestations of respiratory complications affecting the airways, vessels, lung parenchyma, pleura, and respiratory muscles. The major pathological features of CTD are chronic inflammation of blood vessels and connective tissues, which can affect any organ leading to multi-system damage. The human lung is particularly vulnerable to such damage because anatomically it is abundant with collagen and blood vessels. The complex etiology of CTD-ILD includes genetic risks, epigenetic changes, and dysregulated immunity, which interact leading to disease under various ill-defined environmental triggers. CTD-ILD exhibits a broad spectra of clinical manifestations: from asymptomatic to severe dyspnea; from single-organ respiratory system involvement to multi-organ involvement. The disease course is also featured by remissions and relapses. It can range from stability or slow progression over several years to rapid deterioration. It can also present clinically as highly progressive from the initial onset of disease. Currently, the diagnosis of CTD-ILD is primarily based on distinct pathology subtype(s), imaging, as well as related CTD and autoantibodies profiles. Meticulous comprehensive clinical and laboratory assessment to improve the diagnostic process and management strategies are much needed. In this review, we focus on examining the pathogenesis of CTD-ILD with respect to genetics, environmental factors, and immunological factors. We also discuss the current state of knowledge and elaborate on the clinical characteristics of CTD-ILD, distinct pathohistological subtypes, imaging features, and related autoantibodies. Furthermore, we comment on the identification of high-risk patients and address how to stratify patients for precision medicine management approaches.

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Section: Assessment and Treatment Of Ctd-ildmentioning

confidence: 99%

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

et al. 2021

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“…There are other antifibrotic drugs, including pirfenidone. Evidence of the efficacy of pirfenidone in CTD‐ILD is not equally compelling 13 . Pamrevlumab, a recombinant human antibody that binds to connective tissue growth factor, is a potential therapy for IPF 14 .…”

Section: Discussionmentioning

confidence: 99%

“…Evidence of the efficacy of pirfenidone in CTD-ILD is not equally compelling. 13 Pamrevlumab, a recombinant human antibody that binds to connective tissue growth factor, is a potential therapy for IPF. 14 Respiratory rehabilitation is also helpful for severe ILD patients.…”

Section: Other Treatmentsmentioning

confidence: 99%

Assessing prognostic factors correlating with response to nintedanib for connective tissue disease‐associated interstitial lung disease: A real‐world single‐center study

et al. 2023

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Objective For patients with connective tissue disease‐associated interstitial lung disease (CTD‐ILD), early medical intervention would be desirable. This study analyzed the real‐world, single‐center use of nintedanib for CTD‐ILD patients. Methods Patients with CTD who received nintedanib from January 2020 to July 2022 were enrolled. Medical records review and stratified analyses of the collected data were conducted. Results Reduction in the percentage of predicted forced vital capacity (%FVC) was seen in the elderly group (>70 years; P = .210), males (P = .027), the late group who started nintedanib >80 months after confirmation of an ILD disease activity (P = .03), the severe %DLco (diffusing capacity for carbon monoxide as a percentage of predicted) group (<40%; P = .20), the group who had extensive pulmonary fibrosis at the beginning of nintedanib (pulmonary fibrosis score >35%), and the low‐dose group (nintedanib 50‐100 mg/d; P = .40). %FVC did not decrease by >5% in the young group (<55 years), the early group who started nintedanib within 10 months after confirmation of an ILD disease activity, and the group whose pulmonary fibrosis score at the beginning of nintedanib was <35%. Conclusion It is important to diagnose ILD early and start antifibrotic drugs with proper timing for cases in need. It is better to start nintedanib early, especially for patients at risk (>70 years old, male, <40% DLco, and >35% areas of pulmonary fibrosis).

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“…CTD-ILD has been recognized as an emerging organ involvement with a high burden in terms of mortality and associated morbidity, with an average lifespan of almost less than five years [ 39 ], not only amongst individuals with SSc but also across the whole spectrum of systemic diseases, especially rheumatoid arthritis and dermatomyositis. Subsequently the introduction of novel licensed therapies targeting fibrotic processes is of major interest to both patients and physicians dealing with this population.…”

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

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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.

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Antifibrotic drugs in connective tissue disease-related interstitial lung disease (CTD-ILD): from mechanistic insights to therapeutic applications

Cited by 8 publications

References 98 publications

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

Interstitial Lung Disease in Connective Tissue Disease: A Common Lesion With Heterogeneous Mechanisms and Treatment Considerations

Assessing prognostic factors correlating with response to nintedanib for connective tissue disease‐associated interstitial lung disease: A real‐world single‐center study

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

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