TY - JOUR
TI - Mechanisms of progressive fibrosis in connective tissue disease (CTD)-associated interstitial lung diseases (ILDs)
AU - Spagnolo, P.
AU - Distler, O.
AU - Ryerson, C.J.
AU - Tzouvelekis, A.
AU - Lee, J.S.
AU - Bonella, F.
AU - Bouros, D.
AU - Hoffmann-Vold, A.-M.
AU - Crestani, B.
AU - Matteson, E.L.
JO - Annals of the Rheumatic Diseases
PY - 2021
VL - 80
TODO - 2
SP - 143-150
PB - BMJ Publishing Group
SN - 0003-4967, 1468-2060
TODO - 10.1136/annrheumdis-2020-217230
TODO - cyclophosphamide;  dyskerin;  imatinib;  mycophenolate mofetil;  nintedanib;  pirfenidone;  placebo;  telomerase reverse transcriptase;  tocilizumab, chronic myeloid leukemia;  connective tissue disease;  disease association;  disease course;  DKC1 gene;  drug efficacy;  drug safety;  fibrosing alveolitis;  gene;  gene mutation;  genetic analysis;  human;  interstitial lung disease;  NAF1 gene;  PARN gene;  phase 2 clinical trial (topic);  phase 3 clinical trial (topic);  phenotype;  population structure;  priority journal;  Review;  rheumatoid arthritis;  RTEL1 gene;  systemic sclerosis;  TERC gene;  TERT gene;  TINF2 gene;  complication;  connective tissue disease;  disease exacerbation;  fibrosis;  interstitial lung disease;  lung;  lung fibrosis;  pathology, Connective Tissue Diseases;  Disease Progression;  Fibrosis;  Humans;  Lung;  Lung Diseases, Interstitial;  Phenotype;  Pulmonary Fibrosis
TODO - Interstitial lung diseases (ILDs), which can arise from a broad spectrum of distinct aetiologies, can manifest as a pulmonary complication of an underlying autoimmune and connective tissue disease (CTD-ILD), such as rheumatoid arthritis-ILD and systemic sclerosis (SSc-ILD). Patients with clinically distinct ILDs, whether CTD-related or not, can exhibit a pattern of common clinical disease behaviour (declining lung function, worsening respiratory symptoms and higher mortality), attributable to progressive fibrosis in the lungs. In recent years, the tyrosine kinase inhibitor nintedanib has demonstrated efficacy and safety in idiopathic pulmonary fibrosis (IPF), SSc-ILD and a broad range of other fibrosing ILDs with a progressive phenotype, including those associated with CTDs. Data from phase II studies also suggest that pirfenidone, which has a different -yet largely unknown -mechanism of action, may also have activity in other fibrosing ILDs with a progressive phenotype, in addition to its known efficacy in IPF. Collectively, these studies add weight to the hypothesis that, irrespective of the original clinical diagnosis of ILD, a progressive fibrosing phenotype may arise from common, underlying pathophysiological mechanisms of fibrosis involving pathways associated with the targets of nintedanib and, potentially, pirfenidone. However, despite the early proof of concept provided by these clinical studies, very little is known about the mechanistic commonalities and differences between ILDs with a progressive phenotype. In this review, we explore the biological and genetic mechanisms that drive fibrosis, and identify the missing evidence needed to provide the rationale for further studies that use the progressive phenotype as a target population. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
ER -