Is personalised medicine the key to heterogeneity in idiopathic pulmonary fibrosis?
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause, characterised by progressive worsening in lung function and dyspnoea with an associated prognosis similar to or worse than many cancers. As a better understanding emerges around the pathogenesis and mechanisms driving disease pathology, a host of novel agents are being tested both pre-clinically and clinically. However even with this deeper understanding and positive pre-clinical supportive data, negative trial outcomes are frequently reported, highlighting the problems faced in treating such a heterogeneous disease with a varied clinical course. Recently, two therapies that slow disease progression, nintedanib and pirfenidone, have been approved for the treatment of IPF, yet the clinical unmet need is still high for IPF patients given their failure to stop disease progression and their potential side-effect profiles. Efforts are being made to not only understand the underlying pathways and genetics that might influence the clinical course of the disease, but also the non-invasive biomarkers that reflect the activity of specific pathways which in turn may highlight progressive treatment plans for individual patients. The cumulative data may be based on the identification of subgroups of patients via biomarker analysis of ongoing clinical trials, or investigation of cohorts of patients over time to understand the relative role of these mediators in their disease progression. Below we review the ongoing quest for novel therapeutic approaches and highlight, where appropriate attempts have been made to identify patients for which a specific pathway or mediator may be driving disease progression.
MedImmune Ltd, Granta Park, Cambridge CB21 6GH, UK. Electronic address: clarked@medimmune.com.
Deborah L
DL
Clarke
MedImmune Ltd, Granta Park, Cambridge CB21 6GH, UK.
Lynne A
LA
Murray
Service de Pneumologie A, Hôpital Bichat, Inserm U1152, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France.
Bruno
B
Crestani
MedImmune Ltd, Granta Park, Cambridge CB21 6GH, UK.
Matthew A
MA
Sleeman
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D007211:Indoles; D011728:Pyridones; C093844:pirfenidone; C530716:nintedanib
Autoimmunity; Immune dysregulation; Matrix; Mesenchymal cells; TGFβ