Toby M Maher

• MB MSc PhD
• Medical Professional at Imperial College London

Introduction The pathophysiology of respiratory complications in post-acute sequelae of SARS CoV-2 infection (PASC) is poorly understood but a high incidence of progressive pulmonary fibrosis was anticipated. Deupirfenidone (LYT-100) is a selectively deuterated form of pirfenidone which retains antifibrotic and anti-inflammatory activity but with i...

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disease frequently complicated by gastro-oesophageal reflux disease. Although several observational studies and a pilot study have investigated the role of proton pump inhibitors (PPIs) in IPF, their efficacy is unknown and there is much debate in international...

Background Idiopathic pulmonary fibrosis (IPF) is a rare, incurable lung disease with a median survival of 3-5 years after diagnosis. Treatment options are limited. Genetic association studies can identify new genes involved in disease that might represent potential new drug targets, and it has been shown that drug targets with support from genetic...

Background Prostasin is expressed in the lung epithelium where it regulates fluid and electrolyte balance via sodium channel proteolysis. We investigated whether circulating prostasin levels are associated with the presence and severity of IPF and whether prostasin levels, or changes in them, are associated with mortality. Methods Patients with IP...

Objective Safe, effective therapies are urgently needed for patients with systemic sclerosis. However, clinical trial recruitment is challenging given the limited number of people with systemic sclerosis and further restrictions imposed by eligibility criteria. Innovative approaches are needed to accelerate development of new therapies. This articl...

Introduction Idiopathic pulmonary fibrosis (IPF) is a rare progressive lung disease with limited treatment options and poor prognosis. Genome-wide association studies (GWAS) using additive genetic models which assumes an increase in risk for each copy of the coded allele, have identified multiple relevant genes. Since, the genetic variation of comp...

Background Drugs used to treat rheumatic disease are associated with pneumotoxicity (drug-induced lung disease), but little is known about associated risk factors. Aim To determine expert physician-perceived risk factors for developing pneumotoxicity in patients with rheumatologic conditions. Methods A modified international 3-tier Delphi exercis...

Background The clinical course of idiopathic pulmonary fibrosis (IPF) is highly variable and unpredictable, with multiple genetic variants influencing IPF outcomes. Notably, rare pathogenic variants in telomere-related genes are associated with poorer clinical outcomes in these patients. Here we assessed whether rare qualifying variants (QVs) in mo...

Rationale: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. Objectives: Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF. Methods: This phase 2, randomized, d...

Background Biomarkers that change in response to nintedanib in subjects with idiopathic pulmonary fibrosis (IPF) would be valuable. We investigated the effects of nintedanib on circulating biomarkers in subjects with IPF in the INMARK trial. Methods Subjects with IPF were randomised 1:2 to receive nintedanib 150 mg bid or placebo for 12 weeks, aft...

Purpose of review Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a poor prognosis and limited therapeutic options. A multitude of promising compounds are currently being investigated; however, the design and conductance of late-phase clinical trials in IPF has proven particularly challenging. Recent findings Despite promisi...

Introduction: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease of unknown cause with a dismal prognosis. Nintedanib and Pirfenidone are approved worldwide for the treatment of IPF, but they only slow the rate of functional decline and disease progression. Therefore, there is an urgent need for more efficacious...

Background Pulmonary fibrosis (PF) is a shared characteristic of chronic interstitial lung diseases of mixed aetiology. Previous studies on PF highlight a pathogenic role for common and rare genetic variants. This study aimed to identify rare pathogenic variants that are enriched in distinct biological pathways and dysregulated gene expression. Me...

Background Interstitial lung disease (ILD) in autoimmune disease is one of the leading causes of morbidity and mortality. Current treatments slow but do not stop decline in lung function, and novel treatments are needed. In a Phase II study in patients with idiopathic pulmonary fibrosis (IPF), the preferential phosphodiesterase 4B inhibitor BI 1015...

Recent genetic and genomic advancements have elucidated the complex etiology of idiopathic pulmonary fibrosis (IPF) and other progressive fibrotic interstitial lung diseases (ILDs), emphasizing the contribution of heritable factors. This state-of-the-art review synthesizes evidence on significant genetic contributors to pulmonary fibrosis (PF), inc...

Background We used data from the INMARK trial to investigate associations between circulating biomarkers of extracellular matrix (ECM) turnover, inflammation, and epithelial dysfunction and disease progression in subjects with idiopathic pulmonary fibrosis (IPF). Methods Subjects with IPF and FVC ≥80% predicted were randomised 1:2 to receive ninte...

Study question In large multinational patient surveys, spirometry (which requires repeated, reproducible maximal efforts) can be associated with cough, breathlessness and tiredness, particularly in those with idiopathic pulmonary fibrosis (IPF). Oscillometry is an effort-independent test of airways resistance and reactance. We hypothesised that osc...

Background The Gender, Age and Physiology (GAP) model is a simple mortality prediction tool in patients with idiopathic pulmonary fibrosis (IPF) using demographic and physiological variables available at initial evaluation. White blood cell (WBC) variables may have associations with IPF outcomes. We evaluated whether incorporation of blood cell cou...

The use of [18F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [18F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). Methods: We recruited 18 patients with fILD awaiting lung biopsy for [18F]FDG PET/CT. We derived a t...

Rationale: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options. Objectives: To assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in patients with idiopathic pulmonary fibrosis. Methods: NCT03142191 was a phase 2, randomized (1:1:1), double-blind, placebo-controlle...

Rationale: Despite evidence demonstrating a prognostic role for CT scans in IPF, image-based biomarkers are not routinely used in clinical practice or trials. Objectives: Develop automated imaging biomarkers using deep learning based segmentation of CT scans. Methods: We developed segmentation processes for four anatomical biomarkers which wer...

Rationale: Distinguishing connective tissue disease associated interstitial lung disease (CTD-ILD) from idiopathic pulmonary fibrosis (IPF) can be clinically challenging. Objectives: Identify proteins that separate and classify CTD-ILD from IPF patients. Methods: Four registries with 1247 IPF and 352 CTD-ILD patients were included in analyses....

What is this summary about? Two ongoing clinical studies are part of a programme called FIBRONEER. The FIBRONEER studies are testing the drug BI 1015550 as a treatment for people with idiopathic pulmonary fibrosis (IPF) and people with progressive pulmonary fibrosis (PPF). IPF is a severe lung disease where scar tissue builds up in the lungs. The ‘...

Background The rarity of childhood interstitial lung disease (chILD) makes it challenging to conduct powered trials. In the InPedILD trial, among 39 children and adolescents with fibrosing ILD, there was a numerical benefit of nintedanib versus placebo on change in forced vital capacity (FVC) over 24 weeks (difference in mean change in FVC % predic...

Background: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. Methods: The PACIFY COUGH stu...

Background Idiopathic pulmonary fibrosis (IPF) is a chronic lung condition that is more prevalent in males than females. The reasons for this are not fully understood, with differing environmental exposures due to historically sex-biased occupations, or diagnostic bias, being possible explanations. To date, over 20 independent genetic variants have...

Background There is no standard definition of respiratory-related hospitalisation, a common endpoint in idiopathic pulmonary fibrosis (IPF) clinical trials. As diverse aetiologies and complicating comorbidities can present similarly, external adjudication is sometimes employed to achieve standardisation of these events. Methods An algorithm for re...

Background: Idiopathic pulmonary fibrosis (IPF) carries significant mortality and unpredictable progression, with limited therapeutic options. Designing trials with patient-meaningful endpoints, enhancing the reliability and interpretability of results, and streamlining the regulatory approval process are of critical importance to advancing clinic...

Dyspnoea and cough can have a profound impact on the lives of patients with pulmonary fibrosis. We investigated the effects of nintedanib on the symptoms and impact of pulmonary fibrosis in patients with progressive pulmonary fibrosis (PPF) in the INBUILD trial using the Living with Pulmonary Fibrosis (L-PF) questionnaire. Patients had a fibrosing...

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has bee...

Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity...

Introduction Idiopathic pulmonary fibrosis (IPF) is a debilitating, life-limiting fibrotic lung disease. Cough and breathlessness are among the most commonly reported symptoms and confer negative psychological burden, yet its exact relationship with anxiety and depression remains unknown. We aimed to determine the severity of mood disorders in indi...

Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease, whereby scarring of the lungs occurs. IPF is a complex disease and is more prevalent in males than females, however it is not understood why this is. Genome-wide association studies (GWAS), combining males and female, have identified more than 20 independent IPF associated...

Introduction and Objective Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterised by progressive lung fibrosis. Recent studies support the role of infection in IPF development. The Human Leukocyte Antigen (HLA) region has a key role in immune response, and a previous study on idiopathic interstitial pneumonia (IIP)...

Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease. The majority of patients with IPF report cough which is associated with significant negative physical, social and psychological consequences. At present there are no approved treatments for IPF-related cough. We evaluated the effect of low dose controlled-relea...

Background: The majority of patients with idiopathic pulmonary fibrosis (IPF) report cough and it is associated with significant negative physical, social and psychological consequences. Objective: We examined the use of low dose controlled-release morphine sulfate (MST) as an antitussive therapy. Methods: PulmonAry Fibrosis (PAciFy) Cough was a...

Aberrant expansion of KRT5⁺ basal cells in the distal lung accompanies progressive alveolar epithelial cell loss and tissue remodelling during fibrogenesis in idiopathic pulmonary fibrosis (IPF). The mechanisms determining activity of KRT5⁺ cells in IPF have not been delineated. Here, we reveal a potential mechanism by which KRT5⁺ cells migrate wit...

Introduction Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF). However, disease progression appears comparable between PPF and IPF, suggesting a similar underlying pathology relating to pulmonary fibrosis. Following positive results in...

Rationale: Identifying patients with pulmonary fibrosis (PF) at risk of progression can guide management. We explore the utility of combining baseline bronchoalveolar lavage (BAL) and CT in differentiating progressive and non-progressive PF. Methods: The derivation cohort consisted of incident cases of PF, for whom BAL was performed as part of d...

Background and objective: Surrogate endpoints enable determination of meaningful treatment effects more efficiently than applying the endpoint of ultimate interest. We used data from trials of nintedanib in subjects with pulmonary fibrosis to assess decline in forced vital capacity (FVC) as a surrogate for mortality. Methods: Data from the ninte...

Unlabelled: IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550, prevented a decline in forced vital capacity (FVC) in a phase II study in patients with IPF. This study design describes the subsequent pivotal phase III study of BI 1015550 in...

Introduction. Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia marked by progressive lung fibrosis and a poor prognosis. Recent studies have highlighted the potential role of infection in the pathogenesis of IPF and a prior association of the HLA-DQB1 gene with idiopathic fibrotic interstitial pneumonia (including IPF) has be...

Background Data from the randomised placebo-controlled INBUILD trial in subjects with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis suggested that nintedanib may have effects on circulating levels of biomarkers of epithelial injury, inflammation and extracellular matrix (ECM) turnover. Objectives...

Background There is a breadth of evidence supporting a key role for abnormal B-cell function in the pathogenesis of systemic sclerosis and associated interstitial lung disease (SSc-ILD) [1,2] . A previous pilot study investigated the efficacy of belimumab, a recombinant human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody that binds to and ne...

Background Progressive pulmonary fibrosis (PPF) includes any diagnosis of progressive fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF), and occurs in a range of disorders such as connective tissue diseases or hypersensitivity pneumonitis. Patients with PPF have comparable disease progression, lung function dec...

Background Interstitial lung disease (ILD) can have a significant impact on the long-term outcome in patients with rheumatoid arthritis (RA) but international screening guidelines for early diagnosis of RA-ILD are lacking. It is unknown to date how RA patients are screened for ILD in clinical practice. An analysis of patients’ experiences and persp...

Nalbuphine for Cough with Idiopathic Pulmonary FibrosisIn patients with idiopathic pulmonary fibrosis, cough may have a negative impact on daily life. In a randomized, 22-day treatment period, placebo-controlled, crossover trial, extended-release nalbuphine (NAL ER), an opioid agonist-antagonist, was compared to placebo for cough control and advers...

This study provides the first evidence for a role of airway sCSF1R in IPF https://bit.ly/3KTBrCA.

Rationale: Cough is a commonly reported symptom in idiopathic pulmonary fibrosis (IPF) that negatively impacts patient-reported quality of life. However, both the burden of cough at diagnosis and the behaviour of cough over time have not been systematically described in patients with IPF. Objectives: By utilising data prospectively collected as...

Importance: There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective: To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, setting, and participants: The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA...