ERS 2022: What is Hot in Interstitial Lung Diseases
In this session, the experts using clinical data discussed the factors predicting treatment response and the novel drugs for treating ILD.
Idiopathic pulmonary fibrosis (IPF) is defined by fibrosis, progressive loss of pulmonary function and poor survival. Matrix metalloproteinase-7 (MMP-7), a basaloid cell and pro-fibrotic macrophage marker, is a prognostic blood marker of IPF progression and mortality. Blood biomarkers have not yet been used in randomized controlled trials to stratify IPF patients. As a result, patient heterogeneity may complicate the interpretation of IPF clinical trial results. A study was conducted to assess biomarkers concerning patient heterogeneity at baseline and clinical endpoints in ISABELA1 and two studies. The baseline biomarker levels were comparable across studies. Pooled data from studies showed that MMP-7 is a prognostic biomarker of disease progression. Biomarker-based enrichment strategies focused on MMP-7 levels may help guide treatment decisions for individual patients and allow enrichment of forced vital capacity (FVC) decline in clinical trials, enhancing drug development in IPF.
Obstructive sleep apnea (OSA) and nocturnal hypoxemia (NH) are common in patients with fibrotic interstitial lung disease (fILD); however, their relationship with disease outcomes is uncertain. A prospective observational study was conducted to assess the relationship of OSA and NH with survival in patients with fILD. The mean survival was significantly worse in patients with NH than in those without. Overall, patients without NH, even in the presence of OSA, had lower mortality than those with NH. In patients with fILD, NH is common and is linked to increased mortality. This suggests that trials of nocturnal oxygen may be warranted.
Early appropriate treatment of ILD is critical for slowing disease progression and improving survival. The study compared the mortality, all-cause and respiratory-related hospitalizations, and health care costs of ILD patients initially treated in specialized ILD centres (sIc) versus non-specialized centres (nsIc) and explored differences in treatment patterns. Results indicated that initial-sIc treatment is associated with positive effects on mortality and all-cause hospitalization, possibly due to different diagnostic and treatment management. Improved cooperation between sIc and nsIc may benefit ILD patients.
Response to immunosuppressive and antifibrotic treatment in patients with ILD is often difficult to predict. Electronic nose (eNose) sensor technology profiles exhaled volatile organic compounds and can identify ILD patients. A study was conducted to investigate if an eNose can predict treatment response in ILD patients. Breath profiles before treatment differed between patients with and without treatment response, both for immunosuppressive and antifibrotic treatment. The study indicates that eNose technology may predict treatment response in ILD patients before treatment initiation, implying potential value in guiding treatment decisions.
Familial idiopathic pulmonary fibrosis (f-IPF) is characterized by at least two relatives with ILD in a single family. A study aimed to compare pulmonary function decline between sporadic IPF (s-IPF) patients and f-IPF patients. The annual decrease in FVC% prediction was -2.33 percentage points (pp) in s-IPF patients and -4.65 pp in f-IPF patients. Furthermore, a family history of ILD and negative smoking history were significantly associated with FVC decline. In conclusion, the family history of a first-degree relative with ILD predicts FVC decline in IPF patients. Therefore, assessment of comprehensive family history is essential to inform patients about disease evolution.
The minor T-allele of the MUC5B promoter polymorphism rs35705950 is significantly associated with IPF. However, studies on the effect of the MUC5B risk allele on survival in IPF have shown conflicting results. Thus, a study aimed to investigate if MUC5B rs35705950 associates with survival in a real-world setting in the European IPF population. Results showed that MUC5B minor allele carriage was associated with better survival in the European IPF population over 56 in a real-world setting. Furthermore, the study determined a MUC5B associated endotype, especially in the aged patient with IPF, characterized by milder disease behaviour.
Disease behaviour has rarely been investigated in newly diagnosed idiopathic interstitial pneumonia (IIPs) cases. In the JIPS registry, progression-free survival (PFS) and the percentage of cases meeting progressive fibrosing interstitial lung disease (PF-ILD) criteria were longitudinally assessed. 23% and 37% met the PF-ILD criteria for IIPs: 24% and 42% for IPF, and 23% and 39% for unclassifiable IIP after 1 and 2 years, respectively. In patients with newly diagnosed IIP, the prognosis of unclassifiable IIP was similar to that of IPF within 3 years.
In patients with IPF, cough is a significant cause of morbidity, which lacks effective therapies. Mixed opioid agonists/antagonists can reduce chronic cough. An interim analysis of a phase 2 trial evaluating oral nalbuphine (NAL) extended-release (ER) for IPF-related chronic cough was reported. There was a 77.35 reduction from baseline to day 22 in hourly cough frequency for NAL ER. In this interim analysis, NAL ER is the first therapy to demonstrate a significant reduction in hourly daytime chronic cough frequency in IPF.
Antifibrotics (AF), nintedanib and pirfenidone slow the progression of IPF but do not stop it. Clinical data suggests that BI 1015550, a preferential inhibitor of PDE4B, prevents FVC decline in IPF, with or without background AF. In addition, preclinical studies have shown a synergistic effect on inhibiting fibroblast proliferation when BI 1015550 is given with nintedanib. A post hoc analysis of the Phase 2 study evaluated the efficacy and safety of BI 1015550 in IPF. The analysis concluded that BI 1015550 might have a more pronounced additional clinical benefit in preventing FVC decline when taken with nintedanib than with pirfenidone in IPF patients.
Various antifibrotic treatments are available, but there is still an unmet medical need for new effective and well-tolerated treatments for IPF. The ongoing Phase 2 AIR is a multi-centre, open-label, single-arm, 36-week trial that investigated the safety, efficacy, and pharmacokinetics of the angiotensin II type 2 receptor (AT2R) agonist C21, administered at a dose of 100 mg BID, in IPF patients. An interim analysis was performed on the first 21 evaluable subjects enrolled. The analysis suggested that C21 potentially improves lung function in IPF patients not previously treated with antifibrotic therapy. In addition, C21 was well tolerated, with no treatment-related serious adverse events and no signals of gastrointestinal toxicity.
European Respiratory Society (ERS) International Congress 2022, 3rd-6th Sept. 2022, Barcelona
