ERS 2022: How to Prevent Progression in Idiopathic Interstitial Pneumonia
This session has discussed various abstracts on the risk factors, diagnosis and treatment of idiopathic pulmonary fibrosis and interstitial lung diseases.
Pirfenidone and nintedanib slow FVC decline, but they have been inconsistently linked to lower mortality in phase III studies. Additionally, there is limited real-world evidence supporting the potential survival benefit of anti-fibrotic drugs. Therefore, a single-centre observational cohort study was conducted to compare the transplant-free (TPF) survival of idiopathic pulmonary fibrosis patients receiving anti-fibrotic drugs (IPFAF) with an untreated cohort (IPFnon-AF). The median transplant-free survival was 3.4 years in IPFAF compared to 2.2 years in IPFnon-AF. For GAP stage II, IPFAF and IPFnon-AF had a median survival of 3.1 and 1.7 years, respectively. For GAP stage II and III, lower 1- and 2-year cumulative mortality was seen for the IPFAF compared to IPFnon-AF. Therefore, the study demonstrated a survival benefit in IPFAF compared to IPFnon-AF.
Interstitial lung diseases (ILD) are a heterogenous collection of lung disorders. Multidisciplinary discussion (MDD) has emerged as the gold standard in the differential diagnosis of ILDs. A single-centre, retrospective data analysis was conducted to determine how many patients with MDD could establish a final diagnosis and how many patients with no clear diagnosis could be obtained. 71% of the patients received a definite diagnosis. About 11% of the patients were seen as unclassifiable even after multiple MDD introductions and received further recommendations.
Patients with ILD are at increased risk of severe COVID-19 infection. In an observational prospective cohort study, the rate of anti-spike (S-IgG) antibodies after two doses of the BNT162b2 vaccine was evaluated in patients with ILD. Patients with IPF treated with anti-fibrotic therapy produce an adequate immune response after two doses of the BNT162b2 vaccine and maintain a 100% seropositivity rate 4-6 months post-vaccination. In addition, 48% of nonIPF ILD patients receiving anti-inflammatory therapy were seronegative 4-6 months after the second vaccine dose.
Although diagnostic guidelines recommend that patients with suspected IPF undergo autoantibody (AAb) testing during the initial evaluation, the clinical implications of elevated AAbs are unknown. The study evaluated clinical characteristics and outcomes in placebo-treated patients with IPF by AAb status. Overall, 12.3% of the patients were antinuclear antibody+ (ANA+) high, 9.7% were rheumatoid factor+ (RF+) and/or anti-cyclic citrullinated peptide+ (CCP+), and 51.6% of the patients were AAb-. A higher proportion of ANA+ high patients than AAb had a ≥10% decrease in %FVC or death at Week 52.
Despite evidence suggesting that familial cases of fibrotic ILDs have worse outcomes, they are managed differently than sporadic cases. A clinical retrospective cohort study assessed whether family history and telomeric dysfunction affect the diagnosis and follow-up. Despite similar PFT values at diagnosis, familial cases were more likely to have progressive disease. Thus, family history may be useful information for the multidisciplinary committee in diagnosing and predicting the likelihood of fibrotic progression.
The anti-fibrotic drugs nintedanib (Nin) and pirfenidone (Pir) have been shown to improve progression-free survival in patients with IPF; however, both drugs are associated with significant side effects in dose reduction, treatment discontinuation, or a switch to another anti-fibrotic drug. Therefore, a study aimed to assess anti-fibrotic treatment changes among IPF patients treated with Nin or Pir. After 12 months, the treatment patterns had changed, with 17% of the patients receiving a reduced dose, 13% discontinuing or pausing treatment, and 67% receiving full dose treatment. This highlights the importance of high awareness towards strategies for preventing and managing side effects to maintain the patient on anti-fibrotic treatment for as long as possible.
Pirfenidone and nintedanib are anti-fibrotic drugs that alter the course of IPF, but they differ in terms of outcome and safety of use. A multicenter, prospective cohort study was conducted to provide an analysis of pulmonary specialists' therapeutic decisions, especially the anti-fibrotic drug choice in patients with IPF. The majority of the patients for IPF treatment were qualified for anti-fibrotic therapy. The choice of nintedanib was associated with dose protocol and patient preference, whereas the choice of pirfenidone was associated with the comorbidity profile and concomitant medication.
Evidence suggests that pirfenidone is an anti-fibrotic agent that can delay the progression of IPF. However, continuing the full dose of pirfenidone used in clinical trials is challenging. A study aimed to assess the efficacy of low-dose pirfenidone in patients with IPF. FVC was significantly lower in the control group compared to the low-dose and high-dose groups. No significant difference was observed in FVC change between the low-dose and high-dose groups. The study concluded that continuous administration of pirfenidone at low doses would effectively reduce the progression of IPF in real-world practice.
IPF affects approximately 32500 people in the United Kingdom, and 15% of those with non-IPF interstitial lung disease will develop progressive pulmonary fibrosis (PPF). PPF is distinguished by its relentless progression and poor prognosis. A study was conducted to identify PPF priorities defined by people living with PPF, their carers, and healthcare professionals to enable funders to prioritize research projects vital to those affected by PPF. Stakeholders believe that early diagnosis, new treatment, symptom management and quality of life are essential areas that require prioritization of funding and research.
Data on the long-term effect of nintedanib on the overall survival in large IPF cohorts is limited. A study aimed to evaluate nintedanib therapy outcome in a large multicentric real-world cohort of IPF patients with various initial stages of the disease. Overall survival was higher in the nintedanib group than in the enrolment group. Nintedanib therapy showed a consistently favourable outcome in all three groups with different FVC predicted at baseline. Treatment with nintedanib in IPF patients can significantly prolong life expectancy in the real world.
The anti-fibrotic agent nintedanib (NTD) inhibits triple receptors, including the vascular endothelial growth factor (VEGF) receptor. VEGF has been linked to the pathogenesis of acute exacerbations (AE) of IPF and PF-ILD. However, there have been few studies on the impact of NTD on the AE period. A study aimed to evaluate the efficacy and safety of NTD for AE. At 90 days after AE onset, the nintedanib group had a significantly higher survival rate than the non-nintedanib group. In addition, the Nintedanib group had a significantly longer survival time than the non-nintedanib group. Additional nintedanib may be related to better clinical outcomes without severe adverse effects.
The diagnosis of IPF is frequently delayed for up to several years. Therefore, a study was conducted to assess the impact of a diagnostic delay on progression-free survival, quality of life and hospitalization rate. The study concluded that a diagnostic delay of over one year has a negative impact on progression-free survival, quality of life and hospitalization rates in patients with IPF.
SARS-CoV2 infection is associated with an increased risk of COVID-19 and is a significant risk factor for functional deterioration in patients with IPF. Therefore, the authors retrospectively examined all IPF patients treated at the university centre in Hungary for SARS-CoV2 vaccination status beginning in January 2021. SARS-CoV2 vaccination is critical in IPF patients, and regardless of vaccine type, it results in a significantly lower risk of COVID-19 hospitalization.
The commonly used questionnaires to assess dyspnea include the British Medical Research Council (MRC), the University of California San Diego (UCSD), and the St. George's Respiratory Questionnaire (SGRQ). Their usefulness in predicting survival has not been evaluated. A study was conducted to determine the usefulness of baseline dyspnea measured by MRC, UCSD, and SGRQ in the prognosis of ILD. The study concluded that baseline dyspnea assessed by MRC, SGRQ, and particularly by UCSD questionnaires was associated with the risk of dying at 6 months in patients with ILD.
A study was conducted to evaluate the relationship between major urban pollutants and the severity of the non-IPF ILD. Unfortunately, the study could not provide evidence to state that pollutants in Madrid are associated with a higher likelihood of developing severity criteria in non-IPF ILD patients.
Interstitial lung abnormalities (ILA) are a common incidental finding on low-dose computed tomography (LDCT) scans of lung cancer screening (LCS) participants. Few studies have assessed the downstream impact of these findings, specifically how many patients receive pharmacotherapy. A study showed that LCS would detect a small number of patients with significant, unrecognized ILD who qualify for pharmacotherapy.
Immunocompromised individuals, including solid organ transplant recipients, have a weakened immune response to two doses of the SARS-CoV-2 mRNA vaccine. According to research, patients with IPF have a disrupted cellular and humoral immune response. Therefore, a study investigated the immune response after the SARS-CoV-2 mRNA vaccine in patients with IPF. Compared to the general population, patients with IPF did not mount significant anti-spike antibody responses to two doses of the mRNA vaccine BNT162b2.
The only two agents approved for IPF are the anti-fibrotic nintedanib and pirfenidone, but few studies have examined their real-world use and outcomes. Therefore, a study was conducted to determine anti-fibrotic treatment persistence in Veterans Health Administration (VHA) patients and evaluate incident adverse events (AEs), healthcare resource utilization (HCRU), and costs in persistent vs nonpersistent patients. About 19% of the patients received anti-fibrotic; the mean time from diagnosis to treatment was 168 days. During follow-up, persistent patients had a lower AE incidence but significantly higher HCRU and costs than nonpersistent patients. These findings suggest that there are still significant unmet needs among veterans with newly diagnosed IPF, such as increased use of existing anti-fibrotic and more tolerable treatment options.
Hospitalizations are clinically significant events for IPF patients, frequently resulting in health deterioration or death. This study aimed to evaluate the risk factors for death within 30 or 90 days after an acute respiratory hospitalization. Higher levels of LDH at the time of admission, the use of oxygen therapy and high oxygen flows were correlated with death within 30 or 90 days. For patients experiencing an AE-IPF, the 90-day mortality rate was high.
APO1, a novel formulation of inhaled pirfenidone, may have improved efficacy and reduced toxicity than oral pirfenidone in patients with IPF. The serial changes in Quantitative Lung Fibrosis (?QLF) on thoracic High-Resolution Computed Tomography (HRCT) are associated with changes in FVC. The association between longitudinal changes in quality of life (QOL) and ?QLF is less established. AP01-002 was a Phase 1b trial that compared the safety and tolerability of AP01 50mg once daily and 100mg twice daily in IPF. A similar proportion of patients on both regimens showed a reduction in QLF and QLF stabilization. ?QLF and change in FVC demonstrated a stronger correlation in 100mg bd. Patients with improved QLF had higher average KBILD scores from baseline. The study showed a strong and lasting association between HRCT response and KBILD.
European Respiratory Society (ERS) International Congress 2022, 3rd-6th Sept. 2022, Barcelona
