Background:We used data from the European MultiPartner IPF Registry (EMPIRE) and the US Idiopathic Pulmonary Fibrosis-PRospective Outcomes (IPF-PRO) Registry to examine the frequency of hospitalisation, risk factors associated with hospitalisation, and whether hospitalisation affected 5-year mortality in patients with idiopathic pulmonary fibrosis (IPF). Methods:Data from January 2015 to September 2022 in EMPIRE and from June 2014 to December 2023 in the IPF-PRO Registry were analysed. Rates of hospitalisation and death were estimated using the Kaplan-Meier method. Associations between patient characteristics at enrolment and time to hospitalisation were assessed using Cox regression. Results:The EMPIRE and IPF-PRO Registry cohorts comprised 2989 and 1001 patients, respectively. Median follow-up was 36.5 months in EMPIRE and 60 months in the IPF-PRO Registry. Overall, 20.3% of patients in EMPIRE and 70.3% (28.2% over 36 months) in the IPF-PRO Registry had one or more hospitalisation during follow-up. In both registries, lower percentage predicted diffusing capacity of the lungs for carbon monoxide and use of supplemental oxygen at enrolment were associated with an increased risk of hospitalisation in multivariable models. 5-year mortality did not differ between patients who were and were not hospitalised in EMPIRE (54.3% and 53.7%, respectively) or in the IPF-PRO Registry (51.7% and 46.1%, respectively). Conclusions:Data from EMPIRE and the IPF-PRO Registry demonstrate the high risk of hospitalisations and mortality among patients with IPF and suggest there may be differences across countries in risk of hospitalisation. Variability in data collection, healthcare systems and clinical practices should be considered when interpreting differences between countries.

RATIONALE:Idiopathic pulmonary fibrosis (IPF) is an incurable chronic progressive fibrotic lung disease with median survival of 3-5 years from diagnosis. Estimates of incidence rate and prevalence of IPF are outdated and vary widely due to differences in study methodology and diagnostic definitions. OBJECTIVES:To provide an up-to-date estimate of IPF incidence rates and prevalence and describe the comorbidity burden for people with IPF in the United States. METHODS:This non-interventional retrospective study used claims data from the Optum Clinformatics Data Mart database from 2017 to 2022. Individuals were required to have at least 365-day continuous enrollment in the database to enter the study. Individuals with IPF were identified based on claims with the International Classification of Diseases, Tenth Revision code for IPF (J84.112) following study entry. IPF definitions varied by requirement for 1 or 2 qualifying IPF claims and computed tomography scan of the chest and/or lung biopsy. In this analysis, 3 primary case definitions and 2 sensitivity analysis definitions were used to identify individuals with IPF. RESULTS:By primary case definitions, the overall crude and age- and sex-adjusted incidence rates (per 100,000 person-years) were 14.5-26.1 and 9.8-18.4, respectively; the crude and adjusted prevalences (per 100,000 persons) were 46.3-88.9 and 34.4-67.1, respectively. Incidence rate and prevalence increased markedly with age and varied with ethnicity and region. The most frequent comorbidities were systemic hypertension, chronic obstructive pulmonary disease, and coronary artery disease. CONCLUSIONS:This study provides an up-to-date summary of the incidence rate and prevalence of IPF in the United States and shows a substantial burden of comorbidities among patients diagnosed with IPF.

Pulmonary fibrosis may impair an individual’s ability to work. We assessed the extent, cost and factors associated with workplace productivity loss among patients with progressive pulmonary fibrosis (PPF). The multi-center ILD-PRO Registry enrolled US patients with progressive interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis. Workplace productivity loss was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire. Associations between patient characteristics and workplace productivity loss among employed patients were analyzed using logistic regression. Among 175 employed patients of 597 who completed the WPAI questionnaire, 58.3 URL: www.clinicaltrials.gov .

RATIONALE:The optimal treatment of interstitial lung disease resulting from COVID-19 is unknown. OBJECTIVES:We sought to investigate the effect of nintedanib, an antifibrotic medication, on interstitial lung disease in participants who survived severe SARS-CoV-2 infection. METHODS:We conducted a double-blind, randomized, placebo-controlled trial at six sites across the United States. Participants were included if they had evidence of prior SARS-CoV-2 infection that required supplemental oxygen therapy and had interstitial lung disease (ILD) findings on chest imaging ≥ 30 days post-infection. Participants received either nintedanib or placebo (1:1 ratio) for 180 days. Primary outcome was change in forced vital capacity (FVC) at 180 days; other outcomes included changes in chest computed tomography imaging (qualitative and quantitative), six-minute walk distance, and patient-reported outcome measures. MEASUREMENTS AND MAIN RESULTS:In total, 103 of the planned 170 participants were randomized (51 to nintedanib; 52 to placebo); the study closed to enrollment before target sample size was met. FVC at 180 days improved in both nintedanib (+147.55 mL) and placebo groups (+167.72 mL) but were not significantly different (difference, -20.17 mL; 95% CI: -138.54 to 98.20). Similarly, six-minute walk distance, diffusing capacity, qualitative assessments of chest imaging, and patient-reported outcome measures improved in both groups. Quantitative chest imaging, as measured by data-driven textural analysis, showed no difference in fibrotic score changes for those receiving nintedanib or placebo (-4.49 vs -4.06; difference, -0.43; 95% CI: -3.34 to 2.47). CONCLUSIONS:Administration of nintedanib in this limited trial did not result in improved outcomes for participants with post-COVID-19 ILD.

Rationale The diagnosis of bronchiectasis (BE) is increasing in the US. Real-world data can be leveraged to help characterize trends in this disease. Our study aimed to provide a current estimate of the incidence of BE in the US, and summarized potential etiologic characteristics observed in a real-world standard-of-care setting. Methods Subjects with ≥1 day of registration in Optum Clinformatics® Data Mart during the index period (1 January 2018-31 December 2022) were selected. The index date was the earliest date in the index period when patients had ≥365 days of available claims history. People diagnosed with BE before the index date or those with missing/ambiguous age and sex information were excluded. During follow-up, an incident BE case was identified based on ≥2 outpatient claims on separate days with a diagnosis code of BE, or ≥1 hospitalization record with a principal/secondary diagnosis of BE. Crude incidence per 100,000 person-years was calculated and standardized according to the age and sex distribution of the 2022 US population. For people diagnosed with BE, etiologies were summarized and defined as “potential” (causality could not be inferred from the data). The frequency and type of etiologies were summarized over the study period and grouped by pre- and post-BE diagnosis. An etiology was recorded only in the post-diagnosis period if not present/ascertained in the pre-diagnosis period. Results In total, 70,946 incident people with BE (pwBE) were identified, with a mean±SD age of 71.7±11.1 years and 58.7% were female. Over the 5-year period, the crude incidence of BE was 109.1 (95% CI: 108.3-109.9) per 100,000 person-years, while the standardized incidence of BE was 66.4 (95% CI: 65.9-67.0) per 100,000 person-years. Approximately 93% of the pwBE had ≥1 potential etiologic disease present, and the mean±SD number of potential etiologies was 2.5±1.4 per patient. Nearly 75% of pwBE had ≥2 etiologies, and 22% had ≥4. Of these, the five most common etiologies in the cohort included respiratory infection (72.9%), chronic obstructive pulmonary disease (59.0%), gastro-esophageal reflux disease (51.6%), asthma (27.7%), and connective tissue rheumatic disease (9.9%). Conclusions In the US, we found that the incidence of BE has increased in recent years.1 On average, pwBE had 2.5 potential etiologic diagnoses. Our data indicate the need for awareness surrounding BE, since its increasing incidence will result in greater disease burden and healthcare resource needs. 1 Weycker D, et al. Chron Respir Dis. 2017;14(4):377-384.

We used data from the IPF-PRO Registry of patients with idiopathic pulmonary fibrosis (IPF) to identify characteristics that predicted survival for a further > 5 years. Participants had IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Patients were followed prospectively. A Classification And Regression Tree (CART) was used to identify predictors of survival > 5 versus ≤ 5 years following enrollment. The following variables, assessed at enrollment, were considered: age; body mass index (BMI); former smoker; current smoker; time from first imaging evidence, symptoms, or diagnosis of IPF to enrollment; forced vital capacity (FVC)

Patients with fibrosing interstitial lung disease (ILD) experience a decline in lung function with progressive symptoms, poor response to treatment, and reduced quality of life. While supplemental oxygen therapy is commonly prescribed in clinical practice for patients with fibrosing ILD, the long-term outcomes associated with oxygen therapy remain unclear. This study aimed to address this knowledge gap. This non-interventional study used the Optum® Market Clarity database from 01 October 2015 to 30 June 2022. Patients aged ≥ 18 years with newly diagnosed fibrosing ILD (≥ 2 fibrosing ILD diagnoses on different service dates within 365 days) were included. Patients meeting initial selection criteria were assigned to cohorts based on oxygen therapy initiation. Patients who initiated oxygen therapy following the ILD diagnosis (oxygen therapy cohort) were propensity scores matched 1:1 to those who did not yet initiate oxygen therapy (no oxygen therapy cohort). The oxygen cohort’s index date was the first oxygen therapy date. For the no oxygen therapy cohort, it was assigned using the time between the fibrosing ILD diagnosis date and the index date of a matched oxygen therapy patient. Follow-up continued until health plan disenrollment, death, or end of study period (follow-up period). A total of 24,680 patients who initiated oxygen therapy were successfully matched to those who did not. The mean age of the study cohort was 68.9 years and 50.9

RATIONALE: The outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 sparked a global pandemic, leading to an estimated three million deaths worldwide in the first year alone. Millions of survivors live with the sequelae of their acute illness, including a subset of patients who developed parenchymal lung abnormalities resembling interstitial lung disease (ILD) as a consequence of injury from COVID-19 pneumonia. The tyrosine-kinase inhibitor nintedanib has been shown to slow the rate of decline of forced vital capacity (FVC) in patients with a range of progressive fibrosing lung diseases. The role of nintedanib in mediating post-COVID ILD has not been studied in a prospective randomized trial. METHODS: In this multicenter, double-blind, randomized controlled trial, 103 participants with a history of COVID-19 lung injury complicated by respiratory failure requiring oxygen support, and with radiologic evidence of ILD, were randomized in a 1:1 ratio to receive oral nintedanib or placebo. Patients with ILD diagnosed prior to COVID-19 infection were excluded. The primary endpoint was change in baseline forced vital capacity (FVC, mL) at 180 days. Secondary endpoints included change in diffusing capacity for carbon monoxide (DLCO, percent predicted) and six-minute walk test (6MWT, feet) at 180 days. Serious adverse events were assessed. RESULTS: Of the 103 patients randomized, 51 received nintedanib and 52 received placebo. The mean FVC change was 147.55 mL with nintedanib and 167.72 mL with placebo. There was no significant between-group difference in the primary endpoint (mean difference, -20.17; 95% CI, -138.54 to 98.20; P=0.74). Mean change in DLCO did not differ between nintedanib and placebo (0.54% predicted vs. 2.12% predicted, respectively; mean difference, -1.58; 95% CI, -6.10 to 2.94) nor did mean change in the six-minute walk distance (79.98 feet vs. 42.58 feet; mean difference, 37.40; 95% CI, -84.31 to 159.12). The incidence of serious adverse events was similar in the two groups (11.8% for nintedanib vs. 13.5% for placebo). CONCLUSIONS: Administration of nintedanib to subjects with ILD findings following COVID-19-related lung injury did not improve FVC at 180 days when compared with placebo. Participants in both groups demonstrated improvement in FVC over the study period. There was no difference in incidence of serious adverse events between the two groups.

Rationale: Although exposure to air pollution is a known risk factor for adverse pulmonary outcomes, its impact in individuals with idiopathic pulmonary fibrosis (IPF) is less well understood. Objectives: To investigate the effects of long-term exposure to air pollution on disease severity and progression in patients with IPF and to determine whether genomic factors, such as MUC5B promoter polymorphism or telomere length, modify these associations. Methods: We performed analyses at enrollment and after 1 year of follow-up in the IPF-PRO (Idiopathic Pulmonary Fibrosis Prospective Outcomes) Registry, a prospective observational registry that enrolled individuals with IPF at 46 U.S. sites from June 2014 to October 2018. Five-year average pollution exposures (particulate matter ≤2.5 μm in aerodynamic diameter [PM2.5], nitrogen dioxide, ozone) before the enrollment date were estimated at participants' residential addresses with validated national spatiotemporal models. Multivariable regression models estimated associations between pollution exposure and physiologic measurements (forced vital capacity [FVC], diffusing capacity of the lung for carbon monoxide, supplemental oxygen use at rest) and quality-of-life measurements (St. George's Respiratory Questionnaire, EuroQoL, Cough and Sputum Assessment Questionnaire) at enrollment. Cox proportional hazards models estimated associations between pollutants and a composite outcome of death, lung transplant, or >10% absolute decline in FVC percent predicted in the year after enrollment. Models were adjusted for individual-level and spatial confounders, including proxies for disease onset. Gene-environment interactions with MUC5B and telomere length were assessed. Results: Of 835 participants, 94% were non-Hispanic White individuals, 76% were male, and the mean (standard deviation) age was 70 (7.7) years. In fully adjusted analyses, higher PM2.5 exposure was associated with worse quality of life per St. George's Respiratory Questionnaire activity score (3.48 [95% confidence interval (CI), 0.64, 6.32] per 2 μg/m3 PM2.5) and EuroQoL scores (-0.04 [95% CI, -0.06, -0.01] per 2 μg/m3 PM2.5), as well as lower FVC percent predicted and lower diffusing capacity of the lung for carbon monoxide percent predicted at enrollment. Each 3 parts per billion difference in O3 exposure was associated with a 1.57% (95% CI, 0.15, 2.98) higher FVC percent predicted at enrollment, although this effect was attenuated in multipollutant models. There was no association between nitrogen dioxide and enrollment measures or between pollution exposure and 1-year outcomes and no evidence for gene-environment interactions. Conclusions: In the IPF-PRO Registry, long-term exposure to PM2.5 was associated with worse quality of life and lung function at enrollment, but not with short-term disease progression or mortality. There was no evidence of effect modification by interaction of genomic factors with pollution. The reason for the unexpected relationship between O3 exposure and higher FVC is unclear. Clinical trial registered with www.clinicaltrials.gov (NCT01915511).

Rationale: Respiratory hospitalizations are a significant cause of morbidity and mortality in individuals with idiopathic pulmonary fibrosis (IPF). We hypothesized that higher acute exposure to particulate matter with aerodynamic diameter ≤ 2.5 microns (PM2.5) would be associated with respiratory-related hospitalizations in a registry of patients with IPF. Methods: We performed a case cross-over analysis of participants who had at least one non-transplant-related respiratory hospitalization in the IPF-PRO Registry, a multicenter registry of individuals with IPF from 46 sites across the US. Acute exposure to PM2.5 was estimated as the average concentration recorded at the Air Quality Station regulatory monitor nearest to the individual's primary residential address for each day in the week preceding the hospitalization (lag day 0 as day-of-event to lag day -6). Control days were selected using a time-stratified semisymmetric bidirectional design and included the same day of the week within the same month as the case day. Conditional logistical regression estimated the association between average PM2.5 concentration for each lag day and for the 7-day average and the odds of initial respiratory hospitalization, adjusting for time-varying confounders, including temperature, relative humidity and influenza season. We assessed for effect modification by sex, age, MUC5B genotype, telomere length and ani-fibrotic treatment using stratified analyses. Results: Of the 1002 participants enrolled in the registry, 242 had at least one respiratory-related hospitalization and valid PM2.5 estimates. In adjusted analyses, each 5µg/m3 higher PM2.5 on lag day 0 was associated with a 22% (95% confidence interval, 14% to 46%) higher odds of respiratory-related hospitalization. No significant association was observed for PM2.5 in the other days in the week or the average 7-day concentration preceding the hospitalization. There was no evidence of effect modification by the other variables assessed. Conclusions: Higher acute exposure to PM2.5 is associated with an increased risk of same-day hospitalization in individuals with IPF.

Abstract Background Supplemental oxygen therapy is commonly prescribed in clinical practice for patients with fibrosing interstitial lung disease (ILD) to reduce breathlessness and increase physical capacity. Only a few studies have evaluated the incidence of oxygen therapy use, with evidence lacking in its use among fibrosing ILD subtypes including patients with idiopathic pulmonary fibrosis (IPF) and non-IPF ILD. This study aimed to estimate incidence of oxygen therapy and factors associated with oxygen therapy initiation. Methods This non-interventional study used US administrative claims and electronic health record data from 01 October 2015 to 30 June 2022. Patients aged ≥ 18 years with newly diagnosed fibrosing ILD (≥ 2 fibrosing ILD diagnoses in any position on different dates of service within 365 days) were included; the index date was the first date with ILD diagnosis. Patients were followed until the earlier of health plan disenrollment, death, or end of study period. Oxygen therapy use was evaluated among patients without evidence of oxygen therapy before the index date, stratified by the underlying fibrosing disease (i.e., IPF vs. non-IPF ILD). Factors associated with oxygen therapy use were evaluated using Cox proportional hazards regression. Results A total of 114,921 patients (IPF n = 5,555; non-IPF ILD n = 109,366) newly diagnosed with fibrosing ILD were included in the study. The mean (standard deviation) age of patients with ILD was 66.9 (14.2) years, and 47.2% were male. Patients were followed for a mean of 24 months after ILD diagnosis, during which 38% of fibrosing ILD patients initiated oxygen therapy; a higher proportion of patients with IPF initiated oxygen therapy compared to those with non-IPF ILD (68% and 36%, respectively). Factors associated with oxygen therapy initiation included IPF, higher Charlson comorbidity scores, and comorbidities that impair respiratory capacity. Conclusions The study findings demonstrate a substantial proportion of patients with fibrosing ILD initiated oxygen therapy following initial ILD diagnosis, with higher rates of oxygen therapy initiation observed among patients with IPF compared with non-IPF ILD. Respiratory comorbidities were key factors associated with increased initiation of oxygen therapy.

OBJECTIVES:We aimed to describe the demographics, clinical characteristics and care patterns of patients with systemic autoimmune rheumatic diseases (SARD) prior to their interstitial lung disease (ILD) diagnosis. METHODS:We conducted a retrospective cohort study using claims data from Healthcare Integrated Research Database (2006-2023). Adults diagnosed with SARD-ILD were identified, with the earliest ILD diagnosis date designated as the index date. A minimum of 36 months of continuous enrolment before the index date was required. All measures were analysed descriptively. For a subset of patients with respiratory symptoms before ILD diagnosis, the association between type of specialist encounter and time from symptom onset to SARD-ILD diagnosis was assessed using a Cox proportional hazards model. RESULTS:The study included 2526 patients with SARD-ILD. Mean age was 62.6 years and 75.4% were female. Before ILD diagnosis, 61.8% of patients had at least one all-cause hospitalization. Diagnostic tests including chest CT, high-resolution CT, and pulmonary function tests (PFT) were used in 80.1%, 59.0% and 60.3% of patients, respectively. Among the subgroup, patients who saw a pulmonologist within 90 days of initial respiratory symptom onset were 18% more likely to be diagnosed with ILD compared with those who did not (hazard ratio: 1.18, 95% CI: 1.03, 1.35; P = 0.017). CONCLUSION:The study highlights the complex diagnostic journey of patients with SARD-ILD. Findings suggest a multidisciplinary approach involving pulmonologists and rheumatologists could enable timely ILD diagnosis and should be considered for more effective diagnosis and management of SARD-ILD.

To review the epidemiology, general clinical aspects and diagnosis, impact on morbidity and mortality, and general treatment approaches for myositis-associated ILD. The relevant literature was reviewed. The clinical, radiographic, and histopathological features of interstitial lung disease (ILD) in idiopathic inflammatory myopathies (IIM) are similar to idiopathic ILD. Patients with a known diagnosis of myositis require prompt clinical evaluation including the determination of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo a pulmonary function test and high-resolution CT (HRCT) scanning of their lungs. Despite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often concomitantly administered, particularly in patients with severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine. If these agents fail or if the pulmonary features are severe or rapidly progressive, then more aggressive immunosuppressive or immunomodulatory therapy including cyclophosphamide, tacrolimus or cyclosporine, rituximab, IVIg, or tofacitinib can be considered. Further investigations are required to assess the role of novel therapies in the treatment of myositis-associated ILD. Revisar la epidemiología, los aspectos clínicos generales, el diagnóstico, el impacto en la morbilidad y la mortalidad y los enfoques generales de tratamiento para la enfermedad pulmonar intersticial (EPI) asociada a miositis. Se revisó la literatura relevante. Las características clínicas, radiográficas e histopatológicas de la EPI en las miopatías inflamatorias idiopáticas (MII) son similares a las de la EPI idiopática. Los pacientes con un diagnóstico conocido de miositis requieren una evaluación clínica inmediata que incluya la determinación de autoanticuerpos asociados a la miositis. Los pacientes que poseen autoanticuerpos asociados con EPI o aquellos con cualquier síntoma pulmonar deben someterse a una prueba de función pulmonar y una tomografía computarizada de alta resolución (TCAR) de sus pulmones. A pesar de la falta de ensayos controlados con placebo, los glucocorticoides sistémicos se consideran el pilar del tratamiento inicial de la EPI asociada a miositis. Los agentes ahorradores de glucocorticoides a menudo se administran de forma concomitante, particularmente en pacientes con enfermedad grave. Los fármacos inmunosupresores convencionales de primera línea incluyen micofenolato mofetilo o azatioprina. Si estos agentes fallan o si las características pulmonares son graves o rápidamente progresivas, se puede considerar una terapia inmunosupresora o inmunomoduladora más agresiva que incluya ciclofosfamida, tacrolimus o ciclosporina, rituximab, IgIV o tofacitinib. Se requieren más investigaciones para evaluar el papel de las nuevas terapias en el tratamiento de la EPI asociada a la miositis.

Abstract Background The Myositis Interstitial Lung Disease Nintedanib Trial (MINT) is a hybrid trial, which is enrolling patients both at local sites and remotely via a decentralised site. The trial will investigate the efficacy and safety of nintedanib in patients with progressive myositis-associated interstitial lung disease (MA-ILD). Methods/Design MINT is an exploratory, prospective randomised placebo-controlled trial. Eligible patients will have myositis and evidence of fibrosing ILD on high-resolution computed tomography (HRCT), be taking standard of care medications for myositis, and meet criteria for ILD progression within the prior 24 months based on decline in FVC, worsened fibrosis on HRCT, and/or worsened dyspnoea. Patients will be randomised 1:1 to receive nintedanib 150 mg twice daily or placebo for 12 weeks then open-label nintedanib for 12 weeks. Patients will be enrolled at local sites and a decentralised site. Most study visits will be completed remotely using telemedicine or digital health technologies. The primary endpoint is the change in Living with Pulmonary Fibrosis (L-PF) questionnaire dyspnoea domain score at week 12. Other endpoints include changes in other L-PF questionnaire domains, lung function, imaging, and physical activity, and assessment of adverse events. Data collected using remote versus clinic enrolment, and using home versus clinic spirometry, will be compared. Discussion MINT is an innovative, hybrid trial that will evaluate the effects of nintedanib on symptoms, quality of life, and ILD progression in patients with progressive MA-ILD and provide valuable information on the utility of decentralised recruitment and remote data collection in clinical trials. Trial registration Clinicaltrials.gov NCT05799755 (date of registration: 05/04/2023).

Background:Patients with idiopathic pulmonary fibrosis (IPF) experience impairments in health-related quality of life (HRQL). Research Question:What is the trajectory of decline in HRQL in patients with IPF and is this influenced by patients' demographic/clinical characteristics at baseline? Study Design and Methods:The Idiopathic Pulmonary Fibrosis Prospective Outcomes (IPF-PRO) Registry is a registry of patients with IPF. HRQL was assessed at enrollment and during routine clinical care using the following patient-reported outcomes (PROs): the Cough and Sputum Assessment Questionnaire, the St. George's Respiratory Questionnaire, the 12-item Short Form Survey, and the EuroQol score and visual analog scale. Trajectories of PRO scores were estimated using a mixed joint model. Associations between sex, age, FVC and diffusing capacity of the lungs for carbon monoxide (both % predicted), use of supplemental oxygen, and use of antifibrotic therapy at enrollment and trajectories of PRO scores were assessed. Results:The cohort included 957 patients. Estimated mean changes in scores over 48 months were 10.8, 7.0, 13.1, and 10.5 for the St. George's Respiratory Questionnaire total, symptoms, activity, and impact scores; -7.6 and -6.5 for the Cough and Sputum Assessment Questionnaire cough impact and symptoms scores; -2.1 and -7.0 for the 12-item Short Form Survey Mental Component Summary and Physical Component Summary scores; and -0.08 and -9.0 for the EuroQol score and visual analog scale, respectively (P < .001 for all). At enrollment, female sex, lower age, lower FVC and diffusing capacity of the lungs for carbon monoxide % predicted, and use of supplemental oxygen were associated with worse PRO scores. Trajectories of decline in PRO scores were similar across levels of demographic/clinical factors assessed at enrollment. Interpretation:Among patients in the IPF-PRO Registry, a range of PROs showed worsening in HRQL over 48 months. Female sex, lower age, worse lung function, and use of supplemental oxygen were associated with worse HRQL at enrollment and during follow-up. These findings suggest that interventions aimed at preserving HRQL in patients with IPF may be of particular benefit for certain groups of patients. Clinical Trial Registration:ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov.

BACKGROUND: Fibrosing interstitial lung disease (ILD) encompasses more than 200 diverse pulmonary disorders, of which up to 40% become progressive. The 4 underlying ILD types most likely to result in progression are unclassified ILD/idiopathic interstitial pneumonia (IIP), autoimmune ILDs, exposurerelated ILD/hypersensitivity pneumonitis, and sarcoidosis. OBJECTIVE: To compare health care resource utilization (HCRU) and costs among patients with fibrosing ILD that has progressed ("progressive" fibrosing cohort) vs patients whose fibrosis did not meet criteria set for progression ("not yet progressed" cohort). METHODS: This was a noninterventional study of commercial enrollees and Medicare Advantage with Part D beneficiaries, which used administrative claims data for the period from October 1, 2015, through May 31, 2021. Adult patients (aged >= 18 years) with fibrosing ILD and 12 months of continuous health plan enrollment were included. Patients with idiopathic pulmonary fibrosis, baseline ILD diagnoses, or missing demographic data were excluded. Patients were first classified according to the underlying type of fibrosing ILD. For statistical analyses of outcomes, 2 cohorts were compared within each subtype: progressive fibrosing ILD vs not yet progressed ILD. The final study population included propensity score-matched (PSM) patients (1:1) based on pre-ILD baseline demographic and clinical characteristics. HCRU categories included inpatient hospitalization counts and the number of inpatient days and total costs (in 2021 US dollars), analyzed descriptively and weighted by the per -patient -per -month cost. Lin's regression was used to predict 12 -month total cost estimates for comparison by cohort. RESULTS: The distribution by underlying conditions was as follows: autoimmune ILD (n = 4,156), HP (n = 8,181), sarcoidosis (n = 775), and unclassified ILD/IIP (n = 18,635). After PSM, pre-ILD baseline variables were generally well balanced between the progressive and not yet progressed fibrosing ILD cohorts. For all underlying subtypes of ILD, patients in the progressive cohort had significantly more utilization and higher costs compared with patients in the not yet progressed cohort. Progressive cohorts had significantly higher adjusted rates of inpatient days among patients with at least 1 inpatient stay compared with the not yet progressed cohorts (all P < 0.01). In addition, the progressive cohorts had significantly higher adjusted 12 -month total costs, with the differences ranging from $24,493 to $55,072 (all comparisons P <0.001). CONCLUSIONS: Irrespective of underlying ILD type, patients with progressive fibrosing ILD had significantly increased HCRU and cost relative to those whose fibrosing ILD had not yet progressed.

BackgroundTo assess the characteristics of patients enrolled in the ILD-PRO Registry.MethodsThe ILD-PRO Registry is a multicentre US registry of patients with progressive pulmonary fibrosis. This registry is enrolling patients with an interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis who have reticular abnormality and traction bronchiectasis on HRCT, and who meet criteria for ILD progression within the prior 24 months. Patient characteristics were analysed based on the number of patients with available data.ResultsOf the first 491 patients enrolled, the majority were white (75.4%) and female (60.6%); 47.4% had a history of smoking. Reported ILDs were autoimmune disease-associated ILDs (47.2%), hypersensitivity pneumonitis (17.5%), idiopathic non-specific interstitial pneumonia (9.1%), interstitial pneumonia with autoimmune features (8.9%), unclassifiable ILD (7.6%), other ILDs (9.7%). At enrolment, median (Q1, Q3) FVC % predicted was 62.2 (49.4, 72.4) and DLco % predicted was 39.2 (30.2, 49.2). Median (Q1, Q3) total score on the St. George's Respiratory Questionnaire was 50.8 (35.9, 64.7). The most common comorbidities were gastroesophageal reflux disease (61.1%) and sleep apnoea (29.6%). Overall, 64.5% of patients were receiving immunosuppressive or cytotoxic therapy, 61.1% proton-pump inhibitors, 53.2% oral steroids, 19.8% nintedanib and 3.6% pirfenidone.ConclusionsPatients enrolled into the ILD-PRO Registry have a variety of ILD diagnoses, marked impairment in lung function and health-related quality of life, and high medication use. Longitudinal data from this registry will further our knowledge of the course of progressive pulmonary fibrosis.Trial RegistrationClinicalTrials.gov, NCT01915511; registered August 5, 2013.

Background Although inverse associations have been found between medication adherence and healthcare use and spending outcomes in many clinical settings, no studies to date have examined these relationships for patients with idiopathic pulmonary fibrosis (IPF) initiating nintedanib. We build on our prior study that used group-based trajectory modeling (GBTM) to compare inpatient hospitalization and medical care spending outcomes between groups of patients with different nintedanib adherence trajectories. Methods This analysis used 100% Medicare data and included beneficiaries with IPF who initiated nintedanib during 10/01/2014–12/31/2018. The sample consisted of community-dwelling older adults (≥ 66 years) with continuous coverage in Medicare Parts A (inpatient care), B (outpatient care) and D (prescription drugs) for one year before (baseline) and after (follow-up) initiating nintedanib. Patients were assigned to the GBTM-derived adherence trajectory group closest to their own nintedanib adherence experience. All-cause and IPF-related hospitalization events and total medical spending were measured during the follow-up period. Unadjusted and adjusted regression models were estimated to compare outcomes between patients in different nintedanib adherence trajectories. Results Among the 1,798 patients initiating nintedanib, the mean age was 75.4 years, 61.1% were male, and 91.1% were non-Hispanic white. The best-fitting GBTM had five adherence trajectories: high adherence, moderate adherence, high-then-poor adherence, delayed-poor adherence, and early-poor adherence. All-cause hospitalizations and total all-cause medical spending were higher among patients in the high-then-poor, delayed-poor and early-poor adherence trajectories than those in the high adherence trajectory. For example, adjusted total all-cause medical spending was $4,876 (95% CI: $1,470 to $8,282) higher in the high-then-poor adherence trajectory, $3,639 (95% CI: $1,322 to $5,955) higher in the delayed-poor adherence trajectory and $3,907 (95% CI: $1,658 to $6,156) higher in the early-poor adherence trajectory compared with the high adherence trajectory. IPF-related hospitalizations and medical care spending were higher among those in the high-then-poor adherence trajectory compared with those in the high adherence trajectory. Conclusions Poor adherence to nintedanib was associated with all-cause hospitalizations and medical costs. Therefore, improved adherence programs, such as support programs, can be implemented to reduce economic burden.