Pirfenidone in unclassifiable interstitial lung disease: a subgroup analysis by concomitant mycophenolate mofetil and/or previous corticosteroid use

Introduction There are currently no approved treatments solely for unclassifiable interstitial lung disease (uILD); however, a recent trial showed this population can benefit from pirfenidone. We report a subgroup analysis of this trial to assess the effects of immunomodulators (concomitant mycophenolate mofetil [MMF] and/or previous corticosteroids) with pirfenidone in patients with uILD. Methods This was a multicenter, international, double-blind, randomized, placebo-controlled phase II trial of patients with progressive fibrosing uILD (NCT03099187). Patients were randomized (1:1) to receive pirfenidone 2403 mg/day or placebo. This analysis assessed forced vital capacity (FVC) change from baseline measured using site spirometry (key secondary endpoint) and safety over 24 weeks by concomitant MMF use at randomization (pre-specified analysis) and/or previous corticosteroid use (post hoc analysis). Results Overall, 253 patients were randomized, including 45 (17.8%) patients (pirfenidone, n = 23; placebo, n = 22) receiving concomitant MMF with/without previous corticosteroids (MMF subgroup); 79 (31.2%) patients (pirfenidone, n = 44; placebo, n = 35) receiving previous corticosteroids without MMF (corticosteroids/no-MMF subgroup); and 129 (51.0%) patients (pirfenidone, n = 60; placebo, n = 69) not receiving concomitant MMF or previous corticosteroids (no-corticosteroids/no-MMF subgroup). At 24 weeks, difference in mean (95% confidence interval) FVC change from baseline between pirfenidone and placebo was − 55.4 mL (− 206.7, 96.0; P = 0.4645) in the MMF subgroup; 128.4 mL (− 6.4, 263.3; P = 0.0617) in the corticosteroids/no-MMF subgroup; and 115.5 mL (35.1, 195.9; P = 0.0052) in the no-corticosteroids/no-MMF subgroup. All subgroups generally exhibited a similar pattern of treatment-emergent adverse events. Conclusion Although limited by design and small sample sizes, this analysis suggests pirfenidone may be less effective in patients with uILD receiving concomitant MMF, whereas a beneficial treatment effect was observed in patients not receiving concomitant MMF regardless of previous corticosteroid use. Pirfenidone was well tolerated regardless of MMF and/or corticosteroid use. Trial Registration Number ClinicalTrials.gov: NCT03099187

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials an

A review of the challenges, learnings and future directions of home handheld spirometry in interstitial lung disease

Background Patients with interstitial lung disease (ILD) require regular physician visits and referral to specialist ILD clinics. Difficulties or delays in accessing care can limit opportunities to monitor disease trajectory and response to treatment, and the COVID-19 pandemic has added to these challenges. Therefore, home monitoring technologies, such as home handheld spirometry, have gained increased attention as they may help to improve access to care for patients with ILD. However, while several studies have shown that home handheld spirometry in ILD is acceptable for most patients, data from clinical trials are not sufficiently robust to support its use as a primary endpoint. This review discusses the challenges that were encountered with handheld spirometry across three recent ILD studies, which included home spirometry as a primary endpoint, and highlights where further optimisation and research into home handheld spirometry in ILD is required. Abstract body Rate of decline in forced vital capacity (FVC) as measured by daily home handheld spirometry versus site spirometry was of primary interest in three recently completed studies: STARLINER (NCT03261037), STARMAP and a Phase II study of pirfenidone in progressive fibrosing unclassifiable ILD (NCT03099187). Unanticipated practical and technical issues led to problems with estimating FVC decline. In all three studies, cross-sectional correlations for home handheld versus site spirometry were strong/moderate at baseline and later timepoints, but longitudinal correlations were weak. Other issues observed with the home handheld spirometry data included: high within-patient variability in home handheld FVC measurements; implausible longitudinal patterns in the home handheld spirometry data that were not reflected in site spirometry; and extreme estimated rates of FVC change. Conclusions Home handheld spirometry in ILD requires further optimisation and research to ensure accurate and reliable FVC measurements before it can be used as an endpoint in clinical trials. Refresher training, automated alerts of problems and FVC changes, and patient support could help to overcome some practical issues. Despite the challenges, there is value in incorporating home handheld spirometry into clinical practice, and the COVID-19 pandemic has highlighted the potential for home monitoring technologies to help improve access to care for patients with ILD

Serious adverse events in patients with idiopathic pulmonary fibrosis in the placebo arms of 6 clinical trials

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by irreversible loss of lung function and an unpredictable course of disease progression. Methods: The safety data for patients with IPF who received placebo in 6 clinical trials were pooled to examine the categories and frequencies of serious adverse events (SAEs) in this population. Results: In 1082 patients with IPF who received placebo, 673 SAEs were reported. Of these, 93 SAEs resulted in death (8.6% of patients). Respiratory-related conditions were the most frequently reported SAE (225 events, 16.33 per 100 patient-exposure years [PEY]), followed by infections and infestations (136 events, 9.87 per 100 PEY) and cardiac disorders (79 events, 5.73 per 100 PEY); these categories also had the most fatal outcomes (60, 10, and 10 deaths, respectively). The most frequently reported fatal respiratoryrelated SAEs were IPF and respiratory failure (38 and 11 patients, respectively), and the most frequently reported fatal infections and infestations and cardiac disorders were pneumonia (5 patients) and myocardial infarct

Design of a Study Assessing Disease Behaviour During the Peri-Diagnostic Period in Patients with Interstitial Lung Disease: The STARLINER Study

Background/Objectives: This study will aim to characterise disease behaviour during the peri-diagnostic period in patients with suspected interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF), using daily home spirometry and accelerometry. Additionally, this study will aim to increase collaboration between secondary and tertiary centres using a digital collaboration platform. Methods: The STARLINER study (NCT03261037) will enrol approximately 180 symptomatic patients aged 50 years or more with radiological evidence of ILD/IPF from community and tertiary centres in Canada and Europe. Approximately two-thirds of sites will be community centres. Patients will be followed during pre-diagnosis (inclusion to diagnosis; up to a maximum of 12 months) and post-diagnosis (diagnosis to treatment initiation; up to a maximum of 6 months). The study will be facilitated by a digital ecosystem consisting of the devices used for home-based assessments and a digital collaboration platform enabling communication between community and tertiary centres, and between clinicians and patients. Planned Outcomes: The primary endpoint will be time-adjusted semi-annual change in forced vital capacity (FVC; in millilitres) during the peri-diagnostic period. Physical functional capacity and patient-reported outcomes (PROs) will also be assessed. FVC and physical functional capacity will be measured using daily home spirometry and accelerometry, and at site visits using spirometry and the 6-min walk test. PROs will be assessed prior to, or during, site visits and will always be completed in the same order. Conclusions: Findings from this study may help to facilitate the early and accurate diagnosis of ILDs by increasing knowledge about disease progression, enabling collaboration between community and tertiary centres and improving communication between clinicians and patients. Trial Registration Number: NCT03261037. Funding: F. Hoffmann-La Roche, Ltd., Basel, Switzerland. Plain Language Summary: Plain language summary available for this article

Pirfenidone treatment in individuals with idiopathic pulmonary fibrosis: Impact of timing of treatment initiation

International audienceIdiopathic pulmonary fibrosis (IPF) is a debilitating, progressive, fatal, fibrosing lung disease. Pirfenidone and nintedanib are oral antifibrotics with demonstrated efficacy in reducing lung function decline in individuals with IPF, independent of baseline lung function. Intervention with an antifibrotic as early as possible in the disease course might be the most appropriate strategy to preserve lung capacity. However, many physicians are reluctant to initiate antifibrotics at diagnosis, and delay treatment until disease progression is observed. Furthermore, certain countries do not reimburse antifibrotic treatment for individuals with preserved lung function (% predicted forced vital capacity [FVC] > 80%). These post hoc analyses aimed to assess: 1) FVC decline during long-term pirfenidone treatment in RECAP in individuals with IPF categorized by baseline % predicted FVC; and 2) the impact of deferring pirfenidone treatment on annual FVC decline in individuals with IPF during CAPACITY and RECAP

Deferring treatment with pirfenidone results in loss of lung function that is not recovered by later treatment initiation

International audienc