This is the official English summary of the Japanese 2025 guide. The first edition of the guide for the diagnosis and management of connective tissue disease (CTD) associated with interstitial lung disease (ILD) was published in 2020 as a joint initiative by the Japanese Respiratory Society and the Japanese College of Rheumatology. This updated edition reflects major advances over the past five years, incorporating the latest international guidelines, consensus statements, and considerations unique to the Japanese healthcare reimbursement system. The guide is structured to facilitate timely clinical decision-making by highlighting key diagnostic and therapeutic milestones. The newly added content includes a conceptual framework for understanding ILD in CTD, practical clinical flowcharts, screening strategies, and risk factors, an overview of acute exacerbations, and a comprehensive approach to rehabilitation. Notably, treatment algorithms for ILD associated with polymyositis/dermatomyositis and systemic sclerosis have been revised to align with the most recent evidence and disease-specific recommendations, thereby enhancing their relevance to real-world practice. In addition, a provisional algorithm was proposed for the management of rheumatoid arthritis-associated ILD. The updated guide aims to standardize the multidisciplinary management of CTD-associated ILD and offers future perspectives to guide research and improve patient outcomes.
Objective:Progressive pulmonary fibrosis (PPF) is a chronic interstitial lung disease (ILD) characterised by fibrotic progression and poor prognosis, with effective treatment strategies for previously untreated patients remaining unclear. This study evaluated the efficacy and safety of upfront combination therapy with anti-inflammatory and antifibrotic agents in previously untreated PPF patients. Methods:This multicentre, single-arm phase 2 study enrolled 34 patients with ILD (including unclassifiable idiopathic interstitial pneumonia, idiopathic nonspecific interstitial pneumonia, fibrotic hypersensitivity pneumonitis and rheumatoid arthritis-associated ILD) all with evidence of PPF. Tacrolimus (0.0375 mg·kg-1 twice daily) and prednisolone (10 mg once daily) were initiated on day 1, with nintedanib (150 mg twice daily) added on day 8. The tacrolimus dosage was adjusted to maintain blood trough levels. The primary end-point was the change in the relative decline slope for forced vital capacity % predicted (%FVC) between before and after treatment. Results:The protocol treatment was associated with a substantial improvement in the relative %FVC decline slope, from -20.9% per year before to +11.2% per year after treatment. Subgroup analysis revealed greater improvement in patients with an increased lymphocyte percentage in bronchoalveolar lavage fluid or elevated blood biomarkers. Adverse events, such as diarrhoea (67.6%) and hepatic dysfunction (29.4%), were manageable, with no severe cases or treatment discontinuations. Conclusion:Early combination therapy with tacrolimus, prednisolone and nintedanib was associated with improved pulmonary function and was well tolerated in previously untreated PPF patients. Our findings suggest the potential of this regimen as an initial treatment strategy, but further validation in larger randomised controlled trials is warranted.
The objective of this study was to investigate the clinical and imaging features of tepotinib-induced interstitial lung disease (ILD) using real-world data obtained during routine clinical use of tepotinib in Japan. The study was conducted as a voluntary safety-monitoring activity and targeted cases reported during the period from 1st June 2020 (the launch date of tepotinib in Japan) to 31st December 2023. An ILD adjudication committee, composed of external respiratory and radiology experts, assessed the clinical and imaging features of the ILD. The committee expertly identified 35 patients with tepotinib-induced ILD, with an estimated reported incidence of 2.9% (35/1190 patients). The estimated reported incidence of the fatal ILD was 0.9% (11/1190 patients). More than half of the ILDs were classified as ≤grade 2 (19/35 patients), with the predominant imaging pattern of organizing pneumonia (OP) (15/19 patients), followed by hypersensitivity pneumonitis (HP) and diffuse alveolar damage (DAD) patterns (3 and 1/19 patients, respectively). In contrast, among the ≥grade 3 ILDs (15/35 patients), DAD was the most frequently observed pattern (7/15 patients), followed by OP and HP patterns (6 and 2/15 patients, respectively). The median time to onset of the 35 ILDs from the start of tepotinib administration was 50.0 days (range: 4-205 days). Fatal outcomes occurred more frequently in patients with pre-existing ILD/interstitial lung abnormality (ILA) (8/12 patients), whereas most patients without pre-existing ILD/ILA experienced better outcomes of recovered/resolving (19/23 patients). These findings highlight the importance of close monitoring for ILD occurrence during the real-world clinical use of tepotinib.
Although the global emergency phase of the coronavirus disease 2019 (COVID-19) pandemic has ended, antiviral therapy remains crucial for patients at high risk of severe illness. In Japan, the out-of-pocket costs for antiviral drugs shifted from full public coverage to partial patient payment in April 2024. However, the impact of physicians’ background characteristics on antiviral cost perceptions and prescribing behavior remains underexplored. This study involved a secondary analysis of a nationwide, web-based interventional survey of 1,500 physicians treating COVID-19. Participants reported whether they avoided prescribing antivirals owing to drug costs and identified what they considered an appropriate cost per treatment course. Associations between physicians’ characteristics and their cost perceptions were analyzed. Among 1,500 physicians surveyed, 1,193 (79.5
Background Although anti-Ku antibodies have been reported in various connective tissue diseases (CTDs), data on the clinical characteristics of anti-Ku antibody-positive interstitial lung disease (ILD) remain limited. This study investigated the clinical, radiological, and pathological features of anti-Ku antibody-positive ILD. Methods We retrospectively reviewed 13 patients with anti-Ku antibody-positive ILD at our institution between 2018 and 2025. Data on baseline characteristics, imaging, pathology, treatment, and outcomes were collected. Results Seven patients (53.8%) were diagnosed with CTDs. CTD was present in idiopathic inflammatory myopathy (IIM; n = 2), systemic sclerosis (SSc), IIM with SSc overlap, microscopic polyangiitis, rheumatoid arthritis, and Sjögren’s syndrome (n = 1, each). ILD preceded the diagnosis of CTDs in two of these patients. Nonspecific interstitial pneumonia (NSIP) was the most frequent pattern (n = 5, 38.5%) on chest computed tomography, followed by usual interstitial pneumonia (probable UIP, n = 4, 30.8%). On lung histopathology, the patterns were heterogeneous; fibrotic NSIP and NSIP with organizing pneumonia were each observed in two patients, whereas UIP features were present in four patients. During the observation period (mean 51.7 ± 32.1 months), four patients developed progressive pulmonary fibrosis (PPF). Among the seven patients in whom any radiological and/or pathological UIP feature was present, four (57.1%) developed PPF or experienced acute exacerbation. Conclusions Anti-Ku antibody-positive ILD shows a heterogeneous clinical spectrum that includes both CTD-associated and non-CTD phenotypes. Progressive fibrotic disease was observed in both groups, while radiological and/or pathological UIP features may help identify patients at increased risk of disease progression.
