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.
BACKGROUND:Ensitrelvir (ESV) is approved in Japan for the treatment of mild to moderate COVID-19 in standard-risk patients; however, real-world evidence regarding outcomes among hospitalized high-risk patients remains limited. We evaluated whether oral ESV could serve as a feasible alternative to intravenous remdesivir (RDV). METHODS:We conducted a retrospective multicenter cohort study of hospitalized patients with mild to moderate COVID-19 and at least one risk factor for disease progression treated with ESV or RDV between June 2023 and March 2024 at two hospitals in Japan. Patients unable to receive oral therapy were excluded. Propensity score matching adjusted for baseline differences. The primary outcome was a composite of disease progression or all-cause mortality within 28 days. RESULTS:Among 207 patients, 44 received ESV and 163 received RDV. In the overall cohort, the composite outcome occurred in 4 vs. 10 patients (P = 0.49). After matching, 40 patients were included in each group; all patients in the matched cohort had mild disease without oxygen requirement. In the matched cohort, the composite outcome occurred in 4 patients in each group (P > 0.99). Individual components showed no significant differences (mortality: 4 vs. 3; progression: 2 vs. 2). CONCLUSIONS:In this multicenter cohort of hospitalized high-risk patients with mild to moderate COVID-19 able to receive oral therapy, no significant differences were observed between ESV and RDV in the matched cohort of patients with mild disease. ESV may represent a feasible oral alternative in selected high-risk patients able to receive oral therapy.
Interferon-gamma release assays (IGRAs) are widely used for early diagnosis against TB. However, data on their diagnostic utility and clinical significance in elderly patients with active TB remian limited. We retrospectively analyzed patients over 65 years of age who underwent IGRA testing using either T-SPOT.TB (Oxford Immunotec, UK) or QuantiFERON (QFT) (Qiagen, Germany) between 2015–2024. Active pulmonary TB (ATB) was defined as TB confirmed by isolation from respiratory specimens within 90 days of IGRA testing. Latent TB infection (LTBI) was defined as IGRA-positive individuals without microbiological confirmation of TB. For individuals tested multiple times, only the most recent result was included. Values exceeding the detection threshold were recorded as maximum or minimum values. A total of 12,872 T-SPOT.Tb and 7,580 QFT tests were performed during the study period, of which 3,990 and 2,620 tests, respectively, met inclusion criteria. For T-SPOT.TB, 138 (3.5%) were diagnosed with ATB, with a positive rate of 83.3%. The median quantitative scores were 50 (IQR: 16 - 50) for ESAT-6 and 21 (IQR: 9 - 50) for CFP-10. LTBI was identified in 605 patients (15.7%), with median quantitative scores 16 (IQR: 8 - 41) for ESAT-6 and 11 (IQR: 3 - 32) for CFP-10. For QFT, 87 (3.3%) were diagnosed with ATB, with a positive rate of 67.8%. The median quantitative scores were 1.64 (IQR: 0.62 – 4.0) for TB1 and 2.08 (IQR: 0.65 – 4.86) for TB2. The number of LTBI was 198 (7.8 %) with median quantitative scores of 0.85 (IQR: 0.46 – 2.16) for TB1 and 0.94 (IQR: 0.52 – 2.14) for TB2, respectively. The best cut-off values were 3.1 (sensitivity: 23.0%; specificity: 87.4%), 3.6 (sensitivity: 28.7%; specificity: 85.4%) for TB1 and Tb2, 50 (sensitivity: 78.7%; specificity: 42.0%), 33 (sensitivity: 75.5%; specificity: 42.0%) for ESAT-6 and CFP-10, respectively. Quantitative IGRA values were higher in patients with active TB than in those with latent infection. Notably, T.SPOT-TB might be possible to differentiate ATB and LTBI in elderly populations. These findings support the potential clinical utility of TB-SPOT.TB for TB diagnosis in aging populations in Japan. Yoshikazu Mutoh, graduate student, MSD, Co LTD: Honoraria Yusuke Minato, Ph.D., Shionogi & Co., Ltd.: Grant/Research Support Yohei Doi, MD, PhD, GSK: Advisor/Consultant|Meiji Seika Pharma: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria
