Anti-glycyl-tRNA synthetase (anti-EJ) antibody is occasionally positive in patients with interstitial lung disease (ILD). We aimed to define the clinical, radiological and pathological features of patients with anti-EJ antibody-positive ILD (EJ-ILD). We retrospectively analyzed the medical records of 12 consecutive patients with EJ-ILD who underwent surgical lung biopsy. The median follow-up time was 74 months (range, 17–115 months). The median age was 62 years (range, 47–75 years). Seven of 12 patients were female. Eight patients presented with acute onset. Six patients eventually developed polymyositis/dermatomyositis. On high-resolution computed tomography, consolidation and volume loss were predominantly observed in the middle or lower lung zone. Nine patients presented pathologically nonspecific interstitial pneumonia with organizing pneumonia, alveolar epithelial injury and prominent interstitial cellular infiltrations whereas the other three patients were diagnosed with unclassifiable interstitial pneumonia. Although all patients but one improved with the initial immunosuppressive therapy, five patients relapsed. When ILD relapsed, four of the five patients were treated with corticosteroid monotherapy. Four of the six patients without relapse have been continuously treated with combination therapy of corticosteroid and immunosuppressant. Patients with EJ-ILD often had acute onset of ILD with lower lung-predominant shadows and pathologically nonspecific interstitial pneumonia or unclassifiable interstitial pneumonia with acute inflammatory findings. Although the disease responded well to the initial treatment, relapse was frequent. Because of the diversity of the clinical courses, combination therapy of corticosteroid and immunosuppressant should be on the list of options to prevent relapse of EJ-ILD.

Aim: To assess the clinical features/imaging characteristics of pneumonitis reported during nationwide nivolumab postmarketing surveillance in Japan. Patients & methods: Clinical and radiological data were collected from pneumonitis cases reported during/after nivolumab treatment for melanoma or non-small-cell lung cancer. The expert central review committee evaluated each case. Results: Among 144 cases analyzed, 91 (63.2%) had radiological patterns considered typical for drug-induced pneumonitis and 53 (36.8%) patients had previously unobserved patterns with one or more atypical features, including 23 cases (16.0%) with ground glass opacity confined to the area around the tumor (peritumoral infiltration). A higher proportion of patients with (vs without) peritumoral infiltration had an antitumor response to nivolumab. Conclusion: Images of nivolumab-induced pneumonitis showed previously unobserved radiological patterns.

Current clinical practice guidelines for idiopathic pulmonary fibrosis (IPF) conditionally recommend use of pirfenidone and nintedanib. However, an optimal treatment sequence has not been established, and the data of treatment sequence from pirfenidone to nintedanib are limited. This study aimed to evaluate safety, tolerability and efficacy of nintedanib switched from pirfenidone in patients with IPF. Thirty consecutive IPF cases, which discontinued pirfenidone because of a decline in forced vital capacity (FVC) or intolerable adverse event (AE), and newly started nintedanib (150 mg twice daily) from September 2015 to August 2017 (switch-group) were retrospectively reviewed. Subsequently, we compared the characteristics, treatment status, and AEs between the switch-group and other 64 IPF patients newly started nintedanib during the same period without any prior anti-fibrotic treatment (pirfenidone-naïve group). In the switch group, median age, body weight, body mass index (BMI), and %FVC were 72 years old, 54.9 kg, 21.0 kg/m2, and 52.9%, respectively. Most common AE of nintedanib was aspartate aminotransferase/alanine aminotransferase elevation (71.9%), followed by anorexia (46.7%) and diarrhea (46.7%); whereas, anorexia (63.3%) and ≥ 5% weight loss from baseline (56.7%) were common during pirfenidone administration. Sixteen patients (53.3%) discontinued nintedanib within 6 months (early termination). Multivariate logistic regression analysis revealed a significant association between low BMI and early nintedanib termination in the switch-group (p = 0.0239). Nintedanib suppressed FVC decline as compared with that during administration period of pirfenidone in 70% of the patients who could undergo lung function before and after switching to nintedanib. The incidence of early termination of nintedanib was higher in the switch-group than in the pirfenidone-naïve group, whereas body-weight, BMI, absolute FVC values, and %FVC were significantly lower in the switch-group (just before nintedanib initiation) than in the pirfenidone-naïve group. Nintedanib-induced anorexia was more frequent and severer in the switch-group than in the pirfenidone-naïve group, but no significant differences were observed in terms of other AEs. A high incidence of early termination of nintedanib was noted when patients were switched from pirfenidone. Anorexia and weight loss during prior pirfenidone administration may increase the rate of the early termination of subsequent nintedanib treatment.

The different characteristics of usual interstitial pneumonia in patients with primary Sjögren׳s syndrome (UIP/pSS) compared with idiopathic pulmonary fibrosis (UIP/IPF) are not fully understood. This study aimed to compare characteristics, prognosis, and treatment responses in these patients. Among 129 consecutive patients who underwent surgical lung biopsy to diagnose diffuse lung diseases at Kanagawa Cardiovascular and Respiratory Center between 1998 and 2002, we identified 10 and 19 patients with UIP/pSS and UIP/IPF, respectively. Baseline characteristics, chest high-resolution computed tomography (HRCT) and pathological findings, and the clinical course were compared between the two groups. Responses to immunosuppressive therapy were analyzed by comparing pulmonary function and clinical status before and one year after treatment initiation. More patients in the UIP/pSS group tended to be female and older than those in the UIP/IPF group (mean age, 68 years vs. 62 years). In addition, they more commonly exhibited enlarged mediastinal lymph nodes and bronchial wall thickening on HRCT. Pathologically, in the UIP/pSS group, interstitial inflammation, plasma cell infiltration, lymphoid follicles with germinal centers, cysts, bronchiolitis, and pleuritis were significantly more prominent, whereas smooth muscle hyperplasia and fibroblastic foci were milder (all P<0.05). The prognosis was better for UIP/pSS compared with UIP/IPF patients (P=0.01). In addition, immunosuppressive therapy provided better disease control for those with UIP/pSS (83%, 5/6) compared UIP/IPF (7%, 1/15). This study identified distinct clinical, radiological, and pathological characteristics of UIP/pSS compared with UIP/IPF. Immunosuppressive treatment could be a therapeutic option for UIP/pSS.

Objective: Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan. Methods: Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018. Results: The median observation period in the safety analysis population (n = 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade ≥ 3, 0.1% [5/3578]), 5.9% (212/3578; Grade ≥ 3, 1.0% [35/3578]) and 11.4% (409/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval [CI], 75.9–78.9) and 53.2% (95% CI, 51.3–55.1) and overall survival rates were 88.3% (95% CI, 87.2–89.4) and 75.4% (95% CI, 73.8–77.0), respectively. Conclusions: These data support the currently established benefit-risk assessment of osimertinib in this patient population.