In the Phase III INPULSIS® trials, 52 weeks’ treatment with nintedanib reduced decline in forced vital capacity (FVC) versus placebo in patients with idiopathic pulmonary fibrosis (IPF). Patients who completed the INPULSIS® trials could receive nintedanib in an open-label extension trial (INPULSIS®-ON). Patients with FVC <50 % predicted were excluded from INPULSIS®, but could participate in INPULSIS®-ON. In patients with baseline FVC ≤50 % and >50 % predicted at the start of INPULSIS®-ON, the absolute mean change in FVC from baseline to week 48 of INPULSIS®-ON was −62.3 and −87.9 mL, respectively (n = 24 and n = 558, respectively). No new safety signals were identified in INPULSIS®-ON compared with INPULSIS®. The decline in FVC in INPULSIS®-ON in both subgroups by baseline FVC % predicted was similar to that in INPULSIS®, suggesting that nintedanib may have a similar effect on disease progression in patients with advanced disease as in less advanced disease.
A chylothorax and a cholesterol pleural effusion represent the two forms of lipid effusions encountered. Traditionally, a lipid pleural effusion is characterized by the presence of milky fluid. Although these two effusions often share a similar pleural fluid appearance due to the high lipid concentration, they have major differences in the pathogenesis, clinical presentation, diagnosis, predisposing conditions, and management of these effusions. A chylothorax is defined by the presence of chyle in the pleural space resulting from obstruction or disruption of the thoracic duct or one of its major tributaries. A triglyceride concentration > 110 mg/dL is virtually diagnostic, but the presence of chylomicrons confirms the diagnosis. However, a chylothorax defined by these criteria represents a heterogeneous group of clinical entities. The presence of chylomicrons or triglyceride levels > 110 mg/dL in a pleural effusion should be considered evidence of chyle leakage of indeterminate clinical significance. Many cases of a chylous effusion may be associated with other causes of pleural fluid formation. In the case of an acute or chronic chylothorax due to recent or remote thoracic duct injury, this assessment is essential, as surgical ligation of the thoracic duct is often entertained. In other cases, especially lymphoma or chylous ascites, treatment of the underlying condition is indicated regardless, and the assessment of the response to treatment is a reasonable initial approach. In contrast, a cholesterol effusion is typically the result of long-standing pleurisy with elevated cholesterol levels in the pleural space; however, this paradigm has been challenged. Lung entrapment with thickened parietal and visceral pleural membranes is the typical radiographic findings of a cholesterol effusion. Most cases of cholesterol pleural effusions are attributed to tuberculous or rheumatoid pleurisy. Decortication is the mainstay of treatment for a cholesterol effusion in symptomatic patients with restrictive lung function.
We assessed safety and tolerability of treatment with pirfenidone (1602–2403 mg·day−1) and nintedanib (200–300 mg·day−1) in patients with idiopathic pulmonary fibrosis (IPF).This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≥50% and diffusing capacity of the lung for carbon monoxide % pred ≥30%. Before initiating nintedanib, patients had received pirfenidone for ≥16 weeks and tolerated a stable dose of ≥1602 mg·day−1 for ≥28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602–2403 mg·day−1) and nintedanib (200–300 mg·day−1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither.89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatment-related TEAEs.Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF.
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