Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial.

BACKGROUND & AIMS: Topical steroids are effective treatments for eosinophilic esophagitis (EoE). The FLUTE (Fluticasone in EoE) trial evaluated safety and efficacy of APT-1011 (fluticasone propionate oral disintegrating tablet) vs placebo for treatment of EoE. METHODS: In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011 doses or placebo for a 12-week induction period and 40 weeks of maintenance. Primary outcome was histologic response (≤6 eosinophils per high-power field) at Week 12. Secondary outcomes included endoscopic features and dysphagia frequency. RESULTS: Histologic response rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). At Week 12, mean Edema/Rings/Exudates/Furrows/Strictures (EoE Endoscopic Reference Score) total score (max, 9.0) improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. Mean dysphagia frequency over 14 days improved from baseline to Week 12 with all active groups improving more than placebo. Improvements were sustained to Week 52. APT-1011 was safe and well-tolerated, with higher incidence of candidiasis noted at the higher twice daily doses. CONCLUSION: APT-1011 dosing regimens were superior for histologic and endoscopic responses, and for reduction in dysphagia frequency vs placebo. Based on the symptom improvement and assessment of adverse events together with the histologic response rate, 3 mg once daily at bedtime dose showed the most favorable risk-benefit profile. CLINICALTRIALS: gov, Number: NCT03191864.

Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study.

Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results: Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).

Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers: relationships to interstitial fibrosis (ILO profusion score) and pleural thickening.

BACKGROUND: Asbestosis is an interstitial lung disease whose radiographic severity has long been graded by the International Labour Office (ILO) profusion score. Its effect on pulmonary function is further impacted by asbestos related pleural thickening. OBJECTIVES: This report aims to describe the relationships between radiographic grading of interstitial and pleural fibrosis and a key test of pulmonary function, the diffusing capacity, which measures gas exchange and has rarely been assessed in large groups, and to confirm the relationship to an independent test of pulmonary function, the vital capacity, which measures a mechanical property of the lungs. METHODS: The data were derived from a survey during the period 1997-2004 of 5,003 workers (all white males) exposed to asbestos in various trades. Tests included chest radiographs read by a certified expert ("B") reader, forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLco). Cigarette smoking was adjusted for in the predictive equation for DLCO . Workers were evaluated at a mobile facility at work sites in four southern states. RESULTS: Both diffusing capacity and vital capacity were negatively correlated with profusion score over the full spectrum of radiographic severity. ILO profusion scores 0/1 (conventionally classified as normal) and 1/0 (conventionally classified as abnormal) were associated with similar diffusing capacity and vital capacity values. The highest profusion scores were associated with a greater proportionate decrease in diffusing capacity than in FVC. Both tests showed an effect of pleural fibrosis. CONCLUSIONS: Both radiographic severity graded by the profusion score and pleural thickening are correlated with two independent measures of pulmonary function. FVC (which had been reported in smaller work forces) and DLCO (which has not been reported). Both measures show a decrease from normal to intermediate (0/1, 1/0) scores and a further decrease with greater scores, demonstrating the consistency of radiographic and functional assessments.