Efficacy and safety of dupilumab with concomitant topical corticosteroids in Japanese pediatric patients with moderate-to-severe atopic dermatitis: A randomized, double-blind, placebo-controlled phase 3 study.

BACKGROUND: We investigated the efficacy and safety of dupilumab in Japanese patients aged ≥6 months to <18 years old with moderate-to-severe atopic dermatitis not adequately controlled with existing therapies. METHODS: In this randomized, double-blind, phase 3 study, patients received dupilumab (n = 30) or placebo (n = 32) with concomitant topical corticosteroids for 16 weeks, then all patients received dupilumab from 16 to 52 weeks. The primary endpoint was the proportion of patients with ≥75% improvement in Eczema Area and Severity Index (EASI) score from baseline (EASI-75) to Week 16. Key secondary endpoints included changes in EASI score, proportion of patients with investigator global assessment (IGA) scores of 0/1, and changes in worst daily itch numerical rating scale (NRS) scores (evaluated in patients aged ≥6 to <12 years [n = 35]). RESULTS: At Week 16, more patients achieved EASI-75 with dupilumab than placebo (43.3% vs 18.8%; P = 0.0304), and the least squares mean (LSM) difference in percent change in EASI scores at Week 16 of dupilumab vs placebo was -39.4% (P = 0.0003). However, no significant difference in the proportion of patients achieving IGA scores of 0/1 at Week 16 with dupilumab versus placebo were seen (10.0% vs 9.4%; P = 0.8476). The percent change in worst daily itch NRS scores at Week 16 was higher with dupilumab (LSM difference: -33.3%; nominal P = 0.0117). Dupilumab was well tolerated; no new safety signals were identified. CONCLUSIONS: Dupilumab showed consistent efficacy and was well tolerated in Japanese patients aged ≥6 months to <18 years with moderate-to-severe atopic dermatitis previously insufficiently controlled with existing therapies.

Analysis of the intracellular localization of amiodarone using live single-cell mass spectrometry.

Amiodarone is a well-known antiarrhythmic drug with side effects including phospholipidosis. However, it is not clear how amiodarone and its metabolites are localized in the cell. In the present study, the localization of amiodarone in the cytosol, vacuoles, and lipid droplets of a single HepG2 human hepatocellular carcinoma cell was determined directly using live single-cell mass spectrometry. The cytosol, vacuoles, and lipid droplets of a single HepG2 cell treated with amiodarone were separately captured using a nano-spray tip under a fluorescence microscope after visualizing the lipid droplets using a fluorescent probe. This assay showed a linearity in the measurement of amiodarone levels with R2 values of 0.9996 and 0.9998 in the cell lysates and serum, respectively. The peak intensities of amiodarone and its metabolites in lipid droplets and vacuoles were significantly higher than those in the cytosol, while those in lipid droplets were higher than those in vacuoles. Amiodarone metabolites were detected in both lipid droplets and the cytosol. Live single-cell mass spectrometry combined with fluorescence imaging demonstrated clear localization of amiodarone and its metabolites in lipid droplets separately from the vacuole. This assay system combined with fluorescence imaging could be useful for investigating the intracellular localization of various drugs and their metabolites.