Ferric derisomaltose for the treatment of iron deficiency anemia with postpartum hemorrhage: Results of a single-arm, open-label, phase 3 study in Japan.

AIM: Single-arm, open-label, phase 3 study to evaluate the efficacy and safety of ferric derisomaltose (FDI) for iron deficiency anemia (IDA) in Japanese women with postpartum hemorrhage (PPH). METHODS: Postpartum women aged 20-39 years with serum ferritin <25.0 ng/ml, hemoglobin (Hb) <10.0 g/dl, and blood loss ≥500 ml within 24 h post-delivery were eligible to receive high-dose intravenous FDI. The primary endpoint was the maximum change in Hb concentration by Week 8. Key secondary endpoints included change in iron parameters and percentage of patients with a total Edinburgh Postnatal Depression Score (EPDS) ≥9. Safety assessments included treatment-emergent adverse events (TEAEs) and iron concentrations in maternal milk. RESULTS: All (n = 21 [100.0%]) patients received the predetermined total iron dose by Day 8. Hb concentrations increased rapidly and significantly (p < 0.001) following FDI. Serum ferritin levels also increased rapidly and were maintained near or above the upper limit of normal reference value (250 ng/ml). Following FDI, two (9.5%) patients had a total EPDS score of ≥9. TEAEs occurred in 23 of 42 (54.8%) patients and neonates overall, including 18 of 21 (85.7%) patients and 5 of 21 (23.8%) neonates. TEAEs were mild in all adult patients and four neonates, and moderate in one neonate. Iron concentrations in maternal milk remained within normal reference values. Appropriate patient selection and patient-adjusted dosage selection facilitated safe and effective administration of high-dose (≥1000 mg) FDI. CONCLUSIONS: Rapid and sustained improvements in Hb and iron stores occurred following FDI for IDA with PPH, with no new safety signals identified. CLINICAL TRIAL IDENTIFIER: JapicCTI-194888.

Polycyclic aromatic hydrocarbons aggravate antigen-induced nasal blockage in experimental allergic rhinitis.

It has been hypothesized that air pollution has played a role in the increase in allergy prevalence. However, it remains unclear what exact roles are played by polycyclic aromatic hydrocarbons (PAHs), which are encountered in the environment in the form of air pollution, in allergic rhinitis. Thus, we examined whether benzo(a)pyrene (BaP) and 1-nitropyrene (1-NP), representative PAHs, aggravate allergic rhinitis symptoms, using a guinea-pig model. Sensitized animals were repeatedly challenged by inhalation of Japanese cedar pollen once a week. BaP or 1-NP was daily and intranasally administered for 2 weeks (short-term treatment) or for 22 weeks from the time before the sensitization period (long-term treatment). The short-term treatment affected neither nasal blockage nor sneezing induced by antigen. In contrast, the long-term treatment aggravated the antigen-induced nasal blockage that was induced 7 weeks after the start of the treatment with BaP or 1-NP. This aggravation continued during the intranasal treatment with PAH. However, neither sneezing nor Cry j 1-specific IgE antibody production was affected even by the long-term treatment. In conclusion, the long-term treatment with BaP and 1-NP can aggravate allergic rhinitis. The mechanisms underlying this aggravation are not associated with production of Cry j 1-specific IgE.