Social costs of icatibant self-administration vs. health professional-administration in the treatment of hereditary angioedema in Spain.

BACKGROUND: Icatibant is the only subcutaneous treatment for acute Type I and Type II hereditary angioedema with C1-esterase inhibitor deficiency (HAE-C1-INH) licensed for self-administration in Europe. AIM: To compare the economic impact of two icatibant administration strategies: health professional-administration only (strategy 1) versus including the patient self-administration option (strategy 2). METHODS: Economic evaluation model based on the building of a decision tree. Both strategies are assumed to have equivalent effectiveness. The payer (Spanish National Health System) and the social perspectives were considered. All relevant cost-generating factors were taken into account. The time horizon was one year. Sources of information included scientific evidence, official data and experts' opinion. A deterministic sensitivity analysis was carried out to quantify the underlying uncertainty in the model. RESULTS: From the social perspective, which considers both direct (health care costs) and indirect costs (productivity losses), strategy 2 would result into average savings of €121.30 per acute attack compared to strategy 1. For Spain, this would achieve in an annual savings of €551,371. The reduction in direct costs accounts for 74% of the savings and lower indirect costs account for the remaining 26%. Savings per acute attack may range from €79.50 to €169.80; accordingly, the annual savings in Spain may vary between €90,319 and €2,315,360. CONCLUSION: Costs related to the management of acute HAE attacks with C1 inhibitor deficiency may be substantially reduced through interventions targeting home treatment by training patients to self-administer icatibant.

Chronological assessment of mast cell-mediated gut dysfunction and mucosal inflammation in a rat model of chronic psychosocial stress.

Life stress and mucosal inflammation may influence symptom onset and severity in certain gastrointestinal disorders, particularly irritable bowel syndrome (IBS), in connection with dysregulated intestinal barrier. However, the mechanism responsible remains unknown. Crowding is a validated animal model reproducing naturalistic psychosocial stress, whose consequences on gut physiology remain unexplored. Our aims were to prove that crowding stress induces mucosal inflammation and intestinal dysfunction, to characterize dynamics in time, and to evaluate the implication of stress-induced mast cell activation on intestinal dysfunction. Wistar-Kyoto rats were submitted to 15 days of crowding stress (8 rats/cage) or sham-crowding (2 rats/cage). We measured spontaneous and corticotropin-releasing factor-mediated release of plasma corticosterone. Stress-induced intestinal chrono-pathobiology was determined by measuring intestinal inflammation, epithelial damage, mast cell activation and infiltration, and intestinal barrier function. Corticosterone release was higher in crowded rats throughout day 15. Stress-induced mild inflammation, manifested earlier in the ileum and the colon than in the jejunum. While mast cell counts remained mostly unchanged, piecemeal degranulation increased along time, as the mucosal content and luminal release of rat mast cell protease-II. Stress-induced mitochondrial injury and increased jejunal permeability, both events strongly correlated with mast cell activation at day 15. Taken together, we have provided evidences that long-term exposure to psychosocial stress promotes mucosal inflammation and mast cell-mediated barrier dysfunction in the rat bowel. The notable resemblance of these findings with those in some IBS patients, support the potential interest and translational validity of this experimental model for the research of stress-sensitive intestinal disorders, particularly IBS.