Cost-Analysis of Subcutaneous vs Intravenous Administration of Natalizumab Based on Patient Care Pathway in Multiple Sclerosis in Spain.

INTRODUCTION: A subcutaneous (SC) formulation of natalizumab has been recently authorised for multiple sclerosis patients. This study aimed to assess the implications of the new SC formulation, and to compare the annual treatment costs of SC versus intravenous (IV) natalizumab therapy from both the Spanish healthcare system (direct health cost) and the patient (indirect cost) perspectives. METHODS: A patient care pathway map and a cost-minimisation analysis were developed to estimate SC and IV natalizumab annual costs over a 2-year time horizon. Considering the patient care pathway and according to natalizumab experience (IV) or estimation (SC), a national expert panel involving neurologists, pharmacists, and nurses provided information/data regarding resource consumption for drug and patient preparation, administration, and documentation. One hour of observation was applied to the first six (SC) or 12 (IV) doses, and 5 min for successive doses. The Day hospital (infusion suite) facilities at a reference hospital were considered for IV administrations and the first six SC injections. For successive SC injections, either a reference hospital or regional hospital in a consulting room was considered. Productivity time associated with travel (56 min to reference hospital, 24 min to regional hospital) and waiting time pre- and post-treatment (SC 15 min, IV 25 min) were assessed for patients and caregivers (accompanying 20% of SC and 35% of IV administrations). National salaries for healthcare professionals were used for cost estimation (€, year 2021). RESULTS: At years 1 and 2, total time and cost savings (excluding drug acquisition cost) per patient, driven by saving on administration and patient and caregiver productivity for SC at a reference hospital versus IV at a reference hospital, were 116 h (a reduction of 54.6%) and €3682.82 (a reduction of 66.2%). In the case of natalizumab SC at a regional hospital, the total time and cost saving were 129 h (a reduction of 60.6%) and €3883.47 (a reduction of 69.8%). CONCLUSIONS: Besides the potential benefits of convenient administration and improving work-life balance, as suggested by the expert panel, natalizumab SC was associated with cost savings for the healthcare system by avoiding drug preparation, reducing administration time, and freeing up infusion suite capacity. Additional cost savings could be derived with regional hospital administration of natalizumab SC by reducing productivity loss.

EFNA3 long noncoding RNAs induced by hypoxia promote metastatic dissemination.

The presence of hypoxic regions in solid tumors is an adverse prognostic factor for patient outcome. Here, we show that hypoxia induces the expression of Ephrin-A3 through a novel hypoxia-inducible factor (HIF)-mediated mechanism. In response to hypoxia, the coding EFNA3 mRNA levels remained relatively stable, but HIFs drove the expression of previously unknown long noncoding (lnc) RNAs from EFNA3 locus and these lncRNA caused Ephrin-A3 protein accumulation. Ephrins are cell surface proteins that regulate diverse biological processes by modulating cellular adhesion and repulsion. Mounting evidence implicates deregulated ephrin function in multiple aspects of tumor biology. We demonstrate that sustained expression of both Ephrin-A3 and novel EFNA3 lncRNAs increased the metastatic potential of human breast cancer cells, possibly by increasing the ability of tumor cells to extravasate from the blood vessels into surrounding tissue. In agreement, we found a strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patients. Taken together, our results suggest that hypoxia could contribute to metastatic spread of breast cancer via HIF-mediated induction of EFNA3 lncRNAs and subsequent Ephrin-A3 protein accumulation.