Economic burden of highly active relapsing-remitting multiple sclerosis patients in the French national health insurance database.

BACKGROUND: As healthcare management of highly active-relapsing-remitting multiple sclerosis (HA-RRMS) patients is more complex than for the whole multiple sclerosis (MS) population, this study assessed the related economic burden from a National Health Insurance's (NHI's) perspective. RESEARCH DESIGN AND METHODS: Study based on French NHI databases, using individual data on billing and reimbursement of outpatient and hospital healthcare consumption, paid sick leave and disability pension, over 2010-2017. RESULTS: Of the 9,596 HA-RRMS adult patients, data from 7,960 patients were analyzed with at least 2 years of follow-up. Mean annual cost/patient was €29,813. Drugs represented 40% of the cost, hospital care 33%, disability pensions 9%, and all healthcare professionals' visits combined 8%. Among 3,024 patients under 60 years-old with disability pension, disability pension cost €7,168/patient/year. Among 3,807 patients with paid sick leave, sick leave cost €1,956/patient/year. Mean costs were €2,246/patient higher the first year and increased by €1,444 between 2010 and 2015, with a €5,188 increase in drug-related expenditures and a €634 increase in healthcare professionals' visits expenditures but a €4,529 decrease in hospital care expenditures. CONCLUSIONS: The cost of health care sick leaves, and disability pensions of HA-RRMS patients was about twice as high as previously reported cost of MS patients.

Economic Burden of the Out-of-Pocket Expenses for People with Multiple Sclerosis in France.

BACKGROUND: People with chronic diseases in France frequently incur out-of-pocket expenses (OOPE) related to their medical care. OBJECTIVE: The objective of this study was to evaluate OOPE incurred by people with multiple sclerosis (MS) with respect to direct non-medical and medical expenditure. METHODS: Data were collected through a web-based survey using an online patient community platform (Carenity). The survey questionnaire contained 87 questions (numerical response or Likert scale) and took less than 30 min to complete. Participants rated their disability on a ten-point scale. RESULTS: In total, 376 patients, with a mean age of 48.3 years (95% confidence interval [CI] 47.2-49.5), participated in the survey. Participants estimated that they spent an average of €127 each month on OOPE for their MS, principally on physician consultations (mean annual expenditure of €75 by 183 participants), non-physician consultations (€358 by 135 participants) and non-prescription medication (mean expense of €67 per pharmacy visit by 234 patients). In total, 77% of participants who needed adaptations to their home or vehicle because of their MS contributed to the cost. No obvious relationship between OOPE and self-rated disability was observed. A total of 61.4% of participants reported that they had to choose between spending money on MS care or on their family and social life. CONCLUSIONS: Most patients with MS incurred significant OOPE linked to consultations, non-prescription medications or home equipment and medical equipment. These outlays could lead to dilemmas when choosing between spending on MS care or family or social life.

Decreased nucleotide excision repair activity and alterations of topoisomerase IIalpha are associated with the in vivo resistance of a P388 leukemia subline to F11782, a novel catalytic inhibitor of topoisomerases I and II.

PURPOSE: The purpose of the study was to investigate the mechanisms associated with antitumor activity and resistance to F11782, a novel dual catalytic inhibitor of topoisomerases with DNA repair-inhibitory properties. EXPERIMENTAL DESIGN: For that purpose, an F11782-resistant P388 leukemia subline (P388/F11782) has been developed in vivo and characterized. RESULTS: Weekly subtherapeutic doses of F11782 (10 mg/kg) induced complete resistance to F11782 after 8 weekly passages. This resistant P388/F11782 subline retained some in vivo sensitivity to several DNA-topoisomerase II and/or I complex-stabilizing poisons and showed marked collateral sensitivity to cisplatin, topotecan, colchicine, and Vinca alkaloids, while proving completely cross-resistant only to merbarone and doxorubicin. Therefore, resistance to F11782 did not appear to be associated with a classic multidrug resistance profile, as further reflected by unaltered drug uptake and no overexpression of resistance-related proteins or modification of the glutathione-mediated detoxification process. In vivo resistance to F11782 was, however, associated with a marked reduction in topoisomerase IIalpha protein (87%) and mRNA (50%) levels, as well as a diminution of the catalytic activity of topoisomerase IIalpha. In contrast, only minor reductions in topoisomerases IIbeta and I levels were recorded. However, of major interest, nucleotide excision repair activity was decreased 3-fold in these P388/F11782 cells and was more specifically associated with a decreased (67%) level of XPG (human xeroderma pigmentosum group G complementing protein), an endonuclease involved in this DNA repair system. CONCLUSIONS: These findings suggest that both topoisomerase IIalpha and XPG are major targets of F11782 in vivo and further demonstrate the original mechanism of action of this novel compound.