Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme for Patients with Moderate-to-Severe Rheumatoid Arthritis in Finland

Purpose

To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-naïve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland.

Methods

A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015–2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index.

Results

In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of €7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix.

Conclusion

The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients.

Funding

UCB Pharma.

     

Peripheral and liver tissue oxygen tensions in hemorrhagic shock.

BACKGROUND AND METHODS: Hepatic dysfunction after severe hemorrhagic shock is common and may be a consequence of visceral tissue hypoxia. Peripheral tissue PO2 has been suggested to correlate with the development of visceral hypoxia. To test the hypothesis that changes in peripheral tissue PO2 reflect changes in hepatic PO2, we measured subcutaneous PO2, transcutaneous PO2, transconjunctival PO2, and liver tissue PO2, and their relationship with changes in mean arterial blood pressure (MAP) and systemic oxygen transport (DO2), during progressive bleeding in pigs (n = 23). In addition to the tissue PO2, portal vein PO2 and circulating lactate concentrations were also measured in six of the animals. The animals were anesthetized and bled to an MAP of 50 mm Hg within 1 hr. RESULTS: After an induced 10% reduction of MAP, only the DO2 decreased significantly (p less than .05). After a 20% reduction of MAP, the DO2 decreased further and was associated with a significant (p less than .05) reduction of all peripheral tissue PO2 values. A significant (p less than .05) reduction of liver tissue PO2 was observed later during bleeding, after induction of a 30% reduction in MAP. In the subgroup with portal venous PO2 and lactate measurements, reductions of all peripheral tissue PO2 and portal venous PO2 values occurred after a 20% reduction (p less than .05) of MAP. An increase (p less than .05) in the portal venous lactate concentration was observed after a 50% reduction of MAP, and a decrease (p less than .05) in liver tissue PO2 was noted after a 60% reduction of MAP. CONCLUSIONS: Reductions of both peripheral and portal venous PO2 values occur early during hemorrhage. The liver tissue PO2, though initially low, appears to be better defended, suggesting either redistribution of splanchnic blood flow or adaptation in hepatic oxygen demand.     

Multiparametric luminescence method for quantitative cell surface protein expression analysis and imaging

A luminometric method for quantitative cell surface protein expression analysis has been developed in a microtiter plate format. The method is based on immunocytochemistry, the use of long-lived europium(III) and terbium(III) chelates and platinum(II) porphyrin luminescence labels in addition to short-lived syto13 DNA stain, and detection of photoluminescence emission from adhered cells by both time-resolved luminescence and conventional fluorescence. After the immunoreactions, the wells were evaporated to dryness, allowing repeated and postponed luminescence analysis even after months and cellular protein localization studies by microscopy imaging. The multiparametric method assayed the cell surface expression of ?1-integrin, E-selectin and intercellular adhesion molecule 1 (ICAM-1) in HUVE cells (human umbilical vein endothelial cells). The expression of E-selectin and ICAM-1 was enhanced by treating HUVECs with tumor necrosis factor α (TNF-α), while the expression level of ?1-integrin remained unchanged. The sensitivity limit of TNF-α detection by the method was ca. 1 pg/ml and the Z'-factors for the quantification of E-selectin and ICAM-1 were >0.7 suggesting a highly robust method. The novel approach proposed in this paper can be potentially applied to cell surface protein expression analysis in screening applications combined with localization studies of the target proteins by fluorescence microscopy imaging.     

Development of a rapid assay methodology for antimicrobial susceptibility testing of Staphylococcus aureus

Development of a new phenotypic technique for rapid antimicrobial susceptibility testing (AST) of methicillin-resistant Staphylococcus aureus is presented. The new technique combines bacterial culturing and specific immunometric detection in a single separation-free process. The technique uses dry chemistry reagents and the recently developed two-photon excitation detection technology, which allows online detection of bacterium-specific growth. The performance of the new technique was evaluated by monitoring the growth of S. aureus reference strains and determining their susceptibility to oxacillin. In the direct analysis of clinical specimens, method specificity and tolerance to interferences caused by other bacteria present in the sample are pivotal. Other bacteria can compete with the bacteria of interest for nutrients, for example. Specificity and tolerance were studied against Staphylococcus epidermidis reference strains. The results suggest that the new technique could allow rapid AST directly from clinical samples within 6 to 8 h. Such a rapid and simple testing methodology would be a valuable tool in clinical microbiology because it would shorten the turnaround times of microbiologic analyses. Advantages of the new approach in relation to conventional methods are discussed.