Understanding patient preferences and willingness to pay for hemophilia therapies

Shraddha S Chaugule,1 Joel W Hay,1 Guy Young2 1Department of Clinical Pharmacy, Pharmaceutical Economics and Policy, University of Southern California, 2Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA Background: Despite clearly improved clinical outcomes for prophylaxis compared to on-demand therapy, on average only 56% of patients diagnosed with severe hemophilia receive prophylactic factor replacement therapy in the US. Prophylaxis rates generally drop as patients transition from childhood to adulthood, partly due to patients becoming less adherent when they reach adulthood. Assessment of patient preferences is important because these are likely to translate into increased treatment satisfaction and adherence. In this study, we assessed preferences and willingness to pay (WTP) for on-demand, prophylaxis, and longer acting prophylaxis therapies in a sample of US hemophilia patients.Methods: Adult US hemophilia patients and caregivers (N=79) completed a discrete-choice survey that presented a series of trade-off questions, each including a pair of hypothetical treatment profiles. Using a mixed logit model for analysis, we compared the relative importance of five treatment characteristics: 1) out-of-pocket treatment costs (paid by patients), 2) factor dose adjustment, 3) treatment side effects, 4) availability of premixed factor, and 5) treatment effectiveness and dosing frequency. Based on these attribute estimates, we calculated patients’ WTP.Results: Out-of-pocket treatment costs (P<0.001), side effects (P<0.001), and treatment effectiveness and dosing frequency (P<0.001) were found to be statistically significant in the model. Patients were willing to pay US $410 (95$164–$656) out of pocket per month for thrice-weekly prophylaxis therapy compared to on-demand therapy and$360 (95% confidence interval: 145–575) for a switch from thrice-weekly to once-weekly prophylaxis therapy.Conclusion: Improvements in treatment effectiveness and dosing frequency, treatment side effects, and out-of-pocket costs per month were the greatest determinants of hemophilia treatment choice and WTP. The positive preferences and WTP for longer acting prophylactic therapies suggest that the uptake is likely to increase adherence, improving treatment outcomes. These preferences should also inform the Food and Drug Administration’s assessment of new longer acting hemophilia therapies. Keywords: hemophilia, patient, preferences, willingness to pa

A new vertebrate SUMO enzyme family reveals insights into SUMO-chain assembly

SUMO chains act as stress-induced degradation tags or repair factor-recruiting signals at DNA lesions. Although El activating, E2 conjugating and E3 ligating enzymes efficiently assemble SUMO chains, specific chain-elongation mechanisms are unknown. E4 elongases are specialized E3 ligases that extend a chain but are inefficient in the initial conjugation of the modifier. We identified ZNF451, a representative member of a new class of SUMO2 and SUM03 (SUMO2/3)-specific enzymes that execute catalysis via a tandem SUMO-interaction motif (SIM) region. One SIM positions the donor SUMO while a second SIM binds SUMO on the back side of the E2 enzyme. This tandem-SIM region is sufficient to extend a back side-anchored SUMO chain (E4 elongase activity), whereas efficient chain initiation also requires a zinc-finger region to recruit the initial acceptor SUMO (E3 ligase activity). Finally, we describe four human proteins sharing E4 elongase activities and their function in stress-induced SUMO2/3 conjugation