Cost-effectiveness of maribavir versus conventional antiviral therapies for post-transplant refractory cytomegalovirus infection with or without genotypic resistance: A US perspective.

This study evaluated the cost-effectiveness of maribavir versus investigator-assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, or cidofovir) for post-transplant refractory cytomegalovirus (CMV) infection with or without resistance. A two-stage Markov model was designed using data from the SOLSTICE trial (NCT02931539), real-world multinational observational studies, and published literature. Stage 1 (0-78 weeks) comprised clinically significant CMV (csCMV), non-clinically significant CMV (n-csCMV), and dead states; stage 2 (78 weeks-lifetime) comprised alive and dead states. Total costs (2022 USD) and quality-adjusted life years (QALYs) were estimated for the maribavir and IAT cohorts. An incremental cost-effectiveness ratio was calculated to determine cost-effectiveness against a willingness-to-pay threshold of $100 000/QALY. Compared with IAT, maribavir had lower costs ($139 751 vs $147 949) and greater QALYs (6.04 vs 5.83), making it cost-saving and more cost-effective. Maribavir had higher acquisition costs compared with IAT ($80 531 vs $65 285), but lower costs associated with administration/monitoring ($16 493 vs $27 563), adverse events (AEs) ($11 055 vs $16 114), hospitalization ($27 157 vs $33 905), and graft loss ($4516 vs $5081), thus making treatment with maribavir cost-saving. Maribavir-treated patients spent more time without CMV compared with IAT-treated patients (0.85 years vs 0.68 years), leading to lower retreatment costs for maribavir (cost savings: -$42 970.80). Compared with IAT, maribavir was more cost-effective for transplant recipients with refractory CMV, owing to better clinical efficacy and avoidance of high costs associated with administration, monitoring, AEs, and hospitalizations. These results can inform healthcare decision-makers on the most effective use of their resources for post-transplant refractory CMV treatment.

Influenza vaccines: the potential benefits of cell-culture isolation and manufacturing.

Influenza continues to cause severe illness in millions and deaths in hundreds of thousands annually. Vaccines are used to prevent influenza outbreaks, however, the influenza virus mutates and annual vaccination is required for optimal protection. Vaccine effectiveness is also affected by other potential factors such as the human immune system, a mismatch with the chosen candidate virus, and egg adaptation associated with egg-based vaccine production. This article reviews the influenza vaccine development process and describes the implications of the changes to the cell-culture process and vaccine strain recommendations by the World Health Organization since the 2017 season. The traditional manufacturing process for influenza vaccines relies on fertilized chicken eggs that are used for vaccine production. Vaccines must be produced in large volumes and the complete process requires approximately 6 months for the egg-based process. In addition, egg adaptation of seed viruses occurs when viruses adapt to avian receptors found within eggs to allow for growth in eggs. These changes to key viral antigens may result in antigenic mismatch and thereby reduce vaccine effectiveness. By contrast, cell-derived seed viruses do not require fertilized eggs and eliminate the potential for egg-adapted changes. As a result, cell-culture technology improves the match between the vaccine virus strain and the vaccine selected strain, and has been associated with increased vaccine effectiveness during a predominantly H3N2 season. During the 2017-2018 influenza season, a small number of studies conducted in the United States compared the effectiveness of egg-based and cell-culture vaccines and are described here. These observational and retrospective studies demonstrate that inactivated cell-culture vaccines were more effective than egg-based vaccines. Adoption of cell-culture technology for influenza vaccine manufacturing has been reported to improve manufacturing efficiency and the additional benefit of improving vaccine effectiveness is a key factor for future policy making considerations.

Lack of an effect of oral iron administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients.

STUDY OBJECTIVES: To determine if coadministration of polysaccharide iron complex and slow-release ferrous sulfate alter the absorption of mycophenolic acid (MPA), and to examine the potential influence of dosing relative to mycophenolate mofetil (MMF) administration and the effect of immediate- versus sustained-release iron products on the steady-state pharmacokinetics of MPA. DESIGN: Prospective, open-label, three-phase, crossover, steady-state pharmacokinetic study. SETTING: National Institutes of Health-sponsored General Clinical Research Center at a university medical center. PATIENTS: Twelve adult (mean age 50 yrs) renal transplant recipients who were receiving concomitant iron and MMF maintenance therapy. INTERVENTION: Oral iron therapy was coadministered with MMF on days -6-0, MMF was administered alone on days 1-8 (control phase), then oral iron therapy was administered 2 hours after MMF administration on days 9-16. MEASUREMENTS AND MAIN RESULTS: Baseline demographics, concurrent drug regimens, and clinical laboratory values were assessed. Blood samples were obtained at baseline and at 1, 2, 3, 4, 6, 8, and 12 hours after MMF administration on days 0, 8, and 16. The MPA levels were measured by high-performance liquid chromatography. We found no significant differences in the dose-standardized area under the concentration-time curve from 0-12 hours (AUC(0-12)) for MPA between the control phase (39.66 +/- 8.70 mg mg x hr/L) and the concomitant ferrous sulfate or dose-separated ferrous sulfate (37.56 +/- 9.95 or 32.84 +/- 8.43 mg x hr/L, respectively, p>0.05) phases. Dose-standardized AUC(0-12) values for MPA did not significantly differ after the concomitant administration of polysaccharide iron complex from that of the control phase (48.46 +/- 9.68 and 43.80 +/- 9.46 mg x hr/L, respectively, p=0.065). However, the AUC(0-12) for MPA significantly increased when polysaccharide iron complex was administered 2 hours after MMF (53.41 +/- 11.75 mg x hr/L, p=0.012). Maximum concentrations and times to reach maximum concentrations remained consistent across all study phases in each arm of the trial (p>0.05). CONCLUSION: Multiple doses of iron therapy-slow-release ferrous sulfate, or polysaccharide iron complex-did not significantly reduce systemic exposure to MMF, as measured by using AUC(0-12) values.