Pharmacoeconomic study of anti-influenza virus drugs in Japan based on a network meta-analysis.

BACKGROUND: An analysis was conducted in Japan to determine the most cost-effective neuraminidase inhibitor for the treatment of influenza virus infections from the healthcare payer's standpoint. OBJECTIVE: This study reanalysed the findings of a previous study that had some limitations (no probabilistic sensitivity analysis and quality of life scores measured by the EQ-5D-3L instead of the EQ-5D-5L) and used a decision tree model with only three health conditions. METHODS: This study incorporated new data from a network meta-analysis study into the first examination. The second examination involved constructing a new decision tree model encompassing seven health conditions and identifying costs, which consisted of medical costs and drug prices based on the 2020 version of the Japanese medical fee index. Effectiveness outcomes were measured using EQ-5D-5L questionnaires for adult patients with a history of influenza virus infections within a 14-day time horizon. Deterministic and probabilistic sensitivity analyses were performed to examine the uncertainty. RESULTS: In the first examination, the base-case cost-effectiveness analysis confirmed that oseltamivir outperformed laninamivir, zanamivir and peramivir, making it the most cost-effective neuraminidase inhibitor. The second examination revealed that oseltamivir dominated the other agents. Both deterministic and probabilistic sensitivity analyses showed robust results that validated oseltamivir as the most cost effective among the four neuraminidase inhibitors. CONCLUSIONS: This study thus reaffirms oseltamivir's position as the most cost-effective neuraminidase inhibitor for the treatment of influenza virus infections in Japan from the perspective of healthcare payment. These findings can help decision makers and healthcare providers in Japan.

A Cost-Effectiveness Analysis of Neuraminidase Inhibitors for Influenza Virus Infections in an Adult-Outpatient Setting in Japan.

BACKGROUND: Pharmacoeconomic studies have been less performed in Japan. The objective of this study was to clarify which neuraminidase inhibitor (NI; oseltamivir, zanamivir, laninamivir, and peramivir) is most cost-effective in an adult outpatient setting in Japan. OBJECTIVE: To clarify which neuraminidase inhibitor (NI; oseltamivir, zanamivir, laninamivir, and peramivir) is most cost-effective in an adult outpatient setting in Japan. METHODS: Cost-effectiveness analysis was constructed from the healthcare payer's perspective. A decision tree model was constructed with probabilities from relevant randomized controlled trials. Costs included medical costs and drug prices. Medical costs were obtained from the medical fee schedule table (2016 version). We also applied authorized medication costs. Outcomes of effectiveness were measured using EQ-5D-3L questionnaires for adult patients who had experienced influenza virus infections previously. Time horizon was 14 days in this study. RESULTS: Cost-effectiveness ratios for oseltamivir, zanamivir, laninamivir, and peramivir were 393 674 Yen/quality-adjusted life year (QALY; US$3883.41/QALY), 408 241 (US$4027.10), 407 980 (US$4024.53), and 444 264 (US$4382.45), respectively. The cost-effectiveness analysis base-case analysis revealed oseltamivir as the most cost-effective NI. Zanamivir was dominated. Incremental cost effectiveness ratio (ICER) for laninamivir and peramivir were 1 129 459 Yen/QALY (US$11 141.58/QALY) and 1 287 118 (US$12 696.81), respectively. One-way sensitivity analyses revealed that minimum ICERs for laninamivir based on "quality of life (QOL) values (95% confidence interval)" was -596 850 Yen/QALY (US-$5887.64/QALY) owing to high cost and less effective. Also, maximum ICER for peramivir based on"QOL values" was 14 717 518 Yen/QALY (US$145 181.32/QALY); a value more than the 5 000 000 Yen/QALY threshold. CONCLUSIONS: The study results reveal oseltamivir as the most cost-effective NI for the treatment of influenza virus infection in an adult outpatient setting. Our findings may provide decision makers with scientific evidence for clinical and economic evaluation to achieve optimal therapeutic outcomes.

[A CASE OF ANAPHYLAXIS IN THE PEDIATRIC PATIENT WITH MILK ALLERGY DUE TO TRACES OF MILK PROTEIN IN THE LACTOSE USED AS AN EXCIPIENT OF INAVIR INHALATION].

The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as ß-lactoglobulin (ß-LG) by Western blotting using specific monoclonal antibody and patient's sera. The ß-LG in Inavir was supposed to be glycosylated with lactose because the molecular weight was slightly higher than ß-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of ß-LG contaminated in the lactose excipient of Inavir could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients.