Cost-effectiveness analysis comparing ceftazidime/avibactam (CAZ-AVI) as empirical treatment comparing to ceftolozane/tazobactam and to meropenem for complicated intra-abdominal infection (cIAI)

Thitima Kongnakorn, Christian Eckmann, Matteo Bassetti, Eszter Tichy, Roberto Di Virgilio, Nathalie Baillon-Plot, Claudie Charbonneau, Thitima Kongnakorn, Christian Eckmann, Matteo Bassetti, Eszter Tichy, Roberto Di Virgilio, Nathalie Baillon-Plot, Claudie Charbonneau

Abstract

Background: The rising incidence of resistance to currently available antibiotics among pathogens, particularly Gram-negative pathogens, in complicated intra-abdominal infections (cIAIs) has become a challenge for clinicians. Ceftazidime/avibactam (CAZ-AVI) is a fixed-dose antibiotic approved in Europe and the United States for treating (in combination with metronidazole) cIAI in adult hospitalised patients who have limited or no alternative treatment options. The approval was based on the results of RECLAIM, a Phase III, parallel-group, comparative study (RECLAIM 1 [NCT01499290] and RECLAIM 2 [NCT01500239]). The objective of our study was to assess the cost-effectiveness of CAZ-AVI plus metronidazole compared with 1) ceftolozane/tazobactam plus metronidazole and 2) meropenem, as an empiric treatment for the management of cIAI in Italy.

Methods: A sequential, patient-level simulation model, with a 5-year time horizon and 3% annual discount rate (applied to both costs and health benefits), was developed using Microsoft Excel® to demonstrate the clinical course of the disease. The impact of resistant pathogens was included as an additional factor.

Results: In the base-case analysis, the CAZ-AVI sequence (CAZ-AVI plus metronidazole followed by a colistin + tigecycline + high-dose meropenem combination after treatment failure), when compared to sequences for ceftolozane/tazobactam (ceftolozane/tazobactam plus metronidazole followed by colistin + tigecycline + high-dose meropenem after treatment failure) and meropenem (meropenem followed by colistin + tigecycline + high-dose meropenem after treatment failure), had better clinical outcomes with higher cure rates (93.04% vs. 91.52%; 92.98% vs. 90.24%, respectively), shorter hospital stays (∆ = - 0.38 and ∆ = - 1.24 days per patient, respectively), and higher quality-adjusted life years (QALYs) gained per patient (4.021 vs. 3.982; 4.019 vs. 3.960, respectively). The incremental cost effectiveness ratio in the CAZ-AVI sequence was €4099 and €15,574 per QALY gained versus each comparator sequence, respectively, well below the willingness-to-pay threshold of €30,000 per QALY accepted in Italy.

Conclusions: The model results demonstrated that CAZ-AVI plus metronidazole could be a cost-effective alternative when compared with other antibiotic treatment options, as it is expected to provide better clinical benefits in hospitalised patients with cIAI in Italy.

Keywords: Ceftazidime-avibactam plus metronidazole; Ceftolozane/tazobactam plus metronidazole; Complicated intra-abdominal infection; Cost-effectiveness analysis; Economic model; Meropenem.

Conflict of interest statement

Competing interestsTK and ET are employees of Evidera, which received funding from Pfizer in connection with conducting the study, developing this manuscript, and medical writing. RDV, NBP, and CC are employees of Pfizer, and hold Pfizer stock and/or stock options. CE is an employee of Klinikum Peine, Academic Hospital of Medical University Hannover, (Hannover, Germany), and MB is an employee of University of Genoa, Genoa and Hospital Policlinico San Martino – IRCCS, Genoa (Italy), each of which received research funding from Pfizer. Outside the submitted work, MB has received funding for scientific advisory boards, travel and speaker honoraria from Angelini, AstraZeneca, Bayer, Cidara, Cepheid, Cubist, Pfizer, Menarini, MSD, Nabriva, Paratek, Roche, Shionogi, Tetraphase, The Medicine Company and Astellas Pharma Inc.

© The Author(s). 2019.

Figures

Fig. 1
Fig. 1
An overview of flow of each patient’s events. Abbreviations: EOT end-of-treatment visit, LFU late follow-up visit (42–49 days following the initiation of the treatment), TOC test-of-cure visit (28–35 days following the initiation of treatment)
Fig. 2
Fig. 2
Incremental cost outcomes per patient for CAZ-AVI sequence vs. Ceftolozane/Tazobactam sequence. Abbreviations: CAZ-AVI ceftazidime-avibactam. CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Ceftolozane/tazobactam sequence: Ceftolozane/tazobactam plus metronidazole, followed by colistin + tigecycline + high-dose meropenem
Fig. 3
Fig. 3
One-way deterministic sensitivity analysis for CAZ-AVI sequence vs. Ceftolozane/Tazobactam sequence, INB based on a willingness-to-pay threshold. Abbreviations: CAZ-AVI ceftazidime-avibactam, cIAI complicated intra-abdominal infection, EOT end-of-treatment, INB incremental net benefit, Prob probability, TOC test-of-cure, Tx treatment . CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Ceftolozane/tazobactam sequence: Ceftolozane/tazobactam plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Note: A positive INB indicates the CAZ-AVI sequence is cost effective compared to the ceftolozane/ tazobactam sequence, and vice versa
Fig. 4
Fig. 4
Results from probabilistic sensitivity analysis for CAZ-AVI sequence vs. Ceftolozane/Tazobactam sequence, on cost-effectiveness plane. Abbreviations: CAZ-AVI, ceftazidime-avibactam; QALY, quality-adjusted life year; WTP, willingness-to-pay . CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Ceftolozane/tazobactam sequence: Ceftolozane/tazobactam plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Notes: Each dot represents the cost-effectiveness outcome from each iteration. The threshold lines represent cost-effectiveness thresholds of € 30,000 or € 40,000 per QALY (i.e., the maximum amount society is willing to pay for a QALY gained). In cases that fall to the right and below this line, the CAZ-AVI sequence is cost effective compared to the ceftolozane/tazobactam sequence. In cases that fall to left and above this line, the CAZ-AVI sequence is not cost effective compared to the ceftolozane/tazobactam sequence
Fig. 5
Fig. 5
Results from probabilistic sensitivity analysis for CAZ-AVI sequence vs. Ceftolozane/Tazobactam sequence, on cost-effectiveness acceptability curve. Abbreviations: CAZ-AVI ceftazidime-avibactam, QALY quality-adjusted life year. CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Ceftolozane/tazobactam sequence: Ceftolozane/tazobactam plus metronidazole, followed by colistin + tigecycline + high-dose meropenem
Fig. 6
Fig. 6
Incremental cost outcomes per patient for CAZ-AVI sequence vs. meropenem sequence. Abbreviations: CAZ-AVI ceftazidime-avibactam, CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Meropenem sequence: Meropenem, followed by colistin + tigecycline + high-dose meropenem
Fig. 7
Fig. 7
One-way deterministic sensitivity analysis for CAZ-AVI sequence vs. meropenem sequence, INB based on a willingness-to-pay threshold, Abbreviations: CAZ-AVI ceftazidime-avibactam, cIAI complicated intra-abdominal infection, EOT end-of-treatment, INB incremental net benefit, Prob probability, TOC test-of-cure. CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Meropenem sequence: Meropenem, followed by colistin + tigecycline + high-dose meropenem. Note: Positive INB indicates CAZ-AVI sequence was cost effective compared to meropenem sequence, and vice versa
Fig. 8
Fig. 8
Probabilistic sensitivity analysis for CAZ-AVI sequence vs. meropenem sequence (on cost-effectiveness plane). Abbreviations: CAZ-AVI ceftazidime-avibactam, QALY quality-adjusted life year, WTP willingness-to-pay. CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Meropenem sequence: Meropenem, followed by colistin + tigecycline + high-dose meropenem. Notes: Each dot represents cost-effectiveness outcome from each iteration. The threshold lines represent cost-effectiveness thresholds (€ 30,000 or € 40,000 per QALY), the maximum amount society is willing to pay for a QALY gain. In cases that fall to the right and below this line, the CAZ-AVI sequence is cost effective compared to the meropenem sequence. In cases that fall to left and above this line, the CAZ-AVI sequence is not cost effective compared to the meropenem sequence
Fig. 9
Fig. 9
Probabilistic sensitivity analysis for CAZ-AVI sequence vs. meropenem sequence (on cost-effectiveness acceptability curve). Abbreviations: CAZ-AVI ceftazidime-avibactam, QALY quality-adjusted life year. CAZ-AVI sequence: CAZ-AVI plus metronidazole, followed by colistin + tigecycline + high-dose meropenem. Meropenem sequence: Meropenem, followed by colistin + tigecycline + high-dose meropenem

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