Cost-Effectiveness of Imipenem/Cilastatin/Relebactam Compared with Colistin in Treatment of Gram-Negative Infections Caused by Carbapenem-Non-Susceptible Organisms

Abstract

Introduction: Imipenem/cilastatin/relebactam (IMI/REL), a combination b-lactam antibiotic (imipenem) with a novel b-lactamase inhibitor (relebactam), is an efficacious and well-tolerated option for the treatment of hospitalized patients with gram-negative (GN) bacterial infections caused by carbapenem-non-susceptible (CNS) pathogens. This study examines costeffectiveness of IMI/REL vs. colistin plus imipenem (CMS ? IMI) for the treatment of infection(s) caused by confirmed CNS pathogens. Methods: We developed an economic model comprised of a decision-tree depicting initial hospitalization, and a Markov model projecting long-term health and economic impacts following discharge. The decision tree, informed by clinical data from RESTORE-IMI 1 trial, modeled clinical outcomes (mortality, cure rate, and adverse events including nephrotoxicity) in the two comparison scenarios of IMI/REL versus CMS ? IMI for patients with CNS GN infection.Subsequently, a Markov model translated these hospitalization stage outcomes (i.e., death or uncured infection) to long-term consequences such as quality-adjusted life years (QALYs). Sensitivity analyses were conducted to test the model robustness. Results: IMI/REL compared to CMS ? IMI demonstrated a higher cure rate (79.0% vs. 52.0%), lower mortality (15.2% vs. 39.0%), and reduced nephrotoxicity (14.6% vs. 56.4%). On average a patient treated with IMI/REL vs. CMS ? IMI gained additional 3.7 QALYs over a lifetime. Higher drug acquisition costs for IMI/ REL were offset by shorter hospital length of stay and lower AE-related costs, which result in net savings of $11,015 per patient. Sensitivity analyses suggested that IMI/REL has a high likelihood (greater than 95%) of being cost-effective at a US willingness-to-pay threshold of $100,000-150,000 per QALY. Conclusions: For patients with confirmed CNS GN infection, IMI/REL could yield favorable clinical outcomes and may be cost-saving-as the higher IMI/REL drug acquisition cost is offset by reduced nephrotoxicity-related cost-for the US payer compared to CMS ? IMI.

Costs-effectiveness and cost components of pharmaceutical and non-pharmaceutical interventions affecting antibiotic resistance outcomes in hospital patients: a systematic literature review

“…Favourable results were shown for IMI/REL (imipenem/cilastatin/relebactam) compared with CMS+IMI (colistin plus imipenem) usage for gram-negative infections (+3.7 QALYs and lower mortality rates; 15.2% compared with 39%). However, the clinical response rate was limited among the IMI/REL group 51. Additionally, treating patients with complicated intra-abdominal infections following ceftolozane/tazobactam+metronidazole was found to be cost-effective (ICER=$8551 per QALY gained), compared with piperacillin/tazobactam 52.…”

“…However, the clinical response rate was limited among the IMI/REL group. 51 Additionally, treating patients with complicated intra-abdominal infections following ceftolozane/tazobactam+metronidazole was found to be cost-effective (ICER=$8551 per QALY gained), compared with piperacillin/tazobactam. 52 Mennini et al 53 and Vlachaki et al 54 assessed meropenem-vaborbactam versus the best available treatment for CRE patients, revealing ICERs of $11 813 and $20 486 per QALY, respectively.…”