Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis

Clin Drug Investig (2017) 37:795–805 DOI 10.1007/s40261-017-0537-9 ORIGINAL RESEARCH ARTICLE Economic Evaluation of Tobramycin Inhalation Powder for the Treatment of Chronic Pulmonary Pseudomonas aeruginosa Infection in Patients with Cystic Fibrosis Srilekha Panguluri1 • Praveen Gunda1 • Laurie Debonnett2 • Kamal Hamed2 Published online: 22 June 2017 Ó The Author(s) 2017. This article is an open access publication Abstract Background Chronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of patients with cystic fibrosis (CF). This infection further compromises lung function, and significantly contributes to the increased healthcare costs. Objectives Inhaled tobramycin, used to manage P. aeruginosa infection in CF patients, is available as powder (tobramycin inhalation powder, TIP) and solution (tobramycin inhalation solution, TIS). Evidence suggests increased adherence with the use of TIP over TIS. Hence, this analysis aimed to evaluate the potential pharmacoeconomic benefit of increased adherence with TIP over TIS in the US setting. Methods A patient-level simulation model was developed to compare TIP with TIS. Both costs and benefits were predicted over a 10-year time horizon from a payer’s perspective, and were discounted annually at 3%. All costs were presented in 2016 US dollars. Results TIP was associated with greater quality-adjusted life-years (by 0.27) and lower total costs (by US$36,168) as compared with TIS over a 10-year time horizon. TIPtreated patients experienced a decreased mean number of exacerbations than TIS-treated patients (39.24 vs 50.20). Furthermore, administration of TIP via the T-326 Inhaler was associated with significant cost savings per patient, because of the nebulizer required for administering TIS (by US$1596) and exacerbation costs (by US$76,531). Probabilistic sensitivity analysis showed that TIP was dominant over TIS in 100% of the simulations. Conclusion TIP is likely to be a more cost-effective treatment than TIS, and therefore may reduce the economic burden of CF. & Kamal Hamed ; Cystic fibrosis (CF) is a rare, potentially fatal, genetic disorder caused by mutations in the gene encoding the CF transmembrane conductance regulator protein, which acts as a chloride channel [1]. CF is most common in the Caucasian population, although it can affect nearly every 1 Novartis Healthcare Pvt. Ltd., Hyderabad, India 2 Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA Key Points This is the first cost-effectiveness analysis of tobramycin inhalation powder (TIP) versus tobramycin inhalation solution (TIS) for the treatment of chronic pulmonary Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) in the US setting, thus exploring the economic value of dry powder inhaler over aerosolised formulation. Results showed that TIP is associated with lower costs and greater quality-adjusted-life-years as compared with TIS. Use of TIP over TIS is likely to reduce the economic burden of CF in the USA. 1 Introduction 796 race and ethnicity [1]. In the USA, there are over 28,000 paediatric and adult patients with CF and close to 1000 new cases are diagnosed every year [1]. CF is associated with high socioeconomic costs. Major drivers of the total costs are direct healthcare costs in adults (medications, outpatient healthcare visits, acute hospitalisations) and direct non-healthcare informal costs in children (caregivers’ time) [2, 3]. Healthcare costs increase with the patient’s age and severity of the disease [4]. The annual medical cost for a patient with CF in the USA has been reported to be 20-fold greater than that for someone without CF [5]. Chronic lung infection with Pseudomonas aeruginosa occurs in approximately 50% of the patients with CF, and is more common in older adolescents and adults [1]. This infection further compromises lung function and significantly contributes to the increased healthcare costs due to more frequent physician visits and extended hospitalisations, as well as non-healthcare informal costs [1, 2, 6, 7]. Data show that early diagnosis of P. aeruginosa pulmonary infection and aggressive intervention remain key for improving lung function, lowering hospitalisation rates due to acute pulmonary exacerbations, and improving the quality of life (QoL) [8, 9]. The Cystic Fibrosis Pulmonary Guidelines have reported that intravenous antibiotics are the preferred treatment for acute pulmonary exacerbations, while aerosolised or inhaled formulations are preferred for managing chronic pulmonary infections [10]. Tobramycin, an aminoglycoside antibiotic, is used to manage both acute and chronic pulmonary P. aeruginosa infections [11]. A recent review, focused primarily on tobramycin inhalation powder (TIP), reinforced that tobramycin inhalation solution (TIS) was efficacious in improving lung function and reducing P. aeruginosa sputum density, hospitalisation rates, and the frequency of intravenous antibiotic use [12]. However, its twice-daily administration via a nebuliser for about 15–20 min/dose, and the additional time required for cleaning and disinfection of the nebuliser is often bothersome and costly [13–15]. This may place a high burden on patients and their caregivers, leading to poor adherence, and possibly reduced effectiveness in real-world settings [16, 17]. Therefore, new treatment options that can reduce the associated patient or caregiver burden are needed. TIP was the first antibiotic approved by the US Food and Drug Administration (FDA) as a dry powder for inhalation (DPI) formulation for use in patients with CF, and has been recommended as a therapeutic option for the treatment of chronic pulmonary P. aeruginosa infections [18]. Designed to enhance drug delivery, TIP shortens the drug administration time and has been shown to improve patient convenience, satisfaction, and adherence [18, 19]. Although the safety and efficacy profile of TIP was similar to that of TIS over a 6-month period in a randomised, S. Panguluri et al. controlled study (EAGER), the administration time for TIP was significantly shorter as compared with TIS (mean 5.6 vs 19.7 min, respectively; p \ 0.0001) [15]. TIP was associated with both immediate- and long-term benefits with respect to perceived treatment burden, convenience, adherence, and patient satisfaction, when studied alone or in comparison with TIS [15, 17, 20]. In a real-world setting, approximately 33 of 40 (83%) patients treated with TIP for 12 months had excellent ([80%) adherence and lower intravenous antibiotic usage, a marker used for pulmonary exacerbations, as compared to the previous 12 months [17]. Approximately 94% of patients who had previously used TIS, preferred TIP over TIS [17]. TIP was also found to have an acceptable longterm safety profile [21]. Considering these findings, it is important to understand the cost-effectiveness of treatments for efficient distribution of healthcar (...truncated)