Cost-effectiveness of Oral Versus Intravenous Ibuprofen Therapy in Preterm Infants With Patent Ductus Arteriosus in the Neonatal Intensive Care Setting: A Cohort-based Study

Abstract

Purpose: Use of ibuprofen for the patent ductus arteriosus (PDA) has become increasingly common. This study aimed to evaluate the clinical and economic impact of oral ibuprofen versus intravenous ibuprofen for PDA among preterm infants. Methods: This retrospective, cohort-based pilot study examined the clinical and economic associations of oral versus intravenous ibuprofen for PDA. A decision-analytic model was constructed, from the hospital perspective, to follow the oral versus intravenous administrations of ibuprofen for PDA and their clinical and economic consequences. The course regimen of either formulation was an initial 10 mg/kg followed by 5 mg/kg at 24- and 48-h intervals. Clinical and resource utilization data were extracted from Cerner medical database, from 2014 through 2018, at the tertiary neonatal intensive care unit setting in Qatar. The primary outcome measures were the rate of successful closure based on the ductal diameter measure after the first course of treatment and the overall direct medical cost of PDA management. A population of 118 neonates was required for results with 80% power and 0.05 significance. Sensitivity analyses involving unit costs and a subgroup analysis based on gestational age and birth weight, added to a second-order probabilistic analysis of all model inputs, were performed. Findings: Forty infants were available for inclusion in the oral ibuprofen study group, not achieving the desired sample size, with successful PDA closure reported in 64% of cases compared with a reduced success of 36% with intravenous ibuprofen (n = 59) (risk ratio = 0.56; 95% CI, 0.32–0.97; P = 0.04), which was associated with economic advantage to oral ibuprofen. The probabilistic analysis illustrated that oral ibuprofen costs less than intravenous ibuprofen in 72% of patient cases, with QAR 48,751 (US $13,356) (95% CI, QAR 47,500–50,000, US $13,014–$13,699) in mean savings. Sensitivity analyses confirmed the robustness of study conclusions and found that the rate of closure success versus failure was the most influential on results, followed by the occurrence of adverse drug events with both intravenous and oral ibuprofen. Although both ibuprofen formulations had similar safety profiles (P = 0.16), the intravenous formulation was associated with a larger number of adverse drug effects. Implications: This is the first cost-effectiveness evaluation of oral versus intravenous formulations of ibuprofen among infants with PDA. The oral ibuprofen might be associated with an enhanced ductal closure at a considerably lower cost. The study results support recent trends in neonatal intensive care unit practices in favor of the oral administration of ibuprofen.