Model-based alternative dosing strategies for subcutaneous nivolumab to improve cost effectiveness

Wang, Y.; Bukkems, L.H.; Heine, R. ter; Hasselt, J.G.C. van; Koolen, S.L.W.; Hendikx J.J.M.A; Hulle, T. van der; Kapiteijn, E.; Zwaveling, J.; Becker, A.; Heuvel, M.M. van den; Theelen, W.S.M.E.; Oude Munnink, T.H.; Smit, E.F.; Guchelaar, H.J.; Moes, D.J.A.R.

doi:doi:10.1007/s40262-025-01610-4

Background The increasing use of the immune checkpoint inhibitor nivolumab places a significant financial burden on healthcare systems, contributes to environmental concerns, and strains hospital capacities. The nivolumab average exposure and exposure variation of a fixed subcutaneous (SC) dosing regimen (1200 mg every 4 weeks) is significantly higher compared with 3-mg/kg every 2 weeks intravenous dosing. Objectives We aimed to develop alternative dosing regimens for SC nivolumab to reduce drug expenses and lower the treatment burden for patients while ensuring effective exposure. Methods Population pharmacokinetic simulation was conducted using a population pharmacokinetic model developed by the license holder to explore alternative SC regimens. In this process, patients were divided into three weight groups: less than 60 kg, 60-90 kg, and more than 90 kg. Furthermore, two experimental progressive alternative dosing regimens were developed, one based on a minimum effective...Show moreBackground The increasing use of the immune checkpoint inhibitor nivolumab places a significant financial burden on healthcare systems, contributes to environmental concerns, and strains hospital capacities. The nivolumab average exposure and exposure variation of a fixed subcutaneous (SC) dosing regimen (1200 mg every 4 weeks) is significantly higher compared with 3-mg/kg every 2 weeks intravenous dosing. Objectives We aimed to develop alternative dosing regimens for SC nivolumab to reduce drug expenses and lower the treatment burden for patients while ensuring effective exposure. Methods Population pharmacokinetic simulation was conducted using a population pharmacokinetic model developed by the license holder to explore alternative SC regimens. In this process, patients were divided into three weight groups: less than 60 kg, 60-90 kg, and more than 90 kg. Furthermore, two experimental progressive alternative dosing regimens were developed, one based on a minimum effective concentration-driven approach. The second progressive alternative regimen was based on using the 1200-mg SC formulation as an intravenous infusion. Results We developed an alternative bodyweight-based regimen consisting of SC 1200 mg every 7 weeks (<60 kg), 1200 mg every 6 weeks (60-90 kg), and 1200 mg every 5 weeks (>90 kg). This new alternative dosing regimen would save an average of 24,345 (35%) per patient per year compared with SC 1200 mg every 4 weeks. The results for the first experimental, progressive, extended-interval dosing regimen for patients with melanoma indicate that 95% of patients exceed a steady-state trough concentration of 2.5 mg/L when administered SC 1200 mg every 10 weeks. This dosing regimen would decrease the yearly cost from 68,870 to 27,548 (60% less) per patient per year. The second experimental progressive regimen using SC 1200 mg as an intravenous administration every 7 weeks leads to a potential saving of 29,516, which is a 43% decrease compared with the SC 1200-mg approved regimen. Conclusions The developed dosing regimen with a bodyweight-dependent interval offers a cost-effective and patient-friendly method to optimize SC nivolumab use while ensuring adequate exposure, which can be directly implemented in clinical practice. Moreover, the two experimental progressive proposed regimens provide a rationale for a clinical non-inferiority study in which alternative dose regimens are compared to standard dosing according to the drug label.Show less

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Model-based alternative dosing strategies for subcutaneous nivolumab to improve cost effectiveness