AbstractBackgroundPEG‐asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG‐asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions.ProceduresThis Markov model evaluated the cost‐effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard‐risk (SR) B‐ALL patient receiving two asparaginase doses and a high‐risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five‐year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality‐adjusted life years (QALYs). Probabilistic and one‐way sensitivity analyses evaluated model uncertainty.ResultsIn both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes to Erwinia compared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios.ConclusionCompared with other strategies, premedication use and asparaginase level monitoring in children with B‐ALL is potentially cost‐saving.