Comparison of Infection-Related Hospitalization Risk and Associated Costs among Patients Receiving Sargramostim (Leukine®), Filgrastim (Neupogen®), and Pegfilgrastim (Neulasta®) for Chemotherapy-Induced Neutropenia

Abstract Background: Neutropenia is a main side effect of cancer treatment and leads to increased risk of serious infections. Myeloid growth factors, including the granulocyte colony-stimulating factors (G-CSFs) filgrastim (Neupogen®) and pegfilgrastim (Neulasta®) and the granulocyte-macrophage colony stimulating factor (GM-CSF) sargramostim (Leukine®), stimulate neutrophil production and are commonly used as supportive care with myelosuppressive chemotherapy. GM-CSF also stimulates the production and activity of macrophages and dendritic cells, and it is hypothesized that the additional immune protection conferred by GM-CSF might reduce infection risk compared with the G-CSFs. We tested this hypothesis by comparing infection-related hospitalization rates and costs in patients using sargramostim, filgrastim, and pegfilgrastim for chemotherapy-induced neutropenia (CIN). Methods: This retrospective matched cohort study analyzed a large, nationally representative managed care claims database from over 30 health plans in the US during 2000 to 2007. CIN patients were identified as having ≥2 claims of sargramostim or filgrastim or ≥1 claim of pegfilgrastim; ≥1 cancer claim within 120 days prior to the start of a G/GM-CSF treatment episode (index date); and ≥1 chemotherapy claim within 60 days prior to the index date. The treatment episode began with the first G/GM-CSF claim satisfying the 120 day washout period and ended on the last claim date for sargramostim and filgrastim episodes; pegfilgrastim episodes ended on the last claim date plus a mean therapeutic duration of 19 days due to its long-acting nature. A G/GM-CSF claim more than 28 days after a prior claim was considered to be a new treatment episode. This analysis only considered the first treatment episode. Patients had to be ≥18 years old as of the index date and have continuous enrollment. Sargramostim patients were 1:1 matched with filgrastim and pegfilgrastim patients based on gender and year of birth. Outcomes included infection-related hospitalization rates and the associated cost per patient per month. Hospitalization rates were analyzed using univariate and multivariate Poisson methods. Covariates included the Charlson comorbity index, the number of chemotherapy agents received, whether the patient received myleosuppressive agents, and indicator variables for the presence of heart disease, renal disease, liver disease, metastasis, breast cancer, lung cancer, non-Hodgkin’s lymphoma, history of anemia, and neutropenia diagnosis on index date. Results: A total of 990 sargramostim-filgrastim and 982 sargramostim-pegfilgrastim matched pairs were analyzed. Cohorts had similar baseline characteristics, although differences were observed for the fraction of patients with a diagnosis of neutropenia at index date (sargramostim 65%, filgrastim 57%, pegfilgrastim 45%) and the percentage of patients who received myelosuppressive agents (sargramostim 54%, filgrastim 48%, pegfilgrastim 77%). Sargramostim patients experienced infection-related hospitalizations about half as often as patients using filgrastim (p=0.04) or pegfilgrastim (p=0.06). Multivariate analyses adjusted for confounding factors and found that sargramostim patients were 56% less likely to have infection-related hospitalizations compared to filgrastim and pegfilgrastim patients (p=0.03 for both). Infection-related hospitalization costs for sargramostim patients were $728/patient/month ($8,736/patient/year) and $226/patient/month ($2,712/patient/year) less compared to filgrastim (p=0.04) and pegfilgrastim patients (p=0.01), respectively. Conclusions: Among patients with CIN, use of sargramostim is associated with a reduced risk of infection-related hospitalization and lower associated costs compared to filgrastim or pegfilgrastim. Incidence Rate Ratios and Costs of Infection-Related Hospitalizations Univariate Multivariate IRR (95% CI) p-value Adjusted IRR (95% CI) p-value Sargramostim vs. Filgrastim 0.46 (0.22–0.97) 0.0422 0.44 (0.20–0.94) 0.0333 Sargramostim vs. Pegfilgrastim 0.52 (0.26–1.04) 0.0628 0.44 (0.21–0.90) 0.0256 Cost/patient/month Sargramostim Mean (SD) Comparison Group Mean (SD) Incremental Cost p-value Sargramostim vs. Filgrastim $138 ($2,534) $866 ($22,234) −$728 0.0380 Sargramostim vs. Pegfilgrastim $139 ($2,544) $365 ($5,557) −$226 0.0100

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