Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events

Abstract

Background: Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods: Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator.Results: This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2-4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2-4 was also significantly lower for lipegfilgrastim (risk ratio 0. 45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2-4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions: Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.

Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure

“…Numerous studies have compared the efficacy and safety of pegfilgrastim and filgrastim [4,15,[30][31][32]. A recent metaanalysis identified 36 studies that reported a direct, headto-head comparison of pegfilgrastim versus filgrastim [4].…”

Cost-effectiveness and budgetary impact of lipegfilgrastim for the reduction of chemotherapy-induced neutropenia in Brazil

“…The model included three G-CSFs: short-acting filgrastim as well as long-acting lipegfilgrastim and pegfilgrastim. Pegfilgrastim is not currently reimbursed in Brazil; however, as there were no direct randomized head-to-head trials that compared lipegfilgrastim and filgrastim, a meta-analysis was conducted to compare pegfilgrastim with lipegfilgrastim and filgrastim (Bond et al, 2017). Based in part on the results of this meta-analysis, a decision analytic model was constructed using Microsoft Excel ® 2010 to assess: 1) the cost-effectiveness of lipegfilgrastim compared with filgrastim (the primary comparator) as well as pegfilgrastim and 2) the budget impact associated with the introduction of lipegfilgrastim.…”

“…Furthermore, patients experiencing AEs related to their G-CSF treatment (bone pain or nausea) were included as AEs in the model. The clinical data were derived primarily from a recent meta-analysis (Bond et al, 2017) of three lipegfilgrastim clinical trials (Bondarenko et al, 2013;Buchner et al, 2014;Volovat et al, 2015), as well as studies identified from a literature review on the use of G-CSFs in the prevention and treatment of CIN and FN. The objectives of the meta-analysis were to produce a direct comparison of lipegfilgrastim and pegfilgrastim as well as an indirect comparison of lipegfilgrastim and filgrastim.…”

“…Study quality was assessed using guidelines established by the Centre for Reviews and Dissemination (National Collaborating Centre for Methods and Tools 2012). All the studied included utilized prospective, randomized designs and met the following criteria: specified eligibility criteria, adequate sample size, number of patients randomized reported, adequate details of treatment groups at baseline presented, treatment groups comparable at baseline, co-interventions that could affect results similar across groups, and adequate compliance with treatment assignment (Bond et al, 2017).…”

“…The clinical input parameters incorporated into the model are summarized in Table 2. Lipegfilgrastim inputs were based on the three lipegfilgrastim clinical trials (Bondarenko et al, 2013;Buchner et al, 2014;Volovat et al, 2015), whereas the relative risk (RR) ratios from the meta-analysis were used to calculate the filgrastim and pegfilgrastim inputs (Bond et al, 2017). FN was assumed to require hospitalization and the mortality rate due to FN was set to 9.5% across all G-CSF regimens based on prior literature linking mortality to FN (Kuderer et al, 2006).…”