Efficacy and Safety of Filgrastim and Its Biosimilars to Prevent Febrile Neutropenia in Cancer Patients: A Prospective Study and Meta-Analysis

Abstract

Background: The aim of this review and meta-analysis was to identify, assess, meta-analyze and summarize the comparative effectiveness and safety of filgrastim in head-to-head trials with placebo/no treatment, pegfilgrastim (and biosimilar filgrastim to update advances in the field. Methods: The preferred reporting items for systematic reviews and meta-analyses PRISMA statement were applied, and a random-effect model was used. Primary endpoints were the rate and duration of grade 3 or 4 neutropenia, and an incidence rate of febrile neutropenia. Secondary endpoints were time to absolute neutrophil count ANC recovery, depth of ANC nadir (lowest ANC), neutropenia-related hospitalization and other neutropenia-related complications. For filgrastim versus biosimilar filgrastim comparison, the primary efficacy endpoint was the mean difference in duration of severe neutropenia DSN. Results: A total of 56 studies were considered that included data from 13,058 cancer patients. The risk of febrile neutropenia in filgrastim versus placebo/no treatment was not statistically different. The risk ratio for febrile neutropenia was 0.58, a 42% reduction in favor of filgrastim. The most reported adverse event with FIL was bone pain. For pegfilgrastim versus filgrastim, no statistically significant difference was noted. The risk ratio was 0.90 (95% CI 0.67 to 1.12). The overall difference in duration of severe neutropenia between filgrastim and biosimilar filgrastim was not statistically significant. The risk ratio was 1.03 (95% CI 0.93 to 1.13). Conclusions: Filgrastim was effective and safe in reducing febrile neutropenia and related complications, compared to placebo/no treatment. No notable differences were found between pegfilgrastim and filgrastim in terms of efficacy and safety. However, a similar efficacy profile was observed with FIL and its biosimilars.

Comparative Study of Adverse Drug Reactions Associated with Filgrastim and Pegfilgrastim Using the EudraVigilance Database

“…Studying ICSR information on seriousness, 89.8% of cases were serious and mainly attributed to PEG-F. As for safety, comparing once-per-cycle PEG-F and daily injections of FIL, a phase III study revealed that the similar ADR profile between FIL and PEG-F [ 17 , 31 ]. Additionally, a meta-analysis study performed by authors identified 13 studies showing a head-to-head comparison of PEG-F and FIL [ 32 ]. In nine randomized controlled trials (RCTs), FN-related relative risk was lower for PEG-F and was not statistically significant (RR 0.90; p = 0.42).…”

Estudio FIRES: Filgrastim - investigación retrospectiva de efectividad y seguridad en una institución de salud en Colombia

“…19 Según la FDA, el Filgrastim cuenta con aprobación en las siguientes indicaciones: 1) reducir la incidencia de procesos infecciosos y prevenir el desarrollo de neutropenia febril en pacientes con cáncer que reciben quimioterapia mielosupresora; 2) disminuir el tiempo de recuperación del número absoluto de neutrófilos y la duración de la fiebre en pacientes con leucemia mieloide aguda; 3) reducir el tiempo de duración de la neutropenia y las secuelas clínicas relacionadas con la misma en pacientes con patologías oncológicas no mieloides sometidas a quimioterapia mieloablativa seguida de trasplante de médula ósea; 4) movilizar células progenitoras hematopoyéticas autólogas en la sangre periférica para su recolección por leucoféresis; 5) aminorar la incidencia y la extensión de las secuelas de neutropenia grave en pacientes sintomáticos con neutropenia crónica grave y, 6) aumentar la supervivencia de los pacientes expuestos agudamente a dosis mielosupresores de radiación. 3 Una de las principales indicaciones de los G-CSF como se mencionó anteriormente, es la profilaxis de la neutropenia inducida por QT y el riesgo de NF. En este estudio se encontró que los pacientes tratados con Filgrastim presentaron un conteo mayor de neutrófilos, con una diferencia estadísticamente significativa (p= 0.04).…”

“…2 La neutropenia se considera una emergencia médica ya que podría favorecer el desarrollo de infecciones bacterianas y/o micóticas, sometiendo a los pacientes a la administración de antibióticos de amplio espectro, retraso en el esquema de la quimioterapia, reducción no planificada de las dosis y mayor mortalidad y morbilidad de los pacientes. 3 De acuerdo con la categoría de la neutropenia, en el grado 4 (<500 cel/mm3) se presenta el mayor riesgo de infección. 4 Tradicionalmente la neutropenia se define como un recuento absoluto de neutrófilos circulantes <1.500/µL y se diagnostica mediante el hemograma con diferencial: 5 neutrófilos absolutos= (leucocitos) x (% de segmentados + formas inmaduras)/WBC, cuyo valor normal es de 1.500-8.000/µL.…”

Comparison of Short Acting versus Long Acting Filgrastim for Reduction of Chemotherapy Induced Febrile Neutropenia

“…In our study, incidence of FN in filgrastim group was 69.60% and in pegfilgrastim group was 42.90%. In a metaanalysis by Rastogi et al 19 ,the incidence of FN in patients receiving filgrastim as primary prophylaxis ranged from 1% to 38%. Similarly, in prior studies by Holmes et.al.…”