Pathway Analysis of Patients with Severe Acute Respiratory Syndrome.

BACKGROUND: Coronaviruses are emerging threats for human health, as demonstrated by the ongoing coronavirus disease 2019 (COVID-19) pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is closely related to SARS-CoV-1, which was the cause of the 2002-2004 SARS outbreak, but SARS-CoV-1 has been the subject of a relatively limited number of studies. Understanding the potential pathways and molecular targets of SARS-CoV-1 will contribute to current drug repurposing strategies by helping to predict potential drug-disease associations. METHODS: A microarray dataset, GSE1739, of 10 SARS patients and 4 healthy controls was downloaded from NCBI's GEO repository, and differential expression was identified using NCBI's GEO2R software. Pathway and enrichment analysis of the differentially expressed genes was carried out using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis, respectively. RESULTS: Our findings show that the drugs dexamethasone, filgrastim, interferon alfacon-1, and levodopa were among the most significant upstream regulators of differential gene expression in SARS patients, while neutrophil degranulation was the most significantly enriched pathway. CONCLUSION: An enhanced understanding of the pathways and molecular targets of SARS-CoV-1 in humans will contribute to current and future drug repurposing strategies, which are an essential tool to combat rapidly emerging health threats.

Evaluation of a novel medical device for pegfilgrastim administration.

Pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor, has reduced the risk of developing febrile neutropenia, which is associated with an increase in severe infection and prolonged hospitalization. However, pegfilgrastim administration requires that patients visit hospital following cancer chemotherapy, thus imposing a burden on patients and those around them. An on-body injector (OBI), which automatically administers pegfilgrastim about 27 hours after chemotherapy, was used in this study. The OBI, which consists of a main pump unit and infusion set, is a drug delivery device designed to be attached to the patient's body, with a timer-controlled dosing function. This study was conducted in breast cancer patients to evaluate the safety of pegfilgrastim administered subcutaneously via the OBI. The study period consisted of screening and treatment observation periods involving four cycles of neoadjuvant or adjuvant chemotherapy with docetaxel plus cyclophosphamide. One 3.6-mg pegfilgrastim dose was administered subcutaneously via OBI during each cycle of chemotherapy. The study enrolled 35 patients, and no serious adverse events or febrile neutropenia occurred. Administration of pegfilgrastim was successfully completed at all times when the OBI was attached to the patient, and no safety concerns associated with OBI function arose. For outpatients requiring pegfilgrastim following cancer chemotherapy, the use of an OBI was considered to be a safe option to reduce the need for outpatient visits that restrict their activities of daily living.

The Effect of Neutropenia and Filgrastim (G-CSF) on Cancer Patients With Coronavirus Disease 2019 (COVID-19) Infection.

BACKGROUND: Neutropenia is commonly encountered in cancer patients. Recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), a cytokine that initiates proliferation and differentiation of mature granulocytes, is widely given to oncology patients to counteract neutropenia, reducing susceptibility to infection. However, the clinical impact of neutropenia and G-CSF use in cancer patients with coronavirus disease 2019 (COVID-19) remains unknown. METHODS: An observational cohort of 379 actively treated cancer patients with COVID-19 was assembled to investigate links between concurrent neutropenia and G-CSF administration on COVID-19-associated respiratory failure and death. These factors were encoded as time-dependent predictors in an extended Cox model, controlling for age and underlying cancer diagnosis. To determine whether the degree of granulocyte response to G-CSF affected outcomes, the degree of response to G-CSF, based on rise in absolute neutrophil count (ANC) 24 hours after growth factor administration, was also incorporated into a similar Cox model. RESULTS: In the setting of active COVID-19 infection, outpatient receipt of G-CSF led to an increased number of hospitalizations (hazard ratio [HR]: 3.54, 95% confidence interval [CI]: 1.25-10.0, P value: .017). Furthermore, among inpatients, G-CSF administration was associated with increased need for high levels of oxygen supplementation and death (HR: 3.56, 95% CI: 1.19-10.2, P value: .024). This effect was predominantly seen in patients that exhibited a high response to G-CSF based on their ANC increase post-G-CSF administration (HR: 7.78, 95% CI: 2.05-27.9, P value: .004). CONCLUSIONS: The potential risks versus benefits of G-CSF administration should be considered in neutropenic cancer patients with COVID-19, because G-CSF administration may lead to worsening clinical and respiratory status.

Primary Prophylaxis With Biosimilar Filgrastim for Patients at Intermediate Risk for Febrile Neutropenia: A Cost-Effectiveness Analysis.

PURPOSE: Temporary COVID-19 guideline recommendations have recently been issued to expand the use of colony-stimulating factors in patients with cancer with intermediate to high risk for febrile neutropenia (FN). We evaluated the cost-effectiveness of primary prophylaxis (PP) with biosimilar filgrastim-sndz in patients with intermediate risk of FN compared with secondary prophylaxis (SP) over three different cancer types. METHODS: A Markov decision analytic model was constructed from the US payer perspective over a lifetime horizon to evaluate PP versus SP in patients with breast cancer, non-small-cell lung cancer (NSCLC), and non-Hodgkin lymphoma (NHL). Cost-effectiveness was evaluated over a range of willingness-to-pay thresholds for incremental cost per FN avoided, life year gained, and quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty. RESULTS: Compared with SP, PP provided an additional 0.102-0.144 LYs and 0.065-0.130 QALYs. The incremental cost-effectiveness ranged from $5,660 in US dollars (USD) to $20,806 USD per FN event avoided, $5,123 to $31,077 USD per life year gained, and $7,213 to $35,563 USD per QALY gained. Over 1,000 iterations, there were 73.6%, 99.4%, and 91.8% probabilities that PP was cost-effective at a willingness to pay of $50,000 USD per QALY gained for breast cancer, NSCLC, and NHL, respectively. CONCLUSION: PP with a biosimilar filgrastim (specifically filgrastim-sndz) is cost-effective in patients with intermediate risk for FN receiving curative chemotherapy regimens for breast cancer, NSCLC, and NHL. Expanding the use of colony-stimulating factors for patients may be valuable in reducing unnecessary health care visits for patients with cancer at risk of complications because of COVID-19 and should be considered for the indefinite future.