Plain language review: what are biosimilar medicines and how can they be used to treat people with cancer?

WHAT IS THIS SUMMARY ABOUT?: The aim of this plain language review article is to help you to understand biosimilar medicines (called biosimilars) by giving a summary of biologic medicines and biosimilars. It is based on the experience of an international panel of physicians with expertise on biosimilars who discussed and agreed on the topics and information included in this review article. Biologic medicines are medicines that come from living organisms such as bacteria and animal or plant cells. Biosimilars are a group of approved biologic medicines that are similar to original biologic medicines that are already available. This review explains how biosimilars are developed and approved, and how they are used to treat people with cancer. It also answers some common important questions people with cancer might have when taking biosimilars. The purpose of this plain language review is to help you to understand the findings from recent research. This review reports information from peer-reviewed literature and other sources available in the public domain (e.g., regulatory documents or product information labels). The findings may differ from those of other review articles. Health professionals should make treatment decisions based on all available evidence.

Prescription patterns of granulocyte colony-stimulating factors in patients with breast cancer: A real-world study.

BACKGROUND AND OBJECTIVES: Myelosuppressive chemotherapy is effective for breast cancer but carries a potential risk of febrile neutropenia (FN). Clinical practice guidelines have recommended prophylaxis with granulocyte colony-stimulating factor (G-CSF) to reduce the incidence of FN in patients receiving chemotherapy. We aimed to examine the use of G-CSFs for primary prophylaxis for FN and to see whether it follows the guidelines. In addition, we examined the changes in the use of long-acting and short-acting G-CSFs in patients with breast cancer over the past ten years. METHODS: This was a retrospective observational real-world study. The data were obtained from the clinical research database of three hospitals affiliated with Taipei Medical University. Patients with breast cancer who initiated their first chemotherapy regimen between January 1, 2011, and December 31, 2020, were identified by the ICD codes and their use of filgrastim or pegfilgrastim was identified by the Anatomical Therapeutic Chemical codes. Whether and how G-CSF was prescribed during the study patients' first chemotherapy regimen was examined, and the annual change in the total number of short- and long-acting G-CSFs prescribed to the study patients from 2011 to 2020 was analyzed. RESULTS: Among the 2,444 patients who were prescribed at least one of the examined 15 breast cancer chemotherapy drugs, 1,414 did not use any G-CSFs during their first chemotherapy regimen while 145 used G-CSFs for primary prophylaxis and 185 for treatment. Among the patients receiving high FN risk regimens, only 8.6% used G-CSF for primary prophylaxis. The average (± SD) number of days for short-acting G-CSF use was 2.3 (± 1.5) days with a median of 2 days. In addition, it was found that there was a significant reduction in long-acting G-CSF use (p = 0.03) whereas the changes in short-acting G-CSF use over time were not significant (p = 0.50). CONCLUSIONS: Our study results show that G-CSFs are used for primary prophylaxis in a small percentage of patients with breast cancer and the duration of short-acting G-CSF use is relatively short. Considering the significant clinical and economic impact of FN, it is hoped that the prescription patterns of G-CSFs observed can provide an important reference for future clinical practice and reimbursement policy.

Oral ellagic acid attenuated LPS-induced neuroinflammation in rat brain: MEK1 interaction and M2 microglial polarization.

Ellagic acid, the marker component of peels of Punica granatum L., is known traditionally to treat traumatic hemorrhage. In this study, the cellular mechanism underlying ellagic acid-induced anti-inflammation was investigated using lipopolysaccharides (LPSs) as a neuroinflammation inducer. Our in vitro data showed that LPS (1 µg/mL) consistently phosphorylated ERK and induced neuroinflammation, such as elevation in tumor necrosis factor-α (TNF-α) and nitric oxide production in treated BV-2 cells. Incubation of ellagic acid significantly inhibited LPS-induced ERK phosphorylation and subsequent neuroinflammation in treated BV-2 cells. Furthermore, our in vivo study of neuroinflammation employed an intranigral infusion of LPS that resulted in a time-dependent elevation in phosphorylated ERK levels in the infused substantia nigra (SN). Oral administration of ellagic acid (100 mg/kg) significantly attenuated LPS-induced ERK phosphorylation. A four-day treatment of ellagic acid did not alter LPS-induced ED-1 elevation but ameliorated LPS-induced reduction in CD206 and arginase-1 (two biomarkers of M2 microglia). A seven-day treatment of ellagic acid abolished LPS-induced increases in heme-oxygenase-1, cyclo-oxygenase 2, and α-synuclein trimer levels (a pathological hallmark) in the infused SN. At the same time, ellagic acid attenuated LPS-induced increases in active caspase 3 and receptor-interacting protein kinase-3 levels (respective biomarkers of apoptosis and necroptosis) as well as reduction in tyrosine hydroxylase-positive cells in the infused SN. In silico analysis showed that ellagic acid binds to the catalytic site of MEK1. Our data suggest that ellagic acid is capable of inhibiting MEK1-ERK signaling and then attenuated LPS-induced neuroinflammation, protein aggregation, and programmed cell deaths. Moreover, M2 microglial polarization is suggested as a novel antineuroinflammatory mechanism in the ellagic acid-induced neuroprotection.

Improving the Efficiency of Medication Reconciliation in Two Taiwanese Hospitals by Using the Taiwan National Health Insurance PharmaCloud Medication System.

Purpose: Medication reconciliation (MedRec) is a process to ensure complete and accurate communication of patient medication information throughout care transitions to prevent medication errors. Hospitals in Taiwan have stride to implement a universal protocol for MedRec. To establish a feasible protocol indigenously, the World Health Organization (WHO) protocol was incorporated with the Taiwan National Health Insurance (NHI) PharmaCloud patient medication profile. The efficiency and error detection capability of this modified protocol was evaluated in two hospitals. Methods: A prospective, non-randomized, unblinded, multicenter cohort study was conducted. Subjects were recruited among patients admitted for colorectal or orthopedic surgery with at least 4 or more chronic drugs. To obtain the best possible medication history (BPMH), the control group was conducted according to the WHO protocol, and the experimental group used the modified WHO protocol with the medication data from the PharmaCloud system. The time spent on the two protocols was recorded. Admission and discharge orders were reconciled against the BPMH to identify any discrepancies. Discrepancies were evaluated by appropriateness, prescribing intentions, and types of inappropriateness. The levels of potential harm were classified for inappropriate discrepancies. Results: The mean time to obtain BPMH in the control group was 34.3±10.8 minutes and in the experimental group 27.5±11.5 minutes (P = 0.01). The experimental group had more subjects with discrepancies (87.9%) than the control (58.3%) (p < 0.001). The discrepancies in both admission and discharge orders for the experimental group (84.5 and 67.2%) were higher than those of the control (47.9 and 37.5%). Many inappropriate discrepancies were classified as the potential harm of level 2 (77.8%). Conclusion: Through the establishment of BPMH with the medication data from the Taiwan NHI PharmaCloud, MedRec could be achieved with greater efficiency and error detection capability in both the admission and discharge order validation processes.

Assessing Knowledge and Attitude of Healthcare Professionals on Biosimilars: A National Survey for Pharmacists and Physicians in Taiwan.

Despite the first approval of biosimilars' in 2010, biosimilar products usage has remained low in Taiwan. This cross-sectional survey study assessed healthcare professionals' (HCPs)-hospital pharmacists, oncologists, and rheumatologists-knowledge, and attitudes toward biosimilars. More precisely, their knowledge and attitude towards biosimilars' current usage and regulations in Taiwan were analyzed. The mean ± standard deviation knowledge score was 2.56 ± 0.86 out of 4 (n = 395), and a difference in knowledge score was determined according to the hospital types (p = 0.004). Rheumatologists possessed significantly higher confidence in their knowledge of biosimilars than other HCPs (p = 0.001). Pharmacists showed the highest acceptance-and rheumatologists the least-for switching patients from reference drugs to biosimilars (p = 0.02). Hospital type was associated with the respondent's confidence in their knowledge (p = 0.04) and the preference for distinguishable naming of biosimilars (p = 0.007). Their knowledge scores were associated with their confidence in the efficacy and safety of biosimilars (p = 0.02). The study found that the current level of biosimilar knowledge of HCPs in Taiwan is low. The higher the knowledge score, the greater the confidence in biosimilars and the familiarity with relevant regulations.

An evaluation of the healthcare costs of metastatic breast cancer: A retrospective matched cohort study.

ABSTRACT: To determine the economic burden of metastatic breast cancer (MBC) in Taiwan, we conducted a national retrospective claim database analysis to evaluate the incremental healthcare costs and utilization of MBC patients as compared to their breast cancer (BC) and breast cancer free (BCF) counterparts.Data were obtained from the National Health Insurance Claim Database and the Taiwan Cancer Registry database between 2012 and 2015. All healthcare utilization and costs were calculated on a per-patient-per-month (PPPM) basis and were compared among groups using the generalized linear model adjusting for age group, residential area, and Charlson comorbidity index group.A total of 1,606 MBC patients were matched to 6,424 BC patients and 6,424 BCF patients. The majority of overall MBC healthcare costs were attributed to outpatient costs (75.1%), followed by inpatient (23.2%) and emergency room costs (1.7%). The PPPM total healthcare costs of the MBC, BC, and BCF groups were TWD 7,422, 14,425, and 2,114, respectively. The adjusted PPPM total healthcare cost ratio of MBC to BCF was 4.1. Compared to BCF patients, the patients receiving both human epidermal growth factor receptor 2-targeted therapy and endocrine therapy incurred 28.1 times PPPM total costs. The adjusted PPPM total healthcare cost ratio of recurrent MBC to BCF was 2.3, while the ratio was 12.2 in the de novo MBC group.Patients with MBC are associated with substantial economic burden, particularly in outpatient costs. The study findings could be useful for MBC-related economic evaluations and health resource allocation.

Establishing a protocol for the compatibilities of closed-system transfer devices with multiple chemotherapy drugs under simulated clinical conditions.

Closed-system drug transfer devices (CSTDs) are used to prevent occupational exposure to hazardous drugs in health care providers. They are considered Class II medical devices by the US FDA and are cleared but not approved before marketing. While compatibility tests are conducted by CSTD manufacturers, the procuring institution needs to consider performing its own studies before buying these devices. Herein we tested the compatibility of the components of the Needleless® DualGuard CSTD system (vial access clips, vial access spikes, and administration adaptors) with 10 antineoplastic drugs, under simulated clinical conditions, including compounding and administration, and examined drug potency maintenance, plasticizer migration, and device functionality. All drugs maintained potency within 5%. Diisononyl phthalate leakage was observed from the administration adaptors for paclitaxel and concentrated etoposide solution. In addition, white particles were discovered in CSTDs storing busulfan solution and small cracks were observed on devices which stored melphalan. Thus, it was concluded that even in simulated clinical conditions, instead of extreme conditions, there are still concerns regarding the efficacy and safety of CSTD components. The methodology may be used to implement and detect possible interactions between antineoplastic agents and CSTD components before procurement.

Health state utilities for metastatic breast cancer in Taiwan.

BACKGROUND: New developments in medications for metastatic breast cancer (MBC) can be of great benefit to patients, but unfortunately these medicines also increase expenditures. Cost-utility analyses (CUAs) are needed to allocate health resources properly, and health utility values are required to calculate quality-adjusted life years in those CUAs. OBJECTIVE: The aims of this study were to measure health utility values for several MBC-related health states and certain breast cancer treatment-related grade 3/4 adverse drug reactions (ADRs). In addition, we examined whether different methods and respondents' characteristics would influence the utility values elicited. METHODS: A cross-sectional survey was conducted. The visual analogue scale (VAS) and time trade-off (TTO) methods were used to measure health utilities. Four MBC and nine ADR health states were selected for evaluation based on literature review and expert opinion. Information about respondents' demographic and clinical characteristics were collected to examine the relationship between utilities and participant characteristics. RESULTS: A total of 102 patients participated in this study. The TTO-elicited values were higher than the VAS-derived scores except for two MBC-related health states. Among the MBC health states assessed, the TTO preference score ranged from 0.04 (palliative MBC) to 0.62 (responding MBC). For grade 3/4 ADRs, the mean TTO-derived utility values ranged from 0.35 (nausea/vomiting) to 0.79 (fatigue). The ranking of the preference scores derived from the VAS was similar to that of the TTO-elicited scores. CONCLUSION: This study obtained health state utility values for MBC and grade 3/4 ADRs using both the TTO and the VAS, which provides useful data for future CUAs.

Cost-effectiveness of granulocyte colony-stimulating factor prophylaxis in chemotherapy-induced febrile neutropenia among breast cancer and Non-Hodgkin's lymphoma patients under Taiwan's national health insurance system.

RATIONALE, AIM AND OBJECTIVE: The beneficial effects of granulocyte colony-stimulating factor (G-CSF) prophylaxis on reducing the risk of chemotherapy-induced febrile neutropenia (CIFN) were well documented throughout the literature. However, existing data regarding its cost-effectiveness were conflicting. We estimated the cost-effectiveness of G-CSF prophylaxis in CIFN under Taiwan's National Health Insurance (NHI) system. METHODS: Data on clinical outcomes and direct medical costs were derived for 5179 newly diagnosed breast cancer and 629 non-Hodgkin's lymphoma (NHL) patients from the NHI claims database. Patients were further categorized into three subgroups as "primary-", "secondary-" and "no -" prophylaxis based on their patterns of G-CSF use. Generalized estimating equations were applied to estimate the impact of G-CSF use on the incidence of CIFN. The incremental cost-effectiveness ratios of primary and secondary prophylactic G-CSF use were calculated and sensitivity analyses were performed. RESULTS: Primary prophylaxis of G-CSF decreased the incidence of CIFN by 27% and 83%, while secondary prophylaxis by 34% and 22% in breast cancer and NHL patients, respectively. Compared with those with no prophylaxis, the incremental cost per CIFN reduced in primary prophylaxis is $931 and $52 among patients with breast cancer and NHL, respectively. In contrast, secondary prophylaxis is dominated by no prophylaxis and primary prophylaxis in both cancer patients. CONCLUSION: Primary but not secondary prophylactic use of G-CSF was cost-effective in CIFN in breast cancer and NHL patients under Taiwan's NHI system.

Implementing an evidence-based risk assessment tool to predict chemotherapy-induced neutropenia in women with breast cancer.

BACKGROUND: Several studies have documented the efficacy of prophylactic granulocyte colony-stimulating factor in reducing rates of infections and risk of febrile neutropenia. An appropriate risk assessment model is pivotal to identify high-risk patients who would require granulocyte colony-stimulating factor prophylaxis. OBJECTIVE: The objectives of the study were to develop, implement, and evaluate a risk assessment model for neutropenic events in breast cancer patients who were receiving myelosuppressive chemotherapy. METHODS: During the study period, neutropenia risk was assessed for breast cancer patients by using an innovative risk model before the first cycle of chemotherapy. A stepwise logistic regression model was performed to determine significant factors for the prediction. RESULTS: A total of 119 patients were evaluated for neutropenia risk between August 2010 and December 2010. Twenty-nine percent (35/119) of the patients have experienced at least 1 neutropenic event during the initial 3 cycles of chemotherapy. Based on the logistic regression model, only the risk score was retained as the significant predictor; the probability of an individual patient developing neutropenic events increased 1.24 times by increasing 1 score number (odds ratio, 1.24; with 95% confidence interval, 1.063-1.457). CONCLUSIONS: Based on the examination of different cutoff points, the performance of the risk model is best when the risk threshold is set at 6, which was found to have a sensitivity of 0.49 and a specificity of 0.69; the misclassification rate was 0.37, with a positive predictive value of 0.40 and a negative predictive value of 0.76. IMPLICATIONS FOR PRACTICE: The results of this project support incorporating the discussed risk assessment model into routine nursing assessments to prevent neutropenic complications.