Ultrafast 30-min infusion of a rituximab biosimilar (Truxima).
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ABSTRACT:
SUBMITTER: Perez-Persona E
PROVIDER: S-EPMC10660389 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
Publications
Ultrafast 30-min infusion of a rituximab biosimilar (Truxima).
Pérez-Persona Ernesto E Cuevas Palomares Laida L Unamunzaga Cilaurren Ariane A Gutiérrez López de Ocáriz Xabier X Buendía Ureña Buenaventura B Vega González de Viñaspre Ana A Benito Ibarrondo Begoña B Molinillo Fernández María Carmen MC Cordero Osúa Ana A Benítez Delgado Beatriz B García Albás Juan José JJ Andrés Moralejo Miguel Ángel MÁ Guinea de Castro José María JM
EJHaem 20231017 4
In this clinical trial, we demonstrate that ultrarapid fast infusion of rituximab (Truxima) in 30 min with oral premedication is feasible and secure for patients, and reduce the day-care hospital stays. ...[more]
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Project description:BackgroundInfusion-related reactions (IRRs) are the most common adverse event (AE) associated with infusion of rituximab, an anti-CD20 monoclonal antibody.ObjectiveOur objective was to evaluate the impact of dosing/infusion patterns and certain baseline characteristics on IRR occurrence during the first rituximab infusion administered as the biosimilar PF-05280586 (RTX-PF) or reference rituximab sourced from the EU (RTX-EU, MabThera®) in patients with CD20+ low-tumor-burden follicular lymphoma.Patients and methodsRituximab (RTX-PF, n=196; RTX-EU, n=198) was administered (375 mg/m2) on days 1, 8, 15, and 22 (one cycle), with a follow-up period through 52 weeks. The relationships between infusion rate, drug exposure, and IRR incidence were assessed by logistic regression analysis and pharmacokinetic modeling and simulation. Baseline CD20 level, antidrug antibody (ADA) status, and tumor burden according to IRR occurrence (yes/no) were compared descriptively.ResultsMedian rituximab infusion duration on day 1 was 3.50 h for each of the two groups. There was a positive correlation between infusion rate and all-grade IRRs occurring within 24 h after infusion (p < 0.0001). Patients who developed IRRs had a higher median baseline CD20+ level. IRR incidence was unaffected by baseline ADA status. Drug exposure did not predict IRR incidence. Baseline tumor burden was similar between patients with and without IRRs.ConclusionsResults of this analysis provide a better understanding of IRRs after the first rituximab (RTX-PF or RTX-EU) infusion and demonstrate a potential correlation of infusion rate and other factors with IRR at the individual and population levels. Infusion-rate escalation steps continue to be needed to manage IRRs.Trial registration (date of registration)ClinicalTrials.gov Identifier: NCT02213263 (11 August 2014); and EudraCT: 2014-000132-41 (10 October 2014).
| S-EPMC8295162 | biostudies-literature
Project description:ObjectivesTwo randomized Phase I studies in separate populations of healthy adult volunteers investigated the pharmacokinetics, safety and tolerability of daptomycin (Cubicin; Novartis Pharma AG, Basel, Switzerland) administered as a 2 min intravenous (iv) injection, relative to the currently licensed 30 min iv infusion.MethodsStudy 1 was an open-label, single-dose, two-period, crossover study in which each subject received 6 mg/kg daptomycin administered as a 30 min iv infusion (n = 15) and as a 2 min iv injection (n = 16). In Study 2, a single-blind, multiple-dose, parallel-group study, subjects received a once-daily 2 min iv injection of 6 mg/kg daptomycin (n = 12), 4 mg/kg daptomycin (n = 8) or placebo (n = 4) for 7 days. Single-dose pharmacokinetics were assessed at various timepoints up to 36 and 24 h post-dose in Study 1 and Study 2, respectively, and multiple-dose pharmacokinetics were assessed in Study 2 at day 7 for 48 h post-dose.ResultsIn Study 1, pharmacokinetic comparability between the two administration regimens was demonstrated by meeting the bioequivalence criteria for the exposure parameters, AUC(0-t), AUC(0-infinity) and C(max). In Study 2, time-invariant pharmacokinetic properties as well as dose-proportional pharmacokinetics were demonstrated for the daptomycin 2 min iv injection regimen. In both studies, daptomycin was well tolerated and the majority of treatment-emergent adverse events were of mild intensity and considered to be unrelated to daptomycin.ConclusionsThe similar pharmacokinetic and safety profiles of the two administration regimens suggest that the 2 min iv injection may be a convenient treatment option for both patients and healthcare professionals.
| S-EPMC2692502 | biostudies-literature
Project description: Not available
| S-EPMC5709121 | biostudies-literature
Project description:BackgroundRegulatory approval for a biosimilar product is provided on the basis of its comparability to an originator product. A thorough physicochemical and functional comparability exercise is a key element in demonstrating biosimilarity. Here we report the characterization of a proposed biosimilar rituximab (GP2013) and originator rituximab.ObjectiveTo compare GP2013 with originator rituximab using an extensive array of routine analytical and extended characterization methods.MethodsPrimary and higher order protein structures were analyzed using a variety of methods that included high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI-MS), peptide mapping with UV and MS detection, circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy, hydrogen deuterium exchange (HDX) MS, 1D (1)H nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and differential scanning calorimetry (DSC). Charge and amino acid modifications were assessed using cation exchange chromatography (CEX) and peptide mapping using reversed-phase (RP) HPLC. Boronate affinity chromatography was used to determine the relative amount of glycation. Glycans were identified and quantified after 2-aminobenzamide (2-AB) labeling and separation using normal phase HPLC with fluorescence and MS detection, respectively. Glycan site occupancy was determined using reducing capillary electrophoresis with sodium dodecyl sulfate (CE-SDS). Size heterogeneity was determined using reducing and non-reducing CE-SDS, size exclusion chromatography (SEC) and asymmetric flow field flow fractionation (AF4). Biological characterization included a series of bioassays (in vitro target binding, antibody-dependent cell-mediated cytotoxicity [ADCC], complement-dependent cytotoxicity [CDC] and apoptosis) and surface plasmon resonance (SPR) Fc receptor binding assays.ResultsIntact mass analysis of GP2013 and the heavy and light chains using RP HPLC-ESI-MS revealed the expected molecular mass of rituximab. The amino acid sequence was shown to be identical between GP2013 and the originator rituximab. Further sequence confirmation using RP-HPLC-UV/MS peptide mapping showed non-distinguishable chromatograms for Lys-C digested GP2013 and originator rituximab. The higher order structure of GP2013 was shown to be indistinguishable from originator rituximab using a large panel of redundant and orthogonal methods. GP2013 and originator rituximab were comparable with regard to charge variants, specific amino acid modifications and the glycan pattern. GP2013 was also shown to have similar purity, aggregate and particle levels when compared with the originator. Functionally, and by using a comprehensive set of bioassays and binding assays covering a broad range of rituximab's functional activities, GP2013 could not be distinguished from originator rituximab.ConclusionGP2013 was shown to be physicochemically highly similar to originator rituximab at the level of primary and higher order structure, post-translational modifications and size variants. An extensive functional characterization package indicated that GP2013 has the same biological properties as originator rituximab.
| S-EPMC3775154 | biostudies-literature
Project description:Determine if yeast cell in stationary-phase cultures respond to oxidative stress Keywords: time-course
2005-12-01 | GSE3683 | GEO
Project description:Although rituximab is generally well-tolerated, infusion-related reactions (IRRs) are common with the initial dose when administered intravenously according to standard recommendations. To prevent IRRs, premedication and low-speed infusion rates have been recommended. Consequently, intravenous (i.v.) infusion of rituximab can become a labor-intensive process. Rapid i.v. rituximab infusion over 90 min has demonstrated a favorable safety profile for the second and subsequent infusions during the course of therapy. The aim of this study was to investigate the safety and tolerability of 90-min rapid infusion of Sandoz rituximab biosimilar (SDZ-RTX) for patients with CD20+ lymphoma or chronic lymphocytic leukemia (CLL). We retrospectively reviewed all patients with CD20+ lymphoma or CLL who received SDZ-RTX infusions in 90 min from July 2019 to July 2021 at seven Spanish hospitals. The primary end point was the incidence of IRRs. We identified 124 patients and 576 rapid administrations of SDZ-RTX, with an average of five rapid infusions per patient. Most rapid infusions of SDZ-RTX were in combination with CHOP/CHOP-like therapy (48.4%), followed by SDZ-RTX alone (15.1%), in combination with bendamustine (14.5%), or with other regimens (22%). The 90-min SDZ-RTX infusion schedule was well-tolerated with no grade 3/4 IRRs. The incidence of any grade IRR during the first rapid infusion was 1% (5 grade 1 IRRs and 1 grade 2 IRR). In conclusion, rapid 90-min i.v. administration of SDZ-RTX for the second and subsequent infusions during the course of therapy is well-tolerated in patients with CD20+ lymphoma or CLL.
| S-EPMC9926065 | biostudies-literature
Project description:In this work we studied cellular response to doxorubicin by measuring transcriptomics experiments. The AC16 cells were treated with 10 nM doxorubicin for 10 min, 30 min, 360 min. 1 control group was set (0 min treatment).
2025-04-23 | GSE201411 | GEO
Project description:OBJECTIVE:This extension study provided continued treatment to subjects with active rheumatoid arthritis who had participated for ≥16 weeks in a pharmacokinetic similarity study of PF-05280586 (potential rituximab biosimilar). Objectives were to evaluate overall pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of PF-05280586 after transition from rituximab reference products to PF-05280586, and follow-up of biomarker and efficacy assessments. METHODS:Subjects were offered ≤3 additional courses of treatment of PF-05280586, with or without a single transition from rituximab in Europe (rituximab-EU; MabThera) or the US (rituximab-US; Rituxan) to PF-05280586. Each course comprised 2 intravenous infusions (1,000 mg on days 1 and 15, separated by 24 weeks [± 8 weeks]). RESULTS:Of 220 subjects in the parent study, 185 were randomized and included in this study. There were no notable differences in drug concentrations between groups or across courses, with little variation in depletion of CD19+ B cells between groups, and no apparent relationship between infusion-related reactions and antidrug antibodies with or without single transition from rituximab reference products to PF-05280586. Long-term safety and tolerability of PF-05280586 was acceptable in all groups for up to 96 weeks, with a low incidence of treatment-emergent adverse events independent of single drug transition. The percentage of subjects with a low disease activity score and disease activity score remission was similar across groups for all time points, and responses were sustained until end of study. CONCLUSION:This study demonstrated acceptable safety, tolerability, and immunogenicity, with or without single transition from rituximab reference products to PF-05280586, without increased immunogenicity on single transition.
| S-EPMC6221032 | biostudies-literature
Project description:PurposeThere has been no extensive study to compare the efficacy between rituximab originator (Mabthera®) and its biosimilar (Truxima®) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Here, we investigated the clinical effects of rituximab on poor outcomes of MPA and GPA in Korean patients, and compared those between Mabthera® and Truxima®.Materials and methodsWe retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®.ResultsThe median age at diagnosis was 60.1 years and 46 patients were men (97 MPA and 42 GPA patients). Among poor outcomes, patients receiving rituximab exhibited a significantly lower cumulative relapse-free survival rate compared to those not receiving rituximab (p=0.002). Nevertheless, rituximab use did not make any difference in other poor outcomes of MPA and GPA except for relapse, which might be a rebuttal to the fact that rituximab use after relapse eventually led to better prognosis. There were no significant differences in variables at diagnosis and during follow-up between patients receiving Mabthera® and those receiving Truxima®. Patients receiving Truxima® exhibited a similar pattern of the cumulative survival rates of each poor outcome to those receiving Mabthera®.ConclusionTruxima® prevents poor outcomes of MPA and GPA as effectively as does Mabthera®.
| S-EPMC7393299 | biostudies-literature
Project description:PurposeTo provide empirically-supported thresholds for step-based intensity (i.e., peak 30-min cadence; average of the top 30 steps/min in a day) and steps/day in relation to cardiometabolic health outcomes.MethodsReceiver operating characteristic curve analysis was applied to the National Health and Nutrition Examination Survey (NHANES) 2005-2006 accelerometer-derived step data to determine steps/day and peak 30-min cadence as risk screening values (i.e., thresholds) for fasting glucose, body mass index, waist circumference, high blood pressure, triglycerides, and HDL cholesterol. Thresholds for peak 30-min cadence and steps/day were derived that, when exceeded, classify the absence of each cardiometabolic risk factor. Additionally, logistic regression models that included the influence of age and smoking were developed using the sample weights, primary sampling units (PSUs), and stratification variables provided by the NHANES survey. Finally, a decision tree analysis was performed to delineate criteria for at-risk versus healthy populations using cadence bands.ResultsPeak 30-min cadence thresholds across cardiometabolic outcomes ranged from 66-72 steps/min. Steps/day thresholds ranged from 4325-6192 steps/day. Higher thresholds were observed in men compared to women. In men, higher steps/day thresholds were observed in age ranges of 30-39, while in women, higher thresholds were observed in the age-range 50-59 years. Decision trees for classifying being at low risk for metabolic syndrome contained one risk-free leaf at higher cadence bands, specifically for any time accumulated at ≥120 steps/min.ConclusionsMinimum thresholds representing absence of cardiometabolic risk range from 4325-6192 steps/day and 66-72 steps/min for peak 30-min cadence. Any time accumulated at ≥120 steps/min was associated with an absence of cardiometabolic risk. Although based on cross-sectional data, these thresholds represent potentially important and clinically interpretable daily physical activity goals.
| S-EPMC6677301 | biostudies-literature