Current Issue : January - March Volume : 2020 Issue Number : 1 Articles : 6 Articles
Objective: This study compared the pharmacokinetics (PK), safety, and immunogenicity\nof the biosimilar TAB008 monoclonal antibody to bevacizumab (AvastinR) in normal\nhealthy Chinese male volunteers.\nMethods: In this randomized, double-blind, parallel controlled study, a total of 100 healthy\nChinese male subjects were randomized (1:1) to receive a single 1 mg/kg intravenous dose\nof TAB008 or AvastinR over a 90-min infusion. The subjects were followed for 99 days after\ndrug administration. Primary endpoints were bioequivalence of major pharmacokinetic\nparameters�����....
The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept,\nadalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have\nbeen compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not\nbeen compared directly to each other or to an otherwise untreated placebo control. The present\nanalysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic\njoint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network\nmeta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with\ncontrols, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in\nthe network. The previously untested comparison with placebo was performed to estimate not only\nthe effect relative to another drug, but also the absolute attainable effect. Compared to placebo there\nwas a highly significant inhibitory effect on joint destruction of infliximab, etanercept, adalimumab,\ncertolizumab, and golimumab, which was about 0.9% per year as monotherapy and about 1.2% per\nyear when combined with MTX. Although significantly better than MTX and placebo, golimumab\nseemed inferior to the remaining TNFis. There was no difference between original reference drugs\n(Remicade, Enbrel) and the almost identical copy drugs (biosimilars)....
Background: Infliximab (IFX) has changed the management of many life-threatening immune-mediated diseases.\nThe high cost of IFX and its patent expiry have led to pharmaceutical companies developing a biosimilar; however,\nits safety profile remains unknown in the real world. The purpose of this study was to clarify the adverse events\nassociated with IFX originator and its biosimilar using the Japanese Adverse Drug Event Report (JADER) database.\nMethods: Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between the third\nquarter of 2014 and the fourth quarter of 2018. We calculated the reporting odds ratio and 95% confidence interval\nfor each adverse event.\nResults: We obtained 2771 reports of adverse events associated with IFX originator and 402 reports with IFX biosimilar.\nSignals were detected for pneumonia, interstitial lung disease, tuberculosis, and sepsis with both IFX originator and its\nbiosimilar, whereas there was no signal for infection with the biosimilar.\nConclusions: The strength of the association between IFX originator and its biosimilar with adverse events is partly\ndifferent, but reports were quite limited for the biosimilar compared with originator. It is recommended that research\nbe continued in order to accumulate a wide variety of information, and that newly reported data be placed in the\nmultifaceted viewpoints for improvement of care levels....
Oxidation of monoclonal antibodies (mAbs) can impact their efficacy and may therefore\nrepresent critical quality attributes (CQA) that require evaluation. To complement classical CQA,\nbevacizumab and infliximab were subjected to oxidative stress by H2O2 for 24, 48, or 72 h to\nprobe their oxidation susceptibility. For investigation, a middle-up approach was used utilizing\nliquid chromatography hyphenated with mass spectrometry (LC-QTOF-MS). In both mAbs, the Fc/2\nsubunit was completely oxidized. Additional oxidations were found in the light chain (LC) and\nin the Fdâ?? subunit of infliximab, but not in bevacizumab. By direct comparison of methionine\npositions, the oxidized residues in infliximab were assigned to M55 in LC and M18 in Fdâ??. The forced\noxidation approach was further exploited for comparison of respective biosimilar products. Both for\nbevacizumab and infliximab, comparison of posttranslational modification profiles demonstrated high\nsimilarity of the unstressed reference product (RP) and the biosimilar (BS). However, for bevacizumab,\ncomparison after forced oxidation revealed a higher susceptibility of the BS compared to the RP.\nIt may thus be considered a useful tool for biopharmaceutical engineering, biosimilarity assessment,\nas well as for quality control of protein drugs....
Background: Biologic medications have dramatically enhanced the treatment of many chronic paediatric\ninflammatory conditions. Their high cost is a factor that prohibits their broader use. Cheaper generic versions, or\nbiosimilars, are increasingly being used. Healthcare services are switching some patients over to biosimilars for\neconomic reasons, known as â??non-medical switchingâ??. Some patients unsuccessfully switch due to perceived\ndecreases in efficacy or non-specific drug effects. The implications of failed switching include exhaustion of\ntherapeutic options, unnecessary exposure to other medications, increased healthcare utilisation, worse patient\noutcomes and higher overall healthcare costs. Patient perceptions almost certainly play a role in these â??failed\nswitchesâ??.\nMethods: A thematic analysis was performed to better understand patient and parent perceptions on non-medical\nbiosimilar switching. The study was conducted in accordance with the Consolidated Criteria for Reporting\nQualitative Research recommendations. Patients with juvenile idiopathic arthritis currently taking adalimumab were\nincluded.\nResults: Nine families were interviewed just prior to a hospital trust-wide non-medical switch to an adalimumab\nbiosimilar. Several common themes were identified. The most frequent concerns were regarding practical aspects\nof the switch including the medication administration device type; the colour of the medication and administration\ndevice; and whether the injections would sting more. The relative safety and efficacy of the biosimilar was raised\nalthough most families felt that there would be no significant difference. Anxieties about the switch were largely\nplacated by reassurances from the medical team.\nConclusions: We derived recommendations based on existing adult literature and the observations from our study\nto optimise the benefits from non-medical biosimilar switching....
In May 2019, the Food and Drug Administration (FDA) proposed a quality range (QR) method\nfor the comparative analytical assessment in biosimilar studies. In this process, several reference\nproduct lots are necessary, selected from a wide period of manufacturing dates with different shelf lives,\nto calculate the total variability expressed as the standard deviation of reference product lots. This one\ndepends on the between-lots variation and analytic method uncertainty (i.e., within-lots variation).\nDuring this time, the analytical method must be in control and stable but with an appropriate accuracy\nand precision. In such a situation, various control charts were used to fix the method requirements and\ndetect small changes in the process. The results indicate that the method is indeed in control and stable,\nbut does not meet the requirements of the Analytical Target Profile (ATP) approach, independently of\nthe established uncertainty range. However, it does satisfy the traditional approach for an uncertainty\nrange���������....
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