scholarly journals Both IgM and IgG Antibodies against Polyethylene Glycol Can Alter the Biological Activity of Methoxy Polyethylene Glycol-Epoetin Beta in Mice

Pharmaceutics ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 15 ◽  
Author(s):  
Tien-Ching Chang ◽  
Bing-Mae Chen ◽  
Wen-Wei Lin ◽  
Pei-Hua Yu ◽  
Yi-Wen Chiu ◽  
...  
Keyword(s):  
Biological Activity ◽  
Polyethylene Glycol ◽  
Therapeutic Activity ◽  
Igg Antibodies ◽  
Healthy Individuals ◽  
Inhibitory Effects ◽  
Igg Antibody ◽  
Epoetin Beta ◽  
Methoxy Polyethylene Glycol ◽  
Higher Doses

Pre-existing antibodies that bind polyethylene glycol are present in about 40% of healthy individuals. It is currently unknown if pre-existing anti-polyethylene glycol (PEG) antibodies can alter the bioactivity of pegylated drugs with a single long PEG chain, which represents the majority of newly developed pegylated medicines. Methoxy polyethylene glycol-epoetin beta (PEG-EPO) contains a single 30 kDa PEG chain and is used to treat patients suffering from anemia. We find that the pre-existing human anti-PEG IgM and IgG antibodies from normal donors can bind to PEG-EPO. The prevalence and concentrations of anti-PEG IgM and IgG antibodies were also higher in patients that responded poorly to PEG-EPO. Monoclonal anti-PEG IgM and IgG antibodies at concentrations found in normal donors blocked the biological activity of PEG-EPO to stimulate the production of new erythrocytes in mice and accelerated the clearance of 125I-PEG-EPO, resulting in PEG-EPO accumulation primarily in the liver and spleen. Accelerated clearance by the anti-PEG IgG antibody was mediated by the Fc portion of the antibody. Importantly, infusing higher doses of PEG-EPO could compensate for the inhibitory effects of anti-PEG antibodies, suggesting that pre-existing anti-PEG antibodies can be “dosed through.” Our study indicates that the bioactivity and therapeutic activity of PEG-EPO may be reduced in patients with elevated levels of pre-existing anti-PEG antibodies. New pegylated medicines with a single long PEG chain may also be affected in patients with high levels of anti-PEG antibodies.

scholarly journals Detection of antibodies to recombinant truncated flagellin and sonicated whole cell antigen of Burkholderia pseudomallei in acute melioidosis and in healthy Bangladeshi individuals

2020 ◽  
Vol 14 (1) ◽  
pp. 47-52
Author(s):  
Md Shariful Alam Jilani ◽  
Tang Thean Hock ◽  
Sraboni Mazumder ◽  
Fahmida Rahman ◽  
Md Mohiuddin ◽  
...  
Keyword(s):  
Rural Areas ◽  
Burkholderia Pseudomallei ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibodies ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Igg Antibody ◽  
Whole Cell ◽  
Cell Antigen ◽  
The Mean

Background and objectives: Several types of Burkholderia pseudomallei antigens have been used to determine the antibody response in acute and asymptomatic cases. In the present study, we have detected immunoglobulin G (IgG) antibody to recombinant truncated flagellin antigen (RTFA) of B. pseudomallei in the sera of acute melioidosis cases and healthy individuals from melioidosis endemic areas of Bangladesh by indirect enzyme-linked immunosorbent assay (ELISA). In parallel, IgG antibody to sonicated whole cell antigen (SWCA) of B. pseudomallei was determined to compare with anti-RTFA antibody. Methodology: Serum samples from culture confirmed melioidosis cases and from healthy individuals aged 21 years and above residing in melioidosis endemic rural areas were included in the study. Serum IgG antibody to RTFA and SWCA of B. pseudomallei was determined by indirect ELISA. Results: Out of 8 culture confirmed acute melioidosis cases, 7 (87.5%) and 8 (100%) were positive for anti-B. pseudomallei IgG antibodies by RTFA and SWCA methods respectively. Among 361 healthy individuals, the rate of seropositivity by RTFA-ELISA was significantly less than that of SWCA-ELISA (16.1% versus 26.8%; p = 0.001). The mean optical density (OD) of RTFA-ELISA of positive cases was significantly less than that of SWCA-ELISA in both melioidosis and healthy individuals (0.79±0.11 versus 2.4±0.08, p = 0.0001; 0.67±0.01 versus 1.27±0.02, p = 0.0001). The sensitivity and specificity of RTFA-ELISA were 88.9% and 100% respectively. Conclusion: Findings of the study suggest that multiple or combination of antigens should be used to study the seroprevalence of B. pseudomallei infection in a community. Also, prospective study is necessary to find out the duration of persistence of antibodies to different antigenic components of B. pseudomallei after exposure. Ibrahim Med. Coll. J. 2020; 14(1): 47-52

Pharmacokinetic and Pharmacodynamic Properties of Methoxy Polyethylene Glycol-Epoetin Beta Are Unaffected by the Site of Subcutaneous Administration1

2007 ◽  
Vol 47 (11) ◽  
pp. 1390-1397 ◽  
Author(s):  
Steven Fishbane ◽  
Anne Pannier ◽  
Xavier Liogier ◽  
Paul Jordan ◽  
Frank C. Dougherty ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Epoetin Beta ◽  
Methoxy Polyethylene Glycol

scholarly journals Cardiovascular Safety and All-Cause Mortality of Methoxy Polyethylene Glycol-Epoetin Beta and Other Erythropoiesis-Stimulating Agents in Anemia of CKD

2019 ◽  
Vol 14 (12) ◽  
pp. 1701-1710 ◽  
Author(s):  
Francesco Locatelli ◽  
Thierry Hannedouche ◽  
Steven Fishbane ◽  
Zoe Morgan ◽  
Delphine Oguey ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Major Adverse Cardiovascular Events ◽  
Primary Analysis ◽  
Open Label ◽  
Erythropoiesis Stimulating Agents ◽  
Link Type ◽  
Epoetin Beta ◽  
End Point ◽  
All Cause Mortality ◽  
Methoxy Polyethylene Glycol

Background and objectivesErythropoiesis-stimulating agents correct anemia of CKD but may increase cardiovascular risk. We compared cardiovascular outcomes and all-cause mortality associated with monthly methoxy polyethylene glycol-epoetin beta with those of the shorter-acting agents epoetin alfa/beta and darbepoetin alfa in patients with anemia of CKD.Design, setting, participants, & measurementsWe conducted a multicenter, open-label, noninferiority trial in which patients were randomized to receive methoxy polyethylene glycol-epoetin beta or reference erythropoiesis-stimulating agents, stratified by maintenance or correction treatment status and C-reactive protein level. The trial had a prespecified noninferiority margin of 1.20 for the hazard ratio (HR) for the primary end point (a composite of all-cause mortality, nonfatal myocardial infarction or stroke, adjudicated by an independent blinded committee). This trial is registered with ClinicalTrials.gov, number NCT00773513.ResultsIn total, 2818 patients underwent randomization, received methoxy polyethylene glycol-epoetin beta or a reference agent, and were followed for a median of 3.4 years (maximum, 8.4 years). In the modified intention-to-treat analysis, a primary end point event occurred in 640 (45.4%) patients in the methoxy polyethylene glycol-epoetin beta arm, and 644 (45.7%) in the reference arm (HR 1.03; 95% confidence interval [95% CI], 0.93 to 1.15, P=0.004 for noninferiority). All-cause mortality was not different between treatment groups (HR 1.06; 95% CI, 0.94 to 1.19). Results in patient subgroups on dialysis or treated in the correction or maintenance settings were comparable to the primary analysis.ConclusionsIn patients with anemia of CKD, once-monthly methoxy polyethylene glycol-epoetin beta was noninferior to conventional, shorter-acting erythropoiesis-stimulating agents with respect to rates of major adverse cardiovascular events or all-cause mortality.

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