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OBJECTIVE Management of anemia of chronic kidney disease (CKD) often includes subcutaneous or intravenous administration of erythropoietin-stimulating agents (ESAs). Mircera, a pegylated continuous erythropoietin receptor agonist, has a longer duration of action and requires less frequent administration than other ESAs. Pediatric experience with Mircera is limited. We retrospectively reviewed our long-term experience of Mircera in a national pediatric nephrology center. METHODS Patients were identified via an electronic patient record database. Data collected included demographics (sex, age, etiology of CKD, CKD stage, dialysis modality), dosing information, and laboratory data--hemoglobin (Hb), parathormone (PTH), ferritin, hematinics prior to commencing Mircera and all subsequent values associated with dose adjustments. RESULTS Seventy-seven patients aged 2 to 18 years, with CKD stages 2 to 5T had received at least 1 dose of Mircera, with 75 patients having sufficient data and a total of 1473 doses. No patients discontinued Mircera owing to adverse effects. One patient experienced a potential severe adverse drug reaction. Mircera was effective in improving or maintaining Hb =10.0 g/dL in most (58/75, 77.3%) patients. The median dose to achieve Hb =10.0 g/dL was 2.1 µg/kg/4 wk. Most doses (1039, 71.5%) were administered 4-weekly. The doses (161, 11.1%) that were administered 6-weekly remained efficacious. Thirty-two patients started Mircera with Hb <10.0 g/dL; 26 (81%) achieved Hb =10.0 g/dL within a median time of 4 months. Mircera was less effective if given every 8 weeks, or in the presence of hyperparathyroidism or hyperferritinemia. CONCLUSION Mircera appears safe and effective in pediatric patients with CKD. [ABSTRACT FROM AUTHOR]

Methoxy polyethylene glycol (mPEG) is attached to many proteins, peptides, nucleic acids and nanomedicines to improve their biocompatibility. Antibodies that bind PEG are present in many individuals and can be generated upon administration of pegylated therapeutics. Anti-PEG antibodies that bind to the PEG "backbone" can accelerate drug clearance and detrimentally affect drug activity and safety, but no studies have examined how anti-methoxy PEG (mPEG) antibodies, which selectively bind the terminus of mPEG, affect pegylated drugs. Here, we investigated how defined IgG and IgM monoclonal antibodies specific to the PEG backbone (anti-PEG) or terminal methoxy group (anti-mPEG) affect pegylated liposomes or proteins with a single PEG chain, a single branched PEG chain, or multiple PEG chains. Large immune complexes can be formed between all pegylated compounds and anti-PEG antibodies but only pegylated liposomes formed large immune complexes with anti-mPEG antibodies. Both anti-PEG IgG and IgM antibodies accelerated the clearance of all pegylated compounds but anti-mPEG antibodies did not accelerate clearance of proteins with a single or branched PEG molecule. Pegylated liposomes were primarily taken up by Kupffer cells in the liver, but both anti-PEG and anti-mPEG antibodies directed uptake of a heavily pegylated protein to liver sinusoidal endothelial cells. Our results demonstrate that in contrast to anti-PEG antibodies, immune complex formation and drug clearance induced by anti-mPEG antibodies depends on pegylation architecture; compounds with a single or branched PEG molecule are unaffected by anti-mPEG antibodies but are increasingly affected as the number of PEG chain in a structure increases. [Display omitted] [ABSTRACT FROM AUTHOR]

A conjugate of erythropoietin β with 30 kDa linear methoxy poly(ethylene glycol) characterized by the presence of an azo spacer between the protein fragment and poly(ethylene glycol) was developed for import-substitution of Mircera drug in the Russian Federation. The erythropoietic activity of the synthesized conjugate was determined. Its pharmacokinetics in CBA mice were found to be comparable to those of Mircera. The bioequivalence of the proposed azo conjugate and Mircera was established based on the calculated drug pharmacokinetic parameters in mice. [ABSTRACT FROM AUTHOR]

Rationale & Objective: The optimum starting dose of intravenous continuous erythropoietin receptor activator (C.E.R.A.) has been previously determined; this study ascertains the optimum starting dose of subcutaneous C.E.R.A. administration in pediatric patients., Study Design: Phase 2, open-label, single-arm, multicenter study., Setting & Participants: Patients aged 3 months to 17 years with renal anemia and chronic kidney disease (CKD; including those treated with maintenance dialysis and those not treated with dialysis) who were receiving maintenance treatment with erythropoiesis-stimulating agents (ESAs)., Intervention: Subcutaneous C.E.R.A. administration every 4 weeks (starting dose was based on defined conversion factors)., Outcome: The primary outcome was the change in hemoglobin concentration between the baseline and evaluation period for each patient. Secondary efficacy measures and safety were also evaluated., Results: Forty patients aged 0.4-17.7 years were enrolled. The study achieved its primary outcome: the mean change in hemoglobin concentration was an increase of 0.48g/dL; the 95% confidence interval (0.15-0.82) and standard deviation (±1.03) were within the prespecified boundaries (-1 to 1g/dL and<1.5g/dL, respectively). Mean hemoglobin concentrations were maintained within the target 10-12g/dL range in 24 of 38 patients and within±1g/dL of the baseline in 19 of 38 patients, and the median C.E.R.A. subcutaneous dose decreased over time. Efficacy in key subgroups (age group, dialysis type, prior ESA treatment) was consistent with the primary outcome. Thirty-eight patients completed the core period; 25 chose to enter the safety extension period. Safety was consistent with prior studies, with no new signals., Limitations: Single-arm and open-label study; small sample size., Conclusions: Pediatric patients with anemia secondary to CKD who were on, or not on, dialysis could be safely and effectively switched from maintenance ESAs to subcutaneous C.E.R.A. administered every 4 weeks, using defined dose-conversion factors to determine the optimum starting dose., Funding: F. Hoffmann-La Roche Ltd., Trial Registration: The SKIPPER trial registered at ClinicalTrials.gov with study number NCT03552393., Plain-Language Summary: Anemia, a complication of chronic kidney disease, is associated with poor quality of life and an increased risk of hospitalization and mortality. The current treatments for anemia include iron therapy and erythropoiesis-stimulating agents (ESAs); however, the relatively short half-lives of the ESAs epoetin alfa/beta or darbepoetin alfa may require more frequent dosing and hospital visits compared with the ESA known as continuous erythropoietin receptor activator (C.E.R.A.). A previous study demonstrated that children aged 5 years or more with anemia associated with chronic kidney disease who were on hemodialysis could be switched to intravenous C.E.R.A. from their existing epoetin alfa/beta or darbepoetin alfa treatment. This study provides evidence that subcutaneous C.E.R.A. can safely and effectively treat anemia in children, including those aged<5 years and regardless of whether they were on dialysis or the type of dialysis they received (peritoneal dialysis or hemodialysis)., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)