Therapeutic plasma exchange: A technical and operational review

Kaplan, André A.

doi:10.1002/jca.21257

Cited by 118 publications

(138 citation statements)

References 57 publications

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“…45 The extent of plasma IgG reduction achieved in these preclinical investigations and in the clinical study 6 are comparable with the reduction (~ 50–60%) observed following a full course of repeated plasmapheresis procedures in humans, which is one of the current standards of care in autoimmune diseases. 52,53 This suggests that FcRn blockade may not only have clinical efficacy in autoimmune disease, but also that it could be more simply and rapidly administered, and may be more convenient and more specific in its mechanism of action than current treatments. Importantly, when rozanolixizumab dosing was stopped, plasma IgG concentrations returned to pre-dose levels, demonstrating that there was no lasting effect on FcRn.…”

Section: Resultsmentioning

confidence: 99%

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Smith

Kießling

Lledó-García

et al. 2018

mAbs

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Rozanolixizumab (UCB7665), a humanized high-affinity anti-human neonatal Fc receptor (FcRn) monoclonal antibody (IgG4P), has been developed to reduce pathogenic IgG in autoimmune and alloimmune diseases. We document the antibody isolation and compare rozanolixizumab with the same variable region expressed in various mono-, bi- and trivalent formats. We report activity data for rozanolixizumab and the different molecular formats in human cells, FcRn-transgenic mice, and cynomolgus monkeys. Rozanolixizumab, considered the most effective molecular format, dose-dependently and selectively reduced plasma IgG concentrations in an FcRn-transgenic mouse model (no effect on albumin). Intravenous (IV) rozanolixizumab dosing in cynomolgus monkeys demonstrated non-linear pharmacokinetics indicative of target-mediated drug disposition; single IV rozanolixizumab doses (30 mg/kg) in cynomolgus monkeys reduced plasma IgG concentration by 69% by Day 7 post-administration. Daily IV administration of rozanolixizumab (initial 30 mg/kg loading dose; 5 mg/kg daily thereafter) reduced plasma IgG concentrations in all cynomolgus monkeys, with low concentrations maintained throughout the treatment period (42 days). In a 13-week toxicology study in cynomolgus monkeys, supra-pharmacological subcutaneous and IV doses of rozanolixizumab (≤ 150 mg/kg every 3 days) were well tolerated, inducing sustained (but reversible) reductions in IgG concentrations by up to 85%, with no adverse events observed. We have demonstrated accelerated natural catabolism of IgG through inhibition of IgG:FcRn interactions in mice and cynomolgus monkeys. Inhibition of FcRn with rozanolixizumab may provide a novel therapeutic approach to reduce pathogenic IgG in human autoimmune disease. Rozanolixizumab is being investigated in patients with immune thrombocytopenia (NCT02718716) and myasthenia gravis (NCT03052751).

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Section: Resultsmentioning

confidence: 99%

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Smith

Kießling

Lledó-García

et al. 2018

mAbs

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“…TPE is expected to be a logical therapeutic option to consider in a disease condition in which the pathogenesis is linked to a specific toxic biologic substance that has a relatively high molecular mass (.15,000 D), a slow rate of formation, and distribution in the intravascular space (Table 1) (1). In contrast to hemodialysis or hemofiltration in which many substances with lower or middle molecular weights are targeted for removal, the target with TPE is typically a single constituent of plasma ( Figure 1) (2).…”

Section: Introductionmentioning

confidence: 99%

Principles of Separation

Williams

Balogun

2014

Clinical Journal of the American Society of Nephrology

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SummaryExtracorporeal "blood purification," mainly in the form of hemodialysis has been a major portion of the clinical activity of many nephrologists for the past 5 decades. A possibly older procedure, therapeutic plasma exchange, separates and then removes plasma as a method of removing pathogenic material from the patient. In contrast to hemodialysis, therapeutic plasma exchange preferentially removes biologic substances of high molecular weight such as autoantibodies or alloantibodies, antigen-antibody complexes, and Ig paraproteins. These molecular targets may be cleared through two alternative procedures: centrifugal separation and membrane separation. This review presents operational features of each procedure, with relevance to the nephrologist. Kinetics of removal of these plasma constituents are based on the principles of separation by the apheresis technique and by features specific to each molecular target, including their production and compartmentalization in the body. Molecular targets for common renal conditions requiring therapeutic plasma exchange are also discussed in detail.

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“…Our 20 year experience with the Cobe Spectra machine provided us with significant therapeutic outcomes lacking any technical problems. Spectra Optia is a new centrifugation system device by Caridian BCT Inc. 2009 which is being used in USA and Europe [9].…”

Section: Centrifugationmentioning

confidence: 99%

Therapeutic apheresis: Technical modalities and therapeutic applications

Eirini¹,

Dimitrios²

2017

Nephrol Renal Dis

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Apheresis is a Greek word (Αφαίρεσης) which means removal of something from somewhere and was initially used in 1914. So Apheresis is the process by which plasma or cellular components are separated from the whole blood. This procedure is performed either on a blood donor, in order to supply the products to patients with different hematological or cancer diseases, or on a patient, alternatively as a therapeutic method. The process may be conducted by centrifugation and we can remove apart from the plasma, white blood cells, red blood cells as well as platelets. Furthermore, the process may be conducted by dialysis through a high permeability dialyzer which specifically removes plasma. Citrates or heparin are used as anticoagulants whereas fluid replacement comprises of albumin or fresh frozen plasma as well as colloidal starch when the procedure is plasma exchange. Complications are related to the vascular access, the anticoagulant or the replacement fluid (frequently with fresh frozen plasma). Now days an increased number of diseases are treated through apheresis procedures and this fact increased the interest of the medical world.

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Therapeutic plasma exchange: A technical and operational review

Cited by 118 publications

References 57 publications

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration

Principles of Separation

Therapeutic apheresis: Technical modalities and therapeutic applications

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