Removal Characteristics of Immunoglobulin <scp>G</scp> Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange

Ohkubo, Atsushi; Okado, Tomokazu; Kurashima, Naoki; Maeda, Takuma; Arai, Shintaro; Miyamoto, Satoko; Itagaki, Ayako; Seshima, Hiroshi; Iimori, Soichiro; Naito, Seiji; Sohara, Eisei; Uchida, Shinichi; Rai, Tatemitsu

doi:10.1111/1744-9987.12346

Cited by 27 publications

(25 citation statements)

References 20 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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“…The reductions in AChRAb, IgA, and IgM after one session of SeIA were lower than those of IA while retaining coagulation factors such as fibrinogen and FXIII. The SCs of IgG by OP‐05 W and EC‐4A were approximately 1 and 0.5, respectively, and both membrane plasma separators could eliminate IgG regardless of the IgG subclass . The reduction in AChRAb by SeIA can be lower than that by IA because the plasma concentration of IgG and IgG subclasses before IM‐TR in SeIA can be reduced to half of that in IA.…”

Section: Discussionmentioning

confidence: 94%

Removal Characteristics of Immunoadsorption with the Tryptophan‐Immobilized Column Using Conventional and Selective Plasma Separators in the Treatment of Myasthenia Gravis

et al. 2019

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Autoimmune neurological diseases are often treated by immunoadsorption using a conventional plasma separator and tryptophan‐immobilized column (IA). However, there is only one case report on treatment with immunoadsorption using a selective plasma separator and tryptophan‐immobilized column (SeIA) in clinical practice. This study aimed to investigate the removal characteristics of antibodies against acetylcholine receptors (AChRAb), immunoglobulin G, fibrinogen, and factor XIII (FXIII) in IA and SeIA in four patients with myasthenia gravis. A total of 19 sessions of immunoadsorption were performed (five sessions of IA and 14 sessions of SeIA) when the processed plasma volume was 2 L. The corresponding reductions were 52.5% ± 6.2% for AChRAb, 58.8% ± 4.2% for fibrinogen, and 36.9% ± 5.5% for FXIII after one session of IA. The corresponding reductions were 45.2% ± 9.9% for AChRAb, 3.5% ± 6.9% for fibrinogen, and −4.6% ± 11.1% for FXIII after one session of SeIA. The removal rates for AChRAb, fibrinogen, and FXIII in IA were significantly higher than those in SeIA. IA could effectively remove AChRAb, and SeIA could retain fibrinogen and FXIII. IA can be combined with SeIA, resulting in both IgG autoantibodies removal by IA and retention of coagulation factors by SeIA.

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“…Plasma volume (PV) was calculated according to the following equation :

PV = ((),, BW true/ 13) \times ((),, 100 - Ht) true/ 100,

where BW and Ht indicate body weight (kg) and hematocrit (%), respectively. The target PPV was set at 1.2 PV in SePE . A previous study has estimated blood volume as 0.065 of BW , but in the present study, we estimated blood volume as BW divided by 13 (approximately 0.077 of BW).…”

Section: Methodsmentioning

confidence: 99%

“…Selective plasma exchange (SePE) is a new modality of simple plasma exchange that uses a selective membrane plasma separator Evacure EC‐4A10 (EC‐4A) (Kawasumi Laboratories Inc., Tokyo, Japan) . EC‐4A has a relatively small pore size of 0.03 μm, which is around one‐tenth that of conventional plasma separators .…”

mentioning

confidence: 99%

Selective Plasma Exchange for the Removal of Pemphigus Autoantibodies, Fibrinogen, and Factor XIII in Pemphigus Vulgaris

et al. 2017

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Pemphigus vulgaris is a serious autoimmune skin disorder associated with desmoglein 1 and 3. Selective plasma exchange (SePE) for pemphigus vulgaris remains unknown. We investigated the removal characteristics of pemphigus autoantibodies, immunoglobulins, and fibrinogen in three cases. When the mean processed volume for SePE was 1.2 plasma volumes, the mean percent reduction was 50.7% for desmoglein 1, 48.9% for desmoglein 3, 50.3% for IgG, 29.8% for IgA, 1.9% for IgM, and 17.6% for fibrinogen. In one case, the percent reduction after four sessions of SePE within eight days was 87.0% for desmoglein 1, 85.1% for desmoglein 3, 76.6% for IgG, 53.5% for IgA, 7.9% for IgM, 41.6% for fibrinogen, and 31.4% for factor XIII. SePE can effectively remove pemphigus autoantibodies and retain coagulation factors, e.g. factor XIII and fibrinogen. In severe cases, SePE can be useful and safe for induction therapy.

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Removal Characteristics of Immunoglobulin G Subclasses by Conventional Plasma Exchange and Selective Plasma Exchange

Cited by 27 publications

References 20 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

Removal Characteristics of Immunoadsorption with the Tryptophan‐Immobilized Column Using Conventional and Selective Plasma Separators in the Treatment of Myasthenia Gravis

Selective Plasma Exchange for the Removal of Pemphigus Autoantibodies, Fibrinogen, and Factor XIII in Pemphigus Vulgaris

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