Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations - 05/09/20
Abstract |
The neonatal fragment crystallizable (Fc) receptor (FcRn) functions as a recycling mechanism to prevent degradation and extend the half-life of IgG and albumin in the circulation. Several FcRn inhibitors selectively targeting IgG recycling are now moving rapidly toward clinical practice in neurology and hematology. These molecules accelerate the destruction of IgG, reducing pathogenic IgG and IgG immune complexes, with no anticipated effects on IgA, IgM, IgE, complement, plasma cells, B cells, or other cells of the innate or adaptive immune systems. FcRn inhibitors have potential for future use in a much wider variety of antibody-mediated autoimmune diseases. Given the imminent clinical use, potential for broader utility, and novel mechanism of action of FcRn inhibitors, here we review data from 4 main sources: (a) currently available activity, safety, and mechanism-of-action data from clinical trials of FcRn inhibitors; (b) other procedures and treatments that also remove IgG (plasma donation, plasma exchange, immunoadsorption); (c) diseases resulting in loss of IgG; and (d) primary immunodeficiencies with potential mechanistic similarities to those induced by FcRn inhibitors. These data have been evaluated to provide practical considerations for the assessment, monitoring, and reduction of any potential infection risk associated with FcRn inhibition, in addition to highlighting areas for future research.
Il testo completo di questo articolo è disponibile in PDF.Key words : FcRn, neonatal Fc receptor, immunoglobulin, IgG, albumin, hypogammaglobulinemia, autoantibody, antibody-mediated autoimmunity, FcRn inhibitors, infection risk
Abbreviations used : B2M, COVID-19, Fc, FcRn, FcγR, FIH, GI, Gm, HBV, IA, IC, IgRT, ITP, IV, IVIg, MG, PLE, PLEX, QMG, QW, SARS-CoV-2, SC, SID, TEAE, VL, WBC
Mappa
Medical writing support was provided by Sarah Feaver, PhD, on behalf of iMed Comms, an Ashfield Company, part of UDG Healthcare plc, and funded by UCB Pharma in accordance with Good Publications Practice (GPP3) guidelines (gpp3). The authors acknowledge Linda Feighery, PhD, CMPP, and Veronica Porkess, PhD, CMPP, of UCB Pharma for publication and editorial support. The article was reviewed and approved for publication by all authors and the sponsor. |
|
Disclosure of potential conflict of interest: H.-H. Peter is receiving consulting fees from and has acted as a member of data monitoring committees for UCB; is an elected member of the Working Group “Blood” of the Robert Koch Institute, Berlin; and is a member of the Drug Safety Commission of the German Medical Association (no fees). H.D. Ochs has received consulting fees from and has acted as a member of a Data Monitoring Committee for UCB. C. Cunningham-Rundles is on advisory committees for UCB Pharma and Momenta, is a consultant for Pharming Group and Atara Biotherapeutics, and has received clinical trials funding from CSL Behring. D.C. Vinh is supported by the Fonds de la Recherche en Santé du Quebec (FRQS) Clinician-scientist scholar Junior 2 program; has also received consultancy fees, clinical trials funding, and honoraria and taken part in speaker bureaus for Avir Pharma, CSL Behring, Cidara Therapeutics, Janssen, and UCB Pharma; and has received research funding from the Canadian Institutes of Health Research. P. Kiessling and B. Greve are employees of UCB Pharma and may hold stock and/or stock options. UCB Pharma is the manufacturer and sponsor of rozanolixizumab, an FcRn inhibitor, which is currently being investigated in clinical trials in a range of autoimmune disorders. S. Jolles has received consultancy fees from and has acted as a member of a Drug Safety Committee for UCB Pharma; has also received consultancy fees, research funding, meeting support, and honoraria, and taken part in speaker bureaus and clinical trials, for CSL Behring, Shire/Takeda, Octapharma, Biotest, SOBI, Grifols, Sanofi, GlaxoSmithKline, The Binding Site, Weatherden, Zarodex, LFB, and Pharming. |
|
Terms in boldface and italics are detailed in the glossary on page 480. |
Vol 146 - N° 3
P. 479 - Settembre 2020 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
L'accesso al testo integrale di questo articolo richiede un abbonamento.
Già abbonato a @@106933@@ rivista ?