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Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial

Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial
Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial

Background: Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. Objectives: To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. Methods: Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg −1 intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). Results: Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg −1 and 13 of 15 (87%) patients receiving 25 mg kg −1, with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg kg −1 per day (range 0·06–0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2–41 weeks. Conclusions: Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.

0007-0963
Ward, E. Sally
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Goebeler, M.
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Bata-Csorgo, Z.
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De Simone, C
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Didona, B.
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Remenyik, E.
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Reznichenko, N.
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Stoevesandt, J.
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Parys, W.
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de Haard, H
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Dupuy, P.
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Verheesan, P.
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Schmidt, E.
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Joly, P.
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ARGX-113-1701 Investigator Study Group
Ward, E. Sally
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Goebeler, M.
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Bata-Csorgo, Z.
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De Simone, C
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Didona, B.
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Remenyik, E.
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Reznichenko, N.
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Stoevesandt, J.
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Parys, W.
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de Haard, H
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Dupuy, P.
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Verheesan, P.
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Schmidt, E.
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Joly, P.
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ARGX-113-1701 Investigator Study Group (2021) Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open-label feasibility trial. British Journal of Dermatology. (doi:10.1111/bjd.20782).

Record type: Article

Abstract

Background: Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. Objectives: To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. Methods: Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25 mg kg −1 intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). Results: Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10 mg kg −1 and 13 of 15 (87%) patients receiving 25 mg kg −1, with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17 days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26 mg kg −1 per day (range 0·06–0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2–41 weeks. Conclusions: Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.

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Accepted/In Press date: 5 October 2021
e-pub ahead of print date: 5 October 2021
Published date: 5 October 2021
Additional Information: Funding Information: We thank all of the study participants, investigators and trial teams for their participation in the trial. We also thank Katrien Verschueren (argenx, Ghent, Belgium) for statistical support on this manuscript. Amanda M. Justice (independent consultant, Brooklyn, NY) provided editorial support, which was funded by argenx. A full list of the study investigators can be found in the Supporting Information (Table  S1 ). This work was generated in part within the European Reference Network Skin network. Open access funding enabled and organized by ProjektDEAL. Publisher Copyright: © 2021 Argenx - SE. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists

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Local EPrints ID: 452328
URI: http://eprints.soton.ac.uk/id/eprint/452328
ISSN: 0007-0963
PURE UUID: d404dfdb-83c0-4b19-b5fe-aaa7250648ea
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

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Date deposited: 08 Dec 2021 17:30
Last modified: 17 Mar 2024 06:54

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Contributors

Author: E. Sally Ward ORCID iD
Author: M. Goebeler
Author: Z. Bata-Csorgo
Author: C De Simone
Author: B. Didona
Author: E. Remenyik
Author: N. Reznichenko
Author: J. Stoevesandt
Author: W. Parys
Author: H de Haard
Author: P. Dupuy
Author: P. Verheesan
Author: E. Schmidt
Author: P. Joly
Corporate Author: ARGX-113-1701 Investigator Study Group

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