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Record W4390904672 · doi:10.25251/skin.8.supp.344

Overview of the Safety Profile From Efgartigimod Clinical Trials in Participants With Diverse IgG-Mediated Autoimmune Diseases

2024· article· en· W4390904672 on OpenAlexaff
Michelle Sholzberg, Kelly Gwathmey, Catherine M. Broome, Matthias Goebeler, Hiroyuki Murai, Zsuzsanna Bata‐Csörgõ, Adrian C. Newland, Peter Ulrichts, René Kerstens, Jeffrey T. Guptill, Sofiane Agha, Ming Jiang, James F. Howard

Bibliographic record

VenueSKIN The Journal of Cutaneous Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicAutoimmune Bullous Skin Diseases
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsAdverse effectPlaceboDiscontinuationMedicinePemphigusDosingMyasthenia gravisClinical trialIncidence (geometry)AntibodyImmunologyInternal medicinePemphigus vulgarisPharmacology

Abstract

fetched live from OpenAlex

Background Efgartigimod is a first-in-class, human immunoglobulin-G (IgG) Fc fragment that inhibits the neonatal Fc receptor (FcRn) and outcompetes endogenous IgG binding. FcRn inhibition by efgartigimod is a rational therapeutic option for IgG-mediated autoimmune disorders, including immune thrombocytopenia (ITP). Aims To determine the safety profile of efgartigimod for a variety of IgG-mediated autoimmune disorders, including ITP. Methods Intravenous efgartigimod safety was assessed in a phase 3 (ADVANCE) trial in ITP. It was also evaluated in generalized myasthenia gravis (gMG) in phase 2 and 3 (ADAPT) trials and a 3-year open-label extension (ADAPT+) along with an open-label phase 2 trial in pemphigus. Varying dosing regimens of efgartigimod (10-25 mg/kg) were used, including cyclical (gMG) and continuous weekly dosing (ITP, pemphigus). Results Across all indications and doses studied, efgartigimod demonstrated a consistent safety profile, with comparable treatment emergent adverse event (TEAE) rates to placebo (ADVANCE 93.0% efgartigimod vs. 95.6% placebo; ADAPT 77.4% efgartigimod vs. 84.3% placebo; 85% of participants in open label pemphigus study). Most TEAEs across studies were mild to moderate in severity. Discontinuation rates due to adverse events were low across studies (3.5% efgartigimod vs. 2.2% placebo in ADVANCE; 3.6% efgartigimod vs. 3.6% placebo in ADAPT; 3% in pemphigus). No increase in TEAE incidence rates or infections with repeated efgartigimod cycles (up to 19) in ADAPT+ was observed. In ADVANCE, no thromboembolic TEAEs were reported. Efgartigimod did not impair participant ability to generate new specific IgG responses to non-live vaccines, regardless of the timing of vaccinations however, there were transient reductions in specific IgG titers observed. Conclusions Efgartigimod was generally well tolerated across indications and doses studied. Most TEAEs, including infections, were mild or moderate in severity and did not increase in frequency with recurrent dosing. Non-live vaccine responsiveness was preserved. There were no thromboembolic events in those treated for ITP.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.006
metaresearch head score (Gemma)0.015
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMetaresearch, Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.351
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0060.015
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.100
GPT teacher head0.401
Teacher spread0.301 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2024
Admission routes1
Has abstractyes

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