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Record W4382653113 · doi:10.1210/clinem/dgad381

Proof-of-concept and Randomized, Placebo-controlled Trials of an FcRn Inhibitor, Batoclimab, for Thyroid Eye Disease

2023· article· en· W4382653113 on OpenAlexaff
George J. Kahaly, Peter J. Dolman, Jan Wolf, Bert C. Giers, Heike M. Elflein, Amy Patel Jain, Ashok Srinivasan, Lubomir M. Hadjiiski, David R. Jordan, Elizabeth A. Bradley, Marius N. Stan, Anja Eckstein, Susanne Pitz, Christian Vorländer, Sara T. Wester, John Nguyen, Nancy Tucker, Marco Sales‐Sanz, Steven E. Feldon, Christine C. Nelson, Isabelle Hardy, Maravillas Abia Serrano, Philip Tedeschi, Jonathan Janes, Jing Xu, Peter Vue, William L. Macias, Raymond S. Douglas

Bibliographic record

VenueThe Journal of Clinical Endocrinology & Metabolism · 2023
Typearticle
Languageen
FieldMedicine
TopicOphthalmology and Eye Disorders
Canadian institutionsUniversité de MontréalUniversity of OttawaVancouver General HospitalUniversity of British Columbia
Fundersnot available
KeywordsPlaceboMedicineRandomized controlled trialContext (archaeology)Internal medicineThyroidGastroenterologyClinical trialEndocrinologyPathologyBiology

Abstract

fetched live from OpenAlex

CONTEXT: Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED). OBJECTIVE: We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED. DESIGN: Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials. SETTING: Multicenter. PARTICIPANTS: Patients with moderate-to-severe, active TED. INTERVENTION: In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks. MAIN OUTCOME: Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial). RESULTS: The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation. CONCLUSIONS: These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.012
metaresearch head score (Gemma)0.012
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.012
Threshold uncertainty score0.064

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0120.012
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0040.004
Bibliometrics0.0010.001
Science and technology studies0.0010.002
Scholarly communication0.0020.002
Open science0.0020.001
Research integrity0.0060.004
Insufficient payload (model declined to judge)0.0090.001

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 head0.079
GPT teacher head0.433
Teacher spread0.354 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
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

Citations61
Published2023
Admission routes1
Has abstractyes

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