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Abstract 12066: The Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

2021· article· en· W3215227082 on OpenAlexaff
Frederick J. Raal, Robert S. Rosenson, Laurens F. Reeskamp, John J.P. Kastelein, Paolo Rubba, Bart Duell, Masahiro Koseki, Erik S.G. Stroes, Shazia Ali, Poulabi Banerjee, Kuo‐Chen Chan, Nagwa Khilla, Jennifer McGinniss, Robert Pordy, Yi Zhang, Daniel Gaudet

Bibliographic record

VenueCirculation · 2021
Typearticle
Languageen
FieldMedicine
TopicLipid metabolism and disorders
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsMedicineFamilial hypercholesterolemiaInternal medicineGastroenterologyLDL apheresisPediatricsCholesterol

Abstract

fetched live from OpenAlex

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic lipid disorder characterized by marked elevations in LDL-C and premature atherosclerotic cardiovascular disease (ASCVD). EU guidelines recommend LDL-C treatment goals of <55 mg/dL and <70 mg/dL for pts with HoFH with and without ASCVD, respectively. Evinacumab (EVIN; an angiopoietin-like 3 inhibitor) significantly reduced LDL-C and was generally well tolerated in pts with HoFH during the 24-week double-blind treatment period (DBTP) of a pivotal Phase 3 study (NCT03399786). Methods: This post-hoc analysis assessed the long-term effect of EVIN on LDL-C goal attainment in pts with HoFH who participated in the subsequent 24-week open-label treatment period (OLTP) of the pivotal Phase 3 study. All pts received intravenous EVIN 15 mg/kg every 4 weeks. Efficacy by background lipid lowering medication (LLM) subgroups and the effect of EVIN on eligibility for apheresis were also assessed. Results: In total, 65 pts entered the OLTP and 64 pts (98.5%) received OL EVIN. Overall, 50.0% achieved LDL-C <100mg/dL, 31.7% achieved LDL-C <70 mg/dL and 23.3% achieved LDL-C <55 mg/dL at Week 48 (end of OLTP) (Figure 1). For the subgroup with ASCVD (n=36), 50.0%, 37.5% and 31.3% achieved LDL-C <100 mg/dL, <70 mg/dL and <55 mg/dL, respectively. Overall, 43.1%, 24.6% and 38.5% of pts qualified for apheresis at baseline and did not qualify for apheresis at Week 48 (using new US, US and EU criteria); no patient discontinued apheresis. EVIN markedly reduced LDL-C, irrespective of background LLM. Overall, treatment-emergent adverse events (TEAEs) occurred in 47 pts (73.4%) during the OLTP. Serious AEs (all unrelated to EVIN) were reported by 7 pts (10.9%), none led to death or EVIN discontinuation. Conclusions: EVIN enabled 31.7% of all pts to achieve LDL-C <70 mg/dL and 31.3% of those with ASCVD to achieve LDL-C <55 mg/dL. EVIN markedly reduced the proportion of pts qualifying for apheresis.

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)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
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 head0.010
GPT teacher head0.241
Teacher spread0.231 · 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 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

Citations3
Published2021
Admission routes1
Has abstractyes

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