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Record W4403831504 · doi:10.1681/asn.2024xhnty662

Safety and Effectiveness of Switching to Ravulizumab from Eculizumab in Kidney Transplant Recipients with Atypical Hemolytic Uremic Syndrome: A Global Registry Analysis

2024· article· en· W4403831504 on OpenAlexaff
Anja Gaeckler, Imad Al‐Dakkak, Nuria Saval, Hans Dieperink, Margriet Eygenraam, Larry A. Greenbaum, Nicole Isbel, Johan Vande Walle

Bibliographic record

VenueJournal of the American Society of Nephrology · 2024
Typearticle
Languageen
FieldImmunology and Microbiology
TopicComplement system in diseases
Canadian institutionsBrampton Civic Hospital
Fundersnot available
KeywordsEculizumabAtypical hemolytic uremic syndromeMedicineIntensive care medicineNephrologyKidneyInternal medicineImmunologyComplement systemAntibody

Abstract

fetched live from OpenAlex

Background: Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation that causes kidney failure and has a propensity to recur after kidney transplant (KTx) with graft loss. Ravulizumab (RAV) and eculizumab (ECU) are C5 inhibitors approved for the treatment of aHUS. We assessed the real-world safety and effectiveness of switching from ECU to RAV in KTx recipients with aHUS for immediate, complete, and sustained terminal complement inhibition. Methods: The Global aHUS Registry is a multicenter study (NCT01522183) enrolling patients (pts) with aHUS since 2012. Safety and effectiveness outcomes were assessed in KTx recipients with aHUS who switched from ECU to RAV up to April 22, 2024. Safety analyses included pts with a KTx before RAV initiation; pt characteristic and effectiveness analyses included KTx recipients who received RAV for ≥3 months and had ≤1 month between ECU discontinuation and RAV initiation. Results: Overall, 29 pts (25 adults) were included in safety analyses; 21 adverse events (AEs) were reported in 15 pts at or after RAV initiation, and none were unexpected. During RAV treatment, no new AEs of thrombotic microangiopathy or kidney impairment, and no meningococcal infections or deaths were reported. Among 21 pts (20 adults) included in the pt characteristic and effectiveness analyses, median (range) age at RAV initiation was 35 (11–72) years, and 67% had a reported pathogenic complement variant or anti-complement factor H antibodies. Median (range) time on treatment was 66 (4–158) months for ECU and 24 (5–43) months for RAV; median (range) time from last KTx to RAV initiation was 56 (4–184) months. Mean (standard deviation) estimated glomerular filtration rate was 50 (25) mL/min/1.73m2 at last record before or at RAV initiation and 50 (28) mL/min/1.73m2 at last follow-up after RAV initiation. Among 29 KTx events in these 21 pts, no rejections or graft failures were reported after RAV initiation. Conclusion: This analysis from the Global aHUS Registry provides real-world evidence of the successful transition from ECU to RAV in KTx recipients with aHUS, with stable kidney function and no unexpected safety concerns. Funding: Commercial Support - Alexion, AstraZeneca Rare Disease

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.326
Threshold uncertainty score0.483

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.007
GPT teacher head0.254
Teacher spread0.248 · 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.

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

Citations0
Published2024
Admission routes1
Has abstractyes

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