Evidence map›Paper›PMID 36329366›Full record

Trial reportMolecular diagnosis & therapy2023

Exploratory Prognostic Biomarkers of Complement-Mediated Thrombotic Microangiopathy (CM-TMA) in Adults with Atypical Hemolytic Uremic Syndrome (aHUS): Analysis of a Phase III Study of Ravulizumab.

Tobin J Cammett, Katherine Garlo, Ellen E Millman, Kara Rice, Catherine M Toste, Susan J Faas

Erratum issued 2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase III
PubMed Publisher
In one paragraph

Trial report in Molecular diagnosis & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02949128 phase3completednot on this map

Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-naïve Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

TypeinterventionalSponsorAlexion Pharmaceuticals, Inc.Ran2017 to 2023Enrolled58ConditionsAtypical Hemolytic Uremic Syndrome (aHUS)ArmsRavulizumab
NCT05684159 phase2not yet recruitingnot on this mapstarted 2027, after this paper: background citation

A Phase II, Open-Label Study of NM8074 in Patients With Atypical Hemolytic Uremic Syndrome (aHUS)

TypeinterventionalSponsorNovelMed TherapeuticsRan2027 to 2031Enrolled12ConditionsaHUS - Atypical Hemolytic Uremic SyndromeArmsNM8074
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Soluble C5b-9 (sC5b-9) in Pediatrics-A Clinical Assessment.Journal of clinical laboratory analysis · 2025
    Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 2 countries.

Tobin J CammettAlexion, AstraZeneca Rare Disease, Boston, MA, USA. tobin.cammett@alexion.com.
Katherine GarloAlexion, AstraZeneca Rare Disease, Boston, MA, USA.
Ellen E MillmanAlexion, AstraZeneca Rare Disease, Boston, MA, USA.
Kara RiceAlexion, AstraZeneca Rare Disease, Boston, MA, USA.
Catherine M TosteAlexion, AstraZeneca Rare Disease, Boston, MA, USA.
Susan J FaasAlexion, AstraZeneca Rare Disease, Boston, MA, USA.
Alexion Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundClinically validated biomarkers for monitoring of patients with complement-mediated thrombotic microangiopathy (CM-TMA) including atypical hemolytic uremic syndrome (aHUS) are unavailable. Improved characterization of biomarkers in patients with aHUS may inform treatment and monitoring for patients with CM-TMA.

methodsThis analysis used data collected from 55/56 (98.2 %) adult patients with aHUS enrolled in the global Phase III study of ravulizumab (NCT02949128). Baseline (pre-treatment) patient serum, plasma and urine biomarker levels were compared with the maximum observed levels in normal donors and evaluated for associations with pre-treatment plasma exchange/infusion and dialysis status. Biomarkers were also assessed for associations with key clinical measures at baseline and with changes at 26 and 52 weeks from treatment initiation via linear regression analyses.

resultsComplement-specific urine levels (factor Ba and sC5b-9) were elevated in >85 % of patients and are significantly associated with pre-treatment kidney dysfunction. Baseline levels of other evaluated biomarkers were elevated in >70 % of patients with aHUS, except for plasma sC5b-9 and serum sVCAM-1. Lower levels of urine complement markers at baseline are significantly associated with improvements in total urine protein and estimated glomerular filtration rate at 26 and 52 weeks of treatment. Clinical assessment of complement activation by a receiver operating characteristic analysis of Ba and sC5b-9 was more sensitive and specific in urine matrix than plasma.

conclusionThis analysis identified a set of biomarkers that may show utility in the prognosis of CM-TMA, including their potential for measuring and predicting response to anti-C5 therapy. Further studies are required to enhance patient risk stratification and improve management of these vulnerable patients. CLINICAL TRIALS REGISTRATION: NCT02949128, ClinicalTrials.gov.

Indexed as

Atypical Hemolytic Uremic SyndromeThrombotic MicroangiopathiesAdultAntibodies, Monoclonal, HumanizedBiomarkersComplement System ProteinsHumansPrognosisAntibodies, Monoclonal, HumanizedBiomarkersComplement System Proteinsravulizumab

Identifiers

PMID36329366
OpenAlexW4308189239

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.