Evidence map›Paper›PMID 37804344›Full record

Trial reportAnnals of hematology2024

Predictors for improvement in patient-reported outcomes: post hoc analysis of a phase 3 randomized, open-label study of eculizumab and ravulizumab in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria.

Hubert Schrezenmeier, Austin Kulasekararaj, Lindsay Mitchell, Régis Peffault de Latour, Timothy Devos, Shinichiro Okamoto, Richard Wells, Evan Popoff, Antoinette Cheung, Alice Wang and 3 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of hematology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02946463 (A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients With Paroxysmal Nocturnal Hemoglobinuria), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 22% 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.

NCT02946463 phase3completednot on this map

A Phase 3, Randomized, Open-Label, Active-Controlled Study of ALXN1210 Versus Eculizumab in Complement Inhibitor-Naïve Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

TypeinterventionalSponsorAlexion Pharmaceuticals, Inc.Ran2016 to 2023Enrolled272ConditionsParoxysmal Nocturnal Hemoglobinuria (PNH)ArmsRavulizumab, Eculizumab
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 9 institutions in 8 countries.

Hubert SchrezenmeierInstitute of Transfusion Medicine, University of Ulm, Helmholtzstraße 10, 89081, Ulm, Germany. h.schrezenmeier@blutspende.de.ORCID http://orcid.org/0000-0003-1222-6659
Austin KulasekararajKing's College Hospital, National Institute for Health and Care Research/Wellcome King's Clinical Research Facility, London, UK.ORCID http://orcid.org/0000-0003-3180-3570
Lindsay MitchellDepartment of Hematology, University Hospital Monklands, Airdrie, UK.
Régis Peffault de LatourHôpital Saint-Louis AP-HP, Paris, France.ORCID http://orcid.org/0000-0001-6222-4753
Timothy DevosDepartment of Hematology, University Hospitals Leuven, Louvain, Belgium.ORCID http://orcid.org/0000-0002-6881-417X
Shinichiro OkamotoDivision of Hematology, Keio University School of Medicine, Tokyo, Japan.
Richard WellsSunnybrook Health Sciences Centre, Toronto, ON, Canada.
Evan PopoffBroadstreet HEOR, Vancouver, BC, Canada.
Antoinette CheungBroadstreet HEOR, Vancouver, BC, Canada.ORCID http://orcid.org/0000-0003-0335-6611
Alice WangAstraZeneca Rare Disease, Boston, MA, USA.
Ioannis TomazosAstraZeneca Rare Disease, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0290-4583
Yogesh PatelAstraZeneca Rare Disease, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8916-5228
Jong Wook LeeDepartment of Hematology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-2949-4166
AstraZeneca (United States) · USAssistance Publique – Hôpitaux de Paris · FRKeio University · JPKing's College Hospital · GBMonklands Hospital · GBRega Institute for Medical Research · BESunnybrook Health Science Centre · CAThe Catholic University of Korea Seoul St. Mary's Hospital · KRUniversität Ulm · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by uncontrolled terminal complement activation leading to intravascular hemolysis (IVH), thrombosis, and impairments in quality of life (QoL). The aim of this study was to identify the clinical drivers of improvement in patient-reported outcomes (PROs) in patients with PNH receiving the complement component 5 (C5) inhibitors eculizumab and ravulizumab.This post hoc analysis assessed clinical outcomes and PROs from 246 complement inhibitor-naive patients with PNH enrolled in a phase 3 randomized non-inferiority study that compared the C5 inhibitors ravulizumab and eculizumab (study 301; NCT02946463). The variables of interest were lactate dehydrogenase (LDH) levels, a surrogate measure of IVH, and hemoglobin (Hb) levels. PROs were collected using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) to assess fatigue and QoL, respectively.Improvements in absolute mean LDH levels were significantly associated with improvements in mean FACIT-F score (p = 0.0024) and EORTC QLQ-C30 global health (GH) score (p < 0.0001) from baseline to day 183. Improvements in scores were achieved despite a non-significant increase in Hb levels. To understand the interaction between LDH and Hb, a regression analysis was performed: LDH response with Hb improvements was a significant predictor of improvement in fatigue. The independent effect of improved Hb did not significantly affect FACIT-F or EORTC QLQ-C30 GH scores.These findings suggest that LDH levels are an important determinant of fatigue and QoL outcomes in patients with PNH. CTR: NCT02946463, October 27, 2016.

Indexed as

Hemoglobinuria, ParoxysmalQuality of LifeAntibodies, Monoclonal, HumanizedComplement Inactivating AgentsFatigueHemolysisHumansAntibodies, Monoclonal, HumanizedComplement Inactivating AgentseculizumabravulizumabEculizumabFatigueParoxysmal nocturnal hemoglobinuriaQuality of lifeRavulizumab

Identifiers

PMID37804344
PMCPMC10761522
OpenAlexW4387424812

What Socratic holds

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LicenceCC BY
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 Socratic graph.