Evidence map›Paper›PMID 36750531›Full record

ArticleAdvances in therapy2023

Comparative Effectiveness of Pegcetacoplan Versus Ravulizumab and Eculizumab in Complement Inhibitor-Naïve Patients with Paroxysmal Nocturnal Hemoglobinuria: A Matching-Adjusted Indirect Comparison.

Raymond Wong, Jesse Fishman, Koo Wilson, Michael Yeh, Mohammed Al-Adhami, Abigail Zion, Christopher W Yee, Lynn Huynh, Mei Sheng Duh

Erratum issued 2 registry-linked trialsOpen access · hybridAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Advances in 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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 24% 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.

NCT03056040 phase3completednot on this map

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

TypeinterventionalSponsorAlexion Pharmaceuticals, Inc.Ran2017 to 2022Enrolled202ConditionsParoxysmal Nocturnal Hemoglobinuria (PNH)ArmsRavulizumab, Eculizumab
NCT04085601 phase3completednot on this map

A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

TypeinterventionalSponsorApellis Pharmaceuticals, Inc.Ran2019 to 2021Enrolled53ConditionsParoxysmal Nocturnal HemoglobinuriaArmsAPL-2
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Targeting complement in IgA nephropathy.Clinical kidney journal · 2023
    Review
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 4 countries.

Raymond WongSir Y.K. Pao Centre for Cancer and Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong.
Jesse FishmanApellis Pharmaceuticals, Inc., 100 5th Avenue, Waltham, MA, 02451, USA.
Koo WilsonSwedish Orphan Biovitrum AB, Tomtebodavägen 23a, Solna, 171 65, Stockholm, Sweden.
Michael YehApellis Pharmaceuticals, Inc., 100 5th Avenue, Waltham, MA, 02451, USA.
Mohammed Al-AdhamiApellis Pharmaceuticals, Inc., 100 5th Avenue, Waltham, MA, 02451, USA.
Abigail ZionAnalysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA.
Christopher W YeeAnalysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA.
Lynn HuynhAnalysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA. Lynn.Huynh@analysisgroup.com.ORCID http://orcid.org/0000-0003-3110-6775
Mei Sheng DuhAnalysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199, USA.
Analysis Group (United States) · USApellis Pharmaceuticals (United States) · USChinese University of Hong Kong · HKSwedish Orphan Biovitrum (Sweden) · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionIn the absence of head-to-head trials, this study compared treatment outcomes with the C3 complement inhibitor pegcetacoplan versus the C5 complement inhibitor eculizumab or ravulizumab in complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH).

methodsA matching-adjusted indirect comparison was conducted using individual patient data from the pegcetacoplan arm of the PRINCE trial (NCT04085601; n = 34) and aggregate data from the ravulizumab (n = 125) and eculizumab (n = 121) arms of the ALXN1210-PNH-301 trial (NCT03056040). Clinical and quality of life endpoints were evaluated after matching patients in the two trials on baseline characteristics. The weighted Wald test with 95% confidence interval was used to compare categorical and continuous variables (i.e., weighted chi-squared and z tests, respectively). Bias factor analysis was performed to quantify the extent of residual bias from unmeasured confounders.

resultsAfter weighting, treatment with pegcetacoplan was associated with statistically significant improvements in most clinical endpoints compared with ravulizumab or eculizumab treatment. These included: greater absolute and percent reductions in lactate dehydrogenase (LDH) level and increase in hemoglobin level from baseline; shorter time to first occurrence of LDH normalization; larger proportions of patients achieving hemoglobin stabilization and avoiding transfusion, with fewer packed red blood cell units transfused; and a smaller proportion of patients experiencing breakthrough hemolysis (all p < 0.05). Patients receiving pegcetacoplan also had a greater increase in general health status score from baseline compared with those receiving C5 complement inhibitors.

conclusionPegcetacoplan provides clinical benefits as first-line treatment for complement inhibitor-naïve patients with PNH.

trial registrationClinicalTrials.gov identifier, NCT04085601.

Indexed as

Hemoglobinuria, ParoxysmalAntibodies, Monoclonal, HumanizedComplement C5Complement Inactivating AgentsHemoglobinsHumansPeptides, CyclicQuality of LifeAntibodies, Monoclonal, HumanizedComplement C5Complement Inactivating AgentseculizumabHemoglobinspegcetacoplanPeptides, CyclicravulizumabC3/C5 complement inhibitorClinical trialHemolytic diseaseMatching-adjusted indirect comparisonParoxysmal nocturnal hemoglobinuria (PNH)TransfusionTreatment outcome

Identifiers

PMID36750531
PMCPMC10070304
OpenAlexW4319338531

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.