Evidence map›Paper›PMID 38662147›Full record

ArticleRheumatology and therapy2024

Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis.

Patrick Brossard, Christian Laveille

3 registry-linked trialsOpen access · goldAbstract read
In one paragraph

Article in Rheumatology and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 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
1.4field-weighted citation impact, top 19% 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.

NCT01818492 phase2 / phase3completednot on this map

A Phase 2/3 Open-label Single Arm Multicentre Study to Assess Safety Tolerability Pharmacokinetics and Efficacy of i.v. Administrations of NI-0501 an Anti-IFNγ mAb in Paediatric Patients With Primary Haemophagocytic Lymphohistiocytosis

TypeinterventionalSponsorSwedish Orphan BiovitrumRan2013 to 2019Enrolled45ConditionsPrimary Haemophagocytic LymphohistiocytosisArmsNI-0501
NCT02069899 phase2 / phase3completednot on this map

A Multicenter Study for the Long-term Follow-up of HLH Patients Who Received Treatment With NI-0501, an Anti-interferon Gamma Monoclonal Antibody

TypeinterventionalSponsorSwedish Orphan BiovitrumRan2014 to 2021Enrolled58ConditionsHemophagocytic LymphohistiocytosisArmsEmapalumab
NCT03311854 phase2completednot on this map

A Pilot, Open-label, Single Arm, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administrations of Emapalumab, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)

TypeinterventionalSponsorSwedish Orphan BiovitrumRan2018 to 2020Enrolled14ConditionsMacrophage Activation Syndrome, Lymphohistiocytosis, Hemophagocytic, Arthritis, Juvenile, Adult Onset Still DiseaseArmsEmapalumab
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Interferon-JAK-STAT Axis in Bone Metabolism.Current osteoporosis reports · 2026
    Review
  2. Review
  3. Article
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

2 authors at 1 institution in 1 country.

Patrick BrossardSobi, 10 Messeplatz, 4058, Basel, Switzerland. patrick.brossard@sobi.com.
Christian LaveilleCalvagone SAS, Liergues, France.
Calvagone (France) · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionEmapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ by orders of magnitude between patients with primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS; a form of secondary HLH) in systemic juvenile idiopathic arthritis (sJIA). Therefore, this study aimed to develop a population pharmacokinetic model for emapalumab across a patient population with a wide range of total (free and emapalumab-bound) IFNγ levels using observations from patients with primary HLH or MAS in sJIA in clinical trials.

methodsPharmacokinetic data were pooled (n = 58; 2709 observations) from studies enrolling patients administered emapalumab for primary HLH or MAS in sJIA. Patients with primary HLH were administered emapalumab 1 mg/kg (potentially increasing to 3, 6, and up to 10 mg/kg based on clinical response) every 3 days. Patients with MAS in sJIA were administered emapalumab 6 mg/kg, followed by 3 mg/kg every 3 days until day 15 and twice weekly until day 28. An earlier population PK model was re-parameterized using this data.

resultsThe final model for emapalumab comprised a 2-compartment model with first-order elimination. Emapalumab clearance remains constant when the total IFNγ concentration (free and emapalumab-bound) is < ~ 10,000 pg/ml but increases proportionally to total IFNγ concentration above this threshold. Emapalumab clearance was estimated to be 0.00218, 0.00308, 0.00623 and 0.01718 l/h at total serum IFNγ concentrations of 10

conclusionsEmapalumab pharmacokinetics in patients with primary HLH and MAS in sJIA were described by a two-compartment model with fixed allometric exponents and an age-related effect. Differences in total IFNγ levels between patients with primary HLH and MAS may affect emapalumab pharmacokinetics, suggesting that each indication may require different dosing to rapidly control hyperinflammation.

trial registrationClinicaltrials.gov identifiers: NCT01818492, NCT03311854 and NCT02069899.

Indexed as

Adult-onset Still’s diseaseEmapalumabHemophagocytic lymphohistiocytosisHyperinflammationInterferon-gammaModelingPharmacokineticsSystemic juvenile idiopathic arthritis

Identifiers

PMID38662147
PMCPMC11111609
OpenAlexW4395465392

What Socratic 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 Socratic graph.