Trial reportBritish journal of clinical pharmacology2022
Emapalumab in primary haemophagocytic lymphohistiocytosis and the pathogenic role of interferon gamma: A pharmacometric model-based approach.
Trial report in British journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- The efficacy and safety of chidamide in combination with etoposide and glucocorticoids for the treatment of hemophagocytic lymphohistiocytosis in adult patients: an open-label, single-center study.Frontiers in immunology · 2024Trial
- Emapalumab in primary haemophagocytic lymphohistiocytosis and the pathogenic role of interferon gamma: A pharmacometric model-based approach.British journal of clinical pharmacology · 2022Trial
- Emapalumab in pediatric patients with high-grade cytokine release syndrome associated with CAR T-cell therapy.Frontiers in immunology · 2026Article
- Emapalumab in Patients With Macrophage Activation Syndrome Associated With Still's Disease: A Population Pharmacokinetic/Pharmacodynamic Analysis.Clinical and translational science · 2025Article
- Low-dose emapalumab treatment in refractory macrophage activation syndrome secondary to adult onset still's disease/systemic lupus erythematosus: insights from nine cases.Frontiers in immunology · 2025Article
- Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis.Rheumatology and therapy · 2024Article
- Real-world treatment patterns and outcomes in patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab.Blood advances · 2024Article
- Achieving big with small: quantitative clinical pharmacology tools for drug development in pediatric rare diseases.Journal of pharmacokinetics and pharmacodynamics · 2023Review
- Validated graft-specific biomarkers identify patients at risk for chronic graft-versus-host disease and death.The Journal of clinical investigation · 2023Article
- Neutralizing IFNγ improves safety without compromising efficacy of CAR-T cell therapy in B-cell malignancies.Nature communications · 2023Article
- Efficacy and safety of emapalumab in macrophage activation syndrome.Annals of the rheumatic diseases · 2023Article
- Interferon-γ blockade in CAR T-cell therapy-associated macrophage activation syndrome/hemophagocytic lymphohistiocytosis.Blood advances · 2023Article
- Case Report: Successful avoidance of etoposide for primary hemophagocytic lymphohistiocytosis-induced multiple organ dysfunction syndrome using emapalumab.Frontiers in pediatrics · 2023Article
- A pharmacist-led intervention to improve the management of opioids in a general practice: a qualitative evaluation of participant interviews.International journal of clinical pharmacy · 2022Article
- Precision medicine: The use of tailored therapy in primary immunodeficiencies.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimPrimary haemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening, hyperinflammatory syndrome generally occurring in early childhood. The monoclonal antibody emapalumab binds and neutralises interferon γ (IFNγ). This study aimed to determine an emapalumab dosing regimen when traditional dose-finding approaches are not applicable, using pharmacokinetic-pharmacodynamic analyses to further clarify HLH pathogenesis and confirm IFNγ neutralisation as the relevant therapeutic target in pHLH.
methodsInitial emapalumab dosing (1 mg/kg) for pHLH patients participating in a pivotal multicentre, open-label, single-arm, phase 2/3 study was based on anticipated IFNγ levels and allometrically scaled pharmacokinetic parameters estimated in healthy volunteers. Emapalumab dosing was adjusted based on estimated IFNγ-mediated clearance and HLH clinical and laboratory criteria. Frequent dosing and emapalumab dose adaptation were used to account for highly variable IFNγ levels and potential target-mediated drug disposition.
resultsHigh inter- and intra-individual variability in IFNγ production (assessed by total IFNγ levels, range: 10
conclusionsThe variable and unanticipated extremely high IFNγ concentrations in patients with pHLH are reflected in parameters of disease activity. Improved outcomes can be achieved by neutralising IFNγ using frequent emapalumab dosing and dose adaptation guided by clinical and laboratory observations.
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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.