ArticleBlood2024
Differential effects of itacitinib, fedratinib, and ruxolitinib in mouse models of hemophagocytic lymphohistiocytosis.
Article in Blood, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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.
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
17 citing papers in PubMed, 16 citations in OpenAlex.
- HLHRUXO: a prospective trial of a ruxolitinib-containing regimen for children with hemophagocytic lymphohistiocytosis.Blood advances · 2026Trial
- The real-world safety of ruxolitinib in graft-versus-host disease treatment: a pharmacovigilance study based on the FDA adverse event reporting system.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- [Mechanism and clinical progress of JAK inhibitors in hemophagocytic lymphohistiocytosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Selective Janus kinase inhibitors exhibit different effects in murine immune aplastic anemia.HemaSphere · 2026Article
- In vivo inhibition of JAK-STAT signalling enhances high pathogenicity influenza virus replication in ducks.The Journal of general virology · 2026Article
- Dual Inhibition of PB2 and JAK2 for Influenza: A Strategy Combining Antiviral and Host-Directed Immune Modulation.Molecules (Basel, Switzerland) · 2026Article
- The Immunoregulatory and Hematopoietic Effects of Momelotinib in a Murine Bone Marrow Failure Model.Journal of clinical laboratory analysis · 2026Article
- Case Report: Hemophagocytic lymphohistiocytosis masquerading as drug-induced liver injury: successful treatment with low-dose ruxolitinib and glucocorticoids.Frontiers in immunology · 2026Article
- Case Report: refractory hemophagocytic lymphohistiocytosis progression despite complete metabolic response in a patient with stage IV extranodal NK/T-cell lymphoma: clinical observation of "tumor-immune dissociation" phenomenon.Frontiers in immunology · 2026Article
- Thrombotic thrombocytopenic purpura and macrophage activation syndrome secondary to Sjögren's syndrome: a case report.Frontiers in immunology · 2026Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- Article
- Mucosal implications of oral Jak3-targeted drugs in COVID patients.Molecular medicine (Cambridge, Mass.) · 2025Review
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- DEP regimen for the treatment of hemophagocytic lymphohistiocytosis: a review of published experience.Frontiers in pharmacology · 2025Review
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
Corrections and comments
- Commented on by
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
abstractHemophagocytic lymphohistiocytosis (HLH) comprises a severe hyperinflammatory phenotype driven by the overproduction of cytokines, many of which signal via the JAK/STAT pathway. Indeed, the JAK1/2 inhibitor ruxolitinib has demonstrated efficacy in preclinical studies and early-phase clinical trials in HLH. Nevertheless, concerns remain for ruxolitinib-induced cytopenias, which are postulated to result from the blockade of JAK2-dependent hematopoietic growth factors. To explore the therapeutic effects of selective JAK inhibition in mouse models of HLH, we carried out studies incorporating the JAK1 inhibitor itacitinib, JAK2 inhibitor fedratinib, and JAK1/2 inhibitor ruxolitinib. All 3 drugs were well-tolerated and at the doses tested, they suppressed interferon-gamma (IFN-γ)-induced STAT1 phosphorylation in vitro and in vivo. Itacitinib, but not fedratinib, significantly improved survival and clinical scores in CpG-induced secondary HLH. Conversely, in primary HLH, in which perforin-deficient (Prf1-/-) mice are infected with lymphocytic choriomeningitis virus (LCMV), itacitinib, and fedratinib performed suboptimally. Ruxolitinib demonstrated excellent clinical efficacy in both HLH models. RNA-sequencing of splenocytes from LCMV-infected Prf1-/- mice revealed that itacitinib targeted inflammatory and metabolic pathway genes in CD8 T cells, whereas fedratinib targeted genes regulating cell proliferation and metabolism. In monocytes, neither drug conferred major transcriptional impacts. Consistent with its superior clinical effects, ruxolitinib exerted the greatest transcriptional changes in CD8 T cells and monocytes, targeting more genes across several biologic pathways, most notably JAK-dependent proinflammatory signaling. We conclude that JAK1 inhibition is sufficient to curtail CpG-induced disease, but combined inhibition of JAK1 and JAK2 is needed to best control LCMV-induced immunopathology.
Indexed as
Identifiers
What OpenQuestion holds
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.