ReviewDrugs2018
Inhibition of Tissue Factor Pathway Inhibitor (TFPI) as a Treatment for Haemophilia: Rationale with Focus on Concizumab.
Review in Drugs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 29 papers, 2 of them syntheses that pooled 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.
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
29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Non-clotting factor therapies for preventing bleeds in people with congenital hemophilia A or B.The Cochrane database of systematic reviews · 2024Pooled it
- Evaluating the Safety and Efficacy of Concizumab in Hemophilia A/B Patients: A Systematic Review.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisPooled it
- Befovacimab, an anti-tissue factor pathway inhibitor antibody: Early termination of the multiple-dose, dose-escalating Phase 2 study due to thrombosis.Haemophilia : the official journal of the World Federation of Hemophilia · 2022Trial
- Computational modeling of pro-inflammatory cytokine-enhanced blood coagulation.bioRxiv : the preprint server for biology · 2026Article
- Computational Modeling of Pro-inflammatory Cytokine-Enhanced Blood Coagulation.Computational and structural biotechnology journal · 2026Article
- The preclinical profile of SerpinPC: a potential new treatment for hemophilia.Blood advances · 2025Article
- Concizumab, a Non-Replacement Therapy for Persons with Hemophilia with Inhibitors.Journal of clinical medicine · 2025Review
- MEK1/2- and ERK1/2-Mediated Lung Endothelial Injury and Altered Hemostasis Promote Diffuse Alveolar Hemorrhage in Murine Lupus.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Associations of tissue factor and tissue factor pathway inhibitor with organ dysfunctions in septic shock.Scientific reports · 2024Article
- Exploring nonreplacement therapies' impact on hemophilia and other rare bleeding disorders.Research and practice in thrombosis and haemostasis · 2024Article
- The Evolution of Hemophilia Therapeutics: An Illustrated Review.Research and practice in thrombosis and haemostasis · 2024Article
- Long Non-Coding RNAs in Venous Thromboembolism: Where Do We Stand?International journal of molecular sciences · 2023Review
- Concizumab: First Approval.Drugs · 2023Review
- The Tissue Factor Pathway in Cancer: Overview and Role of Heparan Sulfate Proteoglycans.Cancers · 2023Review
- RNAi for the Treatment of People with Hemophilia: Current Evidence and Patient Selection.Journal of blood medicine · 2023Review
- Aptamers Regulating the Hemostasis System.Molecules (Basel, Switzerland) · 2022Review
- Updates on Novel Non-Replacement Drugs for Hemophilia.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Concizumab as a Subcutaneous Prophylactic Treatment Option for Patients with Hemophilia A or B: A Review of the Evidence and Patient's Perspectives.Journal of blood medicine · 2022Review
- Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?Hematology. American Society of Hematology. Education Program · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replacement therapy with missing factor (F) VIII or IX in haemophilia patients for bleed management and preventative treatment or prophylaxis is standard of care. Restoration of thrombin generation through novel mechanisms has become the focus of innovation to overcome limitations imposed by protein replacement therapy. Tissue factor pathway inhibitor (TFPI) is a multivalent Kunitz-type serine protease inhibitor that regulates tissue factor (TF)-induced coagulation through a FXa-dependent feedback inhibition of the TF.FVIIa complex in plasma and on endothelial surfaces. Concizumab is a monoclonal, humanised antibody, specific for the second Kunitz domain of TFPI that binds and inhibits FXa, abolishing the inhibitory effect of TFPI. Concizumab restored thrombin generation in FVIII and FIX deficient plasmas and decreased blood loss in a rabbit haemophilia model. Phase 1 single and multiple dose escalation studies in haemophilia patients demonstrated a dose dependent decrease in TFPI levels and a pro-coagulant effect with increasing d-dimers and prothrombin fragment 1 + 2. A dose dependent increase in peak thrombin and endogenous thrombin potential was observed with values in the normal range when plasma TFPI levels were nearly undetectable. A few haemophilia patients in the highest dose cohorts with complete inhibition of plasma TFPI showed a decreased fibrinogen concentration with normal levels of anti-thrombin and platelets and no evidence of thrombosis. Pharmacokinetic parameters were influenced by binding to the target (TFPI), demonstrating target mediated drug disposition. A trend towards decreasing bleeding tendency was observed and this preventative effect is being studied in Phase 2 studies with additional data gathered to improve our understanding of the therapeutic window and potential for thrombosis.
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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.