A Randomized Multicenter Trial Comparing Low-Dose Prednisolone Versus Observation for Prevention of Recurrences in Adult Immune Thrombocytopenia

Pirunsarn, Arunrat; Kijrattanakul, Pitiphong; Chamnanchanunt, Supat; Polprasert, Chantana; Rojnuckarin, Ponlapat

doi:10.1177/1076029618764843

Cited by 9 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The IC 50 of rilzabrutinib for inhibition of human B cell proliferation was 5 6 2.4 nM. Rilzabrutinib did not block ADCC in combination with anti-CD20 Abs, indicating potential for combination therapies (26).…”

Section: Blockade Of B Cell Activation Igm and Igg Ab Production Wimentioning

confidence: 96%

Preclinical Efficacy and Anti-Inflammatory Mechanisms of Action of the Bruton Tyrosine Kinase Inhibitor Rilzabrutinib for Immune-Mediated Disease

Langrish

Bradshaw

Francesco

et al. 2021

The Journal of Immunology

View full text Add to dashboard Cite

Bruton tyrosine kinase (BTK) is expressed in B cells and innate immune cells, acting as an essential signaling element in multiple immune cell pathways. Selective BTK inhibition has the potential to target multiple immune-mediated disease pathways. Rilzabrutinib is an oral, reversible, covalent BTK inhibitor designed for immune-mediated diseases. We examined the pharmacodynamic profile of rilzabrutinib and its preclinical mechanisms of action. In addition to potent and selective BTK enzyme and cellular activity, rilzabrutinib inhibited activation and inflammatory activities of B cells and innate cells such as macrophages, basophils, mast cells, and neutrophils, without cell death (in human and rodent assay systems). Rilzabrutinib demonstrated dosedependent improvement of clinical scores and joint pathology in a rat model of collagen-induced arthritis and demonstrated reductions in autoantibody-mediated FcgR signaling in vitro and in vivo, with blockade of rat Arthus reaction, kidney protection in mouse Ab-induced nephritis, and reduction in platelet loss in mouse immune thrombocytopenia. Additionally, rilzabrutinib inhibited IgE-mediated, Fc«R-dependent immune mechanisms in human basophils and mast cell-dependent mouse models. In canines with naturally occurring pemphigus, rilzabrutinib treatment resulted in rapid clinical improvement demonstrated by anti-inflammatory effects visible within 2 wk and all animals proceeding to complete or substantial disease control. Rilzabrutinib is characterized by reversible covalent BTK binding, long BTK residence time with low systemic exposure, and multiple mechanistic and biological effects on immune cells. Rilzabrutinib's unique characteristics and promising efficacy and safety profile support clinical development of rilzabrutinib for a broad array of immune-mediated diseases.

show abstract

Section: Blockade Of B Cell Activation Igm and Igg Ab Production Wimentioning

confidence: 96%

Preclinical Efficacy and Anti-Inflammatory Mechanisms of Action of the Bruton Tyrosine Kinase Inhibitor Rilzabrutinib for Immune-Mediated Disease

Langrish

Bradshaw

Francesco

et al. 2021

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“… 8 Long-term corticosteroids should be avoided in most cases because they are poorly effective in maintaining remission at a low dose and do not affect the ITP natural history while generating side effects. 58 , 59 Prednisone 1 mg/kg for 3 weeks or dexamethasone 40 mg/day for 4 days (repeated up to three times if necessary) can be used. A number of controlled studies have suggested a faster and greater platelet response with dexamethasone over prednisolone, but the rate of long-term response was similar in both groups.…”

Section: Itp Treatments: What Tolerance and What Efficacy In Older Pa...mentioning

confidence: 99%

Older Adults and Immune Thrombocytopenia: Considerations for the Clinician

Crickx¹,

Mahévas²,

Michel³

et al. 2023

CIA

View full text Add to dashboard Cite

Many epidemiological studies have shown that the incidence of immune thrombocytopenia (ITP) increases after age 60 years and peaks in patients over age 80 years. Therefore, ITP is a concern for physicians taking care of older patients, especially regarding its diagnosis and management. The diagnostic work-up should exclude other causes of thrombocytopenia and secondary ITP, including myelodysplastic syndrome and drug-induced ITP. The treatment decision is influenced by an increased risk of bleeding, infectious diseases and thrombosis in this population and should take into account comorbidities and concomitant medications such as anticoagulant drugs. First-line treatment is based on short corticosteroids courses and intravenous immunoglobulin, which should be reserved for patients with more severe bleeding complications, with their higher risk of toxic effects as compared with younger patients. Second-line treatment should be tailored to the patient’s history, comorbidities and preferences. Preferred second-line treatments are thrombopoietin receptor agonists for most groups and guidelines given their good efficacy/tolerance ratio, but the thrombotic risk is increased in older people. Other second-line options that can be good alternatives depending on the clinical context include rituximab, dapsone, fostamatinib or immunosuppressive drugs. Splenectomy is less often performed but remains an option for fit patients with chronic refractory disease. Emerging treatments such as Syk or Bruton tyrosine kinase inhibitors and FcRn antagonists are becoming available for ITP and may modify the treatment algorithm in the near future. The aim of this review is to describe the particularities of the diagnosis and treatment of ITP in older people, including the response and tolerance to the currently available drugs. We also discuss some situations related to co-morbidities that can frequently lead to adapt the management strategy in older patients.

show abstract

“…Most patients respond to corticosteroids with a rise in platelet count, but improvements are usually transient and the majority of patients will relapse [5,26]. Although prolonged corticosteroid therapy may maintain a hemostatic platelet count in responding patients, it does not enhance the rate of remission [5,33] and long-term use is linked with a number of side effects that can be…”

Section: Corticosteroidsmentioning

confidence: 99%

Romiplostim in adults with newly diagnosed or persistent immune thrombocytopenia

Lozano

Godeau

Grainger

et al. 2020

Expert Review of Hematology

View full text Add to dashboard Cite

Introduction: Three distinct phases are recognized in immune thrombocytopenia (ITP): newly diagnosed (≤3 months after diagnosis), persistent (>3-12 months after diagnosis), and chronic (>12 months). Several international guidelines/expert recommendations have been released in the past 2 years regarding the treatment of newly diagnosed/persistent ITP. Areas covered: Across the guidelines/expert recommendations, thrombopoietin receptor agonists (TPO-RAs), including romiplostim (the focus of this review), are recommended in newly diagnosed or persistent ITP for patients who fail to respond to corticosteroids or intravenous immunoglobulin (or where these are contraindicated). To identify data relating to romiplostim in adults with newly diagnosed or persistent ITP, we conducted a search of PubMed (with no time limit applied) and abstracts from 2019 EHA/ASH meetings using the term 'romiplostim.' Expert opinion: The findings from nine clinical trials, six real-world studies and ten case reports provide insight into the early use of romiplostim, which could help to reduce exposure to the adverse effects associated with prolonged corticosteroid use, as well as reduce the risk of severe bleeding. Additionally, given the durable responses observed in patients with newly diagnosed/persistent ITP, as well as the potential for treatment-free responses following discontinuation, romiplostim might help to avoid the need for subsequent treatment.

show abstract

A Randomized Multicenter Trial Comparing Low-Dose Prednisolone Versus Observation for Prevention of Recurrences in Adult Immune Thrombocytopenia

Cited by 9 publications

References 21 publications

Preclinical Efficacy and Anti-Inflammatory Mechanisms of Action of the Bruton Tyrosine Kinase Inhibitor Rilzabrutinib for Immune-Mediated Disease

Preclinical Efficacy and Anti-Inflammatory Mechanisms of Action of the Bruton Tyrosine Kinase Inhibitor Rilzabrutinib for Immune-Mediated Disease

Older Adults and Immune Thrombocytopenia: Considerations for the Clinician

Romiplostim in adults with newly diagnosed or persistent immune thrombocytopenia

Contact Info

Product

Resources

About