Evolving treatment modalities for immune thrombocytopenia in adults

Khadka, Sushmita; Kasireddy, Vineela; Dhakal, Pravash; Dadiboyina, Chandrakala

doi:10.1080/20009666.2020.1843237

Cited by 3 publications

(2 citation statements)

References 42 publications

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“…Newer agents such as sutimlimab, fostamatinib and decitabine were shown promising results in recent a ITP study. 74 …”

Section: Discussionmentioning

confidence: 99%

Clinical Epidemiology, Treatment Outcome and Mortality Rate of Newly Diagnosed Immune Thrombocytopenia in Adult Multicentre Study in Malaysia

Hamzah¹,

Yusof²,

Tumian³

et al. 2022

JBM

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Background Immune thrombocytopenia (ITP) is well characterized in Western, European and other Asia-Pacific countries. Nevertheless, the clinical epidemiology, treatment pattern and disease outcome of ITP in Malaysia are still limited and not well known. Objective This study aimed to describe the clinical epidemiology, treatment outcome and mortality of ITP patients in haematology tertiary multicentre in Malaysia. Methods Clinical and laboratory data of newly diagnosed adults with ITP by a platelet count <100 × 10 9 /L from January 2010 to December 2020 were identified and analyzed. Results Out of 500 incident ITP, 71.8% were females with a striking age preponderance of both genders among those aged 18–29 years. The median age was 36 years. The median platelet count was 17.5 × 10 9 /L, 23.0% had a secondary ITP, 34.6% had a Charlson’s score ≥1, 53.0% had bleeding symptoms including 2.2% intracranial bleedings (ICB). Helicobacter pylori screening was performed in <5% of cases. Persistency and chronicity rates were 13.6% and 41.8%, respectively. Most (80.6%) were treated at diagnosis onset and 31.2% needed second-line treatment. Throughout the course of ITP, 11.0% of patients died; 3.0% and 8.0% with bleeding and non-bleeding related ITP. Conclusion This study confirms the epidemiology of ITP is comparable with worldwide studies. Our incidence is high in the female, Malay ethnicity, primary ITP and events of cutaneous bleeding at ITP onset with 18–29 years predominance age group for both genders. The frequency of persistent and chronic ITP is inconsistent with published literature. Corticosteroids and immunotherapies are the most prescribed first-line and second-line pharmacological treatments. Thrombopoietin receptor agonist medications (TPO-RAs) usage is restricted and splenectomy is uncommon. Our mortality rate is similar but ITP related bleeding death is fourth-fold lower than previous studies. Mortality risks of our ITP patients include age ≥60 years, male, severe bleeding at presentation, CCI≥1 and secondary ITP.

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“…Newer agents such as sutimlimab, fostamatinib and decitabine were shown promising results in recent a ITP study. 74 …”

Section: Discussionmentioning

confidence: 99%

Clinical Epidemiology, Treatment Outcome and Mortality Rate of Newly Diagnosed Immune Thrombocytopenia in Adult Multicentre Study in Malaysia

Hamzah¹,

Yusof²,

Tumian³

et al. 2022

JBM

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“…Immune thrombocytopenia (ITP) is a disease with an increased risk of hemorrhage developing on an autoimmune basis, which is caused by increased platelet destruction or decreased platelet production, affecting both children and adults (1-3). While it results in complete remission in 80% of children within 3-6 months, it usually becomes chronic in adults (4). The most common symptoms are petechiae and hemorrhage (5).…”

Section: Introductionmentioning

confidence: 99%

Quadruple Therapy in Patients with Immune Thrombocytopenia

Sahip

2022

Konuralp Tıp Dergisi

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Amaç:İmmün trombositopeni tedavisinde son yıllarda deksametazon, rituksimab ve siklosporin kombinasyon tedavileri umut verici sonuçlar vermiştir. Bu çalışmada, immün trombositopenide verilen kombinasyon tedavilerinin eltrombopag ile birleştirilmesiyle oluşturulan dörtlü tedavinin hastalardaki yanıtlarının araştırılması amaçlanmıştır. Yöntem:İmmun trombositopeni tanısı almış birinci basamak tedavide steroid, 2.basamak tedavide eltrombopag alan, tam ya da kısmı remisyon sağlanamayan 4 hasta retrospektif olarak aldıkları tedavi ve yanıt oranları açısından değerlendirdi. Sonuç:Relaps /refrakter immün trombositopenisi olan hastalar, eltrombopag tedavisine ek olarak oral deksametazon, oral siklosporin ve intravenöz düşük doz rituksimab ile tedavi edildi. Eltrombopag tedavisine 50 mg/gün dozunda devam edildi. Siklosporin için yükleme dozu verilmedi, haftalık kan siklosporin düzeyi toksisite açısından izlendi ve tedavi 200 ile 400 µg/L'lik bir hedef doza titre edildi. Toksisite kaynaklı ölüm, tedaviye bağlı ciddi advers olaylar veya tedaviye uyumsuzluk gözlenmedi. 6 aylık yanıt oranı %75 idi ve tedavi iyi tolere edildi. Hastalarımızdan iki tanesi halen tam yanıtlı olarak tarafımızca takipli iken bir hastamızda 6.aydan sonra relaps olması nedeniyle splenektomi yapılmış olup halen eltrombopag tedavi ile takiplidir. Yanıtsız olan daha önce splenektomili olan hastamıza ise romiplastim tedavisi uygulandı ancak bu tedaviye de yanıt alınamadı. Hasta klinik çalışmaya dahil edildi. Sonuç:Tedaviye dirençli immün trombositopenili hastalarda dörtlü tedavi kombinasyonunun bir tedavi seçeneği olabileceğini gösteren çalışmamız umut vaad etmektedir.

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Antagonism of the Platelet-Activating Factor Pathway Mitigates Inflammatory Adverse Events Driven by Anti-erythrocyte Antibody Therapy in Mice

Won,

Gil Gonzalez,

Cruz-Leal

et al. 2024

The Journal of Immunology

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Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts primarily due to antiplatelet autoantibodies. Anti-D is a donor-derived polyclonal Ab against the rhesus D Ag on erythrocytes used to treat ITP. Unfortunately, adverse inflammatory/hypersensitivity reactions and a Food and Drug Administration–issued black box warning have limited its clinical use. This underscores the imperative to understand the inflammatory pathway associated with anti-erythrocyte Ab-based therapies. TER119 is an erythrocyte-specific Ab with anti-D-like therapeutic activity in murine ITP, while also exhibiting a distinct inflammatory signature involving production of CCL2, CCL5, and CXCL9 but not IFN-γ. Therefore, TER119 has been used to elucidate the potential mechanism underlying the adverse inflammatory activity associated with anti-erythrocyte Ab therapy in murine ITP. Prior work has demonstrated that TER119 administration is associated with a dramatic decrease in body temperature and inflammatory cytokine/chemokine production. The work presented in the current study demonstrates that inhibiting the highly inflammatory platelet-activating factor (PAF) pathway with PAF receptor antagonists prevents TER119-driven changes in body temperature and inhibits the production of the CCL2, CCL5, and CXCL9 inflammatory cytokines in CD-1 mice. Phagocytic cells and a functional TER119 Fc region were found to be necessary for TER119-induced body temperature changes and increases in CXCL9 and CCL2. Taken together, this work reveals the novel requirement of the PAF pathway in causing adverse inflammatory activity associated with anti-erythrocyte Ab therapy in a murine model and provides a strategy of mitigating these potential reactions without altering therapeutic activity.

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Evolving treatment modalities for immune thrombocytopenia in adults

Cited by 3 publications

References 42 publications

Clinical Epidemiology, Treatment Outcome and Mortality Rate of Newly Diagnosed Immune Thrombocytopenia in Adult Multicentre Study in Malaysia

Clinical Epidemiology, Treatment Outcome and Mortality Rate of Newly Diagnosed Immune Thrombocytopenia in Adult Multicentre Study in Malaysia

Quadruple Therapy in Patients with Immune Thrombocytopenia

Antagonism of the Platelet-Activating Factor Pathway Mitigates Inflammatory Adverse Events Driven by Anti-erythrocyte Antibody Therapy in Mice

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