Treating chronic ITP

The heterogeneity of chronic ITP makes treatment challenging, and highlights the need for a personalized approach1

Treating chronic ITP

The heterogeneity of chronic ITP makes treatment challenging, and highlights the need for a personalized approach1

Heterogeneous disease

Immune thrombocytopenia is a heterogeneous disease with a complex, multifactorial pathogenesis2

Immune thrombocytopenia (ITP) is driven by 2 factors: immune-mediated platelet destruction and low platelet production3

Immune-mediated platelet destruction

01

Dysregulation of the immune system leads to production of anti-platelet antibodies4

02

Macrophage recognition of antibody-coated platelets results in unregulated platelet destruction5

03

Lysis process results in an amplified production of anti-platelet antibodies5

Low platelet production

01

Platelet destruction causes decreased levels of thrombopoietin (TPO)2

02

Anti-platelet antibodies may also target megakaryocytes, resulting in impaired megakaryocyte function4

03

Irregular T-cell response may destroy platelets in bone marrow and impede platelet production5

Chronic ITP treatment options

The heterogeneity of chronic ITP makes treatment challenging, and highlights the need for a personalised approach1

Current ITP treatment options either decrease platelet destruction or stimulate platelet production5

Corticosteroids

  • Suppress systemic function and reduce antibody production, resulting in decreased platelet destruction3
  • Standard first-line therapy for recently diagnosed patient7
  • Over time, treatment side effects may outweigh the potential benefits7
  • Most patients relapse upon discontinuation of treatment7

Thrombopoietin receptor agonists (TPO-RAs)

  • Stimulate megakaryocytes in bone marrow to produce platelets5
  • Associated with possible increases in bone marrow fibrosis7
  • There is some evidence that thrombotic events are higher in ITP patients using some TPO-RAs, especially in those older than 60 years7

Intravenous immunoglobulin (IVIG)8

  • Limits platelet destruction through multiple mechanisms, including modulation of Fcγ receptor expression and activity
  • Common first-line therapy often used in combination with corticosteroids, and as rescue treatment
  • Improves platelet counts in 60%-80% of patients
  • Provides rapid, but short-term, increases in platelet counts

Anti-CD20

  • Depletes B cells5
  • A meta-analysis of 5 trials showed that rituximab was not associated with reductions in bleeding7
  • In a study of response durability, only 21% maintained remission at 5 years7

ITP treatment guidelines: International consensus report

Robust treatment evidence: fostamatinib categorised with TPO-RAs and rituximab by the international consensus report on ITP

After initial treatments fail in adults with immune thrombocytopenia (ITP), the International Consensus Report recommends⁷, *, †:

ITP treatment guidelines; subsequent ITP treatment following failure of initial treatment

*Adapted from Provan et al. 2019⁷
†Recommended initial treatments are defined as corticosteroids, intravenous immune globulin (IVIG), and Anti-D.

Chronic ITP Treatment Landscape

Tavlesse redefines the treatment landscape with a targeted mechanism of action

Limiting platelet destruction with the targeted mechanism of action of Tavlesse is a novel way to treat chronic ITP in adults9, 10, 11

Chronic ITP treatment landscape graph based on each treatment mechanism of action.

Tavlesse is indicated for the treatment of chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments.10,11

 
 

Mode of action

Tavlesse inhibits downstream signalling which prevents platelet destruction in chronic ITP with a unique mechanism of action10, 11

ITP: immune thrombocytopenia

References:

  1. Newland A, McDonald V. Fostamatinib: a review of its clinical efficacy and safety in the management of chronic adult immune thrombocytopenia. Immunology.2020;12(18):1325-1340
  2. Cines DB, Bussel JB, Liebman HA, et al. The ITP syndrome: pathogenic and clinical diversity. Blood. 2009; 113(26): 6511-6521.
  3. Raj AB. Immune thrombocytopenia: pathogenesis and treatment approaches. J Hematol Transfus. 2017;5(1):1056-1065.
  4. Shih A, Nazi I, Kelton JG, et al. Novel treatments for immune thrombocytopenia. Presse Med. 2014;43:e87-e95.
  5. Newland A, Lee E, McDonald V, et al. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy. 2018;10(1):9-25.
  6. Olsson B, Ridell B, Carlsson L, et al. Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4 and CX3CR1. Blood. 2008;112(4):1078-1084.
  7. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817.
  8. Kistanguri G, McCrae KR. Immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3):495-520.
  9. Bussel J, Arnold DM, Grossbard E, et al. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018;93(7):921-930.
  10. Tavlesse Summary of Product Characteristics. Great Britain. Grifols. Date of revision: January 2021. Available at https://www.medicines.org.uk/emc/product/11479 . Accessed on 14/2/2022.
  11. Tavlesse Summary of Product Characteristics. Northern Ireland. Grifols. Date of revision: August 2021. Available at https://www.emcmedicines.com/en-gb/northernireland/medicine?id=9c2f7cf0-129d-42a3-a61c-d729ae80e50c. Accessed on 14/2/2022.
  12. Ghanima W, Godeau B, Cines DB, et al. How I treat immune thrombocytopenia: the choice between splenectomy or a medical therapy as a second-line treatment. Blood. 2012;120(5):960-969.
  13. Mizutani H, Furubayashi T, Imai Y. Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1. Blood. 1992;79(4):942-947.
  14. Privigen Summary of Product Characteristics. CSL. Date of revision: November 2020. Available at https://www.medicines.org.uk/emc/medicine/21359#gref. Accessed on 14/2/2022.
  15. Stasi R, Pagano A, Stipa E, et al. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura. Blood. 2001;98(4):952-957.
  16. MabThera Summary of Product characteristics. Roche. Date of revision: September 2021. Available at https://www.medicines.org.uk/emc/product/7819/smpc. Accessed on 14/2/2022.
  17. Doptelet Summary of Product characteristics. SOBI. Date of revision: October 2021. Available at https://www.medicines.org.uk/emc/product/11837. Accessed on 14/2/2022.
  18. Nplate Summary of Product Characteristics. Amgen. Date of revision: January 2021. Available at https://www.medicines.org.uk/emc/product/9325/smpc. Accessed on 14/2/2022.
  19. Revolade Summary of Product characteristics. Novartis. Date of revision: September 2021. Available at https://www.medicines.org.uk/emc/product/7819/smpc. Accessed on 14/2/2022.