Spotlight on ITP: A New Era in Autoimmune Disease Management

By Sherwin DeSouza, MD – Adult Hematologist

What is ITP?

Immune thrombocytopenia (ITP) is a rare autoimmune disorder, mediated by autoantibodies to platelet surface antigens characterized by a low platelet count, which increases the risk of bleeding. Common symptoms include:

• Fatigue
• Heavy menstrual bleeding
• Petechiae (pinpoint skin bruises)
• Blood blisters on mucosal surfaces such as mouth
• Bleeding from mucosal surfaces such as epistaxis

ITP affects approximately 2 to 5 individuals per 100,000 and can occur at any age^1-3. It is more commonly seen in people with existing autoimmune diseases and tends to follow a more chronic course in adults than in children. A similar pattern of immune-mediated thrombocytopenia occurs in Evan’s syndrome, antiphospholipid antibody syndrome, and in relation to immunotherapy used to treat cancer.[i]

ITP remains a diagnosis of exclusion, however in more recent years, platelet antibody testing and variability indices have added to diagnostic armamentarium and accuracy^4,5. Additionally, the increasing availability of myeloid genetic testing allows for early separation of primary myeloid disorders from thrombocytopenia related to autoimmunity.

Challenges in Treatment Over the Past Two Decades

For many adults, ITP is a chronic, relapsing condition, with spontaneous remission occurring in only 10–20% of cases⁶. Acutely, severe thrombocytopenia of autoimmune nature can be managed with intravenous immunoglobulin and steroids, the effect being temporary in most adults. Thereafter generally, treatment has focused on either boosting platelet production (thrombopoietin receptor agonists or TPO-RA) or suppressing the immune system (chemotherapy and immunotherapy), with steroids and IVIG continuing to be rescue options. This expansion of treatment options over the last 10-15 years has helped reduce reliance on corticosteroids. However, in general, more aggressive immunosuppression—such as monoclonal antibodies and chemotherapy—have not significantly improved remission rates and carry risks from infection which have become more apparent after the COVID-19 pandemic. The TPO-RA, on the other hand, carry a risk for thrombosis estimated at 2-3 times higher than ITP patients not treated with TPO-RA and therefore are not suited for a variety of immune-mediated thrombocytopenia clinical scenarios, especially in high risk populations⁷. Therefore, there is certainly room for improvement.

Within the last 5 years, the focus is shifting toward therapies that target the underlying disease mechanisms by immunomodulation. Thus opening the possibility of therapy to a wider range of immune-mediated mechanisms with the hope of a longer lasting duration of remission.

Innovations in Immune Modulation

Since the early 2000s, rituximab and chemotherapy were the primary tools for immune modulation through suppression. While effective and eliciting a response, they often compromise immunity, thereby increasing risk of infections and do not offer a significant remission benefit. Newer therapies like fostamatinib—a spleen tyrosine kinase (Syk) inhibitor— and rilzabrutinib— a recently FDA approved BTK inhibitor—offer a promising alternative^8,9. They can be used for chronic immune thrombocytopenia, do not carry a significant risk for infection nor thrombosis, and can be used in immune thrombocytopenia associated with other conditions.

Expanding Treatment to Evans Syndrome

Evans Syndrome is a rare condition that includes ITP, autoimmune hemolytic anemia, and autoimmune neutropenia, presents additional treatment challenges. It often resists standard therapies and relapses frequently. Immunosuppressive treatments can address both ITP and Autoimmune Hemolytic Anemia (AIHA) cooccurring, which is an additional area where immunomodulatory therapies have potential. There is already data supporting use of fostamatinib in this setting¹⁰.

Why This Is an Exciting Time in ITP Research

The future of ITP treatment is bright, with new therapeutic targets and measures. Beyond managing platelet counts, researchers are now focusing on improving quality-of-life issues, such as heavy menstrual bleeding and fatigue as they relate to ITP. These therapeutic measures are increasingly part of clinical trials for new drugs allowing individualized care. A range of innovative agents are currently under investigation, including:

• Neonatal Fc receptor antagonists – reduce antibody recycling¹¹
• BTK inhibitors – block pathways involved in autoantibody production⁹
• BAFF inhibitors – limit B-cell survival and antibody production¹²
• Anti-CD38 monoclonal antibodies – deplete harmful plasma cells¹³
• Next-generation Syk inhibitors and complement inhibitors – offer new therapeutic avenues for refractory disease

Looking Ahead

With the development of more precise diagnostic tools, targeted therapies, and measures of disease, the landscape of ITP treatment is rapidly evolving. These advancements promise not only better disease control but also improved patient outcomes and quality of life.

Dr. Sherwin DeSouza is an adult hematologist at Innovative Hematology, parent of the Indiana Hemophilia & Thrombosis Center (IHTC) in Indianapolis. Dr. DeSouza’s special interests and expertise thrombocytopenia, neutropenia, anemias, Evans Syndrome, and autoimmune hematologic conditions.

References:

1. Terrell DR, Beebe LA, Neas BR, Vesely SK, Segal JB, George JN. Prevalence of primary immune thrombocytopenia in Oklahoma. Am J Hematol. Sep 2012;87(9):848-52. doi:10.1002/ajh.23262
2. Weycker D, Hanau A, Hatfield M, et al. Primary immune thrombocytopenia in US clinical practice: incidence and healthcare burden in first 12 months following diagnosis. J Med Econ. Feb 2020;23(2):184-192. doi:10.1080/13696998.2019.1669329
3. Abrahamson PE, Hall SA, Feudjo-Tepie M, Mitrani-Gold FS, Logie J. The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review. Eur J Haematol. Aug 2009;83(2):83-9. doi:10.1111/j.1600-0609.2009.01247.x
4. Li N, Heddle NM, Nazy I, Kelton JG, Arnold DM. Platelet variability index: a measure of platelet count fluctuations in patients with immune thrombocytopenia. Blood Adv. Oct 26 2021;5(20):4256-4264. doi:10.1182/bloodadvances.2020004162
5. Sachs UJ, Reich M, Qiu D, Bayat B, Cooper N, Bein G. Platelet autoantibodies have an impact on the platelet count in patients. J Thromb Haemost. Jul 2025;23(7):2322-2326. doi:10.1016/j.jtha.2025.02.016
6. Cuker A, Prak ET, Cines DB. Can immune thrombocytopenia be cured with medical therapy? Semin Thromb Hemost. Jun 2015;41(4):395-404. doi:10.1055/s-0034-1544001
7. Ghanima W, Cooper N, Rodeghiero F, Godeau B, Bussel JB. Thrombopoietin receptor agonists: ten years later. Haematologica. Jun 2019;104(6):1112-1123. doi:10.3324/haematol.2018.212845
8. Bussel JB, Arnold DM, Boxer MA, et al. Long-term fostamatinib treatment of adults with immune thrombocytopenia during the phase 3 clinical trial program. Am J Hematol. May 2019;94(5):546-553. doi:10.1002/ajh.25444
9. Kuter DJ, Ghanima W, Cooper N, et al. Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study. Blood. Jun 12 2025;145(24):2914-2926. doi:10.1182/blood.2024027336
10. Jorge N Ruiz Lopez LS, Debbie Jiang, Lawrence Bailey, Thejaswi Bikkani, Donald C Moore, Irina Murakhovskaya, Caroline Piatek, Mauricio Pineda-Roman, Jin Ping, Jacqueline N Poston, Moritz Stolla, David F. Stroncek, Krystalyn E. Hudson, Sandya R. Panch. Efficacy, Safety and Molecular Response Predictors of Fostamatinib in Warm Autoimmune Hemolytic Anemia (wAIHA) and/or Evans Syndrome (ES): A Multicenter Analysis. presented at: American Society of Hematology, Annual Meeting 2024; 2024; Session Session 101.Red Cells and Erythropoiesis, Excluding Iron.
11. Broome CM, McDonald V, Miyakawa Y, et al. Efficacy and safety of the neonatal Fc receptor inhibitor efgartigimod in adults with primary immune thrombocytopenia (ADVANCE IV): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. Nov 4 2023;402(10413):1648-1659. doi:10.1016/S0140-6736(23)01460-5
12. Adam Cuker HA-S, Wilma Barcellini, Nichola Cooper, Waleed Ghanima, Marc Michel, Raymond SM Wong, Francesco Zaja, Fengkui Zhang, Patrick Urban, Roberto Abi Rached, David J Kuter. . Ianalumab, a Novel Anti-B-Cell Activating Factor (BAFF) Receptor (BAFF-R) Monoclonal Antibody (mAb) in Development for Immune Thrombocytopenia (ITP) and Warm Autoimmune Hemolytic Anemia (wAIHA), Has Demonstrated a Favorable Safety Profile in Sjögren’s Syndrome (SjS), Systemic Lupus Erythematosus (SLE) and Chronic Lymphocytic Leukemia (CLL). presented at: American Society of Hematology, Annual Meeting 2023; 2 NOVEMBER 2023 2023; Session 311.DISORDERS OF PLATELET NUMBER OR FUNCTION: CLINICAL AND EPIDEMIOLOGICAL.
13. Chen Y, Xu Y, Li H, et al. A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia. N Engl J Med. Jun 20 2024;390(23):2178-2190. doi:10.1056/NEJMoa2400409