Immune Thrombocytopenia: Contemporary Pathophysiology, Treatment Gaps, and the Role of Novel Mechanisms in Patient-Centered Care

This supplement was supported by Sanofi.

ABSTRACT

Immune thrombocytopenia (ITP) is a chronic autoimmune disorder associated with platelet destruction and increased bleeding risk, substantial economic burden, and impairment of health-related quality of life. The pathophysiology of ITP involves increased platelet destruction and impaired platelet production due to a multifactorial breakdown of immune tolerance driven by dysregulated B and T cells. Advances in understanding ITP pathophysiology have led to the development of new immune-modulating therapies, such as Bruton tyrosine kinase (BTK) inhibitors. Rilzabrutinib (Wayrilz; Sanofi) is an oral BTK inhibitor recently approved for treatment of adult patients with persistent or chronic ITP who have had an insufficient response to a previous treatment. Rilzabrutinib targets several aspects of ITP disease pathophysiology by modulating multiple immune pathways. Approval was based on results from a phase 3 trial (LUNA 3 [NCT04562766]), in which patients with ITP who received rilzabrutinib demonstrated a rapid, durable platelet response and improvements in fatigue and bleeding with a tolerable safety profile.

Am J Manag Care. 2026;32(suppl 1):S3-S11. https://doi.org/10.37765/ajmc.2026.89888
For author information and disclosures, see end of text.

Introduction

Immune thrombocytopenia (ITP) is an autoimmune platelet disorder characterized by a low platelet count, increased incidence of bleeding, and heightened risk of thrombosis.^1,2 ITP is also associated with significant health-related quality of life (HRQOL) impacts such as fatigue, impaired physical and cognitive functioning, and anxiety.^2,3 Existing therapies exert a high treatment burden in the form of adverse events (AEs) and platelet count fluctuations, and a subset of patients experience persistent disease that underscores the high unmet need for new and improved therapies for ITP.^4-7 Current therapies for ITP managements do not target the underlying immune dysregulation and cannot address its broad clinical manifestations.⁸ Complex immune dysregulation leading to autoimmunity and systemic inflammation is increasingly being recognized to underlie the pathophysiology of ITP, and the role of targeting these dysfunctional pathways is currently being investigated.^9,10 The Bruton tyrosine kinase (BTK) inhibitor rilzabrutinib (Wayrilz; Sanofi) recently received FDA approval for the treatment of adults with persistent or chronic ITP who had an insufficient response to a prior treatment.^11,12 BTK inhibition is a next-generation treatment strategy that targets multiple aspects of ITP disease pathophysiology through multi-immune modulation, offering additional options for patients with persistent and chronic ITP.^9,11

Overview of ITP

The incidence of ITP is estimated at 2 to 5 per 100,000 persons, with peaks in individuals between the ages of 20 and 30 years and again in those older than 60 years.^1,2 There is no singular diagnostic test for ITP.¹ It is typically a diagnosis of exclusion that is established when platelet counts fall below 100 × 10³/μL and other potential causes of thrombocytopenia have been ruled out through additional testing, physical examination, and patient history (Figure 1^1,13).¹ ITP that occurs in the absence of other causes is primary and it accounts for approximately 80% of cases.¹⁴ Secondary ITP comprises other forms of immune-mediated platelet destruction consequent to the inciting cause (Figure 2^1,15-17).¹⁴ ITP is divided into newly diagnosed (< 3 months duration), persistent (3-12 months duration), or chronic (> 12 months duration), with approximately 70% of adults progressing to chronic ITP. ^1,2

Symptoms of ITP are typically characterized by episodes of non–life-threatening bleeding.⁵ Presentation of bleeding includes petechiae and purpura often in the lower extremities, epistaxis, heavy menstrual bleeding (HMB), gingival and gastrointestinal (GI) bleeding, and intracranial hemorrhage.^5,16,18 These can be seen in approximately 60% of patients with ITP,¹⁹ while severe bleeding occurs in approximately 10% of adult patients with primary ITP.²⁰ Other symptoms of ITP such as fatigue, anxiety concerning unstable platelet counts, depression, and cognitive impairment considerably impact patient QOL.^3,21,22

The Underlying Pathophysiology of ITP

In normal physiology, platelet production is driven by thrombopoietin (TPO), a glycoprotein hormone and growth factor that helps to regulate megakaryocyte (MK) proliferation, maturation, and subsequent platelet formation.^23,24 The pathophysiology of ITP involves a multifactorial breakdown of immune tolerance that results in increased platelet destruction and impaired platelet production that are driven by dysregulated B and T cells (Figure 3^1,5,25).¹ The resulting immune dysregulation in ITP appears to have a number of proinflammatory components.²⁶

Immune-Mediated Platelet Destruction and Impaired Production

Immune-mediated destruction of platelets and impairment of platelet production in ITP are multivariate processes. The increased expression of the NLRP3 inflammasome, along with other proinflammatory mechanisms, potentially contributes to thromboinflammation and, therefore, an increased risk of thromboembolic (TE) events in ITP.^8,27 Patients with ITP present with a proinflammatory cytokine profile that contributes to disease pathogenesis; levels of the proinflammatory cytokines interleukin-2 (IL-2), interferon-γ (IFN-γ), and IL-17 are elevated, whereas the regulatory cytokines IL-10 and TGF-β are reduced, an imbalance that leads to autoantibody development.²³

Immunoglobulin G (IgG) autoantibodies (and less commonly IgM or IgA antibodies) target platelet surface glycoproteins (GPs), primarily GPIIb/IIIa and GPIb-IX-V, leading to Fcγ receptor–mediated phagocytosis in the spleen and liver.²³ Antibodies also impair platelet production via inhibition of MK maturation and proplatelet formation, which reduces platelet output.^1,23 Levels of TPO are often normal or mildly decreased in patients, failing to compensate for thrombocytopenia.²³ Further, dysregulation of regulatory B cells (B_regs) arising from and perpetuating loss of tolerance leads to increased plasma cell activity and autoantibody production.²³

As many as 30% to 40% of patients with ITP lack detectable autoantibodies, although whether this results from a lack of robustness in antibody testing or the existence of purely T cell–mediated forms of ITP remains unknown.²³

Immune-Cell Dysregulation and Cytokine Imbalance

T-cell and cytokine abnormalities also contribute to the autoimmune pathophysiology of ITP.¹ Regulatory T cells (T_regs) play a vital role in the maintenance of self-tolerance; their reduction in ITP is thought to be a critical component of the pathophysiology of the disease,²³ and unbalanced T helper cell 1 (Th1), Th17, and Th22 subsets contribute to sustained immune activation. Cytotoxic CD8+ T cells play a dual role in ITP, directly lysing platelets and inhibiting thrombopoiesis in the bone marrow. Dendritic cells demonstrate enhanced self-antigen presentation in ITP; this dysfunction promotes the autoreactive response of immune cells to platelets.²³

Bone Marrow Impairment and Megakaryocyte Dysfunction

Autoreactivity renders the bone marrow microenvironment dysfunctional in ITP, exacerbating thrombopoiesis defects. Autoantibodies against MKs can increase apoptosis or impair MK maturation, leading to reduced platelet production despite normal TPO levels. Mesenchymal stem cells (MSCs) are also impacted; these cells normally sustain MK maturation and platelet formation but become apoptotic in ITP. Further, MSCs lose their immunosuppressive functions in ITP and fail to regulate T-cell activity.²³

Current Therapeutic Landscape and Unmet Needs

The current goal of ITP treatment is to stop active bleeding and prevent future bleeding.¹ The treatment of ITP follows 3 main mechanistic pathways: reducing antiplatelet antibody production, inhibiting platelet clearance, and increasing platelet production (Table^2,5,23).⁵Treatment options for reducing antiplatelet antibody production include corticosteroids, splenectomy, and rituximab, whereas therapies that reduce platelet clearance include corticosteroids, splenectomy, fostamatinib, and intravenous Ig (IVIg).⁵Increasing platelet production is achieved through TPO receptor agonists (TPO-RAs). These treatment pathways are geared toward reducing symptoms and preventing severe bleeding but may not directly address the underlying immune dysregulation associated with ITP.⁵

The decision to observe or initiate pharmacological treatment in newly diagnosed ITP depends on the severity of thrombocytopenia, patient comorbidities, concurrent medications, and age, all of which influence bleeding risk. Additional factors such as disease duration, health care access, QOL considerations, and patient and provider preferences also play a role in management. According to the 2019 guidelines from the American Society of Hematology (ASH), patients with a platelet count of at least 30 × 10³/μL who are asymptomatic or have only minor mucocutaneous bleeding can be managed with observation, whereas those with a platelet count below 30 × 10³/μL typically require treatment with a short course (≤ 6 weeks) of corticosteroids as first-line therapy. Prednisone or dexamethasone may be used, with dexamethasone offering a faster platelet response. Treatment with corticosteroids alone is recommended over combination therapy with rituximab unless long-term remission is prioritized over concerns related to rituximab-associated AEs. Close monitoring is essential to assess corticosteroid-related AEs (eg, hypertension, hyperglycemia, sleep and mood disturbances, osteoporosis) and overall HRQOL. For persistent ITP (≥ 3 months since diagnosis) in corticosteroid-dependent or unresponsive patients, ASH recommends TPO-RAs, rituximab, or splenectomy as second-line options. TPO-RAs and rituximab are recommended interventions for patients who wish to avoid surgery. Splenectomy may be considered for patients who place high importance on achieving a durable response and should generally be delayed for at least 1 year due to the possibility of spontaneous remission.²

The Importance of Individualized ITP Management

Treatment choice should be individualized based on factors such as bleeding severity, response duration, comorbidities, TE risk, adherence, and patient preferences.^2,5 The ASH guidelines emphasize shared decision-making, encouraging clinicians to tailor treatment based on not only age and clinical presentation but also individual patient values, preferences, and support network.² As new therapies become available, this approach supports the importance of individualizing treatment according to each patient’s specific risk profile.⁵ Common comorbid conditions in ITP—such as cardiovascular disease (CVD), diabetes mellitus (DM), and prior venous TE (VTE)—may lead to further thrombosis and complicate therapeutic decisions especially when patients are on anticoagulants or antiplatelet therapy.^2,28,29

Treatment options like corticosteroids, IVIg, and splenectomy carry heightened risks in these populations that may outweigh disease-related morbidity.²⁸ Use of TPO-RAs requires careful consideration of adherence, drug interactions, and thrombotic risk, particularly in patients with comorbidities or polypharmacy.²⁸ These findings reinforce the importance of aligning ITP treatment decisions with each patient’s evolving risk profile and comorbidity burden rather than relying solely on platelet count or bleeding history.²⁹

Patient-Centered Considerations in ITP Management

Research continues to highlight the role of systemic inflammation in the clinical etiology of fatigue, depression, anxiety, and other QOL issues commonly impacting patients with ITP.^2,30 Inflammation has been increasingly recognized as a contributing factor in ITP, with patients showing elevated levels of inflammatory markers such as TNF-α, IL-6, NLRP3-related cytokines (IL-18 and IL-1β), and IFN-γ.^27,31,32 This systemic inflammatory state may further influence disease progression and symptom burden.³²

The impact of ITP reaches beyond hematologic parameters, affecting multiple aspects of daily life.¹ Patients report substantial effects on their physical and emotional well-being, with fatigue emerging as a major burden.³ The Immune Thrombocytopenia World Impact Survey (I-WISh), which included 1507 patients with ITP and 472 health care providers (HCPs), furnished valuable insights into these challenges. The survey, conducted across 13 countries, involved factors including disease symptoms, HRQOL, emotional and financial impact, treatment experiences, and patient-physician relationships. Some 49% of patients surveyed reported reducing, or seriously considering a reduction in, their working hours due to their ITP, and 11% of patients had to stop working because of their disease. Further, among those employed at the time of the survey, 36% believed that ITP negatively impacted their work productivity.³

In the same study, physicians provided perspectives on symptom management and treatment patterns, reinforcing the need for a comprehensive approach to care.³ A discrepancy was identified between patient-reported fatigue at diagnosis and HCP recognition of fatigue. Fifty percent of patients reported fatigue, while HCPs reported that only 38% of their patients were fatigued. Patients in this study also reported anxiety about their ITP management, with 63% worried about fluctuating platelet counts, 63% fearing disease progression, 41% being concerned about mortality, and 39% believing their HCPs underestimated their symptoms. These findings suggest that fatigue and anxiety are significant symptoms for many patients with ITP, although they may be underrecognized or underestimated by HCPs.³

ITP is known to cause HMB in premenopausal women and is an area of more recent research. A cross-sectional cohort study of patients with primary chronic ITP found a prevalence of 39% for HMB among the premenopausal women. The impact of HMB was assessed with the menorrhagia multi-attribute scale (MMAS); the MMAS is scored from 0 to 100, with lower scores indicating more severe impact. The median MMAS score was 79, and only 24% of patients indicated that menstrual symptoms did not impact their daily life. Worse MMAS scores were significantly correlated with fatigue.³³

Additional studies have highlighted potential neurological complications, including cognitive impairment, in patients with ITP.^18,34 A 2022 study using the Cambridge Neuropsychological Test Automated Battery (CANTAB) assessed cognitive function among 69 patients with ITP.³⁴ The results revealed that 50% exhibited cognitive impairment across domains that included episodic memory, executive function, processing speed, working memory, and attention.³⁴A 2024 study by Kuter and colleagues reported similar rates and severity of cognitive impairment in 49 adult patients with persistent or chronic primary ITP.²¹ These results underscore the need for comprehensive care strategies that address both the hematologic and neurological impacts of ITP.²¹

Disease Burden and Unmet Treatment Needs

Recent research on disease burden in ITP reveals high unmet treatment needs across multiple domains. An observational retrospective cohort study evaluated the clinical burden of persistent or chronic primary ITP in patients treated with advanced therapies compared to a matched non-ITP population.²² Using Optum’s de-identified Clinformatics Data Mart Database, researchers identified patients with ITP who began treatment with advanced therapies between 2016 and 2022 and matched them (1:5) to non-ITP individuals based on age, gender, race, ethnicity, and cohort entry year. Clinical events (eg, bleeding, TEs, infections, and mortality) were assessed during follow-up. The study examined 1140 patients with ITP and 5657 individuals not diagnosed with ITP; they found that those with ITP had a higher prevalence of comorbidities, including solid tumors, cardiovascular risk factors, and mental health conditions. During an average follow-up of 2.3 years (ITP) and 2.6 years (non-ITP), those with ITP had significantly higher rates of bleed-related hospitalizations (15.2% vs 4.5%) and TEs (20.3% vs 9.1%) and higher crude rate ratios for infections (3.14; 95% CI, 2.61-3.78) and malignancies (1.57; 95% CI, 1.21-2.04). Mortality was elevated in the ITP cohort (21% vs 10%), with an adjusted HR of 1.45 (95% CI, 1.23-1.71) for death. Despite the use of advanced therapies, oral steroid use remained high in those with ITP. These findings underscore the high clinical burden of ITP, highlighting persistent risks of bleeding, TE complications, infections, malignancies, and cognitive impairment and emphasizing the need for improved management strategies.²²

Additional ITP treatment options are needed.³⁵ The primary treatment goals for ITP historically have focused on controlling active bleeding and reducing the risk of future bleeding.¹ However, there is growing recognition of the importance of addressing immune dysfunction as a key component of treatment.^23,35 Response rates to current therapies vary from 18% to 80% based on platelet count improvements, and some treatments may be associated with AEs, complex dosing regimens, or a limited durability.^1,35 These unmet treatment needs may indicate a niche for a therapy that modulates multiple immune pathways.

Implications for Managed Care and Health Policy

Retrospective analyses have shed light on the incidence, health care use, and economic burden of ITP, offering key insights into its impact on patients and the health care system. One retrospective cohort study used 2010 to 2016 data from 2 US private health care claims databases to estimate the incidence, health care use, and costs of newly diagnosed ITP. This study found an annual incidence of ITP to be 6.1 per 100,000 persons. ITP was more common in females (6.7/100,000 persons) than males (5.5 per 100,000 persons) and was highest in neonates, infants, and children aged 0 to 4 years (8.1/100,000 per 100,000) and in adults 65 years or older (13.7/100,000 persons). Patients averaged 0.33 hospitalizations (95% CI, 0.32-0.35) and 15.3 ambulatory visits (95% CI, 15.1-15.6) in the first year, with mean health care costs of $21,290 per patient. Hospitalizations peaked in the 3 months following diagnosis and were twice as frequent in children. While per-patient expenditures for ITP-related hospitalizations were comparable across age groups, the cost of ambulatory care was much lower for the youngest age group (age 0-4 years, $4321) surveyed compared with costs for the oldest age group (age ≥ 65 years, $13,712). New annual cases of ITP were estimated at nearly 20,000 in the United States, with total first-year health care expenditures exceeding $400 million. This study’s reliance on claims data represents a significant limitation, as these data cannot capture undiagnosed cases; they may include individuals misdiagnosed with ITP.³⁶

Another retrospective analysis examined US hospital data from 2006 to 2012 that detailed ITP-related hospitalizations, revealing that there were 296,870 ITP-associated hospitalizations over the study period.³⁷ These hospitalizations were most commonly attributed to coagulation disorders, followed by splenectomy, septicemia, GI hemorrhage, intracranial hemorrhage, and epistaxis.³⁷ The average length of stay for an ITP-related hospitalization was 6 days, which was 28% longer than the national average for hospital stays. The average cost per ITP-related hospitalization, adjusted to 2024 dollars, was $22,428, which was 48% higher than the average US per-hospitalization cost. These findings highlight the substantial health care burden associated with ITP hospitalizations, which may increase as the US population continues to age.³⁷

Persistent Challenges and Inadequate Responses

The management of ITP remains complex due to diagnostic challenges, treatment limitations, and the need for individualized care.Diagnosis requires extensive testing to exclude secondary causes, and the variable clinical presentation of the disease complicates early detection. First-line corticosteroids are effective for some patients but are often limited by AEs and inconsistent long-term responses. Second-line treatments, including TPO-RAs and rituximab, lack standardized selection criteria, and splenectomy is less favored due to potential long-term complications. Significant challenges in treating ITP remain, including disease that is persistent despite multiple lines of therapy, management of bleeding and thrombotic risks, and steroid overuse contributing to fatigue and metabolic issues.¹⁵

Spotlight on BTK Pathway and Emerging Science

BTK, a critical enzyme in the B-cell receptor signaling pathway, is essential for autoantibody production, cytokine release, and cell proliferation.⁹ BTK is involved in maturation of B cells, production of antibodies, and regulation of the innate inflammatory machinery, including NLRP3 inflammasome and FcγR-mediated signaling pathways in macrophages.⁸ These multimodal effects of BTK in immune-mediated diseases make it a key target in ITP.⁸

BTK inhibitors, a class of targeted therapies, bind to BTK, disrupting malignant B-cell growth. These inhibitors have demonstrated efficacy in treating various B-cell malignancies; they are FDA-approved for conditions such as chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström macroglobulinemia. Beyond oncology, BTK inhibitors are being explored to treat autoimmune diseases due to their role in modulating B-cell activity, and next-generation inhibitors with improved selectivity and safety profiles are being developed to improve target specificity and reduce off-target toxicities. Ongoing clinical trials continue to expand the potential applications of BTK inhibitors, shaping the future of both oncologic and immunologic therapies.⁹

Multi-Immune Modulation Through BTK Inhibition: A Therapeutic Strategy in ITP

BTK inhibitors represent a unique pathway for treating ITP, targeting multiple aspects of disease pathophysiology by addressing B-cell activation, macrophage-mediated platelet destruction, and inflammatory cytokine production.¹⁰ BTK regulates proliferation, differentiation, and autoantibody generation in B cells and promotes phagocytosis and inflammatory cytokine release in macrophages.^4,9 Autoreactive B cells impair megakaryocyte maturation, while macrophages facilitate platelet clearance through phagocytosis; both processes are heavily influenced by BTK signaling.^4,5 Persistent cytokine activity leads to pathologic immune activation, contributing to tissue damage, organ dysfunction, and weakened antimicrobial defenses.⁹ Overactivation of inflammasomes—particularly NLRP3—results in excessive release of IL-1β and IL-18, the inflammatory signature of ITP.^8,9 Given that BTK is a key mediator of inflammation that influences TNFα, IL-6, the NLRP3 inflammasome, and IFN-γ production, it represents a potential therapeutic strategy for multi-immune modulation in ITP.^8,9,38,39

Rilzabrutinib

On August 29, 2025, the FDA approved rilzabrutinib for the treatment of adult patients with persistent or chronic ITP who have had an insufficient response to a previous treatment.^12,40 Approval was based on results from the phase 3 LUNA3 trial (NCT04562766), in which patients with ITP who received rilzabrutinib demonstrated a rapid, durable platelet response versus those given placebo.^11,12 The drug demonstrates high specificity for BTK and a rapid on-rate, with more than 80% BTK occupancy occurring within the first hour of dosing.¹¹ Rilzabrutinib occupancy is maintained over 24 hours; its effect is mediated by inhibition of B-cell activation, reduction of pathogenic autoantibody production, disruption of Fcγ-mediated platelet phagocytosis, and suppression of inflammatory pathways.¹¹

LUNA3 was a phase 3, multicenter, international, placebo-controlled, parallel-group study with open-label and long-term extensions. Investigators randomly assigned 202 adult patients with primary ITP at a 2:1 ratio to receive either 400 mg of oral rilzabrutinib twice daily (n = 133) or placebo (n = 69) for the 24-week double-blind period. Patient randomization was stratified by thrombocytopenia severity (platelet count < 15 × 10³/μL or ≥ 15 × 10³/μL) and prior splenectomy. Those with a platelet response (defined as either ≥ 1 platelet count of ≥ 50 × 10³/μL or 30 × 10³/μL to < 50 × 10³/μL and at least a doubling from baseline in the absence of rescue therapy during the first 12 weeks) were allowed to continue double-blinded treatment through week 24 of the trial; nonresponders could either drop out of the study or enter the 28-week open-label period and receive 400 mg of rilzabrutinib twice daily while remaining blinded to their initial treatment.¹¹

The primary efficacy end point of the trial was durable platelet response (defined as platelet counts ≥ 50 × 10³/μL for two-thirds or more of ≥ 8 weekly platelet measurements during the last 12 weeks of the trial without rescue therapy).¹¹ At least 2 of these platelet counts of at least 50 × 10³/μL had to be taken during the final 6 weeks of the 24-week blinded treatment period. Secondary end points included the number of weeks with a platelet count of at least 50 × 10³/μL or at least 30 × 10³/μL to less than 50 × 10³/μL and at least doubled from baseline in the absence of rescue therapy, the number of weeks with a platelet count of at least 30 × 10³/μL and at least doubled from baseline in the absence of rescue therapy, change from baseline at week 13 on the ITP Patient Assessment Questionnaire (ITQ-PAQ) item 10 (a measure of physical fatigue scored from 0 to 100, with higher score indicating better HRQOL) and change from baseline at week 25 in the idiopathic thrombocytopenic purpura bleeding scale (IBLS). The IBLS is scored from 0 (none) to 2 (marked bleeding) based on assessment of 11 sites on the body.¹¹

At baseline, the median patient age was 47 and 46 years in the rilzabrutinib and placebo arms, respectively. The median duration of ITP was 8.1 years in the rilzabrutinib arm and 6.2 years in the placebo arm. A baseline platelet count of less than 15 × 10³/μL was seen in 49% and 46% of the patients in the rilzabrutinib and placebo arms, respectively. Additionally, 43% of patients in the rilzabrutinib arm and 52% of patients in the placebo arm had at least 5 unique prior therapies; in both arms, 28% of patients had prior splenectomy. Furthermore, 40% of patients in the rilzabrutinib arm were treated with rilzabrutinib monotherapy.¹¹

A platelet response in the first 12 weeks of the study was achieved by 85 (64%) and 22 (32%) of patients given rilzabrutinib or placebo, respectively; these patients were eligible to continue the double-blind period.The primary end point of durable response was met in 31 (23%) versus none (0%) of patients who received rilzabrutinib versus placebo, respectively (P < .0001), and it was identical for both durable response definitions used in the study.¹¹

All prespecified secondary efficacy end points were statistically significant for rilzabrutinib versus placebo.¹¹ In the absence of rescue therapy, the least squares mean difference (SE) in number of weeks with a platelet response for rilzabrutinib versus placebo was 6.46 (0.78) (P < .0001). Patients who received rilzabrutinib also demonstrated significant improvements in fatigue (P = .0003) and bleeding (P = .0006) at week 25 as measured by the ITP-PAQ and IBLS. Rilzabrutinib also reduced the need for rescue therapy by 52% compared to placebo (P = .0007).¹¹ Among 73 patients who received rilzabrutinib during the double-blind period and did not achieve a durable response, 7 (10%) achieved a durable response during the open-label period.¹²

Rilzabrutinib had a tolerable safety profile across the treatment and placebo groups, with all-cause any-grade AEs (83% vs 75%, respectively), serious AEs (9% vs 12%), and AEs of grade 3 or higher (11% vs 14%) occurring at similar rates. Most AEs were grade 1 or 2 in both treatment groups. The most common AEs (≥ 10%) were diarrhea (32% vs 10%), nausea (20% vs 6%), headache (18% vs 7%), abdominal pain (14% vs 1%) and COVID-19 (14% vs 4%) in the rilzabrutinib and placebo arms, respectively.¹² A grade 3 serious AE (peripheral embolism; led to treatment discontinuation) and a grade 4 AE (neutropenia lasting 14 days; no change to treatment) were determined to be related to rilzabrutinib treatment.¹¹

Conclusion

ITP is a disorder of complex immune dysregulation characterized by immune-mediated platelet destruction and impaired platelet production. ITP-related fatigue, bleeding, and standard treatment-related AEs negatively impact QOL, affecting the daily activities and emotional well-being of patients. As research advances, novel therapies that include BTK inhibitors are being investigated for their potential to target the underlying immune dysregulation in ITP more directly. Rilzabrutinib is the first FDA-approved oral BTK inhibitor to treat persistent or chronic ITP in adults who have had an insufficient response to a previous treatment. This multitargeted immune modulator is a valuable addition to the armamentarium of ITP treatment.

Authorship Affiliation: Department of Hematology and Medical Oncology, Texas Oncology, Fort Worth Cancer Center (AD), Fort Worth, TX.

Source of Funding: This supplement was supported by Sanofi.

Author Disclosures: Dr Dean reports taking part in consultancies or paid advisory boards for AVEO Pharmaceuticals, Johnson & Johnson, Eli Lilly, Pharmacyclics, and Sanofi. He also reports receiving honoraria from AVEO Pharmaceuticals, Johnson & Johnson, Eli Lilly, Pharmacyclics, and Sanofi as well as lecture fees for speaking at the invitation of AVEO Pharmaceuticals, Johnson & Johnson, Eli Lilly, Pharmacyclics, and Sanofi.

Authorship Information: Acquisition of data; analysis and interpretation of data; supervision.

Address Correspondence To: Asad Dean, MD, 500 South Henderson St, Fort Worth, TX 76104. Email: asad.dean@usoncology.com

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