Predictors of Response to Emergent Therapies in Pediatric Immune Thrombocytopenia

Introduction: Immune Thrombocytopenia (ITP) is the most common acquired bleeding disorder that affects children. It is associated with a wide spectrum of bleeding symptoms as well as reductions in health-related quality of life (HRQoL). Treatment is guided by the severity of bleeding and the impact on HRQoL, and can generally be divided into 2 groups: emergent therapies and disease-modifying therapies. Emergent therapies are those used to rapidly increase the platelet count in moments of acute bleeding and include intravenous immunoglobulin (IVIG), corticosteroids and intravenous anti-Rho(D) immunoglobulin (Rho-D). Despite the increase in available treatment options, there are still children with ITP that does not respond to multiple therapies. These children represent a challenging group with worse clinical outcomes and have often been referred to as patients with “refractory ITP.” Unfortunately, there are currently no clearly established clinical markers to help predict whether a patient will respond to a specific medication. Thus, treatment of ITP is largely trial and error, exposing patients to potentially ineffective medications which are often expensive and associated with unwanted adverse effects. Through comprehensive characterization of clinical features of pediatric patients with ITP and their response to treatment, we aimed to identify clinical predictors of treatment response to emergent therapies.

Methods: We retrospectively identified patients 0-21 years old receiving care at a single tertiary care pediatric referral center (Texas Children's Cancer and Hematology Center) who were diagnosed with ITP between January 1^st 2020 and December 31^st 2022. Response to each treatment was determined per the International Working Group 2008 Consensus definitions, considering response the attainment of a platelet count equal or greater than 30 x10⁹/L with at least 2-fold increase from baseline count and absence of bleeding. Descriptive statistics were used to summarize patient characteristics and analyses were performed using STATA 18.0.

Results: Among the 264 patients diagnosed with ITP from 2020 - 2022, 51% were female, 55% had Hispanic ethnicity, 81% were white, median age at diagnosis was 5.77 years, 87% had primary ITP, and 27% had chronic ITP. Among those with secondary ITP, the most common underlying etiology was systemic lupus erythematosus (SLE). Within the cohort, 166 (63%) were treated with at least one emergent therapy: 146 received IVIG (of which 29% had no response), 81 received corticosteroids (of which 25% had no response) and 4 received Rho-D (of which 50% had no response). Of patients treated, 15% had no response (NR) to all therapies received but only 2% had NR to all therapies available. When comparing patients with response (R) to IVIG vs. those with NR to IVIG, there was a higher percentage of patients with a positive direct antiglobulin test (DAT) in those that had NR to IVIG. There was also a higher percentage of patients with comorbid autoimmune, rheumatologic or allergic (CARA) conditions (particularly SLE) in patients with NR to IVIG compared to those with R to IVIG. Patients with secondary ITP were more likely to have NR to IVIG than patients with primary ITP (p = 0.016). There was no significant difference between median age at diagnosis of ITP or female gender in patients with NR to IVIG and those with R to IVIG.

Conclusions: In this cohort, we identified high rates of NR to emergent therapies used in pediatric patients with ITP, with as many as 15% having NR to all the medications received, most commonly IVIG and/or corticosteroids. In comparing clinical characteristics of those who did and did not respond to IVIG, we identified the presence of CARA conditions (especially lupus), secondary ITP, and a positive DAT at diagnosis, as possible predictors of NR to IVIG. In the future, we aim to expand our study cohort to identify predictors associated with NR to additional therapies, including disease-modifying therapies.

Kirk:Biomarin: Honoraria; Sobi: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; X4: Honoraria. Grimes:Novartis: Research Funding.