Clinical Burden of Illness in Patients with Persistent or Chronic Primary Immune Thrombocytopenia Treated with Advanced Therapies in the United States

Background Primary immune thrombocytopenia (ITP), an autoimmune disorder characterized by thrombocytopenia that increases the risk of bleeding, and thromboembolic events (TEs), and poor quality of life (including significant fatigue), has a debilitating impact on patients' health. Patients with persistent or chronic primary ITP (disease duration 3−12 or >12 months, resp.) who fail to respond, relapse, or are ineligible to receive corticosteroids, IVIg, or anti-D are treated with advanced therapies (thrombopoietin receptor agonists [TPO-RAs], rituximab, and fostamatinib). This study assesses the incremental clinical burden of illness in patients with ITP. Aim To evaluate the clinical burden of disease among persistent or chronic primary ITP patients treated with advanced therapies vs non-ITP population. Methods This observational retrospective cohort study included ITP patients matched (1:5; on age, gender, race, ethnicity, and year of cohort entry) to non-ITP population identified via Optum's de-identified Clinformatics® Data Mart Database of ~90 million insured users. Patients ≥18 years with primary ITP lasting ≥3 months, initiating advanced therapies (index) between October 1, 2016, and April 4, 2022, were included; those with potential secondary ITP were excluded. Baseline characteristics assessed 365 days prior to index were reported using descriptive statistics. Clinical events (bleeding, TEs, infections, etc.) were assessed during follow-up, which began one-day after index and until end of data, enrollment, or death. Event rates per 1000 person-years (PY) and rate ratios (RR) were estimated using Poisson regression and the hazard ratio (HR) of death using Cox models. Bleeding, TE, and mortality models were adjusted for potential confounders. Patients with chronic ITP were described as subgroup. Results In total, 1140 primary ITP patients and 5657 non-ITP subjects were included. Among ITP cohort, mean (SD) age was 64 (18) years, 50% were female, 70% White, 63% were insured by Medicare Advantage; 60% (n=690) had chronic primary ITP, with 60.7% (n=692) initiating TPO-RAs, 38.4% (n=438) rituximab, and 1.3% (n=15) fostamatinib on index. At baseline, ITP cohort had higher prevalence of solid tumors (15.4% vs 6.3%), infections (14.1% vs 2.7%), and TEs (18.1% vs 5.5%) vs non-ITP cohort. Cardiovascular risk factors were more common in ITP cohort, ie smoking (31.6% vs 14.5%), obesity (26.8% vs 12.8%), diabetes (30.2% vs 14.3%), hypertension (65.4% vs 48.2%), coronary artery disease (25.2% vs 13.9%), and cerebrovascular disease (7.5% vs 2.6%). Higher rates of mental health issues (anxiety [19.7% vs 11.9%] and depression [17.7% vs 10.9%]) were observed in ITP cohort. Oral steroid use was greater in ITP cohort vs non-ITP cohort (62% vs 13%; annual cumulative dose [ACD]: 2900 mg vs 413 mg of prednisone equivalents). During average follow-up of 2.3 (ITP) and 2.6 years (non-ITP), the ITP cohort differed greatly from non-ITP cohort in following outcomes: bleed-related hospitalization (15.2% vs 4.5%), with rates of 103 vs 22 per 1000 PY (crude RR (cRR) [95% CI]: 4.71 [4.00−5.55]; adjusted RR (aRR): 4.15 [3.51−4.91]), TEs (20.3% vs 9.1%) with rates of 216 vs 79 per 1000 PY (cRRs: 3.98 [3.41−4.65] for venous events, 2.09 [1.78−2.47] for CNS arterial events, and 2.20 [1.73−2.80] for non-CNS arterial events; aRRs: 1.73 [1.44−2.08], 1.23 [1.03−1.46], and 1.47 [1.14−1.89], resp.). Oral steroid use was higher in ITP cohort (41% vs 14%; ACD 1791 mg vs 474 mg). ITP cohort had higher cRRs of developing new malignancies 1.57 [1.21−2.04], cognitive impairment 1.65 [1.26−2.18], autoimmune conditions 4.94 [3.32−7.34], and infections 3.14 [2.61−3.78]. Deaths were observed in 21% ITP vs 10% non-ITP cohort with mortality rate of 93 vs 38 per 1000 PY. After adjusting for potential confounders, HR (95%CI) for death was: 1.45 (1.23−1.71) [crude HR: 2.44 (2.10−2.84)]. The findings were similar for patients with chronic ITP. Conclusion Patients with primary ITP have more comorbidities and continue to experience bleeding events requiring hospitalization and have high steroid use despite being on advanced therapies. Rates of TEs, infections, and mortality were significantly higher in ITP patients vs matched non-ITP population. Malignancies, autoimmune conditions, and cognitive impairment occur more frequently in ITP patients. These results highlight the increased clinical burden and unmet needs in ITP patients.