Clinical and economic burden of steroids in primary immune thrombocytopenia: A real-world italian analysis

Abstract Introduction: Primary Immune Thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count and increased bleeding risk. Corticosteroids (CS) are the recommended first-line treatment since the 1950s. Lately, subsequent therapies, including thrombopoietin receptor agonists, rituximab, and fostamatinib, have expanded the range of available options even in the early phases of disease. Around 75% of adult patients respond to CS, but only 20-40% achieve sustained response upon discontinuation. Current guidelines discourage prolonged CS therapy due to the associated CS-related events (CSEs). This real-world analysis investigates the association between different CS dosing regimens and the related chronic and acute CSEs and healthcare costs of ITP in Italy.Methods: During the inclusion period (Jan 2018-Jul 2024), ITP patients were identified through administrative databases of Italian Local Health Units, covering around 12 million health-assisted subjects. ITP cases were detected through disease-specific exemption, hospitalization, or prescription codes, and were included if at least 12 months of characterization and follow-up data were available. The included population was described at baseline for demographic and comorbidity characteristics and stratified into 4 cohorts based on the CS treatment patterns. CS therapies were categorized using two parameters: (1) average prednisolone-equivalent daily dose, with a cutoff of ≤10 mg to distinguish low-dose (LD) and high dose (HD) treatment; and (2) treatment intensity, measured by the medication possession ratio (MPR), with a threshold of 80% to define high vs low intensity (HI vs LI). MPR was calculated as the sum of the days with steroid supply divided by the 365-day observation period. CSEs, identified through diagnosis, exemption code, and treatments, were categorized as either acute or chronic: acute events were recorded during the first year after CS initiation, while chronic events were assessed during the entire follow-up period. The healthcare burden was evaluated as the total annual cost per patient. A generalized linear model (GLM) adjusted for confounding variables was used to estimate the association of CS use with costs. Results: A total of 1,993 adult ITP patients were identified (43% male; 57 [±19.5] years mean age; mean Charlson Comorbidity Index=0.7 [±1.3]). Among incident patients (N=1,643), 74% (N=1,214) received a first line of treatment with CS (N=1,214), and only 37% of the CS-treated patients had treatment cycles shorter than 3 months. The average prednisolone-equivalent daily dose in the first 12 months was 8.4 mg, 60% had an MPR ≥80%, and 67% received a CS monotherapy. The incidence rates of pooled acute and chronic CSEs were 431.4 per 1,000 person-years (PY; 95% confidence interval [CI]: 402.4-462.6) and 210.3 per 1,000 PY (95% CI: 193.6-228.6), respectively. Infectious diseases were the most frequent CSEs, occurring at a rate of 420.6 per 1,000 PY (95% CI: 392.2-451.1). Cardiovascular disorders were the most common chronic CSEs, with an incidence rate of 138.6 per 1,000 PY (95% CI: 125.9-152.6). Patients on HD/HI CS therapy showed a significantly higher risk of chronic CSEs (adjusted hazard ratio [HR]: 1.51, 95% CI: 1.18-1.92) compared to those in the LD/LI group. In contrast, no statistically significant association was observed between CS dose/intensity and acute CSEs (HR:1.15, 95% CI: 0.94-1.41). The overall healthcare burden was significantly higher for the HD/HI group compared to the LD/LI cohort. The total annual cost per patient was €11,397 vs €8,112 in the HD/HI and LD/LI groups, respectively, with an adjusted cost difference of €1,876 (GLM analysis; 95% CI: 299-3,452).Conclusions: This analysis of the ITP population in real-world clinical practice in Italy revealed an association of CS treatment patterns with both the risk of chronic CSEs and healthcare costs. HD/HI steroid therapy resulted in a significantly increased risk of chronic CSEs and a higher healthcare burden compared to the LD/LI therapy. These findings underscore the limitations of prolonged or intensive CS use in the management of ITP. CS therapy, while effective for initial disease control, should be carefully monitored and discontinued when clinically appropriate, as recommended by current guidelines. Transitioning to second-line agents should be preferred to minimize complications and reduce the overall economic burden.