AbstractAdolescents and young adults (AYAs) with immune thrombocytopenia (ITP) exhibit distinct clinical features and needs, defying categorization as either adults or children. Previous findings revealed a 50% risk of chronic disease at 12 months, yet the long-term course remains unclear. This study aimed to delineate the clinical and laboratory characteristics of AYAs with chronic primary ITP. Data from patients aged 12 to 25 years with chronic disease at 1 year were extracted from 3 registries (Pediatric and Adult Registry on Chronic ITP, CEREVANCE, and Cytopénies Auto-immunes Registre Midi-Pyrénéen), covering the period from 2004 to 2021. Sustained complete remission off treatment (SCROT) occurring beyond 12 months was defined as platelet count of >100 × 109/L without treatment for at least 12 months, independently of the previous treatment strategy. A total of 427 AYAs (64% female) with chronic primary ITP were included. Clinical information was available for ∼100% of patients at initial diagnosis and at 6- and 12-month follow-ups (FUs); and for 88%, 77%, and 59% at 24, 36, and 48 months, respectively. Over time, clinical features improved gradually, with fewer patients requiring treatment. Throughout the FU period, second-line drug use increased steadily among treated patients, without affecting the need for corticosteroids and IV immunoglobulins. The proportion of new patients achieving SCROT at 24-, 36-, and 48-month FU was 10% (38/375), 9.5% (31/327), and 12% (30/250), respectively, including 23 who underwent splenectomy. AYAs achieving SCROT between 12 and 36 months displayed higher platelet counts in the first year (excluding the initial period) and received fewer IV immunoglobulin treatments beyond 12 months compared with those with ongoing disease.