Multirefractory Primary Immune Thrombocytopenia in Adults: Prevalence and Burden. Results from the Carmen-France Registry

Introduction: Multirefractory primary immune thrombocytopenia (ITP) is a rare but challenging disease. There is no standard definition of multirefractory ITP, however it is usually defined by the need of several lines of treatments, including thrombopoietin receptor agonists (TPO-RAs). However, the prevalence of multirefractory patients is not known. Data about the clinical burden of these patients are scarce and stem from historical retrospective series. The aim of this study was to assess the prevalence of multirefractory ITP among adults with primary ITP and the burden of these patients in terms of bleeding, infection, thrombosis and hospital contact.

Methods: The data source was the CARMEN-France registry. The CARMEN (Cytopénies Auto-immunes : Registre Midi-PyréneEN) registry is aimed at the prospective, real-world follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013, and has been implemented in other centers of the French Autoimmune cytopenia referral center network since 2016, taking the name of CARMEN-France. Inclusion criteria are adult patients (aged ≥18 years) newly diagnosed with ITP (platelet count <100 x 10⁹/L and exclusion of other causes of thrombocytopenia). The study population was selected in the CARMEN-France registry up to December 2021. Two definitions of multirefractory ITP were used: the need of ITP treatment after exposure to both TPO-RAs marketed in France, eltrombopag and romiplostim (definition 1) and the need of ITP treatment after exposure to eltrombopag, romiplostim and rituximab (definition 2). We assessed the prevalence of multirefractory ITP among all adult patients with primary ITP included in the registry, and the frequency of bleeding, infection, venous thrombosis, arterial thrombosis and hospital contact due to ITP during the follow-up.

Results: Out of 1080 adult patients with incident primary ITP included in the registry during the study period, 845 (78.2%) were treated for ITP, and 448 (41.5%) with a second-line treatment. Multirefractory ITP accounted for 32 (3.0%) patients according to definition 1, and for 24 (2.2%) patients according to definition 2. At ITP diagnosis, median age was 62.5 years (min-max: 25-90) and 66.5 years (min-max: 30-90) respectively; 18 (56.3%) and 12 (50.0%) were men; the median platelet count at ITP diagnosis was 6.0 x 10⁹/L and 6.5 x 10⁹/L; 29 (90.6%) and 21 (87.5%) had bleeding at ITP diagnosis, respectively. With a median follow-up of 30.3 months (min-max: 3.2-93.1), all patients with multirefractory primary ITP according to definition 1 had experienced bleeding, 8 (25.0%) an infection, 3 (9.4%) a venous thrombosis and 1 (3.1%) an arterial thrombosis. The median number of hospital stays for ITP was 6.5 (min-max: 1-17), the median number of outpatient hospital contacts was 9 (min-max: 3-30) with a median cumulative duration of hospital stays for ITP of 32 days (min-max: 6-142). With a median follow-up of 30.3 months (min-max: 6.4-93.1), all patients with multirefractory primary ITP according to definition 2 had experienced bleeding, 7 (29.2%) an infection, 2 (8.3%) a venous thrombosis and 1 (4.2%) an arterial thrombosis. The median number of hospital stays for ITP was 7 (min-max: 2-17), the median number of outpatient hospital contacts was 10 (min-max: 4-30) with a median cumulative duration of hospital stays for ITP of 32 days (min-max: 10-142).

Conclusion: The prevalence of multirefractory ITP among adult patients with primary ITP is low (<5%) despite dynamic inclusions in the registry that may result in a slight underestimation of cases due to a short follow-up in some patients. However, this population has a heavy clinical burden.

Moulis:Sobi: Other: Board; Novartis: Other: Boards, speaker at educational sessions, Research Funding; Grifols: Other: Boards, speaker at educational sessions, Research Funding; Argenx: Other: Board; Amgen: Other: Boards, speaker at educational sessions. Viallard:Amgen: Other: Boards, speaker at educational sessions; Grifols: Other: Boards, speaker at educational sessions; Novartis: Other: Boards, speaker at educational sessions. Comont:Novartis: Other: Boards, speaker at educational sessions; Takeda: Other: Boards, speaker at educational sessions; Celgene: Other: Boards, speaker at educational sessions; AstraZeneca: Other: Boards, speaker at educational sessions; AbbVie: Other: Boards, speaker at educational sessions. Chèze:Bioverativ: Research Funding; Novartis: Research Funding; Protalex: Research Funding; Novartis: Other: Board; Sobi: Other: Board. Audia:grifols: Other: Speaker at educational sessions. Ebbo:Amgen: Other: Speaker at educational sessions; Grifols: Other: Boards, speaker at educational sessions; Novartis: Other: Boards, speaker at educational sessions. Terriou:Amgen: Other: Board; Grifols: Other: Board; Novartis: Other: Board. Bonnotte:Novartis: Other: Speaker at educational session. Michel:argenx: Other: Boards, speaker at educational sessions; Novartis: Other: Boards, speaker at educational sessions; UCB: Other: Boards, speaker at educational sessions; Sobi: Other: Boards, speaker at educational sessions; Amgen: Other: Boards, speaker at educational sessions. Godeau:Amgen: Other: Boards, speaker at educational sessions; Grifols: Other: Boards, speaker at educational sessions; Novartis: Other: Boards, speaker at educational sessions; Sobi: Other: Boards, speaker at educational sessions.

Some drugs (romiplostim, eltrombopag) may have been used off-label because this was a real world study. However, this study does not describe it.