French Observatory of Adult' Chronic Immune Thrombocytopenia (ITP) Treated By Thrombopoietin Receptor Agonists (TPO-RAs)

Immune Thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated low platelet count (<100x10⁹/L) with a variable risk of bleeding. The prevalence of ITP in France is 25/100000. While drug therapy is indicated in patients with platelet count less than 30x10⁹/L and or with bleeding symptoms, discussions remain about therapeutic strategy to be implemented. The SATURNE study aimed to describe the current therapeutic management of adult ITP patients, to focus on TPO-RAs treated patients, and to assess changes in real life treatment strategy since TPO-RAs’ approval.

This study was carried out in referral and non-referral centersby hematologists and internists from hospitals or clinics in France. Enrolled patients were adults suffering from persistent (3 to 12 months after diagnosis) or chronic (>12 months) ITP. Patients with a newly diagnosed ITP (<3 months) and patients with secondary ITP (viral infection, lupus, etc.) were excluded.

Data were collected online by investigators through an eCRF at inclusion (M0). A subgroup of patients initiating a TPO-RAs treatment during the study period was followed up at M3, M6, M12, M18 and M24. Only M0 data are presented in this abstract as interim analysis.

Overall, 48 investigators included 333 patients (278 with chronic ITP and 55 with persistent ITP) over a 19 months period (2012 to 2013). Figure 1 displays the main characteristics including comorbidities and laboratory tests performed at diagnosis. Half ofthe patients (53%) had bleeding manifestations at ITP diagnosis; 10% at time of inclusion. ITP was mainly diagnosed by a hematologist (53%) or an internist (32%) and less frequently by a general practitioner (11%).

Patients completed a median of 2 treatment lines before entering the study. Figure 2 shows treatment-lines distribution according to the ITP phase. Most patients had been treated with corticosteroids ± intravenous immunoglobulin (IVIG) (83%) as 1^st line treatment. Rituximab was the preferred 2^nd line option, far prior to splenectomy (44% vs 14%).

A total of 144 patients (123 chronic/ 21 persistent ITP) received TPO-RAs (39% romiplostim/ 33% eltrombopag / 15% both / 13% non specified): 6%, 20%, 34%, 28% and 12% respectively as a 1^st line treatment, 2^nd, 3^rd, 4^th, 5^th and beyond. At inclusion 75% were still on TPO-RAs. Recently diagnosed patients received 2^nd line TPO-RAs in higher proportions: 40% (of 46 patients diagnosed <2 years) vs 15% (of 65 patients diagnosed 2-5 yrs ago) and 7% (of 72 patients diagnosed >5 yrs). TPO-RAs became the 3^rd line most used treatment (over 76% for diag. <2 yrs). In parallel, the use of splenectomy decreased from 31% (diag. >5 yrs) to 9% (<2 yrs) in 2^nd line, and from 16% to 5% in 3^rd line. TPO-RAs treated patients had a more severe ITP, in particular at diagnosis. More patients in this group showed platelet counts less than 30.10⁹/L (71% vs 51%, p<0.0001 at diagnosis / 23% vs 10%,p<0.001 at inclusion), and bleeding manifestations (64% vs 44%, p<0.001 at diagnosis / 12% vs 8%,p=0.24 at inclusion). They received an average of 3.2 lines of treatment (against 1.7 in TPO-RAs’ non-treated patients, p<0.0001).

The SATURNE study supports epidemiological trends observed in current practice in terms of patients and ITP characteristics, and provides current data on comorbidities.

The results highlight the increasing use of TPO-RAs as 2^nd and 3^rdlines for ITP treatment and the decrease of splenectomy use over time. Initiated in 2012, respectively 1 and 2 years after eltrombopag and romiplostim approval, the SATURNE study points out the changes of the management of adult ITP in France.

 

FIGURE 1	N= 333
Age	57 ± 20yr
Women	190 (57%)
Main ITP characteristics
Chronic /Persistent ITP	278 (84%)/55 (16%)
Mean ITP duration*	6 ±8yr
Platelet count* - diagnosis - inclusion	33±31.109/L 100±83.109/L
Hemorrhagic manifestations - diagnosis - baseline	176 (53%) 32 (10%)
White blood cell*	8±3.109/L
Hemoglobin*	14±5g/dl
Globular volume*	90±6fl
Comorbidities since ITP diagnosis
At least once	36%
Hypertension	17%
Diabetes	8%
Benign/malignant tumors	8%
Cardiovascular disease	6%
Diagnostic tests performed at ITP onset
Viral serology tests	96%
Blood smear	93%
Blood coagulation	93%
Marrow aspirate	78%
Antiplatelet antibody	52%
ITP treatment (at least once since diagnosis all lines combined)
Corticosteroids and/or IVIG	275  (83%)
Rituximab	146 (44%)
TPO-RAs - eltrombopag - and/or romiplostim	144 (43%) 69 (48%) 78 (54%)
Splenectomy	59 (18%)
*mean ± SD