Ps1580 prevalence and Risk Factors for Thrombosis in Adult Itp Patients Treated With Tpo‐ra

Abstract

Background:Thrombopoietin‐receptor‐agonists (TPO‐RA) are effective treatments of immune thrombocytopenia (ITP). Previous long‐term TPO‐RA clinical trials have shown that thrombotic events occurred in 6% of TPO‐RA‐treated ITP patients, with thrombotic events appearing to be more frequent in patients of older age and having at least 1 general risk factor for thrombosis.Aims:To evaluate the prevalence of venous and arterial thrombosis in patients with primary ITP during treatment with TPO‐RA.Methods:Multicenter retrospective study that included 121 adult primary ITP patients from 19 secondary and tertiary Spanish hospitals who had initiated treatment with Romiplostim (ROM) or Eltrombopag (ELT) as long‐term therapy between January 2012 and December 2014. Information on patient characteristics was collected from medical records to assess and compare risk factors of ITP patients with and without vascular events (VE).Results:A total of 121 patients (median age 63 years, range 19–96 years; 68% chronic phase), initiated TPO‐RA (ROM 54; EPG 67). During a 329.3 patient‐year time under treatment (exposure to ROM and ELT of 161.03 and 168.27 patient‐year, respectively) 15 patients experienced 17 vascular episodes (9 arterial, 8 venous). One patient presented antiphospholipid antibodies, five had been diagnosed with neoplasia, one with vascular peripheral disease, two with hypothyroidism –one of whom also had renal disease‐. Seven events occurred with ROM, and 10 with ELT. The annualized risk was 4.2 and 5.9 VE/100 patient‐years in ROM and ELT treated patients, respectively (median 5.2). Most VE occurred in the first year of TPO‐RA therapy (median 276 days; 5–1183), with a trend toward earlier events under ROM than ELT (127 days vs 360 days, respectively; p = 0.070). In the case of ischemic events the median time to arterial events was 165 vs. 606 days in ROM and ELT treated patients; P = 0.029. There were no significant differences in the 15 patients vs. the 106 patients that did not suffer from vascular events in terms of gender, age, diabetes, hypertension, previous vascular events, nor time on prednisone as 1st line therapy. In patients experiencing VE on TPO‐RA, a significant association with previous splenectomy (53.3% vs. 25.5%, P = 0.026), and chronic phase of the disease (93.3% vs. 64.1%, P = 0.024) compared with those not having such characteristic was detected. Surprisingly previous malignancy significantly associated with VE under TPO‐RA treatment (33% vs. 2.8%, P = 0.000009). All patients were reported to have sustained complete remission of previous neoplasias (1 colon carcinoma; 1 Burkitt lymphoma; 1 bladder cancer; 1 breast cancer; 1 patient with history of thyroid, breast and ovarian tumors) and were not receiving antineoplastic therapies. In multivariate analysis with logistic regression only previous malignancy predicted significantly higher odds of VE (Table 1).Summary/Conclusion:In this study, we describe an annualized risk of 5.2 vascular events/100 patient‐years in TPO‐RA treated patients. Venous and arterial thromboembolism are not frequent complications in ITP patients under TPO‐RA, except in particular settings, such as in splenectomized and chronic patients. Our data revealed a novel association of history of previous neoplasia with thrombotic events in patients with TPO‐RA. These results suggest that a history of prior cancer should be systematically screened before TPO‐RA initiation, and if so, alternative therapy should be considered; however, due to the limited sample size, further research is warranted.image