Final results from an observational study (plateau) of adult patients treated with romiplostim for primary immune thrombocytopenia (ITP) in routine clinical practice in Germany

Background: In the European Union, the thrombopoietin-receptor agonist romiplostim (NplateR) is recommended since January 2016 for treatment of ITP in adult patients who are refractory to other treatments (e.g. corticoids, immunoglobulins). Aims: The aim of this study was to assess the use of romiplostim in clinical practice in Germany. Methods: This multicentre, prospective and retrospective observational study (data collected before and after initiation of romiplostim) enrolled ITP patients ≥18 years who received at least one dose of romiplostim in routine clinical practice, with an observation period of 2 years following romiplostim initiation. Endpoints included patient demographics, romiplostim use, platelet counts, adverse drug reactions (ADRs), and other clinically relevant parameters. We report results from a full data set analysis. Results: A total of 59 patients were enrolled (49.4% male; 54% aged 65 years or above) from 38 sites; 22 of them were excluded due to protocol violations (e.g. incomplete documentation, inclusion criteria not met). Of the 137 remaining patients (the full analysis set, FAS), 102 completed the 2-year observation period. Reasons for dropping out included loss to follow-up (10 patients), deaths (6 patients) and ADRs (3 patients). Median (Q1, Q3) time from ITP diagnosis to romiplostim initiation was 21.7 months (4-85) months in the FAS. 123 FAS patients received prior ITP therapies; most of them received corticosteroids (104 [75.9%]). 117 patients (85.4%) were non-splenectomized before romiplostim therapy, for reasons such as refusal of splenectomy, comorbidities, or age. Over the observation period, romiplostim was injected at a median (Q1, Q3) dose of 3.11 mcg/kg/bw (1.8 - 4.8; FAS) over a median (Q1-Q3) treatment period of 103 weeks (33-104). The median platelet count rose sharply from baseline (29.0 × 109/L) to two weeks of treatment (62.5 × 109/L). From week 3 to two years of follow-up, the median count remained in a range between 87.5 × 109/L and 145.5 × 109/L. Since the start of romiplostim therapy, 59 patients out of 137 (43.1%) received concomitant therapies, mostly corticosteroids (49 patients [35.8%]). The overall number of ADRs was 112 in the FAS, affecting 37 patients (27.0%). The most frequent ADRs were gastrointestinal (10.2%) and neurological (11.7%) ADRs, followed by constitutional symptoms (10.9%). Adverse drug reactions pertaining to blood/bone marrow affected 2.9% of patients (vascular/thrombotic events, bone marrow fibrosis), whereas bleeding as an ADR was seen in 0.7% of patients. The exposure-adjusted rate of bleeding events (grade 3 or 4) per 100 patient-years in the FAS was 7.2 before treatment initiation vs. 4.0 after starting the treatment. The rate of ITP-related hospitalization per 100 patient-years decreased from 23.3 before the start of therapy to 15.5 since the start of therapy. Summary/Conclusions: This study of routine clinical practice in Germany showed that treatment with romiplostim in ITP patients resulted in a rapid increase in platelet counts to levels maintained between 50 and 250 × 109/L over time, regardless of the splenectomy status of the patients; most of them were non-splenectomized. The product was well tolerated and achieved a decrease in the rate of ITP-related hospitalization.