Retrospective, Observational, Multicenter Study Assessing the Thrombopoietin Receptor Agonist (TPO-RA) Romiplostim and Other Treatments for Patients with Newly Diagnosed or Persistent Primary Immune Thrombocytopenia (ITP) in Routine Clinical Practice in the United Kingdom (UK)

Background: The clinical course of ITP can be categorized into three phases: newly diagnosed (<3 months post-diagnosis), persistent (≥3-≤12 months) or chronic (>12 months). Romiplostim (a TPO-RA) is now approved in the USA and Europe for use across all phases of ITP in adults refractory to 1st line treatments. This extended indication is aligned with treatment guidelines, which recommend TPO-RAs at earlier stages to help patients avoid adverse events associated with prolonged steroid use (>8 weeks) (Neunert et al. Blood Adv 2019; Provan et al. Blood Adv 2019). To guide future recommendations and improve patient outcomes, further real-world data on romiplostim use in the earlier phases of ITP are warranted.

Methods: A retrospective, observational, UK wide multicenter study of real-world treatment patterns in adult patients diagnosed with newly diagnosed or persistent primary ITP between 2 July 2015-23 March 2020 was undertaken. The study population was divided into two patient groups depending on what treatments they received during the 1st year from ITP diagnosis - Group 1: received romiplostim; Group 2: received other ITP treatments (excluding TPO-RAs). TPO-RAs, including eltrombopag, could be received in either group post 12 months. Patients in either group were able to receive the following therapies throughout the observation period: azathioprine, cyclosporine, danazol, dexamethasone, IVIg, methylprednisolone, mycophenolate (MMF), prednisolone, and/or rituximab. Exclusion criteria were: clinical trial participation in the observation period and eltrombopag within 12 months of ITP diagnosis. At baseline, data were collected on patient demographics and clinical characteristics. For the 24-month period following ITP diagnosis (observation period), data were collected on prescribed ITP treatments, platelet counts, rescue therapies, bleeding episodes and hospitalizations. All analyses were descriptive.

Results: Overall, 78 patients were enrolled at 7 sites in the UK (Group 1: n=14; Group 2: n=64). Baseline demographics are shown in the Table. In Group 1, romiplostim was initiated at a median of 7 weeks from diagnosis and was continuing in 57% of patients (8/14) at the end of the 24-month observation period. Two patients (14%) discontinued romiplostim before 24 months as treatment-free remission was achieved (defined by investigator). The median duration of romiplostim was 46 weeks. The Table summarizes non-TPO-RA treatments received in both groups. The median duration of prednisolone was shorter for Group 1 vs 2 (3 vs 10 weeks for patients who discontinued prednisolone). A similar trend was seen for MMF (18 vs 54 weeks). During the 2nd year of observation, 4 patients in Group 2 received eltrombopag (none in Group 1) and 1 received romiplostim.

At ITP diagnosis (i.e. baseline), the median platelet counts were 4 and 8 ×10⁹/L in Groups 1 and 2, respectively. By the end of the 24-month treatment period, the median (interquartile range [IQR]) platelet counts had increased to 192 (81-279) and 121 (80-196) ×10⁹/L in Groups 1 and 2, respectively. During the observation period in Groups 1 and 2, respectively, bleeding episodes occurred in 50% and 63% of patients, rescue therapies were required by 36% and 31%, and hospitalizations in 50% and 46% (81% and 60% were day cases, the rest inpatient stays). The mean number of rescue therapies/patient was 0.7 and 0.6 in Group 1 and 2, respectively. Thromboembolic events occurred in 1 patient in each group (Group 1: sub-acute left lower limb arterial ischemia; Group 2: stroke).

Conclusion: In this real-world observational study, median platelet counts increased to 192×10⁹/L after 24 months of observation in patients receiving romiplostim in the 1st 12 months of ITP diagnosis. Over the same period, patients receiving other treatments in the 1st year of ITP diagnosis had median platelet counts of 121×10⁹/L. For patients who discontinued prednisolone, the duration of this steroid was 3 vs 10 weeks in those who received romiplostim in the 1^st year vs those who did not. At the time of study data collection, romiplostim was not approved in the UK for use in patients with ITP <1 year from diagnosis. In accordance with treatment guidelines, these findings support further exploring the earlier use of romiplostim for adult patients with primary ITP, including the possibility of reducing prolonged exposure to steroids such as prednisolone.

McDonald:Abbvie: Consultancy, Speakers Bureau; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel to conferences, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Grifols: Research Funding; argenx: Other: travel to conferences; Rigel: Research Funding. Bradbury:BMS Pfizer: Honoraria, Speakers Bureau; Bayer: Honoraria, Other: travel to conferences, Speakers Bureau; Amgen: Honoraria, Other: travel to conferences, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Lilly: Consultancy, Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Portola: Consultancy; Ablynx: Consultancy. Lowe:Novartis: Honoraria; Leo: Honoraria; Sobi: Honoraria; Alexion: Honoraria; Takeda: Honoraria; NovoNordisk: Honoraria; Sanofi: Honoraria. Pavord:SOBI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Andiappan:Amgen: Research Funding. Sandschafer:Amgen Inc.: Current Employment, Current equity holder in publicly-traded company. De Sousa Barbosa:Amgen Inc.: Current Employment, Current equity holder in private company. Stephens:Amgen Ltd: Current Employment, Current equity holder in private company. Cooper:Sanofi, Principia, Novartis, Griffols, Sobi, Argenyx, UCB, Rigel: Consultancy, Honoraria, Research Funding.