Disease Progression, Treatment Effectiveness, and Co-Morbid Burden Among Adult Patients with Primary Immune Thrombocytopenia (ITP): Results From the United Kingdom Registry.
Authors: Sarpatwari Ameet , Bennett Dimitri , Newland Adrian , Sanderson Simon , Provan Drew 
Published: October 2019

Abstract
Abstract 4457

Introduction
Primary immune thrombocytopenia (ITP) is an autoimmune disease resulting from elevated reticuloendothelial destruction and decreased megakaryocytic production of platelets. The epidemiology of the disease remains inadequately described as frequencies of relapse, bleeding events, and co-morbid conditions among adult patients with primary ITP have been seldom investigated and limited long-term data are available.

Objectives
To document disease progression via longitudinal platelet counts and bleeding events, to evaluate treatment patterns and effectiveness, and to measure the pre- and post-diagnosis prevalence and incidence of co-morbid conditions (N=25) in a disease cohort representative of the general population of patients with primary ITP in the United Kingdom. For this report, we detail baseline demographics, prevalence of wet bleeding at presentation, and initial treatment modality utilized and subsequent response for patients whose hospital medical records have been extracted.

Methodology
We established a Registry of adult patients (≥ 16 years) diagnosed with primary ITP (N=790) as defined by 2003 British Committee for Standards in Haematology (BCSH) guidelines. Participants include patients having visited the hematology clinic at The Royal London Hospital (RLH) between 1998 and 2005, having been submitted for enrolment by collaborating hematologists throughout the United Kingdom between 2002 and 2005, and having joined the Registry following its re-launch in May 2008. In addition to undergoing a retrospective evaluation upon enrolment via hospital medical record extraction, participants are encouraged to volunteer whole blood (15 ML, ∼EDTA) or saliva (Qiagen® kit) for DNA extraction and will be prospectively assessed at annual intervals until study closure in 2017.
Time intervals for periods comprising presentation and therapeutic response windows were left to the discretion of the collaborating investigator. For RLH-extracted records, the International Working Group-endorsed definition of complete response (CR) and times to peak response were adopted (Rodeghiero et al., Blood 2008).[1][2] A watch and wait strategy was defined as an absence of ITP-specific therapy during the one month period following diagnosis.

Results
In total, 308 (39.0%) Registry participants across 32 centers were evaluated. A 2.1:1 female to male ratio was observed. Median age and platelet count at presentation were 47.0 years (range: 16.0-94.0 years) and 19×109/L (range: 0-144×109/L) respectively. While platelet counts at presentation were similar between women (median: 20×109/L [range: 0-144×109/L]) and men (median: 14×109/L [range: 0-136×109/L]), presenting females were on average younger (43.6 ± 17.9 v. 51.5 ± 18.5 years; p < 0.001). Wet bleeding was experienced by 120 (38.8% [95% CI: 33.4-44.2%) patients at presentation and did not differ significantly between women (40.0% [95% CI: 33.4-46.6%]) and men (36.4% [95% CI: 26.9-45.9%]).
Among first-line treatment modalities, prednisolone (N=172 [55.7%]) and watch and wait (N=92 [31.7%]) ranked first and second respectively. Combination therapy was utilized (N=24 [7.8%]), with dual prednisolone/IVIg administration featuring foremost (N=15 [4.8%]). Notably, 40 of 154 evaluable (26.0% [95% CI: 19.4% - 32.9%]) patients initially treated with prednisolone alone failed to achieve a CR (defined as a count > 100×109/L).

Conclusion
In this large and comprehensive Registry of adult patients with primary ITP, women outnumbered men and presented at a younger age. Over half of patients were treated with prednisolone as an initial therapy, though one-quarter failed to achieve a CR. Of note, approximately one-third of patients were prescribed a watch and wait strategy. For future updates, the Registry will help characterize disease progression and profile effects of novel therapies, such as thrombopoietin (TPO) receptor agonists, as more patients and follow-up time are accrued.
[1] Owing to reported platelet count frequency, recommended one week intervals to gauge responses to intravenous immunoglobulin (IVIg) and anti-D were extended to two weeks.
[2] Patients with presenting counts > 100×109/L were excluded from CR analyses.

Disclosures:
Sarpatwari: GSK: Consultancy, Research Funding; Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Bennett:GSK: Employment, Equity Ownership. Newland:GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Honoraria, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Provan:GSK: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.