Pf691 Splenectomy in Immune Thrombocytopenia: Do Changing Treatment Patterns for Itp Affect Outcomes? Data From the Uk Itp Registry

Abstract

Background:The advent of medical alternatives to splenectomy, particularly the thrombopoietin receptor agonists (TPO‐RA) has seen reduction in its use for ITP. It is now generally reserved in the UK for patients who fail multiple lines of therapy.Aims:We aimed to evaluate practices around splenectomy in the UK and long term response rates using data from the UK ITP registry, a large national database of primary ITP cases set up in 2007.Methods:We analysed all splenectomy cases from the UK ITP registry entered to December 2018. Data was studied on demographics, response rates, relapse rates and influence on response to medical therapies. Statistical analysis was performed using STATA. To identify the influence of medical therapies, we divided patients into treatment time brackets: 1989–1998, 1999–2008 and 2009–2018. The following response criteria were used:Complete response (CR platelets>100 x 109/l),partial response (PR platelets>30 but <100x109/l or doubling from baseline),overall response (OR = PR+CR).Results:Of 3236 registered patients(ITP diagnosis date ranging 1951 – 2018), 321(9.92%)(62%F/38%M) had undergone splenectomy with a total of 4611patient‐years follow‐up(Median 13.2 years, IQR 6.68,23.6). Median age at splenectomy was 40 years(y)(IQR27.0, 55.5).86.2%(268 patients) were <65y old and 13.8%(43 patients) 65y or older.72 patients were excluded from subsequent analysis due to incomplete data(including patients who had splenectomy <1989).Number of patients undergoing splenectomy decreased over time:1989–1998 34.1%;1999–2008 14.8%;2009–2018 4.8%. Median time from ITP diagnosis to splenectomy was 1.46y(IQR 0,20.3) increasing from 1.51y(IQR0,9.23.) in 1989–1998 to 1.69y(IQR0.14,18.5) in 2009–2018. This was associated with an increase in median number of treatment modalities from 2(IQR1,3) in 1989–1998 to 3 (IQR1,7) in 2009–2018 and median number of treatment episodes from 1(IQR1,2) in 1989–1998 to 3 (IQR1,11) in 2009–2018 pre‐splenectomy. The most common treatment modalities pre‐splenectomy were prednisolone(92%),IV immunoglobulin(50%),Azathioprine(27%),Rituximab(21%),Dexamethasone(12%),Mycophenolate(10%) and Romiplostim(10%).CR/PR and OR rates post‐splenectomy were 63.1%/24.3%/87.4% at 1month and 52.2%/15.3%/67.5% at 6months.67.2% of patients who had OR to splenectomy at 1month still had OR at latest follow‐up(median follow‐up 10.5y,IQR4.37,14.4).OR in patients <65y old were 86.8% at 1month and 51.8% at 6months post‐splenectomy.OR in those 65y and older were 73.9% at 1month and 46.2% at 6months post‐splenectomy.Beyond 6 months there is a trend towards reducing response in >65y group, but currently further analysis is limited by missing data.Overall median duration of response(DOR) was 2.5y(IQR0.51,7.01).The median DOR fell over time from 7.35y(1989–1998) to 0.52y(2009–2018).Median DOR was 3.02y in <65y old(IQR0.60,7.70) and 0.76y in 65y or older(IQR0.17,4.2.93).In patients who relapsed post‐splenectomy, median time to treatment was 2.56y(IQR0.09,35.48).59patients(18.4%) had complications post splenectomy.42patients(13.1%) had infections of which 32cases(76.2%) were attributed to splenectomy.53patients(11.2%) had an arterial or venous thrombotic event post‐splenectomy. Of 4deaths(1.25%),1 was listed as being attributed to splenectomy.Summary/Conclusion:Splenectomy rates for ITP in the UK have fallen since 1989, associated with increased medical treatment. There appears to be a trend to reduced response rates and shortened remission duration when this is used later in the treatment pathway.

Incidence of adult primary immune thrombocytopenia in England—An update

“…Splenectomy, a treatment of choice for many years for patients failing other therapies, has fallen out of favor due to postsplenectomy sequelae, a heightened risk of infection and venous thromboembolism. 19,20 inhibitors undergoing clinical trials. 3,21 However, many of the newer therapies for ITP are high cost (TPO-RA and syk inhibitors) therefore analysis of current incidence rates, influences on incidence and treatment utilization is critical to understanding the potential for resource utilization.…”

“…Intravenous immunoglobulin does not produce sustained responses in ITP and is reserved for rescue treatment. Splenectomy, a treatment of choice for many years for patients failing other therapies, has fallen out of favor due to post‐splenectomy sequelae, a heightened risk of infection and venous thromboembolism 19,20 . Medical therapy for ITP, has evolved over the last two decades.…”

“…Hence, among males the steepest increase in IT over time was for the ≥80 years age group (AAPC: 5.0%). There was a statistically significant increase in incidence over time for each sex-specific age group, except for males aged[18][19][20][21][22][23][24][25][26][27][28][29] nonsignificant). Throughout the study periods, males who were 70-79 years and ≥80 years had higher IRs than their female counterparts of the same age groups.…”

Splenomegaly and Response to Splenectomy in Immune Thrombocytopenia

“…The thirty-day mortality in our cohort exceeded previously reported rates for splenectomy in this setting. Retrospective data for splenectomy for various indications demonstrated overall mortality rates from 0-3.5% [30][31][32]. The two patients who died within thirty days of surgery both died of pulmonary emboli.…”

“…Identifying consistent markers to predict splenectomy outcomes has proven challenging due to variability in preoperative practices [16][17][18]25,30,37]. Given inconsistency across studies, preoperative evaluation remains at the discretion of the referring provider, with substantial variations in practice [38].…”