Influence of Age on Treatment with Thrombopoietin Receptor Agonists in Patients with Immune Thrombocytopenia; A Retrospective Multicenter Study

Background. Increasing age is a risk factor for vascular events but also for bleeding in immune thrombocytopenia (ITP). In elderly, meta-analysis of clinical trials of romiplostim (ROM) and eltrombopag (ELT) show that thrombopoietin receptor agonists (TPO-RA) are effective and safe with the exception of increased thromboembolic risk (Olney et al, 2011; Michel et al 2015). Objective. To analyze how age influences the selection of TPO-RA, bleeding and thrombotic risk, comorbidities, and therapeutic management of ITP patients in a real-world setting. Methods. We conducted a multicenter retrospective study that included 121 adult patients with primary ITP from 19 secondary and tertiary Spanish hospitals who had initiated long-term therapy with ROM or ELT between January 2012 and December 2014. Information was collected from medical records (November 2016 to January 2018) to assess variables related to patient characteristics and outcomes of elderly (> 65 years; n=54) compared with younger individuals (n=67). Results. Patients included initiated TPO-RA (ROM, n=54; ELT, n=67) and maintained this therapy for a median time to collection of data of 35.2 months (1 to 67.3 months). The median age at diagnosis of elderly and younger cohorts was respectively 75 years (66-96 years), and 48 years (19-65 years). Older age was associated with a previous history of vascular events (VE) (P=0.049), with more patients receiving antithrombotic therapy (P=0.001), and with a non-significant trend towards increased risk of current VE under TPO-RA therapy (Table). During treatment, 15 patients experienced 17 VE (9 arterial, 8 venous); no association was found between risk for VE in patients under TPO-RA and past history of thromboembolic or ischemic events (P=0.727). Patients that were offered TPO-RA at younger ages presented at diagnosis with significantly lower platelet counts, and increased cumulative bleeding score (Page et al, 2007) (P=0.003, and P=0.034) than elderly ones. Younger patients also had significantly higher visceral bleeding rates at the onset of TPO-RA therapy (P=0.042) and had increased requirement for hospital care (emergency treatment or hospital admission) both six months before and after the start of TPO-RA (P=0.016, and P=0.002, respectively). Older age was associated with comorbidities such as hypertension and diabetes (P<0.001), and with decreased exposure to splenectomy (P=0.002). In patients over 65 years experiencing VE on TPO-RA, a significant association with previous neoplasia was observed vs. those without that complication (50% vs. 2.2%, P<0.001), whereas in younger patients VE during TPO-RA therapy was only associated with previous splenectomy (100% vs. 33%, P=0.001). There was a trend towards a preferential use of ELT in older patients. While slightly higher platelet response rates to TPO-RA were seen among patients >65 versus ≤65 years, however a more conservative management in terms of discontinuation of therapies was confirmed. Therefore, the rate of tapering off TPO-RA was significantly lower in those >65 years (P=0.028), although the proportion of patients that achieved therapy free response (TFR) (platelet count >50x109/l for at least 6 months) upon discontinuation was similar in both groups (Table). Conclusion. The management of older patients with chronic ITP is still challenging, and widespread effort is made to avoid potential complications such as those related to splenectomy. Our study reflects that the introduction of TPO-RAs has caused a change in the outcomes of these patients. The increased awareness of the unfavorable conditions that are present in this population induces a preferential use of TPO-RAs in elderly patients with a lower bleeding history than in younger patients. Although these drugs associate with a potential risk of increased thrombotic risk, our data indicate that past thrombotic history does not predispose to the development of VE; rather neoplasia in elderly patients, and splenectomy at younger ages are factors that increase the likelihood to suffer from these events. The compromise towards effective therapies in these fragile patients associates with low discontinuation of TPO-RA to test for TFR, although once tapered off, sustained platelet responses are similar to those in younger patients. Disclosures Mingot-Castellano: Novonordisk: Consultancy; Sobi: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Bayer: Consultancy; CSL Behring: Consultancy; Roche: Consultancy; Novartis: Consultancy. Jarque:Abbie: Consultancy, Speakers Bureau; Alexion: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; CellTrion: Consultancy; Gilead: Consultancy, Speakers Bureau; Grifols: Consultancy; Janssen: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Servier: Speakers Bureau; Shionogi: Consultancy, Speakers Bureau; Shire: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Campos:Novartis: Speakers Bureau; Amgen: Speakers Bureau. Lopez Fernandez:Amgen: Consultancy, Speakers Bureau. Valcarcel:MSD: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy, Honoraria, Speakers Bureau; JAZZ: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Casado:Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Álvarez Roman:Takeda: Research Funding; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; NovoNordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau.

Download Full-text

Role of Laparoscopic Splenectomy in Elderly Immune Thrombocytopenia

Open Medicine ◽

10.1515/med-2016-0066 ◽

2016 ◽

Vol 11 (1) ◽

pp. 361-368

Author(s):

Valentina Giudice ◽

Rosa Rosamilio ◽

Bianca Serio ◽

Rosa Maria Di Crescenzo ◽

Francesca Rossi ◽

...

Keyword(s):

Elderly Patients ◽

Laparoscopic Splenectomy ◽

Older Patients ◽

Immune Thrombocytopenia ◽

Remission Rate ◽

Complication Rates ◽

First Line ◽

Thrombopoietin Receptor ◽

Primary Immune Thrombocytopenia

AbstractThe management of older patients with chronic primary immune thrombocytopenia (ITP) is still very challenging because of the fragility of older patients who frequently have severe comorbidities and/or disabilities. Corticosteroid-based first-line therapies fail in most of the cases and patients require a second-line treatment, choosing between rituximab, thrombopoietin-receptor agonists and splenectomy. The choice of the best treatment in elderly patients is a compromise between effectiveness and safety and laparoscopic splenectomy may be a good option with a complete remission rate of 67% at 60 months. But relapse and complication rates remain higher than in younger splenectomized ITP patients because elderly patients undergo splenectomy with unfavorable conditions (age >60 year-old, presence of comorbidities, or multiple previous treatments) which negatively influence the outcome, regardless the hematological response. For these reasons, a good management of concomitant diseases and the option to not use the splenectomy as the last possible treatment could improve the outcome of old splenectomized patients.

Download Full-text

Real-world use of thrombopoietin receptor agonists in elderly patients with primary immune thrombocytopenia

Blood ◽

10.1182/blood.2021010735 ◽

2021 ◽

Author(s):

Francesca Palandri ◽

Elena Rossi ◽

Daniela Bartoletti ◽

Antonietta Ferretti ◽

Marco Ruggeri ◽

...

Keyword(s):

Elderly Patients ◽

Immune Thrombocytopenia ◽

Complete Response ◽

Secondary Prophylaxis ◽

Recurrent Event ◽

Thrombopoietin Receptor Agonists ◽

Receptor Agonists ◽

Thrombopoietin Receptor ◽

Primary Immune Thrombocytopenia ◽

Hemorrhagic Risk

The efficacy and safety of thrombopoietin-receptor agonists (TRAs) in elderly patients with primary immune thrombocytopenia (ITP) is uncertain. In 384 ITP patients treated with TRAs when aged ≥60 years, we investigated TRAs response and switch, thrombotic/hemorrhagic risk, and sustained responses off-treatment (SROT). After 3 months, 82.5% and 74.3% of eltrombopag and romiplostim-treated patients achieved a response, respectively (p=0.09); 66.7% maintained the response (median follow-up: 2.7 years). Eighty-five (22.2%) patients switched to the alternative TRA; while no cross-toxicity was observed, 83.3% of resistant patients had a response after the switch. During TRA, 34 major thromboses (3 fatal) and 14 major hemorrhages (none fatal) occurred in 18 and 10 patients, respectively, and were associated with thrombosis history (SHR: 2.04, p=0.05) and platelet count <20x109/L at TRA start (SHR: 1.69, p=0.04), respectively. A recurrent event occurred in 15.6% of patients surviving thrombosis, in all cases but one during persisting TRA treatment (incidence rate: 7.7 per 100 patient-years). All recurrences occurred in the absence of adequate antithrombotic secondary prophylaxis. Sixty-two (16.5%) responding patients discontinued TRA; 53 (13.8%) patients maintained SROT, which was associated with TRA discontinuation in complete response (p<0.001). Very old age (≥75, 41.1%) was associated with more frequent TRAs start in persistent/acute phase but not with response or thrombotic/hemorrhagic risk. TRAs are effective in elderly ITP patients, with no fatal haemorrhages and with SROT in a significant portion of patients; in patients with thrombosis history caution is warranted and a careful risk/benefit balance should be carried out.

Download Full-text

ACUTE KIDNEY INJURY IN ELDERLY PATIENTS

Wiadomości Lekarskie ◽

10.36740/wlek201908109 ◽

2019 ◽

Vol 72 (8) ◽

pp. 1466-1472

Author(s):

Grażyna Kobus ◽

Jolanta Małyszko ◽

Hanna Bachórzewska-Gajewska

Keyword(s):

Acute Kidney Injury ◽

Renal Failure ◽

Acute Renal Failure ◽

Elderly Patients ◽

Older Patients ◽

Age Groups ◽

Kidney Injury ◽

The Elderly ◽

Younger Patients ◽

Common Cause

Introduction: In the elderly, impairment of kidney function occurs. Renal diseases overlap with anatomic and functional changes related to age-related involutionary processes. Mortality among patients with acute renal injury is approximately 50%, despite advances in treatment and diagnosis of AKI. The aim: To assess the incidence of acute kidney injury in elderly patients and to analyze the causes of acute renal failure depending on age. Materials and methods: A retrospective analysis included medical documentation of patients hospitalized in the Nephrology Clinic during the 6-month period. During this period 452 patients were hospitalized in the clinic. A group of 77 patients with acute renal failure as a reason for hospitalization was included in the study. Results: The prerenal form was the most common cause of AKI in both age groups. In both age groups, the most common cause was dehydration; in the group of patients up to 65 years of age, dehydration was 29.17%; in the group of people over 65 years - 43.39%. Renal replacement therapy in patients with AKI was used in 14.29% of patients. In the group of patients up to 65 years of age hemodialysis was 16.67% and above 65 years of age. -13.21% of patients. The average creatinine level in the group of younger patients at admission was 5.16 ± 3.71 mg / dl, in the group of older patients 3.14 ± 1.63 mg / dl. The size of glomerular filtration GFR in the group of younger patients at admission was 21.14 ± 19.54 ml / min, in the group of older patients 23.34 ± 13.33 ml / min. Conclusions: The main cause of acute kidney injury regardless of the age group was dehydration. Due to the high percentage of AKI in the elderly, this group requires more preventive action, not only in the hospital but also at home.

Download Full-text

Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200531142244 ◽

2020 ◽

Vol 20 ◽

Author(s):

Giuseppe Lassandro ◽

Valentina Palladino ◽

Giovanni Carlo Del Vecchioa ◽

Viviana Valeria Palmieri ◽

Paola Carmela Corallo ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Treatment Options ◽

Thrombopoietin Receptor Agonists ◽

Receptor Agonists ◽

Thrombopoietin Receptor ◽

Related Quality ◽

Health Related

Background and Objective: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safety and effective for the treatment of pediatric ITP. The aim of our research is defining the role of thrombopoietin receptor agonists in the management of pediatric ITP. Method: This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in management of the disease. Results: Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. Conclusion: Although TPO-RAs long term efficacy and safety still require further investigations, their use is gradually expanding in clinical practice of children with ITP.

Download Full-text

Comparison of Adherence, Persistence, and Bleed-Related Event Rates in Patients Diagnosed with Immune Thrombocytopenia and Treated with Thrombopoietin Receptor Agonists

Value in Health ◽

10.1016/j.jval.2018.04.1743 ◽

2018 ◽

Vol 21 ◽

pp. S261

Author(s):

D Stafkey-Mailey ◽

T Lokhandwala ◽

Q Said ◽

M Bhor ◽

A Graves

Keyword(s):

Immune Thrombocytopenia ◽

Related Event ◽

Thrombopoietin Receptor Agonists ◽

Receptor Agonists ◽

Thrombopoietin Receptor ◽

Event Rates

Download Full-text

Absence of bi-directional cross-resistance of thrombopoietin receptor agonists in chronic refractory immune thrombocytopenia: possible role ofMPLpolymorphisms

British Journal of Haematology ◽

10.1111/bjh.12186 ◽

2012 ◽

Vol 161 (1) ◽

pp. 142-144 ◽

Cited By ~ 8

Author(s):

Nicola Polverelli ◽

Francesca Palandri ◽

Ilaria Iacobucci ◽

Lucia Catani ◽

Giovanni Martinelli ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Cross Resistance ◽

Thrombopoietin Receptor Agonists ◽

Receptor Agonists ◽

Thrombopoietin Receptor

Download Full-text

Immune Thrombocytopenia

Hematology ◽

10.1182/asheducation.v2010.1.377.3643150 ◽

2010 ◽

Vol 2010 (1) ◽

pp. 377-384 ◽

Cited By ~ 1

Author(s):

Adam Cuker ◽

Douglas B. Cines

Keyword(s):

Immune Thrombocytopenia ◽

Therapeutic Decision ◽

Platelet Destruction ◽

Aggressive Therapy ◽

Pulse Dose ◽

Thrombopoietin Receptor ◽

History Of ◽

Associated Conditions ◽

Therapeutic Decision Making

Abstract Immune thrombocytopenia (ITP) comprises a heterogeneous group of disorders characterized by autoimmune-mediated platelet destruction and impairment of thrombopoiesis. ITP may occur in the absence of an evident predisposing etiology (primary ITP) or secondary to a growing list of associated conditions (secondary ITP), and must be differentiated from other causes of thrombocytopenia. This review focuses on primary ITP in adults. The traditional goal of therapy in this population is to achieve a hemostatic platelet count of 30 × 109/L or above for most patients while minimizing treatment-related morbidity. This approach has been called into question by the recent advent of well-tolerated and effective agents for the management of ITP, including pulse-dose dexamethasone, rituximab, and the thrombopoietin receptor agonists. Recent studies suggest the potential for aggressive therapy at the time of diagnosis to alter the natural history of ITP and point to the importance of quality-of-life considerations in therapeutic decision making.

Download Full-text