Robert Deuson

The incidence and impact of thrombocytopenia in myelodysplastic syndromes

Thrombocytopenia and platelet dysfunction contribute to hemorrhagic complications in the myelodysplastic syndromes (MDS). Reliable data regarding the frequency and consequences of thrombocytopenia in MDS are lacking. An extensive literature review indicated that the prevalence of thrombocytopenia (platelets <100 × 109/L) in MDS ranged from 40% to 65%; the median frequency of thrombocytopenia prior to any MDS therapy was 65% (range, 23–93%). A retrospective review of patients who were referred to the University of Texas M. D. Anderson Cancer Center (MDACC) identified 1605 of 2410 patients (67%) with thrombocytopenia at referral. Of these, 1756 patients were classified using the International Prognostic Scoring System (IPSS), and 896 patients (51%) had intermediate‐2 or high‐risk disease. Treatment‐related thrombocytopenia was observed in studies that involved azacitidine, tipifarnib, decitabine, lenalidomide, sirolimus, and combination chemotherapy with idarubicin, cytarabine, and topotecan. The reported incidence of hemorrhagic complications in the literature ranged from 3% to 53%, and the frequency of hemorrhagic deaths ranged from 14% to 24%. At MDACC, 460 patients had a coded cause of death: hemorrhage as a contributory cause of death, 20%; hemorrhage as the only cause of death, 10%. Thrombocytopenia was common in MDS, and there was an increased prevalence in higher risk IPSS categories. Many approved and investigational MDS therapies caused or exacerbated preexisting thrombocytopenia. The incidence of severe bleeding in MDS was greater than reported in current guidelines. Cancer 2007.

Short-term and long-term failure of laparoscopic splenectomy in adult immune thrombocytopenic purpura patients: a systematic review.

Splenectomy is a common therapy for adults with chronic idiopathic thrombocytopenic purpura (ITP). Thisstudy was designed to estimate both the short‐term surgical non‐response rate and the long‐term relapse rate after laparoscopic splenectomy. A systematic review was conducted of articles published between January 1, 1991 and January 1, 2008. Selection criteria included: chronic ITP, study enrollment in 1990 or later, ≥12 months of follow‐up, ≥15 patients with ITP, ≥75% of patients at least 14 years of age, not HIV positive, not undergoing a second splenectomy, and type of performed splenectomy clearly reported. Data were pooled across studies to estimate rates. We identified 170 articles, of which 23 met our inclusion criteria (all observational studies). These studies represent 1,223 laparoscopic splenectomies (71 or 5.6% were converted to open splenectomy during surgery). The pooled short‐term surgical non‐response rate among the 18 studies reporting data was 8.2% (95% CI 5.4–11.0). The pooled long‐term relapse rate across all 23 studies was 43.6 per 1,000 patient years (95% CI 28.2–67.2). This translates to an approximate failure rate of 28% at 5 years for all patients undergoing splenectomy. Studies with shorter durations of follow‐up had significantly higher pooled relapse rates than studies with longer follow‐up (P = 0.04). Laparoscopicsplenectomy is effective for most patients. Splenectomy may have higher initial relapse rates, particularly, in the first 2 years after surgery, and the rate may decline over time. Am. J. Hematol. 2009.

Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction and insufficient platelet production. The resulting thrombocytopenia reduces patient health-related quality of life (HRQOL). In a randomized, open-label, 52-week study of non-splenectomized ITP patients treated with romiplostim or medical standard of care (SOC), patients completed the 10-scale ITP-patient assessment questionnaire (PAQ) at the start of the study and after 12, 24, 36, 48,and 52 weeks of treatment. HRQOL changes were examined for all patients in both treatment groups and by responder status, splenectomy status, and after the use of rituximab. Patients in both groups showed marked increases in all HRQOL scales over 52 weeks of treatment.These change scores exceeded the minimally important difference values (a measure of clinical relevance) for most of these scales,especially in responders to treatment. Compared with baseline,patients receiving romiplostim showed statistically significant improvements compared to SOC over 52 weeks for the ITP-PAQ scales of Symptoms, Bother, Activity, Psychological Health, Fear, Overall QOL,and Social QOL. Overall, treatment of ITP was associated with improvement in HRQOL. Patients receiving romiplostim had greater HRQOL improvements than those receiving SOC, but the magnitude ofthe difference is of uncertain clinical benefit.

Pilot study of the effect of romiplostim on child health-related quality of life (HRQoL) and parental burden in immune thrombocytopenia (ITP).

Childhood ITP can have a negative impact on the child and his/her family even though it is typically a benign disorder with low risk of serious bleeding. In adults and now children, romiplostim increases the platelet count without significant adverse effects. In this study, the impact of romiplostim treatment on the HRQoL of children with chronic ITP was assessed using the Kids ITP Tools (KIT).

Cost and mortality associated with hospitalizations in patients with immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is associated with low platelet counts and, consequently, a high risk of adverse events leading to hospitalization. However, there are few data on the clinical and economic burden of hospitalizations for ITP. The Nationwide Inpatient Sample (NIS) database of discharges, a stratified 20% sample of all United States (US) community hospitals across all payers, was used to evaluate discharges in ITP patients. We developed nationally representative numbers of discharges in ITP patients from 2003 to 2006 based on diagnosis codes. Using appropriate weights for each NIS discharge, we created national estimates of average cost, length of stay, and in‐hospital mortality for specific groups of ITP‐related hospitalizations. Approximately 129,000 discharges occurred between 2003 and 2006 in ITP patients. The average cost associated with all discharges in 2008 dollars was 16,476, with a 6.4‐day length of stay and in‐hospital mortality of 3.8%. In contrast, the average cost of all hospitalizations in the US population during the same period was 10,039, the average length of stay was 4.8 days, and in‐hospital mortality was 2.5%. Mortality risk was higher for ITP patients than for the standard US population adjusted for age and gender, with a relative mortality ratio of 1.5 (95% CI: 1.4–1.6). On the basis of a nationally representative sample of US discharge records from 2003 to 2006, hospitalization with ITP represents an economically and clinically important event. ITP was associated with higher costs, longer stays, and more in‐hospital deaths on average than all other hospitalized patients combined. Am. J. Hematol. 2009.

Measurement of utility values in the UK for health states related to immune thrombocytopenic purpura

Abstract Objective: To measure utility values associated with immune (idiopathic) thrombocytopenic purpura (ITP), as perceived by the United Kingdom (UK) general public. Research design and methods: A multi-step process, including clinical trial data, literature review, and patient focus group, was used to develop ITP health states valued in a web survey. Six ITP health states were defined based on platelet levels, risk of bleeding and key adverse events/disease complications. Clinical trial data on bleeding and ITP-specific quality of life data were key sources for developing health-state descriptions. 359 respondents, randomly selected from a managed web panel in the UK, completed the web-based Time Trade-Off survey. Wilcoxon signed-rank test was used to compare differences between each pair of health states. Results: Sample characteristics (mean age: 47.9 ± 16.9 years; 54% female) were comparable to the UK general population. ITP health states were valued as significantly worse than perfect health. Experiencing bleeding episodes was a more important driver than low platelet levels in valuing a health state to be worse. Substantial disutilities were associated with surviving an intracranial haemorrhage. Mean (SD) utility values for each ITP health state are: HS1: platelets ≥50 × 109/L, no outpatient bleed: 0.863 ± 0.15; HS2: platelets ≥50 × 109/L, outpatient bleed: 0.734 ± 0.19; HS3: platelets <50 × 109/L, no outpatient bleed: 0.841 ± 0.19; HS4: platelets <50 × 109/L, outpatient bleed: 0.732 ± 0.19; HS5: intracranial haemorrhage (2–6 months): 0.038 ± 0.46; HS6: steroid treatment adverse events: 0.758 ± 0.20. Potential limitations relate to web user population characteristics and lack of comparative testing of web-based TTO methods. Conclusions: Results provide evidence that the UK general population associate substantial loss of value living with ITP, suggesting an important role for new ITP treatments. Utility values based on these health states may be useful in future cost-effectiveness studies of existing and/or new ITP treatments.

A novel approach to the evaluation of bleeding-related episodes in patients with chronic immune thrombocytopenia

Abstract Objective: In clinical studies of patients with severe thrombocytopenia, rescue treatments are used to prevent or stop bleeding. Estimating risk reductions of bleeding for clinical study medications can be challenging. This study evaluated a new and possibly more accurate way of assessing the effects of a treatment intervention on bleeding-related outcomes. We developed a composite endpoint, termed bleeding-related episodes (BRE). Research design and methods: BREs were assessed in a post-hoc analysis of patients with chronic immune thrombocytopenia (ITP) who participated in two romiplostim, phase 3, placebo-controlled studies. Patients received romiplostim or placebo once weekly for 24 weeks. A BRE was defined as an actual bleeding event and/or the use of rescue medication. In total, 125 patients (41 placebo, 84 romiplostim) with platelet counts <30 K were enrolled. Clinical trial registration: NCT00102323/NCT00102336. Results: The rate of all BREs across all studies was reduced by 56% in patients receiving romiplostim compared with placebo. The rate of BREs using immunoglobulin (IVIg or anti-D Ig) was reduced by 89% in patients receiving romiplostim compared with placebo. BREs were more frequent in both groups at platelet counts <50 × 109/L. Results were similar between splenectomized and nonsplenectomized patients. We believe that prior to the development of this tool, bleeding events were underdiagnosed. The BRE tool allowed the identification of multiple interventions within bleeding episodes, which may have required separate interventions and were therefore considered to be additional BREs. Conclusions: In this study, the composite endpoint of a bleeding event and the use of rescue medication within close proximity of the bleeding event appears to be feasible and informative. The BRE tool allows for more precise understanding of the effect of rescue therapies in ITP and has broader applications to future clinical trials where assessment of bleeding risk can be complicated or masked by rescue interventions. Limitations: This was a post hoc analysis. The assignment of platelet counts to a BRE was based on the platelet count on the first day of a BRE, which may not reflect the platelet count during the entire episode, and the assignment of platelet counts was based on the estimation required for events that occurred between weekly measurements.

Impact of corticosteroid-related symptoms in patients with immune thrombocytopenic purpura: results of a survey of 985 patients.

BACKGROUND Corticosteroid (CS) therapy is effective in many patients with immune thrombocytopenic purpura (ITP), although it is associated with adverse effects. OBJECTIVE This study was conducted to describe the CS-related symptom experience of adult patients with ITP and to compare the symptom experience of current users of CS, previous users of CS, and those who have never used CS. METHODS In 2006, adult members of the Platelet Disorder Support Association (PDSA) who were listed in the organizations database, resided in the United States, and had a diagnosis of ITP were invited to participate in a Web-based survey. Symptom experience was assessed using 33 CS-related symptoms derived from a scale developed for use in patients undergoing organ transplantation. Symptom experience over the past 4 weeks was measured in terms of the occurrence of symptoms (rated on a 5-point scale from 1 [never occurring] to 5 [always occurring]) and the distress associated with those symptoms (rated on a 5-point Likert scale from 0 [not at all distressing] to 4 [extremely distressing]). Respondents were categorized according to 4 patterns of CS use: current users, nonusers, previous users who stopped CS use <6 months earlier, and previous users who stopped CS use >or=6 months earlier. RESULTS The survey was completed by 985 patients with ITP (8.2% of the PDSA membership). The median age of the sample was 47 years, and the ratio of women to men was 3:1. One hundred sixteen patients (11.8%) were current CS users, 171 (17.4%) were nonusers, 99 (10.1%) had stopped CS use <6 months earlier, and 599 (60.8%) had stopped CS use >or=6 months earlier. In all 4 groups, back pain, fatigue, sleep difficulties, muscle weakness, and difficulty seeing well were reported to be the most frequently occurring and most distressing symptoms. Current CS users and those who stopped CS treatment <6 months earlier also reported bruises to be among their most frequent and distressing symptoms. Twenty-five of the 33 symptoms occurred more frequently in current CS users than in nonusers, and 30 symptoms occurred more frequently in current users than in previous users who had stopped CS use >or=6 months earlier. Symptom occurrence was significantly greater for current users compared with those who stopped CS use <6 months earlier for puffy face (q = 0.003), excessive appetite (q = 0.002), changed facial features (q = 0.033), and buffalo hump (q = 0.048). Patients who had stopped CS use <6 months earlier reported 20 of the 33 symptoms significantly more often than those who had stopped CS use >or=6 months earlier (q < 0.05). The only symptoms reported significantly more often in patients who had stopped CS use >or=6 months earlier compared with nonusers were buffalo hump and bruises (q < 0.05). The distress associated with bruises was significantly higher in current users compared with nonusers and compared with previous users who had stopped CS use >or=6 months earlier (both, q = 0.047). Current users also reported significantly greater distress than nonusers for puffy face and excessive appetite (both, q = 0.047). Changed facial features was significantly more distressing in current users compared with those who had stopped CS use >or=6 months earlier (q = 0.047). CONCLUSIONS Different symptom profiles emerged based on the pattern of CS use. Patients who were currently using CS or who had stopped CS treatment <6 months earlier reported more symptoms than did patients who had never received CS or who had stopped CS treatment =6 months earlier.

Comparative net cost impact of the utilization of romiplostim and intravenous immunoglobulin for the treatment of patients with immune thrombocytopenia in Québec, Canada

Abstract Objectives: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction, sub-optimal platelet production, and mild-to-severe bleeding. Nplate® (romiplostim), a thrombopoietin receptor agonist, and intravenous immunoglobulin (IVIg), an expensive and occasionally scarce blood product, are used in the treatment of ITP. The objective of this study was to compare the total cost of treating patients with romiplostim vs IVIg in Québec, Canada. Methods: A net cost impact model was developed to calculate the annual cost of romiplostim compared with IVIg based on actual practice observations in all patients (n = 95) treated for chronic ITP with IVIg from April 2010 to March 2011 in two participating hospitals. The model included costs of: drug acquisition, drug preparation and administration, patient monitoring, and indirect costs. Healthcare practitioners were consulted regarding romiplostim and IVIg treatment algorithms and the resources involved in patient monitoring. Results: The average annual drug acquisition costs of romiplostim and IVIg were

The burden of immune thrombocytopenia in adults: evaluation of the thrombopoietin receptor agonist romiplostim.

48,024 and