scholarly journals Hepatobiliary and Thromboembolic Events during Long-Term E.X.T.E.N.Ded Treatment with Eltrombopag in Adult Patients with Chronic Immune Thrombocytopenia (ITP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1368-1368
Author(s):  
Mansoor N. Saleh ◽  
James B Bussel ◽  
Raymond SM Wong ◽  
Balkis Meddeb ◽  
Abdulgabar Salama ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Adult Patients ◽  
Phase Iii ◽  
First Year ◽  
Thromboembolic Events ◽  
Advisory Committees ◽  
Platelet Counts

Abstract Introduction: ITP, characterized by a reduction in platelets leading to thrombocytopenia, which persists for >12 months is considered chronic (cITP). Eltrombopag is an oral thrombopoietin receptor agonist approved for treatment of patients with cITP aged ≥1 year refractory to other treatments (eg corticosteroids, immunoglobulins). The recently completed Phase III EXTEND (Eltrombopag eXTENded Dosing) study was a global, open-label, extension study of patients with cITP, who received eltrombopag or placebo in prior eltrombopag clinical studies. The primary objective of EXTEND was to describe the long-term safety and tolerability of eltrombopag treatment in these patients. Here, we examine the occurrence of hepatobiliary and thromboembolic events (TEEs) as adverse events (AEs) of special interest in this study. Methods :Adult patients (≥18 years old) diagnosed with cITP according to ASH/BCSH guidelines were enrolled and received eltrombopag starting at 50 mg/day. Dose was titrated to 25-75 mg per day or less often as required, based on individual platelet count responses (targeted range ≥50-200x109/L). Patients who received 2 years of treatment and transitioned off eltrombopag due to commercial availability of eltrombopag were considered to have completed the study, whether or not they continued treatment with eltrombopag. The primary endpoint included detection and documentation of investigator-reported AEs, which included hepatobiliary AEs and TEEs. Analyses were conducted using the safety population, defined as all subjects who entered the study and had taken at least one dose of the study medication. Results:302 patients were enrolled and received at least one dose of eltrombopag: 67% were female; 38% splenectomized; 49% aged 18-49 years. Median duration of exposure was 2.4 years (range, 2 days to 8.8 years) and mean average daily dose was 50.2 (range, 1-75) mg/day. Overall, 259/302 (86%) achieved platelet counts of ≥50×109/L at least once during the study and 126/248 (51%) patients maintained continuous platelet counts ≥50×109/L for at least 31 weeks. Incidence of bleeding symptoms (WHO grades 1-4) generally decreased over time in patients with available data, from 57% (n=171/302) at baseline to 16% at 1 year (n=13/80), and 21% (12/58) at 2 years. 45 (15%) patients experienced at least one hepatobiliary AE, with the highest incidence within the first year of treatment (Figure A). AEs of increased ALT or AST led to the discontinuation of five and three patients, respectively and four patients discontinued due to an AE of increased blood bilirubin. Nine patients experienced ALT and/or AST >3 x upper limit of normal (ULN) and total bilirubin >1.5xULN. 19 (6.3%) patients experienced a total of 23 TEEs. Most events occurred in the first year (Figure B), and none after year 4. TEEs included deep vein thrombosis (n=6), cerebral infarction (stroke) [n=3], myocardial infarction (n=4), transient ischemic attack (n=2), others (n=8, 1 occurrence of each). A clear association with elevated platelet counts was not observed. Platelets >200x109/L at the time of the TEE were recorded in 8/19 patients; 6/19 experienced the TEE at or shortly after achieving their maximum platelet count. In total, 10 patients discontinued because of TEEs. Conclusions: Long-term treatment with eltrombopag in patients with cITP led to sustained platelet increases and reduced bleeding symptoms. The highest incidences of hepatobiliary AEs and TEEs occurred during the first year of treatment, though several events were recorded after 3 years of therapy. Long-term eltrombopag therapy was well-tolerated with a positive benefit-risk relationship in adults with cITP, with decreasing events after the first year of treatment. Disclosures Saleh: GSK: Consultancy, Research Funding, Speakers Bureau. Bussel:Amgen, Novartis & GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingleheim, Prophylix Pharma, Protalex, Rigel Pharmaceuticals: Research Funding; Momenta Pharmaceuticals, Novartis, Prophylix Pharma, Protalex, Rigel Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; UptoDate: Patents & Royalties; Physicians Education Resource: Speakers Bureau. Wong:Bayer, Biogen-Idec and Novartis: Consultancy; Bayer, Biogen-Idec, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pfizer, and Roche: Research Funding; Biogen-Idec and Novartis: Membership on an entity's Board of Directors or advisory committees. El-Ali:Novartis: Employment. Quebe-Fehling:Novartis: Employment.

Thromboembolic Events Observed in Eltrombopag Clinical Trials in Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2423-2423 ◽  
Author(s):  
James B. Bussel ◽  
Gregory Cheng ◽  
Mansoor N. Saleh ◽  
Sandra Vasey ◽  
Manuel Aivado ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Thromboembolic Events ◽  
Study Medication ◽  
Normal Range ◽  
Advisory Committees ◽  
Thrombocytopenic Purpura ◽  
Platelet Counts ◽  
Equity Ownership

Abstract Abstract 2423 Poster Board II-400 BACKGROUND: Eltrombopag (PROMACTA®; GlaxoSmithKline, Collegeville, PA, USA), an oral, small molecule, thrombopoietin receptor agonist, was recently approved in the United States for the treatment of patients with chronic immune thrombocytopenic purpura (ITP). Limited published data indicate that patients with chronic ITP experience thromboembolic events (TEEs) with a frequency of 3% to 6%. (Aledort, Am J Hematol, 2004; Bennett, Haematologica, 2008). OBJECTIVE: To evaluate the incidence of TEEs in patients with chronic ITP treated with eltrombopag and to determine if the occurrence of TEEs was associated with elevated platelet counts. METHODS: Data from 446 patients from 3 placebo-controlled eltrombopag studies (TRA100773A, TRA100773B, and RAISE) and 2 open-label studies (REPEAT and EXTEND) were analyzed. The frequency of TEEs or suspected TEEs before and after the first dose of study medication (placebo or eltrombopag) was examined across the program. Potential risk factors, including platelet counts proximal to the event, were evaluated in patients experiencing a TEE. RESULTS: Prior to the initiation of study medication (placebo or eltrombopag), 16/493 (3.2%) of the patients entering the program had a history of TEEs (one of these patients experienced 2 additional TEEs [TIA, MI] while on treatment with eltrombopag). Across the ITP clinical program, 17/446 patients treated with eltrombopag (3.8%) experienced 22 TEEs. No patient treated with placebo experienced a TEE. The patient-years (PYs) of exposure to study medication was approximately 14 times greater for patients treated with eltrombopag compared to placebo (eltrombopag 377 PYs; placebo 26 PYs). Most patients (13/17) experienced 1 TEE; 3 patients experienced 2, and 1 patient experienced 3 (2 TEEs were 6 months off-therapy). The most common TEEs were deep vein thrombosis (n=8) and pulmonary embolism (n=6). A total of 18/22 events were resolved or resolving at the time of this analysis; all patients experiencing a TEE had at least 1 risk factor for these events other than ITP (eg, use of IVIg [n=3], hospitalization with no prophylactic anticoagulation [n=4], oral corticosteroids [n=6]). The platelet counts proximal to the event ranged from 14,000/μL to 420,000/μL. The majority of patients had platelet counts below 150,000/μL (9; 53%) or between 150,000/μL and 400,000/μL (5; 29%); 2 had platelet counts above 400,000/μL and the platelet count in 1 was unknown. All 446 patients were categorized by the maximum platelet count achieved during treatment with eltrombopag (above normal [>400,000/μL], normal range [150–400,000/μL], below normal range [<150,000/μ]; Table 1). The majority of patients (14; 82%) experienced the TEEs at a platelet count lower than their maximum platelet count, while 3 patients (18%) experienced a TEE proximal to their maximum platelet count. CONCLUSION: TEEs occurred with eltrombopag. None occurred with placebo; however, the PYs of exposure was considerably less with placebo than with eltrombopag. The frequency of TEEs observed during eltrombopag treatment (3.8%) is similar to that reported in the literature and prior to enrollment in the eltrombopag program (3.2%). No discernible correlation has been observed between platelet count increases and TEEs, and these events do not appear to be associated with maximum platelet counts during treatment with eltrombopag. Disclosures: Bussel: Sysmex: Research Funding; Eisai, Inc: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Cheng:GlaxoSmithKline: Research Funding. Saleh:GlaxoSmithKline: Speakers Bureau; Amgen: Speakers Bureau. Vasey:GlaxoSmithKline: Employment. Aivado:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.

scholarly journals Randomized Double-Blind Study of Increasing Doses of Eltrombopag in Patients with Chronic ITP

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1057-1057 ◽  
Author(s):  
Peter J Keefe ◽  
Margaret C Morrissey ◽  
Catherine E. McGuinn ◽  
James B. Bussel
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Active Drug ◽  
Study Drug ◽  
Thromboembolic Events ◽  
Open Label ◽  
Advisory Committees ◽  
Double Blind ◽  
Platelet Counts

Abstract Background: Eltrombopag (Epag) is an oral thrombopoietin receptor agonist used to increase platelet counts in patients with chronic immune thrombocytopenia (cITP). The maximum licensed Epag dose in cITP patients is 75 mg daily, yet some patients do not respond at this dose. Healthy individuals on escalated doses of eltrombopag (100-200 mg) demonstrated a dose dependent platelet response as did patients with thrombocytopenia secondary to chemotherapy. Doses of 100 mg and 150 mg have been approved for use in patients with hepatitis-C induced thrombocytopenia and aplastic anemia respectively. This is the final report of a double-blind, randomized controlled study to determine if Epag, administered at doses up to 150 mg daily, increases platelet counts in cITP patients who failed to respond to 75 mg. Methods: cITP patients³ 1 year old with platelet counts <50,000uL despite >3 weeks of 75mg of Epag daily), stratified by splenectomy status, were enrolled. Patients could continue stable doses of concomitant ITP medications. In the randomized blinded phase (Part 1), patients first received 75 mg daily of active Epag and 25 mg of study drug (Epag or placebo, 2:1). Every two weeks, study drug doses were increased in 25 mg increments to a maximum daily dose of 150 mg. After 8 weeks subjects were unblinded. If on active drug, they entered the open label phase (Part 2); if on placebo, they received open label Epag as per the study protocol escalating to a maximum dose of 150 mg. Two patients entered part 2 before 8 weeks because their counts were >100,000/uL in the blinded phase. Data analysis was descriptive. Mann Whitney U test estimated p-values (α<.05) or platelet count differences between groups. Imputation of platelet counts allowed omitting falsely high or low platelet counts resulting from rescue therapy (e.g. IVIG), or counts in3 patients discontinuing early with good responses after 2, 2, and 4 weeks who thereby did not have counts at weeks 4, 6, and 8. Interim analysis was pre-specified and data is included on 33 of the planned total of 36 patients. Results: As of July 31, 35 patients consented; 26 completed ³8 weeks on study medication. Two patients are in part 1 and 7 dis-enrolled before completing 8 weeks of study drug: 5 failed screening and never received medication; one had bleeding and low counts on placebo; and one had pre-existing reticulin fibrosis 2-3+, discovered after study drug was dispensed but not administered. The most common adverse event (AE) was minor bleeding. Two adults and 2 children developed transaminitis, which was life-threatening in 1 adult on 100mg. The 4 liver AEs occurred between 2 and 20 weeks of Epag dosing with 3/4 subjects on 150 mg daily; 2/4 discontinued Epag. No strokes or thromboembolic events were seen nor did any cataracts develop. Three patients underwent bone marrows: no grade 2-3 fibrosis was seen. Platelet counts for patients on active drug vs placebo separated by week 2 (Figure 1A) and the difference steadily increased until week 8 (p<0.07) reflecting the thrombopoietic effects of increased dose Epag. Increased eltrombopag doses had greater effect in children (avg age 13) than adults (avg age 51) [Figure 1B]. This may reflect more rapid drug metabolism or relative insensitivity to the effects of Epag in children or both; this was first noted in PETIT and PETIT2. Twenty-six patients entered the long-term open-label study. Three discontinued prior to 24 weeks because of transaminase elevation (1) and no response (2); 7 are not yet at 24 weeks; and 6 were also on other treatments, ie IVIG at increased intervals while on Epag, obscuring their responses. Ten patients were on open label medication for >24 weeks past the 8 weeks in part 1 up to 110 weeks. 72% of the long-term counts in these 10 patients were > 50,000/uL while 40% were > 100,000/uL. Six patients took 150 mg daily for >24 weeks while 4 reduced their doses, though not to <75mg daily. Conclusions: The results demonstrate that Eltrombopag at doses of 100-150mg daily can elevate platelet levels in most children and adults with cITP whose platelet counts were <50,000 on 75mg of Epag daily for >3 weeks. Children responded better to increased doses of Epag than did adults and high dose Epag can be used long term without development of cataracts, strokes or other thromboembolic events although an increased frequency of liver events, 12%, occurred. Although the 150 mg dose can be safely continued for many months, monitoring transaminases is essential. Disclosures Off Label Use: Increased doses of eltrombopag. McGuinn:Baxter: Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees. Bussel:Momenta: Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding; BiologicTx: Research Funding; Symphogen: Membership on an entity's Board of Directors or advisory committees; Cangene: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Protalex: Membership on an entity's Board of Directors or advisory committees; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding; Immunomedics: Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Long-Term Treatment of Chronic Immune Thrombocytopenic Purpura with Oral Eltrombopag: Results From the EXTEND Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 682-682 ◽  
Author(s):  
Mansoor N. Saleh ◽  
James B. Bussel ◽  
Gregory Cheng ◽  
Balkis Meddeb ◽  
Bhabita Mayer ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
Thrombocytopenic Purpura ◽  
Once Daily ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Equity Ownership

Abstract Abstract 682 INTRODUCTION: Eltrombopag (PROMACTA; GlaxoSmithKline, Collegeville, PA) is the first oral, small molecule, thrombopoietin receptor agonist approved in the US for the treatment of chronic immune thrombocytopenic purpura (ITP). Eltrombopag is also being evaluated for the treatment of thrombocytopenia due to other causes (eg, hepatitis C, MDS). Chronic ITP is characterized by autoantibody-induced platelet destruction and reduced platelet production, leading to chronically low platelet counts. Eltrombopag has been shown to significantly increase platelet counts and reduce clinically relevant bleeding symptoms in 3 placebo-controlled ITP trials evaluating a total of 429 patients. EXTEND is an ongoing open-label, phase 3 extension study to assess the long-term safety and efficacy of eltrombopag in chronic ITP. METHODS: Patients with previously treated, chronic ITP who completed a prior eltrombopag study were eligible to participate in EXTEND. Eltrombopag treatment was initiated at 50 mg once daily and then adjusted to maintain platelet counts between ≥50,000/μL and <200,000/μL, with doses between 75 mg and 25 mg once daily (or less often if necessary). Patients who achieved platelet counts ≥50,000/μL were considered responders. Bleeding events were prospectively evaluated using the World Health Organization (WHO) Bleeding Scale: grade 0 = no bleeding, grade 1 = mild bleeding, grade 2 = moderate bleeding, grade 3 = gross bleeding, and grade 4 = debilitating blood loss. Bone marrow (BM) biopsy was required after 1 year on treatment. RESULTS: At the time of this analysis, 299 patients (median age 50 years; 66% female) had received eltrombopag (240, 126, 48, and 17 patients exposed for ≥6, 12, 18, and 24 months, respectively). The median duration of eltrombopag treatment was 204 days and ranged from 2–861 days. At baseline, 33% were receiving concomitant ITP medication and 38% had been splenectomized. The majority of patients (70%) had baseline platelet counts <30,000/μL, followed by 17% and 13% with baseline platelet counts from μ30,000/μL to <50,000/μL, and μ50,000/μL, respectively; all had baseline platelet counts <50,000/μL at the time of entry into their previous study. Overall, 86% of patients (257/299) achieved a platelet count μ50,000/μL. Splenectomized and non-splenectomized patients responded equally well (89% and 82%, respectively). Patients responded to eltrombopag regardless of baseline use of concomitant ITP medications (no baseline ITP medications and baseline ITP medications: 86% each). Median platelet counts increased to μ50,000/μL by week 2, and remained μ50,000/μL throughout the observation period of the study (Figure 1). Patients on treatment for μ6 months or μ12 months achieved platelet counts of μ50,000/μL and 2x baseline for 69% (18/26 weeks) and 71% (37/52 weeks) of the time on treatment, respectively. At baseline, 56% of patients reported bleeding symptoms (WHO grades 1–4) compared to 27%, 21%, 40%, and 25% at 6, 12, 18, and 24 months, respectively. Adverse events (AEs) were reported in 248 patients (83%) while on therapy, the majority being mild to moderate. The most common AEs reported were headache (23%), upper respiratory tract infection (17%), nasopharyngitis (17%), fatigue (13%), arthralgia (12%), and diarrhea (11%). Five deaths were reported: 2 occurred on therapy and 3 occurred more than 30 days posttherapy; none considered related to study medication. A total of 24 patients (8%) met any of the hepatobiliary laboratory abnormality screening criteria (ALT ≥3x ULN, AST ≥3x ULN, total bilirubin >1.5x ULN, or alkaline phosphatase >1.5x ULN). Thirteen patients (4%) experienced 16 thromboembolic events (TEEs); 11/13 (85%) experienced the event at a platelet count lower than the maximum platelet count achieved during eltrombopag treatment. Platelet counts proximal to the TEEs ranged from 14,000–407,000/μL. Eighty-six BM biopsies were performed. No clinically relevant effects of eltrombopag on BM were detected. CONCLUSION: Oral eltrombopag treatment for up to 2 years effectively raised platelet counts, decreased bleeding symptoms, and was generally well-tolerated in chronic ITP. Disclosures: Saleh: GlaxoSmithKline: Speakers Bureau; Amgen: Speakers Bureau. Bussel:Genzyme: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Research Funding; Sysmex: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees. Cheng:GlaxoSmithKline: Research Funding. Mayer:GlaxoSmithKline: Employment. Bailey:GlaxoSmithKline: Employment. Aivado:GlaxoSmithKline: Employment.

Cumulative Response to Eltrombopag and Impact of the Number of Prior ITP Therapies: Interim Results of a Long-Term Extension Study,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3297-3297
Author(s):  
James B Bussel ◽  
Christine K Bailey ◽  
Andres Brainsky
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Employment Equity ◽  
Phase 3 ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Equity Ownership

Abstract Abstract 3297 Background: Patients with chronic immune thrombocytopenia (ITP) have an increased risk of bleeding, ranging from minor to life-threatening. The goal of treatment is to increase and maintain platelets in a safe range to prevent bleeding. Guidelines state that achieving platelet counts of 30,000/μL to 50,000/μL in patients without other risk factors avoids the most serious complications of ITP, namely intra-cerebral or gastrointestinal hemorrhage (George 1996; Provan 2010). Many patients are refractory or relapse after multiple treatments. Eltrombopag is an oral, nonpeptide thrombopoietin receptor agonist approved for the treatment of chronic ITP. In 6-week, and 6-month, placebo-controlled trials in patients with heavily pre-treated chronic ITP, eltrombopag increased platelets and reduced bleeding and the need for concomitant ITP therapy (Bussel 2007; Bussel 2009; Cheng 2011). Long-term treatment with eltrombopag is being evaluated in EXTEND, an extension study in chronic ITP patients who completed a previous eltrombopag study (Saleh 2010). Aims: To analyze in EXTEND the ability of eltrombopag to increase platelet counts to ≥50,000/μL in >50% and >75% of assessments and to determine whether the number of prior ITP therapies influences this ability. Methods: Patients in EXTEND received eltrombopag or placebo in 1 of the following prior studies of eltrombopag in chronic ITP: a 6-week phase 2 (TRA100773A; Bussel 2007) or phase 3 (TRA100773B; Bussel 2009) study, a 6-month phase 3 study (RAISE; Cheng 2011), or a phase 3 study of intermittent treatment (REPEAT; Psaila 2008). Dosing in EXTEND is individualized in order to maintain platelet counts ≥50,000/μL and <200,000/μL while minimizing the use of concomitant ITP medications. For the purpose of this analysis, response is defined as a platelet count ≥50,000/μL. Results: Among the 299 patients enrolled in EXTEND between June 2006 and February 2010, 67 (22%), 73 (24%), 47 (16%), and 112 (37%) patients had received 1, 2, 3, and ≥4 prior therapies (excluding eltrombopag). The most commonly used prior therapies were corticosteroids (81%), IVIg (45%), splenectomy (38%), and rituximab (23%). Of the 299 patients enrolled, 70% achieved response in >50% of study assessments and 46% achieved response in >75% of assessments. Among 210 patients treated ≥12 months, 79% achieved response in >50% of assessments and 56% in >75% of assessments. Among 138 patients treated for ≥24 months, 82% achieved response in >50% and 59% in >75% of assessments. Response in >50% and >75% of assessments by the number of prior therapies was similar between the groups (Figure 1). The proportion of patients who achieved a response in >50% of assessments was similar between splenectomized and non-splenectomized patients (65% and 73%, respectively). Conclusion: The majority of patients treated with eltrombopag for ≥12 months achieved a platelet count of ≥50,000/μL in >50% of study assessments. This response was observed even among patients previously treated with 4 or more ITP therapies, suggesting that eltrombopag may be a viable treatment option even for more refractory chronic ITP patients. Disclosures: Bussel: Portola: Consultancy; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cangene: Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sysmex: Research Funding. Bailey:GlaxoSmithKline: Employment, Equity Ownership. Brainsky:GlaxoSmithKline: Employment, Equity Ownership.

Efficacy, Hematologic Effects, and Dose of Ruxolitinib in Myelofibrosis Patients with Low Starting Platelet Counts (50–100 × 109/L): A Comparison to Patients with Normal or High Starting Platelet Counts

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 176-176 ◽  
Author(s):  
Moshe Talpaz ◽  
Ronald Paquette ◽  
Lawrence Afrin ◽  
Solomon Hamburg ◽  
Katarzyna Jamieson ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Phase Iii ◽  
Spleen Volume ◽  
Employment Equity ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Equity Ownership ◽  
Eortc Qlq

Abstract Abstract 176 Background: Ruxolitinib (RUX) has demonstrated clinical benefit for patients with myelofibrosis (MF) with or without the JAK2V617F mutation at starting doses of 15 or 20 mg PO BID by alleviating symptoms, improving quality of life measures, reducing spleen volume and exhibiting an apparent increase in overall survival in the phase III placebo (PBO)-controlled COMFORT-I study. Reversible declines in platelet count and hemoglobin (Hgb) can occur with ruxolitinib but are rarely treatment-limiting. Patients with MF who have low platelet counts represent an important subset of MF patients; given the potential risk of bleeding complications, a dosing strategy for such patients is needed. We assessed an alternative strategy using lower starting doses of ruxolitinib with subsequent dose escalation in patients with MF who have platelet counts of 50–100 × 109/L (Study INCB018424-258; NCT01348490). Methods: RUX dosing started at 5 mg BID. With adequate platelet count, doses could increase by 5 mg once daily every 4 weeks to 10 mg BID. Further increases required evidence of suboptimal efficacy. Assessments include measurement of MF symptoms (MF Symptom Assessment Form v2.0 Total Symptom Score [TSS]); Patient Global Impression of Change (PGIC); EORTC QLQ-C30, measurement of spleen volume by MRI, and safety/tolerability. Results: A total of 50 patients have enrolled, with data available for 41 patients. Nineteen have completed 24 weeks of treatment; >70% of these patients attained a final dose of ≥10 mg BID of RUX. Treatment was generally well tolerated in this study population with no withdrawals for thrombocytopenia or bleeding events. Based on analysis of adverse events, no new safety signals were observed in this population of MF patients with low platelet counts. Data for efficacy parameters, including spleen volume reduction, TSS reduction, and improvement in EORTC-QLQ-C30 subscales and PGIC were consistent with RUX treatment in the COMFORT-I study, and demonstrated clinically meaningful efficacy compared with the COMFORT-I PBO arm (Table). Of 19 patients with platelet count data through Week 24, 5 showed increased platelet count over the duration of the study (range of increase: 20 to 95 x109/L); all 5 patients had optimized dosing to ≥10 mg BID. Compared with the 14 patients showing smaller increases or modest decreases in platelet count, these 5 patients were younger (mean age: 63 years vs. 71 years), had been diagnosed with MF more recently (2.2 years vs. 5.2 years) and had lower DIPSS scores (60% Intermediate-1; 20% Intermediate-2; 20% High vs. 0% Intermediate-1; 79% Intermediate-2; 21% High). Four patients (9.8%) reported adverse events of bleeding (excluding events related to bruising) of any grade (all events were Grade 1 except one Grade 2 hematochezia), consistent with previously reported hemorrhage frequency in the COMFORT-I study (16.8%, RUX; 12.6%, PBO). Conclusions: These preliminary findings suggest that a dosing strategy of a low starting dose of RUX with escalation to 10 mg BID may be appropriate in MF patients who have low platelet counts. Most patients were able to titrate to a dose of ≥10 mg BID of RUX, a dose showing efficacy for both spleen volume and patient-reported outcomes generally consistent with previously reported data from Phase III trials. An increase in platelet counts was observed in approximately one-fourth of patients who completed 24 weeks of RUX treatment. Escalation to, and subsequent maintenance of, a 10 mg BID dose of RUX also preserves both Hgb and platelet count which may be beneficial for MF patients with anemia or thrombocytopenia. Disclosures: Talpaz: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Paquette:Incyte: Consultancy. Jamieson:Sunesis: Membership on an entity's Board of Directors or advisory committees; Blue Distinction Centers for Transplants BlueCross BlueShield Association: Consultancy. Lyons:Amgen: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Novartis: Research Funding. Tiu:Incyte: Honoraria, Speakers Bureau. Winton:Incyte Corporation: Consultancy, Honoraria. Odenike:Incyte: Membership on an entity's Board of Directors or advisory committees; Sanofi-Aventis:Membership on an entity's Board of Directors or advisory committees. Peng:Incyte: Employment, Equity Ownership. Sandor:Incyte: Employment, Equity Ownership. O'Neill:Incyte: Employment, Equity Ownership. Erickson-Viitanen:Incyte: Employment, Equity Ownership. Leopold:Incyte: Employment, Equity Ownership. Levy:Incyte: Employment, Equity Ownership. Kantarjian:Incyte Corporation: grant support Other. Verstovsek:Incyte Corporation: Research Funding.

Plerixafor (Mozobil ®)Plus G-CSF Is Effective in Mobilizing Hematopoietic Stem Cells in Patients with Concurrent Thrombocytopenia Undergoing Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3229-3229 ◽  
Author(s):  
Ivana N Micallef ◽  
Eric Jacobsen ◽  
Paul Shaughnessy ◽  
Sachin Marulkar ◽  
Purvi Mody ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Platelet Counts ◽  
Cd34 Cells ◽  
Low Platelet Count ◽  
Equity Ownership

Abstract Abstract 3229 Poster Board III-166 Introduction Low platelet count prior to mobilization is a significant predictive factor for mobilization failure in patients with non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) undergoing autologous hematopoietic stem cell (HSC) transplantation (auto-HSCT; Hosing C, et al, Am J Hematol. 2009). The purpose of this study is to assess the efficacy of HSC mobilization with plerixafor plus G-CSF in patients with concomitant thrombocytopenia undergoing auto-HSCT. Methods Patients who had failed successful HSC collection with any mobilization regimen were remobilized with plerixafor plus G-CSF as part of a compassionate use program (CUP). Mobilization failure was defined as the inability to collect 2 ×106 CD34+ cells/kg or inability to achieve a peripheral blood count of ≥10 CD34+ cells/μl without having undergone apheresis. As part of the CUP, G-CSF (10μg/kg) was administered subcutaneously (SC) every morning for 4 days. Plerixafor (0.24 mg/kg SC) was administered in the evening on Day 4, approximately 11 hours prior to the initiation of apheresis the following day. On Day 5, G-CSF was administered and apheresis was initiated. Plerixafor, G-CSF and apheresis were repeated daily until patients collected the minimum of 2 × 106 CD34+ cells/kg for auto-HSCT. Patients in the CUP with available data on pre-mobilization platelet counts were included in this analysis. While patients with a platelet count <85 × 109/L were excluded from the CUP, some patients received waivers and were included in this analysis. Efficacy of remobilization with plerixafor + G-CSF was evaluated in patients with platelet counts ≤ 100 × 109/L or ≤ 150 × 109/L. Results Of the 833 patients in the plerixafor CUP database, pre-mobilization platelet counts were available for 219 patients (NHL=115, MM=66, HD=20 and other=18.). Of these, 92 patients (NHL=49, MM=25, HD=8 and other=10) had pre-mobilization platelet counts ≤ 150 × 109/L; the median platelet count was 115 × 109/L (range, 50-150). The median age was 60 years (range 20-76) and 60.4% of the patients were male. Fifty-nine patients (64.1%) collected ≥2 × 109 CD34+ cells/kg and 13 patients (14.1%) achieved ≥5 × 106 CD34+ cells/kg. The median CD34+ cell yield was 2.56 × 106 CD34+ cells/kg. The proportion of patients proceeding to transplant was 68.5%. The median time to neutrophil and platelet engraftment was 12 days and 22 days, respectively. Similar results were obtained when efficacy of plerixafor + G-CSF was evaluated in 29 patients with platelet counts ≤ 100 × 109/L (NHL=12, MM=10, HD=3 and other=4). The median platelet count in these patients was 83 × 109/L (range, 50-100). The median age was 59 years (range 23-73) and 60.4% of the patients were male. The minimal and optimal cell dose was achieved in 19(65.5%) and 3(10.3%) patients, respectively. The median CD34+ cell yield was 2.92 × 106 CD34+ cells/kg. The proportion of patients proceeding to transplant was 62.1%. The median time to neutrophil and platelet engraftment was 12 days and 23 days, respectively. Conclusions For patients mobilized with G-CSF alone or chemotherapy ±G-CSF, a low platelet count prior to mobilization is a significant predictor of mobilization failure. These data demonstrate that in patients with thrombocytopenia who have failed prior mobilization attempts, remobilization with plerixafor plus G-CSF allows ∼65% of the patients to collect the minimal cell dose to proceed to transplantation. Thus, in patients predicted or proven to be poor mobilizers, addition of plerixafor may increase stem cell yields. Future studies should investigate the efficacy of plerixafor + G-CSF in front line mobilization in patients with low platelet counts prior to mobilization. Disclosures Micallef: Genzyme Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jacobsen:Genzyme Corporation: Research Funding. Shaughnessy:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Marulkar:Genzyme Corporation: Employment, Equity Ownership. Mody:Genzyme Corporation: Employment, Equity Ownership. van Rhee:Genzyme Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenia (ITP) Treated with Romiplostim in Two Phase 3 Placebo-Controlled Clinical Trials.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 891-891 ◽  
Author(s):  
Ilene Ceil Weitz ◽  
Miguel A Sanz ◽  
David H. Henry ◽  
Martin Schipperus ◽  
Bertrand Godeau ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Rescue Medication ◽  
Bleeding Event ◽  
Bleeding Events ◽  
Phase 3 ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Chronic Itp

Abstract Abstract 891 Background: Chronic Immune thrombocytopenia (ITP) is characterized by low platelet counts and increased risk of bleeding. Rescue medications used to treat or prevent bleeding produce transient increases in platelet counts but may be associated with additional toxicities and costs. Romiplostim, approved for the treatment of adult chronic ITP, is a TPO mimetic peptibody protein that increases platelet production. Previously published data from phase 3 romiplostim trials showed that despite the increased use of rescue medication in the placebo arm, patient (pt) incidence of bleeding was reduced in the romiplostim arm vs placebo arm: 15% vs 34% (p = 0.02) for bleeding of grade ≥2 severity and 7% vs 12% (p=0.36) for grade ≥3 severity. Objective: To evaluate the effects of romiplostim treatment on bleeding outcomes in the phase 3 placebo controlled studies in chronic ITP pts with and without previous splenectomy. Bleeding events were captured as adverse events making it difficult to identify a single event reported multiple times versus persistent or recurrent bleeding. Further, we have developed a composite endpoint, termed bleeding-related episodes (BREs), which combines bleeding events and rescue medication administration to account for use of rescue medications to prevent bleeding. Methods: Adults with chronic ITP and a mean baseline platelet count <30 × 109/L were eligible. The previously published studies were conducted separately in splenectomized and nonsplenectomized populations. Pts were randomized (2:1) to receive romiplostim or placebo by subcutaneous injection once weekly for 24 weeks, with dose adjustments to maintain platelet counts between 50-200 × 109/L. Rescue medications were permitted to treat or prevent bleeding and included immunoglobulins, platelet transfusions, corticosteroids, or an increase in dose or frequency of a concurrent ITP medication. A BRE was defined as an actual bleeding event and/or the use of rescue medication. To collapse related events into episodes, events (bleeding events and/or the use of rescue medication) that occurred concurrently or within 3 days of each other were considered a single BRE. Bleeding events beginning 7 or more days after the start of the initial bleeding event were considered a new BRE. To account for differences in time spent on-study, rates of BRE per 100 pt-weeks were calculated. Results: A total of 125 pts (41 placebo, 84 romiplostim) were enrolled in the two studies. Baseline characteristics were well-balanced between the placebo and romiplostim-treated groups. During the treatment period, the rate of BREs was lower in the romiplostim group than in the placebo group, and results were consistent between splenectomized and nonsplenectomized pts (Table). Across both studies, the rate of BREs was reduced by 55% in pts receiving romiplostim compared to those receiving placebo (95% CI, 41% to 65%). BREs were more frequent at platelet counts <50 × 109/L (Table). BREs associated with hospitalizations were less common among romiplostim- than placebo-treated pts, and occurred at platelet counts <50 × 109/L in 10 of 11 cases. Corticosteroids (58 romiplostim, 38 placebo) and immunoglobulins (30 romiplostim, 73 placebo), were the most commonly used rescue medications and the rate of BREs including immunoglobulins was reduced by 88% in pts receiving romiplostim compared to placebo. Conclusions: In adults with chronic ITP, romiplostim was associated with a significant reduction in BREs compared to placebo. There was a marked reduction in BREs requiring immunoglobulins in the romiplostim arm compared to the placebo arm. Results were comparable in splenectomized and nonsplenectomized populations. The platelet count for a BRE starting ≥1 day after a platelet count measurement was calculated from the 2 proximal weekly measurements. Disclosures: Weitz: Amgen Inc.: Speakers Bureau. Sanz:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Henry:Amgen Inc.: Research Funding, Speakers Bureau; Orthobiotech: Research Funding, Speakers Bureau; Watson Pharma: Research Funding, Speakers Bureau. Schipperus:Amgen Inc.: Membership on an entity's Board of Directors or advisory committees. Godeau:Amgen Inc.: Consultancy, Research Funding; Laboratoire Français de Fractionnement et de Biotechnologies (LFB): Consultancy; Roche: Research Funding. Gleeson:Amgen Inc.: Consultancy, Research Funding. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

Rituximab Plus Three Cycles of Dexamethasone In the Treatment of Immune Thrombocytopenia (ITP): a Pilot Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3697-3697
Author(s):  
Rebecca Elstrom ◽  
Soo Y. Lee ◽  
James B. Bussel
Keyword(s):  
Platelet Count ◽  
Pilot Study ◽  
Board Of Directors ◽  
Initial Treatment ◽  
Research Funding ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Almost All

Abstract Abstract 3697 Introduction: Rituximab has been a useful treatment for patients with ITP; many hundreds of patients have been treated. 30–40% of patients will achieve a complete remission (CR: platelet count >150 × 109/l) with initial treatment and, of this group, the CR will last at least a year in almost all patients. However, emerging data suggests that at least 40% of these patients in CR will relapse between 1 and 3 years from initial treatment suggesting that long-term “cures” only occur in 20% of the initial patients. Therefore it would be desirable if CR's could be achieved in more patients and especially if these would be durable in more than 20%. One approach would be to use rituximab maintenance, however it results in suppression of B-cells for more than 2 years. Dexamethasone has also been used to achieve “cure” in ITP especially in adults at or near diagnosis. Cheng's study suggested that approximately 50% of patients would achieve a long-term response with only one 4-day cycle of high dose (40 mg/day) dexamethasone (N Engl J Med, 2003). A follow up study from GIMEMA suggested that 3–4 cycles of dexamethasone would be better than 1 cycle (Blood, 2007). Finally, Zaja's study suggested that rituximab plus one cycle of dexamethasone was superior to dexamethasone alone with a > 50% CR rate at 6 months (Blood, 2010). Therefore, we elected to perform a pilot study to explore the combination of rituximab with three cycles of dexamethasone at 14 day intervals. Methods: Patients with ITP with platelet counts < 30,000 off therapy and in need of treatment were enrolled. The standard dose (4 infusions of 375mg/m2) rituximab was given on days 1, 8, 15 and 22 and dexamethasone 40 mg (adjusted for size) on days 1–4, 15–18, and 29–32. Results: Fourteen patients between the ages of 4 and 53 years with ITP were treated with rituximab and dexamethasone (R&D) (Table 1). All had received previous steroid therapy as well as other treatments. The median platelet count was 40,000 at initiation of rituximab (range 7,000-230,000); several patients with low counts started with dexamethasone prior to initiating Rituximab to sustain their counts during initial treatment. Patients received rituximab weekly for between 2 and 4 doses and dexamethasone for either 2 or 3 courses at intervals between 1 and 8 weeks (median 2 week intervals). A summary of the results is shown in table 2 demonstrating short-lived platelet increases in response to dexamethasone in almost all patients. With short follow up, there were 7 CR's, 3 PR's and 4 NR's. If this was divided by duration of ITP prior to R&D, there were 4 CR's and 1 NR for ≤ 12 months and 3 CR, 3 PR, and 3 NR for > 12 months. More of the children who were treated had chronic disease than did adults explaining their apparently poorer response. Observed toxicities included hyperglycemia, grade 1 and 2 liver function abnormalities, weight gain, and 1 episode of colitis requiring hospitalization. Three patients opted to skip the third cycle of dexamethasone. Conclusion: A regimen of rituximab + 2–3 courses of dexamethasone is active in patients with pretreated ITP with appreciable but usually manageable toxicity. It appears to yield superior results if administered to patients within one year of diagnosis. This combination merits further exploration in a prospective clinical trial. Disclosures: Bussel: Portola: Consultancy; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc.: Membership on an entity's Board of Directors or advisory committees; Cangene: Research Funding; Genzyme: Research Funding.

Final Results from an International, Multi-Center, Single-Arm Study Evaluating the Safety and Efficacy of Romiplostim in Adults with Primary Immune Thrombocytopenia (ITP),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3279-3279 ◽  
Author(s):  
Ann Janssens ◽  
Michael D. Tarantino ◽  
Robert Bird ◽  
Maria Gabriella Mazzucconi ◽  
Ralph Vincent V. Boccia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Platelet Response ◽  
Employment Equity ◽  
Advisory Committees ◽  
Platelet Production ◽  
Platelet Counts ◽  
Equity Ownership

Abstract Abstract 3279 Background: ITP is an autoimmune disorder characterized by increased platelet destruction and suboptimal platelet production. Romiplostim stimulates platelet production via the TPO-receptor, and is recommended for second- and third-line treatment of chronic ITP in adults. We report final data from a large prospective study of romiplostim in adults with ITP of varying duration and severity. Methods: Eligibility criteria were broad: patients ≥18 years of age, who had received prior ITP therapies (final protocol amendment: ≥1, previous amendments: ≥3), with low platelet counts (final amendment: ≤ 30 × 109/L, previous amendments: ≤ 10, ≤ 20 × 109/L) or experiencing uncontrolled bleeding. The only excluded comorbidities were: hematological malignancy, myeloproliferative neoplasms, MDS and bone marrow stem cell disorder. Romiplostim was initiated at 1 (final amendment) or 3 (previous amendments) μg/kg/week, with dose adjustments allowed to maintain platelet counts ≥50 × 109/L. Patients could continue on study until they had access to commercially available romiplostim. Rescue medications were allowed at any time; concurrent ITP therapies could be reduced when platelet counts were > 50 × 109/L. Primary endpoint was incidence of adverse events (AEs) and antibody formation. Secondary endpoint was platelet response, defined as either (1) doubling of baseline count and ≥ 50 × 109/L or (2) ≥20 × 109/L increase from baseline. Results: A total of 407 patients received romiplostim, 60% of whom were female. Median (Q1, Q3) time since ITP diagnosis was 4.25 (1.20, 11.40) years (maximum 57.1 years), with 51% of patients splenectomised and 39% receiving baseline concurrent ITP therapies. Seventy-one percent of patients completed the study, with requirement for alternative therapy and withdrawn consent the most common reasons for discontinuation (5% each). Median (Q1, Q3) on-study treatment duration was 44.29 (20.43, 65.86) weeks (maximum 201 weeks), with a total of 20,201 subject-weeks on study. Incidence and type of AEs were consistent with previous studies. The most common serious treatment-related AEs were cerebrovascular accident, headache, bone marrow reticulin fibrosis (with no evidence of positive trichrome staining for collagen and no evidence suggesting primary idiopathic myelofibrosis), nausea, deep vein thrombosis, hemorrhage and pulmonary embolism, with each reported in 2 of 407 (0.5%) patients. All other serious treatment-related AEs were each reported in one patient. Eighteen patients died; 3 deaths (hemolysis, intestinal ischaema, aplastic anemia) were considered treatment-related. No neutralizing antibodies to romiplostim or TPO were reported. Approximately 90% of patients achieved each of the platelet response definitions, regardless of splenectomy status. Overall, median (Q1, Q3) time to response was 2 (1, 4) weeks for response definition 1, and 1 (1, 3) week for response definition 2. Median (Q1, Q3) baseline platelet count was 14 (8, 21) × 109/L. After 1 week of treatment median (Q1, Q3) platelet count had increased to 42 (18, 101) × 109/L. From week 8 onwards, and excluding counts within 8 weeks of rescue medication use, median platelet counts were consistently above 100 × 109/L (range 101.0–269.5 × 109/L). Median (Q1, Q3) average weekly romiplostim dose was 3.62 (1.99, 6.08) μg/kg. Summary/conclusions: This is the largest prospective study in adult ITP reported to date. The data reported here are similar to those reported for previous romiplostim studies, with romiplostim able to safely induce a rapid platelet response in adult ITP patients with low platelet counts or bleeding symptoms. Romiplostim is an important, well-tolerated, treatment option for adult ITP patients, which significantly increases and maintains platelet counts. Adverse Event Subject Incidence Platelet Response Disclosures: Janssens: Amgen: Consultancy; Roche: Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees. Tarantino:Cangene corporation: Research Funding; Baxter: Research Funding; Talecris: Honoraria, Speakers Bureau; Up-to-date: Patents & Royalties; The Bleeding and Clotting Disorders Institute: Board Member. Bird:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees. Boccia:Amgen: Equity Ownership, Honoraria, Speakers Bureau. Lopez-Fernandez:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kozak:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Steurer:Amgen: Honoraria. Dillingham:Amgen Limited: Employment, Equity Ownership. Lizambri:Amgen: Employment, Equity Ownership.

Sports Participation in Children with ITP: A Case for Liberalization?

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3339-3339 ◽  
Author(s):  
Sophie Brigstocke ◽  
Catherine E. McGuinn ◽  
James B Bussel
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Sports Participation ◽  
Contact Sport ◽  
Advisory Committees ◽  
Contact Sports ◽  
Platelet Counts ◽  
Risk Of Injury ◽  
Frequency Of Sports Participation

Abstract Abstract 3339 Background: Children with ITP are at risk for bleeding. ITP is one of many conditions for which the American Academy of Pediatrics advises a pre-sports participation evaluation to assess the risk of injury (Rice 2008). However, restrictions in sports participation might deny the many evidence-based benefits of such physical activity usually accessible for US school-aged youth, thereby presenting significant health and quality of life issues. Aims: To better assess the frequency of sports participation and sports-related injury outcomes relative to contact level by gathering data via questionnaire from a convenience sample of children with persistent and chronic ITP. Methods: Fourteen different types of sports activities were included in this IRB-approved questionnaire and were classified as contact, limited contact, or non-contact as determined by the American Academy of Pediatrics Council on Sports Medicine and Fitness (Rice 2008). Questions were aimed at the frequency of sports participation, types of sports played, sports-related injuries (including bleeding), medical care required for injuries, and comfort regarding continued participation in a sport after sustaining an injury. For each sport not played, questions assessed reasons for the subject's decision to refrain from participation. Patients were categorized according to their platelet levels: counts ≤ 50, 50–150, >150; counts ≤ or >50; counts ≤ or >30 (×109/L). Proportions of data involving 2 groups were compared in a contingency table using Fisher's exact test with trends ≤ 0.01 and significance ≤ 0.025. Results: Twelve subjects (19%) did not participate in any sports. Thirty-six (56%), including patients across all platelet counts, participated in at least one contact sport. There was no statistically significant association (p > 0.1) between the subject's platelet count and the contact level of sport chosen to play. However, a significant association was found between higher frequency of sports participation and higher platelet count (analyzed by groups ≤ or >50 and counts ≤ or >30 (×109/L)) when the highest frequency of participation in any sport (regardless of contact level) was assessed (p < 0.025). When only the sport with the highest contact rating was considered, patients with higher counts played their highest contact sport more frequently than did those patients with lower counts. In particular, subjects with counts ≤ 30 ×109/L played their highest contact sport less frequently, eg more commonly < 1x/month, compared to subjects with platelet counts > 30 ×109/L who played more commonly > 1x/month (p=0.025) [figure]. Twenty injuries were recorded across 10 different sports and 17 patients, but no serious bleeding injuries were reported. There was a statistically significant association (p = 0.002) between higher contact levels and greater incidence of injury. However, there was no statistically significant association (p > 0.1) between estimated platelet count at time of injury and the contact level of sport. As recorded by the patients and/or the patients' parents, 26% of general concerns came from physicians, 53% from parents and 21% from patients themselves. Data collected on the participants' personal concerns showed that higher platelet counts were associated with fewer personal concerns being expressed (p < 0.025). However, when each personal concern was analyzed there were no statistically significant trends or associations (p > 0.1) found between any specific concern and platelet count. Across all contact and limited-contact sports, the most frequently expressed concern was that the sport was too dangerous. The most frequently expressed concern for non-contact sports was that the patient was too tired to play. Conclusions: There was a significant association between higher frequency of sports participation, but not higher contact level, with higher platelet counts. Higher incidences of injury were associated with higher contact levels, but not with lower platelet counts, suggesting that children with ITP can participate in non-contact sports and many contact and limited-contact sports with low risk of injury. Therefore, we believe that sports participation for children with ITP is generally too restricted and greater encouragement for children to be athletic in the sport of their choice is warranted. Disclosures: Bussel: Sysmex: Research Funding; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; IgG of America: Research Funding; Genzyme: Research Funding; GlaxoSmithKline: Family owns GSK stock, Family owns GSK stock Other, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Amgen: Family owns Amgen stock Other, Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Consultancy.

Sign in / Sign up

Export Citation Format

Share Document