Incidence of Thromboembolic Events Across Eltrombopag Clinical Trials In Chronic Immune Thrombocytopenia (ITP)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 70-70 ◽  
Author(s):  
James B. Bussel ◽  
Gregory Cheng ◽  
Mansoor N. Saleh ◽  
Bhabita Mayer ◽  
Sandra Y. Vasey ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Platelet Count ◽  
Odds Ratio ◽  
Incidence Rates ◽  
Thromboembolic Events ◽  
Phase 2 ◽  
Double Blind ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Equity Ownership

Abstract Abstract 70 Introduction: Chronic ITP is characterized by decreased platelet counts resulting from autoantibody-mediated peripheral platelet destruction and suboptimal platelet production. Eltrombopag is an oral, thrombopoietin receptor agonist approved for the treatment of ITP in the USA and elsewhere. Thromboembolic events (TEEs) can occur in patients with ITP; it has been speculated that ITP has prothrombotic characteristics and that low platelet counts may prevent a higher incidence of TEEs (Sarpatwari, 2010; Aledort, 2004; Zelcer, 2003). In the UK General Practice Research Database, incidence rates for TEEs were 1.35/100 patient years (PYs) (95% CI [0.99, 1.79]) for patients with ITP vs 1.16/100 PYs (95% CI [0.99, 1.35]) in patients without ITP (Sarpatwari, 2010). Similar results were found in a US claims database study (Bennett, 2008) and in romiplostim studies (Bussel, 2009). In this study we evaluated the incidence of TEEs in patients with chronic ITP treated with eltrombopag. Methods: Data from 446 patients with chronic ITP exposed to eltrombopag were analyzed from 5 eltrombopag clinical trials: two 6-week, randomized, double-blind, phase 2 and 3 studies, with patients on eltrombopag (n=164) or placebo (n=67) (Bussel, 2007; Bussel, 2009); RAISE, a 6-month, randomized, double-blind, phase 3 study, with 135 patients on eltrombopag and 62 on placebo (Cheng, 2010); REPEAT, a phase 2 study with 66 patients on eltrombopag for 3 cycles of 6 weeks on-therapy followed by up to 4 weeks off therapy (Psaila, 2008); and EXTEND, an ongoing extension study with 299 of the same patients on eltrombopag for at least 2 years (Cheng, 2008). The first occurrence of a TEE was used in the calculation of the incidence rates across the ITP program. Confirmed or suspected cases of TEEs were either reported by investigators or identified after sponsor evaluation based on symptoms reported as adverse events (AEs) that were potentially compatible with a TEE. In an additional analysis, the odds ratio for a TEE at different platelet thresholds was investigated to assess if a direct relationship could be established. Results: Across the ITP program, 20 patients (4.5%, 20/446) exposed to eltrombopag have experienced 27 TEEs. The TEEs were DVT (12), pulmonary embolism (6), MI (4), ischemic stroke (3), suspected prolonged reversible ischemic neurologic deficit (1), and transient ischemic attack (1). No placebo-treated patient experienced a TEE. The PYs of exposure to study medication was approximately 17 times greater than PYs of exposure to placebo (eltrombopag 584.4 PYs; placebo 35.4 PYs). Despite the increased exposure to eltrombopag in the EXTEND study, the incidence of TEEs (3.14/100 PYs, 95% CI [1.92, 4.85]) decreased compared to previously reported data (4.04/100 PYs, 95% CI [2.35, 6.46], Bussel, 2009). There was no clear pattern observed with regard to time to TEE onset; events were reported as early as day 1 and up to day 981 (median time to onset 229 days). The platelet counts most proximal to the events ranged between 14,000/μ L and 482,000/μ L (median 143,000/μ L). The majority of patients (55%, 11) had platelet counts below the normal range at the time of the TEE (<150,000/μ L). 4/20 patients experienced the TEE closest to their maximum platelet count achieved on study, whereas the majority (80%, 16/20) experienced the TEE at a lower platelet count than their maximum platelet count during treatment with eltrombopag. As seen in the Table, no changes in the odds ratio for a TEE at different platelet thresholds were observed. All patients experiencing a TEE had at least one risk factor for TEE; analysis did not reveal any one risk factor that was associated with the majority of cases. Two of 15 patients with TEEs tested had positive results for heterozygous Factor V Leiden mutation. Conclusions: There is no increase in the incidence rate of TEEs across the ITP program despite longer duration of eltrombopag treatment. The data presented here confirm previous observations that there is no evidence of a correlation between platelet count increases and the occurrence of TEEs in patients with chronic ITP on eltrombopag. Disclosures: Bussel: GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Cheng:GlaxoSmithKline: Consultancy, Honoraria, Speakers Bureau. Saleh:GlaxoSmithKline, Novartis, Imcoline, Celgene: Honoraria, Speakers Bureau. Mayer:GlaxoSmithKline: Employment, Equity Ownership. Vasey:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: 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.

Safe and Effective Use Of Romiplostim and Eltrombopag In Children With ITP

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3541-3541 ◽  
Author(s):  
Emily Leven ◽  
Loan Hsieh ◽  
Kavitha Ramaswamy ◽  
Catherine E. McGuinn ◽  
Diane Nugent ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Board Of Directors ◽  
Research Funding ◽  
Randomized Clinical Trials ◽  
Small Sample ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Concurrent Therapy ◽  
Chronic Itp ◽  
Equity Ownership

Abstract Introduction The thrombopoietin (TPO) mimetic agents romiplostim and eltrombopag are used to stimulate platelet production and increase platelet counts in chronic immune thrombocytopenia (ITP) in adults. While two large, randomized trials investigating dosing, safety, and efficacy were ongoing in children, but not near completion, we conducted a retrospective IRB-approved analysis of 33 pediatric (≤21 years) chronic ITP patients from two centers treated with TPO agents off-study. Patients Patients initiated TPO therapy prior to 21 years of age (19 months to 19 years, median 14 years) after an average of 3.6 ITP therapies; 21 patients received romiplostim [11 at Children's Hospital of Orange County (CHOC), 10 at Weill Cornell Medical Center (WCMC)] and 12 eltrombopag [all at WCMC]. Median starting age was 11.5 years for patients on romiplostim and 16.5 years on eltrombopag. Primary response measures were: platelet counts ≥ 50 x 109 per liter or ≥20 x 109 per liter above baseline for 2 consecutive weeks and 50% of platelet counts ≥ 50 x 109 per liter. Duration of treatment and bone marrows with myelofibrosis (MF) consensus grade are shown in Figure 1. Results 27/33 (82%) patients responded to TPO agents; 18/21 to romiplostim and 9/12 to eltrombopag. Ten patients responded to ROMIPLOSTIM as a single agent; 8 romiplostim responders received concurrent medications including: mycophenolate mofetil (MMF), azathioprine (AZA), rituximab, and cyclosporine (CSA). One of two splenectomized patients was able to wean off TPO therapy with adequate counts. Two additional patients successfully discontinued TPO therapy and continued on MMF alone. Two patients (1 CSA, 1 AZA) successfully discontinued TPO therapy and then weaned off concurrent therapy. Eighteen of 21 patients had platelet counts ≥ 50 x 109 per liter or ≥20 x 109 per liter above baseline for 2 consecutive weeks and 18 had 50% of platelet counts ≥ 50 x 109 per liter (table). In this study, duration of successful romiplostim use outside of randomized clinical trials ranged from 6-44 months (11/18 ongoing). 3 patients did not respond and 2/3 went on to have therapeutic splenectomies. 1 patient with Evans syndrome had a transient 1 year response before relapsing. 5 responders to romiplostim had previously received eltrombopag with lesser or no effect. Nine of 12 patients responded to ELTROMBOPAG with platelet counts ≥ 50 x 109 per liter or ≥20 x 109 per liter above baseline for 2 consecutive weeks and 8/12 had 50% of platelet counts ≥ 50 x 109 per liter. One patient had been splenectomized; 7 responded to eltrombopag alone. 2 patients had concurrent therapy with prednisone and IV Anti-D and 1/2 was able to discontinue concurrent prednisone. One patient successfully discontinued eltrombopag with adequate counts for > 1 year. 5 patients attempted unsuccessfully to discontinue therapy. One responder, a previous romiplostim responder, switched to eltrombopag. No other patients were treated with TPO agents prior to starting eltrombopag. Duration of successful eltrombopag use outside of randomized clinical trials ranged from 23-53 months (7/12 are ongoing). Three patients did not respond to eltrombopag; 1/3 was HIV positive. One patient experienced a provoked DVT at site of ankle fracture while using eltrombopag. No other patients on either therapy experienced serious drug-related adverse events. Among 24 bone marrows (both agents; 21 reflecting off study use), only MF grades 0 -1 were seen. 10/24 marrows were performed after greater than 2 years of therapy. Conclusion Retrospective analysis of off-study use of eltrombopag and romiplostim in children shows that these TPO agents effectively increase platelet counts in more than 3/4 of children with chronic ITP, a result consistent with adult TPO use. Despite small sample size, the long-term duration of successful use (6-53 months) without tachyphylaxis supports efficacy. Re safety, the one DVT appeared to be precipitated by a fracture and there were no MF2/3 bone marrows in the 24 samples. In those patients who do not respond to one TPO agent, it may be beneficial to switch to the other form. Disclosures: Nugent: Bayer: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria. Bussel: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; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Amgen: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Symphogen: Membership on an entity’s Board of Directors or advisory committees.

scholarly journals PETIT and PETIT 2: Treatment with Eltrombopag in 171 Children with Chronic Immune Thrombocytopenia (ITP)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1450-1450 ◽  
Author(s):  
James B. Bussel ◽  
John D. Grainger ◽  
Purificacion Garcia de Miguel ◽  
Jenny M. Despotovic ◽  
Franco Locatelli ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Research Funding ◽  
Employment Equity ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Thrombopoietin Receptor ◽  
Count Response ◽  
Equity Ownership

Abstract Background: Eltrombopag (EPAG), an oral thrombopoietin receptor agonist, is approved for treating thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) with insufficient response to prior therapy. Pooled data from 2 similarly designed, randomized, double-blind, placebo (PBO)-controlled studies investigating safety and efficacy of EPAG in pediatric ITP are presented here. Methods: Subjects aged 1 to <18 years with a confirmed diagnosis of persistent or chronic ITP and a platelet count <30 Gi/L at day 1 were randomized 2:1 to EPAG or PBO and stratified by age: 12–17 years (Cohort 1), 6–11 years (Cohort 2), and 1–5 years (Cohort 3). Subjects could continue baseline ITP medications. After the PBO-controlled randomized phase, subjects were permitted to complete 17 or 24 weeks of treatment with open-label (OL) EPAG. Dose was adjusted based on platelet counts to a maximum of 75 mg daily. Results: A total of 174 subjects were enrolled in both studies; 171 received ≥1 dose of EPAG. 159 subjects were randomized (intent-to-treat population), and 157 received ≥1 dose of randomized study treatment (safety population). In the randomized period, 3 EPAG and 1 PBO subject discontinued study treatment, of which 2 EPAG and 1 PBO discontinued due to adverse events (AEs). In the OL-EPAG period, an additional 14 EPAG subjects discontinued study treatment, 6 due to AEs. Males comprised 47% of the EPAG and PBO groups and 20% and 24% were East Asians, respectively. Most subjects (93%) were diagnosed with ITP for ≥12 months, and 13% were receiving ITP medications at baseline. The majority of subjects (81%) received ≥2 prior ITP therapies. Most subjects (59%) had a baseline platelet count <15 Gi/L. All 9 (6%) splenectomized subjects were randomized to the EPAG group. Randomized Period A higher proportion of EPAG versus PBO subjects (62% vs 24%; P < 0.001) achieved a response with platelet counts ≥50 Gi/L at least once between weeks 1–6 (Cohort 1, 64% vs 11%; Cohort 2, 64% vs 27%; Cohort 3, 54% vs 36%, respectively). At each week, a higher proportion of EPAG subjects had a response versus PBO (Fig. 1). A lower proportion of EPAG subjects (13%) received rescue treatment compared with PBO subjects (31%; P = 0.009). The odds of having World Health Organization (WHO) bleeding grades 1–4 (0.19; P = 0.011) and clinically significant (WHO grades 2–4) bleeding (0.29; P = 0.007) were lower for EPAG versus PBO subjects. EPAG-Only Period Sustained reduction or discontinuation of baseline ITP medications, primarily corticosteroids, was achieved by 50% of subjects; 81% of subjects had a platelet count response at least once; 52% (n = 80/154) had a platelet count response for ≥50% of assessments; and 38% (n = 58/154) responded for ≥75% of assessments. For >13 of 24 weeks, 47% of subjects achieved responses (Fig. 2). The median average daily dose for EPAG-exposed patients in Cohorts 1, 2, and 3 were 64.0 mg (0.93 mg/kg), 57.6 mg (1.50 mg/kg), and 37.0 mg (2.02 mg/kg), respectively. AEs Similar proportions of subjects in the EPAG and PBO groups reported an AE during the randomization period. The most common AEs (≥10% of subjects) were headache, upper respiratory tract infection, and nasopharyngitis in the EPAG group, and headache, epistaxis, and vomiting in the PBO group. Serious AEs (SAEs) were reported in 8% of EPAG subjects versus 12% of PBO subjects. No SAEs were reported by >1 subject in either treatment group except epistaxis, which was reported by 2 subjects in the PBO group. No SAEs were common to both treatment groups. In the randomized period, an ALT elevation of ³3 x ULN occurred in 5 (4.7%) subjects in the EPAG group and no subjects in the PBO group. In the OL period, there were an additional 7 subjects with ALT ³3 x ULN. All elevations resolved either while still on treatment or after discontinuation of study treatment. Overall, the hepatobiliary laboratory findings were mostly mild, reversible, and not accompanied by impaired liver function. Fewer EPAG than PBO subjects reported bleeding AEs (17% vs 36%, respectively). No thromboembolic events were reported. Cataract events were experienced by 2 subjects who received EPAG; both had used corticosteroids and 1 had pre-existing cataracts. Conclusions: EPAG was safe and raised platelet counts in 62% of pediatric patients with persistent and chronic ITP during the randomized phase. Treatment with EPAG was well tolerated in both studies as evidenced by the low incidence of treatment discontinuations due to AEs. Disclosures Bussel: Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Rigel: Honoraria; Novartis: Honoraria; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; IgG of America: Research Funding; GlaxoSmithKline: Equity Ownership, Honoraria, Research Funding; Genzyme: Research Funding; Eisai, Inc.: Research Funding; Cangene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Amgen: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Symphogen: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding. Off Label Use: Eltrombopag is a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in adults with chronic ITP. Use in children and adolescents will be discussed.. Grainger:GlaxoSmithKline: Honoraria; Baxter: Honoraria, Research Funding; Amgen: Honoraria. Pongtanakul:GlaxoSmithKline: Research Funding. Komvilaisak:GlaxoSmithKline: I am an investigator on this study. Other. Sosothikul:CSL Behring: Research Funding; GlaxoSmithKline: Research Funding. Drelichman:GlaxoSmithKline: I am investigator on this study. Other. David:GlaxoSmithKline: Research Funding. Marcello:GlaxoSmithKline: Employment. Iyengar:GlaxoSmithKline: Employment. Chan:GlaxoSmithKline: Employment. Chagin:GlaxoSmithKline: Employment. Theodore:GlaxoSmithKline: Employment, Equity Ownership. Bakshi:GlaxoSmithKline: Employment, Equity Ownership. Bailey:GlaxoSmithKline: Employment, Equity Ownership.

EXTEND Study Update: Safety and Efficacy of Eltrombopag In Adults with Chronic Immune Thrombocytopenia (ITP) From June 2006 to February 2010

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 67-67 ◽  
Author(s):  
Mansoor N. Saleh ◽  
Gregory Cheng ◽  
James B. Bussel ◽  
Huiping Sun ◽  
Bhabita Mayer ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Thromboembolic Events ◽  
Bone Marrow Biopsies ◽  
Baseline Platelet Count ◽  
Safety And Efficacy ◽  
Platelet Counts ◽  
Equity Ownership ◽  
Chronic Immune Thrombocytopenia

Abstract Abstract 67 Background: Eltrombopag is an oral thrombopoietin receptor agonist approved for treatment of chronic immune thrombocytopenia (ITP) in the US and other countries. In 6-week and 6-month placebo-controlled trials, eltrombopag safely increased platelet counts and reduced bleeding symptoms in patients with previously treated chronic ITP. The safety and efficacy of eltrombopag treatment are being evaluated in EXTEND, an ongoing open-label, extension study in ITP patients who completed a previous eltrombopag study. Methods: Enrolled patients had previously received eltrombopag or placebo in one of the following studies: two 6-week studies (773A and B), RAISE (6-month), or REPEAT (intermittent treatment). In EXTEND, specific goals include: 1) identification of a dose of eltrombopag that increases platelet counts (≥100,000/μ L) to support reduction of concomitant ITP medications (if taken); 2) identification of minimally effective doses of eltrombopag and concomitant ITP medication to maintain platelet counts ≥50,000/μ L; and 3) evaluation of the safety and efficacy of eltrombopag. Patients who completed at least 2 years of therapy and transitioned off study due to commercial availability of eltrombopag were considered to have completed the study. Results: Of 299 patients enrolled, 8% (23) completed the study, 41% (122) withdrew, and 52% (154) remain on study. The main reasons for withdrawal were adverse events (AEs, 11%), patient decision (11%), and lack of efficacy (10%). At baseline, platelet counts were ≤15, >15–<30, 30–50, and >50,000/μ L in 43%, 27%, 17%, and 13% of patients, respectively; 38% of patients were splenectomized; 33% were receiving concomitant ITP medication at baseline, and 53% had received ≥3 previous ITP therapies. 249, 210, 138, and 24 patients had been taking eltrombopag for ≥26, 52, 104, and 156 weeks, respectively, with a median duration of exposure of 100 weeks at the time of data analysis. The proportion of patients achieving a platelet count ≥50,000/μ L was similar regardless of the following baseline characteristics: splenectomy (84%) vs no splenectomy (89%); use of ITP medication (88%) vs no use of ITP medication (87%); and baseline platelet count <30,000/μ L (83%) vs 30–50,000/μ L (98%) vs >50,000/μ L (95%). Overall, 87% (261/299) of patients achieved a platelet count ≥50,000/μ L on treatment; 37 of these had a baseline platelet count of ≥50,000/μ L. Median platelet counts increased to ≥50,000/μ L by week 2 and remained consistently ≥50,000/μ L through week 164. The incidence of any bleeding symptoms (WHO grades 1–4) declined from 56% at baseline to 16% and 20% at weeks 52 and 104, respectively. Clinically significant bleeding (WHO grades 2–4) was reduced from 16% (47/299) at baseline to 3% (2/77) and 7% (3/41) at weeks 52 and 104, respectively. AEs and SAEs occurred in 88% (262) and 26% (79) of patients, respectively. The most frequent AEs were headache (26%), nasopharyngitis (23%), and upper respiratory tract infection (21%). AEs led to withdrawal of 13% (38) of patients, 9% (27) of which were due to SAEs. Twenty-one thromboembolic events (TEE) have been reported in 5% (16) of patients; the incidence rate is 3.17/100 patient years (95% CI [1.81, 5.15]). The most common TEEs were DVT (8) and MI (4). No association has been observed with elevated platelet counts, as only 3/16 patients experienced the TEE closest to their maximum platelet count achieved on study. Hepatobiliary laboratory abnormalities were reported in 29 patients (10%). All were reversible; the majority while on therapy. Of 299 patients enrolled, 6 (2%) have been withdrawn due to a hepatobiliary AE. After examining bone marrow biopsies from >150 patients treated with eltrombopag for >1 year, no clinically relevant increase in reticulin fiber deposition has been observed. Conclusions: Eltrombopag was effective in increasing and maintaining platelet counts ≥50,000/μ L and reducing bleeding symptoms. Eltrombopag has an overall positive risk/benefit assessment and was well tolerated during treatment of patients with chronic ITP even with exposures of more than 3 years. Bone marrow biopsies will continue to be assessed. Hepatobiliary laboratory abnormalities and thromboembolic events are risks that need to be monitored. Disclosures: Saleh: GlaxoSmithKline, Novartis, Imcoline, Celgene: Honoraria, Speakers Bureau. Cheng:GlaxoSmithKline: Consultancy, Honoraria, Speakers Bureau. Bussel:GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Mayer:GlaxoSmithKline: Employment, Equity Ownership. Bailey:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment.

Evaluation of Bleeding-Related Episodes in Patients with Chronic Immune Thrombocytopenic Purpura (ITP) Receiving Romiplostim or Medical Standard of Care.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1311-1311 ◽  
Author(s):  
Roberto Stasi ◽  
Magaral Murali ◽  
Marc Michel ◽  
Jean-Francois Viallard ◽  
Aristoteles Giagounidis ◽  
...  
Keyword(s):  
Platelet Count ◽  
Treatment Period ◽  
Rescue Medication ◽  
Standard Of Care ◽  
Employment Equity ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Increased Risk ◽  
Medical Standard ◽  
Equity Ownership

Abstract Abstract 1311 Poster Board I-334 Background Chronic ITP is an autoimmune disease characterized by low platelet counts and increased risk of bleeding that may be severe or even fatal. Rescue medications, most commonly intravenous immunoglobulins, are used to treat or prevent bleeding but produce only transient increases in platelet counts in most cases and may have issues with toxicity. Romiplostim is a peptibody protein designed to increase platelet production by binding to and activating the thrombopoietin receptor, and is approved for the treatment of adult chronic ITP. Objective To determine the effects of romiplostim treatment on bleeding outcomes during a phase 3b, randomized, open-label study, in adult nonsplenectomized ITP patients receiving either romiplostim or medical standard of care (SOC). We have developed a clinically-relevant composite endpoint, termed bleeding-related episode (BRE). A BRE was considered to be either an actual bleeding event, and/or the use of rescue medication to treat or prevent bleeding. Methods Patients were randomized (2:1) to romiplostim or SOC. Eligible patients were required to have either a platelet count <50×109/L or have had their platelet count fall to <50×109/L during or after a clinically-indicated taper or discontinuation of current ITP therapy. Once-weekly subcutaneous romiplostim was administered with dose adjustments to target a platelet count between 50 and 200 × 109/L. SOC treatments were prescribed according to standard institutional practices or therapeutic guidelines. Since many types of ITP treatment could be administered in the SOC group, for the purpose of this analysis rescue medication was defined as any use of immunoglobulins (intravenous immunoglobulin or Anti-D), intravenous steroids, or platelet transfusions. In order 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 clinical episode. Rates of BREs per 100 patient-weeks were calculated from the number of events/episodes divided by the number of patient-weeks on study treatment, multiplied by 100. Results During the 52-week treatment period, the total number of patient-weeks for the romiplostim group (N=154) was 7087, and for the SOC group (N=70) was 2571. During the treatment period, the rate of BREs was lower in the romiplostim group than the SOC group (see Table), with a 67% reduction in the rate of BREs in patients receiving romiplostim compared to SOC (95% CI, 60% to 73%). The rate of BREs involving the use of immunoglobulins was also lower in the romiplostim group, with a 95% reduction in the rate of BREs in patients receiving romiplostim compared to those receiving SOC (95% CI, 92% to 97%). Conclusions Compared to SOC, romiplostim was associated with a reduction in all BREs as well as BREs involving immunoglobulin use. Disclosures Stasi: Amgen Inc.: Honoraria, Speakers Bureau; GlaxoSmithKline: Honoraria, Speakers Bureau. Giagounidis:Amgen Inc.: Consultancy, Speakers Bureau. Janssens:Roche: Honoraria. Legg:Amgen Inc.: Employment, Equity Ownership. Danese:Amgen Inc.: Consultancy, Research Funding. Deuson:Amgen Inc.: Employment, Equity Ownership.

A Randomized, Double-Blind, Placebo-Controlled Phase 1/2 Study to Determine the Safety and Efficacy of Romiplostim in Children with Chronic Immune (Idiopathic) Thrombocytopenic Purpura (ITP).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 680-680 ◽  
Author(s):  
George R. Buchanan ◽  
Lisa Bomgaars ◽  
James B. Bussel ◽  
Diane J. Nugent ◽  
David J. Gnarra ◽  
...  
Keyword(s):  
Platelet Count ◽  
Board Of Directors ◽  
Treatment Period ◽  
Research Funding ◽  
Bleeding Events ◽  
Employment Equity ◽  
Advisory Committees ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Equity Ownership

Abstract Abstract 680 Introduction: ITP is an autoimmune disorder characterized by thrombocytopenia due to accelerated destruction as well as suboptimal platelet production. Childhood ITP is most commonly an acute illness; however, chronic ITP (duration > 6 months) develops in 20%–30% of ITP cases. Romiplostim, a peptibody protein designed to increase platelet production, is approved for treating chronic ITP in adults. The objective of this study was to evaluate the safety and efficacy of romiplostim in the treatment of thrombocytopenia in children with chronic ITP. Patients and Methods: ITP patients aged 12 months to <18 years with persistent severe thrombocytopenia for at least six months before enrollment (mean of 2 platelet counts ≥ 30 × 109/L at baseline) were included in this study. Patients were randomized (3:1) to receive romiplostim or placebo and stratified by age: 12 months - <3 years (N=4), 3 - <12 years (N=8), and 12 - <18 years (N=8). Treatment for a 12 week period was followed by a 4 week pharmacokinetic (PK) assessment period for responding patients (those who achieved a platelet count of >20 × 109/L above baseline for 2 consecutive weeks without rescue therapy at any point during the treatment period). Treatment was initiated at 1 μg/kg once weekly by subcutaneous injection. The dose was adjusted in 2 μg/kg increments every two weeks, to a maximum dose of 10 μg/kg/week based on weekly platelet counts. The incidence of adverse events (AEs) during the 12-week treatment period and the number of patients achieving platelet counts >50 × 109/L for 2 consecutive weeks during the treatment period, or achieving an increase in platelet count >20 × 109/L above baseline for 2 consecutive weeks during the treatment period was recorded. Results: A total of 22 (romiplostim, 17; placebo, 5) patients were randomized; 16 (73%) were boys and 6 (27%) were girls. Eight patients had undergone splenectomy. The mean age was 9.5 (SD: 5.1) years, with 4 subjects aged 12 months - <3 years, 10 aged 3 - <12 years, and 8 aged 12 - <18 years. The median baseline platelet count was 13 × 109/L (range 2 to 29 × 109/L) and the median duration of ITP was 2.4 years (range 0.6 to 14 years). All patients completed the study. Sixteen of 17 patients in the romiplostim arm (94%) and 5/5 in the placebo arm (100%) had at least 1 AE during the treatment period. The most common AEs were (romiplostim, placebo, respectively) headache (35%, 40%), epistaxis (35%, 20%), cough (12%, 40%), and vomiting (12%, 40%). Serious AEs were experienced by 1 patient in the romiplostim arm (moderate influenza and sepsis) and none in the placebo arm. AEs considered to be treatment related were reported for 3 (18%) and 1 (20%) subjects in the romiplostim and placebo arms, respectively; none of the treatment-related AEs were serious or of ≥3 grade severity. No patients died during the study and none tested positive for neutralizing antibodies to romiplostim or thrombopoietin. The same group of patients in the romiplostim-treated arm (15/17, 88.2%, 95% CI: 63.6%, 98.5%) achieved both efficacy endpoints during the treatment period. The median platelet count in the romiplostim-treated arm after 6 weeks of treatment was ≥50 × 109/L. The median weekly platelet count in the placebo arm remained stable at approximately 10 × 109/L. None of the placebo-treated patients achieved either platelet count endpoint. Rescue medication was administered to 2/17 (12%) of romiplostim- and 2/5 (40%) of placebo-treated patients during the 12 week treatment period. Twelve (71%) and 2 (40%) subjects in the romiplostim and placebo arms, respectively, experienced bleeding events. The majority of bleeding events (15/17) in the romiplostim arm occurred in the first 6 weeks of treatment. Most bleeding events (14/17) in the romiplostim arm and all bleeding events in the placebo arm occurred when the platelet count was < 30 × 109/L. A total of 14 patients treated with romiplostim entered the PK assessment period. The romiplostim serum concentration results were not different among the 3 age cohorts. The mean weekly dose of romiplostim in the treatment period was 3.4 (SD: 1.6) μg/kg. Conclusion: Treatment with romiplostim appeared to be well tolerated in pediatric ITP patients, with no new safety concerns observed in this study as compared to adults with chronic ITP. Romiplostim was effective in treating thrombocytopenia in children with chronic ITP. Disclosures: Buchanan: Amgen Inc.: Research Funding. Off Label Use: Use of romiplostim, a thrombopoietin mimetic, in treatment of thrombocytopenia in pediatric ITP patients. . Bomgaars:Novartis: Research Funding. Bussel:Eisai, Inc: Research Funding; Sysmex: Research Funding; Shionogi: 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; Immunomedics: Research Funding; 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; Cangene: Research Funding; Genzyme: Research Funding; Scienta: Speakers Bureau. Nie:Amgen Inc.: Employment, Equity Ownership. Eisen:Amgen Inc.: Employment, Equity Ownership. Berger:Amgen Inc.: Employment, Equity Ownership.

Hemostatic Challenges In Patients Treated with Eltrombopag

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2511-2511 ◽  
Author(s):  
Michael D. Tarantino ◽  
Patrick F. Fogarty ◽  
Bhabita Mayer ◽  
Sandra Y. Vasey ◽  
Andres Brainsky
Keyword(s):  
Clinical Trials ◽  
Platelet Count ◽  
Research Funding ◽  
Bleeding Complications ◽  
Blood Products ◽  
Invasive Procedures ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Number Of Patients ◽  
Before And After

Abstract Abstract 2511 Introduction: Chronic immune thrombocytopenia (ITP) is an autoimmune disease in which antiplatelet-antibodies induce platelet destruction and impair platelet production, resulting in chronically low platelet counts. Patients with chronic ITP may require invasive procedures associated with bleeding (hemostatic challenges) that cannot be undertaken if the platelet count is unacceptably low. Eltrombopag is an oral, nonpeptide, thrombopoietin receptor (TPO-R) agonist developed to increase platelet counts in various conditions associated with thrombocytopenia; its use may facilitate undertaking invasive procedures in patients with chronic ITP, reducing the need for additional supportive requirements including cellular blood products. Methods: Across the eltrombopag ITP clinical trials, information about hemostatic challenges was collected retrospectively (TRA100773A and B) and prospectively (REPEAT, RAISE, EXTEND). Basic demographic information, platelet counts before and after the procedures, type of procedure, need for additional treatment to increase platelet counts (one week before and after the intervention), use of blood products, and where possible, assessment of bleeding and bleeding complications were recorded. For the purpose of this analysis, minor invasive procedures (eg, dental cleaning, endoscopy, bone marrow biopsy) were distinguished from major invasive procedures (splenectomy, laparotomy, hip replacement, aortic aneurysm repair, arthroplasty). Results: Seventy-seven patients underwent 120 invasive procedures while enrolled in clinical trials with eltrombopag. The median age of patients undergoing invasive procedures was 54 years; the median duration of treatment at the time of all procedures was 131 days. 112 invasive procedures were performed in patients while receiving eltrombopag, compared to 8 procedures among patients while receiving placebo. 65 (54%) were considered to be major and 55 (46%) were considered to be minor. The median platelet count closest to minor or major invasive procedures in patients receiving eltrombopag was higher than in those receiving placebo (Table). For minor procedures, rescue ITP medication was required in 9/52 (17%) procedures in patients treated with eltrombopag and in 1/3 (33%) procedures in patients receiving placebo. For major procedures, rescue ITP medication was required in 14/60 (23%) procedures in patients treated with eltrombopag and 3/5 (60%) procedures in patients receiving placebo. One bleeding complication was reported in an eltrombopag-treated patient with colon cancer who, on the first post-operative day after a colectomy, experienced a pulmonary embolism requiring anticoagulation and had an intra-abdominal hemorrhage on post-operative day 2. Conclusions: No difference in use of periprocedural blood products between groups was discernable, possibly due to the low frequency of bleeding events reported. Although the number of patients who did not undergo procedures due to thrombocytopenia was not captured, data from 77 patients undergoing 120 invasive procedures suggest that by achieving a sustained platelet increase in patients with chronic ITP, eltrombopag facilitates the undertaking of medical and surgical procedures associated with bleeding. Disclosures: Tarantino: GlaxoSmithKline, Novo Nordisk, Talecris, Baxter, Cangene: Honoraria, Research Funding, Speakers Bureau. Fogarty: GlaxoSmithKline: Honoraria, Research Funding. Mayer: GlaxoSmithKline: Employment, Equity Ownership. Vasey: GlaxoSmithKline: Employment. Brainsky: GlaxoSmithKline: Employment.

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.

Effect on efficacy and safety trial outcomes of also enrolling patients on ongoing glucocorticoid therapy in rheumatoid arthritis clinical trials of tocilizumab or adalimumab or methotrexate monotherapy

2020 ◽  
Vol 79 (4) ◽  
pp. 460-463 ◽  
Author(s):  
Mary Safy-Khan ◽  
Johannes W G Jacobs ◽  
Maria J H de Hair ◽  
Paco M J Welsing ◽  
Michael D Edwardes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Safety Outcomes ◽  
Trial Outcomes

BackgroundIn rheumatoid arthritis (RA) trials, inclusion of patients on background treatment with glucocorticoids (GCs) might impact efficacy and safety outcomes.ObjectivesTo determine if inclusion of patients on background GC use influenced efficacy and safety outcomes of RA randomised clinical trials on initiation of tocilizumab (TCZ) or adalimumab (ADA) or methotrexate (MTX) monotherapy.MethodsData of four double-blind RA randomised controlled trials (AMBITION, ACT-RAY, ADACTA and FUNCTION) with in total four TCZ, one ADA and two MTX monotherapy arms were analysed. Analyses of covariance of changes from baseline to week 24 in efficacy endpoints and radiographic progression up to week 104 were performed, correcting for relevant covariates. Incidence rates of serious adverse events (SAEs) were assessed.ResultsNo statistically significant differences were found in efficacy parameters between background GC users and non-GC users, except for less radiographic progression associated with GC usage in one MTX arm. SAE rates were not statistically significantly different between GC users and non-GC users in the treatment arms.ConclusionNo effect of including patients on background GC treatment on efficacy and safety trial outcomes was found, with the exception of reduced radiological joint damage in one MTX arm.

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