scholarly journals PP025 Thrombopoietin Receptor Agonist For Treatment Of Adults With Chronic Immune Thrombocytopenic Purpura

2017 ◽  
Vol 33 (S1) ◽  
pp. 81-82
Author(s):  
Huang Grace Li Ying ◽  
Gau Churn-Shiouh
Keyword(s):  
Receptor Agonist ◽  
Clinical Effectiveness ◽  
Controlled Trials ◽  
Platelet Response ◽  
Bleeding Events ◽  
Thrombocytopenic Purpura ◽  
Receptor Agonists ◽  
Chronic Itp ◽  
Life Years

INTRODUCTION:This study aims to report the clinical effectiveness and cost-effectiveness of Thrombopoietin (TPO) receptor agonist for the treatment of adults with spontaneous Immune Thrombocytopenic Purpura (ITP) in Taiwan.METHODS:In the clinical effectiveness evaluation section, particularly for the TPO receptor agonist, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials to identify all randomized trials in chronic ITP. In the economic evaluation section, we performed a long-term cost-effectiveness analysis using a Markov model to evaluate the value of TPO receptor agonist to achieve durable platelet response for chronic ITP patients.RESULTS:Our findings revealed that the National Health Insurance (NHI) in Taiwan covers TPO receptor agonists romiplostim and eltrombopag, which have also been recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) of Australia and the National Institute for Health and Care Excellence (NICE) in the United Kingdom. In addition, a systematic review and meta-analysis combining six trials were included to assess the current evidence on the role of TPO receptor agonist in chronic ITP. The primary outcome of randomized controlled trials (RCTs) showed an improving trend in significant bleeding events; however there was not any significant difference between the TPO receptor agonists group and the control group (placebo). The gain in life years and quality-adjusted life-years (QALYs) from introducing long-term use of TPO receptor agonists over current clinical practice were 1.52 years and 1.44 QALYs, respectively. Most of the sensitivity analysis results show that the ICER values were greater than 3GDP per capita in Taiwan.CONCLUSIONS:Compared to placebo, and despite a significantly increased platelet response, there was no evidence to demonstrate that TPO receptor agonists did improve significant bleeding events in chronic ITP. The effect on overall survival awaits further analysis. Although long-term studies are lacking, current data demonstrated that adverse effects of TPO receptor agonists were similar to that of placebo.

scholarly journals Pharmacokinetic Parameter Driven Outcomes Model Predicts a Reduction in Bleeding Events Associated with BAY 81-8973 Versus Antihemophilic Factor (Recombinant) Plasma/Albumin- Free Method in a Chinese Healthcare Setting

2022 ◽  
Author(s):  
Rong Chen ◽  
Dmitry Gultyaev ◽  
Johanna Lister ◽  
Rong Han ◽  
Nan Hu ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Cost Savings ◽  
Standard Of Care ◽  
Healthcare Setting ◽  
Bleeding Events ◽  
Plasma Albumin ◽  
Lifetime Horizon ◽  
Life Years ◽  
Antihemophilic Factor

Abstract Background: Long-term prophylactic therapy is considered the standard of care for hemophilia A patients. This study models the long-term clinical and cost outcomes of two factor VIII (FVIII) products using a pharmacokinetic (PK) simulation model in a Chinese population. Methods: Head-to-head PK profile data of BAY 81-8973 (KOVALTRY®) and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, ADVATE®) were applied to a two-state (alive and dead) Markov model to simulate blood FVIII concentrations at a steady state in prophylactically-treated patients with hemophilia A. Worsening of the Pettersson score was simulated and decline was associated with the probability of having orthopaedic surgery. The only difference between the compounds was FVIII concentration at a given time; each subject was treated with 25 IU/kg every 3 days. The model used a lifetime horizon, with cycle lengths of 1 year. Results: Cumulative bleeding events, joint bleeding events, and major bleeding events were reduced by 19.3%, 9.3% and 19.3%, respectively for BAY 81-8973 compared to rAHF-PFM. Hospitalizations and hospitalization days were also reduced by 19.3% for BAY 81-8973 compared to rAHF-PFM. BAY 81-8973 resulted in both cost savings and a gain in quality adjusted life years (QALYs) compared to rAHF-PFM. Conclusion: Based on modeled head-to-head comparisons, differences in PK-properties between BAY 81-8973 and rAHF-PFM result in a reduced number of bleeding events, leading to reduced costs and increased quality of life for BAY 81-8973. These results should be used to inform clinical practice in China when caring for patients with severe hemophilia A.

scholarly journals Risk of major bleeding during extended oral anticoagulation in patients with first unprovoked venous thromboembolism: a systematic review and meta-analysis protocol

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Faizan Khan ◽  
Miriam Kimpton ◽  
Tobias Tritschler ◽  
Grégoire Le Gal ◽  
Brian Hutton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Venous Thromboembolism ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Bleeding Events ◽  
Major Bleeding Events

Abstract Background The optimal duration of anticoagulation after a first unprovoked venous thromboembolism (VTE) remains controversial. Deciding to stop or continue anticoagulant therapy indefinitely after completing 3 to 6 months of initial treatment requires balancing the long-term risk of recurrent VTE if anticoagulation is stopped against the long-term risk of major bleeding if anticoagulation is continued. However, knowledge of the long-term risk for major bleeding events during extended anticoagulation in this patient population is limited. We plan to conduct a systematic review and meta-analysis to quantify the risk for major bleeding events during extended oral anticoagulation in patients with first unprovoked VTE. Methods Electronic databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials will be systematically searched with the assistance of an information specialist (from inception to March 1, 2019) to identify randomized controlled trials and prospective cohort studies reporting major bleeding during extended oral anticoagulation in patients with first unprovoked VTE, who have completed at least 3 months of initial anticoagulant therapy. Study selection, risk of bias assessment, and data extraction will be performed independently by at least two investigators. The number of major bleeding events and person-years of follow-up will be used to calculate the rate (events per 100 person-years) with its 95% confidence interval for each study cohort, during clinically relevant time periods of extended anticoagulant therapy. Results will be pooled using random effect meta-analysis. Discussion The planned systematic review and meta-analysis will provide reliable estimates of the risk for major bleeding events during extended anticoagulation. This information will help inform patient prognosis and assist clinicians with balancing the risks and benefits of treatment to guide management of unprovoked VTE. Systematic review registration PROSPERO CRD42019128597.

scholarly journals Demographics and Long-Term Outcome of Incident Immune Thrombocytopenic Purpura: A Twelve-Years Nationwide Population-Based Study in Taiwan

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3259-3259
Author(s):  
Bor-Sheng Ko ◽  
Grace Hui-Min Wu ◽  
Yu-Chiao Wang ◽  
Ming Yao ◽  
Churn-Shiouh Gau ◽  
...  
Keyword(s):  
General Population ◽  
Immune Thrombocytopenic Purpura ◽  
Population Based ◽  
Male Gender ◽  
Term Outcome ◽  
Thrombocytopenic Purpura ◽  
Long Term Outcome ◽  
Chronic Itp

Abstract Background and Objectives Immune thrombocytopenic purpura (ITP) is a rare disease, and the epidemiology and long-term outcome are still rarely characterized. This study is then aimed to provide a population-based assessment for the demographics and outcome about ITP in Taiwan, an island in Southeastern Asia with around 23 million inhabitants. Material and Methods This study used claims data from Taiwan's National Health Insurance Research Database (NHIRD). The database included information from a nationwide, mandatory-enrollment and single-payer healthcare system with more than 99% coverage rate in Taiwan since March, 1995. To address adequate medical history tracking and outcome follow-up, only those patients with the first ITP diagnosis from Jan 1st, 2001 to Dec 31st, 2012 were included. Incident ITP was identified first with ICD-9 codes; but those cases with codes for potential ITP-confounding diseases within 6 months from the first ITP code were excluded. Next, only those patients with meaningful pharmacological treatment or splenectomy within 3 months were included in the final analysis. Chronic ITP was defined for those with ICD-9 ITP codes and continuous drug exposure for more than 3 months, or with rituximab or splenectomy. Sex- and age-matched cohorts with 1:10 ratio were selected from Taiwan general population for survival comparison. Results Of the 30673 patients with ITP codes from Jan 1st, 2001 to Dec 31st, 2012, 11437 were identified as incident ITP. The mean age was 42.9+/-27.5 y/o, and 5445 (47.6%) cases had Charlson Comorbidity Index (CCI) score more than 2. The average incidence was 4.16 per 100,000 person-year, and the details are shown in Table 1. The incidence for female was higher than that for male (4.97 vs. 3.38 per 100,000 person-year), and the incidences across the age represented a U-shape distribution, with the highest ones in those aged 0-9 y/o and more than 70 y/o (7.21 and 13.3 per 100,000 person-year, respectively). Some geographic distribution of the incidences existed, with the highest in central part and the lowest in Eastern part of Taiwan (5.33 and 2.64 per 100,000 person-year, respectively). Secondary causes could be identified in 3560 (31.0%) cases, and malignant neoplasma (1743, 49.0%) were most frequently noted. Viral hepatitis B or C were found in 785 (22.1%) cases. Chronic ITP was diagnosed during follow-up in 29.1% (n=3324) of incident ITP patients. Those incident ITP patients aged 0-9 y/o (431/2169 vs. 2893/9268, p<0.001) or male gender (1118/4697 vs. 2206/6740, p<0.001) had a less chance to develop chronic ITP. As compared with the matched cohort from general population, the 10-yr survival rate was significantly inferior for all ITP patients, no matter in those aged below 20 y/o (96.9+/-0.5% vs. 98.8+/-0.1%, p<0.0001) or above 20 y/o (62.5+/-0.8% vs. 83.2+/-0.2%, p<0.0001), as in Figure 1. For chronic ITP, the disadvantaged 10-yr survival rates persisted (for age below 20 y/o: 96.5+/-1.0% vs. 98.6+/-0.2%, p<0.0001; for age above 20 y/o: 72.7+/-1.3% vs. 86.7+/-0.4%, p<0.0001, as in Figure 2). Elder age, male gender and high CCI scores predicted worse survival in multi-variate analysis. Conclusions This study is the largest population-based epidemiology report at nationwide scale till now. Not only the results can provide a valuable demographic description for ITP in Eastern Asia, but also they confirm an inferior long-term outcome for ITP patients, which necessitates more attention to their health care. SD: standard deviation Table 1. Table 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Tang: Novartis: Consultancy, Honoraria.

Long-Term Dosing of AMG 531 in Thrombocytopenic Patients with Immune Thrombocytopenic Purpura: 2-Year Update.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 568-568 ◽  
Author(s):  
James B. Bussel ◽  
D.J. Kuter ◽  
J.Th.M de Wolf ◽  
T.H. Guthrie ◽  
A. Newland ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Neutralizing Antibodies ◽  
Drug Exposure ◽  
Therapeutic Option ◽  
Platelet Response ◽  
Initial Report ◽  
Chronic Itp ◽  
Long Term Treatment

Abstract AMG 531, a novel thrombopoiesis-stimulating peptibody, increases platelet production by stimulating the TPO receptor. This study is an ongoing, open-label extension assessing the safety and efficacy of long-term, weekly, SC administration of AMG 531 in patients with chronic ITP who completed a previous AMG 531 study. Patients previously treated with AMG 531 received the same starting dose as the final dose given in the previous study; placebo-treated patients began the extension at 1μg/kg. Doses could be adjusted based on platelet response. As of an April 2007 analysis, 137 patients were enrolled and 136 had received AMG 531. The longest treatment duration was 122 weeks; 22 patients were followed for 96 weeks or longer. At baseline, 91 women and 46 men had a mean age of 53±15(SD) years and a median (range) platelet count of 18(1–50)x109/L; 82 patients (60%) had undergone splenectomy. The most frequently reported adverse events (AEs) were headache (overall incidence 31%), contusion (27%), fatigue (24%), diarrhea (24%), epistaxis (23%), nasopharyngitis (21%), and arthralgia (20%). Exposure-adjusted analysis showed no trend for AEs to increase in frequency with increased drug exposure (table). Eleven patients had serious AEs judged by investigators as treatment-related including 3 withdrawn from study (vaginal hemorrhage, increased reticulin in the bone marrow reported as myelofibrosis, and initial report of multiple myeloma later reclassified as monoclonal gammopathy of undetermined significance - 1 report each) and 8 who continued on-study (bone marrow disorder/reticulin fibrosis - 3, unacceptably high platelet count - 2, thrombosis - 2, and cerebral thrombosis/papilloedema/temporary blindness - 1). One patient developed neutralizing antibodies to AMG 531 (absent on retesting 4 months after drug cessation), with no clinical sequelae and no cross-reactive antibodies to TPO. Overall, 112 patients (82%) achieved a platelet response (≥50x109/L and doubling of baseline). From week 4 onward, weekly incidence of platelet response ranged from 52–73% (figure). Median number of weeks to first response was 2 (median dose 3μg/kg). Of 30 patients with baseline use of concurrent ITP therapies, 13 were able to discontinue them and 6 additional patients had a >25% dose reduction. Individualized weekly doses of AMG 531 provide a therapeutic option for long-term treatment of chronic ITP. The safety profile has been acceptable, and most patients have been able to maintain a platelet response and discontinue or reduce concurrent ITP therapies. Exposure-Adjusted incidence of AEs with Overall Incidence ≥ 20% Platelet Response (≥ 50x109/L and Doubling of Baseline) by Study Week Platelet Response (≥ 50x109/L and Doubling of Baseline) by Study Week

Evaluation of Bleeding and Thrombotic Events during Long-Term Use of Romiplostim in Patients with Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3422-3422 ◽  
Author(s):  
Michael Tarantino ◽  
Usha Sunkara ◽  
James George ◽  
Louis M. Aledort ◽  
Matthew Guo ◽  
...  
Keyword(s):  
Phase Iii ◽  
Extension Study ◽  
Bleeding Events ◽  
Thrombocytopenic Purpura ◽  
Platelet Production ◽  
Platelet Counts ◽  
Phase Iii Trials ◽  
Life Threatening ◽  
Grade 3

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune hematologic disorder of increased platelet destruction and sub-optimal platelet production. Patients (pts) often have low platelet counts (<50 x 109/L) and present with bleeding, purpura, and petechiae; at very low counts, there is a risk of spontaneous intracranial or other life-threatening bleeding. Romiplostim is an investigational thrombopoiesis-stimulating Fc-peptide fusion protein (peptibody) that increases platelet production via binding to and activating the megakaryocyte thrombopoietin receptor. Objective: This study evaluated bleeding and thrombotic events (TEs) occurring in adults with ITP treated with romiplostim during two phase III, randomized, placebo-controlled, 24-week studies, and an open-label extension study. Patients with platelet counts <50 x 109/L were eligible to enter the extension study in which all pts received romiplostim; rates of bleeding events (up to 48 weeks of treatment) and TEs (up to 84 weeks) for these pts were analyzed. Results: In the phase III trials, 84 pts received weekly subcutaneous injections of romiplostim (initial dose 1μg/kg, dose adjusted to maintain platelet counts of 50–200x109/L) and 41 pts received placebo. 115 pts completed the phase III trials, and 101 pts (romiplostim N=68; placebo N=33) entered the extension study. Bleeding events were captured as adverse events (AEs) and graded according to severity. Clinically significant bleeding AEs (i.e. severity grade ≥2 or higher, where 2= moderate, 3=severe, 4=life-threatening, or 5=fatal) were noted in 16% of romiplostim- and 34% of placebo-treated patients (P=0.018). The percentage of pts experiencing bleeding AEs ≥ grade 3 severity was 7% and 12% in the romiplostim and placebo groups, respectively (P=0.36) None of the pts with bleeding events ≥ grade 3 had achieved a durable platelet response (defined by platelet count of ≥50x 109/L during at least 6 of the last 8 weeks of treatment). No bleeding AEs ≥ grade 3 occurred in pts with platelet counts >20 x 109/L while no bleeding AEs of grade ≥2 occurred at counts >50 x 109/L. During the extension study, the percentage of pts with a bleeding AE of any severity decreased from 36% (Weeks 1–12) to 12% (Weeks 36–48). The percentage of pts with bleeding AEs of grade 2 or higher severity decreased steadily from 16% (Weeks 1–12) to 5% (Weeks 37–48). In the phase III studies, the incidence of TEs was 2.4% in both the romiplostim and placebo groups. In the romiplostim group, one patient had a cerebrovascular accident while another had a right popliteal arterial embolism; one placebo-treated patient had a fatal pulmonary embolism. During the extension study, 7 additional TEs occurred in four more pts (patient incidence: 4%): one patient with coronary artery occlusion; one with a calf vein thrombosis; two pts with multiple events. Platelet counts at the time of TEs in all studies ranged from 3 x 109/L to 948 x 109/L. Seven of the 10 TEs occurred at counts below the median peak platelet count for all pts treated with romiplostim in both the phase III and extension studies (167 x 109/L). Furthermore all pts who experienced thrombotic AEs had multiple risk factors for thrombosis including congestive heart failure, antiphospholipid antibodies, coronary artery disease, hypertension, cancer, and/or a history of thrombotic events. Conclusion: Romiplostim appears to be an efficacious and well-tolerated treatment for adults with chronic ITP. The severity of bleeding events decreased during short-term (24-weeks) treatment, and long-term (up to 48 weeks) treatment resulted in further decreases in severe bleeding AEs and overall bleeding frequency. Thrombosis occurred in pts with risk factors, but did not appear to be related to higher than normal platelet counts.

Thrombopoietin (TPO)-Receptor Agonists In Myelodysplastic Syndromes (MDS): A Systematic Review and Meta-Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2806-2806 ◽  
Author(s):  
Anca Prica ◽  
Michelle Sholzberg ◽  
Rena Buckstein
Keyword(s):  
Systematic Review ◽  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Platelet Transfusion ◽  
Meta Analysis ◽  
Outcome Data ◽  
Controlled Trials ◽  
Bleeding Events ◽  
Receptor Agonists ◽  
Platelet Transfusions

Abstract Background Thrombocytopenia is a common (40-65%) manifestation of MDS. The incidence of bleeding ranges from 3% to 56% encompassing minor bleeds such as petechiae and gingival bleeding, and more serious bleeds (18%), such as gastrointestinal (GI, 6-7%) and intracranial (3-5%) bleeding. Lenalidomide and azacitidine are not specifically used or approved for the treatment of thrombocytopenia in MDS and while effective in some patients, may in fact engender a thrombocytopenia that is dose limiting. The interaction between thrombopoietin (TPO) and its receptor c-Mpl is essential for platelet production. Romiplostim and Eltrombopag are two TPO-receptor agonists presently approved by the FDA. They have been tested in MDS, with some evidence of benefit, but there are safety concerns regarding progression to acute myeloid leukemia (AML). Purpose To determine the safety, as well as the clinical outcomes of adding a TPO-receptor agonist to standard treatment in patients with myelodysplastic syndromes. Methods A systematic literature search strategy was conducted up to February 2013, using MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, as well as conference proceedings. All randomized controlled trials (RCTs) that enrolled adult patients with myelodysplastic syndromes were included if the RCT compared a TPO-R agonist (Romiplostim or Eltrombopag) to placebo or no treatment. A meta-analysis of the effects was performed. Pooled treatment effects were calculated as risk ratios (RR) for binary data, using a random effects model. Bleeding and platelet transfusion rates were also reported as exposure-adjusted rates per patient-month, as it was felt to be a meaningful time period for this disease. The exposure adjusted rate was defined as the number of events per person-time at risk and captures the total cumulative bleeding events (even multiple events within the same patient). Months of person time were defined as months from first dose date to study end date. Results Four RCTs met all inclusion criteria, and a total of 358 patients were included in the systematic review. 2 studies included only lower risk MDS patients (IPSS low/int-1) and 2 studies included lower and higher risk patients (IPSS low/int-1 and int-2). Romiplostim was compared to placebo in all 4 trials, but each trial had a different backbone for MDS therapy (lenalidomide, azacitidine, decitabine and just placebo). Two trials compared 2 dosing regimens to placebo (500ug weekly and 750ug weekly) and 2 trials used the higher dosing of 750ug weekly. Three studies of eltrombopag vs. placebo are ongoing, and results were not available for inclusion. Relative risk (RR) of bleeding with romiplostim vs. placebo was 0.84 (95% CI: 0.57-1.24; I2:12%). Exposure-adjusted bleeding rate per patient month was significantly less with romiplostim vs. placebo at 0.92 (95% CI: 0.86-0.99; I2:0%). Only one study reported severe grade 3-4 bleeding events, and the rates were very low, at 1/27 in the intervention arms (4%) and 2/13 (13%) in the control group, giving a favourable RR of 0.24, but very wide 95% CI of 0.02 to 2.42. The exposure-adjusted platelet transfusion rate per patient month was also significantly less with romiplostim at 0.69 (95% CI: 0.53-0.88; I2:34%). The RR of AML progression with romiplostim vs. placebo was 1.36 (95% CI: 0.54-3.40; I2:0%), however the AML progression outcome data were felt to be at high risk of bias because of the early termination of one trial. Mortality was reported as a proportion of deaths during the study period for all 4 trials, giving a RR with romiplostim of 0.90 (95% CI: 0.54-1.50; I2: 30%). Conclusions Romiplostim is promising in its ability to decrease patient-important outcomes: cumulative bleeding events and the need for platelet transfusions. However, most of those bleeding events were likely grade 2, which are not necessarily clinically important, and platelet transfusion reduction may not be as relevant for those practicing therapeutic (not prophylactic) platelet transfusions. Although the risk of AML progression was not increased, the outcome data were felt to be at high risk for bias, and thus this safety concern cannot be ignored. Therefore, romiplostim cannot yet be routinely recommended. Results of ongoing eltrombopag studies are awaited. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Psychological and psychosocial interventions for cannabis cessation in adults: a systematic review short report

2015 ◽  
Vol 19 (56) ◽  
pp. 1-130 ◽  
Author(s):  
Katy Cooper ◽  
Robin Chatters ◽  
Eva Kaltenthaler ◽  
Ruth Wong
Keyword(s):  
Population Studies ◽  
Contingency Management ◽  
Clinical Effectiveness ◽  
Psychosocial Interventions ◽  
Cannabis Use ◽  
Controlled Trials ◽  
Limited Data ◽  
Improved Outcomes

BackgroundCannabis is the most commonly used illicit drug worldwide. Cannabis dependence is a recognised psychiatric diagnosis, often diagnosed via theDiagnostic and Statistical Manual of Mental Disorderscriteria and theInternational Classification of Diseases, 10th Revision. Cannabis use is associated with an increased risk of medical and psychological problems. This systematic review evaluates the use of a wide variety of psychological and psychosocial interventions, such as motivational interviewing (MI), cognitive–behavioural therapy (CBT) and contingency management.ObjectiveTo systematically review the clinical effectiveness of psychological and psychosocial interventions for cannabis cessation in adults who use cannabis regularly.Data sourcesStudies were identified via searches of 11 databases [MEDLINE, EMBASE, Cochrane Controlled Trials Register, Health Technology Assessment (HTA) database, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, NHS Economic Evaluation Database, PsycINFO, Web of Science Conference Proceedings Citation Index, ClinicalTrials.gov andmetaRegister of Current Controlled Trials] from inception to February 2014, searching of existing reviews and reference tracking.MethodsRandomised controlled trials (RCTs) assessing psychological or psychosocial interventions in a community setting were eligible. Risk of bias was assessed using adapted Cochrane criteria and narrative synthesis was undertaken. Outcomes included change in cannabis use, severity of cannabis dependence, motivation to change and intervention adherence.ResultsThe review included 33 RCTs conducted in various countries (mostly the USA and Australia). General population studies: 26 studies assessed the general population of cannabis users. Across six studies, CBT (4–14 sessions) significantly improved outcomes (cannabis use, severity of dependence, cannabis problems) compared with wait list post treatment, maintained at 9 months in the one study with later follow-up. Studies of briefer MI or motivational enhancement therapy (MET) (one or two sessions) gave mixed results, with some improvements over wait list, while some comparisons were not significant. Four studies comparing CBT (6–14 sessions) with MI/MET (1–4 sessions) also gave mixed results: longer courses of CBT provided some improvements over MI. In one small study, supportive–expressive dynamic psychotherapy (16 sessions) gave significant improvements over one-session MI. Courses of other types of therapy (social support group, case management) gave similar improvements to CBT based on limited data. Limited data indicated that telephone- or internet-based interventions might be effective. Contingency management (vouchers for abstinence) gave promising results in the short term; however, at later follow-ups, vouchers in combination with CBT gave better results than vouchers or CBT alone. Psychiatric population studies: seven studies assessed psychiatric populations (schizophrenia, psychosis, bipolar disorder or major depression). CBT appeared to have little effect over treatment as usual (TAU) based on four small studies with design limitations (both groups received TAU and patients were referred). Other studies reported no significant difference between types of 10-session therapy.LimitationsIncluded studies were heterogeneous, covering a wide range of interventions, comparators, populations and outcomes. The majority were considered at high risk of bias. Effect sizes were reported in different formats across studies and outcomes.ConclusionsBased on the available evidence, courses of CBT and (to a lesser extent) one or two sessions of MI improved outcomes in a self-selected population of cannabis users. There was some evidence that contingency management enhanced long-term outcomes in combination with CBT. Results of CBT for cannabis cessation in psychiatric populations were less promising, but may have been affected by provision of TAU in both groups and the referred populations. Future research should focus on the number of CBT/MI sessions required and potential clinical effectiveness and cost-effectiveness of shorter interventions. CBT plus contingency management and mutual aid therapies warrant further study. Studies should consider potential effects of recruitment methods and include inactive control groups and long-term follow-up. TAU arms in psychiatric population studies should aim not to confound the study intervention.Study registrationThis study is registered as PROSPERO CRD42014008952.FundingThe National Institute for Health Research HTA programme.

Eltrombopag: A Thrombopoietin Receptor Agonist for Idiopathic Thrombocytopenic Purpura

2009 ◽  
Vol 25 (3) ◽  
pp. 176-182
Author(s):  
Min Zhu
Keyword(s):  
Adverse Effects ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Receptor Agonist ◽  
Relevant Information ◽  
World Health ◽  
Dependent Manner ◽  
Thrombocytopenic Purpura ◽  
Safety And Efficacy ◽  
Platelet Counts ◽  
Chronic Itp

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of eltrombopag in previously treated patients with chronic idiopathic thrombocytopenic purpura (ITP). Data Sources: Articles were identified through a search of the MEDLINE (1950–December 2008) database for English-language articles containing the key words eltrombopag, SB-497115, idiopathic thrombocytopenic purpura, and immune thrombocytopenic purpura. References from publications identified in this search were reviewed for relevant information. Unpublished data received from the manufacturer was also included in this review. Study Selection and Data Extraction: All articles identified from the data search were reviewed for relevant information. Applicable information was included in this review. Data Synthesis: Eltrombopag is a new oral thrombopoietic receptor agonist approved by the FDA in November 2008 as second-line treatment of chronic ITP. It stimulates human megakaryocyte differentiation and proliferation, leading to increased platelet production. Eltrombopag has been shown in clinical trials to increase platelet counts in a dose-dependent manner regardless of splenectomy status, baseline platelet counts, and concurrent ITP therapy. Available data show a statistically significant decrease in the incidence of any bleeding (World Health Organization Grades 1–4) and clinically significant bleeding (Grades 2–4). Common adverse effects are mild and typically do not lead to treatment discontinuation. Results from clinical studies demonstrated significant increase in platelet counts with minimal adverse effects. Conclusions: Eltrombopag treatment provides a potential new resource for clinicians to use in the pharmacotherapy of ITP. Further studies are needed to explore its long-term safety and efficacy in patients with chronic ITP. ACPE Universal Program Number: 407-000-09-054-H01-P (Pharmacists)

Initial and Long-Term Outcomes of Splenectomy in Adult Immune Thrombocytopenic Purpura (ITP) Patients: A Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1321-1321
Author(s):  
Joseph Mikhael ◽  
Craig M. Kessler ◽  
Mark Danese ◽  
Robert Deuson
Keyword(s):  
Failure Rate ◽  
Relapse Rate ◽  
Laparoscopic Splenectomy ◽  
Response Rate ◽  
Meta Analysis ◽  
Platelet Response ◽  
Open Splenectomy ◽  
Chronic Itp

Abstract Splenectomy serves as a common therapy in treating adults with chronic ITP. Laparoscopic splenectomy was introduced in 1991 with the goal of reducing complication rates. This study was designed to estimate both the initial surgical non-response rate and the long-term relapse rate of splenectomy in the post-laparoscopic era. A systematic literature review was conducted by searching PubMed for articles published between January 1, 1991 and October 3, 2006. Selection criteria included: chronic ITP, study enrollment in 1990 or later, ≥12 months of follow-up, ≥15 patients with ITP, ≥75% of patients at least 14 years of age, not HIV positive, and not undergoing a second splenectomy. Response rates for surgery were collected according to an author-defined platelet response criterion (platelet counts <50x109/L or <30x109/L in 75% of studies). Relapse rates post-splenectomy (using the same platelet response criteria) were also collected. A meta-analysis was conducted to estimate a pooled surgical non-response rate as well as a pooled relapse rate in responders by weighting the study-specific estimates by the inverse of their variances, using Stata 9™. The pooled relapse rate was converted to a probability using the exponential formula, e(-rate x time). We identified 161 articles for detailed review. Of these, 24 met our inclusion criteria, all of which were observational studies. These studies represent 1,138 laparoscopic splenectomies (66 or 5.8% were converted to open splenectomy during surgery), and 317 open or undefined splenectomies. The average surgical non-response rate across 21 studies reporting data was 12.2% (95% CI: 10.3–14.3%). The average long-term relapse rate per person year across all studies was 53 per 1,000 patient years (95% CI: 45.0–62.0%). This corresponds to a 5% per year failure rate, or 32% failure rate after 5 years, for all patients initiating surgery. Initial non-response rate to planned splenectomy is 12% in adults with ITP. For patients undergoing laparoscopic splenectomy, 6% required conversion to open splenectomy. The 5 year relapse rate post-splenectomy is 32%. Splenectomy, although the current standard of care, is not always initially successful and does not provide a durable response in all patients. The benefits and risks of splenectomy must be weighed in light of newer options of therapy currently available. Relapse Rate per 1,000 Patient-years of Follow-up for Each Study Relapse Rate per 1,000 Patient-years of Follow-up for Each Study

Time to Splenectomy Failure in Patients with Recurrent or Refractory Chronic Immune Thrombocytopenic Purpura.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3522-3522
Author(s):  
Gregory Cheng ◽  
Terry Gernsheimer ◽  
Harold J. Olney ◽  
James B. Bussel ◽  
Palvi Shah ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Immune Thrombocytopenic Purpura ◽  
Research Funding ◽  
Therapeutic Option ◽  
Advisory Committees ◽  
Thrombocytopenic Purpura ◽  
Chronic Immune Thrombocytopenic Purpura ◽  
Chronic Itp ◽  
Equity Ownership

Abstract Abstract 3522 Poster Board III-459 INTRODUCTION Splenectomy has been perceived as a potentially curative treatment for patients with chronic immune thrombocytopenic purpura (ITP). Historical data demonstrate that the risk of relapse is between 33% and 50% in patients with long-term follow-up (Fabris, Br J Haematol, 2001; Schwartz, Am J Hematol, 2003). No clear pattern of time to relapse after splenectomy has been described which complicates the decision making process for physicians who are considering this irreversible therapeutic option. Splenectomized patients are at risk for: early and late surgical complications (Kojouri, Blood, 2004; Portielje, Blood, 2001); infections secondary to impaired immunity (BCSH 1996; Moffett, JAAPA, 2009; Oren 2008); thrombotic and/or cardiovascular disease (Schilling, J Thromb Haemost, 2008; Fontana, Thromb Res, 2008); and pulmonary hypertension (Schilling, J Thromb Haemost, 2008; Bonderman, Circulation, 2007). Splenectomy requires preoperative vaccinations, general anesthesia with antibiotic prophylaxis, and subsequent long-term vigilance with early antibiotic treatments. These factors not only impact the utilization of medical resources but also, due to clinically problematic outcomes, may lead to a requirement for additional treatments. OBJECTIVE: To describe the time from splenectomy to splenectomy failure among patients with chronic ITP enrolled in the eltrombopag clinical program. METHODS: Date of splenectomy and prior medications for ITP were reviewed in patients enrolled in 5 clinical trials using eltrombopag. Splenectomy was considered to have failed upon administration of the first treatment for ITP after surgery or when patients were not able to taper or interrupt concomitant ITP treatments in the 30 days following splenectomy. Of the 495 patients enrolled in the ITP program, 192 (39%) were splenectomized and 185 patients were evaluable for this analysis. The analysis does not describe overall effectiveness of splenectomy as the patient population is limited to splenectomy failure patients who required additional treatment for their ITP. RESULTS: Fifty-one percent of patients required ITP medications within 1 year of splenectomy (Figure 1). Five years after splenectomy, 27% of patients still had a response; this percentage decreased to 18% after 10 years. CONCLUSION: This retrospective analysis demonstrates that success of splenectomy appears to diminish over time. In patients requiring further ITP treatment, most splenectomized patients who relapse do so within 5 years. The treatment of chronic ITP has advanced as more data on the safety and efficacy of new medications like the thrombopoietin receptor agonists have become available. As physicians and patients become more familiar with the risks and benefits of all treatments, options other than splenectomy may be preferred for certain patients. Disclosures: Cheng: GlaxoSmithKline: Research Funding. Gernsheimer:GlaxoSmithKline: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Olney:GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. 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. Shah:GlaxoSmithKline: Employment. Brainsky:GlaxoSmithKline: Employment. Grotzinger:GlaxoSmithKline: Employment. Aivado:GlaxoSmithKline: Employment.

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