title: TPO receptor agonist for chronic idiopathic thrombocytopenic purpura.
abstract: BACKGROUND
  Chronic idiopathic thrombocytopenic purpura (ITP) is an acquired autoimmune disorder that is characterized predominantly by a low platelet count. Thrombopoietin (TPO) receptor agonists increase production of platelets by stimulating the TPO receptor in people with chronic ITP.
  
  
  OBJECTIVE
  To determine the efficacy and safety of TPO receptor agonists in chronic ITP patients.
  
  
  METHODS
  We searched MEDLINE (from 1950 to March 2011), EMBASE (from 1974 to March 2011), and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3) to identify all randomized trials in chronic ITP. We also contacted authors of included studies and TPO receptor agonists manufacturers.
  
  
  METHODS
  Randomized controlled trials (RCTs) comparing TPO receptor agonists alone, or in combination with other drugs, to placebo, no treatment, other drugs, splenectomy or another TPO receptor agonist in patients with chronic ITP.
  
  
  METHODS
  Two review authors independently screened papers, extracted data and assessed the risk of bias in the included studies.
  
  
  RESULTS
  Six trials with 808 patients were included. Five studies compared TPO receptor agonists with placebo (romiplostim: 100, eltrombopag: 299, placebo: 175); one study compared TPO receptor agonists with standard of care (SOC) (romiplostim: 157; SOC: 77). SOC included a variety of therapies, such as glucocorticoid, anti-D immune globulin, intravenous immune globulin, rituximab, azathioprine, and so on. Overall survival, one of our primary outcomes, was not studied by these RCTs and we could not estimate number needed to treat (NNT). Another primary outcome, improving significant bleeding events, did not reveal any significant differences between the TPO receptor agonists group and the control group (placebo or SOC) (versus placebo risk ratio (RR) 0.48, 95% confidence interval (CI) 0.20 to 1.15; versus SOC RR 0.49, 95% CI 0.15 to 1.63).For secondary outcomes, TPO receptor agonists statistically significantly improved overall platelet response (versus placebo RR 4.06, 95% CI 2.93 to 5.63; versus SOC RR 1.81, 95% CI 1.37 to 2.37), complete response (versus placebo RR 9.29, 95% CI 2.32 to 37.15) and durable response (versus placebo RR 14.16, 95% CI 2.91 to 69.01). There was a significant reduction in overall bleeding events (WHO grades 1 to 4) when compared to placebo (RR 0.78, 95% CI 0.68 to 0.89), but not when compared to SOC(RR 0.97, 95% CI 0.75 to 1.26).Total adverse events (Grades 1 to 5) were not statistically significantly different between the treatment and control groups(both placebo and SOC) (versus placebo RR 1.04, 95% CI 0.95 to 1.15; versus SOC RR 0.97, 95% CI 0.75 to 1.26). Total serious adverse events (Grade 3 and higher adverse events) were increased when patients receiving treatment with SOC (RR 0.61, 95% CI 0.40 to 0.92), but not receiving treatment with placebo (RR 0.92, 95% CI 0.61 to 1.38).There are selective and performance biases because of open-label and inadequate allocation.
  
  
  CONCLUSIONS
  There was currently no evidence to support that TPO receptor agonists are effective in chronic ITP. Compared to placebo or SOC, despite 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 adverse effects of TPO receptor agonists were similar to that of placebo and SOC.
authors: Department of Hematology, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, China, 610041.
authors: Yan
authors: Y
authors: Zeng
authors: Xin
authors: X
authors: Duan
authors: Jiajun
authors: J
authors: Xu
authors: Xun
authors: X
authors: Ni
mesh_terms: D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use; D002908:Chronic Disease; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011961:Receptors, Fc / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000819:agonists*; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013926:Thrombopoietin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag