***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective : To investigate the safety and efficacy of eltrombopag for adult patients with chronic immune thrombocytopenia ( cITP ) . Methods : It was a r and omised , single-centre , 6 weeks , placebo-controlled study . Beginning in January 29(th ) , 2013 , 35 patients were enrolled , and the trial was completed on May 16(th ) , 2014 . 17 patients were assigned to receive eltrombopag ( starting dose 25 mg/d ) and 18 were assigned to receive placebo . Results : A total of 35 cases of adult cITP , 6 males and 29 females with a median age of 42(22 - 66 ) years were enrolled . One patient withdrew from eltrombopag treatment group for the adverse event ( AE ) and discontinued treatment . In first two weeks , 27.78 % ( 5/18 ) of placebo-treated compared with 64.71%(11/17 ) of eltrombopag-treated patients achieved platelet counts ≥ 30 × 10(9)/L(P=0.031 ) ; Treatment 6 weeks , the proportion of platelet counts reached ≥50 × 10(9)/L and ≥ 30 × 10(9)/L in eltrombopag-treated were higher than placebo-treated ones with statistically significant differences in both groups [ 64.71%(11/17 ) vs 11.11 % ( 2/18 ) , P=0.001 ; 76.47 % ( 13/17 ) vs 38.89 % ( 7/18 ) , P=0.028 ] ; The study also indicated a statistically significant difference in favour of eltrombopag compared with placebo in the odds of achieving the outcome of a platelet count ≥ 50 × 10(9)/L at least once during 6-week treatment ( 94.11 % vs 33.33 % , P<0.001 ) , and 70.59%(12/17 ) of patients with the platelet count continuously ≥ 50 × 10(9)/L in 50 % of treatment time in eltrombopag-treated group was more than placebo-treated one [ 11.11%(2/18 ) , P<0.001 ] . Proportions of patients who required rescue treatment were 44.44 % in placebo group and none in eltrombopag-treated one , respectively ( P=0.002 ) ; The odds of bleeding symptoms with the WHO bleeding scale had no difference in both groups after 6 weeks ( P=0.066 ) . Adverse events that occurred more frequently due to eltrombopag than placebo included increased transaminase ( 3/17 ) and blood bilirubin ( 5/17 ) , cerebral infa rct ion(1/17 ) . Conclusions : The thrombopoietin receptor agonist eltrombopag was a suitable therapeutic option for Chinese adults with cITP BACKGROUND Immune thrombocytopenia is characterised by immune-mediated destruction and suboptimum production of platelets . Despite the absence of supporting evidence , rituximab is frequently used off-label in patients with immune thrombocytopenia . We aim ed to assess the efficacy of rituximab as compared with placebo as a splenectomy-sparing treatment in patients who were previously treated with corticosteroids . METHODS In this multicentre , r and omised , double-masked , placebo-controlled trial , we enrolled corticosteroid unresponsive adult patients ( aged ≥18 years ) with primary immune thrombocytopenia and a platelet count of less than 30 × 10(9 ) platelets per L. Patients were r and omly assigned ( 1:1 ) to four weekly infusions of 375 mg/m(2 ) rituximab or placebo . Concurrent treatment with corticosteroids only was allowed during the study . The primary endpoint was rate of treatment failure within 78 weeks -- a composite of splenectomy or meeting criteria for splenectomy after week 12 if splenectomy was not done , assessed in all patients who received at least one dose of study treatment . Secondary endpoints were response rates , relapse rates , and duration of response . Efficacy endpoints were assessed with the Kaplan-Meier method . Safety endpoints were assessed in all patients who received at least one dose . This trial is registered with Clinical Trials.gov , number NCT00344149 . FINDINGS Between Aug 17 , 2006 , and June 30 , 2011 , we enrolled 112 patients . 32 ( 58 % ) of 55 patients in the rituximab group and 37 ( 69 % ) of 54 patients in the placebo group had treatment failure within 78 weeks ( Kaplan-Meier cumulative incidence 46 % for rituximab vs 52 % for placebo ( hazard ratio [ HR ] 0·89 , 95 % CI 0·55 - 1·45 ; p=0·65 ) . The cumulative incidence of overall response was 81 % in the rituximab group versus 73 % in the placebo group ( p=0·15 ) and complete response was 58 % in the rituximab group versus 50 % in the placebo group ( p=0·12 ) . Of those achieving an overall response , 68 % relapsed in the rituximab group and 78 % relapsed in the placebo group , and of those achieving complete response , 50 % relapsed in the rituximab group and 62 % relapsed in the placebo group . Time to relapse in the rituximab group was longer in patients who achieved overall response ( 36 vs 7 weeks ; p=0·01 ) but not complete response ( 76 vs 49 weeks ; p=0·19 ) . Rates of bleeding were similar in the two groups ( 21 [ 38 % ] in the rituximab group vs 27 [ 50 % ] in the placebo group ; p=0·08 ) as were rates of infection ( 22 [ 40 % ] vs 13 [ 24 % ] ; p=0·09 ) . INTERPRETATION Despite no reduction in the rate of long-term treatment failure with rituximab , a small benefit can not be ruled out , as suggested by an apparently longer duration of response and numerically higher response rates with rituximab . FUNDING South-East Regional Health Authority and Østfold Hospital , Norway ; Roche , France ; and Roche , Norway This r and omized trial was performed to investigate the efficacy of low-dose rituximab in combination with glucocorticoids for treatment of patients with immune thrombocytopenia ( ITP ) . Sixty-two patients were r and omly separated into the glucocorticoids ( control ) and the experimental ( glucocorticoids + rituximab ) groups . Patients in both groups received dexamethasone 40 mg/day on days 1–4 , followed by decrements of prednisone 60 , 30 , 15 , 10 mg/day on days 5–7 , 8–14 , 15–21 , 22–28 , respectively . Patients in the experimental group also received rituximab 100 mg on days 7 , 14 , 21 , 28 . The overall response ( OR ) was similar in both groups at day 28 ( experimental group vs. glucocorticoids group : 80.6 vs. 74.2 % , P = .938 ) ; however , sustained response ( SR ) was more pronounced in the experimental group as compared to that in the glucocorticoids group ( 77.4 vs. 38.7 % , P < .001 ) . Both groups showed similar incidence of adverse events ( experimental group vs. glucocorticoids group : 9.7 vs. 6.5 % , P = .325 ) . As expected , B cell depletion was seen in the experimental group . In addition , both groups experienced a significant up-regulation in Treg cell levels , but the up-regulation in the experimental group was maintained at an even higher level and persisted a longer time than those in the glucocorticoids group . Thus , low-dose rituximab combined with short-term glucocorticoids provides an alternative treatment for ITP prior to splenectomy To determine whether inhibition of Syk would be useful in FcgammaR-dependent cytopenias such as immune thrombocytopenic purpura ( ITP ) or autoimmune hemolytic anemia , mouse models were used to evaluate efficacy of R406 , an inhibitor of Syk function , in treating cytopenia . Both disease models responded favorably to treatment , with amelioration of ITP being more dramatic . Thus , phase 2 clinical trial was initiated to study the effects of Syk inhibition in humans with ITP . Sixteen adults with chronic ITP were entered into an open-label , single-arm cohort dose-escalation trial beginning with 75 mg and escalating as high as 175 mg twice daily . Doses were increased until a persistent response was seen , toxicity occurred , or 175 mg twice daily was reached . Eight patients achieved persistent responses with platelet counts greater than 50 x 10(9)/L ( 50 000 mm(3 ) ) on more than 67 % ( actually 95 % ) of their study visits , including 3 who had not persistently responded to thrombopoietic agents . Four others had nonsustained responses . Mean peak platelet count exceeded 100 x 10(9)/L ( 100 000 mm(3 ) ) in these 12 patients . Toxicity was primarily GI-related with diarrhea ( urgency ) and vomiting ; 2 patients had transaminitis . In conclusion , inhibition of Syk was an efficacious means of increasing and maintaining the platelet count in half the patients with chronic refractory ITP . ( Clinical Trials.gov , no. NCT00706342 ) The benefit of adding rituximab to st and ard treatment in nonsplenectomized patients with primary immune thrombocytopenia ( ITP ) is uncertain . We performed a pilot r and omized trial to determine the feasibility of recruitment , protocol adherence , and blinding of a larger trial of rituximab versus placebo ; and to evaluate the potential efficacy of adjuvant rituximab in ITP . Nonsplenectomized adults with newly diagnosed or relapsed ITP who were receiving st and ard ITP therapy for a platelet count below 30 × 10(9)/L were r and omly allocated to receive 4 weekly infusions of 375 mg/m(2 ) rituximab or saline placebo .  Sixty patients were recruited over 46 months , which was slower than anticipated . Protocol adherence and follow-up targets were achieved , and blinding was successful for research staff but not for patients . After 6 months , there was no difference between rituximab and placebo groups for the composite outcome of any platelet count below 50 × 10(9)/L , significant bleeding or rescue treatment once st and ard treatment was stopped ( 21/32 [ 65.6 % ] vs 21/26 [ 80.8 % ] ; relative risk = 0.81 , 95 % confidence intervals , 0.59%-1.11 % ) . Timely accrual poses a challenge to the conduct of a large r and omized trial of rituximab for presplenectomy ITP . No difference in the frequency of the composite outcome was observed in this pilot trial ( registered at www . clinical trials.gov NCT00372892 ) Spleen tyrosine kinase ( Syk ) signaling is central to phagocytosis‐based , antibody‐mediated platelet destruction in adults with immune thrombocytopenia ( ITP ) .  Fostamatinib , an oral Syk inhibitor , produced sustained on‐treatment responses in a phase 2 ITP study . In two parallel , phase 3 , multicenter , r and omized , double‐blind , placebo‐controlled trials ( FIT1 and FIT2 ) , patients with persistent/chronic ITP were r and omized 2:1 to fostamatinib ( n = 101 ) or placebo ( n = 49 ) at 100 mg BID for 24 weeks with a dose increase in nonresponders to 150 mg BID after 4 weeks . The primary endpoint was stable response ( platelets ≥50 000/μL at ≥4 of 6 biweekly visits , weeks 14‐24 , without rescue therapy ) . Baseline median platelet count was 16 000/μL ; median duration of ITP was 8.5 years . Stable responses occurred in 18 % of patients on fostamatinib vs. 2 % on placebo ( P = .0003 ) . Overall responses ( defined retrospectively as ≥1 platelet count ≥50 000/μL within the first 12 weeks on treatment ) occurred in 43 % of patients on fostamatinib vs. 14 % on placebo ( P = .0006 ) . Median time to response was 15 days ( on 100 mg bid ) , and 83 % responded within 8 weeks . The most common adverse events were diarrhea ( 31 % on fostamatinib vs. 15 % on placebo ) , hypertension ( 28 % vs. 13 % ) , nausea ( 19 % vs. 8 % ) , dizziness ( 11 % vs. 8 % ) , and ALT increase 
    Output:
    
According to pooled results , romiplostim appears to be the most suitable treatment in terms of OR , followed by avatrombopag , eltrombopag , fostamatinib , and rituximab .
Avatrombopag produced more satisfactory outcomes than romiplostim , eltrombopag , and rituximab in terms of ER ; severe AEs profiles were similar across all treatment arms .
Conclusion : Romiplostim appears to be the best option for patients who fail to respond to prior treatment or relapse thereafter , while avatrombopag and eltrombopag are reasonable alternatives .
Rituximab monotherapy is not recommended , as it produces the lowest OR and ER rates