Deviation from Guidelines in Use of Eltrombopag and Romiplostim in Clinical Practice for Children with Primary Immune Thrombocytopenia; Multi-Center Egyptian Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4907-4907
Author(s):  
Mohsen Saleh Elalfy ◽  
Tamer Hassan ◽  
Khalid Elsayh ◽  
Mohamed Maebid ◽  
Hoda Hassab ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Escalation ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Severe Bleeding ◽  
Inadequate Response ◽  
Serious Adverse Events ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Primary Immune Thrombocytopenia

Background: Primary immune thrombocytopenia (ITP) has been treated with steroids or immune-suppressive. Thrombopoietin receptor agonists (TPO-RAs), changed the treatment landscape for ITP. Romiplostim and Eltrombopag were FDA approved for use in pediatric patients ≥1 year with ITP of >6 months' duration and insufficient response to previous therapy. Following the guidelines is not always feasible in practice. Aim and Methodology Centers treating more than 25 new cases/year with good recording system were included; aiming to report outcome, adverse events (AEs) and deviation from guidelines. Newly diagnosed ITP children were excluded. Data was collected from January 2017- June 2019; children age >1 to 18 years with persistent ITP (3-<12 months) or chronic (≥12 months), who had previously been treated with ≥1 previous ITP therapy, and had platelet counts (PC) persistently <30×109/l with moderate-severe bleeding. Eltrombopag was described in a dose of 25 mg/day for those > 1 to 12 years; or in 50 mg/day for those >12-18 years; dose was escalated to 50 or 75mg/day for those 6-12 and >12 years respectively on failure to have PC > 50 x 109/L. Weekly CBC and self-record of bleeding for 1st 24 week then bi-weekly. Failure to show a good response; Eltrombopag dosing should be adjusted to achieve that goal and not to exceed 200 × 109/L. Romiplostim was used in 1 ug/kg and escalated up to 10 ug/kg according to response. Serious AEs were reported to ethical committee within 24 hours. Results Two years Observational study of 204 out of 1080 primary ITP (268 persistent and 812 chronic); 55% females median age 8 years, received Eltrombopag (n=186), Romiplostim (n= 18) from 3-30 months was prescribed after failure of 1-5 lines of therapy in 15% of Persistent ITP and 20% of chronic ITP. Adequate response at 24 weeks in 60% on Eltrombopag or Romiplostim had a significant reduction in both skin-related and non-skin-related bleeding symptoms). However 50% discontinued treatment; (40% due to inadequate response, 8% irregular availability and 2% due to SAEs). Deviation from guidelines in 40%; (15% started Eltrombopag early between 3-6 months who showed a higher response rate; half of them could stop it without drop of PC); while 20% continued Eltrombopag for >12 month with lack of response after dose escalation at 24th week and 5% were not following the described dose or the regular monitoring. 40% of chronic ITP patients achieved platelet counts of >50 x 109/L or more at least twice. Common adverse events included; headache (10%). myalgia (10%), rhinitis (8%), diarrhea 8% Serious adverse events occurred in 4 (1 elevated transaminases, one unrelated life-threatening bleeding and two high PC; >1000 x109/L). Conclusion: TPO-RAs were used in almost 15% of persistent and 20% of chronic ITP as 2nd line or more therapy and in 90% was Eltrombopag; which produced an excellent response for those 3-6 months; deviating from guidelines. It showed a sustained platelet response in 40% of patients with chronic ITP, however it should be stopped if showing poor response after dose escalation. Disclosures No relevant conflicts of interest to declare.

scholarly journals Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice

2021 ◽  
Vol 5 (19) ◽  
pp. 3799-3806
Author(s):  
Xiaoling Cheng ◽  
LingLing Fu ◽  
Jingyao Ma ◽  
Hao Gu ◽  
Zhenping Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pediatric Patients ◽  
Complete Response ◽  
Term Treatment ◽  
Serious Adverse Events ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Long Term Treatment ◽  
Concomitant Medications

Abstract Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.

Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia

Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2755-2762 ◽  
Author(s):  
Francesco Zaja ◽  
Michele Baccarani ◽  
Patrizio Mazza ◽  
Monica Bocchia ◽  
Luigi Gugliotta ◽  
...  
Keyword(s):  
Platelet Count ◽  
Adverse Events ◽  
Salvage Therapy ◽  
Immune Thrombocytopenia ◽  
Sustained Response ◽  
Effective Treatment Option ◽  
Serious Adverse Events ◽  
Primary Immune Thrombocytopenia ◽  
Grade 3 ◽  
To Receive

Abstract Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 × 109/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m2 rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count ≥ 50 × 109/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, −0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, −0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.

Romiplostim Treatment in Adults with Immune Thrombocytopenia of Varying Duration and Severity

2015 ◽  
Vol 134 (4) ◽  
pp. 215-228 ◽  
Author(s):  
Ann Janssens ◽  
Michael Tarantino ◽  
Robert J. Bird ◽  
Maria Gabriella Mazzucconi ◽  
Ralph V. Boccia ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Type I Collagen ◽  
Type I ◽  
Serious Adverse Events ◽  
True Incidence ◽  
Platelet Counts ◽  
New Class ◽  
Third Line ◽  
Uncontrolled Bleeding

Romiplostim is recommended for the second- and third-line treatment of primary immune thrombocytopenia (ITP). We conducted a large, single-arm study (clinicaltrials.gov; NCT00508820) with broad entry criteria to evaluate the safety of romiplostim in adult ITP. Patients (n = 407) with ITP lasting 0.03-57.14 years and low platelet counts (median 14.0 × 109/l) or uncontrolled bleeding received romiplostim for up to 4 years. The rates of treatment-related, serious adverse events, serious hemorrhage events, thromboembolic events and fatal events were similar to those reported in previous romiplostim trials (0.2, 0.4, 0.2 and 0.1/100 patient-weeks, respectively). Bone marrow reticulin was observed in 4 patients, but biopsies were not routinely performed so the true incidence of this event cannot be determined. Type I collagen (nonserious, unrelated) was reported in 1 patient who likely had myelodysplastic syndrome. No new class of adverse events was reported. Platelet responses were achieved by >90% of the patients, typically within 1-2 weeks of the initiation of romiplostim treatment. From week 8, median platelet counts were >100 × 109/l; 47% of the patients received rescue medications (the use decreased over time). This study confirms and extends the tolerability/efficacy findings of previous romiplostim clinical studies. It was performed on a large ITP population, which is likely more representative of clinical practice.

A randomized, double-blind study of romiplostim to determine its safety and efficacy in children with immune thrombocytopenia

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 28-36 ◽  
Author(s):  
James B. Bussel ◽  
George R. Buchanan ◽  
Diane J. Nugent ◽  
David J. Gnarra ◽  
Lisa R. Bomgaars ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Double Blind Study ◽  
Weekly Dose ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Subcutaneous Injections ◽  
Platelet Counts ◽  
Short Term Study ◽  
Thrombopoietin Mimetic

Abstract Romiplostim, a thrombopoietin-mimetic peptibody, increases and maintains platelet counts in adults with immune thrombocytopenia (ITP). In this first study of a thrombopoietic agent in children, patients with ITP of ≥ 6 months' duration were stratified by age 1:2:2 (12 months-< 3 years; 3-< 12 years; 12-< 18 years). Children received subcutaneous injections of romiplostim (n = 17) or placebo (n = 5) weekly for 12 weeks, with dose adjustments to maintain platelet counts between 50 × 109/L and 250 × 109/L. A platelet count ≥ 50 × 109/L for 2 consecutive weeks was achieved by 15/17 (88%) patients in the romiplostim group and no patients in the placebo group (P = .0008). Platelet counts ≥ 50 × 109/L were maintained for a median of 7 (range, 0-11) weeks in romiplostim patients and 0 (0-0) weeks in placebo patients (P = .0019). The median weekly dose of romiplostim at 12 weeks was 5 μg/kg. Fourteen responders received romiplostim for 4 additional weeks for assessment of pharmacokinetics. No patients discontinued the study. There were no treatment-related, serious adverse events. The most commonly reported adverse events in children, as in adults, were headache and epistaxis. In this short-term study, romiplostim increased platelet counts in 88% of children with ITP and was well-tolerated and apparently safe. The trial was registered with http://www.clinicaltrials.gov as NCT00515203.

Recombinant Human Thrombopoietin and Rituximab vs Rituximab Monotherapy in Corticosteroid-Resistant Primary Immune Thrombocytopenia: a Multicenter Randomized Controlled Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 329-329
Author(s):  
Miao Xu ◽  
Ping Qin ◽  
Xiaoyuan Dong ◽  
Jie Li ◽  
Haiyan Zhang ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Wilcoxon Test ◽  
Fixed Dose ◽  
Combination Group ◽  
Monotherapy Group ◽  
Platelet Counts ◽  
Primary Immune Thrombocytopenia ◽  
Time To Relapse

Abstract Background Though great progresses had been achieved in the management of primary immune thrombocytopenia (ITP), still 25%-30% of the patients show no response to the conventional therapy. Both thrombopoietin (TPO) and rituximab (RTX) are recommended as the second-line treatments. TPO has shown potent activity in ITP, but the therapeutic efficacy is dependent on continual administration. Rituximab is an anti-CD20 chimeric monoclonal antibody which could induce prolonged remission in ITP. However, longer time to response was also reported. The combination of rhTPO and rituximab could complement each other in both mechanism of action and time window, exert powerful effect, which may be a choice for the glucocorticosteroids-resistant/relapsed patients. Method Patients with platelet counts ≤ 30 x109/L, or ≤ 50 x109/L with bleeding symptoms from 12 centers were enrolled in the study. Subjects enrolled in the study were assigned randomly as 1: 2 to RTX group and rhTPO plus RTX group. Eligibility criteria were set according to the recently published guideline (Rodeghiero F, et al, Blood 2009). Approval for the study was obtained from the Ethics Committee of the School of Medicine and Qilu Hospital. Informed consent in accordance with the Declaration of Helsinki was given to each patient. Rituximab (MabThera; Roche) was given with a fixed dose of 100mg weekly for four weeks. And in the combination group, rhTPO (Tebiao, 3SBio, China) was added in the regimen with a dose of 300U/kg/day in the first 14 days, and a modified frequency of rhTPO was given according to the platelet counts after two weeks, but no longer than four weeks. Primary outcomes include response (R), complete response (CR), no response (NR) and relapse. All the criteria were consent with the definition and outcome criteria. (Rodeghiero F, et al. Blood, 2009.) Secondary outcomes are listed below. Time to response (TTR) was considered as the duration from baseline to response. Time to relapse was also measured with Kaplan-Meier analysis. Besides, safety was reflected as adverse events graded according to the Common Toxicity Criteria. This clinical trial was registered at http://clinicaltrials.gov as NCT 01525836. Result A total of 114 patients were recruited: monotherapy group (n = 35) and combination group (n = 79). All patients failed to response to glucocorticosteroids or relapsed after corticosteroids treatment. Response rate was reached in 71.4% (25/35) of patients in monotherapy group vs. 78.5% (62/79) in the RTX and rhTPO combination group, while complete responses were achieved as 10/35 (28.6%) in RTX monotherapy group and 34/79 (43.0%) in rhTPO plus RTX group respectively. Median time to response was 28 days (range 4-90 days) in RTX group, while in RhTPO plus RTX group, TTR was 7 days (range 4-28 days) (P = 0.002). There was significantly longer time to relapse in the combination group (shown in Fig. 1). Adverse effects were observed in RTX group in 5 patients, most of whom were affected with inflammation. One patient was reported as viral myocarditis, and there were also complaints about chill, rash and hyperpyrexia. And incidence of adverse events was slightly increased in rhTPO plus RTX group. There were 14 adverse effects reported in the combination group, such as fatigue, pulmonary inflammatory, but all were below Grade 2. Conclusion Our findings suggest that combination of RTX and RTX in ITP yields shorter time to response compared with monotherapy of RTX, and moreover, combination extended time to relapse. Thus, combination therapy may represent an effective treatment option for glucocorticosteroids-resistant or relapsed patients. The results were compared with Gehan-Breslow-Wilcoxon Test. (P = 0.0140) Disclosures: No relevant conflicts of interest to declare.

scholarly journals IVMP+IVIG raises platelet counts faster than IVIG alone: results of a randomized, blinded trial in childhood ITP

2020 ◽  
Vol 4 (7) ◽  
pp. 1492-1500
Author(s):  
Manuel Carcao ◽  
Mariana Silva ◽  
Michele David ◽  
Robert J. Klaassen ◽  
MacGregor Steele ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Adverse Events ◽  
Immune Thrombocytopenia ◽  
Controlled Study ◽  
Severe Bleeding ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Platelet Counts ◽  
Life Threatening ◽  
Blinded Trial

Abstract Children with immune thrombocytopenia (ITP) rarely suffer from life-threatening bleeds (eg, intracranial hemorrhage). In such settings, the combination of IV methylprednisolone (IVMP) with IV immune globulin (IVIG) is used to rapidly increase platelet counts (PCs). However, there are no controlled data to support using combination therapy over IVIG alone. We conducted a randomized, double-blind, placebo-controlled study to evaluate the rapidity of the PC increment and associated adverse events (AEs) between 2 regimens: A (IV placebo) and B (IVMP 30 mg/kg), both given over 1 hour, followed in both cases by IVIG (Gamunex 10%) 1 g/kg over 2-3 hours in children 1-17 years old with primary ITP and PCs &lt;20 × 109/L in whom physicians had decided to treat with IVIG. Thirty-two children (ages: median, 8 years; range, 1.2-17.5 years) with a mean baseline PC of 9.2 × 109/L participated. Eighteen were randomized to regimen A and 14 to regimen B. By 8 hours after initiating therapy, 55% of all children had a PC ≥20 × 109/L (no group difference). By 24 hours, mean PCs were 76.9 × 109/L (B) vs 55 × 109/L (A) (P = .06; P = .035 when adjusted for intergroup differences in patient ages). No patient experienced severe bleeding/unexpected severe AEs. There were statistically fewer IVIG-related headaches in the group receiving combination therapy (P = .046). Our findings show a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations. This trial was registered at www.clinicaltrials.gov as #NCT00376077.

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP

Blood ◽  
2009 ◽  
Vol 113 (10) ◽  
pp. 2161-2171 ◽  
Author(s):  
James B. Bussel ◽  
David J. Kuter ◽  
Vinod Pullarkat ◽  
Roger M. Lyons ◽  
Matthew Guo ◽  
...  
Keyword(s):  
Severe Bleeding ◽  
Self Administration ◽  
Bleeding Events ◽  
Serious Adverse Events ◽  
Safety And Efficacy ◽  
True Incidence ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Long Term Treatment

AbstractChronic immune thrombocytopenic purpura (ITP) is characterized by low platelet counts and mucocutaneous bleeding. In previous studies romiplostim (AMG531), a thrombopoiesis-stimulating protein, increased platelet counts in most patients with chronic ITP. This ongoing, long-term open-label, single-arm study investigated safety and efficacy in patients who completed a previous romiplostim study and had platelet counts less than 5 × 109/L. One hundred forty-two patients were treated for up to 156 weeks (mean, 69 weeks). Platelet responses (platelet count ≥ 50 × 109/L and double baseline) were observed in 87% of all patients and occurred on average 67% of the time in responding patients. In 77% of patients, the romiplostim dose remained within 2 μg/kg of their most frequent dose at least 90% of the time. Ninety patients (63%) received treatment by self-administration. Treatment-related serious adverse events were reported in 13 patients (9%). Bone marrow reticulin was observed in 8 patients; marrows were not routinely performed in this study, so the true incidence of this event cannot be determined. Severe bleeding events were reported in 12 patients (9%). Thrombotic events occurred in 7 patients (5%). In conclusion, romiplostim increased platelet counts in most patients for up to 156 weeks without tachyphylaxis and had an acceptable safety profile. (ClinicalTrials.gov Identifier NCT00116688).

Efficacy and Safety Of Eltrombopag In Korean Adult Patients With Refractory Chronic Immune Thrombocytopenia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4758-4758
Author(s):  
Yeo-Kyeoung Kim ◽  
Sung-Hoon Chung ◽  
Jae-Sook Ahn ◽  
Deok-Hwan Yang ◽  
Il-Kwon Lee ◽  
...  
Keyword(s):  
Platelet Count ◽  
Treatment Outcome ◽  
Maintenance Dose ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Platelet Counts ◽  
Chronic Itp ◽  
Insufficient Response ◽  
Korean Adult

Introduction Eltrombopag is a synthetic non-peptide thrombopoietin receptor agonist (TPO-RA), which shows an excellent treatment outcome in immune thrombocytopenia (ITP) patients. For East Asians, starting dose of eltrombopag is generally recommended as a 25 mg/day and maximal dose is restricted as a 50 mg/day because of higher plasma eltrombopag AUC values. Furthermore, sensitivity to TPO-RA may increase or decrease over time. Here, we attempted to analyze the effective eltrombopag doses to achieve and maintain safe platelet counts in Korean ITP patients. Methods A total of twelve adult chronic ITP patients were enrolled, which showed insufficient response to previous ITP treatments (platelet counts less than or equal to 30,000/uL). All patients were allowed to take concomitant low dose prednisolone or danazol. Ten patients started eltromobopag at a dose of 25 mg/day and two patients started 25 mg every other day (EOD) because of previously detected hepatic problem. The doses increased every two weeks to achieve a target platelet count (equal to or more than 50,000/uL). For patients achieving platelet count within the range of 50,000 to 200,000/uL, firstly, we reduced concomitant ITP medications and then reduced eltrombopag doses to find the lowest effective dose of eltrombopag to maintain platelet counts more than 50,000/uL (maintenance dose). Results Before starting eltrombopag treatment, patients received median 4 (ranges; 3-9) ITP treatments including 1 case of splenectomy (Table 1). Bone marrow (BM) examinations including reticulin / Masson-trichrome staining were performed and all patients confirmed not to have BM fibrosis before eltrombopag treatment. Follow-up BM examinations were performed at 1 and 2 year of eltrombopag medication. Of total 12 patients, 10 (83.3%) achieved platelet counts more than 100,000/uL, 1 (8.3%) achieved platelet between 50,000-100,000/uL and 1 (8.3%) failed to increase platelet counts. One failed patient was diagnosed as ITP 114 months ago and received eight ITP treatments before starting eltrombopag. Eleven (91.7%) patients who achieved the target platelet counts (equal to or more than 50,000/uL) could quit or reduce the dose of concomitant ITP medications and median time to achieve the target platelet counts was 21 days (6-151 days). Most common initially required dose to achieve the target platelet counts was 25 mg/day (63.6%). Others were 25 mg EOD (9.1%), 50 mg/day (18.2%) and 75 mg/day (9.1%). After achieving the target platelet counts, most common adjusted maintenance dose was 25 mg/day (63.6%). Others were 25 mg twice a week (27.3%) and 50 mg/day (9.1%). There was no more than gr. 2 bleeding episode during eltrombopag treatment. One patient who required 75 mg/day to achieve the target platelet was diagnosed as ITP 91 months ago and received nine ITP treatments before starting eltrombopag. In 11 responded patients, 9 discontinued eltrombopag medication. Among them, 6 (66.7%) were relapsed and median relapse-free survival (RFS) was 11 days (6-574 days). In an aspect of adverse events, seven (58.3%) showed hepatobiliary laboratory abnormalities (HBLA, two gr. 3), however, all HBLA resolved after reduction or short-term discontinuation of eltrombopag. Eight patients underwent follow-up BM assessment. In 2 year BM, one patient revealed gr. 1 BM fibrosis during eltrombopag medication, however, there was no significant hematologic abnormality or lactate dehydrogenase (LDH) elevation in peripheral blood and no definitive abnormal immature cell clusters in his BM specimen. Conclusions Eltrombopag was generally well tolerated and showed an excellent treatment outcome in refractory chronic ITP patients in Korea. Low doses eltrombopag (25 mg/day or 25 mg twice a week) were effective to maintain safe platelet counts in most Korean patients. However, some of the patients needed longer time and higher doses (50 or 75 mg/day) to initially achieve and to maintain the target platelet counts, especially in heavily pre-treated patients with longer time from diagnosis to starting eltrombopag treatment. Disclosures: No relevant conflicts of interest to declare.

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study

2017 ◽  
Vol 76 (12) ◽  
pp. 2065-2070 ◽  
Author(s):  
Lisa K Stamp ◽  
Peter T Chapman ◽  
Murray Barclay ◽  
Anne Horne ◽  
Christopher Frampton ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Escalation ◽  
Controlled Trial ◽  
Serum Urate ◽  
Extension Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Extension ◽  
Randomised Controlled ◽  
Kidney Impairment

ObjectivesTo determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout.MethodsPeople, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24.ResultsThe mean (SE) change in SU from month 12 to 24 was −1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups.ConclusionsThe majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment.Trial registration numberACTRN12611000845932

scholarly journals Efficacy and safety of eltrombopag in the treatment of severe chronic immune thrombocytopenia in children of China: A single-center observational study

2019 ◽  
Vol 33 ◽  
pp. 205873841987212 ◽  
Author(s):  
Xiaoling Cheng ◽  
Kuo Yan ◽  
Jingyao Ma ◽  
Zhenping Chen ◽  
Libo Zhao ◽  
...  
Keyword(s):  
Adverse Events ◽  
Observational Study ◽  
Immune Thrombocytopenia ◽  
Response Rates ◽  
Drug Dosage ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Serious Adverse Events ◽  
Durable Response ◽  
Chronic Immune Thrombocytopenia

The treatment of severe chronic immune thrombocytopenia (SCITP) in pediatric patients is challenging. We evaluated the clinical efficacy and safety of eltrombopag in children with SCITP in China. This observational study was carried out at the Hematology Oncology Center, Beijing Children’s Hospital between April 2017 and July 2018. Patients with SCITP who had at least 12 weeks of eltrombopag treatment and follow-up data were included. Baseline data, such as age, drug dosage, pre-study platelet count, concomitant medications, and bleeding severity, were collected. Treatment response rates, durable response rates, bleeding events, and adverse events were assessed during eltrombopag therapy for at least 12 weeks. The median duration of eltrombopag therapy was 16 (12–48) weeks. The overall, complete, and partial response rates were 75% (15/20), 35% (7/20), and 40% (8/20), respectively. The durable response rate was 70% (14/20). No serious bleeding events or serious adverse events occurred during the study period. Eltrombopag appears to be effective and safe in children with SCITP, although additional research is needed to confirm this.

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