Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis

Key Points Older age, insidious onset, no preceding infection, mild bleeding, and higher platelet count are the strongest risk factors for chronic ITP. Intravenous immunoglobulin treatment seems to protect against development of chronic ITP.

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Eltrombopag versus romiplostim in treatment of children with persistent or chronic immune thrombocytopenia: a systematic review incorporating an indirect-comparison meta-analysis

Scientific Reports ◽

10.1038/s41598-017-19099-8 ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 3

Author(s):

Jiaxing Zhang ◽

Yi Liang ◽

Yuan Ai ◽

Xiaosi Li ◽

Juan Xie ◽

...

Keyword(s):

Systematic Review ◽

Immune Thrombocytopenia ◽

Meta Analysis ◽

Indirect Comparison ◽

Chronic Immune Thrombocytopenia

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Bleeding manifestations and management of children with persistent and chronic immune thrombocytopenia: data from the Intercontinental Cooperative ITP Study Group (ICIS)

Blood ◽

10.1182/blood-2012-12-466375 ◽

2013 ◽

Vol 121 (22) ◽

pp. 4457-4462 ◽

Cited By ~ 52

Author(s):

Cindy E. Neunert ◽

George R. Buchanan ◽

Paul Imbach ◽

Paula H. B. Bolton-Maggs ◽

Carolyn M. Bennett ◽

...

Keyword(s):

Drug Therapy ◽

Immune Thrombocytopenia ◽

Study Group ◽

Severe Thrombocytopenia ◽

Major Hemorrhage ◽

Chronic Itp ◽

Key Points ◽

Chronic Immune Thrombocytopenia

Key Points Severe thrombocytopenia is rare and major hemorrhage is uncommon in children with persistent and chronic ITP. In children with persistent or chronic ITP, there is a trend toward reserving drug therapy for those experiencing significant bleeding.

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Systematic Review and Meta-Analysis Of Rituximab For The Treatment Of Immune Thrombocytopenia In Adults

Blood ◽

10.1182/blood.v122.21.1681.1681 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1681-1681 ◽

Cited By ~ 1

Author(s):

Shaan Chugh ◽

Donald Arnold ◽

Wendy Lim ◽

Mark A. Crowther ◽

Saeed Darvish-Kazem

Keyword(s):

Systematic Review ◽

Platelet Count ◽

Board Of Directors ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Meta Analysis ◽

Risk Of Infection ◽

Advisory Committees ◽

Count Response

Abstract Background Rituximab, a monoclonal anti-CD20 antibody is commonly used to treat immune thrombocytopenia (ITP). Results of randomized controlled trials (RCTs) evaluating the efficacy of rituximab are conflicting. We conducted a systematic review and meta-analysis of RCTs to determine a more precise estimate of the effect of rituximab on platelet count response in adults with ITP. Methods We searched MEDLINE (from 1946), EMBASE (from 1980), and the Cochrane database using the MeSH terms antibodies, monoclonal, and purpura thrombocytopenia idiopathic and the textwords rituximab, rituxan, mabthera, and immune thrombocytopenic purpura. In duplicate, two reviewers independently assessed study eligibility, abstracted data and assessed each study for methodological quality. Results We identified 4 RCTs (n=360) that met our eligibility criteria. Each trial compared rituximab to placebo combined with other ITP treatments, including dexamethasone, or standard of care. Each trial enrolled non-splenectomized patients only. The likelihood of achieving a platelet count >100 x109/L at 6 months was greater with rituximab than placebo (relative risk [RR] 1.38, 95% CI 1.08-1.76). More patients receiving rituximab achieved a platelet count greater than 50 x109/L at 6 months (RR 1.46, 95% CI 1.18-1.80) compared to placebo. Rituximab was not associated with a reduction in the risk of any bleeding (RR 1.49, 95% CI 0.55-4.04) or an increase in the risk of infection (RR 1.33, 95% CI 0.74-2.38). Conclusions Rituximab is associated with a modest increase in the likelihood of achieving a platelet count greater than >100 x109/L at 6 months compared to placebo. No significant reduction in bleeding or increased risk of infection was observed at 6 months. Randomized trials were generally small, with relatively short follow-up. Large pragmatic multicenter comparative trials are needed to examine durability of response over a longer period of follow-up. Disclosures: Arnold: Amgen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; GlaxoSmithKline: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Hoffman-LaRoche: Research Funding. Lim:Leo Pharma: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Crowther:Asahi Kasai: Membership on an entity’s Board of Directors or advisory committees; Baxter: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; CSL Behring: Speakers Bureau; Leo Pharma: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck: Consultancy; Octapharma: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Viropharma: Membership on an entity’s Board of Directors or advisory committees.

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Rituximab As Second-Line Treatment For Chronic Immune Thrombocytopenia: Investigator-Initiated Clinical Trial In Japan

Blood ◽

10.1182/blood.v122.21.3554.3554 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3554-3554

Author(s):

Yoshitaka Miyakawa ◽

Shinya Katsutani ◽

Takahiro Yano ◽

Shosaku Nomura ◽

Kaichi Nishiwaki ◽

...

Keyword(s):

Clinical Trial ◽

Platelet Count ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Pharmaceutical Research ◽

Japanese Patients ◽

Efficacy And Safety ◽

Platelet Counts ◽

Chronic Itp ◽

Chronic Immune Thrombocytopenia

Abstract The American Society of Hematology guidelines recommend rituximab as second-line treatment, as well as splenectomy and thrombopoietin receptor agonists (TPO-RAs), for chronic immune thrombocytopenia (ITP). However, rituximab has not been approved for the treatment of chronic ITP in Japan. To establish chronic ITP as a new indication for rituximab, we conducted an investigator-initiated clinical trial to clarify the efficacy and safety of rituximab for Japanese patients with ITP. This study was designed as a single-arm, multicenter phase III study. Patients diagnosed with chronic ITP who were previously treated with at least one therapy for ITP and whose platelet count was ≤ 30,000/μL were included. Patients with a past history or current hepatitis B virus, hepatitis C virus or HIV infection, who were treated with splenectomy within 12 weeks or with TPO-RA within 4 weeks were excluded. Rituximab at a dose of 375 mg/m2was intravenously infused once weekly for 4 weeks. Patients were premedicated with acetaminophen, restamin and hydrocortisone to prevent infusion reactions. Platelet counts, bleeding symptoms, and B lymphocyte counts were observed once monthly following the protocol. The primary endpoint was the proportion of patients whose platelet count was ≥ 50,000/μL 24 weeks after treatment with rituximab. Between October 2011 and January 2013, 26 patients were enrolled in this study from 10 hospitals in Japan. Median age of the patients was 40 years and 89% were female. Baseline platelet counts were 23,000/μL. Median interval from diagnosis of ITP to commencing rituximab therapy was 5.9 years. Previous treatment of ITP was corticosteroids (69%), splenectomy (15%), TPO-RA (27%) and intravenous immunoglobulins (39%). At baseline, 58% of patients had some bleeding symptoms. Median number of previous ITP treatments was two. All patients completed the study. At 24 weeks after treatment, 30.8% (95% CI: 14.3–51.8%) of patients achieved platelet counts > 50,000/μL. Seven of eight responders demonstrated improvement until 8 weeks. Platelet count was significantly increased compared with baseline (P<0.001). No unknown severe adverse events were observed. Subgroup analyses showed that ITP duration was numerically associated with the efficacy rate (46% vs 15% for duration< median vs ≥ median, respectively). Bleeding symptoms measured with the WHO bleeding scale were improved compared with baseline. We demonstrated the efficacy and safety of rituximab in Japanese patients with chronic ITP. The response rate was similar to that in previous reports in the US and Europe. We plan to propose that the Japanese government approve chronic ITP as a new indication for rituximab. Disclosures: Miyakawa: Fuji film: Consultancy; Alexion pharmaceuticals: Honoraria; GlaxoSmithKline: Consultancy, Honoraria; KyowaHakkoKirin: Consultancy, Honoraria; Shire: Honoraria. Off Label Use: rituximab, clinical trial. Nishiwaki:Chugai pharmaceutical: Research Funding; Zenyaku Kogyo: Research Funding. Higashihara:Alexion: Honoraria; Asahi Kasei Pharma: Honoraria; Janssen pharma: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Shionogi: Honoraria, Research Funding; Nippon Shinyaku: Honoraria, Research Funding; GlaxoSmithKline: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Boehringer-Ingeheim: Honoraria; Daiichi Sankyo: Honoraria; Yakurt: Honoraria; Astellas: Research Funding; Pfizer: Research Funding; Teijin: Research Funding; Meiji Seika pharma: Research Funding; Venesis: Research Funding; Baxter: Research Funding; Torii pharmaceutical: Research Funding; Bristol-Myers Squibb: Research Funding; Dainippon Sumitomo: Research Funding; Taiho: Research Funding; Taisho Tomiyama: Research Funding; MSD: Research Funding. Nishikawa:Daiichi-Sankyo: Research Funding. Ozaki:Chugai pharmaceutical: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Kyowa Hakko Kirin: Honoraria. Kanakura:Alexion Pharmaceuticals: Research Funding, Speakers Bureau. Okamoto:Novartis : Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; GlaxoSmithKlein: Honoraria, Research Funding; KyowaHakkoKirin: Honoraria, Research Funding; Chugai: Honoraria, Research Funding.

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Is There a Role for Biweekly Romiplostim in the Management of Chronic Immune Thrombocytopenia (ITP)? A Report of Three Cases

Case Reports in Hematology ◽

10.1155/2018/6037494 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6

Author(s):

Jasjit Kaur Rooprai ◽

Karima Khamisa

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Dose Interval ◽

Bleeding Complications ◽

Case Review ◽

Retrospective Case ◽

Weekly Injection ◽

Chronic Itp ◽

Select Group ◽

Chronic Immune Thrombocytopenia

Romiplostim is a peptibody, which stimulates platelet production by a mechanism similar to that of endogenous thrombopoietin. It has an established indication as second-line therapy in patients with chronic immune thrombocytopenia (ITP). The agent is typically administered weekly; however, there are instances where a biweekly (i.e., alternate week) dosing may be feasible in a select group of patients. We conducted a retrospective case review to evaluate the efficacy and safety of biweekly administration of romiplostim in maintaining a platelet count of >30 × 109/L in three patients with chronic ITP. Treatment was started with a weekly injection (1 µg/kg) with a dose escalation to achieve a platelet count >30 × 109/L. Once stable on weekly romiplostim, these patients received biweekly administration. No bleeding complications were noted during biweekly dosing for these patients. The current findings suggest that lengthening the dose interval of romiplostim is feasible in select patients with chronic ITP to maintain stable platelet counts. Additional studies are therefore warranted to further evaluate biweekly dosing for romiplostim to increase convenience and decrease costs for patients with chronic ITP.

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