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CADTH Health Technology Review
Authors; Daphne Hui, Angela Barbara, and Sarah C. McGill.
Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by a low platelet count (< 100,000/μL) resulting from platelet destruction and impaired platelet production.1,2 The cause of ITP is not always known but it may be caused by a viral infection or an immune response.3 The Canadian Paediatric Society reported that ITP affects approximately 5 in 100,000 children in Canada per year.3 There is a greater incidence of ITP in individuals between the ages of 2 years to 5 years and a lower incidence during adolescence.3,4 ITP typically presents with bruising, bleeding, and/or a sudden petechial rash in an otherwise healthy child.4 Apart from bleeding of the skin and mucous membranes, systemic symptoms tend to be absent. Therefore, thrombocytopenia may be detected incidentally during evaluation of complete blood counts (including platelets), such as during routine or presurgical assessments.4 Approximately, 10% to 20% of children will develop chronic ITP, defined as platelet count of less than 100,000/μL persisting beyond 12 months from the time of initial presentation.2 Factors correlated with increased risk of chronic disease include older age, gradual and subtle onset of symptoms, higher platelet count at initial diagnosis, and lack of preceding infection or vaccination before development of ITP.2 Newly diagnosed and persistent ITP are defined as ITP within 3 months from diagnosis and ongoing ITP between 3 months and 12 months from initial diagnosis, respectively.5
Management of newly diagnosed ITP in children is based largely on the severity of bleeding, risk factors, degree of thrombocytopenia (condition of low blood platelet count), quality of life, and values and preferences of the patient, caregiver, and family. Initial management includes watchful waiting (i.e., no interventions used) or pharmacological interventions. Pharmacological interventions for newly diagnosed ITP include IV immune globulin (IVIG), anti-D immunoglobulin, and glucocorticoids such as methylprednisolone.5
Management of chronic ITP depends on the symptom type and duration.2 For instance, some patients will experience intermittent episodes of thrombocytopenia but remain relatively asymptomatic sometimes, whereas other patients may require continuous or intermittent therapy for ongoing or recurrent bleeding symptoms or risks. Selecting a particular pharmacologic treatment depends on risk factors for bleeding (e.g., active lifestyle, sports), continuous bleeding symptoms, concomitant medications and medical conditions (e.g., anxiety, fatigue), and access to care.2 Acute interventions for bleeding or risk of bleeding are similar to the first-line pharmacological interventions including IVIG, anti-D immunoglobulin, and glucocorticoids.2 However, clinicians prefer steroid-sparing agents such as rituximab and thrombopoietic agents, which include thrombopoietin receptor agonists (TRAs or TPO-RAs in some publications).2 TRAs (e.g., eltrombopag and romiplostim), which stimulate the production of platelets (thrombopoiesis) through the thrombopoietin receptor, may be used in children with chronic ITP. Based on evidence from randomized and non-randomized studies, eltrombopag and romiplostim appear to have comparable efficacy and produce a durable platelet response with less frequent bleeding-related adverse events.2 One randomized study on long-term use of romiplostim (n = 17) or placebo (n = 5) suggested that platelet levels can be maintained for over 4 years with good tolerability and without major toxicity.2
Dapsone is an immunosuppressive agent that may be used in children with late persistent or chronic ITP; however, it has not been demonstrated to exhibit a curative effect and is associated with some toxicity (e.g., hepatotoxicity).2 Splenectomy is an option that may be considered in a small percentage of patients who have severe thrombocytopenia with excessive bleeding requiring repeated or continuous pharmacologic interventions.2
The purpose of this Rapid Review is to evaluate recent evidence-based guidelines regarding the use of dapsone, rituximab, and TRAs for the treatment of ITP in children. There will be separate reports summarizing the clinical effectiveness and cost-effectiveness of these interventions for the treatment of ITP in children. CADTH is also conducting a systematic review (SR) on treatments for adults with ITP.
A limited literature search was conducted by an information specialist on key resources including MEDLINE and Embase through the Ovid platform, the Cochrane Database of Systematic Reviews, the International HTA Database, the websites of Canadian and major international health technology agencies, as well as a focused internet search. The search strategy comprised both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were immune thrombocytopenia and pediatrics. CADTH-developed search filters were applied to limit retrieval to guidelines. If possible, retrieval was limited to the human population. The search was also limited to English-language documents published between January 1, 2017, and April 12, 2021.
One reviewer screened citations and selected studies. In the first level of screening, titles and abstracts were reviewed and potentially relevant articles were retrieved and assessed for inclusion. The final selection of full-text articles was based on the inclusion criteria presented in Table 1.
Selection Criteria.
Articles were excluded if they did not meet the selection criteria outlined in Table 1, were duplicate publications, or were published before 2017. Guidelines with unclear methodology were also excluded. Of note, guidelines on avatrombopag, (a TRA used to treat thrombocytopenia in people with ITP) are not discussed in this report because the drug is undergoing a CADTH Reimbursement Review.
The included publications were critically appraised by 1 reviewer using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument6 for guidelines as a guide. Summary scores were not calculated for the included studies; rather, the strengths and limitations of each included publication were described narratively.
A total of 35 citations were identified in the literature search. Following screening of titles and abstracts, 30 citations were excluded and 5 potentially relevant reports from the electronic search were retrieved for full-text review. 7 potentially relevant publications were retrieved from the grey literature search for full-text review. Of the 12 potentially relevant articles, 8 were excluded for various reasons; 4 evidence-based guidelines1,7-9 met the inclusion criteria and were included in this report. Figure 1 presents the PRISMA10 flow chart of the study selection.
Additional references of potential interest are provided in Appendix 5.
A total of 4 evidence-based guidelines were included in this review.1,7-9 Additional details regarding the characteristics of the included publications are provided in Table 2.
The 2021 guideline by the Working Group of Chinese Guideline for the Diagnosis and Treatment of Childhood Primary Immune Thrombocytopenia, referred to as the 2021 Chinese-adapted guidelines herein, is an adaptation of published guidelines in consideration of values, resources, and social and cultural factors specific to China.9 The adaptation was performed through a systematic search for guidelines (which would be adapted) and supplementary evidence (study design not reported) following ADAPTE methodology and the WHO Handbook for Guideline Development.9 Evidence levels based on the source of the evidence and grade of recommendations based on evidence requirements were adopted from the 2019 Updated International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia.7,9 Evidence levels were designated as follows: Ia = evidence obtained from meta-analysis of RCTs; Ib = 1 or more RCTs; IIa = 1 or more well-designed controlled studies without randomization; IIb = 1 or more other type of well-designed quasi-experimental studies; III = well-designed nonexperimental descriptive studies (such as comparative studies, correlated studies, and case studies); and IV = expert committee reports or opinions and/or clinical experience of respected authorities). Grades of the recommendations were defined as follows: A = requires at least 1 RCT as part of a body of literature of overall good quality and consistency addressing specific recommendation; B = requires well-conducted clinical studies but not RCT on the topic of recommendation; and C = requires expert committee reports or opinions and/or clinical experiences of respective authorities.9 The Cochrane risk of bias tool and quality assessment tool for case series were used to evaluate methodological quality of RCTs and case series, respectively. The adapted guidelines and rationale were revised, improved, and finalized following 2 rounds of Delphi survey and an online consensus meeting.9
The 2019 guidelines for ITP by the American Society of Hematology (ASH) were developed based on SRs (performed following the general methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions) of effects of interventions and evidence pertaining to baseline risks, costs, values, and preferences.1 Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology was used to assess certainty in the evidence (i.e., quality of the evidence) for each effect estimate of the outcomes through 4 levels from very low to high.1 Various GRADE domains were considered, such as risk of bias, inconsistency, indirectness, imprecision, and publication bias. The strength of the recommendation was rated as strong (“recommends”) or conditional (“suggests”).1 Interpretations of the strength of the recommendations were reported separately for patients, clinicians, policy-makers, and researchers.1 Risk of bias was assessed at the outcome level using Cochrane tools for randomized and non-randomized studies. Guidelines were established based on consensus among the panel; however, in rare occasions, voting was implemented (e.g., 80% majority was required for a strong recommendation).1
The 2019 Updated International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia (referred to as the 2019 updated international consensus report on primary ITP herein) is an update to a report published in 2010.7 This 2019 report was developed based on a search of PubMed for publications published between January 1, 2009, and July 23, 2018, to retrieve articles published since the last literature search of the original report. The updated recommendations followed the principles of the CheckUp guidelines.7 Two panel meetings were conducted to discuss the identified literature, draft consensus statements, and finalize updated recommendations. Consensus was required; however, 100% consensus was not reached on every recommendation — 85% of recommendations achieved 85% agreement. Recommendations were rated for the level of evidence: Ia = meta-analysis of RCTs, Ib = 1 or more RCTs, IIa = 1 or more well-designed controlled studies without randomization, IIb = 1 or more other well-designed quasi-experimental studies, III = well-designed nonexperimental descriptive studies (e.g., comparative studies, case studies), and IV = expert committee reports or opinions and/or experience of respected authorities. Grades of the recommendations were defined as follows: A = 1 or more RCTs of overall good quality and consistency addressing specific recommendations (Ia and Ib), B = well-conducted clinical studies when there are no randomized clinical trials available (IIa, IIb, and III); and C = evidence from expert committee reports or opinions and/or experiences of respected authorities which suggests absence of directly applicable clinical studies of good quality (IV).7 All authors provided input on each draft of the manuscript and approved the final version for submission.7
The 2018 guidelines from an interdisciplinary European working group did not report the methodology associated with development of the guidelines but were included because a grading system was used for supporting evidence and the recommendations, which indicates that the guidelines were evidence-based.8 The recommendations were developed by an interdisciplinary working group of experts from the German Society for Hematology and Medical Oncology, German Society for Transfusion Medicine and Immunohematology, Austrian Society for Hematology and Medical Oncology, Swiss Society for Hematology, and Society for Pediatric Oncology and Hematology.8 The recommendations were based on relevant publications published up to November 2017. Abstracts were also considered if they were presented at meetings in 2015 and thereafter. Rating of evidence levels followed the Oxford Centre of Evidence-Based Medicine: Levels of Evidence (March 2009) and grading of recommendations followed the National Program for Medical Service Guidelines Method Report of 2010.8 The grading designations for the recommendations were defined as follows: A = strong recommendation (“must”); B = recommendation (“should”); 0 = open recommendation (“can”); and expert consensus which was provided when there was insufficient supporting data.8 The authors noted this was when “there is insufficient scientific data.” Information such as the use of voting or a consensus system and validation methodology were not reported.8
The 2021 Chinese-adapted guidelines were devised for clinical practice in China.9
The 2019 ASH guidelines did not specify a country where the guidelines were meant to apply. It was noted that the guidelines should be interpreted with consideration of local clinical practice, availability of resources, institutional policies, and limitations of time.1
The 2019 updated international consensus report on primary ITP was intended to provide a global perspective, with representation from Europe (13 individuals), North America (US: 4 individuals; Canada: 1 individual), China (2 individuals), Australia (1 individual), and Japan (1 individual) on the development panel.7
The 2018 interdisciplinary European working group guidelines did not specify a country where the guidelines were meant to apply. However, they were devised by experts representing Germany (2 societies). Austria (1 society), Switzerland (1 society), and another society that was not identified by country.8
The target population of the 2021 Chinese-adapted guidelines was children with primary ITP aged 1 month to 18 years living in China. Intended users were clinicians, health care decision-makers, and researchers.9
The 2019 ASH guidelines focused on adults and children with ITP (newly diagnosed, persistent, and chronic ITP refractory to first-line treatment) and non–life-threatening bleeding. Intended users were patients, clinicians, policy-makers, and other decision-makers.1
The 2019 updated international consensus report on primary ITP focused on adults, pregnant adults, and children with primary ITP. The intended users were not explicitly reported but appears to be individuals involved with the diagnosis and management of primary ITP.7
The 2018 interdisciplinary European working group guidelines focused on adults, children, and adolescents with ITP. Intended users were not reported but it was noted that the document was intended as an aid for medical decision-making.8
The interventions in the 2021 Chinese-adapted guidelines relevant to this report included rituximab and thrombopoietic agents.9 However, the recommendations did not specify the exact type of thrombopoietic agents.9
The 2019 ASH guidelines focused on first-line therapy (for newly diagnosed) and second-line management of ITP. The interventions relevant to this report included rituximab and TRAs.1
The 2019 updated international consensus report on primary ITP focused on emergency treatment and first-line therapy and beyond for children with persistent or chronic primary ITP (i.e., could include up to third-line treatment this is not specified).7
The 2018 interdisciplinary European working group guidelines focused on various pharmacological and surgical interventions for ITP. The interventions relevant to this report included treatment of chronic ITP. No specific treatments were mentioned in the recommendation although eltrombopag and romiplostim (TRAs) were discussed.8
The 2021 Chinese-adapted guidelines considered medical resources, the environment, cost-effectiveness, feasibility, values, and preferences of parents and/or guardians. These factors served as the basis for the rationale of the guidelines.9
The 2019 ASH guidelines were developed based on a population perspective considering a balance of harms and benefits with comparators, extent of resource use associated with alternative options, and assumptions of values and preferences. The guidelines were intended to provide recommendations based on patient-reported outcomes, adverse events, treatment impact, and platelet count response.1
The outcomes considered by the guideline panel in the 2019 updated international consensus report on primary ITP were not clearly reported. Eligible outcomes in the literature included from the PubMed search were also not reported. Nevertheless, implementation considerations (e.g., dosing), benefits, and risks were reported among the supporting evidence.7
The 2018 interdisciplinary European working group guidelines also did not report on the outcomes considered during development or if and which outcomes were eligible during selection of supporting evidence. However, common side effects were mentioned.8
Overall, the 4 evidence-based guidelines were clear regarding clarity of presentation; namely, recommendations were specific, unambiguous, and easily identified and different management options were presented.1,7-9
The 2018 interdisciplinary European working group did not report the methodology associated with guideline development. However, its recommendations were rated using the National Program for Medical Service Guidelines Method Report of 2010 and supporting evidence levels were rated using the Oxford Centre of Evidence-Based Medicine: Levels of Evidence (March 2009).8 The guidelines went through an external review process, and the working group noted that the document was intended exclusively to aid medical decision-making and the guidelines were not suitable to define medical standards. Notable limitations in all the guidelines include limiting recommendations to the class of intervention without information about specific drugs. For example, the guidelines reporting on TRAs did not provide recommendations specific to romiplostim or eltrombopag.1,7,9 Further, the 2019 updated international consensus report recommendation was unclear about the place in therapy (e.g., first line or second line) of the treatment options for children with persistent or chronic ITP.7 Standards of practice and availability to certain treatments may differ across clinical practices across countries and within countries.
Regarding the scope and purpose, all guidelines clearly reported the objectives and the population to whom the guideline apply; however, the related health questions were not reported in the 2019 Updated International Consensus Report on Primary ITP and the 2018 Interdisciplinary European Working Group guidelines.7,8 The target users of the guideline were clearly defined for the 2021 Chinese-adapted guidelines and 2019 ASH guidelines and were not reported in the 2019 updated international consensus report and the 2018 interdisciplinary European working group guidelines.1,7-9 Regarding stakeholder involvement, 3 guidelines were developed with groups comprising clinical and methodological experts in addition to patient and guardian representation.1,7,9 The 2018 interdisciplinary European working group guidelines included clinical experts in the development group (a combination of hematology, oncology, and immunohematology experts), but there was no mention of patient and/or caregiver representation or consultation.8
Regarding rigour of development, systematic methods were used to search for evidence for the 2021 Chinese-adapted guidelines, 2019 ASH guidelines, and 2019 updated International consensus report.1,7,9 The 2021 Chinese-adapted guidelines reported the databases, main search terms, and inclusion criteria and performed quality assessments; however, the assessment tools were not reported.9 The 2019 ASH guidelines and 2019 updated international consensus report did not report details such as the inclusion and exclusion criteria; however, the ASH guidelines noted that they followed the methods of the Cochrane Handbook for SRs.1,7 The 3 guidelines had additional strengths, including consideration of the health benefits, side effects, and risks in the development of recommendations as well as reporting of guideline development methodology and supporting evidence.1,7,9 The 2019 ASH guidelines and 2019 updated international consensus report clearly reported methodology and explicit links between the recommendations and supporting evidence.1,7,9 However, the methodology and links between the recommendations and supporting evidence was not very clear in the 2021 Chinese-adapted guidelines.9 Moreover, the 2021 Chinese-adapted guidelines, 2019 ASH guidelines, and 2019 updated international consensus report did not clearly report the strengths and limitations of the evidence supporting the recommendations.1,7,9 The 2021 Chinese-adapted guidelines reported favourable and unfavourable implementation factors and the 2019 ASH guidelines reported the limitations of the guidelines.1,7,9 The 2019 ASH guidelines and 2019 updated international consensus report also reported procedures for updating the guidelines.1,7,9 The 2018 interdisciplinary European working group guidelines did not clearly describe the links between the recommendations and supporting evidence.8 All 4 guidelines underwent external review by experts before publication.1,7-9
The 2021 Chinese-adapted guidelines, 2019 ASH guidelines, and 2019 updated international consensus report reported information regarding applicability, facilitators and barriers to application, advice and/or tools on how put the recommendations into practice, and consideration of potential resource implications.1,7,9 The 2021 Chinese-adapted guidelines provided implementation instructions, the 2019 ASH guidelines reported good practice statements that were not based on a SR of available evidence, and the 2019 updated international consensus report provided dosages and considerations such as platelet count.1,7,9 The 2018 interdisciplinary European working group guidelines did not report facilitators and barriers to application, and it was unclear if potential resource implications of applying recommendations were considered; however, dosages for frequently used drugs for ITP were reported.8 Only the 2019 ASH guidelines reported monitoring and/or auditing criteria, which indicates ongoing review by experts and survey for new evidence will be conducted.1
Regarding editorial independence, all guideline documents reported competing interests. The 2021 Chinese-adapted guidelines reported the funding source as well.9 The 2019 updated international consensus report and 2018 interdisciplinary European working group guidelines did not report the funding of the guideline development although financial conflict of interest(s) were reported for authors.7,8 The ASH guidelines were likely influenced by ASH because funding of the work, panel formation, management of conflicts of interest, internal and external review, and organizational approval was guided by ASH policies and procedures. ASH also appointed the members of the guideline panel.1
Additional details regarding the strengths and limitations of included publications are provided in Appendix 3.
A total of 4 evidence-based guidelines were included in this review.1,7-9 No guidelines informed the use of dapsone, 3 guidelines informed the use of rituximab,1,7,9 and 3 guidelines informed the use of TRAs (e.g., romiplostim, eltrombopag)1,7,9 as treatment for pediatric populations with ITP. The 2018 interdisciplinary European working group guidelines did not specify particular treatments in the recommendations.8 Appendix 4 presents the main study findings and authors’ conclusions.
No evidence-based guidelines were identified for the use of dapsone for pediatric patients with ITP.
For children with ITP who do not respond to first-line treatment, the Chinese-adaptation guideline development group suggest choosing conventional second-line treatment with rituximab rather than splenectomy (level III evidence, grade B recommendation).9
For children with ITP who do not respond to first-line treatment and have non-life-threatening mucosal bleeding and/or diminished health-related quality of life, the ASH guideline panel suggests the use of rituximab rather than splenectomy (conditional recommendation, very low certainty in the evidence) (recommendation 2).1
For children with ITP who do not respond to first-line treatment, the Chinese-adaptation guideline development group suggest choosing conventional second-line treatment with thrombopoietic agents rather than splenectomy (level Ib evidence, grade A recommendation).9
For children with ITP who do not respond to first-line treatment and have non-life-threatening mucosal bleeding and/or diminished health-related quality of life, the ASH guideline panel suggests the use of TRAs rather than splenectomy (conditional recommendation, very low certainty in the evidence) (recommendation 20).1
For treatment of children with persistent or chronic ITP, the 2019 updated international consensus report on primary ITP recommends the use of TRAs for demonstrated good response, reduction in bleeding frequency, and absence of side effects in most patients (evidence level Ib, grade A recommendation). In patients with no response to 1 TRA or when an initial response is lost, an alternative TRA may be used alone or in combination with mycophenolate mofetil or another immunosuppressant (evidence level not reported, grade C recommendation). Rituximab and dexamethasone should be considered in those who fail TRAs, especially adolescent females (evidence level III, grade C recommendation).7
For children with ITP who have grade 4 bleeding, the Chinese-adaptation guideline suggest rescue therapy with combined platelet transfusion, pulse therapy of high-dose methylprednisolone, and pulse therapy of high-dose IVIG to ensure the most effective and rapid elevation of platelet counts for effective hemostasis. The addition of a thrombopoietic agent may be considered at the same time.9
The 2019 updated international consensus report on primary ITP recommended that TRAs be considered for emergency treatment of children with ITP of any stage to aid the acute response and prevent a decrease in platelet count if initial response to emergency therapy is lost (evidence level not reported, grade C recommendation).7
The 2018 interdisciplinary European working group noted that TRAs are effective for the treatment of chronic ITP in children and adolescents and provided supporting references. However, the group also stated that there is no standard treatment for chronic ITP in children and adolescents and patients should be referred to centres with expertise in pediatric hematology.8
For children with ITP who do not respond to first-line treatment, the Chinese-adaptation guideline development group suggests conventional second-line treatment with thrombopoietic agents rather than rituximab (level Ib evidence, grade A recommendation).9
For children with ITP who do not respond to first-line treatment and have non-life-threatening mucosal bleeding and/or diminished health-related quality of life, the ASH guideline panel suggests the use of TRAs rather than rituximab (conditional recommendation, very low certainty in the evidence) (recommendation 19).1
Overall, the 4 evidence-based guidelines were associated with a few limitations as discussed in the Summary of Critical Appraisal section.1,7-9 The 2018 interdisciplinary European working group did not report the methodology associated with guideline development.8
None of the evidence-based guidelines included in this report provided recommendations for the use of dapsone in patients with ITP younger than 18 years of age. Moreover, none of the evidence-based guidelines were specific to the Canadian health care system, which limits generalizability because of differences in implementation considerations including access to treatments between countries and within Canadian jurisdictions (e.g., provincial public drug plans).
In the 3 guidelines that informed the use of TRAs (e.g., romiplostim, eltrombopag)1,7,9 as treatment for pediatric populations with ITP, the recommendations were not reported separately for the specific types of TRAs. The 2021 Chinese-adapted guidelines were provided for thrombopoietic agents and the 2019 ASH guidelines and the 2019 updated international consensus report on primary ITP were provided for TRAs. The broad reference to these interventions may not be informative because there are different drugs within these categories.2 Although there is evidence suggesting similar efficacy of romiplostim and eltrombopag in children with chronic ITP, data directly comparing the 2 drugs are not available.2
This report included information from 4 evidence-based guidelines,1,7-9 3 of which reported on the use rituximab and TRAs (e.g., romiplostim, eltrombopag)1,7,9 for the treatment of pediatric populations with ITP.
For children with ITP who do not respond to first-line treatment, rituximab, thrombopoietic agents, and TRAs were recommended over splenectomy as second-line treatment.1,9 For children with persistent or chronic ITP, it was recommended to switch to another TRA and/or consider combining with mycophenolate mofetil or another immunosuppressant if there is no response to 1 TRA or if the initial response is lost, and to consider using rituximab plus dexamethasone in those who fail TRAs, especially adolescent females.7 The 2018 interdisciplinary European working group stated there were no standard treatments for chronic ITP in children and adolescents, but noted that TRAs (e.g., eltrombopag and romiplostim) are effective for treatment of chronic ITP in children and adolescents.8
For rescue treatment of children with ITP who have grade 4 bleeding, the Chinese-adaptation guideline development group recommended considering thrombopoietic agent therapy combined with platelet transfusion, pulse therapy of high-dose methylprednisolone, and pulse therapy of high-dose IVIG.9 For emergency treatment of children with ITP of any stage, the 2019 updated international consensus report recommended TRAs be considered.7
Overall, there is a need for evidence-based guidelines specific to Canadian health care settings, with specific information on various TRAs, for the treatment of ITP in pediatric populations. Dapsone, rituximab, and romiplostim are used off-label in Canada to treat pediatric ITP. There are also data suggesting that newer generations of anti-CD20 monoclonal antibodies such as obinutuzumab may be more effective and better tolerated than rituximab, a first generation anti-CD20 monoclonal antibody.11 Therefore, there is a need for well-designed studies to support evidence-based guidelines that investigate the use of dapsone, rituximab, and newer anti-CD20 monoclonal antibody drugs in direct comparison with romiplostim and eltrombopag in the Canadian health care setting for the treatment of ITP children. No evidence-based guidelines were identified that recommended using dapsone to treat ITP in pediatric patients. Overall, the recommendations of the guidelines included in this report should be interpreted with caution due to methodological limitations and unknown generalizability in the Canadian context.
American Society of Hematology
immune thrombocytopenia
IV immune globulin
randomized controlled trial
systematic review
thrombopoietin receptor agonist
Selection of Included Studies.
Characteristics of Included Guidelines.
Note that this appendix has not been copy-edited.
Strengths and Limitations of Guidelines Using AGREE II.
Note that this appendix has not been copy-edited.
Summary of Recommendations in Included Guidelines.
Note that this appendix has not been copy-edited.
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