SAFETY AND EFFICACY/EFFECTIVENESS OF SECOND-LINE TREATMENTS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA: A SYSTEMATIC REVIEW OF THE LITERATURE
(Abstract release date: 05/19/16)
EHA Library. Mehta B. 06/09/16; 132966; E1417
Ms. Bhakti Mehta
Contributions
Contributions
Abstract
Abstract: E1417
Type: Eposter Presentation
Background
Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. Typical first-line therapies include corticosteroids, intravenous immunoglobulin, and anti-D. Patients who fail initial treatment or relapse may require second-line treatment, yet definitive guidelines in this setting are lacking, presumably because of a paucity of relevant rigorous clinical research.
Aims
To systematically review studies evaluating the safety and efficacy/effectiveness of therapies used to treat ITP in the 2nd-line setting (splenectomy, azathioprine, cyclophosphamide, cyclosporine A, danazol, dapsone, eltrombopag, mycophenolate mofetil, rituximab, romiplostim, and vinca alkaloids), with a focus on randomized controlled trials (RCTs).
Methods
Using comprehensive search strings, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PubMed, EMBASE, and clinicaltrials.gov were searched with no time or geographic constraints. Studies in which these agents were used as first-line therapy; with <20 patients; in populations of children, pregnant women, or patients with secondary thrombocytopenia; or not published in English were excluded. Studies were reviewed for several safety and efficacy endpoints. Twelve prospective, randomized, placebo- or standard-of-care (SOC)-controlled studies were further evaluated given their comparable study designs and levels of evidence provided. Outcomes common to multiple studies (bleeding, overall and complete platelet response, and use of rescue therapies) were summarized and indirectly compared using forest plots of calculated risk or response ratios for each outcome from each study.
Results
Final abstraction was performed on 165 articles meeting inclusion criteria. The majority of studies were observational in nature and none represented interventional studies providing head-to-head comparisons of the second-line therapies. Twelve prospective, randomized, placebo- or SOC-controlled studies evaluated the efficacy and safety of either one of two thrombopoietin-receptor (TPO-R) agonists (romiplostim [n=5] and eltrombopag [n=5]) or rituximab (n=2). Although aspects of study design, outcome definitions, and specific subject inclusion/exclusion criteria varied across the studies, patients receiving romiplostim, eltrombopag, or rituximab tended to demonstrate a reduced risk of bleeding and use of rescue therapy and an increased likelihood of platelet response compared with patients receiving either placebo or SOC almost without exception. These risk/response differences tended to be greatest in trials involving a TPO-R agonist (e.g., the range of response ratios for overall platelet response was 1.81-34.28 for romiplostim versus placebo/SOC; 1.40-14.00 for eltrombopag versus placebo; and 0.86-1.09 for rituximab versus placebo).
Conclusion
Data from rigorous RCTs are still currently limited for most second-line ITP treatment options. Twelve prospective, randomized placebo- or SOC-controlled studies were identified but covered only three (eltrombopag, rituximab, and romiplostim) of the several second-line medical treatment options available. These studies provide high-quality evidence regarding the efficacy and safety of these three therapies and, in the absence of head-to-head data, offer insights regarding how they compare to one another in terms of clinical outcomes.
Session topic: E-poster
Keyword(s): Idiopathic thombocytopenic purpura (ITP), Systematic review, Treatment
Type: Eposter Presentation
Background
Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. Typical first-line therapies include corticosteroids, intravenous immunoglobulin, and anti-D. Patients who fail initial treatment or relapse may require second-line treatment, yet definitive guidelines in this setting are lacking, presumably because of a paucity of relevant rigorous clinical research.
Aims
To systematically review studies evaluating the safety and efficacy/effectiveness of therapies used to treat ITP in the 2nd-line setting (splenectomy, azathioprine, cyclophosphamide, cyclosporine A, danazol, dapsone, eltrombopag, mycophenolate mofetil, rituximab, romiplostim, and vinca alkaloids), with a focus on randomized controlled trials (RCTs).
Methods
Using comprehensive search strings, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PubMed, EMBASE, and clinicaltrials.gov were searched with no time or geographic constraints. Studies in which these agents were used as first-line therapy; with <20 patients; in populations of children, pregnant women, or patients with secondary thrombocytopenia; or not published in English were excluded. Studies were reviewed for several safety and efficacy endpoints. Twelve prospective, randomized, placebo- or standard-of-care (SOC)-controlled studies were further evaluated given their comparable study designs and levels of evidence provided. Outcomes common to multiple studies (bleeding, overall and complete platelet response, and use of rescue therapies) were summarized and indirectly compared using forest plots of calculated risk or response ratios for each outcome from each study.
Results
Final abstraction was performed on 165 articles meeting inclusion criteria. The majority of studies were observational in nature and none represented interventional studies providing head-to-head comparisons of the second-line therapies. Twelve prospective, randomized, placebo- or SOC-controlled studies evaluated the efficacy and safety of either one of two thrombopoietin-receptor (TPO-R) agonists (romiplostim [n=5] and eltrombopag [n=5]) or rituximab (n=2). Although aspects of study design, outcome definitions, and specific subject inclusion/exclusion criteria varied across the studies, patients receiving romiplostim, eltrombopag, or rituximab tended to demonstrate a reduced risk of bleeding and use of rescue therapy and an increased likelihood of platelet response compared with patients receiving either placebo or SOC almost without exception. These risk/response differences tended to be greatest in trials involving a TPO-R agonist (e.g., the range of response ratios for overall platelet response was 1.81-34.28 for romiplostim versus placebo/SOC; 1.40-14.00 for eltrombopag versus placebo; and 0.86-1.09 for rituximab versus placebo).
Conclusion
Data from rigorous RCTs are still currently limited for most second-line ITP treatment options. Twelve prospective, randomized placebo- or SOC-controlled studies were identified but covered only three (eltrombopag, rituximab, and romiplostim) of the several second-line medical treatment options available. These studies provide high-quality evidence regarding the efficacy and safety of these three therapies and, in the absence of head-to-head data, offer insights regarding how they compare to one another in terms of clinical outcomes.
Session topic: E-poster
Keyword(s): Idiopathic thombocytopenic purpura (ITP), Systematic review, Treatment
Abstract: E1417
Type: Eposter Presentation
Background
Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. Typical first-line therapies include corticosteroids, intravenous immunoglobulin, and anti-D. Patients who fail initial treatment or relapse may require second-line treatment, yet definitive guidelines in this setting are lacking, presumably because of a paucity of relevant rigorous clinical research.
Aims
To systematically review studies evaluating the safety and efficacy/effectiveness of therapies used to treat ITP in the 2nd-line setting (splenectomy, azathioprine, cyclophosphamide, cyclosporine A, danazol, dapsone, eltrombopag, mycophenolate mofetil, rituximab, romiplostim, and vinca alkaloids), with a focus on randomized controlled trials (RCTs).
Methods
Using comprehensive search strings, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PubMed, EMBASE, and clinicaltrials.gov were searched with no time or geographic constraints. Studies in which these agents were used as first-line therapy; with <20 patients; in populations of children, pregnant women, or patients with secondary thrombocytopenia; or not published in English were excluded. Studies were reviewed for several safety and efficacy endpoints. Twelve prospective, randomized, placebo- or standard-of-care (SOC)-controlled studies were further evaluated given their comparable study designs and levels of evidence provided. Outcomes common to multiple studies (bleeding, overall and complete platelet response, and use of rescue therapies) were summarized and indirectly compared using forest plots of calculated risk or response ratios for each outcome from each study.
Results
Final abstraction was performed on 165 articles meeting inclusion criteria. The majority of studies were observational in nature and none represented interventional studies providing head-to-head comparisons of the second-line therapies. Twelve prospective, randomized, placebo- or SOC-controlled studies evaluated the efficacy and safety of either one of two thrombopoietin-receptor (TPO-R) agonists (romiplostim [n=5] and eltrombopag [n=5]) or rituximab (n=2). Although aspects of study design, outcome definitions, and specific subject inclusion/exclusion criteria varied across the studies, patients receiving romiplostim, eltrombopag, or rituximab tended to demonstrate a reduced risk of bleeding and use of rescue therapy and an increased likelihood of platelet response compared with patients receiving either placebo or SOC almost without exception. These risk/response differences tended to be greatest in trials involving a TPO-R agonist (e.g., the range of response ratios for overall platelet response was 1.81-34.28 for romiplostim versus placebo/SOC; 1.40-14.00 for eltrombopag versus placebo; and 0.86-1.09 for rituximab versus placebo).
Conclusion
Data from rigorous RCTs are still currently limited for most second-line ITP treatment options. Twelve prospective, randomized placebo- or SOC-controlled studies were identified but covered only three (eltrombopag, rituximab, and romiplostim) of the several second-line medical treatment options available. These studies provide high-quality evidence regarding the efficacy and safety of these three therapies and, in the absence of head-to-head data, offer insights regarding how they compare to one another in terms of clinical outcomes.
Session topic: E-poster
Keyword(s): Idiopathic thombocytopenic purpura (ITP), Systematic review, Treatment
Type: Eposter Presentation
Background
Immune thrombocytopenia (ITP) is a rare disorder characterized by low platelet counts and an increased tendency to bleed. Typical first-line therapies include corticosteroids, intravenous immunoglobulin, and anti-D. Patients who fail initial treatment or relapse may require second-line treatment, yet definitive guidelines in this setting are lacking, presumably because of a paucity of relevant rigorous clinical research.
Aims
To systematically review studies evaluating the safety and efficacy/effectiveness of therapies used to treat ITP in the 2nd-line setting (splenectomy, azathioprine, cyclophosphamide, cyclosporine A, danazol, dapsone, eltrombopag, mycophenolate mofetil, rituximab, romiplostim, and vinca alkaloids), with a focus on randomized controlled trials (RCTs).
Methods
Using comprehensive search strings, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PubMed, EMBASE, and clinicaltrials.gov were searched with no time or geographic constraints. Studies in which these agents were used as first-line therapy; with <20 patients; in populations of children, pregnant women, or patients with secondary thrombocytopenia; or not published in English were excluded. Studies were reviewed for several safety and efficacy endpoints. Twelve prospective, randomized, placebo- or standard-of-care (SOC)-controlled studies were further evaluated given their comparable study designs and levels of evidence provided. Outcomes common to multiple studies (bleeding, overall and complete platelet response, and use of rescue therapies) were summarized and indirectly compared using forest plots of calculated risk or response ratios for each outcome from each study.
Results
Final abstraction was performed on 165 articles meeting inclusion criteria. The majority of studies were observational in nature and none represented interventional studies providing head-to-head comparisons of the second-line therapies. Twelve prospective, randomized, placebo- or SOC-controlled studies evaluated the efficacy and safety of either one of two thrombopoietin-receptor (TPO-R) agonists (romiplostim [n=5] and eltrombopag [n=5]) or rituximab (n=2). Although aspects of study design, outcome definitions, and specific subject inclusion/exclusion criteria varied across the studies, patients receiving romiplostim, eltrombopag, or rituximab tended to demonstrate a reduced risk of bleeding and use of rescue therapy and an increased likelihood of platelet response compared with patients receiving either placebo or SOC almost without exception. These risk/response differences tended to be greatest in trials involving a TPO-R agonist (e.g., the range of response ratios for overall platelet response was 1.81-34.28 for romiplostim versus placebo/SOC; 1.40-14.00 for eltrombopag versus placebo; and 0.86-1.09 for rituximab versus placebo).
Conclusion
Data from rigorous RCTs are still currently limited for most second-line ITP treatment options. Twelve prospective, randomized placebo- or SOC-controlled studies were identified but covered only three (eltrombopag, rituximab, and romiplostim) of the several second-line medical treatment options available. These studies provide high-quality evidence regarding the efficacy and safety of these three therapies and, in the absence of head-to-head data, offer insights regarding how they compare to one another in terms of clinical outcomes.
Session topic: E-poster
Keyword(s): Idiopathic thombocytopenic purpura (ITP), Systematic review, Treatment
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