Anemia

James B. Bussel, MD

GENEVA—A recent trial shows that eltrombopag can, with minimal toxicity, improve platelet levels and reduce bleeding in patients with chronic idiopathic thrombocytopenic purpura (ITP).

The phase 3, randomized, controlled trial evaluated the safety and efficacy of eltrombopag treatment in patients with chronic idiopathic thrombocytopenic purpura (ITP).

James B. Bussel, MD, from Weill Medical College of Cornell University in New York, presented the results at the recent meeting of the International Society on Thrombosis and Haemostasis.

A phase 1 study, reported in a 2007 issue of Blood, administered eltrombopag in active doses of 30, 50, and 75 mg. In normal volunteers, it takes a week for platelet counts to increase. Although increases were seen at all 3 dose levels, the optimal dose of 50 mg was chosen for subsequent studies.

In the phase 3 study, patients were randomized to receive placebo (n=38) or 50 mg of eltrombopag (n=76) once daily for 6 weeks (dose increase to 75 mg allowed). Investigators assessed bleeding according to the World Health Organization bleeding scale.

At the end of treatment (day 43), there was a significant increase in platelet levels in the eltrombopag arm vs the placebo arm. The median platelet count at the end of study was 18,000/μL in the placebo arm and 69,000/μL in the eltrombopag arm. The endpoint of >50,000 platelets/μL was reached in up to 42 days of dosing.

Eighteen out of 76 patients achieved platelet increases to >200,000/μL. The platelet counts fell 2 weeks after the end of therapy. There was a reduction in grade 2/4 bleeding of 18% in the placebo arm, and there were no specific findings of adverse events.

Platelet antibodies are still present as platelet levels fall after the cessation of therapy. Dr Bussel said this study confirmed previous findings with eltrombopag. Treatment not only increased platelet levels, but was able to reduce bleeding.

ITP results in reduced production of marrow platelets and platelet destruction by antibodies. Treatment of ITP is necessary to avoid major bleeding by increasing platelets to >50,000/μL. Eltrombopag is a small molecule, can be used orally, binds to a different region of receptor than thrombopoietin, and signals through the JAK/STAT pathway.

James B. Bussel, MD

GENEVA—A recent trial shows that eltrombopag can, with minimal toxicity, improve platelet levels and reduce bleeding in patients with chronic idiopathic thrombocytopenic purpura (ITP).

The phase 3, randomized, controlled trial evaluated the safety and efficacy of eltrombopag treatment in patients with chronic idiopathic thrombocytopenic purpura (ITP).

James B. Bussel, MD, from Weill Medical College of Cornell University in New York, presented the results at the recent meeting of the International Society on Thrombosis and Haemostasis.

A phase 1 study, reported in a 2007 issue of Blood, administered eltrombopag in active doses of 30, 50, and 75 mg. In normal volunteers, it takes a week for platelet counts to increase. Although increases were seen at all 3 dose levels, the optimal dose of 50 mg was chosen for subsequent studies.

In the phase 3 study, patients were randomized to receive placebo (n=38) or 50 mg of eltrombopag (n=76) once daily for 6 weeks (dose increase to 75 mg allowed). Investigators assessed bleeding according to the World Health Organization bleeding scale.

At the end of treatment (day 43), there was a significant increase in platelet levels in the eltrombopag arm vs the placebo arm. The median platelet count at the end of study was 18,000/μL in the placebo arm and 69,000/μL in the eltrombopag arm. The endpoint of >50,000 platelets/μL was reached in up to 42 days of dosing.

Eighteen out of 76 patients achieved platelet increases to >200,000/μL. The platelet counts fell 2 weeks after the end of therapy. There was a reduction in grade 2/4 bleeding of 18% in the placebo arm, and there were no specific findings of adverse events.

Platelet antibodies are still present as platelet levels fall after the cessation of therapy. Dr Bussel said this study confirmed previous findings with eltrombopag. Treatment not only increased platelet levels, but was able to reduce bleeding.

ITP results in reduced production of marrow platelets and platelet destruction by antibodies. Treatment of ITP is necessary to avoid major bleeding by increasing platelets to >50,000/μL. Eltrombopag is a small molecule, can be used orally, binds to a different region of receptor than thrombopoietin, and signals through the JAK/STAT pathway.

James B. Bussel, MD

GENEVA—A recent trial shows that eltrombopag can, with minimal toxicity, improve platelet levels and reduce bleeding in patients with chronic idiopathic thrombocytopenic purpura (ITP).

The phase 3, randomized, controlled trial evaluated the safety and efficacy of eltrombopag treatment in patients with chronic idiopathic thrombocytopenic purpura (ITP).

James B. Bussel, MD, from Weill Medical College of Cornell University in New York, presented the results at the recent meeting of the International Society on Thrombosis and Haemostasis.

A phase 1 study, reported in a 2007 issue of Blood, administered eltrombopag in active doses of 30, 50, and 75 mg. In normal volunteers, it takes a week for platelet counts to increase. Although increases were seen at all 3 dose levels, the optimal dose of 50 mg was chosen for subsequent studies.

In the phase 3 study, patients were randomized to receive placebo (n=38) or 50 mg of eltrombopag (n=76) once daily for 6 weeks (dose increase to 75 mg allowed). Investigators assessed bleeding according to the World Health Organization bleeding scale.

At the end of treatment (day 43), there was a significant increase in platelet levels in the eltrombopag arm vs the placebo arm. The median platelet count at the end of study was 18,000/μL in the placebo arm and 69,000/μL in the eltrombopag arm. The endpoint of >50,000 platelets/μL was reached in up to 42 days of dosing.

Eighteen out of 76 patients achieved platelet increases to >200,000/μL. The platelet counts fell 2 weeks after the end of therapy. There was a reduction in grade 2/4 bleeding of 18% in the placebo arm, and there were no specific findings of adverse events.

Platelet antibodies are still present as platelet levels fall after the cessation of therapy. Dr Bussel said this study confirmed previous findings with eltrombopag. Treatment not only increased platelet levels, but was able to reduce bleeding.

ITP results in reduced production of marrow platelets and platelet destruction by antibodies. Treatment of ITP is necessary to avoid major bleeding by increasing platelets to >50,000/μL. Eltrombopag is a small molecule, can be used orally, binds to a different region of receptor than thrombopoietin, and signals through the JAK/STAT pathway.

VIENNA—Long-term treatment with eculizumab, a recombinant humanized monoclonal antibody, significantly reduces the risk of thrombosis in patients with paroxysmal nocturnal hemoglobinuria (PNH), according to the results of a recent multicenter study.

Peter Hillmen, MD, of the Leeds Teaching Hospitals NHS Trust, reported the results of the study at the 12th Congress of the European Hematology Association in June 2007.

Dr Hillmen and colleagues prospectively examined the aggregate thromboembolism (TE) event rate in eculizumab-treated patients from 3 recent parent studies, as well as a subsequent common extension study. They compared those rates to the TE rate in the same patients’ pre-eculizumab treatment.

Eculizumab, which is designed to inhibit activation of terminal complement components that have been implicated in the development of PNH, reduced the TE rate in each of the three parent studies.

Most importantly, the aggregate TE event rate during eculizumab treatment was significantly reduced by 85% (P=<0.001), when compared with the same patients before eculizumab treatment.

With restriction of the pretreatment observation period to the 12 months immediately preceding eculizumab treatment, the TE event rate during treatment was reduced by 94% (P=0.002). The TE event rate in patients with TE prior to the trials was also reduced by 89% (P=<0.001).

Most TE events prior to eculizumab treatment occurred in patients receiving antithrombotics, either therapeutically or prophylactically. This indicates that the therapy may be insufficient to prevent thrombosis.

Pre-eculizumab treatment, 195 patients experienced 124 TE events. Of the 195 patients, 103 were on antithrombotics.

Of the 103 patients on antithrombotics, there were 54 TE events in 30 patients pre-eculizumab, compared to 1 TE event during eculizumab treatment. This demonstrates that eculizumab significantly reduces the risk of thrombosis in PNH patients, despite treatment with antithrombotics (P=<0.001).

Pre-eculizumab, TE was frequent in patients with lower levels of hemolysis and with mild anemia. Eculizumab significantly reduced TE across these and other subgroups (P=<0.001).

Dr Hillman said these data demonstrate the efficacy of long-term eculizumab treatment in its ability to significantly reduce the occurrence of thrombosis in PNH patients. Because TE accounts for the majority of deaths in PNH, it is reasonable to expect that eculizumab treatment, by decreasing the risk of TE, will increase the life-expectancy in PNH.

PNH is a rare, acquired, and potentially life-threatening disease of the blood characterized by hemolytic anemia, thrombosis, and red-colored urine, resulting from the breakdown of red blood cells.

TE is one of the most feared complications associated with PNH and accounts for approximately 45% of PNH patient deaths. The disease can occur even in individuals who have no previous history of thrombosis.

Patients with PNH are usually treated with anticoagulants on a prophylactic basis. However, these anticoagulants increase the risk of life-threatening hemorrhage without eliminating the potential for thrombosis, which can occur in as many as 30% of the patients who receive anticoagulant treatment. 

VIENNA—Long-term treatment with eculizumab, a recombinant humanized monoclonal antibody, significantly reduces the risk of thrombosis in patients with paroxysmal nocturnal hemoglobinuria (PNH), according to the results of a recent multicenter study.

Peter Hillmen, MD, of the Leeds Teaching Hospitals NHS Trust, reported the results of the study at the 12th Congress of the European Hematology Association in June 2007.

Dr Hillmen and colleagues prospectively examined the aggregate thromboembolism (TE) event rate in eculizumab-treated patients from 3 recent parent studies, as well as a subsequent common extension study. They compared those rates to the TE rate in the same patients’ pre-eculizumab treatment.

Eculizumab, which is designed to inhibit activation of terminal complement components that have been implicated in the development of PNH, reduced the TE rate in each of the three parent studies.

Most importantly, the aggregate TE event rate during eculizumab treatment was significantly reduced by 85% (P=<0.001), when compared with the same patients before eculizumab treatment.

With restriction of the pretreatment observation period to the 12 months immediately preceding eculizumab treatment, the TE event rate during treatment was reduced by 94% (P=0.002). The TE event rate in patients with TE prior to the trials was also reduced by 89% (P=<0.001).

Most TE events prior to eculizumab treatment occurred in patients receiving antithrombotics, either therapeutically or prophylactically. This indicates that the therapy may be insufficient to prevent thrombosis.

Pre-eculizumab treatment, 195 patients experienced 124 TE events. Of the 195 patients, 103 were on antithrombotics.

Of the 103 patients on antithrombotics, there were 54 TE events in 30 patients pre-eculizumab, compared to 1 TE event during eculizumab treatment. This demonstrates that eculizumab significantly reduces the risk of thrombosis in PNH patients, despite treatment with antithrombotics (P=<0.001).

Pre-eculizumab, TE was frequent in patients with lower levels of hemolysis and with mild anemia. Eculizumab significantly reduced TE across these and other subgroups (P=<0.001).

Dr Hillman said these data demonstrate the efficacy of long-term eculizumab treatment in its ability to significantly reduce the occurrence of thrombosis in PNH patients. Because TE accounts for the majority of deaths in PNH, it is reasonable to expect that eculizumab treatment, by decreasing the risk of TE, will increase the life-expectancy in PNH.

PNH is a rare, acquired, and potentially life-threatening disease of the blood characterized by hemolytic anemia, thrombosis, and red-colored urine, resulting from the breakdown of red blood cells.

TE is one of the most feared complications associated with PNH and accounts for approximately 45% of PNH patient deaths. The disease can occur even in individuals who have no previous history of thrombosis.

Patients with PNH are usually treated with anticoagulants on a prophylactic basis. However, these anticoagulants increase the risk of life-threatening hemorrhage without eliminating the potential for thrombosis, which can occur in as many as 30% of the patients who receive anticoagulant treatment. 

VIENNA—Long-term treatment with eculizumab, a recombinant humanized monoclonal antibody, significantly reduces the risk of thrombosis in patients with paroxysmal nocturnal hemoglobinuria (PNH), according to the results of a recent multicenter study.

Peter Hillmen, MD, of the Leeds Teaching Hospitals NHS Trust, reported the results of the study at the 12th Congress of the European Hematology Association in June 2007.

Dr Hillmen and colleagues prospectively examined the aggregate thromboembolism (TE) event rate in eculizumab-treated patients from 3 recent parent studies, as well as a subsequent common extension study. They compared those rates to the TE rate in the same patients’ pre-eculizumab treatment.

Eculizumab, which is designed to inhibit activation of terminal complement components that have been implicated in the development of PNH, reduced the TE rate in each of the three parent studies.

Most importantly, the aggregate TE event rate during eculizumab treatment was significantly reduced by 85% (P=<0.001), when compared with the same patients before eculizumab treatment.

With restriction of the pretreatment observation period to the 12 months immediately preceding eculizumab treatment, the TE event rate during treatment was reduced by 94% (P=0.002). The TE event rate in patients with TE prior to the trials was also reduced by 89% (P=<0.001).

Most TE events prior to eculizumab treatment occurred in patients receiving antithrombotics, either therapeutically or prophylactically. This indicates that the therapy may be insufficient to prevent thrombosis.

Pre-eculizumab treatment, 195 patients experienced 124 TE events. Of the 195 patients, 103 were on antithrombotics.

Of the 103 patients on antithrombotics, there were 54 TE events in 30 patients pre-eculizumab, compared to 1 TE event during eculizumab treatment. This demonstrates that eculizumab significantly reduces the risk of thrombosis in PNH patients, despite treatment with antithrombotics (P=<0.001).

Pre-eculizumab, TE was frequent in patients with lower levels of hemolysis and with mild anemia. Eculizumab significantly reduced TE across these and other subgroups (P=<0.001).

Dr Hillman said these data demonstrate the efficacy of long-term eculizumab treatment in its ability to significantly reduce the occurrence of thrombosis in PNH patients. Because TE accounts for the majority of deaths in PNH, it is reasonable to expect that eculizumab treatment, by decreasing the risk of TE, will increase the life-expectancy in PNH.

PNH is a rare, acquired, and potentially life-threatening disease of the blood characterized by hemolytic anemia, thrombosis, and red-colored urine, resulting from the breakdown of red blood cells.

TE is one of the most feared complications associated with PNH and accounts for approximately 45% of PNH patient deaths. The disease can occur even in individuals who have no previous history of thrombosis.

Patients with PNH are usually treated with anticoagulants on a prophylactic basis. However, these anticoagulants increase the risk of life-threatening hemorrhage without eliminating the potential for thrombosis, which can occur in as many as 30% of the patients who receive anticoagulant treatment. 

Hemoglobin concentrations in the high normal range in patients with anemia due to chronic kidney disease result in an excess risk of major adverse events, reported Arintaya Phrommintikul, MD, and colleagues from Monash University, Melbourne, Australia.

Adverse events include death, arteriovenous access thrombosis, and poorly controlled hypertension.

The investigators conducted a meta-analysis of 9 randomized controlled studies that enrolled 5143 patients treated with recombinant human erythropoietin.

Patients in the group targeted for a higher hemoglobin level (120-160 g/L) had a higher risk for all-cause mortality than patients in the lower hemoglobin target group (< 120 g/L) (risk ratio 1.17, P = 0.031).

There was also a higher risk for arteriovenous access thrombosis (risk ratio 1.34, P=0.0001) as well as a significantly higher risk of poorly controlled blood pressure (risk ratio 1.27, P=0.004) in the higher hemoglobin target group. The incidence of myocardial infarction was similar in the two groups.

Current guidelines recommend the maintenance of hemoglobin concentrations at 110 g/L or higher, based mainly on evidence of benefit in quality-of-life measures.

Current guidelines do not include an upper limit for the target hemoglobin concentration. The authors suggest that an upper limit should be added in future revisions of guideline recommendations.

The study was published in the 3 February 2007 issue of Lancet. 

Hemoglobin concentrations in the high normal range in patients with anemia due to chronic kidney disease result in an excess risk of major adverse events, reported Arintaya Phrommintikul, MD, and colleagues from Monash University, Melbourne, Australia.

Adverse events include death, arteriovenous access thrombosis, and poorly controlled hypertension.

The investigators conducted a meta-analysis of 9 randomized controlled studies that enrolled 5143 patients treated with recombinant human erythropoietin.

Patients in the group targeted for a higher hemoglobin level (120-160 g/L) had a higher risk for all-cause mortality than patients in the lower hemoglobin target group (< 120 g/L) (risk ratio 1.17, P = 0.031).

There was also a higher risk for arteriovenous access thrombosis (risk ratio 1.34, P=0.0001) as well as a significantly higher risk of poorly controlled blood pressure (risk ratio 1.27, P=0.004) in the higher hemoglobin target group. The incidence of myocardial infarction was similar in the two groups.

Current guidelines recommend the maintenance of hemoglobin concentrations at 110 g/L or higher, based mainly on evidence of benefit in quality-of-life measures.

Current guidelines do not include an upper limit for the target hemoglobin concentration. The authors suggest that an upper limit should be added in future revisions of guideline recommendations.

The study was published in the 3 February 2007 issue of Lancet. 

Hemoglobin concentrations in the high normal range in patients with anemia due to chronic kidney disease result in an excess risk of major adverse events, reported Arintaya Phrommintikul, MD, and colleagues from Monash University, Melbourne, Australia.

Adverse events include death, arteriovenous access thrombosis, and poorly controlled hypertension.

The investigators conducted a meta-analysis of 9 randomized controlled studies that enrolled 5143 patients treated with recombinant human erythropoietin.

Patients in the group targeted for a higher hemoglobin level (120-160 g/L) had a higher risk for all-cause mortality than patients in the lower hemoglobin target group (< 120 g/L) (risk ratio 1.17, P = 0.031).

There was also a higher risk for arteriovenous access thrombosis (risk ratio 1.34, P=0.0001) as well as a significantly higher risk of poorly controlled blood pressure (risk ratio 1.27, P=0.004) in the higher hemoglobin target group. The incidence of myocardial infarction was similar in the two groups.

Current guidelines recommend the maintenance of hemoglobin concentrations at 110 g/L or higher, based mainly on evidence of benefit in quality-of-life measures.

Current guidelines do not include an upper limit for the target hemoglobin concentration. The authors suggest that an upper limit should be added in future revisions of guideline recommendations.

The study was published in the 3 February 2007 issue of Lancet.