Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial

David J. Kuter; James B. Bussel; Roger M. Lyons; Vinod Pullarkat; Terry B. Gernsheimer; Francis M. Senecal; Louis M. Aledort; James N. George; Craig M. Kessler; Miguel A. Sanz; Howard A. Liebman; Frank T. Slovick; J. Th M. de Wolf; Emmanuelle Bourgeois; Troy H. Guthrie; Adrian Newland; Jeffrey S. Wasser; Solomon I. Hamburg; Carlos Grande; François Lefrère; Alan Eli Lichtin; Michael D. Tarantino; Howard R. Terebelo; Jean François Viallard; Francis J. Cuevas; Ronald S. Go; David H. Henry; Robert L. Redner; Lawrence Rice; Martin R. Schipperus; D. Matthew Guo; Janet L. Nichol

doi:10.1016/S0140-6736(08)60203-2

Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial

David J. Kuter, James B. Bussel, Roger M. Lyons, Vinod Pullarkat, Terry B. Gernsheimer, Francis M. Senecal, Louis M. Aledort, James N. George, Craig M. Kessler, Miguel A. Sanz, Howard A. Liebman, Frank T. Slovick, J. Th M. de Wolf, Emmanuelle Bourgeois, Troy H. Guthrie, Adrian Newland, Jeffrey S. Wasser, Solomon I. Hamburg, Carlos Grande, François LefrèreAlan Eli Lichtin, Michael D. Tarantino, Howard R. Terebelo, Jean François Viallard, Francis J. Cuevas, Ronald S. Go, David H. Henry, Robert L. Redner, Lawrence Rice, Martin R. Schipperus, D. Matthew Guo, Janet L. Nichol

Hematology

Research output: Contribution to journal › Article › peer-review

629 Scopus citations

Abstract

Background: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. Methods: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30×10⁹/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50×10⁹/L to 200×10⁹/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count ≥50×10⁹/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. Findings: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23·4-52·8], p=0·0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38·7-73·7], p<0·0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0·0001). Patients given romiplostim achieved platelet counts of 50×10⁹/L or more on a mean of 13·8 (SE 0·9) weeks (mean 12·3 [1·2] weeks in splenectomised group vs 15·2 [1·2] weeks in non-splenectomised group) compared with 0·8 (0·4) weeks for those given placebo (0·2 [0·1] weeks vs 1·3 [0·8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. Interpretation: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.

Original language	English (US)
Pages (from-to)	395-403
Number of pages	9
Journal	The Lancet
Volume	371
Issue number	9610
DOIs	https://doi.org/10.1016/S0140-6736(08)60203-2
State	Published - 2008

ASJC Scopus subject areas

General Medicine

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10.1016/S0140-6736(08)60203-2

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Kuter, D. J., Bussel, J. B., Lyons, R. M., Pullarkat, V., Gernsheimer, T. B., Senecal, F. M., Aledort, L. M., George, J. N., Kessler, C. M., Sanz, M. A., Liebman, H. A., Slovick, F. T., de Wolf, J. T. M., Bourgeois, E., Guthrie, T. H., Newland, A., Wasser, J. S., Hamburg, S. I., Grande, C., ... Nichol, J. L. (2008). Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. The Lancet, 371(9610), 395-403. https://doi.org/10.1016/S0140-6736(08)60203-2

Kuter, DJ, Bussel, JB, Lyons, RM, Pullarkat, V, Gernsheimer, TB, Senecal, FM, Aledort, LM, George, JN, Kessler, CM, Sanz, MA, Liebman, HA, Slovick, FT, de Wolf, JTM, Bourgeois, E, Guthrie, TH, Newland, A, Wasser, JS, Hamburg, SI, Grande, C, Lefrère, F, Lichtin, AE, Tarantino, MD, Terebelo, HR, Viallard, JF, Cuevas, FJ, Go, RS, Henry, DH, Redner, RL, Rice, L, Schipperus, MR, Guo, DM & Nichol, JL 2008, 'Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial', The Lancet, vol. 371, no. 9610, pp. 395-403. https://doi.org/10.1016/S0140-6736(08)60203-2

@article{7f60c5a6c9a34f8288454671ae8df3f0,

title = "Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial",

abstract = "Background: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. Methods: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30×109/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50×109/L to 200×109/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count ≥50×109/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. Findings: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23·4-52·8], p=0·0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38·7-73·7], p<0·0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0·0001). Patients given romiplostim achieved platelet counts of 50×109/L or more on a mean of 13·8 (SE 0·9) weeks (mean 12·3 [1·2] weeks in splenectomised group vs 15·2 [1·2] weeks in non-splenectomised group) compared with 0·8 (0·4) weeks for those given placebo (0·2 [0·1] weeks vs 1·3 [0·8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. Interpretation: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.",

author = "Kuter, {David J.} and Bussel, {James B.} and Lyons, {Roger M.} and Vinod Pullarkat and Gernsheimer, {Terry B.} and Senecal, {Francis M.} and Aledort, {Louis M.} and George, {James N.} and Kessler, {Craig M.} and Sanz, {Miguel A.} and Liebman, {Howard A.} and Slovick, {Frank T.} and {de Wolf}, {J. Th M.} and Emmanuelle Bourgeois and Guthrie, {Troy H.} and Adrian Newland and Wasser, {Jeffrey S.} and Hamburg, {Solomon I.} and Carlos Grande and Fran{\c c}ois Lefr{\`e}re and Lichtin, {Alan Eli} and Tarantino, {Michael D.} and Terebelo, {Howard R.} and Viallard, {Jean Fran{\c c}ois} and Cuevas, {Francis J.} and Go, {Ronald S.} and Henry, {David H.} and Redner, {Robert L.} and Lawrence Rice and Schipperus, {Martin R.} and Guo, {D. Matthew} and Nichol, {Janet L.}",

note = "Funding Information: This study was funded by Amgen Inc, Thousand Oaks, CA, USA. In collaboration with the investigators, Amgen designed the study, did statistical analyses, and interpreted the data, which Amgen holds. Amgen collected the data and representatives (JLN and DMG) participated in the writing of this report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: DJK receives research support from Amgen and GSK. JBB receives research support from Amgen, Biogen-IDEC, Cangene, Genentech, GSK, and Sysmex. He participates for Baxter in their speaker's bureau programme. He owns stock in Amgen and GSK. He participates in Advisory Boards for Amgen, GSK, and Baxter. RML, JNG, and TBG have received consultant fees and research support from Amgen. LMA has received a research grant from Amgen. CMK has received consultancy fees and research fees from Amgen, AKARX, and GSK. HAL has received research support from Amgen. AN has received consultancy fees from Amgen and GSK and research support from GSK. JSW has received research support from Amgen. AEL has received research support from Amgen and has participated in an advisory board meeting for Amgen. DHH has received a research grant from and participated in a speaker's bureau for Amgen. LR has been on an Amgen advisory board that focused on erythropoietic hormones 2 years ago. DMG and JLN are employees of Amgen. VP, MS, FTS, JTMdeW, EB, THG, SIH, CG, FL, MDT, HRT, J-FV, FJC, RSG, RLR, MRS, and FMS declare that they have no conflict of interest. ",

year = "2008",

doi = "10.1016/S0140-6736(08)60203-2",

language = "English (US)",

volume = "371",

pages = "395--403",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier Limited",

number = "9610",

}

TY - JOUR

T1 - Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura

T2 - a double-blind randomised controlled trial

AU - Kuter, David J.

AU - Bussel, James B.

AU - Lyons, Roger M.

AU - Pullarkat, Vinod

AU - Gernsheimer, Terry B.

AU - Senecal, Francis M.

AU - Aledort, Louis M.

AU - George, James N.

AU - Kessler, Craig M.

AU - Sanz, Miguel A.

AU - Liebman, Howard A.

AU - Slovick, Frank T.

AU - de Wolf, J. Th M.

AU - Bourgeois, Emmanuelle

AU - Guthrie, Troy H.

AU - Newland, Adrian

AU - Wasser, Jeffrey S.

AU - Hamburg, Solomon I.

AU - Grande, Carlos

AU - Lefrère, François

AU - Lichtin, Alan Eli

AU - Tarantino, Michael D.

AU - Terebelo, Howard R.

AU - Viallard, Jean François

AU - Cuevas, Francis J.

AU - Go, Ronald S.

AU - Henry, David H.

AU - Redner, Robert L.

AU - Rice, Lawrence

AU - Schipperus, Martin R.

AU - Guo, D. Matthew

AU - Nichol, Janet L.

N1 - Funding Information: This study was funded by Amgen Inc, Thousand Oaks, CA, USA. In collaboration with the investigators, Amgen designed the study, did statistical analyses, and interpreted the data, which Amgen holds. Amgen collected the data and representatives (JLN and DMG) participated in the writing of this report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Funding Information: DJK receives research support from Amgen and GSK. JBB receives research support from Amgen, Biogen-IDEC, Cangene, Genentech, GSK, and Sysmex. He participates for Baxter in their speaker's bureau programme. He owns stock in Amgen and GSK. He participates in Advisory Boards for Amgen, GSK, and Baxter. RML, JNG, and TBG have received consultant fees and research support from Amgen. LMA has received a research grant from Amgen. CMK has received consultancy fees and research fees from Amgen, AKARX, and GSK. HAL has received research support from Amgen. AN has received consultancy fees from Amgen and GSK and research support from GSK. JSW has received research support from Amgen. AEL has received research support from Amgen and has participated in an advisory board meeting for Amgen. DHH has received a research grant from and participated in a speaker's bureau for Amgen. LR has been on an Amgen advisory board that focused on erythropoietic hormones 2 years ago. DMG and JLN are employees of Amgen. VP, MS, FTS, JTMdeW, EB, THG, SIH, CG, FL, MDT, HRT, J-FV, FJC, RSG, RLR, MRS, and FMS declare that they have no conflict of interest.

PY - 2008

Y1 - 2008

N2 - Background: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. Methods: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30×109/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50×109/L to 200×109/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count ≥50×109/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. Findings: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23·4-52·8], p=0·0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38·7-73·7], p<0·0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0·0001). Patients given romiplostim achieved platelet counts of 50×109/L or more on a mean of 13·8 (SE 0·9) weeks (mean 12·3 [1·2] weeks in splenectomised group vs 15·2 [1·2] weeks in non-splenectomised group) compared with 0·8 (0·4) weeks for those given placebo (0·2 [0·1] weeks vs 1·3 [0·8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. Interpretation: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.

AB - Background: Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. We assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP. Methods: In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30×109/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain platelet counts of 50×109/L to 200×109/L. The primary objectives were to assess the efficacy of romiplostim as measured by a durable platelet response (platelet count ≥50×109/L during 6 or more of the last 8 weeks of treatment) and treatment safety. Analysis was per protocol. These studies are registered with ClinicalTrials.gov, numbers NCT00102323 and NCT00102336. Findings: A durable platelet response was achieved by 16 of 42 splenectomised patients given romplostim versus none of 21 given placebo (difference in proportion of patients responding 38% [95% CI 23·4-52·8], p=0·0013), and by 25 of 41 non-splenectomised patients given romplostim versus one of 21 given placebo (56% [38·7-73·7], p<0·0001). The overall platelet response rate (either durable or transient platelet response) was noted in 88% (36/41) of non-splenectomised and 79% (33/42) of splenectomised patients given romiplostim compared with 14% (three of 21) of non-splenectomised and no splenectomised patients given placebo (p<0·0001). Patients given romiplostim achieved platelet counts of 50×109/L or more on a mean of 13·8 (SE 0·9) weeks (mean 12·3 [1·2] weeks in splenectomised group vs 15·2 [1·2] weeks in non-splenectomised group) compared with 0·8 (0·4) weeks for those given placebo (0·2 [0·1] weeks vs 1·3 [0·8] weeks). 87% (20/23) of patients given romiplostim (12/12 splenectomised and eight of 11 non-splenectomised patients) reduced or discontinued concurrent therapy compared with 38% (six of 16) of those given placebo (one of six splenectomised and five of ten non-splenectomised patients). Adverse events were much the same in patients given romiplostim and placebo. No antibodies against romiplostim or thrombopoietin were detected. Interpretation: Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications. Stimulation of platelet production by romiplostim may provide a new therapeutic option for patients with ITP.

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Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial

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