Related Experiment Video
Updated: May 16, 2026
Use of Hematopoietic Stem Cell Transplantation to Assess the Origin of Myelodysplastic Syndrome
Published on: October 3, 2018
Romiplostim dose-response in patients with myelodysplastic syndromes
Juan Jose Perez Ruixo1, Sameer Doshi, Yow-Ming C Wang
1Amgen SA, Barcelona, Spain. juanjose@amgen.com
Aim:
To characterize the romiplostim dose-response in subjects with low or intermediate-1 risk myelodysplastic syndromes (MDS) receiving subcutaneous romiplostim.
Methods:
Data from 44 MDS subjects receiving subcutaneous romiplostim (dose range 300-1500 μg week(-1) ) were used to develop a pharmacodynamic model consisting of a romiplostim-sensitive progenitor cell compartment linked to the peripheral blood compartment through four transit compartments representing the maturation in the bone marrow from megakaryocytes to platelets. A kinetics of drug effect model was used to quantify the stimulatory effect of romiplostim on the proliferation of sensitive progenitor cells and pharmacodynamics-mediated disposition was modelled by assuming the kinetics of drug effect constant (kDE ) to be proportional to the change in platelet count relative to baseline.
Results:
The estimated values (between subject variability) for baseline platelet count, mean transit time, and kDE were 24 × 10(9) l(-1) (47%), 9.6 days (44%) and 0.28 days(-1) , respectively. MDS subjects had a shorter platelet lifespan (42 h) than healthy subjects (257 h). Romiplostim effect was described for responders (78%) and non-responders (22%). The average weekly stimulatory effect of romiplostim on the production rate of sensitive progenitor cells at baseline was 269% per 100 μg week(-1) for responders. Body weight, age, gender and race were not statistically related to romiplostim pharmacodynamic parameters. Visual predictive checks confirmed the model adequacy.
Conclusion:
The time course of platelet counts in MDS subjects receiving subcutaneous administration of escalating doses of romiplostim was characterized and showed a linear dose-response for romiplostim responders to increase the platelet counts.
Insights
Romiplostim showed a linear dose-response in myelodysplastic syndromes (MDS) patients, effectively increasing platelet counts in responders. This study characterized the drug
Area of Science:
- Pharmacodynamics and pharmacokinetics
- Hematology
- Drug response modeling
Background:
- Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic stem cell disorders.
- Thrombocytopenia is a common complication in MDS, increasing bleeding risk.
- Romiplostim is a thrombopoietin receptor agonist used to increase platelet counts.
Purpose of the Study:
- To characterize the dose-response relationship of subcutaneous romiplostim in MDS patients.
- To develop a pharmacodynamic model to describe romiplostim's effect on platelet production.
Main Methods:
- A pharmacodynamic model was developed using data from 44 MDS subjects treated with romiplostim (300-1500 μg/week).
- The model incorporated romiplostim-sensitive progenitor cells, maturation transit compartments, and a kinetics of drug effect model.
- Model adequacy was confirmed using visual predictive checks.
Main Results:
- MDS subjects exhibited a shorter platelet lifespan (42 hours) compared to healthy individuals (257 hours).
- Romiplostim responders (78%) demonstrated a significant increase in platelet counts.
- The average weekly stimulatory effect for responders was 269% per 100 μg/week; no demographic factors influenced parameters.
Conclusions:
- The study successfully characterized the time course of platelet count changes in MDS patients receiving romiplostim.
- A linear dose-response was observed for romiplostim responders, indicating predictable increases in platelet counts with escalating doses.
