Immune Thrombocytopenia (ITP)


Nplate® (romiplostim) is indicated for the treatment of adult patients with immune thrombocytopenia (ITP) who have an insufficient response to other medications (corticosteroids and immunoglobulins) or splenectomy. This medication is also indicated for pediatric patients at least 1 year old who have had ITP for at least 6 months and an insufficient response to other medications (corticosteroids and immunoglobulins) or splenectomy.1

Mechanism of Action

The active substance in Nplate is romiplostim, a thrombopoietin receptor agonist (TPO-RA).1 Romiplostim, a second-generation TPO-RA produced in Escherichia coli with recombinant DNA technology,1,2 is an Fc-peptide fusion protein (peptibody) containing 2 identical single-chain subunits. Each subunit consists of a human immunoglobulin G1 Fc domain covalently linked at the C-terminus to a peptide that contains 2 thrombopoietin receptor-binding domains.1

Thrombopoietin plays an important role in several hematopoietic pathways and the production of platelets.2 Like endogenous thrombopoietin, romiplostim binds to thrombopoietin receptors on megakaryocyte precursors in bone marrow, thereby activating various signaling pathways that promote cell viability and growth, megakaryocyte maturation, and platelet production. As a result of this activation, platelet counts increase.2 

By increasing platelet production, romiplostim decreases the need for platelet transfusions or other treatments.2 Romiplostim is approved for use in patients with ITP in the United States, European Union, Australia, and several countries in Africa and Asia.2 Initial US approval dates from 2008.1 

Read more about ITP experimental therapies

Administration

The recommended initial dose of Nplate for patients with ITP is 1 µg/kg once weekly, administered as a subcutaneous injection. The dose should be adjusted according to the platelet response in adults and the platelet response and body weight in pediatric patients.1 Nplate use is recommended only in patients with ITP whose degree of

thrombocytopenia and clinical condition increases the risk for bleeding.1

Read more about ITP treatment

Adverse Effects

The most common adverse reactions in adults with ITP include arthralgia, dizziness, insomnia, myalgia, extremity pain, abdominal pain, shoulder pain, dyspepsia, and paresthesia.1 The increase in the platelet count may lead to thrombotic/thromboembolic complications. Patients should be evaluated for the development of neutralizing antibodies if they develop severe thrombocytopenia during treatment with Nplate.1

Warnings and Precautions

Nplate should only be used to treat thrombocytopenia due to ITP and should only be used for patients with high bleeding risk. If Nplate is used for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS), there is increased risk for progression to myelogenous leukemia. Patients with chronic liver disease have reported portal vein thrombosis, and patients should be observed for thrombotic complications.1

Get full prescribing information for Nplate at MPR

Safety and Efficacy in Clinical Trials

The safety and efficacy of Nplate were assessed in 2 double-blind, placebo-controlled phase 3 clinical studies in adult patients with ITP. One of the trials enrolled patients in whom ITP had been diagnosed in the last 2 years and who had not undergone a splenectomy. The other trial evaluated patients who had undergone a splenectomy after a diagnosis of ITP.3,4 Patients were randomized (2:1) to receive Nplate or a placebo for 24 weeks.1 In the first trial, patients with ITP for approximately 2 years had previously received a median of 3 treatments. In the second trial, patients with ITP for approximately 8 years had received a median of 6 treatments. Treatments included corticosteroids, immunoglobulins, rituximab, cytotoxic therapies, danazol, and azathioprine.1 The median weekly dose of Nplate was 2 µg/kg in the first study and 3 µg/kg in the second study, and the use of rescue therapies (including corticosteroids, intravenous immunoglobulin, platelet transfusions, and anti-D immunoglobulin) was allowed to manage bleeding, wet purpura, and immediate risk for hemorrhage.1

In these studies, a durable platelet response was defined as a weekly platelet count of 50×109/L or higher for any 6 of the previous 8 weeks without rescue medication during the defined 24-week treatment period. This response was achieved by 61% of patients in the first trial and 38% in the second trial.1 Patients who completed one of these trials could enter into a long-term, open-label phase 3 extension study. This study revealed that the platelet counts in these patients were increased and maintained regardless of whether they had previously received Nplate or placebo.5

A phase 2 clinical trial was performed to evaluate the safety and efficacy of Nplate in adult patients with an insufficient response to first-line therapy. In this study, the duration of ITP was less than 3 months in 60% of the patients and was 3 months or longer in the remaining 40%. Nplate was administered for 12 months.1,6 Results indicated that 93% of the patients had a platelet response of 50×109/L or higher during the treatment period, and that a platelet count of 50×109/L or higher was maintained in 32% of the patients for at least 6 months without Nplate and other medication for ITP.1

Double-blind, placebo-controlled phase 3 and phase 1/2 clinical trials were performed to assess the safety and efficacy of Nplate in pediatric patients.7,8 A long-term phase 3 pediatric study was also conducted.9

Read more about ITP clinical trials

References

1. NPLATE® (romiplostim) for injection, for subcutaneous use. Highlights of prescribing information. Amgen; 2022. Accessed October 6, 2022.

2. Bussel JB, Soff G, Balduzzi A, Cooper N, Lawrence T, Semple JW. A review of romiplostim mechanism of action and clinical applicability. Drug Des Devel Ther. 2021;15:2243-2268. doi:10.2147/DDDT.S299591

3. AMG 531 treatment of thrombocytopenic subjects with immune (idiopathic) thrombocytopenic purpura (ITP) prior to splenectomy. ClinicalTrials.gov. January 28, 2005. Updated September 10, 2022. Accessed October 6, 2022.

4. AMG 531 treatment of thrombocytopenic subjects with immune (idiopathic) thrombocytopenic purpura (ITP) refractory to splenectomy. ClinicalTrials.gov. January 28, 2005. Updated September 10, 2022. Accessed October 6, 2022.

5. Open label extension study of romiplostim (AMG 531) in thrombocytopenic patients with immune (idiopathic) thrombocytopenic purpura (ITP). ClinicalTrials.gov. July 1, 2005. Updated December 18, 2013. Accessed October 6, 2022.

6. Interventional study in adults with immune thrombocytopenia purpura (ITP) receiving romiplostim. ClinicalTrials.gov. June 14, 2010. Updated September 21, 2022. Accessed October 6, 2022.

7. Safety and efficacy study of romiplostim to treat immune thrombocytopenia (ITP) in pediatric patients. ClinicalTrials.gov. September 30, 2011. Updated February 9, 2017. Accessed October 6, 2022.

8. Safety and efficacy study of romiplostim (AMG 531) to treat ITP in pediatric subjects. ClinicalTrials.gov. August 13, 2007. Updated July 25, 2014. Accessed October 6, 2022.

9. Long-term study of romiplostim in thrombocytopenic pediatric patients with immune thrombocytopenia (ITP). ClinicalTrials.gov. October 30, 2014. Updated June 23, 2022. Accessed October 6, 2022.

Reviewed by Harshi Dhingra, MD, on 10/13/2022.