Romiplostim

Romiplostim is a fusion protein produced by recombinant DNA technology that is indicated for the treatment of patients with primary immune thrombocytopenia who are refractory to other therapies. It is a thrombopoietin receptor agonist that leads to an increase in platelet levels. In ITP, the platelet count is significantly reduced due to increased breakdown and reduced formation of new platelets.

Romiplostim is a recombinant Fc peptide fusion protein ("peptibody"). The molecule consists of a human immunoglobulin IgG1 Fc domain in which each single chain subunit is covalently bound at the C-terminus to a peptide chain with two TPO receptor-binding domains. Binding to the TPO receptor results in the growth of bone marrow megakaryocyte colony-forming cells, which leads to increased platelet production via JAK2 and STAT5 kinase pathways.

After subcutaneous application of 3 to 15 μg/kg romiplostim, maximum serum concentrations in ITP patients were reached after 7 to 50 hours. Serum concentrations vary within the patient population and do not correlate with the dose applied.

Elimination: The elimination half-life of romiplostim in ITP patients varied from 1 to 34 days (median 3.5 days). The elimination of serum romiplostim depends in part on the TPO receptor on the platelets. As a result, for an applied dose, patients with high platelet counts have low serum concentrations and vice versa.

Romiplostim is applied subcutaneously once a week.

Romiplostim is generally well tolerated and the undesirable effects are usually moderate. The following side effects may occur very frequently (≥1/10) during treatment:

• Infection of the upper respiratory tract
• hypersensitivity
• Headache
• Pain in the oropharynx and/or upper abdomen
• The most severe side effects include:
• recurrence of thrombocytopenia and bleeding after discontinuation of treatment
• Reticulin proliferation in the bone marrow
• thrombotic/thromboembolic complications
• Linear IgA dermatosis (Heyer S et al. 2023)

When Romiplostim is combined with other drugs for ITP treatment, platelet counts should be monitored to ensure that they are not outside the recommended range. In clinical trials, corticosteroids, danazol and/or azathioprine, intravenous immunoglobulins and anti-D immunoglobulins have been used for ITP treatment in combination with romiplostim. These can be reduced or discontinued if used concomitantly. CAve: Monitoring of platelet counts.

Romiplostim must not be used in case of hypersensitivity to the active substance or any of the other ingredients of the medicinal product. In addition, Romiplostim should not be used in patients with moderate to severe hepatic impairment (Child-Pugh classification ≥ 7) unless the expected benefit exceeds the known risk of portal vein thrombosis in these patients with TPO agonist-treated thrombocytopenia associated with hepatic insufficiency.

1. Biondo L et al. (2013) Erythematous rash following romiplostim administration in a patient with autoimmune lymphoproliferative syndrome. Ann Pharmacother 47:e7.
2. Bussel JB et al. (202w1) A Review of Romiplostim Mechanism of Action and Clinical Applicability. Drug Des Devel Ther 15:2243-2268.

3. Heyer S et al. (2023) 33-year-old man with plaques and blisters. JDDG 22: 857-859

4. Noda-Narita S et al. (2018) TAFRO syndrome with refractory thrombocytopenia responding to tocilizumab and romiplostim: a case report. CEN Case Rep 7:162-168.