Update on romiplostim therapy for immune thrombocytopenic purpura

The median platelet count in the romiplostim group was significantly higher (P = 0.039) than that in the placebo group within 1 week of the first dose of romiplostim (1 μg/kg) and remained so at 3 weeks after the end of treatment (15 weeks total; median platelet count of 47.5 × 109/L vs 19.0 × 109/L; P = 0.001). Changes in platelet count in the romiplostim group were dose-dependent, with a median peak platelet count of 73.5 × 109/L reached after 5 weeks, when the dose was 5 μg/kg. Eleven of the 12 patients in the romiplostim group (93%) reached the target range of greater than 50 × 109/L by the fifth week. At week 12 (end of treatment), 10 romiplostim patients (83%) versus no placebo patients were at target levels. Six romiplostim-treated patients (50%) maintained target platelet count levels at 3 weeks after treatment.

Adverse events occurred in 50% of patients in each group. The most frequent adverse events were headache, epistaxis, cough, and vomiting, which occurred in one patient each in the romiplostim group (8%) and placebo group (17%). Two romiplostim-treated patients (17%) developed a skin rash. None of the patients had thrombocytosis or rebound thrombocytopenia, and none of the romiplostim-treated patients developed bone marrow fibrosis by week 18 of follow up.

How I treat ITP Immune thrombocytopenic purpura (ITP) and its associated problems are frequently encountered by the practicing hematologist. When it comes treatment, there are several options:

• If the platelet count is at least 30,000/μL and there is no active bleeding, close observation is the most prudent approach. In anticipation of the possibility of splenectomy at some point in their course, patients are offered immunization against Streptococcus pneumoniae, Hemophilus influenza, and Neisseria meningitides. In addition, I screen for exposure to hepatitis B virus (HBV), because patients may at some point receive treatment with rituximab (Rituxan), which is associated with HBV reactivation.
• For patients with a platelet count below 30,000/μL, evidence of impending bleeding (such as wet purpura), or frank bleeding, treatment is indicated. Typically, this involves the use of glucocorticoids, often in combination with IV gamma globulin (IVIG) or, occasionally, anti-D immunoglobulin.
• For a platelet count below 10,000/μL, I give methylprednisolone, 1,000 mg/d IV, for 5 consecutive days with IVIG, 1 g/kg daily, for 2 consecutive days. I then shift the patient to oral prednisone, 1 mg/kg daily, for 1 week, followed by tapering the dose by 10 mg/wk, as allowed by the platelet count, which should remain at ≥ 30,000/μL. Failure of this approach, or the inability to reduce the prednisone dose to 10 mg/d or less, would raise the options of either giving rituximab, 375 mg/m2 per week, for 4 weeks or performing a therapeutic, laparoscopic-assisted splenectomy, the single intervention still the most likely to provide meaningful, long-lasting benefit.
• In the setting of asplenia (including the absence of accessory splenic tissue), I favor a trial of a thrombopoietin mimetic, either romiplostim (Nplate) or eltrombopag (Promacta).

In the truly refractory patient, other options include calcineurin inhibitors, cytotoxic agents, danazol, tumor necrosis factor-alpha inhibitors, and staphylococcal A column immunoadsorption.

— David M.J. Hoffman, MD, FACP

Rescue medication, consisting of IVIG 1 g/kg for two doses, was given to one romiplostim-treated patient (8%) due to head trauma and loss of consciousness and two placebo-treated patients (33%) during the 12-week study period, with no interruption of study drug being required. The number of romiplostim-treated patients with grade 3 bleeding decreased from four (33%) prior to the study to none during the study, and the number with grade 2 bleeding decreased from six (50%) to two (17%; P = 0.002).

These findings are similar to results observed in another small study of romiplostim in children with ITP.3,4 An open-label phase III study designed to study the long-term safety of romiplostim and the durability of platelet responses to the drug in pediatric patients currently is in the recruitment stage.5 In this extension trial, approximately 20 patients aged 1 to 18 years with ITP are to receive weekly SC injections of romiplostim, starting at 1 μg/kg (or prior dose) and escalated to 10 μg/kg (based on the platelet count) over a period of 3 years. The primary outcome measure is the incidence of adverse events, including significant changes in laboratory values and the incidence of antibody formation. Secondary outcome measures include the platelet response (> 50 × 109/L) in the absence of rescue medication and the need for concurrent ITP medication (corticosteroids, danazol, or azathioprine) over the duration of the study.