Efficacy and safety of romiplostim versus medical standard of care as chronic therapy for nonsplenectomized patients with immune thrombocytopenia (ITP)

BACKGROUND:

Chronic ITP is an autoimmune disease characterized by low platelet counts due to both increased platelet destruction and suboptimal platelet production. Conventional ITP therapies that target the immune system have variable response rates and issues regarding toxicity. Romiplostim is an Fc-peptide fusion protein (peptibody) that increases platelet counts by a mechanism similar to thrombopoietin, and has recently been approved in the EU, US, Canada, and Australia for the treatment of chronic ITP. Aims. To evaluate the ability of romiplostim versus medical standard of care (SOC) to reduce the incidence of splenectomy and treatment failures in adult nonsplenectomized ITP patients during a 52-week treatment period.

DESIGN AND METHODS:

Patients provided informed consent and were randomized (2:1) to romiplostim or SOC and stratified by geographic region. Eligible patients either had a platelet count <50x109/L or had their platelet count fall to <50x109/L during or after a clinically-indicated taper or discontinuation of current ITP therapy. Once-weekly subcutaneous romiplostim was administered with dose adjustments based on platelet count. SOC treatments were prescribed by the investigator according to standard institutional practices or therapeutic guidelines; the only treatments not allowed were investigational agents (rituximab was allowed) or other thrombopoietic agents. The first primary endpoint was the incidence of splenectomy or study discontinuation. The second primary endpoint was the incidence of treatment failure (defined as: platelet count 20x109/L for 4 consecutive weeks at the highest recommended dose and schedule, or major bleeding event, or change in therapy due to intolerable side-effect or bleeding symptoms) or study discontinuation.

RESULTS:

In total, 234 patients were randomized (SOC, 77; romiplostim, 157). In romiplostim treated patients, there was a significantly lower incidence of splenectomy or study discontinuation (OR, 0.169; 95% CI.: 0.081, 0.351; p<0.0001) and treatment failure or study discontinuation (OR, 0.374; 0.188, 0.744; p=0.0039) than in patients receiving SOC. A sensitivity analysis, applied to patients who did not discontinue the study, showed a consistent trend in the incidence of splenectomy and treatment failure with both of the primary endpoint results. Safety analyses included all patients who received ≥1 dose of romiplostim or 1 type of SOC for ITP. Adverse events were experienced by 92% (69/75) of patients receiving SOC and by 95% (146/154) of patients receiving romiplostim. The most common adverse events in the SOC group were epistaxis (23%), nasopharyngitis (19%), and contusion (19%); and in the romiplostim group were headache (35%), fatigue (27%), and nasopharyngitis (23%). Treatment-related serious adverse events were reported by 8% (6/75) of SOC and 5% (7/154) of romiplostim patients. Three patients died during the 52-week treatment period: 2 SOC patients (cardio-respiratory arrest, hepatic failure), and 1 romiplostim patient (pneumonia). None of the deaths were deemed related to study treatment. Bleeding events with grade ≥3 severity were reported by 8% (6/75) of patients in the SOC group, compared with 3% (5/154) in the romiplostim group.

CONCLUSIONS:

Romiplostim significantly reduced incidences of splenectomy and treatment failure in nonsplenectomized ITP patients compared to standard of care. The safety profile was comparable between patients receiving romiplostim and those receiving SOC.