Romiplostim (Nplate) is a thrombopoietin receptor agonist that is currently indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. In a recently reported phase III trial,1 romiplostim treatment was associated with a number of benefits compared with the standard of care in nonsplenectomized ITP patients: higher platelet response rate, lower rates of treatment failure and splenectomy, fewer bleeding events, and fewer blood transfusions.

The safety and efficacy of romiplostim in children with ITP have not yet been established. A recently reported placebo-controlled trial indicates good response and good tolerability of romiplostim in children with chronic refractory ITP.2

Romiplostim versus standard of care in adult nonsplenectomized patients

In a 52-week, multicenter, openlabel trial,1 patients with ITP who had not undergone splenectomy, had received at least one prior treatment for ITP, and had a platelet count of less than 50 × 109/L were randomized to receive weekly SC injections of romiplostim (n = 157) or standard-ofcare treatment (n = 77). Romiplostim was started at a dose of 3 μg/kg, which could be increased up to a maximum of 10 μg/kg to achieve a target platelet count of 50–200 × 109/L. Standardof- care treatment was selected by the treating physician based on standard institutional practices or therapeutic guidelines. Throughout the study, patients in either treatment group could receive additional therapies for ITP, including short-term rescue therapy, such as IV immune globulin (IVIG), but excluding other thrombopoietin mimetics, as deemed medically necessary by investigators.

Study population, endpoints, other treatments

The median ages of patients in the romiplostim and standard-of-care groups were 58 and 57 years, respectively; 54% and 60% were women; the median duration since ITP diagnosis was 2.1 and 2.3 years; baseline median platelet counts were 33 × 109/L and 27 × 109/L; and 13% and 6% were receiving medications, primarily glucocorticoids (11% and 3%), for ITP at baseline. Splenectomy could be performed if study therapy was considered to be ineffective or was associated with severe side effects.

The primary endpoints of the trial were the incidence of splenectomy and the incidence of treatment failure, with treatment failure defined as a platelet count of 20 × 109/L or lower for 4 consecutive weeks, a major bleeding event, or a requirement for a change in therapy (including splenectomy) due to an adverse event or bleeding. In primary endpoint analyses, patients who received any study treatment and then discontinued study participation were counted as having both treatment failure and splenectomy.

During the study, ITP treatments other than romiplostim were received by 44% of patients in the romiplostim group and 79% of patients in the standard- of-care group, including glucocorticoids in 37% versus 63%, IVIG in 7% versus 33%, rituximab (Rituxan) in 1% versus 20%, azathioprine in 1% versus 9%, danazol in 2% versus 7%, other medications in 6% versus 19%, and platelet transfusions in 6% versus 16%.

Efficacy

The incidence of treatment failure was 11% in the romiplostim group versus 30% in the standard-of-care group (P < 0.001). Time to treatment failure was significantly prolonged in the romiplostim group (Figure 1a). The incidence of splenectomy was 9% in the romiplostim group versus 36% in the standard-of-care group (P < 0.001), and time to splenectomy was significantly prolonged in the include bleeding, thrombosis, hematologic cancer or myelodysplastic syndromes, and increased bone marrow reticulin.