Romiplostim is recommended as an option for treating adults with chronic immune (idiopathic) thrombocytopenic purpura, within its marketing authorisation (that is, in adults who have had a splenectomy and whose condition is refractory to other treatments, or as a second-line treatment in adults who have not had a splenectomy because surgery is contraindicated), only if:

• their condition is refractory to standard active treatments and rescue therapies, or
• they have severe disease and a high risk of bleeding that needs frequent courses of rescue therapies

People currently receiving romiplostim whose disease does not meet the criteria above,should be able to continue treatment until they and their clinician consider it appropriate to stop.

The technology

Romiplostim (Nplate, Amgen) is a protein that mimics the action of thrombopoietin by acting as an agonist at thrombopoietin receptors. It stimulates the differentiation and proliferation of bone marrow cells responsible for producing platelets (megakaryocytes), thereby increasing platelet production and platelet counts (concentrations).

Immune (idiopathic) thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder characterised by increased platelet destruction and, in some cases, inadequate platelet production. The disorder can result in low platelet counts and bleeding.

Chronic ITP is defined as that which lasts longer than 12 months. Clinicians in the UK treat people with ITP as needed with ‘rescue therapies’ (corticosteroids, intravenous immunoglobulins and platelet infusions) and thereafter, as needed, with ‘active treatments’ (rituximab, immunosuppressive agents including azathioprine, mycophenolate mofetil and ciclosporin, danazol, dapsone, and cytotoxic agents including cyclophosphamide and vinca alkaloids).

Romiplostim has a marketing authorisation ‘for adult chronic immune (idiopathic) thrombocytopenic purpura (ITP) splenectomised patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins)’.

The marketing authorisation also states that romiplostim ‘may be considered as second line treatment for adult non-splenectomised patients where surgery is contra-indicated’.

The summary of product characteristics (SPC) states that the recommended initial dose of romiplostim is 1 microgram/kg of actual body weight, administered once weekly as a subcutaneous injection. The dose may be increased by increments of 1 microgram/kg until a platelet count equal to or above 50 × 109 platelets per litre of blood is reached. A maximum dose of 10 micrograms/kg once weekly should not be exceeded.

Platelet counts should be measured weekly until a stable count equal to or above 50 × 109 platelets per litre is observed for at least 4 weeks without adjusting the dose. Thereafter, platelet counts should be measured monthly.

Treatment with romiplostim should be stopped if the platelet count does not increase sufficiently to avoid clinically significant bleeding after 4 weeks of romiplostim therapy at the highest weekly dose of 10 micrograms/kg.
Romiplostim should also be stopped if a peripheral blood smear indicates increased bone marrow reticulin as well as if a loss of efficacy is observed. For full details of dose and administration, see the SPC.

The SPC lists special warnings and precautions for the use of romiplostim, including: recurrence of thrombocytopenia and bleeding after stopping treatment; increased bone marrow reticulin; thrombotic and/or thromboembolic complications (described by the SPC as a ‘theoretical risk’ from platelet counts above the reference range); and loss of response (which could result from immunogenicity or increased bone marrow reticulin).

The SPC lists headache as a ‘very common’ undesirable effect. For full details of side effects and contraindications, see the SPC.

The cost of treatment varies depending on the patient’s weight and the dosing regimen. The cost will also be affected by any waste that results from discarding any unused drug from the single use of a 250 microgram vial.
The SPC states that romiplostim is a sterile but unpreserved product and therefore is intended for single use only.

Dr G Mohan.