16 November 2010
NICE recommends denosumab▼ (Prolia®) as a treatment option for the primary and secondary prevention of osteoporotic fragility fractures in postmenopausal women. However, it should only be used in those who are unable to comply with the administration regimens for oral bisphosphonates, are intolerant of those drugs or for whom such treatment is contra-indicated. For primary prevention, NICE recommends that certain other criteria are met before considering use of denosumab.
Local decision making bodies should engage with all stakeholders to agree a protocol for implementation of this guidance. This includes identifying those patients for whom the drug might be appropriate, as well as discussing appropriate shared-care arrangements. NICE concluded that whilst treatment with denosumab may be started in secondary care, it will be subsequently delivered almost exclusively in primary care. Local discussions around these arrangements will therefore be required if current policies are different to this.
Whatever the local policy is, secondary care prescribers will need to inform the patient’s GP that a denosumab injection has been administered. Audit or other monitoring arrangements will be needed for optimum implementation, as well as to monitor patients for adverse effects.
Denosumab is a fully human monoclonal antibody to RANKL, a cytokine which is involved in mediating osteoclast activity. It is administered as a 60mg dose by subcutaneous injection every six months at a cost of £366 per year (plus VAT). Administration should be performed by an individual who has been adequately trained in the appropriate injection technique. The pre-filled syringes must be stored in a refrigerator, but can be stored at room temperature if used within 30 days. Patients must be adequately supplemented with calcium and vitamin D. More details on the use of the drug can be found in the Summary of Product Characteristics.
NICE guidance recommends that the first choice agents for prevention of osteoporotic fractures in postmenopausal women who have certain risk factors for fracture are oral bisphosphonates (first with alendronate and then either risedronate or etidronate if alendronate is unsuitable). However, some women are unable to comply with the instructions for administration of oral bisphosphonates, or have a contra-indication to or are intolerant of these drugs. These NICE Technology Appraisals recommend that such women may receive either no treatment or strontium ranelate for primary prevention (as described in NICE TA 160), or strontium ranelate or raloxifene for secondary prevention as advised in NICE TA 161. Treatment usually takes place in primary care.
What does NICE say about denosumab?
The manufacturer’s submission was made on the premise that denosumab was not expected to compete with oral bisphosphonates given the wide availability of generic preparations at relatively low acquisition cost, and with a range of dosage regimens including weekly, monthly and yearly. Oral bisphosphonates have precise administration regimens to minimise the risk of interactions with drugs and minerals, and to reduce the risk of gastro-intestinal adverse effects.
Hence NICE recommends that denosumab is a treatment option for the primary prevention of osteoporotic fragility fractures only in postmenopausal women at increased risk of fractures who:
- are unable to comply with the special instructions for the administration of alendronate and either risedronate or etidronate, or are intolerant of or have a contraindication to oral bisphosphonates and
- also have a specific combination of T-score, age and number of independent clinical risk factors for fracture as defined within a table in the guidance.
The independent risk factors are defined in the guidance as parental history of hip fracture, four or more units of alcohol per day and rheumatoid arthritis.
Denosumab is recommended as a treatment option for the secondary prevention of osteoporotic fragility fractures only in postmenopausal women at increased risk of fractures who:
- are unable to comply with the special instructions for the administration of alendronate and either risedronate or etidronate, or are intolerant of or have a contraindication to these treatments.
The NICE committee concluded that whilst treatment with denosumab may be started in secondary care, it will be subsequently delivered almost exclusively in primary care. The six monthly administration by subcutaneous injection may improve adherence to treatment.
What was the key evidence informing this guidance?
The key study submitted to NICE is the FREEDOM trial which showed that subcutaneous denosumab was more effective than placebo at reducing the risk of new radiographic vertebral fracture (cumulative incidence over 36 months: 2.3% in the denosumab group and 7.2% in placebo patients, relative risk 0.32, 95% confidence interval 0.26 to 0.41, P<0.001, a number needed to treat (NNT) of 21 over 36 months). Further information is available in our OTH Rapid Review.
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