Costing statement: Denosumab for the prevention of osteoporotic fractures in postmenopausal women Resource impact The guidance Denosumab for the prevention of osteoporotic fractures in postmenopausal women (NICE technology appraisal guidance 204) is unlikely to have a significant impact on the use of NHS resources. However, because of variation in practice across the country, organisations may incur costs or savings depending on their circumstances. Therefore, organisations are encouraged to assess costs locally. Introduction The Secretary of State and the Welsh Assembly Minister for Health and Social Services have issued directions to the NHS on implementing NICE technology appraisal guidance. When a NICE technology appraisal recommends use of a drug or treatment, or other technology, the NHS must usually provide funding and resources for it within 3 months of the guidance being published. If the Department of Health issues a variation to the 3-month funding direction, details will be available on the NICE website. When there is no NICE technology appraisal guidance on a drug, treatment or other technology, decisions on funding should be made locally. Background of this technology appraisal NICE technology appraisal guidance 160 recommends strontium ranelate as an option for the treatment of the primary prevention of osteoporotic fragility fractures in postmenopausal women who are unable to comply with the special instructions for the administration of alendronate and etidronate or risedronate or who are intolerant of or contraindicated to those treatments and meet the criteria of T-score, age and number of independent clinical risk factors (see below). NICE technology appraisal guidance 161 recommends strontium ranelate or raloxifene as alternative treatment options for the secondary prevention of postmenopausal women 1 of 5
osteoporotic fragility fractures in postmenopausal women who are unable to comply with the special instructions for the administration of alendronate and etidronate or risedronate or who are intolerant of or contraindicated to those treatments and meet the T-score, age and number of independent clinical risk factors (see below). Clinical risk factors For the purposes of this guidance, independent clinical risk factors for fracture are parental history of hip fracture, alcohol intake of 4 or more units per day, and rheumatoid arthritis. Primary prevention of osteoporotic fragility fractures Denosumab is recommended as 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 administering alendronate and either risedronate or etidronate; or have an intolerance of, or a contraindication to, those treatments and who have a combination of T-score 1, age and number of independent clinical risk factors for fracture (see above) as indicated in the following table. 1 T-score measures bone mineral density using central (hip and/or spine) dual-energy X-ray (DXA) scanning, and is expressed as the number of standard deviations (SD) below peak bone mineral density. postmenopausal women 2 of 5
T-scores (SD) at (or below) which denosumab is recommended when alendronate and either risedronate or etidronate are unsuitable Age (years) Number of independent clinical risk factors for fracture 0 1 2 65 69 a 4.5 4.0 70 74 4.5 4.0 3.5 75 or older 4.0 4.0 3.0 a Treatment with denosumab is not recommended. Secondary prevention of osteoporotic fragility fractures 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 administering alendronate and either risedronate or etidronate, or have an intolerance of, or a contraindication to, those treatments. The technology Denosumab (Prolia, Amgen) is a monoclonal antibody that reduces osteoclast activity, and so reduces bone breakdown. Denosumab has a UK marketing authorisation for the treatment of osteoporosis in postmenopausal women at increased risk of fractures. The summary of product characteristics states in the indication that denosumab significantly reduces the risk of vertebral, nonvertebral and hip fractures. Cost impact Denosumab is an alternative treatment option for the prevention of both primary and secondary osteoporotic fragility fractures in certain postmenopausal women. The initial prescribing will be started in secondary care via a hospital outpatient appointment. It will subsequently be delivered almost exclusively in primary care. However, it is acknowledged that GPs may be cautious about administering a new therapy, particularly a monoclonal antibody, in a primary care setting following initiation in secondary care. If denosumab is not administered in primary care after the initial dose, commissioners will have recurring costs due to additional outpatient postmenopausal women 3 of 5
appointments. Commissioners are advised to check local practice for administration of the drug when considering the cost impact of implementation. Expert opinion suggests that the change in prescribing may affect up to 25% of the eligible population. However, the manufacturers of Denosumab suggest that the change in prescribing may be as high as 50%. It is, therefore, important that commissioners are aware of their local circumstances and monitor trends locally. If uptake of denosumab is below 70% then the net cost of implementation of the guidance is estimated to be less than 1 million for the whole of England. The costs of each of the treatment options currently recommended by NICE are shown in the table below. Costs may vary in different settings because of negotiated procurement discounts. Drug Annual cost per patient Denosumab (Prolia)* 366.00 Strontium ranelate (Protelos) 333.71 Raloxifene (Evista) 240.66 *The first year costs of Denosumab will be 622, which includes 256 for administration of the first dose in secondary care in an outpatient setting. The administration cost for the first dose of denosumab is the cost for a first outpatient attendance for Rheumatology (specialty 410) per 2010/11 Outpatient Attendance National Tariff (WF01B). If practice differs locally, costs will vary. The manufacturers' submission identified a cohort of patients who are currently not receiving any treatment for the prevention of either primary or secondary osteoporotic fractures. The manufacturer of denosumab estimated that this cohort is between 11,000 and 18,000 patients. Expert opinion suggests that it is unlikely that this cohort of patients will not be receiving any treatment at all. This group of patients was not included in estimating the national cost but commissioners are advised to check practice locally when implementing the guidance. postmenopausal women 4 of 5
Non-recurrent costs Additional non-recurrent costs may also be incurred for the training of GPs in the administration of denosumab in a primary care setting. The requirement for this training will need to be determined at a local level. Savings and benefits Some patients who are eligible to receive denosumab as set out in the recommendations, may have already tried several drugs. Denosumab is an additional treatment option for patients, with the aim of preventing osteoporotic fragility fractures and the associated costs of care. There will, therefore, be savings from a reduced number of initial hospital treatments, and from a reduction in costs of follow-up rehabilitation appointments and social care. Compliance with NICE guidance is one of the criteria of good risk reduction strategies, and in combination with meeting other criteria could lead to a discount on contributions to the NHS Litigation Authority schemes, including Clinical Negligence Scheme for Trusts (CNST). Implications for commissioners This technology falls into the programme budgeting category 215X Problems of the musculoskeletal system. Conclusion Because denosumab is one of several treatment options recommended by NICE for the prevention of osteoporotic fragility fractures and additional patients receiving denosumab may incur both costs and savings (from a reduction in secondary care activity), we do not anticipate that its use within the NHS will result in a significant impact on NHS resources. The recommendations in NICE technology appraisals 160 and 161 relating to strontium ranelate are currently being reviewed. We are considering the production of a more comprehensive costing model which will incorporate this guidance and all other current NICE guidance once this review is complete. postmenopausal women 5 of 5