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No advantage shown for newer OADs Two new systematic reviews have found no evidence that newer antidiabetic agents, excluding sitagliptin (Januvia) and exenatide (Byetta), offer advantages over metformin in the treatment of type 2 diabetes. A Cochrane review of 18 randomised trials involving 3888 people treated with rosiglitazone (Avandia) concluded that, compared with older agents, it improved HbA1c to a similar extent but there was no evidence of benefits in mortality, morbidity, adverse effects, costs or quality of life ( Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD006063. DOI: 10.1002/14651858. CD006063.pub2). By contrast, rosiglitazone is associated with an increased risk of oedema and fractures. This review could not confirm recent concerns about an increased cardiovascular risk but noted that available data tended to support such a link. The second review included 216 trials and cohort studies of oral antidiabetic agents ( Ann Intern Med 2007; published online 17 July 2007). Evidence on clinical end‐points was inconclusive. Most agents improved glycaemic control to a similar extent, with weaker effects noted with nateglinide (Starlix) and alpha‐glucosidase inhibitors. Only rosiglitazone increased levels of HDL‐cholesterol (but also of LDL‐cholesterol) only metformin reduced LDL‐cholesterol. Other than metformin, most agents increased body weight by 1‐5kg. The risk of hypo‐glycaemia was greatest with sulphonylureas and repaglinide (Prandin) glitazones had the highest risk of heart failure; and metformin carried the highest risk of GI reactions. HF still undertreated Most PCTs have procedures to implement NICE guidance on treating heart failure but fewer have adequate measures to monitor treatment and organise care, according to a report by the Healthcare Commission ( www.healthcarecommission.org.uk ). Pushing the Boundaries reviews provision of heart failure services in the wake of several Government initiatives to raise standards. It found that prescribing of ACE inhibitors has increased to over 80 per cent of all patients, though there is wide variation between PCTs. Although adherence to NICE and National Service Framework (NSF) guidance appears to be high, the Commission was unable to check how closely the guidelines were followed in practice and less than a fifth of organisations met the standards for audit. Varenicline approved NICE has approved the use of varenicline (Champix) for smoking cessation. Its latest technology appraisal recommends the drug as one option for smoking cessation, preferably – but not essentially – as part of a programme of behavioural support. Varenicline is a partial agonist at a nicotinic acetylcholine receptor; it alleviates craving and withdrawal symptoms and reduces the rewarding effects of smoking. The commonest adverse effects are nausea and vomiting. Pfizer's evidence to NICE showed that abstinence at 12 months was 60‐70 per cent more likely with varenicline than NRT or bupropion (Zyban). A 12‐week course of treatment costs approximately £164; a second course is also a licensed option. HRT debate rekindled The charity Women' Health Concern (WHC) has criticised current interpretations of evidence on the risks associated with HRT, saying it resulted in a 50 per cent drop in treatment. Concerns about increased cardiovascular risk in HRT users arose from two epidemiological studies the Women' Health Initiative (WHI) and the Million Women Study (MWS). WHC says analysts wrongly concluded that age at first use did not affect cardiovascular risk and failed to adjust for risk factors for breast cancer. The charity adds that HRT should be considered first‐line therapy for relief of menopausal symptoms, and for prevention of osteoporosis in women aged under 60 with increased risk for the disease. These women are not at increased risk for at least seven years, except for thrombosis associated with combined preparations; this risk can be reduced by use of a low‐dose HRT product. WISDOM, a randomised study of HRT in older postmenopausal women (mean age 63), recently reported an increased risk of cardiovascular events and thromboembolism during a mean follow‐up of one year ( BMJ 2007; doi:10.1136/bmj. 39266.425069.AD). Counterfeits unretrieved The MHRA has recovered only a small proportion of counterfeit medicines identified in recent years, according to the Pharmaceutical Journal (2007;279:7). The Agency's own statistics reveal that only 6 per cent of fake packs of sibutramine (Reductil) in 2004 and 14 per cent of fake packs of atorvastatin (Lipitor) in 2005 were retrieved, and only 0.4 per cent of fake atorvastatin was retrieved in 2006. Community incidents are under‐reported There is ‘significant’ under‐reporting of patients safety incidents occurring in the community, according to the National Patient Safety Agency (NPSA). Safety in Doses: Medication Safety Incidents in the NHS shows that medication accounts for 8 per cent of all reported safety incidents and, of these, 80 per cent were reported by acute trusts despite the fact that medication accounts for a greater proportion of incidents reported in the community (30 per cent) than elsewhere. Wrong doses, omitted medicines and wrong medicines accounted for most incidents, and children aged 0‐4 were disproportionately at risk compared with other age groups. Higher spending does improve health Increased NHS expenditure in England has achieved better health outcomes, according to The Health Foundation ( www.health.org.uk ). A report from the independent Quest for Quality and Improved Performance initiative concluded that spending on treatments for circulatory diseases was more cost effective than cancer therapies (£8,000 vs £13 100 per life‐year saved), but both were relatively cheap compared with the NICE threshold of £20 000‐£30 000 per quality‐adjusted life‐year. PCTs appear to be targeting expenditure appropriately, the report adds, but some evidence suggests that nonwhite ethnic groups do not receive a fair share of funding. New NICE programme The Department of Health has added seven new technology appraisals to the current work programme for NICE, including treatments for gout, hepatitis B, psoriasis and juvenile arthritis. NICE is to begin consultations on items for its next work programme, including new clinical guidelines (bed wetting, autism, hypertension in pregnancy and mental illness associated with substance misuse), public health guidance (needle exchange, uneven uptake of vaccination) and combined guidance (alcohol use disorders). New technologies under consideration include new treatments for cancer and opioid‐induced bowel dysfunction, and the prevention of deep vein thrombosis. New from NICE Rituximab for the treatment of rheumatoid arthritis. NICE final appraisal determination, July 2007 Rituximab (MabThera) is a monoclonal antibody that targets B cells expressing the CD20 marker, inhibiting their activation and differentiation. A course of treatment comprises two 1000mg iv injections administered two weeks apart; the basic cost of one course is £3492. NICE recommends rituximab in combination with methotrexate as an option for the treatment of adults with severe active rheumatoid arthritis (RA) who have had an inadequate response to or intolerance of other disease‐modifying antirheumatic drugs (DMARDs), including treatment with at least one anti‐TNF agent. Treatment should be continued only when there is evidence of a response (defined as an improvement in the disease activity score, DAS28, of at least 1.2). Repeat courses should not be prescribed more often than every six months. The cost‐effectiveness of rituximab was estimated at £18 823 per quality‐adjusted life year (QALY) gained compared with standard therapy including an anti‐TNF agent. Treatment pathways for RA are determined by an individual' response to NSAIDs, DMARDs and anti‐TNF agents. Rituximab plus methotrexate achieves a response in about 40 per cent more patients than methotrexate alone (26 per cent), and has efficacy similar to combined treatment with methotrexate and anti‐TNF therapy. NICE does not currently recommend a second anti‐TNF agent when the first is unsuccessful; however, this is common clinical practice and NICE is reviewing its guidance. Natalizumab for the treatment of adults with highly active relapsing‐remitting multiple sclerosis. NICE final appraisal determination, June 2007 Natalizumab (Tysabri) is a monoclonal antibody targeted at the adhesion molecule 4,1‐integrin. It probably acts by blocking the migration of leucocytes, suppressing inflammation and the recruitment of immune cells into inflamed sites. It is administered as an infusion of 300mg every 28 days; the basic cost of a year' treatment is £14 730. NICE recommends natalizumab as an option for the treatment only of rapidly evolving severe relapsing‐remitting multiple sclerosis (RES). RES is defined by two or more disabling relapses in one year, and one or more gadolinium‐enhancing lesions on brain magnetic resonance imaging (MRI) or a significant increase in T2 lesion load compared with a previous MRI. Treatment already under way, but falling outside this indication, may be continued. NICE does not recommend natalizumab monotherapy for patients with a suboptimal response to beta‐interferon. The incremental cost per QALY for this indication was at least £43 400, not making it cost‐effective for the NHS. Natalizumab is not licensed for use with an interferon on safety grounds. In patients with RES, natalizumab reduces the risks of progression and relapse by 50‐60 per cent compared with beta‐interferon. The cost per QALY for natalizumab compared with beta‐interferon was probably no greater than £32 000 and, in view of its potential benefits and the reduced life expectancy of patients, this was considered cost‐effective. Primary and secondary prevention of osteoporotic fragility fractures in postmenopausal women. NICE final appraisal determination, June 2007 NICE guidance relates only to postmenopausal women with osteoporosis not due to corticosteroids. Recommendations for primary and secondary prevention depend on age and fracture risk. Primary prevention is recommended for women with confirmed osteoporosis, defined as a T‐score of ‐2.5 or less by DXA scan. A scan is recommended for women over 70 who have at least one clinical factor suggesting an increased risk, eg family history of fracture, or a medical condition suggesting reduced bone mineral density (BMD), eg ankylosing spondylitis, untreated premature menopause. Women aged over 75 with at least two clinical risk factors do not necessarily need a scan. A DXA scan should be offered to women under 70 when risk assessment reveals at least one clinical risk factor and a medical condition suggesting reduced BMD; opportunistic DXA scanning is not cost‐effective in this age group. Secondary prevention is recommended for postmenopausal women who have sustained a clinically apparent fracture and who have a T‐score of ‐2.5 or less; women aged 75 or older need not have a DXA scan. NICE used the same clinical trial evidence to assess efficacy in primary and secondary prevention, regardless of fracture status and BMD at baseline. The drug of choice for initiating primary or secondary prevention is alendronate, using the cheapest formulation and assuming a cost of £95 per year. Etidronate, risedronate (Actonel), raloxifene (Evista) and strontium ranelate (Protelos) are not recommended as initial therapy. Meta‐analysis of clinical trials suggests that alendronate reduces the risk of vertebral fracture (by about 45 per cent), hip fracture (40 per cent), wrist fracture (30 per cent) and other nonvertebral fractures (20 per cent). The costs per QALY of the recommended strategies are not clear but appear to be less than £20 000 for primary prevention and less than £30 000 for secondary prevention. Copyright © 2007 Wiley Interface Ltd