This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of
rimonabant for the treatment of obese or
overweight patients based upon a review of the manufacturer's submission to the National Centre for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's main evidence came from four randomised controlled trials.
Rimonabant resulted in a significantly greater benefit than placebo for all primary
weight loss outcomes. At 1 year,
rimonabant had a statistically significant beneficial effect on systolic
blood pressure, high-density
lipoprotein cholesterol,
triglycerides and fasting plasma
glucose in diabetics and non-diabetics, and glycosylated haemoglobin in diabetics. Improvements were maintained over 2 years with
rimonabant; withdrawal of
rimonabant at 1 year resulted in a reduction in
weight loss until there was no difference from placebo at 2 years. Psychiatric adverse events were experienced by 26% and 14% of
rimonabant and placebo patients respectively; figures for symptoms of depression were 9% and 5% respectively. Pairwise comparisons of
orlistat,
sibutramine and
rimonabant showed beneficial effects of
rimonabant over
orlistat and
sibutramine for
weight loss outcomes; however, response hurdles imposed on
orlistat or
sibutramine in clinical practice may not have been applied in the
orlistat and
sibutramine trials. The manufacturer's Markov cohort model evaluated
rimonabant versus
orlistat,
sibutramine and diet and exercise alone for three base-case populations. The incremental cost-effectiveness ratio (ICER) of
rimonabant varied from 10,534 pounds to 13,236 pounds per quality-adjusted life-year (QALY) versus diet and exercise, to 8977 pounds to 12,138 pounds per QALY versus
orlistat, to 1463 pounds to 3908 pounds per QALY versus
sibutramine. In subgroup analysis there was a wider variation in the ICER estimates although none exceeded 20,000 pounds per QALY. The ICER of
rimonabant remained under 20,000 pounds per QALY in reanalyses by the manufacturer and the ERG, with the results sensitive to the source of health-related quality of life (HRQoL) benefits in the model. Four treatment strategies were modelled in comparisons of
rimonabant versus diet and exercise alone and
orlistat and
sibutramine in which
rimonabant was continued only in patients achieving 5%
weight loss at 3, 6, 9 or 12 months. In pairwise comparisons
rimonabant remained below a threshold of 30,000 pounds per QALY in 70% of the comparisons reported. The results were most sensitive to the decrement applied to depression and the costs of screening for depression. In conclusion, areas of uncertainty remain in relation to the clinical effectiveness and cost-effectiveness of
rimonabant, for example lack of evidence on long-term outcomes and the effect of
rimonabant on cardiovascular events, developing diabetes and mortality, and lack of data on the HRQoL benefits associated with
rimonabant. The lack of response hurdles applied to
sibutramine and
orlistat means that the comparator strategies were not considered by the ERG to reflect their respective product licenses or current NHS use. The NICE guidance issued as a result of the STA states that
rimonabant is recommended as an adjunct to diet and exercise for adults who are obese or
overweight and who have had an inadequate response to, are intolerant of or are contraindicated to
orlistat and
sibutramine.