13 December 2010
The Scottish Medicines Consortium (SMC) has recently concluded that the Glusartel®▼ brand of glucosamine sulphate cannot be recommended for use in NHS Scotland for the relief of symptoms in mild to moderate osteoarthritis (OA) of the knee, as the economic case was not sufficiently robust.
Health professionals should continue to follow NICE guidance and not usually prescribe glucosamine products for the management of OA. However, if patients want to try over-the-counter glucosamine, they should be advised to purchase glucosamine sulphate 1500mg/day with the proviso that the potential benefit observed so far is related to a reduction in pain (in some people, and to only a mild or modest degree). Patients should be advised to evaluate their pain before starting treatment and to review the benefits of glucosamine after 2-3 months. The MHRA has warned that people who have seafood allergies or those who are taking warfarin should avoid glucosamine.
What is the background to this?
Glucosamine is an endogenous substance which helps to generate and maintain the thickness and elasticity of synovial fluid in joints and vertebrae. NICE OA guidance clearly states that the use of glucosamine and/or chondroitin is not recommended for the treatment of OA under the NHS, based on a review of the evidence. We recently discussed the findings of a network meta-analysis which concluded that glucosamine and chondroitin, given either separately or together, do not affect pain intensity in OA to a clinically meaningful extent compared with placebo. This SMC review provides further useful information for local decision makers.
What do SMC say?
The SMC reviewed two three-year placebo-controlled studies and one short-term active-comparator study. In this latter trial, 318 patients were randomised to glucosamine sulphate 1500mg once daily, paracetamol 1g three times daily or placebo for six months. The primary outcome was the difference between groups in the change from baseline in the Lequesne index (questions on knee pain and function, activities of daily living and walking distance). At six months, the difference in mean scores between the glucosamine sulphate and placebo groups was significant (mean difference -1.2; 95% confidence interval [CI] -2.3 to -0.8).
In the first of the placebo-controlled studies (n=212), the combined primary outcome was a measure of joint-space narrowing in the signal joint and assessment of symptom modification using the WOMAC osteoarthritis index (using a 100mm visual analogue scale; worst total score 2400mm). The mean difference in joint-space narrowing after 3 years was 0.24mm (95%CI 0.01 to 0.48). The difference in the %change in mean total WOMAC index score was 21.6% (95%CI 3.5% to 39.6%).
In the second placebo-controlled study (n=202), the combined primary outcome was a measure of joint-space narrowing in the signal joint and assessment of symptoms using the WOMAC osteoarthritis index (Likert version; worst score 120) and Lequesne indices (worst score 24). The difference in mean joint-space narrowing after 3 years was 0.23mm (95%CI 0.09 to 0.37). The difference in the change in mean WOMAC score was 3.1 (95%CI 0.77 to 5.5) and the Lequesne score was 0.91 (95%CI 0.34 to 1.5).
Glucosamine sulphate was significantly superior to placebo for all primary endpoints in both placebo-controlled studies. Neither of the studies showed any differences between groups in terms of requirement for rescue medication (paracetamol or a NSAID) and there was no apparent relationship between use and change in joint structure or symptom outcomes.
The SMC expressed concerns about the generalisability of the trials. For example, in the comparative study the dose of paracetamol was 3g daily, which reflected the maximum licensed dose in Europe, but is less than that licensed in the UK. Also, in this study the effect size on the primary outcome measure for glucosamine as compared to placebo was considered small and therefore the clinical relevance of the study was regarded as uncertain.
The manufacturer submitted a cost-utility analysis comparing glucosamine sulphate to paracetamol and placebo using Spanish costs, which appeared to be different to Scottish costs. Other concerns such as the exclusion from the cost-utility analysis of around 20% of patients included in the comparative trial due led the SMC to conclude that the economic case was not sufficiently robust.
The SMC has previously rejected glucosamine hydrochloride (Alateris®▼) for use in Scotland citing the lack of direct clinical trial evidence of efficacy and safety as well as insufficiently robust economic analysis.
Summary of licensed products
|Trade name||Strength/ formulation||Salt||Legal category||Cost per 30 days (MIMS Dec 2010)|
|Glusartel®||1500mg sachets to make oral solution||Sulphate||POM||£18.40|
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