MD, PhD, FMedSci, FSB, FRCP, FRCPEd

The two dietary supplements chondroitin and glucosamine have been around for some time. They are being promoted mostly for osteoarthritis; some claim that they reduce pain, others even believe that they restore the damaged cartilage and thus reverse the disease process. But neither for a symptomatic nor causal therapy has the evidence so far been truly convincing. A new trial might change this situation.

This study compared the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.

 TheDouble-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA’ (MOVES) was conducted in France, Germany, Poland and Spain and evaluated treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2–3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0–500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.

The results show that the adjusted mean change (95% CI) in WOMAC pain was −185.7 (−200.3 to −171.1) (50.1% decrease) with CS+GH and −186.8 (−201.7 to −171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of −40: −1.11 (−22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were rare and similarly distributed between groups.

The authors concluded that CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.

This is a rigorous trial, and I do trust its findings. However, I am not entirely sure what they actually mean: is CS+GH as effective or as ineffective as the COX-2-inhibitor celecoxib? The most recent meta-analysis on the subject found that diclofenac (150 mg/day) was likely to be more effective in alleviating pain than celecoxib (200 mg/day). But that does, of course, not necessarily imply that celecoxib is ineffective.

The other big issue here is safety. COX-2-inhibitors had a bad press because of the risk of cardiovascular side-effects. In comparison, the CS+GH supplement is an almost risk-free alternative. Bearing in mind that we are dealing with long-term treatments here, I think the results of this study might persuade me, had I to choose between these two treatments, to opt for the dietary supplement.

3 Responses to New evidence on chondroitin/glucosamine for osteoarthritis

  • Um, but without a placebo control we really don’t know what to conclude

    The design means that both groups were subject to the effects of regression to the mean, Hawthorne effect and ‘real’ placebo effect, which would combine to give an improvement versus baseline assessment that would obscure treatment group differences.

    I agree that it is striking that NSAID did not seem better than the supplement, but I am content to accept that NSAIDs may not much affect on objective measures disease progression.

    I also thought that large trials of those supplements versus placebo have been tending to show no useful effect for the macromolecule chondoitin, which is not surprising given the biology of digestion, but leave the door open for some effect from glucosamine, which I also find more biologically plausible. I’ve stopped recommending joint supplements, especially the expensive combination products, but support a decision to give s patient cheap glucosamine.

    Putting that all together, perhaps this study’s results derive for a real effect from glucosamine and NSAID heavily confounded with experimental artefact. But the size of the real effect from the active interventions are undefinable from this study’s data.

    What are your thoughts on those points?

  • Celecoxib versus diclofenac in the management of osteoarthritis of the knee.
    McKenna F1, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS

    From the Scandinavian Journal of Rheumatology 2001;30(1):11-8 (Reference: http://www.ncbi.nlm.nih.gov/pubmed/11252686 )

    Obviously not conclusive but surely this study (abstract below) provides some comfort that the performance of diclofenac is superior to a placebo and therefore supports the finding that CS+GH probably has some beneficial effect.

    OBJECTIVE:
    A clinical trial was conducted in 600 patients with OA of the knee to test the hypothesis that the specific COX-2 inhibitor, celecoxib, has equivalent efficacy and a superior tolerability/safety profile when compared to diclofenac, the current worldwide standard of care.
    METHODS:
    Patients were administered celecoxib 100 mg BID, diclofenac 50 mg TID or placebo for 6 weeks in a multicentre, double-blind. placebo-controlled trial.
    RESULTS:
    Primary efficacy measures (index joint pain by VAS, WOMAC index) indicated statistically significant improvement versus placebo for both celecoxib and diclofenac and no statistically significant differences between celecoxib and diclofenac. American Pain Society (APS) measures to assess the rapidity of onset of action showed statistically significant and comparable pain relief versus placebo within 24 h for both celecoxib and diclofenac. More diclofenac patients reported GI side effects than patients treated with either placebo or celecoxib. Diclofenac-treated patients experienced statistically significant elevations in mean hepatic transaminases and serum creatinine and reductions in haemoglobin concentration when compared to placebo, events not observed with celecoxib.
    CONCLUSION:
    Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving signs and symptoms of OA of the knee, including pain, and has a rapid onset of action. However, celecoxib appears to have a superior safety and tolerability profile.

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