Chondroitin-Glucosamine Reduced Pain in Knee Arthritis in RCT

Janis C. Kelly

January 30, 2015

A new randomized controlled clinical trial has provided some support for the suggestion raised in the 2008 Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) that glucosamine plus chondroitin sulfate might provide clinically significant pain relief for patients with moderate to severe knee osteoarthritis (OA) pain, despite being ineffective against milder OA pain.

Marc C. Hochberg, MD, from the University of Maryland School of Medicine, Baltimore, and colleagues from France, Germany, Poland, and Spain report in an article published online January 14 in the Annals of the Rheumatic Diseases that a combination glucosamine/chondroitin sulfate product produced a 50.1% decrease in Western Ontario and McMaster OA index (WOMAC) pain, which is comparable to the 50.2% decrease seen in patients randomly assigned to receive celecoxib. Bioibérica, SA, maker of the glucosamine/chondroitin sulfate preparation used in the trial, funded the study.

The Multicentre Osteoarthritis Intervention trial with SYSADOA (symptomatic slow-acting drug for OA; MOVES) trial was a double-blind study that enrolled 606 patients with Kellgren and Lawrence grade 2 or grade 3 knee OA. Inclusion criteria included moderate to severe pain, defined as a WOMAC score of 301 or higher on a scale from 0 to 500.

Patients received either chondroitin sulfate 400 mg plus glucosamine hydrochloride 500 mg (CS+GH; Droglican, Bioibérica SA) three times a day or celecoxib 200 mg every day for 6 months.

The primary outcome was the mean decrease in WOMAC pain score at 6 months. Secondary outcomes included WOMAC function and stiffness, pain visual analog scale, presence of joint swelling/effusion, use of rescue medications, and Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) response criteria and EuroQoL-5D health status at 6 months.

The change in WOMAC pain score was −185.7 (−50.1%) with CS+GH vs −186.8 (−50.2%) with celecoxib (P = .92). This met the noninferiority criterion of a −40-unit decrease in WOMAC. At 6 months, at least 79% of patients in each group fulfilled the OMERACT-OARSI criteria. There were also no significant differences in decrease in pain visual analog scale (48.0% with CS+GH vs 48.8% with celecoxib) or in patients' and physicians' global assessments of disease activity, in response rate (79% in both groups), and in reductions in joint swelling and effusions. Health-related quality-of-life measures were similar for both groups.

The CS+GH group used more rescue medication during the first month of study, but rescue medication use was low and similar for both groups thereafter.

The rates of treatment-related adverse events were 51.0% with CS+GH and 50.5% with celecoxib. The rates of serious adverse events were 2.3% with CS+GH and 3.3% with celecoxib. Twenty-two patients in each treatment group discontinued medication.

The authors conclude, "The MOVES trial found that a fixed-dose combination of chondroitin sulfate plus glucosamine has comparable efficacy to celecoxib in reducing pain in patients with [OA] of the knee with moderate-to-severe pain after 6 months of treatment. The reduction in pain was both clinically important and statistically significant (50% reduction in both groups), as was the improvement in stiffness (46.9% reduction with the combination vs 49.2% with celecoxib), and function (45.5% vs 46.4%, respectively).... These results both confirm and extend those from the GAIT study in patients with severe knee pain."

The researchers note that the study excluded patients with high cardiovascular or gastrointestinal risk. They also warn that that although results from this trial were consistent with those from the GAIT patient subgroup with severe knee OA, they would not be directly compared with other studies with CS+GH or celecoxib because of differences in study design.

The authors also point out that clinical evidence is conflicting regarding the efficacy of chondroitin sulfate and the two commercially available salts of glucosamine hydrochloride or sulfate available by prescription in the European Union, and that current evidence-based guidelines advise against them because of lack of efficacy, but not because of safety concerns. However, they also suggest that the current study supports the use of the combination as an alternative to nonsteroidal anti-inflammatory drugs for patients with cardiovascular or gastrointestinal conditions.

Study limitations of concern to clinicians in the United Kingdom and the United States are that the CS+GH combination used in this trial has been approved as a prescription drug in Europe, but not elsewhere, and that results in this trial cannot be generalized to other mixtures, such as over-the-counter dietary supplements, or to treatment with the individual components.

Thomas Osborn, MD, a rheumatologist at the Mayo Clinic in Rochester, Minnesota, who was not involved in the MOVES trial, told Medscape Medical News. "The data and investigators are very solid. I am convinced. There does not appear to be anything overlooked. While they used a particular preparation of glucosamine/chondroitin, it would seem US clinicians should at least expect similar results with similar preparations found in the US."

Dr Osborn noted that many clinicians treating patients with OA have already faced patients asking about the use of over-the-counter glucosamine and chondroitin products sold as dietary supplements. "Most clinicians have already decided whether to encourage the patient to continue or try glucosamine/chondroitin or tell them they should not waste their money on it. I doubt that this study will change many clinicians' minds. If my patients ask, my suggestions are to try it and to be very objective. If they get no pain relief, stop after 1 to 2 months. My experience has been about 1 in 20 get significant relief of pain for a while."

Harriet A. Hall, MD, a retired family physician and former US Air Force flight surgeon who writes about alternative medicine at The SkepDoc, and who was not involved in the study, told Medscape Medical News, "I remain skeptical. The GAIT study found a benefit in the moderate-to-severe pain subset but was not powered to draw any conclusions from those data. This new study was designed to have adequate power, but in science we can never go by the results of a single study. Initial studies that are positive are all too often followed by better studies that are negative."

Dr Hall added, "The published evidence on glucosamine/chondroitin is mixed…. I'm withholding judgment until this study is replicated by other researchers and until the weight of evidence falls more clearly on one side or the other. I'm particularly skeptical about the mechanism of action, since neither glucosamine nor chondroitin was effective when used alone, and both of them are produced by the body in far greater amounts than the pills can provide. What really made me skeptical of the GAIT findings was that there was no effect in the patients with mild to moderate pain: I don't know of anything else that relieves moderate to severe pain but has no effect on milder pain."

The study authors did not did not respond to interview requests from Medscape Medical News.

The trial was funded by Bioibérica SA, Barcelona, Spain, which provided the study medication and participated in the study design and data interpretation. Bioibérica also funded the work of Sophie Rushton-Smith, PhD, from Medlink Healthcare Communications, United Kingdom, who drafted the paper based on information provided by Dr Hochberg and who coordinated and integrated the comments and modifications of the other coauthors. Dr Hochberg is a consultant to Bioibérica SA, Bristol Myers Squibb, Eli Lilly, EMD Serono SA, Iroko Pharmaceuticals, Novartis Pharma AG, Pfizer, Samumed LLC, and Theralogix LLC, and owns stock in Theralogix LLC. One coauthor is a shareholder of ArthroLab and has received consulting fees from AbbVie, Bioibérica, Merck & Co, Servier, and TRB Chemedica. Another coauthor received personal fees for lectures from Bioibérica SA and Merck Sharp & Dohme. Another coauthor reported grants from Abbvie, Amgen, Bioibérica, Bristol Mayer, Celgene, Celltrion, Cellerix, Grunenthal, Gebro Pharma, Lilly, MSD, Merck Serono, Pfizer, Pierre-Fabra, Roche, Sanofi, Servier, Tedec-Meiji, and UCB. Another coauthor received speaker fees from IBSA, Bioibérica, and Expanscience; consulting fees from Galapagos, Flexion, Tilman SA, Artialis SA, and Synolyne Pharma; and research grants from Nestec, Bioibérica, Royal Canin and Artialis SA. Another coauthor acts as a consultant for WEX Pharmaceuticals and has received payment for lectures from Bioibérica. Another coauthor is a shareholder of ArthroLab and has received consulting fees from AbbVie, Bioibérica, Merck & Co, Servier, and TRB Chemedica. The other authors, Dr Hall, and Dr Osborn have disclosed no relevant financial relationships.

Ann Rheum Dis. Published online January 14, 2015. Full text

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