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Embargoed For Release at 5:30 pm PT, Sunday Nov. 13, 2005

Arthritis News

GLUCOSAMINE AND CHONDROITIN SULFATE MAY BE USEFUL FOR PATIENTS WITH MODERATE TO SEVERE PAIN FROM KNEE OSTEOARTHRITIS

SAN DIEGO, CALIFORNIA – Glucosamine and chondroitin sulfate may be an effective combination in reducing pain associated with osteoarthritis of the knee, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Diego, California.

Glucosamine is an amino sugar naturally produced by the body and widely distributed to the connective tissues, including cartilage. The body also produces chondroitin sulfate, a complex carbohydrate molecule which, among its other roles, helps retain water in cartilage. Over the past 25 years, oral glucosamine and chondroitin sulfate, derived from animal products, have become popular dietary supplements with patients attempting to combat the cartilage wear and tear associated with osteoarthritis. The precise biologic mechanisms that enable oral supplements to emulate the body's natural products, however, remain undefined.

GAIT (The Glucosamine/Chondroitin Arthritis Intervention Trial) funded by the National Institutes of Health, was designed to rigorously assess the effectiveness and safety of these supplements when taken separately or in combination. Almost 1,600 patients with painful knee osteoarthritis were recruited from 16 U.S. academic rheumatology centers for the study. The patients, who had experienced significant knee pain for more than six months and had x-ray evidence of knee osteoarthritis, were evaluated at the beginning of the study, and at weeks 4, 8, 16 and 24. Each was randomly assigned to receive glucosamine hydrochloride, sodium chondroitin sulfate, both supplements, celecoxib, or placebo therapy and allowed up to 4,000 mg daily of acetaminophen. The primary outcome measure was a 20 percent improvement in knee pain by week 24.

“As expected, celecoxib improved knee pain in patients with osteoarthritis. For the study as a whole, the supplements were not shown to be effective; however, an exploratory analysis suggested that the combination of glucosamine and chondroitin sulfate might be effective in osteoarthritis patients who had moderate to severe knee pain,” stated Daniel O. Clegg, MD, Chief, Division of Rheumatology, University of Utah School of Medicine, Salt Lake City, Utah. Adverse events that were seen in GAIT were generally mild and evenly distributed across all groups. Dr. Clegg continued, “Given the results of this study, patients might want to discuss treatment options with their physicians.”

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see www.rheumatology.org/annual.

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Editor's Notes: Dr. Clegg will present this research during a scientific session at the ACR Annual Scientific Meeting from 10:45 am-12:30pm PT on Monday, November 14, 2005 in Ballroom 20 A-D of the San Diego Convention Center. He will be available for media questions and briefing at 8:30 am PT on Tuesday, November 15, in Room 23 A of the Convention Center.

Presentation Number: 622

The Efficacy of Glucosamine and Chondroitin Sulfate in Patients with Painful Knee Osteoarthritis (OA): The Glucosamine/chondroitin Arthritis Intervention Trial (GAIT)

Daniel O. Clegg 1, Domenic J. Reda 2, Crystal L. Harris 3, Marguerite A. Klein 4, for the GAIT Investigators. 1 University of Utah, Salt Lake City, UT; 2 VACSP, Hines, IL; 3 VACSP, Albuquerque, NM; 4 NCCAM/NIH, Bethesda, MD

PURPOSE: Glucosamine (G) and chondroitin sulfate (CS) are widely promoted to “reduce joint pain and provide support for healthy cartilage and joint function.” GAIT was designed to rigorously assess the efficacy and safety of these agents alone and in combination. G and CS were required to meet pharmaceutical standards as GAIT was conducted under an Investigational New Drug application.

METHODS: Patients were =40 years of age with knee pain (WOMAC Pain 125-400 mm) of at least 6 months duration and x-ray evidence of knee OA [Kellgren-Lawrence (KL) Grades 2 or 3]. Patients were randomly assigned double-blind to placebo (P); G(Glucosamine HCl 500 mg) tid; Sodium CS 400 mg tid; G+CS at the above doses tid; or celecoxib (CE) 200 mg daily. All patients were allowed up to 4000 mg daily of acetaminophen (APAP) as rescue analgesia, except within 24 hours of study visits. Allocation was stratified by Center and by WOMAC Pain severity (125-300mm and 301-400mm). Patients were evaluated at baseline and weeks 4, 8, 16 and 24. The primary outcome measure was a 20% improvement from baseline in WOMAC Pain at week 24. Adverse events were documented at each visit. Analysis was based on intention-to-treat.

RESULTS: 3238 patients were screened at 16 US academic rheumatology centers. 1583 were randomized and 1258 (80%) completed the study. Baseline characteristics were: mean age 58.6 years, BMI 31.7 kg/m 2 , OA symptoms 10 years, 64% female, summed mean WOMAC Pain 236±73mm (206mm for 125-300mm stratum, 341mm for 301-400mm stratum), 59% KL Grade 2, and 78% were in the 125-300mm WOMAC Pain stratum and were evenly distributed across all arms.

The response rate for CE (70.1%) was higher than the response rate for P (60.1%) in the primary outcome analysis of all patients (p=0.008). In the 301-400 mm WOMAC pain stratum, the response rate for G+CS (79.2%) was higher than P (54.3%) (p=0.002). Secondary outcomes in the 301-400 mm stratum, including 50% WOMAC Pain response, WOMAC Stiffness, WOMAC Function, HAQ, patient assessments, and use of rescue APAP all demonstrated changes consistent with the primary outcome. Adverse events were generally mild and evenly distributed among the groups.

Response Rates by Treatment Group and Pain Stratum

CONCLUSIONS : Combination G+CS is effective in treating moderate to severe knee pain due to OA. The lack of response in patients with mild pain may be due to a floor effect, limiting ability to detect response. All study agents were well tolerated.

Disclosure: D.O. Clegg, Pfizer 2; McNeil 5;  D.J. Reda, None;  C.L. Harris, None;  M.A. Klein, None.