Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

Abstract

Objectives: To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.

Methods: Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating 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.

Results: 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 low and similarly distributed between groups.

Conclusions: 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.

Trial registration number: NCT01425853.

Keywords: Analgesics; NSAIDs; Osteoarthritis.

Figure 1

Flow diagram of Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) patients. Hba_1c, glycated haemoglobin; ITT, intention to treat; PP, per protocol.

Figure 2

Western Ontario and McMaster osteoarthritis index (WOMAC) (A) pain, (B) stiffness and (C) function subscales, and (D) visual analogue scale by visit; (E) Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria, (F) joint swelling, (G) joint effusion and (H) consumption of rescue medication, by visit. The p values compare values between treatments. Data are least-square means±SEM. CE, celecoxib; CS+GH, chondroitin sulfate plus glucosamine hydrochloride.

Figure 3

Mixed models for repeated measurements analysis, conducted using the following approaches for handling missing data: (A) imputation using drop-out reason (IUDR); (B) baseline observation carried forward (BOCF); and (C) available data only (ADO). The p value is for the superiority test. CE, celecoxib; CS+GH, chondroitin sulfate plus glucosamine hydrochloride; ITT, intention to treat; PP, per protocol.