Background/Purpose: The analgesic efficacy of combined glucosamine and chondroitin sulfate (CS) in knee osteoarthritis (OA) remains controversial. Criticism to previous studies includes small sample size, short term evaluation and lack of intent-to-treat (ITT) analysis. Glucosamine sulfate (GS) or hydrochloride (GH) formulations and dosing schedule relevance are also not clearly defined.

Methods: 1,120 subjects with radiographic knee OA (Kellgren/Lawrence grades 2-3) and moderate-severe knee pain flare after analgesic washout were randomized (1:1:1) at 16 centers in Brazil to receive GS 500mg/CS 400mg three times daily capsules (GI) or once daily sachet (GII), or GH 500mg/CS 400mg three times daily capsules (GIII) for a 16 week trial. Acetaminophen up to 3,750mg daily was a rescue medication. Primary outcome (ITT) was patient reported pain intensity in the affected knee and variation of Lequesne’s index (LI) at 16 weeks. Monthly secondary outcomes were mean changes from baseline in patient reported pain and LI, patient and physician global assessments of disease activity, acetaminophen consumption, and adherence. Sample size calculation considered a non-inferiority evaluation allowing a difference of less than 1.7 points in the LI and a decrease of pain less than 18mm in GI and GII, as compared to GIII. Safety evaluations were done at each monthly visit.

Results: The ITT population comprised 302, 301, and 306 patients in GI, GII and GIII, respectively, and 911 patients for safety. Demographic data were equally comparable in all groups. The criterion for non-inferiority analysis of GI and GII in relation to GIII, based on confidence interval (95%), was met for pain intensity and LI. The mean of pain reduction (GI: -30.9±1.5; GII: -28.7±1.5; GIII: -29.7±1.5 mm) was significant for all groups at week 16 (P<0.001). Similarly, the mean of LI decrease was significant in all groups (GI: -3.8±0.2; GII: -3.7±0.2; GIII: -3.9±0.2) (P<0.001). Moreover, reduction of acetaminophen consumption (-5, -3, and -5 weekly tablets for GI, GII, and GIII, respectively) was also significant in all groups (P<0.005). Withdrawal rate was 18.2%, 19.3%, and 19.3% for GI, II, and III. Patients that did not complete the study were 77 (44.8%) for lack of adherence, 16 (9.3%) consent withdrawal, 11 (6.4%) adverse events, 8 (4.7%) lost to follow-up, and 17 (9.9%) for other causes.

Conclusion: This is the largest study showing that GS/CS and GH/CS provide clinically meaningful and sustained analgesia in knee OA regardless of dose fractionation. GS/CS (capsule or sachet) and GH/CS formulations are equally effective and safe to treat symptomatic knee OA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/combined-glucosamine-and-chondroitin-sulfate-once-of-three-times-daily-provide-clinically-relevant-analgesia-in-knee-osteoarthritis/