Combination therapy involving chondroitin sulfate and glucosamine sulfate proved no better than placebo for the management of pain and functional impairment brought on by knee osteoarthritis, in a double-blind, randomized trial.
“This is the first RCT sponsored by a pharmaceutical company to evaluate the efficacy of a combination of CS [chondroitin sulfate] plus GS [glucosamine sulfate] and including a [Data and Safety Monitoring Board] composed of independent experts charged with ensuring participant safety and accurate, bias-free data,” wrote the authors, led by Jorge A. Roman-Blas, MD, of Fundación Jiménez Díaz in Madrid (Arthritis Rheumatol. 2016 Jul 31. doi: 10.1002/art.39819).
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Dr. Roman-Blas and his coinvestigators recruited patients with Kellgren-Lawrence stages II-III knee osteoarthritis from one orthopedic surgery and nine rheumatology centers across Spain. The study was split into two parts; the first part would have half of the patients complete the study in 6 months, followed by an interim analysis and evaluation of the data. If deemed okay by the Data and Safety Monitoring Board, the second part of the study would proceed, in which half of the patients would again complete the study in 6 months.
Ultimately, the study comprised 164 patients. They were randomized in a 1:1 ratio into cohorts receiving either a placebo or a regimen of 1,200 mg CS derived from bovine tracheal cartilage plus 1,500 mg of crystalline GS derived from crustaceans. The primary endpoint was reduction in pain from baseline evaluation, which was based on the visual analog scale (VAS) of 1-100 mm.
Patients in the combination therapy cohort had a lower average reduction in pain at 6 months than did those taking the placebo. In the modified intention-to-treat population, those taking CS+GS therapy had an average reduction of 11.8 ± 2.4 mm, or 19%, compared with baseline. On the other hand, those in the placebo cohort recorded a 20.5 ± 2.4 mm, or 33%, reduction in pain (P = .029). Based on this analysis, the trial was stopped early at 6 months to prevent “overexposure of additional patients to placebo treatment,” the investigators said.
However, pain measured by VAS did not differ between the groups in a per-protocol analysis. Furthermore, when taking Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores into account, there was no significant difference in improvement between CS+GS therapy and placebo in pain and function, for both intention-to-treat and per-protocol subjects.
Although placebo was more effective in pain reduction in the modified intent-to-treat analysis than was CS plus GS combination treatment, the effect size of placebo was small and the effect size of CS plus GS in this study was smaller than in previous studies, the investigators noted. “These findings may be related to the fact that GS may interfere with the absorption of CS and therefore reduce its local effect. Eventually, our patients may have had less severe pain than those in other studies, which would justify a lesser effect after the pharmacological intervention,” the authors wrote. “Furthermore, when the main outcome studied is particularly subjective, the placebo effect can overcome the effect of the active drug.”
Tedec Meiji Farma SA of Madrid funded the study. Dr. Roman-Blas and his coauthors did not report any relevant financial disclosures.