Abstract
Background and Objective: According to international guidelines, glucosamine and chondroitin, regarded as slow-acting drugs for osteoarthritis (SYSADOAs), have been first-line treatments for knee osteoarthritis (OA); however, their efficacies remain controversial. Additionally, the efficacies of plant extract cocktails, SKI306X, and its newer formulation, SKCPT, have not been well investigated. To evaluate the effectiveness and safety of symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) in patients with knee OA. Materials and Methods: Electronic databases were systematically searched to identify randomized controlled trials (RCTs) assessing the effectiveness and safety of SYSADOAs, including chondroitin sulfate, glucosamine sulfate, and SKCPT/SKI306X. The outcomes included pain relief, functional improvements, and safety profiles. The outcome measurements were compared between the treatment and control groups, including placebo and non-placebo groups, within and after 3 months of follow-up. Results: Analysis of 21 RCTs showed significantly greater improvement in pain relief in the treatment group compared with the placebo group both within (standard mean difference [SMD], 0.38; 95% confidence interval [CI], 0.18-0.57; p < 0.001) and after 3 months of follow-up (SMD, 0.22; 95%CI, 0.03-0.42 p = 0.023). The treatment group also showed significantly greater functional improvements regardless of follow-up. Pain and functional improvement did not differ significantly between the treatment and non-placebo groups. Regarding the safety profile, the risk ratios did not differ significantly between the treatment and control groups, including the placebo and non-placebo subgroups. Conclusions: Glucosamine, chondroitin, and SKCPT/SKI306X improved the pain and function and were non-inferior to pharmacologic drugs for up to 12 months. These findings support the clinical use of these SYSADOAs to treat knee OA. Level of Evidence: Therapeutic Level II.