A prospective, randomized, double-blind, multicenter comparative study on the safety and efficacy of Celecoxib and GCSB-5, dried extracts of six herbs, for the treatment of osteoarthritis of knee joint.

ETHNOPHARMACOLOGICAL RELEVANCE: This prospective, randomized, double-blind, multicenter study compared the efficacy and safety of Celecoxib and GCSB-5, a new product from extracts of six herbs, for the treatment of knee osteoarthritis. MATERIALS AND METHODS: A total of 198 eligible patients were randomly assigned to the Celecoxib group (n=99 patients) or the GCSB-5 group (n=99 patients) for the 12-week study. The amount of change and percentage of the change in Western Ontario and McMaster Universities (WOMAC) Arthritis Index from the baseline, the change in pain on walking by visual analogue scale (VAS), physician's global assessment on response to therapy (PGART) by five point Likert scale, and the amount of rescue medicine taken were used as parameters for efficacy. Adverse drug reactions (ADRs) were carefully investigated. RESULTS: The WOMAC score improved in both the Celecoxib group and GCSB-5 group by 20.5 and 21.3 (P=0.79). The percentage of the change in WOMAC score were -42.0% and -38.9% (P=0.54). The pain VAS score decreased by 29.9 and 27.9 (P=0.58). The responders by PGART were 95.3% and 93.8% (P= 0.66), and the median amount of rescue medicine taken were 2.0 and 6.5 tablets (P=0.06). The incidence of ADRs were 31.3% and 21.2% (P=0.11). The most common ADRs were gastrointestinal system related; 17.2% in GCSB-5 group and 22.2% in Celecoxib group. Any severe ADR was not observed in either group. CONCLUSIONS: The result of this study supports that GCSB-5 is comparable to Celecoxib in terms of the efficacy and safety for the treatment of osteoarthritis of knee joint.

Analysis of Repeated Measured VAS in a Clinical Trial for Evaluating a New NSAID with GEE Method.

OBJECTIVE: To compare the efficacy between SKI306X and Diclofenac by using generalized estimating equations (GEE) methodology in the analysis of correlated bivariate binary outcome data in Osteoarthritis (OA) diseases. METHODS: A randomized, double-blind, active comparator controlled, non-inferiority clinical trial was conducted at 5 institutions in Korea with the random assignment of 248 patients aged 35 to 75 years old with OA of the knee and clinical evidence of OA. Patients were enrolled in this study if they had at least moderate pain in the affected knee joint and a score larger than 35mm as assessed by VAS (Visual Analog Scale). The main exposure variable was treatment (SKI 306X vs. Diclofenac) and other covariates were age, sex, BMI, baseline VAS, center, operation history (Yes/No), NSAIDS (Y/N), acupuncture (Y/N), herbal medicine (Y/N), past history of musculoskeletal disease (Y/N), and previous therapy related with OA (Y/N). The main study outcome was the change of VAS pain scores from baseline to the 2nd and 4th weeks after treatment. Pain scores were obtained as baseline, 2nd and 4th weeks after treatment. We applied GEE approach with empirical covariance matrix and independent (or exchangeable) working correlation matrix to evaluate the relation of several risk factors to the change of VAS pain scores with correlated binary bivariate outcomes. RESULTS: While baseline VAS, age, and acupuncture variables had protective effects for reducing the OA pain, its treatment (Joins/Diclofenac) was not statistically significant through GEE methodology (ITT: aOR=1.37, 95% CI= (0.8200, 2.26), PP: aOR=1.47, 95% CI= (0.73, 2.95) ). The goodness-off it statistic for GEE (6.55, p=0.68) was computed to assess the adequacy of the fitted final model. CONCLUSIONS: Both ANCOVA and GEE methods yielded non statistical significance in the evaluation of non-inferiority of the efficacy between SKI306X and Diclofenac. While VAS outcome for each visit was applied in GEE, only VAS outcome for the fourth visit was applied in ANCOVA. So the GEE methodology is more accurate for the analysis of correlated outcomes.

Clinical efficacy and safety of Lyprinol, a patented extract from New Zealand green-lipped mussel (Perna Canaliculus) in patients with osteoarthritis of the hip and knee: a multicenter 2-month clinical trial.

OBJECTIVE: To validate the clinical efficacy and safety of Lyprinol (a patented extract from Perna Canaliculus), a 5-LOX inhibitor in patients with osteoarthritis. METHODS: In this multicenter trial, 60 patients with symptomatic osteoarthritis of the knee and hip were included to receive Lyprinol at a dose of 2 capsules twice a day. After a 4- and 8-week treatment period, the following parameters were analyzed: visual analogue scale; Lequesne functional index; global assessment by patients; global assessment by physician; and adverse effects. RESULTS: Lyprinol treatment led to significant improvement of the signs and symptoms of osteoarthritis as determined by all efficacy measures. After a 4- and 8-week treatment period, 53% and 80% (respectively) of patients experienced significant pain relief, and improvement of joint function. There was no reported adverse effect during this clinical trial. CONCLUSION: Lyprinol was very effective and is a promising anti-inflammatory product that relieves the signs and symptoms of osteoarthritis, without adverse effect.