Efficacy and Safety of Zhuanggu Joint Capsules in Combination with Celecoxib in Knee Osteoarthritis

Abstract

Background:Knee osteoarthritis (KOA) is a chronic joint disease that manifests as knee pain as well as different degrees of lower limb swelling, stiffness, and movement disorders. The therapeutic goal is to alleviate or eliminate pain, correct deformities, improve or restore joint functions, and improve the quality of life. This study aimed to evaluate the efficacy and safety of Zhuanggu joint capsules combined with celecoxib and the benefit of treatment with Zhuanggu alone for KOA.Methods:This multi-center, randomized, double-blind, double-dummy, parallel controlled trial, started from December 2011 to May 2014, was carried out in 6 cities, including Beijing, Shanghai, Chongqing, Changchun, Chengdu, and Nanjing. A total of 432 patients with KOA were divided into three groups (144 cases in each group). The groups were treated, respectively, with Zhuanggu joint capsules combined with celecoxib capsule simulants, Zhuanggu joint capsules combined with celecoxib capsules, and celecoxib capsules combined with Zhuanggu joint capsule simulants for 4 weeks consecutively. The improvement of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the decreased rates in each dimension of WOMAC were evaluated before and after the treatment. Intergroup and intragroup comparisons of quantitative indices were performed. Statistically significant differences were evaluated with pairwise comparisons using Chi-square test (or Fisher's exact test) and an inspection level of α = 0.0167.Results:Four weeks after treatment, the total efficacies of Zhuanggu group, combination group, and celecoxib group were 65%, 80%, and 64%, respectively, with statistically significant differences among the three groups (P = 0.005). Intergroup pairwise comparisons showed that the total efficacy of the combination group was significantly higher than that of the Zhuanggu (P = 0.005) and celecoxib (P = 0.003) groups. The difference between the latter two groups was not statistically significant (P > 0.0167). Four weeks after discontinuation, the efficacies of the three groups were 78%, 95%, and 65%, respectively, with statistically significant differences (P < 0.0001). Intergroup pairwise comparisons revealed that the efficacy of the combination group was significantly better than that of the Zhuanggu and the celecoxib groups (P < 0.0001). The difference between the latter two groups was not statistically significant (P > 0.0167). The incidences of adverse events in Zhuanggu group, combination group, and celecoxib group were 8.5%, 8.5%, and 11.1%, respectively, with insignificant differences (P > 0.05).Conclusions:Zhuanggu joint capsules alone or combined with celecoxib showed clinical efficacy in the treatment of KOA. The safety of Zhuanggu joint capsules alone or combined with celecoxib was acceptable.Trial Registration:Chinese Clinical Trial Registry, ChiCTR-IPR-15007267; http://www.medresman.org/uc/project/projectedit.aspx?proj=1364.

Are Kidney-Tonifying and Blood-Activating Medicinal Herbs Better than NSAIDs for Knee Osteoarthritis? A Systematic Review and Meta-Analysis

“…All the studies, including 2012 patients from the treatment group and 1982 individuals in the control group, were recruited into this systematic review. Two different diagnostic criteria of KOA were used in most of the included trials: 19 studies [19, 30, 36–38, 41, 42, 44–54, 58] used the 1995 American College of Rheumatology Guidelines for The Medical Management of Osteoarthritis (ACR criteria-1995) and 15 studies [26, 27, 31, 33–35, 39, 40, 43, 55–57, 60–62] used the 2007 Chinese Medical Association Guidelines for The Diagnosis and Treatment of Osteoarthritis (CMA criteria-2007). One study [28] used the Guiding Principles for Clinical Research of New Chinese Medicine, two studies [29, 32] referred to the Criteria for the Diagnosis and Therapeutic Effect of Diseases and Syndromes in Traditional Chinese Medicine, and only one study [59] did not explicitly mention diagnostic criteria.…”

“…All studies investigated oral KTBAMs, including multi-ingredient CHM, and the top 20 forms used based on frequency are listed (Table 2). The preparation forms of the multi-ingredient CHM formulas were decoctions in 28 studies [28–30, 32, 35–39, 41–50, 52–55, 57–60, 62], tablets in two studies [40, 51], capsules in five studies [27, 33, 34, 56, 61], and pills in the others [19, 26, 31]. All studies used KTBAMs compared with NSAIDs.…”

“…All studies used KTBAMs compared with NSAIDs. Among the included trials, KTBAMS were compared with meloxicam in six studies [30, 32, 35, 41, 47, 62], with celecoxib in 17 studies [26, 31, 34, 36, 38–40, 42, 43, 45, 48, 49, 56, 57, 59–61], with diacerein in three studies [28, 33, 58], with diclofenac in six studies [19, 27, 46, 52–54], with loxoprofen in two studies [37, 55], with fenbid in two studies [44, 50], and with ibuprofen [51] or etodolac [29] in the remaining studies.…”

“…The treatment durations were 2 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, and 12 weeks. Only one study [31] had a posttreatment follow-up phase of 4 weeks. Ten studies [19, 31, 38–40, 48, 56, 58, 60, 62] reported dropouts during the treatment phase with reasons provided.…”

“…The others [19, 30, 32, 35–38, 41, 43–47, 50–52, 54, 57, 59] had unclear risk for not providing detailed information regarding random sequence generation. Three studies [26, 27, 31] were assessed as high risk because they generated the sequence according to the order in which the patients attended the clinic. For allocation concealment, one study [58] was at low risk for using allocation concealment, and other studies were at unclear risk because they lacked the relevant information.…”