Featured contentOriginal researchThe Efficacy of Diacerein in Hand Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Study
Introduction
Osteoarthritis (OA) affects >30% of the elderly population (65 years and older) and commonly involves the knees, hips, spine, and hands.1 The reported prevalence of hand OA in the elderly varies according to which diagnostic criteria are applied; it ranges from 6% to 20% with clinical criteria to 80% with radiologic criteria.2 OA typically affects the distal and proximal interphalangeal and the first carpometacarpal joints, resulting in a variable degree of pain and stiffness. The impact of hand OA on health-related quality of life is estimated to be almost equivalent to that of rheumatoid arthritis.3, 4, 5, 6
Evidence-based treatment guidelines for hand OA are incomplete because there is a scarcity of well-designed randomized studies.7 NSAIDs are effective in controlling symptoms but are associated with serious adverse events such as gastrointestinal hemorrhage. The efficacy of disease-modifying OA drugs in terms of joint symptoms and structures remains unknown. Although 1 report found that chondroitin polysulfate partially prevented radiographic progression in OA, its efficacy in symptom control is unclear.8
Diacerein is a drug that was developed specifically for the treatment of OA. It has inhibitory effects on both interleukin (IL)-1β and metalloproteases such as collagenase and stromelysin, while exerting no effects on phospholipase A2, cyclooxygenase, or lipoxygenase.9, 10, 11 Diacerein has exhibited anti-inflammatory effects and reduced structural changes in various OA animal models.12, 13, 14 In recent meta-analyses, diacerein showed modest efficacy and a good safety profile in the treatment of human knee and hip OA.15, 16, 17 The most common adverse effect was diarrhea, which was reported in ∼30% of patients. Despite the proven efficacy of diacerein in lower-extremity OA, the efficacy and safety of diacerein in hand OA remain to be clarified. The aim of the current study was to investigate the clinical efficacy and tolerability of diacerein in hand OA by performing a double-blind, randomized, placebo-controlled study.
Section snippets
Study Population
Patients fulfilling the American College of Rheumatology criteria for hand OA18 were enrolled at a rheumatologic clinic in the Seoul National University Hospital between June 2008 and May 2009. Eligible patients were >40 years old, had >1 tender joint, and had joint pain >30 mm according to a visual analog scale (100 mm) after a 2-week washout period. Patients with a history of hand joint surgery or treatment with oral corticosteroids, intra-articular corticosteroids, or hyaluronic acid
Demographic Data
Eighty-six patients were enrolled (42 diacerein, 44 placebo). A CONSORT flow chart is shown in Figure 1. All baseline demographic data between the diacerein and placebo groups were comparable, with the exception of body mass index, which was higher in the placebo group (24.7 vs 23.5 kg/m2; P = 0.026) (Table 1). The mean disease duration for the diacerein and placebo groups was 4.9 and 4.6 years, respectively (P = 0.758). The percentage of patients who remained in the study in the diacerein
Discussion
To the best of our knowledge, the current study is the first double-blind, randomized, placebo-controlled trial to investigate the efficacy of diacerein in hand OA. Although diacerein 50 mg BID was found to be well tolerated in patients with hand OA, its efficacy was not superior to placebo for the primary end point. The only difference in the secondary end points was for physician global assessment, which was superior in the diacerein group.
The role of pro-inflammatory cytokines in the early
Conclusion
The results of this trial indicate that the safety profile of diacerein 50 mg BID is acceptable, although the regimen may be unsuccessful in controlling the symptoms of hand OA.
Conflicts of Interest
Dr. E.B. Lee is a consultant to Pfizer Inc. The other authors have indicated that they have no conflicts of interest regarding the content of this article.
Acknowledgment
The authors thank the Medical Research Collaborating Center of Seoul National University College of Medicine for their assistance with the statistical analyses. This study was funded by Myungmoon Pharmaceutical Co, Ltd. The company was not involve in the study design, data acquisition, or interpretation of this study.
Dr. Shin was responsible for the data interpretation and writing of the manuscript. Dr. E.B. Lee was responsible for the study design, data collection and interpretation. Drs. Kim,
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