Elsevier

Clinical Therapeutics

Volume 35, Issue 4, April 2013, Pages 431-439
Clinical Therapeutics

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Original research
The Efficacy of Diacerein in Hand Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Study

https://doi.org/10.1016/j.clinthera.2013.02.009Get rights and content

Abstract

Background

Diacerein is a drug used in osteoarthritis (OA) that elicits an inhibitory effect on interleukin-1 and metalloproteases. Although diacerein has shown modest efficacy and safety in the treatment of knee and hip OA, there have been no placebo-controlled clinical trials for hand OA.

Objective

The aim of the current study was to investigate the efficacy and tolerability of diacerein in patients with hand OA.

Methods

Patients fulfilling the American College of Rheumatology criteria for hand OA participated in this randomized, double-blind, placebo-controlled study. Eligible patients were >40 years of age, had at least 1 tender joint, and had a joint pain visual analog scale of >30 mm. Patients received diacerein (50 mg) or placebo BID for 12 weeks. The primary end point was the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score at 4 weeks. Secondary end points were AUSCAN pain score at 12 weeks and AUSCAN physical function and stiffness score, patient and physician global assessment, functional index of hand OA scores, and multidimensional health assessment questionnaire results at 4 weeks and 12 weeks.

Results

Eighty-six Korean patients were enrolled (42 diacerein, 44 placebo). The intention-to-treat and per-protocol analyses revealed no significant differences between the 2 groups in terms of change in AUSCAN pain score at 4 weeks, except for improvement in physician global assessment at 4 weeks (per-protocol analysis, P = 0.004). The safety profile of diacerein was comparable to placebo, except for frequent discoloration of the urine (88% vs 20%).

Conclusion

These results suggest that diacerein 50 mg BID may be ineffective in controlling the symptoms of hand OA. ClinicalTrials.gov identifier: NCT00685542.

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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