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,
References (38)
- et al.
Clinical update: treating osteoarthritis
Lancet
(2007) - et al.
Diacerein suppresses the increase in plasma nitric oxide in rat adjuvant-induced arthritis
Eur J Pharmacol
(2001) - et al.
Symptomatic efficacy and safety of diacerein in the treatment of osteoarthritis: a meta-analysis of randomized placebo-controlled trials
Osteoarthritis Cartilage
(2010) - et al.
Dimensionality and clinical importance of pain and disability in hand osteoarthritis: development of the Australian/Canadian (AUSCAN) Osteoarthritis Hand Index
Osteoarthritis Cartilage
(2002) - et al.
Clinimetric properties of the AUSCAN Osteoarthritis Hand Index: an evaluation of reliability, validity and responsiveness
Osteoarthritis Cartilage
(2002) - et al.
Design and conduct of clinical trials in patients with osteoarthritis of the hand: recommendations from a task force of the Osteoarthritis Research Society International
Osteoarthritis Cartilage
(2006) - et al.
Association of erosive hand osteoarthritis with a single nucleotide polymorphism on the gene encoding interleukin-1 beta
Osteoarthritis Cartilage
(2003) - et al.
Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: a meta-analysis of randomised placebo-controlled trials
Eur J Pain
(2007) - et al.
The efficacy, safety and carry-over effect of diacerein in the treatment of painful knee osteoarthritis: a randomised, double-blind, NSAID-controlled study
Osteoarthritis Cartilage
(2007) - et al.
Hand osteoarthritis
Semin Arthritis Rheum
(2005)
Prevalence and determinants of one month hand pain and hand related disability in the elderly (Rotterdam study)
Ann Rheum Dis
SACRAH: a score for assessment and quantification of chronic rheumatic affections of the hands
Rheumatology (Oxford)
Health-related quality of life in women with symptomatic hand osteoarthritis: a comparison with rheumatoid arthritis patients, healthy controls, and normative data
Arthritis Rheum
Assessing health-related quality of life in hand osteoarthritis: a literature review
Ann Rheum Dis
American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee
Arthritis Care Res (Hoboken)
Systems to assess the progression of finger joint osteoarthritis and the effects of disease modifying osteoarthritis drugs
Clin Rheumatol
Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling
Arthritis Res Ther
In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes
J Rheumatol
Diacerhein and rhein reduce the interleukin 1beta stimulated inducible nitric oxide synthesis level and activity while stimulating cyclooxygenase-2 synthesis in human osteoarthritic chondrocytes
J Rheumatol
Cited by (29)
Experts Document About an Adequate Utilization of SYSADOAs in Controversial Clinical Situations
2021, Reumatologia ClinicaChoice of control group treatments in hand osteoarthritis trials: A systematic review and meta-analysis
2021, Seminars in Arthritis and RheumatismCitation Excerpt :Table 1 summarizes characteristics of the studies and Supplementary Table S2 shows the individual results. Thirty-three placebo [4,5,33,38-67], 16 add-on treatment [13,14,34,36,68-79], 12 no-treatment [35, 80-90], and 12 active-treatment control groups [91-102] were included with a total of 3386 hand OA patients. There were two cross-over designs and one factorial design.
Systematic review of non-surgical therapies for osteoarthritis of the hand: an update
2017, Osteoarthritis and CartilageCitation Excerpt :A formal meta-analysis was to be performed, if feasible. A total of 95 RCTs were analyzed in this systematic review6–99. There were 2 RCTs published between 1970 and 1979, 5 between 1980 and 1989, 14 between 1990 and 1999, 34 between 2000 and 2009, and 40 between 2010 and December 2015.
Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial
2016, Clinical TherapeuticsCitation Excerpt :All types of adverse events (AEs) were captured at each visit. We reported previously that after 4 weeks of placebo administration, the mean (SD) improvement in AUSCAN pain score in patients with hand OA was +7.8 (23.6) (on a 0–100 scale).20 Assuming that GCSB-5 improves the AUSCAN pain score by >10 relative to placebo, and assuming an α level of 0.05 (2-tailed), a power of 0.80, and a dropout rate of 20%, the sample size calculation revealed that 220 patients were needed for enrollment.21–24
Current recommendations and evidences on the treatment of osteoarthritis
2015, FMC Formacion Medica Continuada en Atencion PrimariaAnti-inflammatory and antipyretic analgesics and drugs used in gout
2014, Side Effects of Drugs AnnualCitation Excerpt :The efficacy was similar between both groups, as was the safety profile. However, frequent discolouration of the urine – which disappeared spontaneously – occurred more often in the diacerein group (88%) than in the placebo group (20%) [48c]. Cardiovascular: The effect of nefopam timing on early postoperative hyperalgesia after cardiac surgery was evaluated in a double-blind, randomized trial between March 2007 and December 2009.