Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis

Pham, Thao; Hénanff, Anne Le; Ravaud, Philippe; Dieppe, Paul; Paolozzi, L; Dougados, Maxime

doi:10.1136/ard.2003.019703

Cited by 118 publications

(94 citation statements)

References 37 publications

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“…These include a high placebo effect, the design of the study, and the lack of efficacy of the drug itself (25). IA procedure, notably with injections of HA into the knee, is commonly associated with a high placebo response that might limit the ability to detect benefits of the treatment (8,22,25). However, in the present study we did not observe a high placebo response that may have skewed the results observed in the treatment group.…”

Section: Discussioncontrasting

confidence: 55%

“…Several hypotheses could explain the lack of efficacy of a potentially active treatment in an RCT. These include a high placebo effect, the design of the study, and the lack of efficacy of the drug itself (25). IA procedure, notably with injections of HA into the knee, is commonly associated with a high placebo response that might limit the ability to detect benefits of the treatment (8,22,25).…”

Section: Discussionmentioning

confidence: 99%

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Effect of hyaluronic acid in symptomatic hip osteoarthritis: A multicenter, randomized, placebo‐controlled trial

Richette¹,

Ravaud²,

Conrozier³

et al. 2009

Arthritis & Rheumatism

106

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Objective. To evaluate the efficacy and tolerability of a single intraarticular (IA) injection of hyaluronic acid (HA) for the treatment of hip osteoarthritis (OA).Methods. A multicenter, randomized, parallelgroup, placebo-controlled trial was conducted over 3 months. Patients (older than 30 years) with symptomatic hip OA (pain score of >40 mm on a visual analog scale [VAS]) and a Kellgren/Lawrence grade of 2 or 3 were randomly assigned to receive 1 fluoroscopically guided IA injection of HA (2.5 ml) or placebo (2.5 ml). Patients were followed up for 3 months. The main outcome measure was pain score on a VAS (100 mm) at month 3 compared with baseline. Secondary outcome measures were the proportion of responders defined by Osteoarthritis Research Society International criteria; Western Ontario and McMaster Universities Osteoarthritis Index subscores for pain, stiffness, and disability; and patient and physician global assessment. Randomization was computer generated. HA and placebo preparations were placed in numbered identical containers, and syringes were covered with masking tape. Physicians assessing outcomes were blinded with regard to group assignment.Results. Eighty-five patients were randomized to the HA group (n ‫؍‬ 42) or placebo group (n ‫؍‬ 43). Baseline characteristics were similar between the 2 groups. At 3 months, the decrease in pain score did not differ between the HA and placebo groups in the intentto-treat analysis (mean ؎ SD decrease 7.8 ؎ 24.9 mm with HA versus 9.1 ؎ 27.4 mm with placebo; P ‫؍‬ 0.98). The responder rates were 33.3% and 32.6% in the HA and placebo groups, respectively (P ‫؍‬ 0.94). Other secondary end points did not differ between the groups, nor did use of rescue medication or frequency of adverse events.Conclusion. Our findings indicate that a single IA injection of HA is no more effective than placebo in treating the symptoms of hip OA.Osteoarthritis (OA) is the most common type of arthritis and the major cause of disability in elderly populations worldwide. Hip OA is the second most frequent form of OA affecting a large joint, and its prevalence ranges from 3% to 11% in populations older than 35 years (1-3).Current therapies for hip OA include a combination of nonpharmacologic and pharmacologic treatments (4-6). Viscosupplementation is an intraarticular (IA) therapeutic modality that is based on the physiologic importance of hyaluronic acid (HA) in synovial ClinicalTrials.gov identifier: NCT00330135.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Effect of hyaluronic acid in symptomatic hip osteoarthritis: A multicenter, randomized, placebo‐controlled trial

Richette¹,

Ravaud²,

Conrozier³

et al. 2009

Arthritis & Rheumatism

106

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“…Using such a change score might reduce the power or precision of an individual study. 49 The trials included in the analysis of Lo and associates 8 differed slightly from those in our analysis: we identified and included 4 published studies 17,19,25,38 not used by Lo and associates, whereas those authors included 3 studies that we did not (2 published only as abstracts 50,51 and 1 in which the patient's other knee served as the control [i.e., observations may not be independent] 52 ). Lo and associates concluded that at best there is a small effect.…”

Section: Favours Interventionmentioning

confidence: 91%

Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis

Arrich

Piribauer²,

Mad³

et al. 2005

Canadian Medical Association Journal

281

182

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Review SynthèseO steoarthritis affects about 10% of the population over 55 years of age. Of those, one-quarter are severely disabled.1 The condition is characterized by degeneration of the articular cartilage and subsequent subchondral bone changes. The underlying mechanisms remain unknown, but the glycosaminoglycan-proteoglycan matrix may play a major role. 2 Hyaluronic acid, a glycosaminoglycan, is widely used for the treatment of osteoarthritis of the knee. A survey of 2 general practices in the United Kingdom showed that about 15% of patients with osteoarthritis received intraarticular treatment with glucosamine sulfates. 3 The costs of such treatment are significant. At present, 1 syringe of hyaluronic acid costs at least Can$130 (US$110). The treatment of knee osteoarthritis is covered by the US Medicare program but not by provincial formularies in Canada. In Austria (which has 8 million inhabitants) more than 10 million euros (approximately US$12 million or Can$15 million) is spent by social insurance programs annually for hyaluronic acid preparations (excluding the cost of application).Hyaluronic acid has beneficial effects in vitro. 4 Because of its viscoelastic quality, it may replace synovial fluid. Furthermore, it may reduce the perception of pain. Beneficial molecular and cellular effects have also been reported. 2,4Hyaluronic acid is frequently applied by intra-articular injection, but the evidence concerning its clinical relevance is conflicting. The European League against Rheumatism (EULAR) recommends the intra-articular application of hyaluronic acid as "category 2" evidence (at least 1 controlled study without randomization). 5 The American College of Rheumatology recommends intra-articular hyaluron therapy for patients with no response to nonpharmacologic therapy and simple analgesics. 6 In contrast, other specialists have concluded that "hyaluronate sodium is not efficacious" in the treatment of osteoarthritis. 7 The first state-of-the-art systematic review and meta-analysis was published recently, 8 and its authors concluded "that intra-articular hyaluronic acid, at best, has a small effect."We performed a systematic review and meta-analysis of Abstract Background: Osteoarthritis of the knee affects up to 10% of the elderly population. The condition is frequently treated by intra-articular injection of hyaluronic acid. We performed a systematic review and meta-analysis of randomized controlled trials to assess the effectiveness of this treatment. Methods: We searched MEDLINE, EMBASE, CINAHL, BIOSISand the Cochrane Controlled Trial Register from inception until April 2004 using a combination of search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. We extracted data on pain at rest, pain during or immediately after movement, joint function and adverse events. Results: Twenty-two trials that reported usable quantitative information on any of the predefined end points were identified and included in the systematic review. Even though pain at res...

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“…Those trials are limited to knee and hip OA and are of short duration, except for one, which followed patients for 3 years for structural outcome measures [9]. Several studies have concluded that diacerein is a slow-acting, symptommodifying OA agent [4,5,8] with a carry-over effect; others have reported negative outcomes in regard to symptomatic [9] and structural effects [12]. The Cochrane Collaboration published the most comprehensive review in 2014, which included ten studies [2].…”

Section: Trial Reviewmentioning

confidence: 99%

“…From this, we selected large clinical trials (N [ 100) and the most upto-date meta-analyses published in English. The included trials were RCTs comparing diacerein with placebo [5,8,9], as well as an NSAID comparator study [4], a trial of diacerein versus placebo and a hyaluronic acid compound [12], and two meta-analyses [2,3]. Most reviewed RCTs had pain as their primary outcome, measured by a visual analogue scale (VAS) or the Western Ontario and McMaster Universities Osteoarthritis Index section A (WOMAC A).…”

Section: Study Design and Analysismentioning

confidence: 99%

Benefit–Risk Assessment of Diacerein in the Treatment of Osteoarthritis

Панова

Jones

2015

Drug Saf

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Osteoarthritis (OA) is the leading musculoskeletal cause of disability. Despite this, there is no consensus on the precise definition of OA and what is the best treatment to improve symptoms and slow disease progression. Current pharmacological treatments include analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors. None of those treatments are disease-modifying agents that target the core pathological processes in OA. Diacerein, a semi-synthetic anthraquinone derivative, inhibits the interleukin-1-beta (IL-1β) cytokine which, according to animal studies, plays a key role in the pathogenesis of OA. Diacerein was synthesized in 1980 and licensed in some European Union and Asian countries for up to 20 years. It has shown modest efficacy and acceptable tolerability in a number of trials of low to moderate quality. Early this year, the European Medicines Agency (EMA) conducted a review and restricted the use of diacerein-containing medicines. This was because of major concerns about the frequency and severity of diarrhoea and liver disorders in OA patients. In addition, the EMA's Pharmacovigilance Risk Assessment Committee (PRAC) questioned the limited clinical benefits of diacerein, which, in their view, did not outweigh its risks. The aim of this review is to provide a benefit-risk assessment of diacerein in the treatment of OA, based on asystematic evaluation of the published efficacy and safety data. Overall, there is evidence that diacerein is modestly effective for symptoms and possibly for radiographic changes, but this needs to be balanced against higher rates of gastrointestinal toxicity.

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Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis

Cited by 118 publications

References 37 publications

Effect of hyaluronic acid in symptomatic hip osteoarthritis: A multicenter, randomized, placebo‐controlled trial

Effect of hyaluronic acid in symptomatic hip osteoarthritis: A multicenter, randomized, placebo‐controlled trial

Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: systematic review and meta-analysis

Benefit–Risk Assessment of Diacerein in the Treatment of Osteoarthritis

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