Symptomatic Slow-acting Drugs For Osteoarthritis Research Articles

Efficacy and safety of glucosamine sulfate in the management of osteoarthritis: Evidence from real-life setting trials and surveys.

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm recommends chronic symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) including glucosamine sulfate (GS) and chondroitin sulfate (CS) as first-line therapy for knee osteoarthritis (OA). Numerous studies are published on the use of SYSADOAs in OA; however, the efficacy of this class is still called into question largely due to the regulatory status, labeling and availability of these medications which differ substantially across the world. Examination of the evidence for the prescription patented crystalline GS (pCGS) formulation at a dose of 1500mg once-daily demonstrates superiority over other GS and glucosamine hydrochloride (GH) formulations and dosage regimens. Thus, the ESCEO task force advocates differentiation of prescription pCGS over other glucosamine preparations. Long-term clinical trials and real-life studies show that pCGS may delay joint structural changes, suggesting potential benefit beyond symptom control when used early in the management of knee OA. Real-life pharmacoeconomic studies demonstrate a long-term reduction in the need for additional pain analgesia and non-steroidal anti-inflammatory drugs (NSAIDs) with pCGS, with a significant reduction of over 50% in costs associated with medications, healthcare consultations and examinations over 12 months. Furthermore, treatment with pCGS for at least 12 months leads to a reduction in the need for total joint replacement for at least 5 years following treatment cessation. Thus, pCGS (1500mg od) is a logical choice to maximize clinical benefit in OA patients, with demonstrated medium-term control of pain and lasting impact on disease progression.

Effects of glucosamine sulfate on the use of rescue non-steroidal anti-inflammatory drugs in knee osteoarthritis: Results from the Pharmaco-Epidemiology of GonArthroSis (PEGASus) study.

The use of Symptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) may be expected to decrease the use of concomitant medications for rescue analgesia, including non-steroidal anti-inflammatory drugs (NSAIDs). The Pharmaco-Epidemiology of GonArthroSis (PEGASus) study was designed to assess this possibility. PEGASus was a cohort study of continuous recruitment of patients with "dynamic" exposure to the investigated SYSADOA (crystalline glucosamine sulfate, glucosamine hydrochloride, chondroitin sulfate, diacerein, and avocado-soybean unsaponifiables, all at approved dosages). Investigators were rheumatologists or general practitioners randomly selected from French telephone lists. Patients diagnosed with knee osteoarthritis (OA) were recruited when consulting an investigator for a symptom flare and were prescribed, or not, one of the SYSADOAs as per clinical judgment. Follow-up visits were as per routine medical practice in the 12 months following enrollment, with telephone interviews after 1 month and at 4-month intervals thereafter up to 24 months. Use of NSAIDs was recorded, as well as the dynamism of treatment exposure consisting of continuing the prescribed SYSADOA, switching, discontinuation or initiation of a SYSADOA. Patient exposure was expressed in 2-month time units, with any NSAID use as Yes/No binary outcome during each unit. Odds ratios [OR and 95% confidence interval (CI)] of NSAID use were calculated for periods of exposure to each SYSADOA, by multivariate logistic regression for an 80% power and 95% confidence to see a decrease of at least 15%. This report consists of the full data pertaining to crystalline glucosamine sulfate, while results of other SYSADOAs were summarized as available from the French Health Authority (HAS) website (www.has-sante.fr). Of 6451 patients in the PEGASus cohort, 315 patients received crystalline glucosamine sulfate, they were exposed for 481 2-month time units and had an incident use of NSAIDs of 18.7%. In the control cohort (9237 time units) NSAID incident use was 23.8%. Crystalline glucosamine sulfate significantly decreased the risk of NSAID consumption by up to 36% (OR = 0.64; 95% CI: 0.45-0.92) in the primary analysis foreseen by the protocol; OR was 0.74 (95% CI: 0.54-1.01), i.e. at the very limit of significance, in a sensitivity analysis accounting for an extension of the study and of the control cohort. None of the other SYSADOAs showed any hint of a decrease in the use of NSAIDs. Crystalline glucosamine sulfate was the only SYSADOA that decreased the use of NSAIDs in this pharmaco-epidemiology study in patients with knee OA.

Short-term effect of the combination of hyaluronic acid, chondroitin sulfate, and keratin matrix on early symptomatic knee osteoarthritis

In the last years, symptomatic slow-acting drugs for osteoarthritis (SYSADOA) have been vastly studied and have generated considerable interest among clinicians. SYSADOA are generally used as a ground therapy with the main rationale to reduce the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) and thus limit the related adverse events. In this study, we evaluated the short-term effect of an oral combination of hyaluronic acid, chondroitin sulfate, and keratin matrix on early symptomatic knee osteoarthritis. Forty patients were treated for 1 month and were allowed to assume analgesics or NSAIDs if necessary. At 2 months, the mean reduction of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was 36% (p<0.001), and the mean reduction of the WOMAC pains score was 40% (p<0.001). Only two patients reported a sporadic need to assume analgesics; no patient reported any side effect during the study period. This data demonstrates that the oral combination of hyaluronic acid, chondroitin sulfate, and keratin matrix is safe, well tolerated, and shows a rapid action reducing pain and improving joint function and stiffness in early symptomatic knee osteoarthritis.

ESTIMATION OF DIACEREIN TOLERABILITY IN REAL CLINICAL PRACTICE: RESULTS OF THE RACADA (RETROSPECTIVE ASSESSMENT OF CLINICAL ASPECTS OF USING DIAFLEX IN OSTEOARTHRITIS)

Diacerein (DR) is widely used to treat osteoarthritis (OA) and belongs to a group of symptomatic slow-acting drugs for OA (SYSADOA). One of the major benefits of this drug is a low risk of serious adverse events(AE). However,Russiahas not conducted its own large-scale trials of the safety of DR despite its popularity. Objective: to estimate the frequency of AE of DR (Diaflex®, Romfarm) in real clinical practice. Subject s and methods. The use of DR was retrospectively analyzed in 3479 patients (60.4% women and 39.6% men; mean age 57.6±12.6 years) with OA and back pain. DR was used in a dose of 100 mg/day; treatment results were assessed following 30 days. The patients received combination therapy: in addition to DR, 62.6% took nonsteroidal anti-inflammatory drugs, as well as myorelaxants, local glucocorticoid injections, other SYSADOA, etc. The efficiency of therapy (visual analogue scale (VAS) pain changes and treatment satisfaction), and the frequency and nature of AE were assessed. Results. Combination therapy using DR was effective in the majority of patients: VAS pain intensity decreased from 71.2±17.5 to 22.6±16.3 mm; 76% of the patients rated their treatment results as good or excellent. Major AE involved the gastrointestinal tract; obvious gastralgia, nausea, and a sensation of heaviness were observed in only 1.7, 1.8, and 2.4% of the patients, respectively. There were frequent stools: 5.91±1.9 defecation episodes per week at baseline; 7.3±2.8 episodes per week after 30 days of DR administration (p < 0.001). Only 30 (0.86%) patients developed marked diarrhea. There was a considerable (more than two-fold higher than the upper reference limits) increase in alanine aminotransferase and aspartate aminotransferase (ALT/AST) levels in only 20 (0.57%) patients. Conclusion. Combination treatment using DR is effective in reducing pain in patients with OA and low back pain. DR is well tolerated and rarely causes serious AE. Marked diarrhea and significantly elevated ALT/AST levels are seen in less than 1% of the patients taking

Do male and female general practitioners differently prescribe chronic pain drugs to older patients?

The aim of this study was to identify the relationship between general practitioner (GP) gender and prescribing practice of chronic pain drugs in older adults. Cross-sectional observational study. GPs in private practice throughout France. Two hundred and sixty GPs (80.8% male and 19.2% female) enrolled 1,379 (28.4% male and 71.6% female) noninstitutionalized patients over 65 years of age, suffering from chronic pain. A comparison of prescribing habits between male and female GPs was performed on baseline data with univariate analyses followed by multivariate analyses after taking several confounding factors into account. No significant differences were found when comparing male and female GPs' prescriptions of World Health Organization step 1, step 2, and step 3 analgesics. Male GPs were more likely than female GPs to prescribe antineuropathic pain drugs (11.3% of patients with male GPs versus 4.8% of patients with female GPs, P = 0.004) and less likely to prescribe symptomatic slow-acting drugs for osteoarthritis (SySADOA) (10.2% of male GPs' patients versus 18.8% of female GPs' patients, P = 0.0003). After adjusting for several confounding factors, male GPs were still more likely to prescribe antineuropathic pain drugs (OR 2.43, 95% CI 1.15-5.14, P = 0.02) and less likely to prescribe symptomatic slow-acting drugs (OR 0.64, 95% CI 0.42-0.97, P = 0.03). Male and female GPs prescribe analgesics in a similar manner. However, male GPs prescribe more antineuropathic pain drugs, but fewer SySADOA.

Discrepancies in composition and biological effects of different formulations of chondroitin sulfate.

Osteoarthritis is a common, progressive joint disease, and treatments generally aim for symptomatic improvement. However, SYmptomatic Slow-Acting Drugs in Osteoarthritis (SYSADOAs) not only reduce joint pain, but slow structural disease progression. One such agent is chondroitin sulfate—a complex, heterogeneous polysaccharide. It is extracted from various animal cartilages, thus has a wide range of molecular weights and different amounts and patterns of sulfation. Chondroitin sulfate has an excellent safety profile, and although various meta-analyses have concluded that it has a beneficial effect on symptoms and structure, others have concluded little or no benefit. This may be due, at least partly, to variations in the quality of the chondroitin sulfate used for a particular study. Chondroitin sulfate is available as pharmaceutical- and nutraceutical-grade products, and the latter have great variations in preparation, composition, purity and effects. Moreover, some products contain a negligible amount of chondroitin sulfate and among samples with reasonable amounts, in vitro testing showed widely varying effects. Of importance, although some showed anti-inflammatory effects, others demonstrated weak effects, and some instances were even pro-inflammatory. This could be related to contaminants, which depend on the origin, production and purification process. It is therefore vitally important that only pharmaceutical-grade chondroitin sulfate be used for treating osteoarthritis patients.

An antinociceptive effect of chondroprotectors: a myth or a reality?

Authors reviewed the literature on the efficacy of chondroprotectors in the treatment of chronic pain syndromes in comparison with placebo and other analgesics to discover the own antinociceptive effect of these drugs and mechanisms by which it occurs. Authors evaluated the results of various clinical studies on the effect of symptomatic slow-acting drugs for osteoarthritis (SYSADOA) on chronic pain syndrome in osteoarthritis and low back pain. We compared their effects with those of NSAIDs, celecoxib, or placebo. Assessment of pain and functional status was performed using WOMAC, VASandLeken's index as well as the Roland--Morrisquality of life questionnaire. The review of a number of clinical studies revealed a definite antinociceptive and anti-inflammatory effect of SYSADOA comparable with NSAIDs not only in the treatment of osteoarthritis, but also in chronic back pain, which is characterized by early onset and gradual development with a long-term retention of the result even after discontinuation of therapy. It has been shown that SYSADOA are able to reduce the level of inflammatory cytokines in the blood (IL-6, C-reactive protein) and to activate the production of anti-inflammatory cytokine IL-10 in the synovial membrane. It is shown that blocking of the effects of interleukin 1-beta and thereby inhibition of inflammatory enzymes like nitric oxide synthase and cyclooxygenase-2 is one of the points of glucosamine chondrocytes application. The data obtained in numerous studies that confirm the ability of SYSADOA to inhibit proinflammatory cytokines open the new perspectives for their use in the treatment of not only joint pain but also other chronic pain syndromes.

The 2014 guidelines for the management of osteoarthritis: Place of hyaluronic acid preparations

The paper gives data on the prevalence of osteoarthritis (OA) and the rate of comorbidities in this disease. It discusses problems of adequate and safe therapy in these patients. The basic provisions of the 2015 clinical guidelines for the rational use of nonsteroidal antiinflammatory drugs (NSAIDs), as well as assessment of risk factors for NSAID-related complications are presented. The place of symptomatic slow-acting drugs for OA (SYSАDOA) and a clash of opinions as to their efficacy among different national or international communities of specialists are discussed. The 2014 ESCEO International Committee guidelines for the management of OA patients, which confirm the necessity of prescribing SYSDOA as initial treatment, are presented. The properties and function of synovial fluid in health and OA are depicted. Clinical and experimental findings have shown that, by improving the lubricating properties of synovial fluid, exogenous hyaluronon has many anticatabolic and anabolic effects and affects pathogenetically significant factors in OA. The results of randomized clinical trials (RCTs) comparing hyaluronans of different molecular weight are given. There are data of RCTs on the clinical efficacy and structuremodifying activity of hylan G-F 20 and on its significant pain relief in OA patients. The paper demonstrates benefits in surviving the analgesic effect of hylan G-F 20 versus intraarticular administration of glucocorticoids.

Condrosulf&lt;sup&gt;&amp;#174;&lt;/sup&gt;: Structural Characterization, Pharmacological Activities and Mechanism of Action

Condrosulf(®) is a pharmaceutical formulation containing chondroitin sulfate (CS) as an active component possessing high quality and purity and standardized properties. CS is currently applied as a SYSADOA (Symptomatic Slow Acting Drug for Osteoarthritis) agent in Europe in the treatment of osteoarthritis (OA). Furthermore, Condrosulf(®) and pharmaceutical grade CS have also been proven to possess structure-modifying effects belonging to the S/DMOAD (structure/disease modifying anti-osteoarthritis drug) class. This review summarizes current knowledge on CS/Condrosulf(®) structure and its properties, its pharmacological activity as proved by many clinical trials and metaanalysis studies and focuses attention on its mechanisms of action in the pathophysiology of osteoarthritic joint tissues. Finally, future perspectives are discussed in connection with the possibility to apply new outcome measures, such as MRI and biomarkers, which can yield important advances in the use of Condrosulf(®) as well as the development of new drugs with different structures useful in particular for the treatment of inflammatory symptoms and able to retard the progression of arthritis.

Osteoarthritis: The Challenge of Establishing a Personalised Treatment

The symposium, co-chaired by Prof Johanne Martel-Pelletier and Prof Antonello Pietrangelo, opened with a discussion of metabolic syndrome-associated osteoarthritis (OA) and a brief overview of treatment options by Prof Francis Berenbaum. Prof Jean-Pierre Pelletier then discussed the use of symptomatic slow-acting drugs for OA (SYSADOA) for knee OA within the context of the new European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommendations. Finally, Dr Burkhard Leeb concluded the session by discussing the indications, contraindications, and side-effect management of diacerein.

Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study

The purpose of this study is to estimate the risk of nonfatal acute myocardial infarction (AMI) associated with traditional NSAIDs (tNSAIDs), non-narcotic analgesics (paracetamol and metamizole), and symptomatic slow-acting drugs in osteoarthritis (SYSADOAs) overall and in different subgroups of patients. We performed a nested case-control study using a Primary Care Database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria), over the study period, 2001-2007. We included patients aged 40-90 years, with nonfatal AMI and randomly selected controls matched for age, sex and calendar year. Exposure to drugs was assessed within a 30-day window before the index date. We did not find an association with nonfatal AMI in patients at low-intermediate background cardiovascular risk (odds ratio = 0.92; 95% confidence interval: 0.76-1.12), whereas there was a moderate significant association among those at high risk (1.28; 1.06-1.54) or when tNSAIDs were used for longer than 365 days (1.43; 1.12-1.82). The greatest risk occurred when these two conditions were combined (1.80; 1.26-2.58). The risk varied across individual tNSAIDs, with ibuprofen (0.95; 0.78-1.16) in the lower and aceclofenac (1.59; 1.15-2.19) in the upper part of the range. Low-dose aspirin did not modify the risk profile showed by any of the individual tNSAIDs examined. Paracetamol (0.84; 0.74-0.95), metamizole (1.06; 0.87-1.29) and SYSADOAs (0.68; 0.47-0.99) were not associated with an increased risk overall or in any subgroup of patients. The risk of nonfatal AMI varied with individual tNSAIDs, duration of treatment and background cardiovascular risk. Paracetamol, metamizole and SYSADOAs did not increase the risk in any of the conditions examined.

Estado actual del tratamiento de la artrosis

Osteoarthritis is the most frequent cause of joint pain and it is estimated that it is the most common cause of incapacity and adults. The objectives of the treatment are relief of symptoms, maintain or improve joint mobility, limit physical dysfunction and improve quality of life. The patient's should receive a personalized treatment plan that includes education, plan of approach for exercise and joint rest, control of obesity, reduction of adverse mechanical factors (for example, the use of appropriate shoes) and to consider aids for walking and other technical aids. The self-care programs and other psychosocial interventions, manual therapies, thermal agents, TENS or tai-chi may be useful in some patients. The pharmacological treatment is based on the combined use of analgesics, NSAIDs, local infiltrations or topical medication. Paracetamol with or without tramadol is the first step of the treatment although the NSAIDs are more effective. In some cases, the chronic use of opiates may be justified. Symptomatic slow-acting drugs for osteoarthritis (SYSADOA) have limited efficacy. If these measures fail, performing an arthroscopy, osteotomy or prosthetic replacement of the joint may be necessary.

SAT0321 Use of Drug Combinations in Patients with Osteoarthritis: a Population-Based Cohort Study.

BackgroundPatients with osteoarthritis (OA) use different drugs in search for relief, with potential impact on both safety and costs. There is a scarcity of data on drug utilization in these...

AB0966 In vitro effects of cuivramine and glucosamine sulfate on the IL-1β stimulated C-20/A4 chondrocyte cell line, a comparative study

BackgroundThe pathogenesis of primary osteoarthritis involves an imbalance between anabolic and catabolic pathways in chondrocytes where the reactive oxygen species (ROS) could play a central role. The expression of matrix...

SAT0338 Tolerance and efficacy of a new formulation of diacerein: Results of a multicenter, randomized, double-blind, controlled trial in patients with knee osteoarthritis

BackgroundDiacerein [Symptomatic Slow-Acting Drugs in Osteoarthritis (SYSASOA)], has demonstrated its efficacy in patients with hip or knee osteoarthritis in several randomized placebo controlled clinical trials. The efficacy/safety balance of diacerein...

PC0005 Evaluating the public health impact of symptomatic slow-acting drugs for osteoarthritis in primary care: The pegase cohort

BackgroundSymptomatic slow-acting drugs for osteoarthritis (SySADOA) are medications used to alleviate long-term manifestations of osteoarthritis (OA). They differ pharmacologically from NSAIDs with little or no effect on the enzyme cyclooxygenase.It...

AB0067 Chondroitin sulfate regulates two anti-angiogenic factors in human osteoarthritic synovial fibroblasts

BackgroundThe symptomatic slow acting drug for osteoarthritis (SYSADOA), chondroitin sulfate, has attracted much interest as a biological agent for its use in the effective relief of disease symptoms. This is...

Use of drug combinations in patients with osteoarthritis: a population-based cohort study

Background Patients with osteoarthritis (OA) use different drugs in search for relief, with potential impact on both safety and costs. There is a scarcity of data on drug utilization in these patients. Objectives We used a large database including primary care medical records and pharmacy invoice data to explore use of the following drugs in OA patients in the period 2006-2010: non-steroidal anti-inflammatory drugs (NSAIDs), Symptomatic Slow Acting Drugs for OA (SYSADOA), COX-2 inhibitors (COX2i), opioids, and other analgesics (paracetamol and metamizol). Methods SIDIAP contains anonymised clinical information from primary care records and pharmacy invoice data for a representative >5 million people in Catalonia (North-East Spain). We screened this database (www.sidiap.org) to identify those aged 40 years or older with a new diagnosis of OA using ICD-10 codes. Among these, we ascertained prevalence of use of oral NSAIDs, COX2i, SYSADOA, opioids, and analgesics (all alone and in combination) in the period 2006-2011. We estimated prevalence (and 99% Confidence Intervals) of use of these drugs and their combinations, and the proportion of occasional (MPR≥25%) and regular (MPR≥50%) users for each of them. Results We identified 281,356 patients with an incident clinical diagnosis of OA. Among these, 128,314(45.6%) were treated with 3 or more drugs, and 57,835(20.6%) with none of the drugs studied. The 3 most common combinations of two drugs were: oral NSAID+analgesic (12.2%); 2.topical NSAID+analgesic (2.5%); and oral NSAID+SYSADOA (1.8%). Besides, 34,672(12.3%) patients received only 1 drug, the 3 most common being, in descending order: oral NSAID, analgesics, and SYSADOA. The proportions of occasional and regular users were highest for SYSADOA (24.5% occasional and 6.9% regular users), and lowest for opioids (7.3% occasional and 1.9% regular users). Conclusions About 75% of OA patients are treated with at least 2 drugs, and above half of them with 3 or more. However, compliance with these drugs is very low, and hence both clinical benefits and safety issues are difficult to predict using data from clinical trials, where compliance is high. These data are of interest for health care provision and clinical management of patients with OA. Disclosure of Interest D. Prieto-Alhambra Grant/research support from: Unrestricted grant from BIOIBERICA SA, N. Wilson: None Declared

Condroitín sulfato reduce la pérdida del cartílago articular y las lesiones en el hueso subcondral

The management of osteoarthritis (OA) is a major challenge. Most published recommendations aim to control OA symptoms, i.e. reduce pain and improve joint function. However, the main aim of the treatment of OA is to halt or delay disease progression. In line with this aim, the various therapies should help to preserve articular structure by controlling cartilage degradation, synovitis and sclerosis of subchondral bone, the three tissues involved in the physiopathology of OA. This aim should be kept in mind both in the development of future treatments and in currently available drugs. Chondroitin sulfate is a symptomatic slow-acting drug for osteoarthritis (SYSADOA). There is, however, an increasing body of evidence showing the effect of disease modifying osteoarthritis drugs (DMOAD), i.e. slow-acting drugs for OA able to modify structure. This review aims to synthesize the information on the protective effect of chondroitin sulfate on cartilage, as well as its ability to preserve the structure of subchondral bone.

Secretome analysis of chondroitin sulfate-treated chondrocytes reveals anti-angiogenic, anti-inflammatory and anti-catabolic properties

IntroductionChondroitin sulfate (CS) is a symptomatic slow-acting drug for osteoarthritis (OA) widely used in the clinic. The aim of this work is to find proteins whose secretion from cartilage cells under proinflammatory stimuli (IL-1β) is regulated by CS, employing a novel quantitative proteomic approach.MethodsHuman articular chondrocytes released from three normal cartilages were grown in SILAC medium. When complete incorporation of the heavy isotope was achieved, chondrocytes were stimulated with IL-1β 5 ng/ml with or without CS pretreatment (200 µg/ml). Forty-eight hours later, chondrocyte secretomes were analyzed by nano-scale liquid chromatography-mass spectrometry. Real-time PCR, western blot and immunohistochemistry analyses were employed to confirm some of the results.ResultsWe could identify 75 different proteins in the secretome of human articular chondrocytes. Eighteen of these were modulated by CS with statistical significance (six increased and 12 decreased). In normal chondrocytes stimulated with IL-1β, CS reduces inflammation directly by decreasing the presence of several complement components (CFAB, C1S, CO3, and C1R) and also indirectly by increasing proteins such as TNFα-induced protein (TSG6). TSG6 overexpression correlates with a decrease in pro-matrix metalloproteinase activation (observed in MMP1 and MMP3 levels). Finally, we observed a strong CS-dependent increase of an angiogenesis inhibitor, thrombospondin-1.ConclusionWe have generated a quantitative profile of chondrocyte extracellular protein changes driven by CS in the presence of IL-1β. We have also provided novel evidences of its anti-angiogenic, anti-inflammatory, and anti-catabolic properties. Demonstration of the anti-angiogenic action of CS might provide a novel therapeutic approach for OA targeting.