Summary Objective To develop concise, up-to-date, patient-focused, evidence-based, expert consensus guidelines for the management of knee osteoarthritis (OA), intended to inform patients, physicians, ...and allied healthcare professionals worldwide. Method Thirteen experts from relevant medical disciplines (primary care, rheumatology, orthopedics, physical therapy, physical medicine and rehabilitation, and evidence-based medicine), three continents and ten countries (USA, UK, France, Netherlands, Belgium, Sweden, Denmark, Australia, Japan, and Canada) and a patient representative comprised the Osteoarthritis Guidelines Development Group (OAGDG). Based on previous OA guidelines and a systematic review of the OA literature, 29 treatment modalities were considered for recommendation. Evidence published subsequent to the 2010 OARSI guidelines was based on a systematic review conducted by the OA Research Society International (OARSI) evidence team at Tufts Medical Center, Boston, USA. Medline, EMBASE, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials were initially searched in first quarter 2012 and last searched in March 2013. Included evidence was assessed for quality using Assessment of Multiple Systematic Reviews (AMSTAR) criteria, and published criticism of included evidence was also considered. To provide recommendations for individuals with a range of health profiles and OA burden, treatment recommendations were stratified into four clinical sub-phenotypes. Consensus recommendations were produced using the RAND/UCLA Appropriateness Method and Delphi voting process. Treatments were recommended as Appropriate, Uncertain, or Not Appropriate, for each of four clinical sub-phenotypes and accompanied by 1–10 risk and benefit scores. Results Appropriate treatment modalities for all individuals with knee OA included biomechanical interventions, intra-articular corticosteroids, exercise (land-based and water-based), self-management and education, strength training, and weight management. Treatments appropriate for specific clinical sub-phenotypes included acetaminophen (paracetamol), balneotherapy, capsaicin, cane (walking stick), duloxetine, oral non-steroidal anti-inflammatory drugs (NSAIDs; COX-2 selective and non-selective), and topical NSAIDs. Treatments of uncertain appropriateness for specific clinical sub-phenotypes included acupuncture, avocado soybean unsaponfiables, chondroitin, crutches, diacerein, glucosamine, intra-articular hyaluronic acid, opioids (oral and transdermal), rosehip, transcutaneous electrical nerve stimulation, and ultrasound. Treatments voted not appropriate included risedronate and electrotherapy (neuromuscular electrical stimulation). Conclusion These evidence-based consensus recommendations provide guidance to patients and practitioners on treatments applicable to all individuals with knee OA, as well as therapies that can be considered according to individualized patient needs and preferences.
Abstract The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) published a treatment algorithm for the management of knee osteoarthritis (OA) in 2014, ...which provides practical guidance for the prioritization of interventions. Further analysis of real-world data for OA provides additional evidence in support of pharmacological interventions, in terms of management of OA pain and function, avoidance of adverse events, disease-modifying effects and long-term outcomes, e.g., delay of total joint replacement surgery, and pharmacoeconomic factors such as reduction in healthcare resource utilization. This article provides an updated assessment of the literature for selected interventions in OA, focusing on real-life data, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA in primary care clinical practice, in support of the clinicians’ individualized assessment of the patient. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) is recommended, for which high-quality evidence is provided only for the prescription formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs without the systemic safety concerns. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk:benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability.
Osteoarthritis (OA) is a degenerative disorder of the joint, principally occurring during aging, and characterized by a focal degradation of cartilage. It is the most prevalent rheumatic disease in ...industrialized countries and represents the second cause of disability in France. However, the etiology of OA remains unclear. There is only one cell type found in cartilage, chondrocyte, which is responsible for its repair and the synthesis of the elements of the extra-cellular matrix. A dysfunction of these cells results in an imbalance between repair and degradation in cartilage, leading to its destruction.
Recently, a link between OA and metabolic syndrome (MetS) has been suggested, introducing a notion of metabolic OA, and a new vision of the disease. MetS is characterized by a cluster of factors (insulin resistance, hypertension, dyslipidemia, visceral obesity), although there is still no clear definition of it. During the 20th century, MetS dramatically increased with changes in population lifestyle, becoming a major health issue in industrialized countries. MetS concerns 10–30% of the worldwide population, but is prevalent in 59% of OA patients. Patients with both OA and MetS have more severe symptoms, occurring sooner than in the general population. Indeed, OA is generally a disease concerning the population over 65 years old, but with an associated MetS the target population is around 50 years old.
In this review, we will focus on common factors in OA and MetS, such as hypertension, obesity, dyslipidemia, mitochondrial dysfunction and hyperglycemia, linking one disease to the other.
•OA is the most common rheumatic disease in the world.•Adipokines levels are involved in development and progression of MetS as well as OA.•Mitochondrial dysfunctions are involved in OA and MetS development and progression.•Hyperglycemia leads to type 2 diabetes and to chondrocyte dysfunctions.•OA and MetS are linked in many ways implying to consider OA as a metabolic disorder.
We evaluated the ability of Coll2-1, a type II collagen peptide, to activate pro-inflammatory pathways in synovial cells and to induce arthritis in Lewis rats.
Human synoviocytes and chondrocytes ...from knee OA patients were cultured for 24 h with/without Coll2-1 and/or purified immunoglobulin G (AS0619) binding specifically this peptide, and/or CLI-095, a TLR-4 signaling inhibitor and/or apocynin and diphenyleneiodonium, Reactive oxygen species (ROS) production inhibitors. The Interleukin (IL)-8 and Vascular Endothelium Growth Factor (VEGF) expression, the IL-8 production, the IκB-α and p65 phosphorylation and ROS were evaluated. Coll2-1 peptide, bovine type II collagen (CIA), streptococcal cell wall (SCW) or saline solution were injected into Lewis rats. The Coll2-1 peptide was injected subcutaneously (SC; 20–200μg/100μl/animal) or intra-articularly (IA; 0.5–5μg/50μl/animal) and compared to CIA injected in SC (200μg/100μl/animal) and SCW in IA (5μg/50μl/animal). The animals were injected on day 0 and monitored for 28 days. Histological lesions assessment was performed using an arthritis score.
Coll2-1 peptide significantly increased IL-8 gene expression and production by synoviocytes. AS0619 and CLI-095 significantly decreased IL-8 expression. Coll2-1 induced p65 and IκBα phosphorylation and oxidative stress inhibitors decreased it. In human chondrocytes culture, Coll2-1 significantly increased MMP-3 and VEGF gene expression. In Lewis rats, CIA, SCW or Coll2-1 injection triggered arthritis. Like CIA or SCW, Coll2-1 induced synovitis, loss of cartilage proteoglycans, cartilage structure lesion and subchondral bone remodeling.
Coll2-1 activates synoviocytes to produce IL-8 and induces arthritis in rat. These findings suggest that neutralizing Coll2-1 could be a therapeutic approach of arthritis.
As one of the leading causes of disability in adults worldwide, its toll on patients and its economic burden for payers are substantial. The issue of change in OA management with the evolution of ...reimbursement schemes needs to be addressed.
To assess the impact of terminating the reimbursement of symptomatic slow-acting drugs in OA (SYSADOAs) in France in terms of volume and cost, from a healthcare payer perspective.
We obtained costs and volumes from French public national databases. We considered three exposure periods around cutoff dates according to decisions of decreased then terminated SYSADOA reimbursement. The periods included 19 345 (control), 20 066 (secondary), and 16 200 (primary) patients, respectively. Mean ages were 66.2 (±11.8), 65.3 (±11.6) and 64.6 (±11.5) years and about 70% were women. The volume of nonsteroidal anti-inflammatory drug (NSAID) deliveries estimated by defined daily doses (DDDs) decreased during the periods from 40.5 (±76.3) DDDs per patient in 2008 to 29.6 (±66.4) in 2015. The volume of analgesic deliveries increased slowly over the three periods, from 70.2 (±108.9) DDDs in 2008 to 76.9 (±123.1) in 2015 for all patients.
Our results did not show a measurable impact of terminating SYSADOA reimbursement on the delivery of NSAIDs and analgesics or on hospitalizations. However, neither do they allow for concluding that terminating SYSADOA reimbursement did not generate an increase in deliveries of non-reimbursed drugs, with their associated potential risks for public health.
Importance Physical therapy could be of interest to reduce disability of systemic sclerosis (SSc) patients. Objective To develop a physical therapy program for SSc and compare its efficacy with that ...of usual care. Design 12-month, parallel-group randomized controlled trial involving a modified Zelen design conducted between September 2005 and October 2011. Randomization was computer-generated with allocation concealment by fax to a central coordinating office. Investigators were not blinded, but participants in the control group were blinded to study hypothesis. Setting Four tertiary-care hospitals. Participants Patients were enrolled if they had a SSc diagnosis, a disability rating ≥ 0.5 on the Health Assessment Questionnaire Disability Index (HAQ-DI) or complaints of decreased mouth opening or limited range of motion of at least one joint. Interventions The experimental intervention was a 1-month personalized supervised physical therapy program provided by specifically trained care providers followed by home sessions. The comparator was usual care. Main outcomes and measures The primary outcome was the HAQ-DI score at 12 months. Results In the intention-to-treat analysis, as compared with the usual care group ( n = 108), patients in the physical therapy group ( n = 110) showed reduced disability at 1 month (HAQ-DI between-group difference (0.14; 95% confidence interval CI –0.24 to –0.03; P = 0.01), at 6 months the HAQDI scores between-group difference was –0.12; 95% CI, –0.23 to 0.01; P = 0.054. There was no statistically significant difference at 12 months (between-group difference at 12 months, –0.01; 95% CI –0.15 to 0.13; P = 0.86). There was a statistically significant difference for hand mobility and function, and pain, at 1 month but no difference at 12 months. Microstomia was lower in the physical therapy group at 1, 6 and 12 months (between-group difference at 12 months, 1.62; 95% CI 0.32 to 2.93; P = 0.01). No differences in adverse effects were observed between the two treatment groups. Conclusions and relevance A 1-month personalized supervised physical therapy program followed by home exercise sessions had short-term benefits for patients with SSc but did not reduce disability at 12 months. The program had long-term benefits for microstomia. Trial registration clinicaltrials.gov identifier NCT00318188.
PDF
