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Y Yazici, T E McAlindon, R Fleischmann, A Gibofsky, N E Lane, A J Kivitz, N Skrepnik, E Armas, C J Swearingen, A DiFrancesco, J R S Tambiah, J Hood, M C Hochberg
OBJECTIVE: To assess the safety, pharmacokinetics, and exploratory efficacy of SM04690, a novel Wnt pathway inhibitor, as a potential disease modifying treatment for knee osteoarthritis (OA). DESIGN: Subjects with Kellgren-Lawrence grade 2-3 knee OA were randomized in successive dose-escalation cohorts to receive a knee intra-articular (IA) injection with 0.03, 0.07, or 0.23 mg SM04690, or placebo (PBO) (4:1 ratio). Safety, pharmacokinetics, efficacy (WOMAC Total/Function/Pain, Pain VAS, Physician Global Assessment [MDGA], and OMERACT-OARSI Response), OA-related biomarker (P1NP, ß-CTX, and cartilage oligomeric matrix protein [COMP]), and radiographic/imaging data were collected at baseline and during 24-week follow-up...
July 13, 2017: Osteoarthritis and Cartilage
Robert J Buck, Marie-Pierre Hellio Le Graverand, Wolfgang Wirth, Felix Eckstein
INTRODUCTION: In knee osteoarthritis, local increase and decrease in cartilage thickness has been observed over short time intervals. Hence, averaging cartilage change across large regions may not capture the complexity of structural alterations in disease progression. This study aims to examine the relative performance of different metrics of cartilage thickness change for different clinical studies scenarios. MATERIALS AND METHODS: Metrics for assessing cartilage thickness change were characterized by conventional measures of change versus absolute values (the magnitude) of change, and by different methods of summarizing change over (sub-) regions...
May 30, 2017: Seminars in Arthritis and Rheumatism
Weiyu Han, Shicai Fan, Xiaochun Bai, Changhai Ding
The articular cartilage and subchondral bone may have potential crosstalk in the development and progression of osteoarthritis (OA). Strontium ranelate (SrR) has the ability to dissociate the bone remodeling process and to change the balance between bone resorption and bone formation. Its effect on subchondral bone makes it a potential disease- modifying osteoarthritis drug (DMOAD) in the treatment of OA. The aim of the current review is to summarize up-to-date pharmacological and clinical data of SrR for OA treatment...
March 2017: Expert Opinion on Investigational Drugs
Shuang Zheng, David J Hunter, Jianhua Xu, Changhai Ding
Osteoarthritis (OA) is a multifactorial chronic joint disease, and so far, there are no approved disease-modifying anti-OA drugs (DMOADs). There is an urgent need to develop therapies for different phenotypes of OA. Monoclonal antibodies (mAb) may slow structural progression, control inflammation and relieve pain, and thus have the potential to be DMOADs. Areas covered: In this review, the authors searched the literature on PubMed, EMBASE and the Cochrane Library using keywords, including mAbs, biological agents, OA and osteoarthritis, electronically up to May 2016...
December 2016: Expert Opinion on Biological Therapy
Ali Mobasheri, Mark Batt
INTRODUCTION: Osteoarthritis (OA) is one of the most common forms of arthritis. There is accumulating evidence to suggest that OA is an inflammatory disease of the entire synovial joint and has multiple phenotypes. This presents the OA research community with new challenges and opportunities. The main challenge is to understand the root cause of the disease and identify differences and similarities between OA phenotypes. The key opportunity is the possibility of developing personalized and individualized prevention and treatment strategies for OA patients with different phenotypes of the disease...
December 2016: Annals of Physical and Rehabilitation Medicine
M A Karsdal, M Michaelis, C Ladel, A S Siebuhr, A R Bihlet, J R Andersen, H Guehring, C Christiansen, A C Bay-Jensen, V B Kraus
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying treatments for OA. Insights gleaned from these attempts suggest that these failures arose from unrealistic hypotheses, sub-optimal selection of patient populations or drug dose, and/or inadequate sensitivity of the trial endpoints...
December 2016: Osteoarthritis and Cartilage
Anthony Robin Poole
There has been important recent progress in our understanding of the molecular pathology of osteoarthritis (OA) and how it might be treated. New technologies have been developed and others refined to identify patients for recruitment in clinical trials who exhibit measurable progression. Combined with the ability to determine more effectively short-term efficacy of treatment, significant obstacles are being removed that have negated or led to the failure of earlier trials. The future for disease-modifying osteoarthritis drug (DMOAD) development and more effective pain control is therefore much more encouraging...
2016: Swiss Medical Weekly
Veronica Mantovani, Francesca Maccari, Nicola Volpi
Osteoarthritis is a disabling affliction expected to increase in the coming decades, and disease- modifying osteoarthritis drugs (DMOADs) would be highly desirable adjuncts to symptomatic relief and structure reconstruction as they may delay the disease process. Chondroitin sulfate and glucosamine have been observed to exert beneficial effects on the metabolism of various cells involved in osteoarthritis as well as in animal models and clinical trials. Clinical trials have reported beneficial effects of both these biological agents, alone or in combination, on pain and functions as well as their structure-modifying capacity reported and analyzed in recent meta-analyses...
2016: Current Medicinal Chemistry
K Marhardt, N Muurahainen
No abstract text is available yet for this article.
November 2015: Drug Research
Frank Buttgereit, Gerd-Rüdiger Burmester, Johannes W J Bijlsma
After the successful treatment of inflammatory rheumatic diseases with targeted therapies, the greatest challenge in rheumatic diseases remains the treatment of the most common chronic joint disorder, osteoarthritis. Osteoarthritis (OA) commonly affects the knee, with an age-standardised and sex-standardised incidence of 240 per 100.000 person-years. With the aging of the population and rising obesity throughout the world, it is anticipated that the burden of OA will increase and become a major problem for health systems globally...
2015: RMD Open
Johannes T H Nielen, Frank de Vries, Pieter C Dagnelie, Bart J F van den Bemt, Pieter J Emans, Arief Lalmohamed, Anthonius de Boer, Annelies Boonen
AIMS: Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs...
February 2016: British Journal of Clinical Pharmacology
Janina S Ried, Klaus Flechsenhar, Eckart Bartnik, Daniel Crowther, Axel Dietrich, Felix Eckstein
OBJECTIVE: To evaluate the extent to which the current designs of clinical trials in knee osteoarthritis (OA) permit detection of a therapeutic effect of disease-modifying OA drugs (DMOADs) on the incidence of knee replacement, and to provide estimates of the required sample sizes. METHODS: We selected distinct subcohorts of the Osteoarthritis Initiative (OAI), based on available information on eligibility criteria for clinical knee OA trials ( and additional subcohorts stratified for age, sex, and the severity of radiographic OA...
December 2015: Arthritis & Rheumatology
Felix Eckstein, Marie-Pierre Hellio Le Graverand
Osteoarthritis (OA) is the most common disease of synovial joints and currently lacks treatment options that modify structural pathology. Imaging is ideally suited for directly evaluating efficacy of disease-modifying OA drugs (DMOADs) in clinical trials, with plain radiography and MRI being most often applied. The current article is based on a debate held on April 26, 2014, at the World Congress of Osteoarthritis: The authors were invited to contrast strengths and limitations of both methods, highlighting scientific evidence on reliability, construct-validity, and correlations with clinical outcome, and comparing their sensitivity to change in knee OA and sensitivity to DMOAD treatment...
December 2015: Seminars in Arthritis and Rheumatism
Ying-Ying Leung, Julian Thumboo, Bak Siew Wong, Ben Haaland, Balram Chowbay, Bibhas Chakraborty, Mann Hong Tan, Virginia B Kraus
BACKGROUND: Despite the high prevalence and global impact of knee osteoarthritis (KOA), current treatments are palliative. No disease modifying anti-osteoarthritic drug (DMOAD) has been approved. We recently demonstrated significant involvement of uric acid and activation of the innate immune response in osteoarthritis (OA) pathology and progression, suggesting that traditional gout therapy may be beneficial for OA. We therefore assess colchicine, an existing commercially available agent for gout, for a new therapeutic application in KOA...
April 30, 2015: Trials
Bibhu R Das, Arnab Roy, Faisal R Khan
Osteoarthritis (OA) is a major public concern as it is one of the leading causes of morbidity and lays a huge medical and economic burden on health resources. Early detection of OA has been a clinical challenge as early signs of joint inflammation are often not evidently identifiable on routine radiographic images. This presents a dire unmet medical need for a biomarker, which could detect early signs of joint inflammation much before irreversible joint damage and radiographic changes set in. Besides, the treatment of OA has remained mainly symptomatic...
January 2015: Perspectives in Clinical Research
Amy L McNulty, Holly A Leddy, Wolfgang Liedtke, Farshid Guilak
Biomechanical factors play a critical role in regulating the physiology as well as the pathology of multiple joint tissues and have been implicated in the pathogenesis of osteoarthritis. Therefore, the mechanisms by which cells sense and respond to mechanical signals may provide novel targets for the development of disease-modifying osteoarthritis drugs (DMOADs). Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable cation channel that serves as a sensor of mechanical or osmotic signals in several musculoskeletal tissues, including cartilage, bone, and synovium...
April 2015: Naunyn-Schmiedeberg's Archives of Pharmacology
Rodolfo Gómez, Amanda Villalvilla, Raquel Largo, Oreste Gualillo, Gabriel Herrero-Beaumont
Osteoarthritis (OA), the most common rheumatic disease, is characterized by joint-space narrowing due to progressive cartilage degradation and alterations in subchondral bone and the synovial membrane. These articular disturbances can have severe consequences, including pain, disability and loss of joint architectural integrity. Although the aetiology of OA is not understood, chondrocyte-mediated inflammatory responses triggered by the activation of innate immune receptors by damage-associated molecules are thought to be involved...
March 2015: Nature Reviews. Rheumatology
S Maschek, W Wirth, C Ladel, M-P Hellio Le Graverand, F Eckstein
OBJECTIVE: To compare the rate and sensitivity to change of quantitative cartilage thickness change with magnetic resonance imaging (MRI) across specific radiographic strata of knee osteoarthritis (KOA) from central expert readings of the Osteoarthritis Initiative (OAI). Specifically, we explored whether Kellgren Lawrence grade (KLG) 2 knees with radiographic joint space narrowing (JSN) displayed greater cartilage loss than those without JSN, and whether knees with medial JSN grade2 had greater loss than those with grade1...
October 2014: Osteoarthritis and Cartilage
S Cotofana, O Benichou, W Hitzl, W Wirth, F Eckstein
OBJECTIVE: Anti-catabolic disease modifying drugs (DMOADs) aim to reduce cartilage loss in knee osteoarthritis (KOA). Testing such drugs in clinical trials requires sufficient rates of loss in the study participants to occur, preferably at a mild disease stage where cartilage can be preserved. Here we analyze a "progression" model in mild radiographic KOA (RKOA), based on contra-lateral radiographic status. METHODS: We studied 837 participants (62.4 ± 9 yrs; 30 ± 4...
December 2014: Osteoarthritis and Cartilage
Nicola Volpi
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...
2014: Current Medicinal Chemistry
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