Patient Evaluation and OA Study Design: OARSI/Biomarker Qualification

Kraus, Virginia B.

doi:10.1007/s11420-011-9234-z

Cited by 3 publications

(3 citation statements)

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“…This is in part because there is no precedent. Furthermore, OA generally progresses slowly, and there are no current validated biomarkers for cartilage destruction (joint space narrowing, assessed on X-ray, is the only Food and Drug Administration approved end point in a clinical trial) ( 7 ) . Issues of toxicity, in a disease that is not life-threatening, can also make drug development problematic.…”

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confidence: 99%

The potential for dietary factors to prevent or treat osteoarthritis

et al. 2014

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Osteoarthritis (OA) is a degenerative joint disease for which there are no disease-modifying drugs. It is a leading cause of disability in the UK. Increasing age and obesity are both major risk factors for OA and the health and economic burden of this disease will increase in the future. Focusing on compounds from the habitual diet that may prevent the onset or slow the progression of OA is a strategy that has been under-investigated to date. An approach that relies on dietary modification is clearly attractive in terms of risk/benefit and more likely to be implementable at the population level. However, before undertaking a full clinical trial to examine potential efficacy, detailed molecular studies are required in order to optimise the design. This review focuses on potential dietary factors that may reduce the risk or progression of OA, including micronutrients, fatty acids, flavonoids and other phytochemicals. It therefore ignores data coming from classical inflammatory arthritides and nutraceuticals such as glucosamine and chondroitin. In conclusion, diet offers a route by which the health of the joint can be protected and OA incidence or progression decreased. In a chronic disease, with risk factors increasing in the population and with no pharmaceutical cure, an understanding of this will be crucial.Osteoarthritis: Diet: Cartilage: Bioactive: Polyphenol: Phytochemical: Flavonoid Osteoarthritis (OA) is a degenerative joint disease characterised by degradation of articular cartilage, thickening of subchondral bone and osteophyte formation. Incidence and prevalence of OA has been difficult to assess, in part because of heterogeneity in definitions of the disease. A recent meta-analysis suggested that overall prevalence of OA at different anatomical sites was 23·9 % (knee), 10·9 % (hip) and 43·3 % (hand), although only the prevalence of knee OA showed a gender difference between women and men (27·3 and 21 %, respectively)(1) . Osteoarthritis is a leading cause of disability in the UK. A recent survey (2) found 8·5 million people in the UK with OA, with 71 % of these in constant pain. There are no effective disease-modifying drugs to treat OA and drugs that relieve pain are often insufficient. Joint replacement is offered to patients at end-stage disease with 66 436 hip and 77 578 knee replacements due to OA performed in the UK in 2011 (3) . Two major risk factors for OA are increasing age (most affected patients are aged >45 years and the greatest morbidity is seen in patients aged >60 years) (4) and increasing obesity (5) . With changing demographics, OA is an increasing public health and economic burden. The economic costs of OA in the UK are largely unknown, but direct costs have been estimated at approximately £1 billion/year. With inclusion of indirect costs, estimates from the USA range up to £8 billion/ year (6) .*Corresponding author: I. M. Clark, fax 01603-592250, email i.clark@uea.ac.uk †These authors contributed equally to this review.Abbreviations: ADAMTS, a disintegrin and metalloproteina...

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confidence: 99%

The potential for dietary factors to prevent or treat osteoarthritis

et al. 2014

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“…They have been proposed to monitor drug efficacy [ 3 ]. Their use in clinical trial is highly recommended [ 25 ] for their qualification. The other challenge in OA is to find a cure that could not only reduce symptoms (i.e.…”

Section: Discussionmentioning

confidence: 99%

Effect of chondroitin sulfate on soluble biomarkers of osteoarthritis: a method to analyze and interpret the results from an open-label trial in unilateral knee osteoarthritis patients

Möller¹,

Gharbi²,

Serrano

et al. 2016

BMC Musculoskelet Disord

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BackgroundThe aim of this study was to investigate the effects of chondroitin sulfate (CS) on the serum levels of Coll2-1 in patients with knee OA.MethodsSeventy two patients with unilateral symptomatic knee OA were involved in a post-authorization open-label study evaluating CS (800 mg/day). The primary outcome was the % relative change in serum Coll2-1 (sColl2-1). The secondary outcomes were the evaluation of pain (VAS) and function (Lequesne’s Index). Responders and non-responders were classified according to OMERACT-OARSI recommendations. Finally, an original cut-off method was applied to categorize patients and interpret individual variations in serum levels of Coll2-1.ResultsPatients showed no difference in the sColl2-1 levels at baseline. When considering responders and non-responders from the ITT population, a significant difference was found for Coll2-1 at 3 months (p = 0.030) and 6 months (p = 0.038). A decrease in pain (VAS) and an improvement in function (LI) were recorded throughout the visits (p < 0.01). Considering an intra-batch cut-off of 21 %, CS decreased Coll2-1 serum levels between baseline and 1-month visit compared to the value of Coll2-1 before treatment (screening visit) which can be interpreted as a drastic reduction of the proportion of patients with an increase of Coll2-1 over 21 % (reduction from 13 to 3 %). It also consisted in a more important proportion of patients with a decrease in Coll2-1 (from 5 to 10 %).ConclusionThis study proposes a new approach for the analysis and the interpretation of the individual variation in biomarker levels and introduces the notion of metabolic responders.Trial registrationID ISRCTN63795830. The trial was retrospectively registered on 2 October, 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1268-4) contains supplementary material, which is available to authorized users.

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“…Until now, none of the existing biomarker has been considered as a surrogate biomarker. The clinical qualification of biomarkers is a prerequisite in order to better designed clinical trial and to develop efficient therapies (Karsdal et al, 2014 ; Kraus, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Soluble biomarkers development in osteoarthritis: from discovery to personalized medicine

et al. 2015

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Context: Specific soluble biomarkers could be a precious tool for diagnosis, prognosis and personalized management of osteoarthritic (OA) patients. Objective: To describe the path of soluble biomarker development from discovery to clinical qualification and regulatory adoption toward OA-related biomarker qualification. Methods and results: This review summarizes current guidance on the use of biomarkers in OA in clinical trials and their utility at five stages, including preclinical development and phase 1 to phase 4 trials. It also presents all the available regulatory requirements. Conclusions: The path through the adoption of a specific soluble biomarker for OA is steep but is worth the challenge due to the benefit that it can provide.

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Patient Evaluation and OA Study Design: OARSI/Biomarker Qualification

Cited by 3 publications

References 4 publications

The potential for dietary factors to prevent or treat osteoarthritis

The potential for dietary factors to prevent or treat osteoarthritis

Effect of chondroitin sulfate on soluble biomarkers of osteoarthritis: a method to analyze and interpret the results from an open-label trial in unilateral knee osteoarthritis patients

Soluble biomarkers development in osteoarthritis: from discovery to personalized medicine

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