This “Year in review” presents a selection of research themes and individual studies from the clinical osteoarthritis (OA) field (epidemiology and therapy) and includes noteworthy descriptive, ...analytical-observational, and intervention studies. The electronic database search for the review was conducted in Medline, Embase and medRxiv (15th April 2020 to 1st April 2021). Following study screening, the following OA-related themes emerged: COVID-19; disease burden; occupational risk; prediction models; cartilage loss and pain; stem cell treatments; novel pharmacotherapy trials; therapy for less well researched OA phenotypes; benefits and challenges of Individual Participant Data (IPD) meta-analyses; patient choice-balancing benefits and harms; OA and comorbidity; and inequalities in OA. Headline study findings included: a longitudinal cohort study demonstrating no evidence for a harmful effect of non-steroidal anti-inflammatory drugs (NSAIDs) in terms of COVID-19 related deaths; a Global Burden of Disease study reporting a 102% increase in crude incidence rate of OA in 2017 compared to 1990; a longitudinal study reporting cartilage thickness loss was associated with only a very small degree of worsening in pain over 2 years; an exploratory analysis of a non-OA randomised controlled trial (RCT) finding reduced risk of total joint replacement with an Interleukin -1β inhibitor (canakinumab); a significant relationship between cumulative disadvantage and clinical outcomes of pain and depression mediated by perceived discrimination in a secondary analysis from a RCT; worsening socioeconomic circumstances were associated with future arthritis diagnosis in an innovative natural experiment (with implications for unique research possibilities arising from the COVID-19 pandemic context).
A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical ...management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.
To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.
Double-blind Multicentre ...Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2-3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0-500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.
The adjusted mean change (95% CI) in WOMAC pain was -185.7 (-200.3 to -171.1) (50.1% decrease) with CS+GH and -186.8 (-201.7 to -171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of -40: -1.11 (-22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups.
CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.
NCT01425853.
Summary Objective In an effort to evolve semi-quantitative scoring methods based upon limitations identified in existing tools, integrating expert readers’ experience with all available scoring tools ...and the published data comparing the different scoring systems, we iteratively developed the magnetic resonance imaging (MRI) Osteoarthritis Knee Score (MOAKS). The purpose of this report is to describe the instrument and its reliability. Methods The MOAKS instrument refines the scoring of bone marrow lesions (BMLs) (providing regional delineation and scoring across regions), cartilage (sub-regional assessment), and refines the elements of meniscal morphology (adding meniscal hypertrophy, partial maceration and progressive partial maceration) scoring. After a training and calibration session two expert readers read MRIs of 20 knees separately. In addition, one reader re-read the same 20 MRIs 4 weeks later presented in random order to assess intra-rater reliability. The analyses presented here are for both intra- and inter-rater reliability (calculated using the linear weighted kappa and overall percent agreement). Results With the exception of inter-rater reliability for tibial cartilage area (kappa = 0.36) and tibial osteophytes (kappa = 0.49); and intra-rater reliability for tibial BML number of lesions (kappa = 0.54), Hoffa-synovitis (kappa = 0.42) all measures of reliability using kappa statistics were very good (0.61–0.8) or reached near-perfect agreement (0.81–1.0). Only intra-rater reliability for Hoffa-synovitis, and inter-rater reliability for tibial and patellar osteophytes showed overall percent agreement <75%. Conclusion MOAKS scoring shows very good to excellent reliability for the large majority of features assessed. Further iterative development and research will include assessment of its validation and responsiveness.
MRI provides unparalleled visualisation of all the anatomical structures involved in the osteoarthritis (OA) process. There is a need for reliable methods of quantifying abnormalities of these ...structures. The aim of this work was to assess the reliability of a novel MRI scoring system for evaluating OA of the knee and explore the validity of the bone marrow lesion (BML) scoring component of this new tool.
After review of the relevant literature, a collaborative group of rheumatologists and radiologists from centres in the UK and USA established preliminary anatomical divisions, items (necessarily broadly inclusive) and scaling for a novel semi-quantitative knee score. A series of iterative reliability exercises were performed to reduce the initial items, and the reliability of the resultant Boston-Leeds Osteoarthritis Knee Score (BLOKS) was examined. A further sample had both the BLOKS and WORMS (Whole Organ MRI Score) bone marrow lesion (BML) score performed to assess the construct validity (relation to knee pain) and longitudinal validity (prediction of cartilage loss) of each scoring method.
The BLOKS scoring method assesses nine intra-articular regions and contains eight items, including features of bone marrow lesions, cartilage, osteophytes, synovitis, effusions and ligaments. The scaling for each feature ranges from 0-3. The inter-reader reliability for the final BLOKS items ranged from 0.51 for meniscal extrusion up to 0.79 for meniscal tear. The reliability for other key features was 0.72 for BML grade, 0.72 for cartilage morphology, and 0.62 for synovitis. Maximal BML size on the BLOKS scale had a positive linear relation with visual analogue scale (VAS) pain, however the WORMS scale did not. Baseline BML was associated with cartilage loss on both BLOKS and WORMS scale. This association was stronger for BLOKS than WORMS.
We have designed a novel scoring system for MRI OA knee, BLOKS, that demonstrates good reliability. Preliminary inspection of the validity of one of the components of this new tool supports the validity of the BLOKS BML scoring method over an existing instrument. Further iterative development will include validation for use in both clinical trials and epidemiological studies.
Summary Objective Despite a growing body of Magnetic Resonance Imaging (MRI) literature in osteoarthritis (OA), there is little uniformity in its diagnostic application. We envisage in the first ...instance the definition requiring further validation and testing in the research setting before considering implementation/feasibility testing in the clinical setting. The objective of our research was to develop an MRI definition of structural OA. Methods We undertook a multistage process consisting of a number of different steps. The intent was to develop testable definitions of OA (knee, hip and/or hand) on MRI. This was an evidence driven approach with results of a systematic review provided to the group prior to a Delphi exercise. Each participant of the steering group was allowed to submit independently up to five propositions related to key aspects in MRI diagnosis of knee OA. The steering group then participated in a Delphi exercise to reach consensus on which propositions we would recommend for a definition of structural OA on MRI. For each round of voting, ≥60% votes led to include and ≤20% votes led to exclude a proposition. After developing the proposition one of the definitions developed was tested for its validity against radiographic OA in an extant database. Results For the systematic review we identified 25 studies which met all of our inclusion criteria and contained relevant diagnostic measure and performance data. At the completion of the Delphi voting exercise 11 propositions were accepted for definition of structural OA on MRI. We assessed the diagnostic performance of the tibiofemoral MRI definition against a radiographic reference standard. The diagnostic performance for individual features was: osteophyte C statistic = 0.61, for cartilage loss C statistic = 0.73, for bone marrow lesions C statistic = 0.72 and for meniscus tear in any region C statistic = 0.78. The overall composite model for these four features was a C statistic = 0.59. We detected good specificity (1) but less optimal sensitivity (0.46) likely due to detection of disease earlier on MRI. Conclusion We have developed MRI definition of knee OA that requires further formal testing with regards their diagnostic performance (especially in datasets of persons with early disease), before they are more widely used. Our current analysis suggests that further testing should focus on comparisons other than the radiograph, that may capture later stage disease and thus nullify the potential for detecting early disease that MRI may afford. The propositions are not to detract from, nor to discourage the use of traditional means of diagnosing OA.
Non-steroidal anti-inflammatory drugs (NSAIDs) represent a diverse class of drugs and are among the most commonly used analgesics for arthritic pain worldwide, though long-term use is associated with ...a spectrum of adverse effects. The introduction of cyclooxygenase-2-selective NSAIDs early in the last decade offered an alternative to traditional NSAIDs with similar efficacy and improved gastrointestinal tolerability; however, emerging concerns about cardiovascular safety resulted in the withdrawal of two agents (rofecoxib and valdecoxib) in the mid-2000s and, subsequently, in an overall reduction in NSAID use. It is now understood that all NSAIDs are associated with some varying degree of gastrointestinal and cardiovascular risk. Guidelines still recommend their use, but little is known of how patients use these agents. While strategies and guidelines aimed at reducing NSAID-associated complications exist, there is a need for evidence-based algorithms combining cardiovascular and gastrointestinal factors that can be used to aid treatment decisions at an individual patient level.
Summary Objective The Osteoarthritis Research Society International initiated a number of working groups to address a call from the US Food and Drug Administration (FDA) on updating draft guidance on ...conduct of osteoarthritis (OA) clinical trials. The development of disease-modifying osteoarthritis drugs (DMOADs) remains challenging. The Assessment of Structural Change (ASC) Working Group aimed to provide a state-of-the-art critical update on imaging tools for OA clinical trials. Methods The Group focussed on the performance metrics of conventional radiographs (CR) and magnetic resonance imaging (MRI), performing systematic literature reviews for these modalities. After acquiring these reviews, summary and research recommendations were developed through a consensus process. Results For CR, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness of metric measurement of joint space width (JSW). Trials off at least 1 and probably 2 years duration will be required. Although there is much less evidence for hip JSW, it may provide greater responsiveness than knee JSW. For MRI cartilage morphometry in knee OA, there is some evidence for construct and predictive validity, with good evidence for reliability and responsiveness. The responsiveness of semi-quantitative MRI assessment of cartilage morphology, bone marrow lesions and synovitis was also good in knee OA. Conclusions Radiographic JSW is still a recommended option for trials of structure modification, with the understanding that the construct represents a number of pathologies and trial duration may be long. MRI is now recommended for clinical trials in terms of cartilage morphology assessment. It is important to study all the joint tissues of the OA joint and the literature is growing on MRI quantification (and its responsiveness) of non-cartilage features. The research recommendations provided will focus researchers on important issues such as determining how structural change within the relatively short duration of a trial reflects long-term change in patient-centred outcomes.
Growing evidence from epidemiological studies suggests that osteoarthritis (OA) is linked to atheromatous vascular disease. This hypothesis article proposes that OA, or at least OA structural ...progression, may be an atheromatous vascular disease of subchondral bone. Further epidemiological studies, imaging investigations of relevant blood vessels, and trials of the effects of statins on the prevention and treatment of OA are needed to examine this hypothesis.
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