OA Trial Research Articles

Exercise Therapy Compared To Usual Care In People With Early-Stage Knee Oa: An Individual Patient Data Meta-Analysis From The Oa Trial Bank

Exercise Therapy Compared To Usual Care In People With Early-Stage Knee Oa: An Individual Patient Data Meta-Analysis From The Oa Trial Bank

New developments in osteoarthritis pharmacological therapies.

OA is an increasingly common, painful condition with complex aetiology and limited therapies. Approaches to expanding our therapeutic armamentarium have included repurposing existing therapies used for other rheumatological conditions, modifying existing OA preparations to enhance their benefits, and identifying new therapeutics. HCQ and low-dose MTX have been unsuccessful in improving hand OA pain or reducing structural progression. Anti-IL-6 and anti-GM-CSF also did not improve symptoms in hand OA trials, but IL-1 remains an intriguing target for large-joint OA, based on reduced joint replacements in a post hoc analysis from a large cardiovascular disease trial. The peripheral nociceptive pathway appears an attractive target, with mAbs to nerve growth factor and IA capsaicin demonstrating efficacy; tropomyosin receptor kinase A inhibitors are at an earlier stage of development. Limited evidence suggests pharmacological therapies can modify cartilage and bone structural progression, though evidence of synchronous symptom benefits are lacking.

Fully automated pipeline for quantitative MRI evaluation of knee articular cartilage for longitudinal OA trials

tfmkPurpose: Osteoarthritis longitudinal studies, whether related to the progression of the disease or the effect of new therapies, require very precise measurements of cartilage structure and in some cases of its composition. Meanwhile new tools are also needed to meet the growing needs for fast and reliable image analysis. The purpose of this study was to develop a fully automated reproducible tool for analysis of morphological and compositional quantitative MR parameters in well-defined cartilage sub-fields across the human knee.

No treatment effects of oral glucosamine for subgroups of knee and hip osteoarthritis patients; an individual patient data meta-analysis from the OA trial bank

No treatment effects of oral glucosamine for subgroups of knee and hip osteoarthritis patients; an individual patient data meta-analysis from the OA trial bank

Bone curvature changes can predict the impact of treatment on cartilage volume loss in knee osteoarthritis: data from a 2-year clinical trial.

Knee bone curvature assessed by MRI was associated with OA cartilage loss. A recent knee OA trial demonstrated the superiority of chondroitin sulfate over celecoxib (comparator) at reducing cartilage volume loss (CVL) in the medial compartment (condyle). The main objectives were to identify which baseline bone curvature regions of interest (BCROI) best associated with CVL and investigate whether baseline BCROI and 2-year change are correlated with the protective effect of chondroitin sulphate on CVL. This post hoc analysis of a clinical trial used the according-to-protocol population (chondroitin sulphate, n = 57; celecoxib, n = 63) baseline and 2-year MRI to assess bone curvature and CVL. Global optimum search identified the BCROI in the medial condyle using celecoxib as reference. Statistical analyses were performed with Pearson's correlation, Mann-Whitney U -test, Student's t -test and analysis of covariance. The BCROI including the medial posterior condyle and lateral central condyle was found to correlate best with medial condyle CVL at 2 years ( r = 0.33, P = 0.008). In patients with a baseline BCROI value less than the median (more flattened bone), chondroitin sulphate demonstrated a protective effect on CVL compared with celecoxib in the medial compartment (P = 0.037). In patients with 2-year BCROI changes greater than the median (greater severity of bone flattening), chondroitin sulphate protected against CVL in the medial compartment, condyle and central plateau (P ⩽ 0.030). This study is the first to demonstrate the feasibility and usefulness of bone curvature measurements to predict effectiveness of OA treatment on CVL. The results identify bone curvature as a potential novel biomarker for knee OA clinical trials.

Ability of a Urine Assay of Type II Collagen Cleavage by Collagenases to Detect Early Onset and Progression of Articular Cartilage Degeneration: Results from a Population-based Cohort Study.

To evaluate the association of a sandwich assay for cartilage collagenase-mediated degradation, the C2C human urine sandwich assay (IB-C2C-HUSA), with early and late knee cartilage pathology and with progression of cartilage damage. A population-based cohort with knee pain, age 40-79 years, was evaluated at baseline (n = 253) and after mean 3.3 years (n = 161). We evaluated the IB-C2C-HUSA and a related competitive inhibition assay (C2C). The C2C assay was applied to serum (sC2C) and urine (uC2C). Based on knee radiographs and magnetic resonance imaging (MRI), 3 subgroups [no cartilage pathology, preradiographic cartilage pathology, and radiographic osteoarthritis (ROA)] were evaluated cross-sectionally for association with biomarker levels. Longitudinally, we evaluated whether baseline assays predict subsequent progression of cartilage degeneration, defined by MRI cartilage loss. Cross-sectionally, statistically significant differences were seen in the 3 subgroups for IB-C2C-HUSA (p < 0.001), with the highest levels seen in ROA, and for sC2C (p = 0.023), while no differences were seen for uC2C (p = 0.501). Baseline IB-C2C-HUSA levels were higher in progressors vs nonprogressors (p = 0.003). In logistic regression analysis, only baseline IB-C2C-HUSA was associated with an increased risk of progression of cartilage damage (OR 1.78, 95% CI 1.03-3.09). The IB-C2C-HUSA degradation assay detects the generation of a pathology-related cartilage collagen peptide(s) that increase(s) with onset of degeneration of knee articular cartilage. The baseline values are associated with progression of cartilage degeneration over 3 subsequent years. This assay may have value in clinical OA trials. Further, it points to collagenase activity as a therapeutic target for controlling degeneration of articular cartilage.

Composite symptom outcome measures in OA trials: do they have greater sensitivity to change than single outcomes?

Composite symptom outcome measures in OA trials: do they have greater sensitivity to change than single outcomes?

The levels of the adipokines adipsin and leptin are associated with knee osteoarthritis progression as assessed by MRI and incidence of total knee replacement in symptomatic osteoarthritis patients: a post hoc analysis.

Limited studies have explored the association between adipokines and knee OA structural progression using quantitative MRI (qMRI), and very few have included total knee replacement (TKR) as a disease outcome. The objective of this study was to compare serum levels of five adipokines to cartilage volume loss (CVL) and investigate their predictive value for TKR. The according-to-protocol population (n = 138) of a knee OA trial was used. Serum levels of adipsin (complement factor D), leptin, adiponectin, resistin and serpin E1, and cartilage volume were determined at baseline and 24 months with specific ELISAs and qMRI, respectively. Study knee TKR incidence up to 4 years post-trial was also assessed. Greater baseline values of adipsin and leptin correlated with increased CVL in the global knee and medial femur (P ⩽ 0.032) and of adipsin in the lateral compartment and femur (P ⩽ 0.028). Adiponectin showed an inverse correlation in the medial compartment and femur (P ⩽ 0.027). Resistin and serpin E1 were not associated with CVL. Multivariate analyses revealed that patients in the highest tertile at baseline of adipsin presented a greater odds ratio of CVL in the lateral compartment and femur (⩾2.87; P ⩽ 0.011), and those in the highest tertile of leptin in the medial compartment (2.78; P = 0.038). Most clinically relevant, patients in the highest tertile of adipsin or leptin at baseline had significantly greater incidence of TKR (P = 0.027). Data demonstrate that both adipsin and leptin predict greater CVL over time in the lateral and medial compartment, respectively. Importantly, this study also demonstrates that higher baseline levels of adipsin or leptin are associated with higher incidence of TKR.

Effects of supplementation with branched chain amino acids and ornithine aspartate on plasma ammonia and central fatigue during exercise in healthy men.

Our previous studies showed only slight improvement in central fatigue, measured indirectly by psychomotor performance, after branched chain amino acids (BCAA) supplementation during various efforts in healthy men. It is hypothesised that hyperammonaemia resulting from amino acids metabolism may attenuate their beneficial effect on psychomotor performance; therefore, the L-ornithine L-aspartate (OA) as an ammonia decreasing agent was used. The aim of this study was to investigate the effectiveness of oral BCAA + OA supplementation to reduce plasma ammonia concentration and enhance psychomotor performance during exhaustive exercise in healthy men. Eleven endurance-trained men (mean age 32.6 ± 1.9 years) performed two sessions (separated by one week) of submaximal cycloergometer exercise for 90 minutes at 60% of maximal oxygen uptake followed by graded exercise until exhaustion with randomised, double-blind supplementation with a total of 16 g BCAA and 12 g OA (BCAA + OA trial) or flavoured water (placebo trial). Before exercise, during both efforts and after 20 minutes of recovery multiple choice reaction time (MCRT), perceived exertion, heart rate and oxygen uptake were measured and venous blood samples were taken for plasma leucine, valine, isoleucine, ornithine, aspartate, free tryptophan (fTRP), ammonia, lactate and glucose determination. After ingestion, during both efforts and after 20 minutes of recovery the plasma concentrations of all supplemented amino acids were significantly increased, while the fTRP/BCAA ratio decreased in the BCAA + OA trial more than in the placebo trial. At the end of graded exercise plasma fTRP was lower and MCRT shorter in BCAA + OA than in the placebo trial (p < 0.05). At the end of prolonged exercise the plasma ammonia concentration was higher in BCAA + OA than in placebo trial (p < 0.05). Decreases in plasma ammonia during recovery were significantly higher in BCAA + OA than in the placebo trial. Plasma ammonia positively correlated with the total plasma BCAA and MCRT only in the BCAA + OA trial. The fTRP/BCAA ratio positively correlated with MCRT only in the placebo trial. Supplementation with BCAA and OA is a useful way to improve MCRT during high-intensity exercise and accelerate the elimination of ammonia at the recovery stage after exercise in healthy young men.

The OA trial bank: meta-analysis of individual patient data show that patients with severe pain or with inflammatory signs detected by ultrasound especially benefit from intra-articular glucocorticoids for knee or hip OA

The OA trial bank: meta-analysis of individual patient data show that patients with severe pain or with inflammatory signs detected by ultrasound especially benefit from intra-articular glucocorticoids for knee or hip OA

AB0599 The oa trial bank: individual patient data meta-analysis of trials investigating the effectiveness of intra-articular corticosteroid injections in patients with knee or hip oa

BackgroundBased on small to moderate effect size of the wide range of symptomatic treatments in osteoarthritis (OA), and the heterogeneity of OA patients, treatment guidelines for OA have stressed the...

The OA trial bank: individual patient data meta-analysis of trials investigating the effectiveness of intra-articular corticosteroid injections in patients with knee or hip OA

s / Osteoarthritis and Cartilage 21 (2013) S63–S312 S259 activities as putting on their clothes. In addition, individuals with multiple co-morbidities had even more complex and challenging selfmanagement experiences, which resulted in family and friends taking on additional “work” to compensate. The multi-joint nature of OA and other co-morbidities further complicated self-management. Many participants described experiencing pain or stiffness in multiple joints at the same time as a result of OA. Additionally, several participants had other health conditions that affected their ability to participate in selfmanagement activities. Conclusions: These findings suggest that previous research on OA selfmanagement overlooks the everyday modifications patients already make to manage their disease prior to surgery, and additionally focuses solely on the individual patient, ignoring the social context of their lives. We found that self-management is not an individual activity but rather can involve the individual's spouse, children, friends and/or co-workers. Further, self-management is complicated by the multi-joint nature of OA and by comorbidities. Future approaches to self-management in OA need to consider these additional issues/aspects as well as the various psychosocial factors that may influence patients’ experiences. 498 THE OA TRIAL BANK: INDIVIDUAL PATIENT DATA META-ANALYSIS OF TRIALS INVESTIGATING THE EFFECTIVENESS OF INTRA-ARTICULAR CORTICOSTEROID INJECTIONS IN PATIENTS WITH KNEE OR HIP OA M. van Middelkoop y, K. Dziedzic z, M. Doherty x, W. Zhang x, J. Bijlsma k, T. McAlindon {, S. Lohmander , S.M. BiermaZeinstra y. y Erasmus MC Med. Univ., Rotterdam, The Netherlands; z Primary Care Sci. Keele Univ., Keele, United Kingdom; xUniv. of Nottingham, Nottingham, United Kingdom; kUniv. Med. Ctr. Utrecht, Utrecht, The Netherlands; { Tufts Univ., Boston, MA; # Lund Univ., Lund,

302 COMPARING MAGNETIC RESONANCE IMAGING-BASED DEFINITIONS OF KNEE OSTEOARTHRITIS TO X-RAY-BASED KELLGREN-LAWRENCE GRADE FOR PREDICTING DISEASE SEVERITY

304 – Table 1. Responder rates according to various definitions of response in a RCT in knee OA PP dataset F60027 group Hylan G F-20 group Global population Baseline pain score (0-100, mm) (sd) 68.6 (13.2) 67.5 (11.6) 68.1 (12.5) Mean change from baseline at week 24 (mm) (sd) -38.8 (24.7) -37.1 (25.4) -38.0 (25.0) N (%) of patients at PASS for pain at week 24 ≤32.3 mm 71 (59.7%) 78 (66.7%) 149 (63.1%) N (%) of patients achieving MCII(absolute) on pain at week 24≥ 19.9 mm 96 (80.7%) 88 (75.2%) 184 (78%) N (%) of patients achieving MCII (%) on pain at week 24 ≥40.8% improvement 83 (69.7%) 83 (70.9%) 166 (70.3%) OMERACT/OARSI response criteria 77 (64.7%) 79 (67.5%) 156 (66%) Baseline LFI score 13.6 (3.2) 13.2 (2.9) 13.4 (3.1) Mean LFI score change from baseline at week 24 -5.7 (3.8) -5.6 (4.0) -5.7 (3.9) non inferiority design. The main outcome was the Lequesne index score (LFI). The secondary outcome was global pain on a Visual Analog Scale (VAS). 236 patients were available in the main analysis (per protocol analysis, PP). Demographic and knee OA characteristics were identical to those usually reported in knee OA trials. Since no value of the PASS is validated for the LFI yet, the results on pain VAS were used to classify patients as responders or not using OMERACT/OARSI modified criteria, PASS and MCII (using absolute value or % of improvement). Results are reported as mean (sd) and number (%). Results: Table 1 below shows the response rates according to the different criteria. Rates of responders varied considerably: from 60 to 80% in each group and from 63% to 78% in the overall population (both treatment groups can be merged since non-inferiority was proven). The most liberal definition seems to be MCII (absolute), while the strictest appears to be PASS. Conclusions: Reporting clinical trial results at a patient level using response rates might be meaningful in knee OA. However this study clearly demonstrate that results significantly vary according to the response criterion used which is likely to lead to positive or negative results accordingly. More work is needed to help assessing the most clinically relevant response definition in knee OA. Acknowledgement: This work was possible thanks to a grant from Pierre Fabre Labs.