ArthroLab Inc.

Montréal, Canada

ArthroLab Inc.

Montréal, Canada
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Martel-Pelletier J.,University of Montréal | Raynauld J.-P.,University of Montréal | Mineau F.,University of Montréal | Abram F.,ArthroLab Inc | And 3 more authors.
Arthritis Research and Therapy | Year: 2017

Background: There is an obvious need to identify biomarkers that could predict patient response to an osteoarthritis (OA) treatment. This post hoc study explored in a 2-year randomized controlled trial in patients with knee OA, the likelihood of some serum biomarkers to be associated with a better response to chondroitin sulfate in reducing cartilage volume loss. Methods: Eight biomarkers were studied: hyaluronic acid (HA), C reactive protein (CRP), adipsin, leptin, N-terminal propeptide of collagen IIα (PIIANP), C-terminal crosslinked telopeptide of type I collagen (CTX-1), matrix metalloproteinase-1 (MMP-1), and MMP-3. Patients were treated with chondroitin sulfate (1200 mg/day; n = 57) or celecoxib (200 mg/day; n = 62). Serum biomarkers were measured at baseline. The cartilage volume at baseline and its loss at 2 years were assessed by quantitative magnetic resonance imaging (MRI). Statistical analysis included analysis of covariance. Results: As data from the original MOSAIC trial showed no differences in cartilage volume and loss in the lateral compartment of the knee joint between the two treatment groups in any comparison, only the medial compartment and its subregions were studied. Stratification according to the median biomarker levels was used to discriminate treatment effect. In patients with levels of biomarkers of inflammation (HA, leptin and adipsin) lower than the median, those treated with chondroitin sulfate demonstrated less cartilage volume loss in the medial compartment, condyle, and plateau (p ≤ 0.047). In contrast, patients treated with chondroitin sulfate with higher levels of MMP-1 and MMP-3, biomarkers of cartilage catabolism, had less cartilage volume loss in the medial compartment, condyle, and plateau (p ≤ 0.050). Patients with higher levels of PIIANP and CTX-1, biomarkers related to collagen anabolism and bone catabolism, respectively, had reduced cartilage volume loss in the medial condyle (p ≤ 0.026) in the chondroitin sulfate group. Conclusion: This study is suggestive of a potentially greater response to chondroitin sulfate treatment on cartilage volume loss in patients with knee OA with low level of inflammation and/or greater level of cartilage catabolism. Trial registration: This is a post hoc study. Original trial registration: ClinicalTrials.gov, NCT01354145. Registered on 13 May 2011. © 2017 The Author(s).


PubMed | ArthroLab Inc., Groupe de recherche en Rhumatologie et Maladies Osseuses Inc., University of Montréal, StatSciences Inc. and Université de Sherbrooke
Type: Journal Article | Journal: Arthritis research & therapy | Year: 2016

In osteoarthritis (OA) treatment, although chondroitin sulfate (CS) was found in a number of studies using radiography to have a structure-modifying effect, to date CS use is still under debate. A clinical study using quantitative magnetic resonance imaging (qMRI) is therefore of the utmost importance. Here we report data from a 24-month, randomised, double-blind, double-dummy, controlled, comparative exploratory study of knee OA. The primary endpoint was to determine the effect of CS 1200mg/day versus celecoxib 200mg/day on cartilage volume loss (CVL) in the lateral compartment over time as measured by qMRI. Secondary endpoints included assessment of the OA structural changes and signs and symptoms of OA.qMRI was performed at baseline and at 12 and 24months. CVL, bone marrow lesion size, and synovial thickness were evaluated using qMRI. The primary statistical analysis was carried out on the modified intention-to-treat (mITT) population (n=138) using chi-squared, Fishers exact, Wilcoxon Mann-Whitney, and Students t tests and analysis of covariance. Analyses were also conducted on the according-to-protocol (ATP; n=120) population.In the adjusted mITT analysis, compared with celecoxib treatment, patients treated with CS had a significant reduced CVL at 24months in the medial compartment (celecoxib -8.1%4.2, CS -6.3%3.2; p=0.018) and medial condyle (-7.7%4.7, -5.5%3.9; p=0.008); no significant effect was seen in the lateral compartment. In the ATP population, CS reduced CVL in the medial compartment at 12months (celecoxib -5.6%3.0, CS -4.5%2.6; p=0.049) and 24months (celecoxib -8.4%4.2, CS -6.6%3.3; p=0.021), and in the medial condyle at 24months (celocoxib -8.1%4.7, CS -5.7%4.0; p=0.010). A trend towards a statistically reduced synovial thickness (celecoxib +17.9633.73mm, CS -0.6622.72mm; p=0.076) in the medial suprapatellar bursa was observed in CS patients. Both groups experienced a marked reduction in the incidence of patients with joint swelling/effusion and in symptoms over time. Data showed similar good safety profiles including cardiovascular adverse events for both drugs.This study demonstrated, for the first time in a 2-year randomised controlled trial using qMRI, the superiority of CS over celecoxib at reducing CVL in knee OA patients.ClinicalTrials.gov NCT01354145 . Registered 13 May 2011.


PubMed | ArthroLab Inc., University of Tasmania, Monash University and University of Montréal
Type: | Journal: BMC musculoskeletal disorders | Year: 2016

Change in knee cartilage volume is frequently used as a proxy for change in knee joint space width over time, but longitudinal data on these associations is limited. We aimed to determine whether change in knee cartilage volume, new or worsening meniscal extrusion (ME), meniscal tears and cartilage defects over 2.4 years correlated with change in joint space width (JSW) over 5 years in older community dwelling adults.Participants (n=153) had their right knee imaged using MR imaging and x-ray at baseline, and after 2.4 years (MRI) and 5 years (x-ray). Cartilage volume, cartilage defects, meniscal extrusions and meniscal tears were assessed on sagittal T1-weighted fat-suppressed MRI. JSW was assessed using standard fixed semi-flexed view radiographs, and scored on those with adequate alignment.Participants were 51-79 (mean 62) years old; 48% were female. Cartilage volume reduced over time (medial -134202 L/year, lateral -106165 L/year, p<0.001), as did JSW (medial -0.050.16 mm/year, lateral -0.120.24 mm/year, p<0.001). In multivariable analysis, the only consistent predictor of change in JSW was new or worsening ME (medial tibia R(2) 3.1%, p=0.031; medial femur R(2) 3.2%, p=0.024); change in cartilage volume correlated with change in JSW laterally (R(2) 4.8%, p=0.007) and was borderline medially (R(2) 2.2%, p=0.064); there was no association for meniscal tears or cartilage defects. The magnitude of these associations were similar albeit somewhat greater for ME in participants with radiographic OA (R(2) 6.2%, p=0.017).Change in ME and cartilage volume weakly predict change in JSW, but the vast majority of the variation remains unexplained. Since MRI examines cartilage directly while radiographs examine it indirectly, these results cast doubt on the validity of using JSW as a proxy measure of cartilage loss.


Martel-Pelletier J.,University of Montréal | Roubille C.,University of Montréal | Abram F.,ArthroLab Inc. | Hochberg M.C.,University of Maryland, Baltimore | And 4 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of conventional osteoarthritis (OA) pharmacological treatment and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes. Methods: Six hundred patients with knee OA were stratified based on whether or not they received for 24 consecutive months the OA conventional pharmacological treatment and/or Glu/CS. The main outcomes were knee structural changes, including the loss of joint space width (JSW) and of cartilage volume measured by quantitative MRI. Results: Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p<0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline. In the -analgesic/NSAIDs group, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial central plateau (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in participants with a higher severity of the disease (JSW≤median). In the +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of cartilage volume in the global plateau at 12 months (p=0.05), and in the central plateau at 24 months (p=0.05). These effects occurred in participants with less disease severity (JSW>median). By contrast, no significant reduction in JSW was found between all groups. Conclusions: In +analgesic/NSAIDs groups and -analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of cartilage volume over 24 months in subregions when assessed with qMRI, arguing for a disease-modifying effect of Glu/CS which could not be identified by X-rays. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism.


PubMed | University of Maryland, Baltimore, University of Montréal, StatSciences Inc. and ArthroLab Inc.
Type: Journal Article | Journal: Annals of the rheumatic diseases | Year: 2015

To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of conventional osteoarthritis (OA) pharmacological treatment and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes.Six hundred patients with knee OA were stratified based on whether or not they received for 24 consecutive months the OA conventional pharmacological treatment and/or Glu/CS. The main outcomes were knee structural changes, including the loss of joint space width (JSW) and of cartilage volume measured by quantitative MRI.Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p<0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline. In the -analgesic/NSAIDs group, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial central plateau (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in participants with a higher severity of the disease (JSWmedian). In the +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of cartilage volume in the global plateau at 12 months (p=0.05), and in the central plateau at 24 months (p=0.05). These effects occurred in participants with less disease severity (JSW>median). By contrast, no significant reduction in JSW was found between all groups.In +analgesic/NSAIDs groups and -analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of cartilage volume over 24 months in subregions when assessed with qMRI, arguing for a disease-modifying effect of Glu/CS which could not be identified by X-rays.


Pelletier J.-P.,University of Montréal | Roubille C.,University of Montréal | Raynauld J.-P.,University of Montréal | Abram F.,ArthroLab Inc. | And 3 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objective: To explore, using MRI, the disease-modifying effect of strontium ranelate (SrRan) treatment on cartilage volume loss (CVL) and bone marrow lesions (BMLs) in a subset of patients from a Phase III clinical trial in knee osteoarthritis (OA) (SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA)). Material and methods: Patients with primary symptomatic knee OA were randomised to receive either SrRan 1 g/day or 2 g/day or placebo (SEKOIA study). A subset of these patients had MRIs at baseline, 12, 24 and 36 months to assess the knee cartilage volume and BMLs. Missing values were imputed and the analyses were adjusted according to Bonferroni. Results: In this MRI subset, the distribution of patients (modified intention-to-treat; n=330) was 113, 105 and 112 for SrRan 1 g/day, 2 g/day and placebo, respectively. The groups were fairly balanced at baseline regarding demographics, clinical symptoms or imaging characteristics. Treatment with SrRan 2 g/day significantly decreased CVL on the plateaus at 12 (p=0.002) and 36 (p=0.003) months compared with placebo. Of note, in the medial femur and plateau, SrRan 1 g/day, but not SrRan 2 g/day, had more CVL than placebo. In patients with BML in the medial compartment at baseline, the BML score at 36 months was decreased in both treatment groups compared with the placebo group (SrRan 1 g/day, p=0.002 and SrRan 2 g/day p=0.001, respectively), and CVL significantly decreased with SrRan 2 g/day (p=0.023) in the plateau compared with placebo. Conclusions: In knee OA patients, treatment with SrRan 2 g/day was found to have beneficial effects on structural changes by significantly reducing CVL in the plateau and BML progression in the medial compartment. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism.


Raynauld J.-P.,University of Montréal | Pelletier J.-P.,University of Montréal | Abram F.,ArthroLab Inc. | Dodin P.,ArthroLab Inc. | And 2 more authors.
Arthritis Care and Research | Year: 2016

Objective: To examine the long-term (6-year) effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on cartilage volume in knee osteoarthritis (OA). Methods: Participants were from the Osteoarthritis Initiative progression and incidence subcohorts, had magnetic resonance imaging (MRI) of the target knee at baseline and 6 years, joint space width >1 mm, and data available on Glu/CS consumption (n = 1,593). They were stratified into 2 main groups based on whether or not they had medial meniscal extrusion at baseline. The group with meniscal extrusion (n = 429) was further stratified into subgroups based on exposure or no exposure to Glu/CS as follows: not exposed, 1 year, 2–3 years, and 4–6 years. Cartilage volume was assessed using fully automated quantitative MRI technology. Results: The Jonckheere-Terpstra trend test indicated that treatment with Glu/CS significantly reduced the cartilage volume loss in the global knee, associated with the lateral compartment. Multivariate analysis further demonstrated that the extent of the treatment's positive effect was related to exposure time to treatment, the protective effect at 6 years being significant in participants exposed to ≥2 years of treatment. Conclusion: These findings provide future support for the long-term protective structure-modifying effects of Glu/CS treatment in knee OA subjects. © 2016, American College of Rheumatology


Roubille C.,University of Montréal | Martel-Pelletier J.,University of Montréal | Raynauld J.-P.,University of Montréal | Abram F.,ArthroLab Inc | And 3 more authors.
Arthritis Research and Therapy | Year: 2015

Introduction: To evaluate the impact of meniscal extrusion (Ext) on knee osteoarthritis (OA) structural progression and on response to strontium ranelate (SrRan) treatment at 36months in patients with (+) or without (-) Ext, in association (+) or not (-) with bone marrow lesions (BML) in the medial compartment using X-rays (JSW) and qMRI. Methods: Patients from the qMRI substudy of the SEKOIA trial (SrRan 1g/day, n=113; SrRan 2g/day, n=105; placebo, n=112) were stratified based on whether meniscal extrusion and/or BML were present or not in the medial compartment. Results: In the placebo group, Ext+patients (n=26) had more JSW loss (p=0.002) and cartilage volume loss in the global knee (p=0.034) and plateau (p=0.005), and medial compartment (p=0.0005) than Ext- patients (n=86). Ext-BML+ patients (n=18) demonstrated more JSW loss (p=0.003) and cartilage volume loss in the global (p=0.020) and medial femur (p=0.055) than Ext-BML- (n=68). Compared to Ext+BML- (n=14), Ext+BML+ patients (n=12) had more cartilage volume loss in the global femur (p=0.028), with no change in JSW. The JSW loss (p=0.0004) and cartilage volume loss (global knee, p=0.033, medial compartment, p=0.0005) were greater when Ext and BML were simultaneously present in the medial compartment. SrRan 2g/day treatment demonstrated a reduction in OA knee structural progression with qMRI, but not with JSW, in which less cartilage volume loss was found in the plateaus (p=0.007) in Ext+patients (n=15), and in the medial plateau (p=0.046) in patients in whom both Ext and BML were co-localized. Conclusion: The findings of this study are novel and could have an impact on future strategies regarding clinical trials. Indeed, data first argue for a combined, cumulative effect of meniscal extrusion and bone marrow lesions on cartilage loss and, secondly, they showed that SrRan may have protective effects in OA patients with meniscal extrusion as well as when both meniscal extrusion and BML are co-localized. © Roubille et al.; licensee BioMed Central.


Wildi L.M.,University of Montréal | Martel-Pelletier J.,University of Montréal | Abram F.,ArthroLab Inc. | Moser T.,University of Montréal | And 2 more authors.
Arthritis Care and Research | Year: 2013

Objective To evaluate the impact of 2 magnetic resonance imaging (MRI) sequences on cartilage defect assessment in knee osteoarthritis (OA) patients and the sensitivity to change over time comparing cartilage defect (semiquantitative) with cartilage volume loss (quantitative) methods. Methods Gradient-echo (GRE) and intermediate-weighted fast spin-echo (IW-FSE) sequences were compared. Knee OA MRIs were from two 2-year studies (cohort 1, n = 55; cohort 2, n = 143). For both cohorts, a GRE sequence was used and patients in cohort 1 underwent an additional IW-FSE sequence. Cohort 2 included patients from a previous trial. Cartilage defects and cartilage volume were evaluated. Results The cartilage defect assessment provided consistently significantly higher scores in IW-FSE than in GRE sequences at baseline and 2 years. However, there was no difference in the change at 2 years between the sequences. The standardized response mean (SRM) for change did not show a difference between the 2 sequences, but was consistently higher (2-2.5-fold) for the quantitative method. The cartilage defect score change between the 2 treatment groups revealed a trend toward significance only in the medial tibial plateau, whereas the change in cartilage volume loss demonstrated a significant difference in the global knee, global femur, lateral femur, and lateral compartment. The SRMs for the treatment groups combined were markedly higher for cartilage volume loss than for the defect scoring by 4.3- to 6.0-fold. Conclusion The direct comparison between GRE and IW-FSE sequences did not suggest superior sensitivity to cartilage defect change over time of one sequence over the other. Interestingly, the quantitative cartilage volume assessment was more sensitive than the semiquantitative scoring in the detection of treatment effect on OA cartilage changes. Copyright © 2013 by the American College of Rheumatology.


PubMed | University of Montréal and ArthroLab Inc.
Type: Journal Article | Journal: Arthritis care & research | Year: 2016

To examine the long-term (6-year) effect of combined glucosamine (Glu) and chondroitin sulfate (CS) treatment on cartilage volume in knee osteoarthritis (OA).Participants were from the Osteoarthritis Initiative progression and incidence subcohorts, had magnetic resonance imaging (MRI) of the target knee at baseline and 6 years, joint space width >1 mm, and data available on Glu/CS consumption (n=1,593). They were stratified into 2 main groups based on whether or not they had medial meniscal extrusion at baseline. The group with meniscal extrusion (n=429) was further stratified into subgroups based on exposure or no exposure to Glu/CS as follows: not exposed, 1 year, 2-3 years, and 4-6 years. Cartilage volume was assessed using fully automated quantitative MRI technology.The Jonckheere-Terpstra trend test indicated that treatment with Glu/CS significantly reduced the cartilage volume loss in the global knee, associated with the lateral compartment. Multivariate analysis further demonstrated that the extent of the treatments positive effect was related to exposure time to treatment, the protective effect at 6 years being significant in participants exposed to 2 years of treatment.These findings provide future support for the long-term protective structure-modifying effects of Glu/CS treatment in knee OA subjects.

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