Patient Experience with the SensoReady® Autoinjector Pen versus a Comparator Device: Results from a Canadian Patient Survey in Rheumatoid Arthritis and Crohn´s Disease.

Purpose: Medication delivery device design impacts treatment satisfaction, adherence, and compliance in patients receiving biologics. This survey assessed autoinjector attributes that are important to patients, and assessed patient perceptions and preferences between an adalimumab biosimilar autoinjector (Hyrimoz® SensoReady® Pen [SDZ-ADL pen]) and the reference adalimumab autoinjector (Humira® Pen [ref-ADL pen]) in patients with rheumatoid arthritis (RA) or Crohn's disease (CD) in Canada. Patients and Methods: In this survey, adult patients were recruited for web-assisted telephone interviews. Patients had ≥ 3 months' experience with the ref-ADL pen and 1-12 months' experience with the SDZ-ADL pen. Results: The survey included 120 patients with RA (n = 32) or CD (n = 88). Mean experience with the ref-ADL pen was 7 years for RA or 5 years for CD vs 9 months with the SDZ-ADL pen. The most important autoinjector attributes were the ability to use the pen independently and the ease and simplicity of self-injection. When comparing the two autoinjectors, patients significantly preferred the SDZ-ADL pen over the ref-ADL pen for nearly every attribute evaluated, with the greatest differences reported for visual and audible feedback mechanisms, ease of self-injection, and ability to use the device independently. Overall, 82% of patients preferred the SDZ-ADL pen over the ref-ADL pen, with buttonless activation and less injection pain being the main drivers for this preference. Conclusion: Patients with RA or CD indicated a preference for the SDZ-ADL pen over the ref-ADL pen, independent of the duration of use of the pen. The preference for a biosimilar device within 1 year of switching provides reassurance of rapid patient acceptance of biosimilars and may simplify the switching process. These results confirm the importance of ensuring autoinjector design supports independent self-administration of medication and align with previous data showing high patient satisfaction with the SDZ-ADL pen.

Which advanced treatment should be used following the failure of a first-line anti-TNF in patients with rheumatoid arthritis? 15 years of evidence from the Quebec registry RHUMADATA.

BACKGROUND: Since 2000, advanced therapies (AT) have revolutionized the treatment of moderate to severe rheumatoid arthritis (RA). Randomized control trials as well as observational studies together with medication availability often determine second-line choices after the failure of first Tumor Necrosis Factor inhibitors (TNFi). This led to the observation that specific sequences provide better long-term effectiveness. We investigated which alternative medication offers the best long-term sustainability following the first TNFi failure in RA. METHODS: Data were extracted from RHUMADATA from January2007. Patients were followed until treatment discontinuation, loss to follow-up, or November 25, 2022. Kaplan-Meier and Cox regression models were used to compare discontinuation between groups. Missing data were imputed, and propensity scores were computed to reduce potential attribution bias. Complete, unadjusted, and propensity score-adjusted imputed data analyses were produced. RESULTS: 611 patients (320 treated with a TNFi and 291 treated with molecules having another mechanism of action (OMA)) were included. The mean age at diagnosis was 44.5 and 43.9 years, respectively. The median retention was 2.84 and 4.48 years for TNFi and OMAs groups. Using multivariable analysis, the discontinuation rate of the OMA group was significantly lower than TNFi (adjHR: 0.65; 95% CI: 0.44-0.94). This remained true for the PS-adjusted MI Cox models. In a stratified analysis, rituximab (adjHR: 0.39; 95% CI: 0.18-0.84) had better retention than TNFi after adjusting for patient characteristics. CONCLUSION: Switching to an OMA, especially rituximab, in patients with failure to a first TNFi appears to be the best strategy as a second line of therapy.

Risk factors for the long-term incidence and progression of knee osteoarthritis in older adults: role of nonsurgical injury.

Background: For one of the most chronic medical conditions, osteoarthritis, uncertainties remain on the impact of injury chronology, the role of repeat injury on the incidence/progression of this disease and the need for knee arthroplasty. Objectives: To explore, in an older adult population, how nonsurgical knee injuries relate to osteoarthritis incidence/progression and the weight of independent risk factors for arthroplasty. Design: A cohort study design evaluates the long-term impact of injuries on knee osteoarthritis outcomes. Methods: Knees with no prior injury (n = 6358) and with at least one injury (n = 819) ⩽20 years before study inclusion were from the Osteoarthritis Initiative cohort. Sociodemographic, clinical and structural [X-ray, magnetic resonance imaging (MRI)] data at study inclusion and changes within 96 months were analysed. Statistics included a mixed model for repeated measurements, generalized estimating equations and multivariable Cox regression with covariates. Results: At inclusion, knees with prior injury demonstrated greater incidence and severity of osteoarthritis (p ⩽ 0.001). At 96 months, there was a greater increase in symptoms [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, p = 0.002], joint space width (JSW, p = 0.039) loss, medial cartilage volume loss (CVL, p ⩽ 0.001) and bone marrow lesion size (BML, p ⩽ 0.049). Knees with/without injury at inclusion but with new ones over time had a pronounced increase in symptoms (all WOMAC scores, p ⩽ 0.001), JSW loss, lateral (without) and medial CVL, lateral (without) and medial meniscal extrusion and medial BML (without; all p ⩽ 0.030). Levels of lateral and medial meniscal extrusion (without) and symptoms (with/without; all WOMAC scores, p ⩽ 0.001) were all accentuated with a repeated new injury. Risk factors associated with the highest knee arthroplasty occurrence are new meniscal extrusion and new injury (p ⩽ 0.001). Conclusion: This study highlights the importance of nonsurgical knee injury in older adults as an independent risk factor for knee osteoarthritis and arthroplasty. These data will be beneficial in clinical practice as they will help identify individuals at greater risk of significant disease progression and worst disease outcomes for a customized therapeutic approach.

Risk factors associated with the occurrence of total knee arthroplasty in patients with knee osteoarthritis: a nested case-control study.

Objectives: The aim of this study was to investigate changes over time in osteoarthritis risk factors most closely associated with the occurrence of total knee arthroplasty (TKA). We hypothesize that the robustness of a longitudinal case-control study will provide new information on the association between changes in various clinical and structural parameters in different time frames before TKA. Methods: Cases (195; TKA after cohort entry) and controls (468) matched for age, gender, income, WOMAC pain, Kellgren-Lawrence grade and follow-up duration were from the Osteoarthritis Initiative cohort. Associations between changes in sociodemographic, clinical, imaging and osteoarthritis therapies with the occurrence of TKA were performed using conditional logistic regression analyses. Results: Worsening of WOMAC scores (cOR 1.02-1.20, p ⩽ 0.012), KOOS (1.02-1.04, p ⩽ 0.014), knee injuries sustained in the previous 30-40 years (women 2.70, p = 0.034) and valgus alignment (1.10, p = 0.052) were associated with the occurrence of TKA. Also associated with TKA was cartilage volume loss in the lateral (overall 1.76, p = 0.025; women 1.93, p = 0.047) and medial compartments (⩾10%, overall 1.54, p = 0.027; men 2.34, p = 0.008), occurrence of medial meniscal extrusion (overall 1.77, p = 0.046; men 2.86, p = 0.028), and increase in bone marrow lesions (BMLs) for women (1.09, p = 0.048). The association of risk factors with TKA was reinforced when both an increase in WOMAC pain and cartilage volume loss (1.85, p = 0.001) were combined. Pain medication usage, mainly narcotics and intra-articular steroid injections (IASI), was also associated with TKA, with no impact on changes in cartilage loss or structure. Conclusion: This study provides new information about gender differences in risk factors associated with the occurrence of TKA. Worsening of valgus alignment, cartilage volume loss in the lateral compartment, BMLs and older injuries are important risk factors in women, while medial compartment cartilage loss and meniscal extrusion are in men. The use of pain medication and IASI although associated was found not causal with TKA.

Intra-articular corticosteroid knee injection induces a reduction in meniscal thickness with no treatment effect on cartilage volume: a case-control study.

Although intra-articular corticosteroid injections (IACI) are commonly used for the treatment of knee osteoarthritis (OA), there is controversy regarding possible deleterious effects on joint structure. In this line, this study investigates the effects of IACI on the evolution of knee OA structural changes and pain. Participants for this nested case-control study were from the Osteoarthritis Initiative. Knees of participants who had received an IACI and had magnetic resonance images (MRI) were named cases (n = 93), and each matched with one control (n = 93). Features assessed at the yearly visits and their changes within the follow-up period were from MRI (cartilage volume, meniscal thickness, bone marrow lesions, bone curvature, and synovial effusion size), X-ray (joint space width), and clinical (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] pain score) data. Participants who received IACI experienced a transient and significantly greater rate of loss of the meniscal thickness (p = 0.006) and joint space width (p = 0.011) in the knee medial compartment in the year they received the injection, compared to controls. No significant effect of the IACI was found on the rate of cartilage loss nor on any other knee structural changes or WOMAC pain post-treatment. In conclusion, a single IACI in knee OA was shown to be safe with no negative impact on structural changes, but there was a transient meniscal thickness reduction, a phenomenon for which the clinical relevance is at present unknown.

An international, multicentre, double-blind, randomized study (DISSCO): effect of diacerein vs celecoxib on symptoms in knee osteoarthritis.

OBJECTIVE: The objective of this study was to investigate whether diacerein has comparable efficacy with celecoxib in pain reduction for treatment in symptomatic knee OA patients. METHODS: This randomized double-blind multicentre non-inferiority trial evaluated diacerein vs celecoxib treatment in patients with Kellgren-Lawrence grade 2-3 and pain scoring ≥4 (10-cm VAS). Patients were randomized to 6 months of treatment with diacerein 50 mg (n = 187) once daily for 1 month and twice daily thereafter, or celecoxib 200 mg (n = 193) once daily. The primary outcome was the change in WOMAC pain score (0-50 cm) at 6 months, and the secondary outcomes were WOMAC sub-scores, VAS pain score, and the OMERACT-OARSI responder rate. RESULTS: In the per protocol population, the adjusted mean change from baseline in the WOMAC pain score was -11.1 ( 0.9) with diacerein (n = 140) and -11.8 (0.9) with celecoxib (n = 148). The intergroup difference was 0.7 (95% CI: -1.8, 3.2; P = 0.597), meeting the non-inferiority margin. Supportive analysis of the intention-to-treat population gave similar results. Other outcomes showed no significant difference between treatment groups. The incidence of treatment-related adverse events was low and balanced between groups, but a greater incidence of diarrhoea occurred with diacerein (10.2% vs 3.7%). Diarrhoea was considered mild-to-moderate in all but one case with complete resolution. CONCLUSIONS: Diacerein was non-inferior to celecoxib in reducing knee OA pain and improving physical function. Diacerein also demonstrated a good safety profile. TRIAL REGISTRATION: A multicentre study on the effect of DIacerein on Structure and Symptoms vs Celecoxib in Osteoarthritis is a National Institutes of Health (NCT02688400) and European Clinical Trial Database (2015-002933-23) registered phase III (Canada) or IV (Europe) study.

Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients.

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

Persistence rates of abatacept and TNF inhibitors used as first or second biologic DMARDs in the treatment of rheumatoid arthritis: 9 years of experience from the Rhumadata® clinical database and registry.

BACKGROUND: Treatment persistence is an important consideration when selecting a therapy for chronic conditions such as rheumatoid arthritis (RA). We assessed the long-term persistence of abatacept or a tumor necrosis factor inhibitor (TNFi) following (1) inadequate response to a conventional synthetic disease-modifying antirheumatic drug (first-line biologic agent) and (2) inadequate response to a first biologic DMARD (second-line biologic agent). METHODS: Data were extracted from the Rhumadata® registry for patients with RA prescribed either abatacept or a TNFi (adalimumab, certolizumab, etanercept, golimumab, or infliximab) who met the study selection criteria. The primary outcome was persistence to abatacept and TNFi treatment, as first- or second-line biologics. Secondary outcomes included the proportion of patients discontinuing therapy, reasons for discontinuation, and predictors of discontinuation. Persistence was defined as the time from initiation to discontinuation of biologic therapy. Baseline characteristics were compared using descriptive statistics; cumulative persistence rates were estimated using Kaplan-Meier methods, compared using the log-rank test. Multivariate Cox proportional hazard models were used to compare the persistence between treatments, controlling for baseline covariates. RESULTS: Overall, 705 patients met the selection criteria for first-line biologic agent initiation (abatacept, n = 92; TNFi, n = 613) and 317 patients met the criteria for second-line biologic agent initiation (abatacept, n = 105; TNFi, n = 212). There were no clinically significant differences in baseline characteristics between the treatments with either first- or second-line biologics. Persistence was similar between the first-line biologic treatments (p = 0.7406) but significantly higher for abatacept compared with TNFi as a second-line biologic (p = 0.0001). Mean (SD) times on first-line biologic abatacept and TNFi use were 4.53 (0.41) and 5.35 (0.20) years, and 4.80 (0.45) and 2.82 (0.24) years, respectively, as second-line biologic agents. The proportion of patients discontinuing abatacept and TNFi in first-line was 51.1% vs. 59.5% (p = 0.1404), respectively. In second-line, it was 57.1% vs. 74.1% (p = 0.0031). The main reasons for stopping both treatments were inefficacy and adverse events. CONCLUSIONS: Abatacept and TNFi use demonstrated similar persistence rates at 9 years as a first-line biologic agent. As a second-line biologic agent, abatacept had better persistence rates over a TNFi.

Rationale, study design, and descriptive data of the Lucky Bone™ Fracture Liaison Service.

The study design of a multidisciplinary Fracture Liaison Service (2-year follow-up) aiming to optimize fragility fracture management in an outpatient setting is presented. Patient characteristics, investigation, and treatment initiation data at baseline were recorded. Results corroborate the care gap in osteoporosis management, reinforcing the need for secondary fracture prevention programs. PURPOSE: This paper describes the study design, implementation, and baseline characteristics of a multidisciplinary Fracture Liaison Service (FLS) in Quebec (Canada). METHODS: A FLS was implemented as a prospective cohort study. After identification, fracture risk was assessed and patients were started on treatment or referred, according to guidelines and risk assessment. Thereafter, patients were systematically followed over 2 years. Clinical data (fractures, bone density, blood testing (bone turnover markers), quality of life, physical disability) as well as administrative data (pharmacological, health services, hospitalization) was collected. Baseline descriptive data was analyzed and presented. RESULTS: Of 542 recruited participants, 532 underwent baseline assessment (85.7% female, mean age 63.4 years). Overall, 29.7% of participants either withdrew from the study or were lost to follow-up. Almost 27% were referred to a specialist, while > 70% received anti-osteoporosis medication prescriptions through the FLS at baseline. Mean femoral T-score was - 1.6 ± 1.0 and vertebral T-score was - 1.7 ± 1.4. Nearly 19% of subjects reported being under anti-osteoporosis medication at the time of incident fracture. Thirty-three percent of participants reported a prior fracture history, of which 29.7% reported being given anti-osteoporosis therapy. Most fracture sites were to the wrist and ankle, while < 19% were hip/femur or vertebral fractures. CONCLUSIONS: These results highlight the important care gap in fragility fracture management and reinforce the need for secondary fracture prevention programs. This prospective study will allow the evaluation of key performance indicators for outpatient clinic-based FLS, such as medication usage, by combining prospective clinical and administrative data.

Impact of oral osteoarthritis therapy usage among other risk factors on knee replacement: a nested case-control study using the Osteoarthritis Initiative cohort.

BACKGROUND: The aim of this study was to measure the association between exposure to commonly used oral osteoarthritis (OA) therapies and relevant confounding risk factors on the occurrence of knee replacement (KR), using the Osteoarthritis Initiative (OAI) database. METHODS: In this nested case-control design study, participants who had a KR after cohort entry were defined as "cases" and were matched with up to four controls for age, gender, income, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, Kellgren-Lawrence grade, and duration of follow up. Exposure to oral OA therapies (acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, narcotics, and glucosamine/chondroitin sulfate) was determined within the 3 years prior to the date of the KR. Conditional regression analyses were performed to estimate the association between KR and exposure to oral OA therapies and other potential confounding risk factors. RESULTS: A total of 218 participants who underwent a KR (cases) were matched to 540 controls. The median time to KR was 4.3 years among cases. The majority in both groups were Caucasian with mean age of 69 years and 61% were female. Numerically, cases were more exposed to acetaminophen, NSAIDs, and COX-2 inhibitors. Exposure to narcotics and glucosamine/chondroitin sulfate was relatively similar between cases and controls. No significant association was found between the occurrence of KR and exposure to any of the oral OA therapies within the 3 years prior to KR. A significantly higher occurrence of KR was found in Caucasian subjects (OR 1.84; 95% CI, 1.13-2.99; p = 0.015) and subjects with body mass index (BMI) ≥ 27 kg/m2 (OR 1.65; 95% CI, 1.06-2.58; p = 0.027). CONCLUSION: This study provides evidence that the main risk factors leading to KR are disease severity, symptoms and high BMI. Importantly, exposure to oral OA therapies was not associated with the occurrence of KR.

Exploring determinants predicting response to intra-articular hyaluronic acid treatment in symptomatic knee osteoarthritis: 9-year follow-up data from the Osteoarthritis Initiative.

BACKGROUND: The weight of recommendation for intra-articular therapies such as hyaluronic acid injections varies from one set of guidelines to another, and they have not yet reached unanimity with respect to the usefulness of intra-articular hyaluronic acid (IAHA) injections for the symptomatic treatment of knee osteoarthritis (OA). Among the reasons for the controversy is that the current literature provides inconsistent results and conclusions about such treatment. This study aimed at identifying determinants associated with a better response to IAHA treatment in knee OA. METHODS: Subjects were selected from the Osteoarthritis Initiative database. Participants were subjects who had radiographic OA, received one IAHA treatment, and had data on demographics and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores at visits before (T0) and after (T1; within 6 months) treatment. Pain was analyzed for demographic, clinical, and imaging characteristics at T0 and change over time (T0 to T1). Subjects with WOMAC pain > 0 at T0 were subdivided into Low, Moderate, and High pain groups based on tertile analysis. Further analyses were done with the High pain group (score ≥ 8), which was divided into responders (improvement in pain ≥ 20%) and nonresponders (unchanged or worsening of pain). RESULTS: Participants (n = 310) received a total of 404 treatments (one per knee). In the Low and Moderate pain groups vs the High pain group, participants had significantly lower score at T0 (p < 0.001), and the Low vs High pain group had significantly lower BMI (p = 0.002), greater joint space width (JSW) (p = 0.010) and knee cartilage volume (p ≤ 0.009), and smaller synovial effusion (p = 0.033). In the High pain group, responders vs nonresponders were usually younger (p = 0.014), with greater cartilage volume in the medial compartment (p = 0.046), a trend toward greater JSW, and a significant improvement in all WOMAC scores (p < 0.001), while nonresponders showed worsening of symptoms. CONCLUSIONS: This study identified reliable predictive determinants that can distinguish patients who could best benefit from IAHA treatment: high levels of knee pain, younger, and less severe structural damage. These could be implemented in clinical practice as a useful guide for physicians.

Intra-articular hyaluronic acid in the treatment of knee osteoarthritis: a Canadian evidence-based perspective.

Osteoarthritis (OA) is a chronic condition characterized by a loss of joint cartilage and is a major cause of disability in Canada, with an estimated CN$195 billion annual cost. Knee OA leads to persistent pain and loss of function, and treatment goals primarily focus on symptom relief and retention of function. Intra-articular hyaluronic acid (IAHA) has therapeutic benefits, and numerous recently published meta-analyses (MAs) and commentaries have highlighted new evidence on the role of IAHA therapy for knee OA. A diverse, multidisciplinary group of specialists met independently in closed sessions to review findings from eight MAs with literature search end dates no earlier than 2012 to address controversies surrounding IAHA therapy for mild-to-moderate knee OA within the Canadian treatment context. Outcomes from a total of eight MAs were reviewed, and consistent and statistically significant improvements in pain, function and stiffness up to 26 weeks were found with IAHA therapy compared with IA placebo or controls, regardless of MA size or trial quality. These findings are in line with those of a Cochrane review, another recent systematic review and patient satisfaction survey. Overall, three MAs reported outcomes based on molecular weight (MW), with the two reporting effect sizes showing significantly improved pain outcomes for higher compared with lower MW HAs. Recent evidence suggests that HA therapy is well tolerated with no increased risk of serious adverse events compared with placebo and the full therapeutic effect of IAHA therapy appears to have considerable clinical importance, consisting of the combined IA placebo and HA therapeutic effects. IAHA therapy is a well-tolerated and effective option for patients with mild-to-moderate knee OA failing first-line pharmacological therapy.

Levels of serum biomarkers from a two-year multicentre trial are associated with treatment response on knee osteoarthritis cartilage loss as assessed by magnetic resonance imaging: an exploratory study.

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.

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

Objectives: 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. Methods: 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. Results: 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). Conclusion: 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.

Chondroitin sulfate efficacy versus celecoxib on knee osteoarthritis structural changes using magnetic resonance imaging: a 2-year multicentre exploratory study.

BACKGROUND: 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 1200 mg/day versus celecoxib 200 mg/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. METHODS: qMRI was performed at baseline and at 12 and 24 months. 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, Fisher's exact, Wilcoxon Mann-Whitney, and Student's t tests and analysis of covariance. Analyses were also conducted on the according-to-protocol (ATP; n = 120) population. RESULTS: In the adjusted mITT analysis, compared with celecoxib treatment, patients treated with CS had a significant reduced CVL at 24 months 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 12 months (celecoxib -5.6 % ± 3.0, CS -4.5 % ± 2.6; p = 0.049) and 24 months (celecoxib -8.4 % ± 4.2, CS -6.6 % ± 3.3; p = 0.021), and in the medial condyle at 24 months (celocoxib -8.1 % ± 4.7, CS -5.7 % ± 4.0; p = 0.010). A trend towards a statistically reduced synovial thickness (celecoxib +17.96 ± 33.73 mm, CS -0.66 ± 22.72 mm; 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. CONCLUSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01354145 . Registered 13 May 2011.

Long-Term Effects of Glucosamine and Chondroitin Sulfate on the Progression of Structural Changes in Knee Osteoarthritis: Six-Year Followup Data From the Osteoarthritis Initiative.

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.