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1.
Sci Rep ; 10(1): 13789, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796866

RESUMO

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.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32521015

RESUMO

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.

4.
Arthritis Res Ther ; 22(1): 5, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059

RESUMO

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.


Assuntos
Doenças Autoimunes/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imunossupressores/uso terapêutico , Miosite/induzido quimicamente , Miosite/etiologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/tratamento farmacológico , Feminino , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Quimioterapia de Indução/métodos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , Estudos Retrospectivos
5.
Arthritis Res Ther ; 21(1): 138, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171024

RESUMO

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.


Assuntos
Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , Resistência a Medicamentos , Sistema de Registros , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Suspensão de Tratamento
7.
Arch Osteoporos ; 14(1): 19, 2019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30756193

RESUMO

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.


Assuntos
Assistência Ambulatorial/métodos , Osteoporose/complicações , Fraturas por Osteoporose/prevenção & controle , Medição de Risco/métodos , Prevenção Secundária/métodos , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Canadá , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Projetos de Pesquisa
8.
Arthritis Res Ther ; 20(1): 172, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30086786

RESUMO

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.


Assuntos
Artroplastia do Joelho/estatística & dados numéricos , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/cirurgia , Idoso , Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Índice de Massa Corporal , Estudos de Casos e Controles , Sulfatos de Condroitina/uso terapêutico , Feminino , Glucosamina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
Arthritis Res Ther ; 20(1): 40, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29490683

RESUMO

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.


Assuntos
Ácido Hialurônico/uso terapêutico , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Fatores Etários , Idoso , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intra-Articulares , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Dor/fisiopatologia , Medição da Dor , Prognóstico , Fatores de Risco , Resultado do Tratamento
11.
Ther Adv Musculoskelet Dis ; 9(9): 231-246, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28932293

RESUMO

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.

12.
Arthritis Res Ther ; 19(1): 169, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28728606

RESUMO

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.


Assuntos
Biomarcadores/sangue , Cartilagem Articular/efeitos dos fármacos , Sulfatos de Condroitina/uso terapêutico , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Cartilagem Articular/patologia , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Resultado do Tratamento
14.
Rheumatology (Oxford) ; 56(6): 989-998, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339999

RESUMO

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.


Assuntos
Doenças Ósseas/patologia , Osteoartrite do Joelho/patologia , Adulto , Idoso , Doenças das Cartilagens/patologia , Cartilagem Articular/patologia , Celecoxib/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologia , Osteoartrite do Joelho/tratamento farmacológico
15.
Arthritis Res Ther ; 18(1): 256, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27809891

RESUMO

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.


Assuntos
Celecoxib/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/patologia , Idoso , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Método Duplo-Cego , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Resultado do Tratamento
16.
Arthritis Care Res (Hoboken) ; 68(10): 1560-6, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26881338

RESUMO

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.


Assuntos
Sulfatos de Condroitina/administração & dosagem , Progressão da Doença , Glucosamina/administração & dosagem , Osteoartrite do Joelho/patologia , Idoso , Cartilagem Articular/patologia , Feminino , Seguimentos , Humanos , Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/tratamento farmacológico , Tempo , Resultado do Tratamento
17.
Rheumatology (Oxford) ; 55(4): 680-8, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26660640

RESUMO

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.


Assuntos
Artroplastia do Joelho , Leptina/sangue , Osteoartrite do Joelho/diagnóstico , Idoso , Biomarcadores/sangue , Índice de Massa Corporal , Cartilagem Articular/patologia , Fator D do Complemento/metabolismo , Progressão da Doença , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Índice de Gravidade de Doença
18.
Semin Arthritis Rheum ; 45(3): 257-67, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26094904

RESUMO

OBJECTIVE: In the perspective of personalized management of osteoarthritis (OA), a clinically relevant concern is the impact of meniscal extrusion (Ext) on response to treatment. This study aimed at determining the effects of conventional OA pharmacological treatments and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes in the presence or absence of Ext, using data from the progression cohort of the Osteoarthritis Initiative. METHODS: In this longitudinal study, knee OA participants were stratified based on whether (+) or not (-) they received analgesics/NSAIDs (+ and -analgesics/NSAIDs) and/or Glu/CS (+ and -Glu/CS) for 24 consecutive months and on the presence (Ext+) or absence (Ext-) of medial meniscal extrusion at baseline. The main outcomes were knee structural changes including the loss of joint space width (JSW) and cartilage volume loss measured by quantitative MRI. RESULTS: In both - and +analgesics/NSAIDs groups (n = 300 each), the Ext+ participants had more-advanced disease at baseline (T0) and more JSW loss and cartilage volume loss in the medial compartment (p ≤ 0.003, univariate; p ≤ 0.049, multivariate analyses) at both 12 (T12) and 24 (T24) months compared to Ext- participants. In the -analgesics/NSAIDs group, Ext+ participants taking Glu/CS had significantly less cartilage volume loss in the medial plateau at T24 (p ≤ 0.010, univariate and multivariate analyses). In the +analgesics/NSAIDs group at T24, Ext- participants taking Glu/CS had less cartilage volume loss in the global (p ≤ 0.002, univariate and multivariate analyses) and medial and lateral plateaus (p = 0.034 and p = 0.013, respectively, multivariate analysis). No significant difference in JSW loss was found between the groups. CONCLUSION: This study is the first to demonstrate, using qMRI, that meniscal extrusion can modify the response to Glu/CS treatment in knee OA patients, depending on the severity of the disease.


Assuntos
Cartilagem Articular/patologia , Articulação do Joelho/patologia , Meniscos Tibiais/patologia , Osteoartrite do Joelho/tratamento farmacológico , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia
19.
Arthritis Res Ther ; 17: 82, 2015 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-25888851

RESUMO

INTRODUCTION: To evaluate the impact of meniscal extrusion (Ext) on knee osteoarthritis (OA) structural progression and on response to strontium ranelate (SrRan) treatment at 36 months 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 1 g/day, n = 113; SrRan 2 g/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 2 g/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.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Progressão da Doença , Meniscos Tibiais/patologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/tratamento farmacológico , Tiofenos/uso terapêutico , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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