Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 851
Filtrar
1.
Best Pract Res Clin Rheumatol ; 33(4): 101419, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31810550

RESUMO

As primary care clinicians are typically the first point of contact for patients with musculoskeletal problems, they are crucial to the early diagnosis and treatment of patients with an incident inflammatory arthritis, like rheumatoid arthritis. Current UK and international guidelines recognise this, recommending the prompt referral of patients with suspected persistent synovitis to secondary care. In England and Wales, this is advised to occur within 3 working days. However, recent audit data suggests this recommendation is infrequently met, with some patients waiting many months for referral. In this review article we will discuss the various challenges to achieving the early referral of patients with a new-onset inflammatory arthritis from primary to secondary care. We will also describe how these challenges could potentially be overcome, with the ultimate goal of ensuring that the right patients are referred to the right services, and at the right time.


Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Reumáticas , Sinovite , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Atenção Primária à Saúde , Encaminhamento e Consulta , Doenças Reumáticas/tratamento farmacológico , Sinovite/tratamento farmacológico
2.
Am J Vet Res ; 80(11): 1001-1006, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31644340

RESUMO

OBJECTIVE: To investigate the ability of a proprietary antagonist of E-type prostanoid receptor (EP) 4, grapiprant, and carprofen to attenuate lameness attributable to urate-induced synovitis in dogs. ANIMALS: 5 purpose-bred hound-cross dogs. PROCEDURES: A blinded, 3-way crossover study was performed. Dogs received each of 3 treatments (L-766, a proprietary antagonist of EP4; 4.0 mg/kg), grapiprant (an antagonist of EP4; 2.0 mg/kg), and carprofen (4.4 mg/kg); dogs received 4 doses of each treatment (14 and 2 hours before and 22 and 46 hours after urate injection). Synovitis was induced by intra-articular injection of sodium urate. Measurements (vertical ground reaction forces and clinical lameness scores) were obtained immediately before (0 hours; baseline) and 6, 12, 24, 36, and 48 hours after sodium urate injection. All data were analyzed with repeated-measures ANOVA. RESULTS: Lameness scores at 6 hours were significantly higher than baseline lameness scores for all treatments. Lameness scores for the grapiprant treatment remained significantly higher at 12 and 24 hours, compared with baseline lameness scores. Lameness scores for the carprofen treatment were significantly lower than lameness scores for the grapiprant treatment at 6, 12, and 24 hours. Analysis of peak vertical force and vertical impulse data revealed a pattern similar to that for lameness scores. Treatment with L-766 resulted in a significantly higher vertical impulse at 48 hours than did treatment with carprofen or grapiprant. CONCLUSIONS AND CLINICAL RELEVANCE: In these dogs, carprofen was the most effective treatment for attenuating lameness induced by injection of sodium urate, and grapiprant was the least effective treatment.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Carbazóis/uso terapêutico , Doenças do Cão/tratamento farmacológico , Coxeadura Animal/tratamento farmacológico , Receptores de Prostaglandina E Subtipo EP4/antagonistas & inibidores , Compostos de Sulfonilureia/uso terapêutico , Sinovite/veterinária , Animais , Carbazóis/farmacologia , Estudos Cross-Over , Cães , Marcha , Injeções Intra-Articulares/veterinária , Coxeadura Animal/induzido quimicamente , Masculino , Método Simples-Cego , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico , Ácido Úrico
3.
Medicine (Baltimore) ; 98(33): e16714, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415364

RESUMO

To investigate the efficiency and clinical safety of intra-articular triamcinolone acetonide (TA) injection under the guide of ultrasonography combined with standard treatment for treating refractory small joints arthritis in rheumatoid arthritis (RA) patients.TA was injected upon confirmation of the needle inserting into the articular cavity. The dose was 40 mg for the wrist, 20 mg for the metacarpophalangeal (MCP) joint and 20 mg for the proximal interphalangeal (PIP) joint, respectively. Visual analogue scale (VAS) for joint pain, swelling, tenderness, synovial hyperplasia and power Doppler signal scores were evaluated at pretreatment, and post-treatment 24 hours, 1 week, 4 weeks as well as 12 weeks.The VAS for pain and tenderness scores showed gradual improvement at 24 hours, 1 week, 4 weeks and 12 weeks after treatment compared with the baseline levels (P' < .005). The swelling showed no changes at 24 hours after treatment compared with the baseline, and showed gradual improvement at 1 week, 4 weeks and 12 weeks after treatment (P' < .005). Significant decrease was noticed in the synovial hyperplasia score at 4 weeks and 12 weeks compared with the baseline level. Power Doppler signal score showed significant decrease at post-treatment 24 hours, which showed further decrease at 1 week and 4 weeks.Ultrasound-guided intra-articular TA injection is effective for treating RA patients with refractory small joints arthritis without changing the original treatment plan.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artrite Reumatoide/complicações , Sinovite/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Ultrassonografia de Intervenção/métodos , Adolescente , Adulto , Idoso , Feminino , Articulações dos Dedos/efeitos dos fármacos , Humanos , Injeções Intra-Articulares , Masculino , Articulação Metacarpofalângica/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Sinovite/etiologia , Sinovite/patologia , Resultado do Tratamento , Articulação do Punho/efeitos dos fármacos , Adulto Jovem
4.
Reumatol. clín. (Barc.) ; 15(4): 218-222, jul.-ago. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-184414

RESUMO

Background: Rheumatoid arthritis (RA) patients with disease in clinical remission might show subclinical synovitis, which can be related to the progress of structural joint damage. Objective: To determine and compare the degree of synovial inflammation by ultrasound (US) in patients with RA in clinical remission, treated with DMARD or combination therapy with DMARD and anti-TNF. Methods: Hospital-based cross-sectional study of 58 patients with RA in sustained remission for at least 6 months by DAS28 <2.6, who attended the Rheumatology Service at the Hospital Universitario de Caracas. Patients underwent clinical, functional, and laboratory assessments. Ultrasound was performed in hands measuring synovial effusion, synovial hypertrophy and power Doppler signal; using a semiquantitative 4-point scale of 0=none to 3=severe. Chi-square and t-test were used to compare the clinical, functional, laboratory and US assessments between the DMARD (N=37) and combination therapy with DMARD and anti-TNF (N=21) groups. A p-value <0.05 was considered statistically significant. Results: Out of 58 patients, 25.9% had remission by US and 74.1% had synovial effusion or hypertrophy or positive power Doppler signal. Non-significant differences in US synovitis between the two groups were found. Conclusions: Persistent US activity was evident in a high percentage of rheumatoid arthritis patients in clinical remission by DAS28. No differences in subclinical synovitis measured by US were found between patients with DMARD and anti-TNF-induced clinical remission


Introducción: Los pacientes con artritis reumatoide (AR) con enfermedad en remisión clínica pueden mostrar sinovitis subclínica, que puede estar relacionada con el progreso del daño articular estructural. Objetivos: Determinar y comparar el grado de inflamación sinovial medida por ultrasonido (US) en pacientes con AR en remisión clínica, tratados con FAME o FAME y anti-TNF. Métodos: Estudio transversal con sede en hospital, donde se evaluaron 58 pacientes con AR en remisión sostenida durante al menos 6 meses por DAS28<2,6, que asistieron al Servicio de Reumatología del Hospital Universitario de Caracas. Se realizó evaluación clínica, funcional y de laboratorio. Se practicó US en manos evaluando derrame, hipertrofia sinovial y presencia de señal power Doppler, utilizando una escala semicuantitativa de 4 puntos 0=ninguno a 3=severo. Se compararon los hallazgos entre los pacientes con FAME (n=37) y FAME y anti-TNF (n=21), utilizando las pruebas de Chi-cuadrado y t de Student. Se consideró significación estadística si el valor de p era<0,05. Resultados: De los 58 pacientes, el 25,9% tuvo remisión por US y el 74,1% presentó derrame, hipertrofia sinovial o señal power Doppler positiva. No hubo diferencias significativas en la presencia de sinovitis medida por US entre los 2 grupos. Conclusiones: En pacientes en remisión clínica por DAS28, la actividad persistente medida por US fue evidente en un alto porcentaje. No hubo diferencias en la sinovitis subclínica medida por US entre los pacientes en remisión clínica inducida con FAME y FAME y anti-TNF


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Sinovite/tratamento farmacológico , Artrite Reumatoide/complicações , Antirreumáticos/uso terapêutico , Terapia Biológica/métodos , Doenças Assintomáticas , Sinovite/etiologia , Sinovite/diagnóstico por imagem , Resultado do Tratamento , Estudos Transversais
5.
Acta Vet Scand ; 61(1): 28, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221173

RESUMO

BACKGROUND: Dexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis. RESULTS: Inflammation was induced in the radiocarpal joint of six horses by injection of 2 ng lipopolysaccharide (LPS). Two hours later either saline or dexamethasone was injected in the same joint in a two treatment cross over design. Each horse was treated once with one of the six doses dexamethasone used (0.01, 0.03, 0.1, 0.3, 1 or 3 mg) and once with saline. Dexamethasone was quantified by means of UHPLC-MS/MS. Dexamethasone disposition was characterised by means of a non-linear mixed effects model. Lameness was evaluated both objectively with an inertial sensor based system and subjectively scored using a numerical scale (0-5). Joint circumference, skin temperature over the joint and rectal temperature were also recorded. The LPS-challenge induced lameness in all horses with high inter-individual variability. Dexamethasone significantly decreased lameness compared with saline. Other variables were not statistically significant different between treatments. Objective lameness scoring was the most sensitive method used in this study to evaluate the lameness response. A pharmacokinetic/pharmacodynamic model was successfully fitted to experimental dexamethasone and lameness data. The model allowed characterization of the dexamethasone synovial fluid concentration-time course, the systemic exposure to dexamethasone after intra-articular administration and the concentration-response relation in an experimental model of synovitis. CONCLUSIONS: The quantitative data improve the understanding of the pharmacology of dexamethasone and might serve as input for future experiments and possibly contribute to maintain integrity of equine sports.


Assuntos
Dexametasona/administração & dosagem , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/tratamento farmacológico , Lipopolissacarídeos , Sinovite/veterinária , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Dexametasona/farmacocinética , Cavalos , Injeções Intra-Articulares/veterinária , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico
7.
J Med Invest ; 66(1.2): 112-118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31064921

RESUMO

Polymyalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome are common inflammatory rheumatic diseases in the elderly. In this study, we investigate predictive factors which correspond to subsequent disease control of PMR and RS3PE syndrome. Twenty four patients, which contained 18 PMR and 6 RS3PE syndrome, were treated with initial dosages of 10-20 mg per day oral prednisolone, and the dosage of prednisolone was then tapered. Significantly higher initial CRP was observed in patients with poor disease control than in those with good disease control afterwards. The number of patients with negative CRP after 4 weeks was significantly more in patients with good disease control after 1 year than in those with poor disease control. Patients were shown to be in good disease control status after 1 year when CRP after 4 weeks became negative even if they had initial high CRP. Our study clarify that to make CRP negative after 4 weeks is associated with subsequent suppression of the disease activity and with decreased dosages of corticosteroids. J. Med. Invest. 66 : 112-118, February, 2019.


Assuntos
Edema/tratamento farmacológico , Polimialgia Reumática/tratamento farmacológico , Prednisolona/uso terapêutico , Sinovite/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Edema/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimialgia Reumática/sangue , Estudos Retrospectivos , Síndrome , Sinovite/sangue
9.
Pharmazie ; 74(4): 212-220, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30940304

RESUMO

Rheumatoid arthritis is an autoimmune pathology that manifests as chronic inflammatory arthropathy and synovitis. Treatment of rheumatoid arthritis is based on the administration of different types of drugs, including leflunomide, an antirheumatic drug. However, the long-term systemic use of leflunomide may be associated with adverse effects. Local therapy could be an efficient strategy to treat synovitis triggered by rheumatoid arthritis without inducing adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) implants (leflunomide PCL implants) were evaluated as local drug delivery systems capable of attenuating inflammation and angiogenesis, which represent events of synovitis. Leflunomide PCL implants were designed by hot molding technique; and they were characterized by FTIR and DSC. These analytical techniques demonstrated the chemical integrity and dispersion of drug into the polymeric chains. Then, a spectrophometric method was developed and validated to quantify the leflunomide incorporated into the PCL implants and released from them. Linearity was obtained by ordinary least squares regression method to estimate the linear regression equation. Residues were evaluated considering normality, independence and homoscedasticity. Precision was lower than 5 %, and accuracy ranged from 98 to 104.5 %. Quantitation limit was 2.0 µg mL-1. PCL implants provided controlled and sustained release of leflunomide for 30 consecutive days after inserting these systems in the subcutaneous tissue of mice. The main mechanisms of drug delivery were solubilization and diffusion from polymer. Then, a non-biocompatible sponge was inserted into the subcutaneous tissue of mice to function as a frame to develop the inflammatory and angiogenic processes. Leflunomide PCL implants were inserted in direct contact with the sponge. At 4, 7 and 10 days after-sponge implantation, the key components of inflammatory angiogenesis were measured to verify the regression of these events induced by drug. Leflunomide controlled released from polymeric implants downregulated the neutrophil and monocyte/macrophage infiltration due to the reduced expression of myeloperoxidase (MPO) and N-acetyl-ß-d-glucosaminidase (NAG), respectively. As the influx of these pro-inflammatory cells was modulated by leflunomide, the production of nitric oxide (NO), a pro-inflammatory substance, reached low concentrations in the sponge. As a consequence of the modulation of inflammation at the pathological site, the angiogenic process was downregulated, since the hemoglobin levels in the sponge were drastically reduced. The accumulation of leflunomide in the pathological site did not induce nephrotoxicity or hepatototoxicity, as confirmed by histological analyses. Finally, intra-articular leflunomide PCL implants represent a potential therapeutic alternative to treat locally the synovitis triggered by rheumatoid arthritis without inducing systemic adverse effects.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Leflunomida/administração & dosagem , Sinovite/tratamento farmacológico , Animais , Antirreumáticos/farmacologia , Antirreumáticos/toxicidade , Varredura Diferencial de Calorimetria , Modelos Animais de Doenças , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Implantes de Medicamento , Feminino , Inflamação/tratamento farmacológico , Inflamação/patologia , Leflunomida/farmacologia , Modelos Lineares , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Óxido Nítrico/metabolismo , Poliésteres/química , Espectrofotometria/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Sinovite/patologia
10.
J Nutr Sci Vitaminol (Tokyo) ; 65(1): 8-18, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30814416

RESUMO

The present study was conducted to assess the effect of all-trans retinoic acid (ATRA) on synovial explants from rats with rheumatoid arthritis (RA) induced by lipopolysaccharides (LPS). In our study, synovial membranes were excised from the knees of healthy adult Wistar female rats under sterile conditions. We first investigated the synoviums incubated in a control medium or in a medium containing 10 µg/mL LPS, each for 24, 48, and 72 h (LPS-experiment). The changes in inflammatory response from the synoviums were observed at different culture times. Then, we assessed the synoviums exposed to different ATRA concentrations for 24 h (ATRA-experiment). The controls (blank, model group, and solvent groups) were set up. The effects of ATRA on synovitis were evaluated by measuring the production of cytokines, and nitric oxide (NO) and the expression of cartilage damage related proteases. In the LPS-experiment, LPS contributed to the release of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and matrix metalloproteinase-9 (MMP-9) in synovial explants. Importantly, LPS did not cause a significant pathological damage. The inflammatory response observed in this model was significant for 24 h, suggesting that LPS-induced synovial explants were successfully established. In the ATRA-experiment, ATRA suppressed the expression of IL-6, TNF-α, NO, a disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS-4), MMP-3, and MMP-9. Taken together, ATRA exhibited inhibitory effects on LPS-induced synovial immune inflammatory response stimulated by the regulation of inflammatory mediators and cartilage damage related proteases in synovial explants, demonstrating a potential protective effect on synovitis and joint destruction in the patients with RA.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Reumatoide/tratamento farmacológico , Articulação do Joelho/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Tretinoína/farmacologia , Animais , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Lipopolissacarídeos , Óxido Nítrico/metabolismo , Ratos , Ratos Wistar , Sinovite/induzido quimicamente , Sinovite/tratamento farmacológico , Sinovite/metabolismo
11.
Scand J Rheumatol ; 48(4): 279-283, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30843453

RESUMO

Objective: Intra-articular glucocorticoid (IAGC) injection treatment is an easy and effective way to treat the signs and symptoms of arthritis, but there is limited knowledge on the adequate dosing for different joints. The aim of this study was to compare the outcome between two common doses of intra-articular triamcinolone hexacetonide (THA) for knee synovitis using the relapse rate during 6 months. Methods: A total of 159 adult patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) and active knee synovitis were randomized to IAGC injection with 20 mg or 40 mg THA. Participants were blinded to the treatment dose. The primary endpoint was relapse of arthritis. When symptoms from the treated joint recurred and signs of arthritis could be confirmed on a subsequent clinical examination, a relapse was recorded and the duration of response survival was calculated. At the end of the observation period, patients without relapse were telephoned to verify the persistence of the good treatment response. Results: The proportion of relapse after 6 months was equal in the 20 mg and 40 mg THA treatment arms (30% vs 32%, respectively, p = 0.822), and no significant differences were found in the subgroups with RA and PsA patients. Conclusion: As no difference in outcome was found between the compared doses, the lower 20 mg THA dose should be preferred in IAGC treatment for knee synovitis in chronic polyarthritis. This may also reduce pharmaceutical costs and metabolic side effects. EudraCT number: 2014-000993-20, Clinical Trials.gov identifier: NCT02437461.


Assuntos
Artrite Psoriásica/complicações , Artrite Reumatoide/complicações , Glucocorticoides , Articulação do Joelho , Sinovite/tratamento farmacológico , Triancinolona Acetonida/análogos & derivados , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Relação Dose-Resposta a Droga , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Injeções Intra-Articulares/métodos , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Prevenção Secundária/métodos , Sinovite/diagnóstico , Sinovite/etiologia , Resultado do Tratamento , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/efeitos adversos
12.
BMC Musculoskelet Disord ; 20(1): 76, 2019 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764805

RESUMO

BACKGROUND: Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA. METHODS: Data was acquired from participants who took part in a randomised placebo-controlled trial (UK VIDEO) investigating the effect of vitamin D therapy (800 IU cholecalciferol daily) on radiographic joint space narrowing. A subsample had serial CE MRI scans acquired during the trial. Subjects with serial images were assessed (N = 50) for STV and subchondral BML volume. The difference in the mean change from baseline in these structural outcomes between intervention and placebo groups was assessed using random-effects modelling. RESULTS: The mean age of the 50 subjects (24 active group, 26 placebo group) who contributed data to the analysis was 63.3 years (SD 6.5) and 74% were female. There was no significant difference at 2 years follow-up between the vitamin D and placebo groups in the mean change from baseline for STV (93.9 mm3, 95% CI -1605.0 to 1792.7) and subchondral BML volume (- 313.5 mm3, 95% CI -4244.7 to 3617.7). CONCLUSIONS: Vitamin D supplementation does not appear to have an effect on synovitis or BML volume in patients with symptomatic knee OA. TRIAL REGISTRATION: VIDEO was registered with EudraCT: ref. 2004-000169-37. The protocol for the trial can be accessed at https://www.ctu.mrc.ac.uk/studies/all-studies/v/video/.


Assuntos
Medula Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Membrana Sinovial/efeitos dos fármacos , Sinovite/tratamento farmacológico , Vitaminas/administração & dosagem , Idoso , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Colecalciferol/efeitos adversos , Método Duplo-Cego , Inglaterra , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Sinovite/diagnóstico por imagem , Sinovite/patologia , Fatores de Tempo , Resultado do Tratamento , Vitaminas/efeitos adversos
13.
Arthritis Rheumatol ; 71(7): 1056-1069, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30653843

RESUMO

OBJECTIVE: To assess the efficacy and safety of the anti-interleukin-1α/ß (anti-IL-1α/ß) dual variable domain immunoglobulin lutikizumab (ABT-981) in patients with knee osteoarthritis (OA) and evidence of synovitis. METHODS: Patients (n = 350; 347 analyzed) with Kellgren/Lawrence grade 2-3 knee OA and synovitis (determined by magnetic resonance imaging [MRI] or ultrasound) were randomized to receive placebo or lutikizumab 25, 100, or 200 mg subcutaneously every 2 weeks for 50 weeks. The coprimary end points were change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at week 16 and change from baseline in MRI-assessed synovitis at week 26. RESULTS: The WOMAC pain score at week 16 had improved significantly versus placebo with lutikizumab 100 mg (P = 0.050) but not with the 25 mg or 200 mg doses. Beyond week 16, the WOMAC pain score was reduced in all groups but was not significantly different between lutikizumab-treated and placebo-treated patients. Changes from baseline in MRI-assessed synovitis at week 26 and other key symptom- and most structure-related end points at weeks 26 and 52 were not significantly different between the lutikizumab and placebo groups. Injection site reactions, neutropenia, and discontinuations due to neutropenia were more frequent with lutikizumab versus placebo. Reductions in neutrophil and high-sensitivity C-reactive protein levels plateaued with lutikizumab 100 mg, with further reductions not observed with the 200 mg dose. Immunogenic response to lutikizumab did not meaningfully affect systemic lutikizumab concentrations. CONCLUSION: The limited improvement in the WOMAC pain score and the lack of synovitis improvement with lutikizumab, together with published results from trials of other IL-1 inhibitors, suggest that IL-1 inhibition is not an effective analgesic/antiinflammatory therapy in most patients with knee OA and associated synovitis.


Assuntos
Imunoglobulinas/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Sinovite/tratamento farmacológico , Idoso , Proteína C-Reativa/imunologia , Método Duplo-Cego , Feminino , Humanos , Reação no Local da Injeção/etiologia , Interleucina-1alfa/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutrófilos , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/imunologia , Sinovite/diagnóstico por imagem , Sinovite/etiologia , Sinovite/imunologia , Resultado do Tratamento
15.
Rev Med Interne ; 40(5): 330-333, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-30391043

RESUMO

INTRODUCTION: Polymyalgia rheumatica (PMR) can be associated with distal swelling indicating an associated RS3PE syndrome. We report a case of PMR associated with oedema of the lower limbs, which resolved rapidly under glucocorticoid therapy. CASE REPORT: A 85-year-old woman presented with a 4 month history of PMR responding to the 2012 EULAR/ACR classification criteria. Examination of the lower limbs revealed pitting oedema bilaterally up to the knees, with mild erythema and warmth. Hypoalbuminemia (30g/L) was present. There was no cardiac, renal or hepatic cause to explain leg swelling. FDG-PET/CT demonstrated increased metabolism in the periarticular area of shoulders and hips. There was no sign of aortitis or neoplasia. Under treatment with prednisone 10mg/day leg swelling disappeared concomitantly to a weight loss of 8kg within 8days. CONCLUSION: This case, the first to report leg swelling of inflammatory origin in the context of PMR, could indicate an increased vascular permeability caused by inflammation in the elderly.


Assuntos
Edema/diagnóstico , Edema/tratamento farmacológico , Perna (Membro)/patologia , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Idoso de 80 Anos ou mais , Edema/etiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Inflamação/complicações , Inflamação/diagnóstico , Inflamação/tratamento farmacológico , Polimialgia Reumática/complicações , Síndrome , Sinovite/complicações , Sinovite/diagnóstico , Sinovite/tratamento farmacológico
16.
Clin Exp Rheumatol ; 37(1): 120-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30148433

RESUMO

OBJECTIVES: To determine the long-term outcomes of RA patients in sustained clinical remission under different therapeutic strategies and explore the risk factors to relapse. METHODS: RA patients in sustained clinical remission (DAS28(CRP) ≤2.6 for at least 6 months) were enrolled. Their baseline clinical features, ultrasonography and x-ray of hands were collected. The usage of conventional synthetic disease-modified anti-rheumatic drugs (csDMARDs) at baseline and every follow-up visits were recorded. Patients were divided into maintain-therapy group or de-escalate-therapy group according to their treatment during follow-up. The time-point of follow-up visits reaching 2 years or flare (DAS28(CRP)>2.6) was defined as the endpoint of the study. The risk factors to predict flare was analysed by logistic regression model. RESULTS: 94 patients were enrolled in the study, with 59 in de-escalate-therapy group and 35 in maintain-therapy group. During an average of 20.8 months of follow-up, 40 (42.6%) patients relapsed, with 31 (52.5%) from de-escalate-therapy group and 9 (25.7%) from maintain-therapy group. De-escalate-therapy increased the risk of flare by 2.3 times (OR=3.38, p=0.044). Baseline DAS28(CRP) (OR=6.97, p=0.038), presence of subclinical synovitis (OR=3.67, p=0.024), combination of 2 csDMARDs (OR=3.72, p=0.030) were the risk factors for relapse, and the best cut-off value of DAS28(CRP) for relapse prediction through ROC curve was 1.82. Taking the three parameters into the model for a combined prediction probability, the area under the ROC curve was 0.722 (95% CI 0.61, 0.82, p=0.000). CONCLUSIONS: De-escalation therapy was associated with higher risk of relapse in RA patients with sustained clinical remission. A combination model of DAS28(CRP)<1.82 and no subclinical synovitis may help to predict successful csDMARDs reduction in RA patients with sustained clinical remission receiving csDMARDs monotherapy.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Humanos , Recidiva , Indução de Remissão , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Resultado do Tratamento
17.
Int Immunopharmacol ; 65: 233-243, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30336338

RESUMO

Imbalance of Treg/Th17 and chronic synovitis characterized by the recruitment and infiltration of inflammatory cells are the typical features of rheumatoid arthritis (RA). IL-6 promotes the differentiation and function of Th17 cells, which contributes to the imbalance of Treg/Th17 and aggravates lymphocytic infiltration in joints. DC32, a dihydroartemisinin derivative, was found to have anti-inflammatory and immunosuppressive activities in previous study. The aim of this study is to evaluate the effects and mechanisms of DC32 in immunodeficiency and inflammatory infiltration of RA. In vivo, the antirheumatic effect of DC32 was evaluated in a collagen-induced arthritis (CIA) mouse model in DBA/1 mice. The percentages of Treg and Th17 and transcription of IL-6 in the spleen were assayed. In vitro, a coculture system of ConA-activated lymphocytes and fibroblast-like synoviocytes (FLSs) from rat with adjuvant arthritis (AA) was established. The effects and mechanisms of DC32 on synovitis were investigated. It was shown that DC32 inhibited footpad swelling and lymphocytic infiltration in mice with CIA and significantly restored the Treg/Th17 balance by reducing the transcription of IL-6 in splenocytes. DC32 significantly inhibited the lymphocyte-induced invasion and migration of FLSs by decreasing the secretion of MMPs (MMP-2, MMP-3) in vitro. DC32 also reduced the transcription of chemokines (CXCL12, CX3CL1) and IL-6 in FLSs, as well as IL-6 levels in the supernatant. These results demonstrated that DC32 may attenuate RA by restoring Treg/Th17 balance and inhibiting lymphocytic infiltration through downregulation of the expression and transcription of IL-6. This study supports the potential of DC32 to down-regulate IL-6 for the treatment of RA and other related autoimmune diseases.


Assuntos
Antirreumáticos/uso terapêutico , Artemisininas/uso terapêutico , Artrite Experimental/tratamento farmacológico , Interleucina-6/metabolismo , Sinovite/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Antirreumáticos/química , Artemisininas/farmacologia , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Ratos , Ratos Sprague-Dawley
18.
Med Ultrason ; 20(3): 328-334, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30167586

RESUMO

AIM: Patients describe rheumatoid arthritis (RA) remission as the absence of any symptoms or return to normality. Residual ultrasound (US) synovitis was frequently described in remission cohorts in previous studies. US tenosynovitis evaluation and scoring seems to better follow clinical remission scores compared with synovitis in RA. Our objective was to verify the presence of US findings suggestive of persistent inflammation in a cohort of patients in remission according to their own opinion. MATERIALS AND METHODS: Forty-three RA patients were prospectively enrolled in this pilot study between 2015-2017 according to their positive answer to the question "Are you feeling free of symptoms, just like before your RA symptomsstarted?". Clinical evaluation of tender and swollen joints was performed in the same day with US evaluation of 24 joints and 26 tendon sites and lab C-reactive protein (CRP) evaluation. DAS28-CRP and SDAI were calculated. RESULTS: A total of 72.9% (35 of 43) of patients were in remission per DAS28 criteria. Except for CRP value, no other variables were significantly different in the 35 of 43. PD scoring in tenosynovitis of the ankle and feet was 100% overlapping remission felt by patients. PD tenosynovitis in both upper and lower limbs was found in less than 10% of patients, and only grade 1 (minimal). CONCLUSION:  A combination of patients' opinion and PDUS evaluation could be a starting point for RA treatment tapering.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Amplitude de Movimento Articular/fisiologia , Ultrassonografia Doppler/métodos , Adulto , Idoso , Artrite Reumatoide/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Medição de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Sinovite/diagnóstico por imagem , Sinovite/tratamento farmacológico , Sinovite/fisiopatologia , Tenossinovite/diagnóstico por imagem , Tenossinovite/tratamento farmacológico , Tenossinovite/fisiopatologia , Resultado do Tratamento , Adulto Jovem
19.
Indian J Ophthalmol ; 66(10): 1483-1485, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30249847

RESUMO

The classic entity of autosomal dominant Blau syndrome (BS) consists of arthritis, dermatitis, and uveitis, occurring as a result of mutations in the NOD2 gene pattern recognition receptor. Sporadic cases are those in which no known gene mutation is identifiable. Uveitis in BS can be refractory to conventional therapy. We report a case of sporadic Blau uveitis managed with adalimumab monotherapy after failing to respond to topical steroids, systemic steroids, methotrexate, and infliximab therapy sequentially. Uveitis resolved completely with adalimumab and the patient has had a disease-free period over a 2-year follow-up with bi-monthly injections for arthritis control.


Assuntos
Adalimumab/administração & dosagem , Artrite/complicações , Sinovite/complicações , Uveíte/etiologia , Anti-Inflamatórios/administração & dosagem , Artrite/diagnóstico , Artrite/tratamento farmacológico , Pré-Escolar , Relação Dose-Resposta a Droga , Humanos , Injeções Subcutâneas , Masculino , Sinovite/diagnóstico , Sinovite/tratamento farmacológico , Tomografia de Coerência Óptica , Uveíte/complicações , Uveíte/diagnóstico , Uveíte/tratamento farmacológico
20.
PLoS One ; 13(9): e0203607, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30188942

RESUMO

BACKGROUND: Neoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization. OBJECTIVE: To explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA. PATIENTS AND METHODS: Serum levels of eight angiogenic markers were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints. RESULTS: Serum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2 were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF) were associated with PDUS features indicating residual disease activity. CONCLUSION: Our results support the relevance of measuring serum levels of vascular markers to evaluate the intensity and extent of synovial vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable surrogate of active synovitis and their place in relation to PDUS in clinical practice deserve further investigation.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Membrana Sinovial/patologia , Sinovite/tratamento farmacológico , Adulto , Idoso , Análise de Variância , Antirreumáticos/uso terapêutico , Artrite Reumatoide/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Sinovite/patologia , Ultrassonografia Doppler , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA