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1.
J Rheumatol ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371648

RESUMO

OBJECTIVE: To analyse the prevalence of pre-existing palindromic rheumatism (PR) in patients with established rheumatoid arthritis (RA) and evaluate whether these patients have a distinctive clinical and serological phenotype. METHODS: Cross-sectional study in patients with established RA. Pre-existing PR was determined using a structured protocol and confirmed by retrospective review of medical records. Demographic, clinical, radiological, immunological and therapeutic features were compared in patients with and without PR. RESULTS: 158 patients with established RA (78% female) with a mean disease duration since RA onset of 5.1 ± 2.7 years were included. Pre-existing PR was recorded in 29 patients (18%). The median time from the onset of PR to progression to RA was 1.2 years. No between-group differences in demographic features, current disease activity radiographic erosive disease or disability were observed. Patients with PR had a higher prevalence of smoking (72% vs. 40%). Positive rheumatoid factor, anti-citrullinated peptide antibodies and anti-carbamylated protein antibodies were numerically higher in patients with PR. No differences in treatment were observed except for greater hydroxychloroquine use in patients with PR (38% vs. 6%). Palindromic flares persisted in a significant proportion of patients during the RA course, including patients in clinical remission or receiving biological DMARDs. CONCLUSION: Eighteen percent of patients with RA had a history compatible with PR previous to RA onset. No specific clinical or serological phenotype was identified in these patients, although higher hydroxychloroquine use and smoking prevalence were identified. Palindromic flares may persist during the RA disease course despite treatment.

2.
Br J Clin Pharmacol ; 85(8): 1710-1718, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30958574

RESUMO

AIMS: Tocilizumab has a direct effect on inflammatory markers. Therefore, composite measures for disease activity assessment in rheumatoid arthritis (RA) using these inflammatory markers may not be suitable for tocilizumab treatment. We used a modelling approach to describe the tocilizumab exposure-response relationship and to investigate the different dynamics of the individual components of the routinely used continuous composite measures. METHODS: Pharmacokinetic (PK), clinical and laboratory data were obtained from a prospective, observational, single-centre study involving 35 subjects with RA treated with intravenous tocilizumab. A population PK/pharmacodynamic analysis was performed using nonlinear mixed effects models. RESULTS: The population for model development comprised 1086, 1083 and 1082 observations calculated with the disease activity score based on 28 joint (DAS28) and the simplified and clinical disease activity scores (SDAI, CDAI). The tocilizumab exposure-response relationship was described with an indirect-response model. Two main groups of individual components were identified based on their different dynamics under tocilizumab treatment: (i) tender and swollen joint counts and patient and evaluator global assessment showed a slower decrease of their baseline value (half-life: 4.6 weeks, RSE: 24%) and the need for higher serum drug concentration (EC50 : 4.60 µg/mL, RSE: 103%, IIV: 359%) than (ii) C-reactive protein and erythrocyte sedimentation rate (half-life: 2.3 weeks, RSE 19%; EC50 : 0.878 µg/mL, RSE: 41%, IIV: 238%). CONCLUSION: Our study confirms a different dynamics of the individual components of the most frequently used continuous composite measures under tocilizumab treatment which should be taken into account to avoid misassessment of disease activity.

3.
Reumatol. clín. (Barc.) ; 15(2): 102-108, mar.-abr. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: ibc-ET1-3371

RESUMO

Objectives: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). Methods: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. Results: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. Conclusions: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal


Objetivos: Describir la prevalencia de comorbilidades en pacientes con AR en España y discutir sobre su manejo en la clínica diaria utilizando los datos de la cohorte española del estudio internacional COMORA. Métodos: Subanálisis nacional del estudio COMORA en el que se analizaron las características demográficas y clínicas de 200 pacientes con AR (1987 ACR) y las prácticas rutinarias para el cribado y la prevención de eventos cardiovasculares (CV), gastrointestinales y pulmonares, infecciones, cáncer, osteoporosis y depresión. Resultados: Los pacientes tenían una edad media de 58 años, una duración media de la enfermedad de 10 años, un DAS28 de 3,3 y el 25% estaba en remisión (DAS28 <2,6). El 22% de los pacientes presentaba al menos una comorbilidad, principalmente depresión (27%) y obesidad (26%). El 5% tenía historia de infarto de miocardio, el 1% de ictus y el 6% de tumor sólido. Una puntuación de Framingham >20% (51%), tener hipercolesterolemia (46%), hipertensión (41%) y fumar (25%) fueron los factores de riesgo CV más comunes. En relación con el cáncer de próstata, colon y piel, solo el 9, 10 y el 18% de los pacientes, respectivamente, estaban óptimamente controlados. Las infecciones tampoco se manejaban de forma óptima, con solo el 7 y el 17% de los pacientes vacunados contra la influenza y neumococo, respectivamente, al igual que la osteoporosis, con el 47% suplementados con la vitamina D y el 56% con una densitometría realizada. Conclusiones: En España, la prevalencia de comorbilidades y factores de riesgo CV en pacientes con AR establecida y avanzada es relativamente alta, y su manejo en la clínica diaria continúa siendo subóptimo

4.
Arthritis Res Ther ; 20(1): 275, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30545393

RESUMO

BACKGROUND: Calprotectin is a biomarker of disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and predicts relapse in juvenile idiopathic arthritis. Higher drug trough serum levels are associated with a good response in patients treated with tumor necrosis factor inhibitors (TNFi). Power Doppler ultrasound synovitis is predictive of relapse and structural damage progression in patients in clinical remission. The purpose of this study was to analyze the accuracy of serum calprotectin levels, drug trough serum levels (TSL), and power Doppler (PD) activity as predictors of relapse in RA and PsA patients in remission or with low disease activity receiving TNFi. METHODS: This was a longitudinal, prospective, 1-year single-center study of 103 patients (47 RA, 56 PsA) receiving TNFi in remission or with low disease activity (28-joint Disease Activity Score (DAS28) ≤ 3.2). The predictive value of serum calprotectin, TNFi TSL, and PD were assessed using receiver operating characteristic (ROC) analyses. To illustrate the predictive performance of calprotectin, TNFi TSL, and PD score, Kaplan-Meier curves were constructed from baseline to relapse. Associations between baseline factors and relapse were determined using Cox regression models. Multivariate models were constructed to analyze the effect of covariates and to fully adjust the association between calprotectin, TNFi TSL, and PD score with relapse. A generalized estimating equation model with an identity link for longitudinal continuous outcomes was used to assess the effect of covariates on TNFi TSL. RESULTS: Ninety-five patients completed 1 year of follow-up, of whom 12 experienced a relapse. At baseline, relapsers had higher calprotectin levels, lower TNFi TSL, and higher PD activity than nonrelapsers. ROC analysis showed calprotectin fully predicted relapse (area under the curve (AUC) = 1.00). TNFi TSL and PD had an AUC of 0.790 (95% confidence interval (CI) 0.691-0.889) and 0.877 (95% CI 0.772-0.981), respectively. Survival analyses and log rank tests showed significant differences between groups according to calprotectin serum levels (p < 0.001), TNFi TSL (p = 0.004), and PD score (p < 0.001). Univariate Cox regression models showed that time-to-remission/low disease activity (hazard ratio (HR) = 1.17, p < 0.001), calprotectin levels (HR = 2.38, p < 0.001), TNFi TSL (HR = 0.47, p = 0.018), and PD score (HR = 1.31, p < 0.001) were significantly associated with disease relapse. In the multivariate analysis, only baseline calprotectin levels independently predicted disease relapse (HR = 2.41, p = 0.002). The generalized estimating equation analysis showed that only disease activity by DAS28-erythrocyte sedimentation rate (ESR) was significantly associated with longitudinal changes in TNFi TSL (regression coefficient 0.26 (0.0676 to 0.0036), p = 0.001). CONCLUSION: Time-to-remission/low disease activity, calprotectin serum levels, TNFi TSL, and PD score were significantly associated with disease relapse. However, only baseline calprotectin serum levels independently predicted disease relapse in RA and PsA patients under TNFi therapy.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Complexo Antígeno L1 Leucocitário/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso , Artrite Psoriásica/sangue , Artrite Psoriásica/diagnóstico , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Recidiva , Indução de Remissão , Fator de Necrose Tumoral alfa/metabolismo
6.
Reumatol. clín. (Barc.) ; 14(supl.2): 55-62, jun. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-176068

RESUMO

Actualmente, las diferentes guías de tratamiento de la artritis reumatoide recomiendan el uso de los fármacos biológicos en combinación con metotrexato (u otros fármacos antirreumáticos modificadores de la enfermedad de naturaleza sintética) siempre que sea posible. Pero la realidad de prescripción, según diferentes registros, muestra que los tratamientos biológicos se utilizan en muchas ocasiones en monoterapia. En la actualidad existen 2 fármacos biológicos inhibidores del receptor de la IL-6 aprobados por la European Medicines Agency para el tratamiento de la artritis reumatoide, uno con amplia experiencia clínica, tocilizumab, y otro a punto de su comercialización en nuestro país, sarilumab. Estos fármacos biológicos inhibidores de la IL-6 en monoterapia serían más efectivos que otros biológicos en monoterapia en el tratamiento de la artritis reumatoide, según demuestran diversos estudios. El objetivo de esta revisión es proporcionar los datos disponibles sobre el uso de los distintos fármacos biológicos inhibidores de IL-6 en monoterapia en la artritis reumatoide, y analizar de forma comparativa el papel de los otros agentes biológicos en monoterapia en esta enfermedad


The current recommendations and guidelines for the treatment of RA include the use of biological DMARDs (bDMARDs) in combination with methotrexate or other conventional synthetic DMARDs whenever possible. However, bDMARDS are frequently used in monotherapy according to data from several registries. Nowadays, two bDMARDS aimed at the IL-6 receptor have been approved by the European Medicines Agency (EMA) for treating RA: tocilizumab, with extensive clinical experience, and sarilumab, which will soon be commercialised in Spain. Several studies have confirmed that both IL-6 inhibitors are more effective than other bDMARDs when used in monotherapy. The aim of this review is to update the available information on the use of IL-6 inhibitors in monotherapy and to analyse the comparative role of the remaining bDMARDS when used in monotherapy in RA


Assuntos
Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Terapia Biológica , Interleucina-6/antagonistas & inibidores , Dose Única , Etanercepte/administração & dosagem , Adalimumab/administração & dosagem , Certolizumab Pegol/administração & dosagem , Infliximab/administração & dosagem , Metotrexato/administração & dosagem , Abatacepte/administração & dosagem , Rituximab/administração & dosagem
7.
Immunotherapy ; 10(6): 447-464, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29495891

RESUMO

Rheumatoid arthritis (RA) is the most prevalent immune-mediated chronic rheumatic disease and is associated with joint destruction and disability. Therapeutic strategies, including biological disease-modifying antirheumatic drugs (bDMARDs) have improved the prognosis and quality of life of RA patients. Tocilizumab (TCZ) is a humanized monoclonal antibody against IL-6 receptor licensed in 2009 that has demonstrated clinical efficacy in various adult RA populations. RA management guidelines and recommendations consider TCZ as one of the bDMARDS indicated after methotrexate or other conventional synthetic DMARDs and/or TNF inhibitors failure in adult RA. Of particular interest is the demonstration of its effectiveness in monotherapy in comparison with other bDMARDs. Recent observational studies have shown good results for the safety profile of TCZ with no new alert signals.

8.
Br J Clin Pharmacol ; 84(4): 716-725, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29314183

RESUMO

AIMS: Intravenous tocilizumab is currently dosed on body weight, although a weak correlation between body weight and clearance has been described. The aim of the study was to assess the current dosing strategy and provide a scientific rational for dosing using a modelling and simulation approach. METHODS: Serum concentrations and covariates were obtained from intravenous tocilizumab treated subjects at a dose of 4, 6 or 8 mg every 28 days. A population pharmacokinetic analysis was performed using nonlinear mixed effects modelling. The final model was used to simulate tocilizumab exposure to assess a dosing strategy based on body weight or fixed dosing, using as target a cumulative area under the curve at 24 weeks of treatment above 100 × 103  µg h ml-1 . RESULTS: A one-compartment disposition model with parallel linear and nonlinear elimination best described the concentration-time data. The typical population mean values for clearance, apparent volume of distribution, maximum elimination rate and Michaelis-Menten constant were 0.0104 l h-1 , 4.83 l, 0.239 mg h-1 and 4.22 µg ml-1 , respectively. Interindividual variability was included for clearance (17.0%) and volume of distribution (30.8%). Significant covariates for clearance were patient body weight and C-reactive protein serum levels. An estimated exponent for body weight of 0.360 confirms the weak relationship with tocilizumab clearance. Simulations demonstrate that patients with lower weights are at risk of underdosing if the weight-based dosing approach is used. However, fixed-dosing provides a more consistent drug exposure regardless of weight category. CONCLUSIONS: Our study provides evidence to support fixed dosing of intravenous tocilizumab in rheumatoid arthritis patients since it reduces variability in tocilizumab exposure among weight categories compared to the current weight-based dosing approach.

9.
Reumatol Clin ; 2017 Jul 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-28711461

RESUMO

OBJECTIVES: To describe the prevalence of comorbidities in patients with RA in Spain and discuss their management and implications using data from the Spanish cohort of the multinational study on COMOrbidities in Rheumatoid Arthritis (COMORA). METHODS: This is a national sub-analysis of the COMORA study. We studied the demographics and disease characteristics of 200 adults patients diagnosed with RA (1987 ACR), and routine practices for screening and preventing the following selected comorbidities: cardiovascular, infections, cancer, gastrointestinal, pulmonary, osteoporosis and depression. RESULTS: Patients had a mean age of 58 years and a mean RA duration of 10 years. Mean DAS28 score was 3.3 and approximately 25% of patients were in remission (DAS28 <2.6). Forty-four (22%) patients had ≥1 comorbidity, the most frequent being depression (27%) and obesity (26%). A history of myocardial infarction or stroke was observed in 5% and 1% of patients, respectively, and any solid tumor in 6%. Having a Framingham Risk Score >20% (51%), hypercholesterolemia (46%) or hypertension (41%) and smoking (25%) were the most common CV risk factors. For prostate, colon and skin cancers, only 9%, 10% and 18% of patients, respectively, were optimally monitored. Infections were also inadequately managed, with 7% and 17% of patients vaccinated against influenza and pneumococcal, respectively, as was osteoporosis, with 47% of patients supplemented with vitamin D and 56% with a bone densitometry performed. CONCLUSIONS: In Spain, the prevalence of comorbidities and CV risk factors in RA patients with established and advanced disease is relatively high, and their management in clinical daily practice remains suboptimal.

10.
Arthritis Res Ther ; 19(1): 141, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28619044

RESUMO

BACKGROUND: To analyze differences in the recognition of anti-citrullinated peptide/protein antibody (ACPA) citrullinated epitopes and isotypes in patients with palindromic rheumatism (PR) and rheumatoid arthritis (RA). METHODS: ACPA fine specificities (citrullinated peptides of enolase, fibrin, and vimentin) and isotypes (IgG, IgM, and IgA) were analyzed in 54 patients with longstanding PR and 54 patients with established RA. RESULTS: CCP2 tested positive in 66.7% of patients with PR and RA. The ACPA distribution of fine specificities and isotypes differed between PR and RA patients. PR patients had a lower frequency of fine ACPA specificities than RA patients, which was significant in the case of a peptide derived from vimentin (PR 24.1% vs. 59.3% RA; p < 0.001). The mean number of ACPA specificities was lower in PR than in RA patients, and only 25.9% of PR patients recognized ≥2 additional specificities compared with 46.3% of RA patients. Significantly less isotype usage, especially IgA, was observed in PR patients. CONCLUSION: The ACPA immune response differed in patients with PR and RA, with fewer fine specificities and isotype usage in patients with PR. Some patients with PR may have impaired maturation of the B-cell response against citrullinated peptides with no progression to RA.


Assuntos
Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Adulto , Idoso , Especificidade de Anticorpos , Estudos Transversais , Feminino , Humanos , Isotipos de Imunoglobulinas , Masculino , Pessoa de Meia-Idade
11.
Semin Arthritis Rheum ; 47(3): 303-309, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28549731

RESUMO

OBJECTIVE: To determine clinical and sonographic biomarkers predicting structural damage progression at 12 months of follow-up as measured by magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) patients in clinical remission. PATIENTS AND METHODS: We included patients with RA in clinical remission, defined as 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for >6 months. Ultrasound scans of both hands and knees and MRI of the dominant hand were performed at baseline and at 12 months. RESULTS: Out of 55 patients, 42 completed the follow-up. Among them, 78% were female, aged (median) 54 years; disease duration was 93 months. In total, 12 (28%) patients were taking oral prednisone, 34 (81%) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 20 (47%) biological therapies. At baseline, 45% fulfilled criteria previously defined for ultrasound-defined active synovitis (UdAS) [PD (power Doppler) signal + synovial hyperplasia ≥2]. Multivariate analysis showed significant associations between baseline MRI erosion score, body mass index (BMI), disease duration, prednisone treatment, absence of biologic and csDMARDs, UdAS, and MRI erosion score progression after 12 months. In an exploratory analysis, serum levels of calprotectin correlated significantly with bone edema progression. CONCLUSIONS: We identified clinical and sonographic markers of structural damage progression after 12 months follow-up in patients with RA in clinical remission. Meeting the criteria of ultrasound active synovitis, defined as simultaneous relevant synovial hyperplasia and PD, was associated with erosion progression after 12 months. Calprotectin was associated with bone edema, in an exploratory analysis.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Progressão da Doença , Edema/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Sinovite/diagnóstico por imagem , Ultrassonografia/métodos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/patologia , Biomarcadores/sangue , Sedimentação Sanguínea , Edema/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Articulação da Mão/diagnóstico por imagem , Articulação da Mão/patologia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Complexo Antígeno L1 Leucocitário/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prednisona , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Sinovite/sangue , Sinovite/patologia
12.
Clin Exp Rheumatol ; 35(1): 74-79, 2017 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27749227

RESUMO

OBJECTIVES: To analyse clinical, serological and sonographic differences between rheumatoid arthritis (RA) and polyarticular psoriatic arthritis (PsA) patients on anti-TNF therapy in clinical remission. METHODS: Angiogenic and proinflammatory cytokine serum levels were determined by multiplex ELISA in patients with RA and PsA in clinical remission (DAS28-ESR<2.6), clinically-active RA patients (DAS28>3.2) and healthy controls. Ultrasound (US) scans were made of both wrists and hands. RESULTS: 30 RA and 47 PsA patients in remission, 22 active RA patients and 20 healthy controls were included. PsA patients had significantly lower disease activity according to DAS28-ESR (p=0.006) but not according to DAS28-CRP (p=0.319), and lower serum levels of proinflammatory and angiogenic cytokines than RA patients in remission. PsA patients had cytokine levels similar to healthy controls, while RA patients in remission had similar levels to those of active RA patients. Globally, 31 (40.25%) patients in remission had a PD signal and 12 had SH>2 plus PD [1 PsA vs. 11 RA (p=0.0001)], meeting the criteria for ultrasound-defined active synovitis (UdAS). Patients with UdAS had significantly higher levels of IL-6, IL-20, PIGF and SDF1. More PsA patients were on tapered doses of anti-TNF (63.8%), and more frequently as monotherapy (72.3%), compared with RA patients (26.6% and 20%, respectively). CONCLUSIONS: Polyarticular PsA patients in remission had lower levels of local (US synovitis) and systemic inflammation than RA patients in remission, even though a significantly higher percentage of PsA patients were on tapered doses of anti-TNF, mainly in monotherapy.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Citocinas/sangue , Inflamação/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Idoso , Artrite Psoriásica/sangue , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/patologia , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/patologia , Progressão da Doença , Feminino , Articulação da Mão/diagnóstico por imagem , Humanos , Inflamação/sangue , Inflamação/diagnóstico por imagem , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia , Articulação do Punho/diagnóstico por imagem
13.
ESMO Open ; 1(1): e000032, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27843587

RESUMO

Immune checkpoint inhibitors, such as ipilimumab (an anti-CTLA4 antibody), have become a commonly used therapy in cancer. To date, safety data of patients with underlying autoimmune disease is limited. We present a case of a patient with rheumatoid arthritis who was diagnosed of a BRAF-mutant metastatic melanoma. The patient was treated with ipilimumab and presented with high-grade colitis requiring immunosuppressors. Despite of the immune-related adverse event, no exacerbation of the rheumatoid arthritis was observed and the patient achieved a complete response. This case report contributes to the scarce literature on the use of immune checkpoint inhibitors in patients with an underlying autoimmune condition.

14.
Arthritis Res Ther ; 18(1): 160, 2016 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-27391315

RESUMO

BACKGROUND: Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. METHODS: We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate <3.2). Associations of calprotectin, TNFi trough serum levels and acute phase reactants with PDUS synovitis were assessed using correlation and linear regression analyses. The accuracy and discriminatory capacity in detecting PDUS synovitis was assessed using ROC curves. RESULTS: PDUS synovitis was found in 62.4 % of RA patients and 32 % of PsA patients. Both RA and PsA patients with PDUS synovitis had higher calprotectin levels and lower TNFi trough serum levels. Calprotectin positively correlated with ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was ≥1.66 µg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC <0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN. CONCLUSIONS: Calprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Psoriásica/sangue , Artrite Reumatoide/sangue , Complexo Antígeno L1 Leucocitário/sangue , Sinovite/diagnóstico por imagem , Fator de Necrose Tumoral alfa/sangue , Adalimumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Etanercepte/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Sinovite/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ultrassonografia Doppler
15.
Arthritis Res Ther ; 18: 74, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27036513

RESUMO

BACKGROUND: Patients with rheumatoid arthritis (RA) in clinical remission may have ultrasound-defined synovitis according to the presence of power Doppler (PD) signal. The objective was to describe the immunopathologic characteristics of ultrasound-defined synovitis compared with synovitis in patients with clinically active RA. METHODS: We included between 6 and 8 ultrasound-guided synovial biopsies per patient from 20 patients with RA in clinical remission (DAS28-ESR <2.6) with PD signal, 22 synovial tissue samples (ST) from patients with clinically active RA (swollen joint with confirmed inflammatory synovial fluid) as inflammatory controls, and 10 ST from non-inflammatory controls. Immunostaining for CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD117 (mast cells), hsp47 (fibroblasts), bFGF and CXCL12 (angiogenic factors) was made and quantified by digital image analysis. The number of CD31 vessels/mm(2) was quantified. RESULTS: RA patients in remission with PD signal had significantly reduced synovial T-cell, B-cell, mast cell and fibroblast density, but similar macrophage infiltration compared with patients with clinically active RA. Vascularity, bFGF and CXCL12 were partially reduced in RA patients in remission with PD signal compared to those with active RA, but were significantly higher compared with ST from non-inflammatory controls. During the 12-month follow up, 8/20 RA patients (40 %) lost remission: all had synovial hypertrophy grade ≥2 and significantly more synovial B cells and mast cells than patients maintaining remission. CONCLUSIONS: Asymptomatic ultrasound-defined synovitis and clinically active arthritis differ in the degree of infiltrating lymphoid, mast cells and fibroblast density, but are similar with respect to macrophage infiltration. Persistently increased angiogenic factor expression and vascularity may explain the persistence of a PD signal.


Assuntos
Artrite Reumatoide/patologia , Sinovite/diagnóstico por imagem , Sinovite/imunologia , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/imunologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Biópsia Guiada por Imagem/métodos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Sinovite/etiologia , Ultrassonografia
16.
Arthritis Care Res (Hoboken) ; 68(7): 899-906, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26841119

RESUMO

OBJECTIVE: To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels. METHODS: We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]). RESULTS: Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with ≥1 swollen joint (1.74 µg/ml versus 3.04 µg/ml; P = 0.010). Using DAS28 ≥2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was ≥2.47 µg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (ρ = -0.671, P < 0.001) and IFX (ρ = -0.729, P = 0.017). CONCLUSION: Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acute-phase reactants, even in patients with low inflammatory activity.


Assuntos
Proteínas da Fase Aguda/análise , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Complexo Antígeno L1 Leucocitário/sangue , Adalimumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Artrite Reumatoide/sangue , Estudos Transversais , Etanercepte/uso terapêutico , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Fator de Necrose Tumoral alfa/antagonistas & inibidores
17.
Rheumatology (Oxford) ; 54(12): 2239-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26242859

RESUMO

OBJECTIVE: To compare the accuracy of serum calprotectin levels, CRP and ESR in stratifying disease activity in RA patients receiving tocilizumab (TCZ). METHODS: Cross-sectional study of 33 RA patients receiving TCZ. DAS28, Simplified Disease Activity Index, Clinical Disease Activity Index, joint counts and serum levels of CRP, ESR, calprotectin and TCZ were measured. Associations between calprotectin, ESR and CRP and articular indices were analysed by correlation and linear regression. The accuracy and discriminatory capacity of calprotectin was assessed by receiver operating characteristic curves (area under the curve). RESULTS: Calprotectin levels, but not CRP or ESR, were strongly correlated with all composite indices (all r coefficients over 0.50). Calprotectin, but not CRP or ESR, was significantly lower in patients in remission compared with those with low disease activity [1.57 µg/ml (s.d. 1) vs 3.35 µg/ml (s.d. 1), P = 0.001]. In a fully adjusted model (R(2) = 0.82), DAS28-ESR increased 0.48 units per µg/ml calprotectin increase (P < 0.001). Using a DAS28 >3.2 as the reference variable, calprotectin showed an area under the curve of 0.922, and the best cut-off was 5.19 µg/ml (odds ratio 11.5). CRP levels, but not calprotectin, were dependent on detectable TCZ trough serum levels. CONCLUSION: Calprotectin serum levels seem to be an accurate biomarker for assessing disease activity in RA patients receiving TCZ.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/metabolismo , Complexo Antígeno L1 Leucocitário/sangue , Adulto , Artrite Reumatoide/sangue , Biomarcadores/sangue , Sedimentação Sanguínea , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
18.
J Rheumatol ; 41(8): 1650-5, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25028368

RESUMO

OBJECTIVE: To investigate the presence of subclinical synovitis by ultrasound (US) and the clinical phenotype in patients with palindromic rheumatism (PR) according to anticitrullinated protein antibody (ACPA) status. METHODS: Fifty-four patients with PR were studied. Clinical, demographic, serological, and therapeutic characteristics were compared in ACPA-positive and ACPA-negative patients. US searching for synovial hypertrophy (SH) and power Doppler signal (PDUS) in 22 joints of the hands was performed in the intercritical period. The results were compared according to ACPA status and with a healthy control group (n = 30). In 10 patients, US was performed during the joint attack. RESULTS: Most patients were female (63%) with a mean disease duration of 11.6 ± 10.7 years. Thirty-six patients (66.7%) were ACPA-positive. ACPA-positive patients had a shorter duration of attacks, a younger age, and less knee involvement at disease onset. US examination showed SH grade ≥ 1 in 79.6% of patients with PR and 50% of controls. Significant US results (SH ≥ 2 or PDUS) were observed in 2.7% and 1.4% of joints assessed and in 33% and 25.9% of patients with PR, respectively. Only 4 patients (7.4%) had US active synovitis (SH ≥ 2 plus PDUS) in at least 1 joint. US assessment showed no significant differences between ACPA-positive and ACPA-negative patients. PDUS was observed in 7 out of 10 patients during attacks. CONCLUSION: Some differences emerged in the clinical phenotype of PR according to ACPA status. Most patients with PR do not have US subclinical synovitis in the intercritical period, even those who are ACPA-positive.


Assuntos
Anticorpos Anti-Idiotípicos/sangue , Artrite Reumatoide/complicações , Peptídeos Cíclicos/imunologia , Sinovite/diagnóstico por imagem , Sinovite/diagnóstico , Adulto , Idoso , Anticorpos Anti-Idiotípicos/imunologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Hipertrofia , Masculino , Pessoa de Meia-Idade , Fenótipo , Índice de Gravidade de Doença , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Sinovite/imunologia , Ultrassonografia
20.
Reumatol. clín. (Barc.) ; 10(1): 10-16, ene.-feb. 2014.
Artigo em Espanhol | IBECS | ID: ibc-120439

RESUMO

Objetivo. Analizar la frecuencia y características de la reducción de dosis de fármacos biológicos en una cohorte de pacientes con artritis crónica, en condiciones de práctica clínica de un hospital de tercer nivel. Material y métodos. Estudio descriptivo y transversal, que incluyó a todos los pacientes visitados consecutivamente durante 6 meses(junio de 2011-noviembre de 2011) por un solo investigador, con pacientes que habían recibido al menos una dosis de fármaco biológico durante el año 2011. Resultados. Se incluyeron 153 pacientes: artritis reumatoide (AR) (n = 82), espondilitis anquilosante (n = 29), artritis psoriásica (n = 20)y grupo miscelánea (n = 22) con una evolución media de 14,9 ± 7,7 años. En el momento del análisis, 70 pacientes (45,7%) estaba con dosis reducida (un 50% en el grupo miscelánea; un 50% en artritis psoriásica; un 48,2% en espondilitis anquilosante, y un 42,6% en AR). El tiempo medio de reducción de dosis fue de 17,4 ± 17,5 meses. Los fármacos biológicos más utilizados a dosis reducidas fueron: etanercept, adalimumab y tocilizumab; el 57,6, el 54,9 y el 40 respectivamente de los pacientes tratados con estos agentes lo hacían a dosis reducidas. Los pacientes con dosis reducidas en comparación con aquellos con dosis normales tenían un mismo tiempo de evolución de la enfermedad, pero recibían menos FAME, glucocorticoides y AINE, con un tiempo similar de uso del agente biológico. Los pacientes con AR y dosis reducidas tenían, en el momento del análisis, mayores índices de remisión que los pacientes con dosis normales (82,9 vs. 34%, p < 0,0001). La decisión terapéutica en el momento del análisis fue mantener la dosis reducida en la práctica totalidad de los pacientes. Conclusión. En nuestra práctica clínica, el 45,7% de los pacientes con artritis crónica reciben terapia biológica a dosis reducidas, tras haber alcanzado la remisión o baja actividad a dosis estándares, manteniendo la mayoría de ellos un buen control de la enfermedad (AU)


Objective: To analyze the frequency and characteristics of dose reduction of biological agents in a cohort of patients with chronic arthritis, in clinical practice conditions in a tertiary level hospital. Material and methods: Descriptive, cross-sectional study, which included all patients, followed consecutively during 6 months (June 2011-November 2011), by one investigator, with patients who at least have received one dose of biological agents in 2011. Results: We included 153 patients: Rheumatoid arthritis (RA) (n = 82), ankylosing spondylitis (n = 29), psoriatic arthritis (n = 20), and miscellaneous group (n = 22). Mean disease duration was 14.9 ± 7.7 years. At the time of analysis, 70 patients (45.7%) were receiving low doses of biological therapy (50% in miscellaneous group group, 50% in psoriatic arthritis, 48.2% in ankylosing spondylitis, and 42.6% in RA). Mean time of dosage reduction was 17.4 ± 17.5 months. The most common biological agents used in low dose were: etanercept, adalimumab and tocilizumab; 57.6%, 54.9% and 40% respectively, in patients with a reduced dose of biological therapy. The patients at low dose of biological therapy compared with standard dose, had similar mean disease duration, but received significantly less DMARDs, glucocorticoids and NSAIDs, and similar biological agent duration. RA patients with reduced biological treatment, at the time of analysis, had higher remission rates versus patients receiving a standard dose (82.9% vs 34%, p < 0.0001). The medical decision at the time of analysis was to maintain low-dosage biological treatment in almost all patients. Conclusion: In our clinical practice, 45.7% of our chronic arthritis patients receive low dose of biological therapy, after achieving remission or low activity at standard doses, maintaining a good control of the disease (AU)


Assuntos
Humanos , Masculino , Feminino , Terapia Biológica/instrumentação , Terapia Biológica/métodos , Terapia Biológica , Doenças Reumáticas/terapia , Artropatia Neurogênica/terapia , Artrite/terapia , Artrite Reumatoide/terapia , Terapia Biológica/estatística & dados numéricos , Terapia Biológica/tendências , Estudos de Coortes , Estudos Transversais/métodos , Estudos Transversais/tendências , Estudos Transversais , Estudos Retrospectivos
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