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1.
Rheumatol Int ; 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31396686

RESUMO

With the aim to develop and validate a clinical + ultrasound (US) inflammation score in rheumatoid arthritis (RA) for use in clinical practice, a mixed-method study was conducted. The theoretical development of the index was achieved with qualitative methodology (discussion group and Delphi survey). Subsequently, a cross-sectional study was carried out to analyse issues related to scoring and validation of the new index. RA patients underwent clinical [28 swollen and tender joints count, patient and physician global assessment (PhGA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)], and US assessments [synovitis or tenosynovitis by grey-scale (GS) and power Doppler (PD) of 42 structures]. An index was created based on statistical models and expert interaction. Construct validity was tested by correlation with DAS28, SDAI, CDAI, and PhGA. Reliability was evaluated in a subgroup of patients with the intraclass correlation coefficient (ICC). US assessment, CRP, and swollen joints were the items that passed the prioritization phase (Delphi study). For the cross-sectional study, 281 patients were randomly divided into design (n = 141) and validation samples (n = 140). The combination of US sites chosen (7 bilaterally) detected the maximum proportion of synovitis and PD present. Three scoring methods were tested: semiquantitative (0-3 GS + 0-3 PD), dichotomous (0/1 GS + 0/1 PD), and qualitative (0/1 based on algorithm). All showed strong correlation with activity measures (ρ ≥ 0.60), and reliability (ICC 0.89-0.93). The index with best parameters of validity, feasibility, and reliability was the qualitative. The final index chosen was the sum of swollen joint count, US qualitative score, and CRP. The UltraSound Activity score is a valid and reliable measure of inflammation in RA equal to the sum of 28 SJC, a simplified (0/1) US assessment of 11 structures and CRP. It is necessary further investigation to demonstrate additional value over existing indices.

2.
Mediators Inflamm ; 2019: 2473164, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944545

RESUMO

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.


Assuntos
Linfócitos B/metabolismo , Linfócitos B/patologia , Plaquetas/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/patologia , Linfócitos/metabolismo , Linfócitos/patologia , Adulto , Ligante de CD40/sangue , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade
3.
Medicine (Baltimore) ; 98(6): e14361, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30732168

RESUMO

Rheumatoid arthritis (RA) has been related to an impairment of the nutritional status. Body mass index (BMI) has been used but questions arise about how to properly evaluate nutritional status in RA patients. Few studies have evaluated it by dual-energy X-ray absorptiometry.In women with RA, to analyze:Case-control study including 89 women with RA. The control group was composed by 100 patients affected by non-inflammatory rheumatic disorders. Study variables included age, RA duration, history, activity and disability, and in relation to nutritional status: BMI, serum albumin (ALB), whole body DXA assessment, and skeletal muscle index (SMI).Mean age of patients was 62 ±â€Š8 years, mean duration of RA was 14 ±â€Š9 years, mean disease activity score (DAS28) was 3.7 ±â€Š1.4 and mean Health Assessment Questionnaire was 0.88 ±â€Š0.77. BMI was 27.43 ±â€Š5.16 Kg/m in patients and 27.78 ±â€Š3.98 Kg/m in controls (P: ns). ALB was within normal range in all patients.By whole body DXA, RA patients presented a statistically significant lower lean mass in all locations and lower fat mass in limbs than controls. Patients had a redistribution of fat mass to trunk. Lean mass directly correlated with fat mass.Neither BMI nor ALB correlated with DXA parameters.BMI, appendicular lean mass and SMI correlated inversely with disease duration. Trunk lean mass correlated inversely, and fat mass directly, with RA disability parameters.RA patients fulfilled criteria of sarcopenia in 44% of cases versus 19% of controls (P <.001). In RA patients, regarding SMI, BMI showed a high specificity to detect sarcopenia (94% of the patients with low BMI had sarcopenia) but low sensitivity (47% of the patients with normal BMI or overweight had sarcopenia).RA patients have an impairment of nutritional status associated to disease duration that looks like sarcopenia and that is not predicted by BMI.


Assuntos
Absorciometria de Fóton/métodos , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/patologia , Estado Nutricional , Idoso , Composição Corporal , Índice de Massa Corporal , Estudos de Casos e Controles , Avaliação da Deficiência , Feminino , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Sobrepeso/epidemiologia , Fatores de Risco , Sarcopenia/epidemiologia , Albumina Sérica/análise , Fatores Socioeconômicos , Espanha
4.
Ann Rheum Dis ; 78(3)2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30552173

RESUMO

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

5.
Reumatol Clin ; 2018 Sep 17.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30236749

RESUMO

OBJECTIVES: To assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. MATERIALS AND METHODS: SONAR (NCT01526434), a 12-week, open-label, prospective, observational, multicenter study. Patients with active RA for ≥3 months, according to ACR criteria, were treated with CZP (400mg at Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint was change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS). Joint inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB to Week 12 in synovial hypertrophy, effusion and PD signal indices. RESULTS: A total of 77/80 enrolled patients received ≥1 dose of CZP. The 12-week mean reduction from baseline (SD) was -0.6 (0.6) for HAQ-DI and -2.2 (1.5) for DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: -36.8 [26.8]) and improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy, effusion and PD signal indices were reduced from baseline to Week 12. One death was reported during the study. CONCLUSIONS: Spanish patients with RA demonstrated improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP treatment. No new safety signals were identified, and the safety profile was in line with previous CZP studies. These results support previous clinical trial findings investigating CZP treatment for active RA.

6.
Reumatol. clín. (Barc.) ; 14(supl.2): 42-48, jun. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-176066

RESUMO

En junio de 2017, la European Medicines Agency aprobó sarilumab para el tratamiento de la artritis reumatoide, un nuevo anticuerpo monoclonal (subtipo IgG1) totalmente humano, que impide la unión de la interleucina (IL) 6 a las formas soluble y unida a la membrana del receptor de la IL-6, e inhibe la señal a través de IL-6. Administrado cada 2 semanas en dosis de 200 mg (con una dosis de 150 mg cada 2 semanas para el tratamiento de anormalidades de laboratorio), tiene una afinidad por el receptor muy elevada y ha demostrado ser un fármaco eficaz y seguro en el tratamiento de la artritis reumatoide. Esta eficacia se ha demostrado en diferentes ensayos clínicos evaluados en distintos escenarios: falta de respuesta a metotrexato, intolerancia y/o fallo a antifactor de necrosis tumoral alfa y en pacientes con intolerancia a metotrexato. Su doble dosis, su doble dispositivo de administración, su mecanismo dual y su beneficio reconocido lo sitúan como una nueva alternativa potencial en el tratamiento de la artritis reumatoide


In June 2017, the EMA approved sarilumab for the treatment of rheumatoid arthritis, a new monoclonal (subtype IgG1) fully human antibody directed against the alpha subunit of the interleukin-6 receptor complex that inhibits the signal through IL-6. The drug is administered every other week at a dose of 200 mg (or a dose of 150 mg every two weeks if there are laboratory abnormalities), shows very high affinity for the receptor and has proven to be an effective and safe drug in the treatment of rheumatoid arthritis (RA). Its efficacy has been demonstrated in several clinical trials in a variety of scenarios (lack of response to MTX, intolerance and / or failure to anti-TNF). Due to its double dose, the availability of two different devices for its administration, and its dual signaling mode of action and recognised benefit, sarilumab is a new potential alternative in the treatment of RA


Assuntos
Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Terapia Biológica , Interleucina-6/antagonistas & inibidores , Resultado do Tratamento , Eficácia/estatística & dados numéricos , Segurança do Paciente , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Anticorpos Monoclonais/efeitos adversos , Ensaios Clínicos como Assunto
7.
Rheumatol Ther ; 5(1): 243-253, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29204859

RESUMO

INTRODUCTION: The objective of the study was to evaluate changes regarding main European League Against Rheumatism (EULAR) recommendations on diagnosis and treatment of gout compared to a previous assessment. METHODS: The GEMA-2 (Gout Evaluation and MAnagement) is a transversal assessment of practice for gout by rheumatologists. Main outcome variables were improvement of the previous GEMA assessment regarding the rate of crystal-proven diagnosis and that reaching therapeutic serum urate target below 6 mg/dl at last visit. Other management variables (prophylaxis, treatment of flares, lifestyle change advice) were also evaluated along with general characteristics. The sample was powered to include at least 483 patients for up to 50% change. RESULTS: Data on management of 506 patients were retrieved from 38 out of 41 rheumatology units that participated in the previous GEMA audit. Crystal-proved diagnosis rate increased from 26% to 32% (31% improvement) and was higher in gout-dedicated practices; ultrasonography contributed to diagnosis in less than 1% of cases. Therapeutic serum urate at last visit improved from 41% to 64% of all patients (66% of patients on urate-lowering medications), in any case over 50% improvement from the previous assessment. The use of any urate-lowering medication available was not prescribed as per label dosing in patients who failed to achieve target serum urate. Clinical inertia to increase doses of either allopurinol or febuxostat was still present in clinical practice. CONCLUSION: Over 50% improvement in targeting therapeutic serum urate has been observed, but clinical inertia is still present. Diagnosis is still mostly clinically based, ultrasonography not being commonly contributive. FUNDING: Menarini España.

8.
Semin Arthritis Rheum ; 47(6): 757-764, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29157669

RESUMO

BACKGROUND: IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses. METHODS: Heparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients. RESULTS: Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups. CONCLUSIONS: RA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Interleucina-6/sangue , Receptores de Interleucina-6/sangue , Adulto , Idoso , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Rheumatol Int ; 37(6): 891-896, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28258474

RESUMO

Ultrasonography (US) has shown to be more sensitive than physical examination for diagnosis and assessment of rheumatoid arthritis (RA). It is also a useful approach for accurate monitoring and intensive treatment adjustment. However, there is limited information concerning the impact of US on therapeutic decision-making in routine daily practice. A single-center cross-sectional study in routine daily practice was conducted to determine the percentage of patients with rheumatoid arthritis (RA) in which treatment decision was modified on the basis of results of musculoskeletal ultrasonography. All consecutive patients with RA visited for the control of their disease between September and November 2014 were included. Patients were visited by their attending rheumatologist, who made a therapeutic decision according to the results of physical examination and laboratory tests. Thereafter, a musculoskeletal ultrasound (US) was performed by an independent expert sonographer. According to US findings, a change in therapeutic decision was considered, and categorized as 'negative' (maintenance of the therapeutic attitude) or 'positive' (intensification or reduction of treatment). A total of 78 patients (83% women, mean age 63.3 years) were included. In 29 patients [32%, 95% confidence interval (CI) 26.5-48.9], a change in the therapeutic decision was made, which included intensification of treatment in 18 (62.1%) and reduction of treatment in 11 (37.9%). Change of treatment was more frequent in patients with intermediate disease activity (low and moderate) than in those in clinical remission or with high activity (41.4 vs. 25%), in men than in women (53.8 vs. 33.8%), and in the presence than in the absence of bone erosions (43.6 vs. 21.7%), although differences were not statistically significant. We conclude that in patients with RA, joint US is a relevant complementary tool for treatment decisions in daily practice, particularly in patients with intermediate disease activity.


Assuntos
Artrite Reumatoide/diagnóstico por imagem , Tomada de Decisão Clínica , Articulações/diagnóstico por imagem , Ultrassonografia Doppler , Adulto , Idoso , Idoso de 80 Anos ou mais , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Estudos Transversais , Feminino , Humanos , Articulações/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Espanha , Adulto Jovem
11.
J Immunol ; 198(8): 3099-3108, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28250158

RESUMO

Soluble factors released from platelets can modulate the immune response of leukocytes. We and others have recently found that T lymphocytes with bound platelets have reduced proliferation and IFN-γ and IL-17 production. Thus, we speculate that if we induce the binding of platelets to lymphocytes, we will be able to regulate the inflammatory response. When we cocultured platelets with lymphocytes at different ratios, we were able to increase the percentage of lymphocytes with bound platelets. The coculture of platelets with lymphocytes in the presence of stimulation decreased the production of IFN-γ and TNF-α, T cell proliferation, and the expression of CD25, PD-L1, and SLAM. However, this coculture increased CD39 expression. All of these effects were dependent on the dose of platelets and operated indistinctly with platelets from different healthy donors. When platelets were cocultured in the same compartment with lymphocytes, we observed less IFN-γ and TNF-α production and T lymphocyte proliferation than in cultures with platelets separated from lymphocytes by a 0.4-µm pore size filter. The binding of platelets to lymphocytes was blocked with anti-P-selectin Abs, and when this occurred we observed higher IFN-γ and TNF-α production than in nonblocked conditions. The cocultures of platelets with synovial fluid cells from rheumatoid arthritis patients reduced inflammatory cytokine production and increased IL-10 production. These results suggest that platelet binding to lymphocytes effectively regulates T lymphocyte function. This mechanism could be easily applied to reduce inflammatory responses.


Assuntos
Artrite Reumatoide/imunologia , Plaquetas/imunologia , Citocinas/biossíntese , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Técnicas de Cocultura , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
13.
Reumatol. clín. (Barc.) ; 12(4): 201-205, jul.-ago. 2016.
Artigo em Inglês | IBECS | ID: ibc-153623

RESUMO

Primary Sjögren syndrome (PSS) is a chronic inflammatory autoimmune disease. Interstitial lung disease (ILD) can be an extraglandular complication. Objective. To evaluate the clinical characteristics of patients diagnosed with PSS with ILD. Methods. Multicentre cohort study with 25 patients diagnosed with PSS and ILD. Data of PSS, prognostic factors, pulmonary involvement variables, complementary tests that suggest a worse diagnosis and treatment given were collected. EULAR index was measured for Sjögren's syndrome. Results. We identified 25 patients. In 15/25 the diagnosis of ILD was done before the diagnosis of PSS. The histopathological patterns found were: 12 NSIP, 5 UIP, 4 OP, 2 LIP. PFRs showed restrictive pattern. The majority of the patients received glucocorticoid therapy, antimalarial or immunosuppressive treatment. Conclusions. Patients affected with PSS must be screened to catch a precocious diagnosis of ILD. The majority of the patients were diagnosed of ILD before being diagnosed of PSS. Multicenter cohorts are increasingly demanded and a multidisciplinary management is needed (AU)


El síndrome de Sjögren primario (SSP) es una enfermedad inflamatoria autoinmune. La enfermedad pulmonar intersticial (EPI) puede ser una complicación extraglandular. Objetivo. Evaluar las características clínicas de los pacientes diagnosticados de SSP con EPI. Métodos. Estudio de cohortes multicéntrico con 25 pacientes diagnosticados de SSP y EPI. Se recopilaron datos propios del SSP, factores pronóstico, variables de medida de la afectación pulmonar, pruebas complementarias que sugieren un peor pronóstico, así como el tratamiento recibido. Se calculó el índice EULAR para el síndrome de Sjögren. Resultados. Se identificaron 25 pacientes. Quince de ellos fueron diagnosticados de EPI antes que de SSP. Los patrones histopatológicos encontrados fueron 12 con neumonía intersticial inespecífica, 5 con neumonía intersticial común, 4 con neumonía organizada, 2 con neumonía intersticial linfocítica. Las pruebas de función respiratoria mostraron un patrón restrictivo. La mayoría de los pacientes recibió un tratamiento con glucocorticoides, antipalúdicos o inmunodepresores. Conclusiones. Los pacientes afectados por SSP deben ser sometidos a pruebas para detectar un diagnóstico precoz de EPI. La mayoría de los pacientes fueron diagnosticados de EPI antes que de SSP. Los estudios de cohortes multicéntricos son cada vez más demandados y se precisa una gestión multidisciplinar (AU)


Assuntos
Humanos , Masculino , Feminino , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologia , Diagnóstico Precoce , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/fisiopatologia , Síndrome de Sjogren , Prognóstico , Bronquiolite/complicações , Bronquiectasia/complicações , Bronquiectasia , Estudos de Coortes
14.
Reumatol. clín. (Barc.) ; 12(3): 146-150, mayo-jun. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-152855

RESUMO

Objetivo. Analizar el retraso diagnóstico y terapéutico en pacientes con AR de reciente comienzo en 19 centros de Catalunya. Métodos. Encuesta epidemiológica en 183 pacientes en que se cuantificaron los tiempos en relación con el retraso diagnostico midiendo: 1) aparición del primer síntoma hasta la primera visita a Reumatología; 2) desde la derivación hasta la primera visita de Reumatología; 3) entre aparición del primer síntoma hasta el diagnóstico, y 4) entre aparición del primer síntoma hasta el inicio del primer FAME. Se definió la existencia de 6 dispositivos asistenciales diferenciados. Resultados. El tiempo medio desde el inicio de los síntomas hasta la instauración de un FAME en pacientes con AR en Catalunya es muy largo (11 meses). Pacientes atendidos en dispositivos como consultas de AR, consultas especializadas en atención primaria y sobre todo en consultas de artritis de inicio son tratados de manera más temprana con FAME. Conclusión. La existencia de determinados dispositivos asistenciales es fundamental para mejorar la atención precoz en la AR (AU)


Objective. Diagnosis and therapy of patients with early onset rheumatoid arthritis (RA) is influenced by accessibility to specialized care devices. We attempted to analyze the impact of their availability. Methods. We analyzed time related to diagnosis delay measuring: 1) Time from first clinical symptoms to the first visit with the Rheumatologist; 2) Time from referral to the first visit of Rheumatology; 3) Time between first symptom until final diagnosis; 4) time between first symptom until the initiation of the first disease-modifying antirheumatic drug (DMARD). The presence of these 6 rheumatology devices was defined: 1) early arthritis monographic clinics, 2) RA monographic clinics, 3) Mechanisms for fast programming, 4) Algorithms for referral from primary care (PC), 5) rheumatology consultation services in PC and 6) consulting services in PC. Results. The mean time from onset of symptoms to diagnosis or the establishment of a DMARD in RA patients in Catalonia is very long (11 months). Patients seen in rheumatology devices such as RA monographic clinics, rheumatology consultation in PC and specially in early arthritis clinics are treated early with DMARDs. Conclusion. the existence of monographic clinics or consulting in primary care centers is essential to improve early care of RA patients (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Diagnóstico Precoce , Doenças Musculoesqueléticas/epidemiologia , Inquéritos e Questionários/normas , Inquéritos e Questionários , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/tendências , Estudos Transversais/métodos , Estudos Transversais/tendências , Modelos Logísticos , Análise Multivariada
15.
Reumatol Clin ; 12(3): 146-50, 2016 May-Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26362843

RESUMO

OBJECTIVE: Diagnosis and therapy of patients with early onset rheumatoid arthritis (RA) is influenced by accessibility to specialized care devices. We attempted to analyze the impact of their availability. METHODS: We analyzed time related to diagnosis delay measuring: 1) Time from first clinical symptoms to the first visit with the Rheumatologist; 2) Time from referral to the first visit of Rheumatology; 3) Time between first symptom until final diagnosis; 4) time between first symptom until the initiation of the first disease-modifying antirheumatic drug (DMARD). The presence of these 6 rheumatology devices was defined: 1) early arthritis monographic clinics, 2) RA monographic clinics, 3) Mechanisms for fast programming, 4) Algorithms for referral from primary care (PC), 5) rheumatology consultation services in PC and 6) consulting services in PC. RESULTS: The mean time from onset of symptoms to diagnosis or the establishment of a DMARD in RA patients in Catalonia is very long (11 months). Patients seen in rheumatology devices such as RA monographic clinics, rheumatology consultation in PC and specially in early arthritis clinics are treated early with DMARDs. CONCLUSION: the existence of monographic clinics or consulting in primary care centers is essential to improve early care of RA patients.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Diagnóstico Tardio/estatística & dados numéricos , Acesso aos Serviços de Saúde/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/tratamento farmacológico , Estudos Transversais , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Atenção Primária à Saúde , Encaminhamento e Consulta/estatística & dados numéricos , Espanha , Fatores de Tempo
16.
Reumatol Clin ; 12(4): 201-5, 2016 Jul-Aug.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26573882

RESUMO

UNLABELLED: Primary Sjögren syndrome (PSS) is a chronic inflammatory autoimmune disease. Interstitial lung disease (ILD) can be an extraglandular complication. OBJECTIVE: To evaluate the clinical characteristics of patients diagnosed with PSS with ILD. METHODS: Multicentre cohort study with 25 patients diagnosed with PSS and ILD. Data of PSS, prognostic factors, pulmonary involvement variables, complementary tests that suggest a worse diagnosis and treatment given were collected. EULAR index was measured for Sjögren's syndrome. RESULTS: We identified 25 patients. In 15/25 the diagnosis of ILD was done before the diagnosis of PSS. The histopathological patterns found were: 12 NSIP, 5 UIP, 4 OP, 2 LIP. PFRs showed restrictive pattern. The majority of the patients received glucocorticoid therapy, antimalarial or immunosuppressive treatment. CONCLUSIONS: Patients affected with PSS must be screened to catch a precocious diagnosis of ILD. The majority of the patients were diagnosed of ILD before being diagnosed of PSS. Multicenter cohorts are increasingly demanded and a multidisciplinary management is needed.


Assuntos
Doenças Pulmonares Intersticiais/etiologia , Síndrome de Sjogren/complicações , Adulto , Idoso , Feminino , Seguimentos , Humanos , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/patologia
17.
Semin Arthritis Rheum ; 45(4): 386-90, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26254548

RESUMO

OBJECTIVE: To identify predictors of early response to tocilizumab (TCZ) in patients with active rheumatoid arthritis (RA) seen in daily routine clinical practice. METHODS: A multicenter ambispective observational study of 126 RA patients treated with TCZ as a first- or second-line biological therapy. The variables associated to achieve the therapeutic goal (remission defined as a DAS28-ESR < 2.6) at 3 and 6 months were identified using regression analysis. RESULTS: TCZ was administered as the first biologic in 26% of patients. Overall, 34% of patients received TCZ as monotherapy. EULAR response and remission were obtained in 82% and 31% of patients at 3 months and in 86% and 40% at 6 months. In the multivariate analysis, the predictive factors increasing the likelihood of clinical remission at 3 months were baseline ESR > 30 mm/h (OR = 19.07, 95% CI: 2.720-133.716), baseline CRP > 10 mg/L (OR = 4.95; 95% CI: 1.464-13.826), and the presence of extra-articular manifestations of the disease (OR = 15.45, 95% CI: 2.334-102.319). The factors that decreased it were higher concentrations of hemoglobin (OR = 0.53, 95% CI: 0.319-0.910), higher baseline DAS28-ESR (OR = 0.30, 95% CI: 0.145-0.635) and the number of previous DMARDs (OR = 0.41, 95% CI: 0.221-0.779), and biological therapies used (OR = 0.33, 95% CI: 0.155-0.734). The only factor that remained statistically significant at 6 months was higher baseline DAS28-ESR (OR = 0.55, 95% CI: 0.347-0.877). No relationship was found with the neutrophil count or with the RF or ACPA positivity. CONCLUSION: In routine clinical practice, strong acute phase response, the presence of extra-articular manifestations, and the number of previous DMARDs and biological therapies used may help to identify patients who will have a rapid response to TCZ. However, it is likely that no parameter will predict response if taken separately.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do Tratamento
18.
Pharmacogenomics ; 17(1): 25-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26652611

RESUMO

BACKGROUND: Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients. AIM: To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX. PATIENTS & METHODS: We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes. RESULTS: We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively). CONCLUSION: FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Artrite Reumatoide/tratamento farmacológico , Metotrexato/farmacocinética , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/genética , Artrite Reumatoide/fisiopatologia , Feminino , Glucosidases/genética , Humanos , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Peptídeo Sintases/genética , Proteína Carregadora de Folato Reduzido/genética
19.
Ann Rheum Dis ; 74(10): 1875-81, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25990289

RESUMO

OBJECTIVE: Copy number variants (CNVs) have been associated with the risk to develop multiple autoimmune diseases. Our objective was to identify CNVs associated with the risk to develop psoriatic arthritis (PsA) using a genome-wide analysis approach. METHODS: A total of 835 patients with PsA and 1498 healthy controls were genotyped for CNVs using the Illumina HumanHap610 BeadChip genotyping platform. Genomic CNVs were characterised using CNstream analysis software and analysed for association using the χ(2) test. The most significant genomic CNV associations with PsA risk were independently tested in a validation sample of 1133 patients with PsA and 1831 healthy controls. In order to test for the specificity of the variants with PsA aetiology, we also analysed the association to a cohort of 822 patients with purely cutaneous psoriasis (PsC). RESULTS: A total of 165 common CNVs were identified in the genome-wide analysis. We found a highly significant association of an intergenic deletion between ADAMTS9 and MAGI1 genes on chromosome 3p14.1 (p=0.00014). Using the independent patient and control cohort, we validated the association between ADAMTS9-MAGI1 deletion and PsA risk (p=0.032). Using next-generation sequencing, we characterised the 26 kb associated deletion. Finally, analysing the PsC cohort we found a lower frequency of the deletion compared with the PsA cohort (p=0.0088) and a similar frequency to that of healthy controls (p>0.3). CONCLUSIONS: The present genome-wide scan for CNVs associated with PsA risk has identified a new deletion associated with disease risk and which is also differential from PsC risk.


Assuntos
Proteínas ADAM/genética , Artrite Psoriásica/genética , Moléculas de Adesão Celular Neuronais/genética , Deleção de Genes , Proteína ADAMTS9 , Adulto , Idoso , Estudos de Casos e Controles , Variações do Número de Cópias de DNA , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/genética , Fatores de Risco
20.
PLoS One ; 10(4): e0123392, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25830224

RESUMO

OBJECTIVE: In agreement with EULAR recommendations, a DMARD in combination with a biotherapy is the reference treatment because of the superior long-term clinical and radiographic outcomes. Methotrexate (MTX) is the cornerstone of combination therapy but is in some cases contra-indicated or poorly tolerated. This observational study aimed to compare the effectiveness and safety of TCZ in combination with either MTX or leflunomide (LEF) in the treatment of patients with active rheumatoid arthritis (RA) and an inadequate response to one or more DMARDs and/or biological agents in a real-world setting. METHODS: We performed an ambispective review of 91 patients with active RA who were routinely treated with TCZ plus MTX or LEF. A comparative study between the two combinations of treatment was performed at 6 months of follow-up considering 3 outcomes: improvement of RA disease activity, evolution of functional disability, and tolerability and side effect profile. RESULTS: Of the 91 patients, 62 received TCZ with MTX and 29 received TCZ with LEF. Eighty-one patients were followed for 6 months, and the remaining 10 patients discontinued treatment due to serious adverse events. At baseline, there were no significant differences between the groups in terms of the main clinical and laboratory data or in the number of previous DMARDs and biological agents used. At 6 months, there were no significant differences between the combinations in terms of disease activity and functional disability. Serious adverse events occurred in 11% and 10% of the patients treated in combination with MTX and LEF, respectively. CONCLUSION: Our preliminary data support the argument that LEF is an effective and safe (equivalent) alternative to MTX for combination treatment with TCZ.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Isoxazóis/uso terapêutico , Metotrexato/uso terapêutico , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Isoxazóis/efeitos adversos , Leflunomida , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Estudos Retrospectivos , Resultado do Tratamento
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