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1.
Clin Exp Rheumatol ; 37(2): 215-221, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30299251

RESUMEN

OBJECTIVES: The aim of this study was to assess the clinical and genetic characteristics associated with the presence of peripheral arthritis (PA) at disease onset in patients with ankylosing spondylitis (AS). METHODS: 456 Spanish AS patients, diagnosed according to the modified New York Criteria, who had at least ten years of follow-up since initial disease onset were selected from the National Spondyloarthropathies Registry (REGISPONSER). 18.9% of AS patients initially presented PA. Clinical variables and 384 single nucleotide polymorphisms (SNPs) distributed in 190 genes were analysed. SNP genotyping was performed using the Illumina GoldenGate genotyping platform. Association tests for allele frequencies and for categorical clinical variables were performed by the χ2 test and with the unpaired t-test for continuous variables. p-values of <0.05 were considered statistically significant. RESULTS: AS patients with PA showed an earlier age of disease onset (p=0.021), longer disease duration (p=0.020) and longer duration of AS symptoms from onset (p=0.034) than AS patients without PA. We found significant associations with the presence of PA at disease onset in 14 SNPs located in 10 genes: HLA-DQB2 (rs2857210 and rs9276615), HLA-DOB (rs2857151, rs2621332 and rs1383261), JAK2 (rs7857730), IL-23R (rs11209008 and rs10489630), CYP1B1 (rs1056836), NELL1 (rs8176786), KL (rs564481), and MEFV (rs224204), IL-2RB (rs743777) and IL-1A (rs1800587). CONCLUSIONS: Both clinical and genetic factors are associated with the presence of PA at disease onset in Spanish AS patients. The results suggest that this subset of AS patients with PA at disease onset might have differentiation factors involved in disease pathogenesis.


Asunto(s)
Polimorfismo de Nucleótido Simple , Espondilitis Anquilosante , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígeno HLA-B27 , Humanos , Pirina , Sistema de Registros , Espondilitis Anquilosante/genética
2.
Rheumatology (Oxford) ; 53(2): 353-60, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24196385

RESUMEN

OBJECTIVE: The objective of this study was to analyse the performance of the Assessment of SpondyloArthritis International Society (ASAS) criteria for the classification of SpA in early SpA clinics. METHODS: We used a cross-sectional study of patients referred to early SpA units within the ESPERANZA programme (a Spanish nationwide health management programme designed to provide excellence in diagnosis and care for early SpA). Patients were eligible if they were <45 years of age and had any of the following: (i) a 2-year history of inflammatory back pain; (ii) back or joint pain with psoriasis, anterior uveitis, radiographic sacroiliitis, family history of SpA or positive HLA-B27; or (iii) asymmetric arthritis. We excluded patients for whom imaging (X-rays/MRI) or HLA-B27 results were not available. We analysed the performance (sensitivity and specificity) of different classification criteria sets, taking the rheumatologist's opinion as the gold standard. RESULTS: The analysis included 775 patients [mean age 33 (s.d. 7) years; 55% men; mean duration of symptoms 11 (s.d. 6) months]; SpA was diagnosed in 538 patients (69.5%). A total of 274 (67.9%) patients with chronic back pain met the ASAS axial criteria, 76 (56.3%) patients with arthritis but not chronic back pain fulfilled the ASAS criteria for peripheral SpA and 350 (65.1%) fulfilled all the ASAS criteria. The sensitivity and specificity of the ASAS criteria set were 65% and 93%, respectively (axial criteria: sensitivity 68%, specificity 95%). The sensitivity and specificity for the ESSG and Amor criteria were 58% and 90% and 59% and 86%, respectively. CONCLUSION: Despite performing better than the Amor or ESSG criteria, the ASAS criteria may be limited to detection of early forms, particularly in populations in which MRI is not extensively available or in populations with a low prevalence of HLA-B27.


Asunto(s)
Programas Nacionales de Salud , Espondiloartritis/clasificación , Espondiloartritis/diagnóstico , Adulto , Biomarcadores/sangre , Clasificación/métodos , Estudios de Cohortes , Estudios Transversales , Manejo de la Enfermedad , Femenino , Antígeno HLA-B27/sangre , Humanos , Masculino , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , España , Espondiloartritis/sangre , Espondiloartritis/patología
3.
Rheumatol Int ; 34(6): 793-801, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24337767

RESUMEN

The objective of this study is to identify single-nucleotide polymorphisms (SNPs) predictors of treatment nonresponse to the first anti-TNF-alpha agent in ankylosing spondylitis (AS). Patients were classified as "nonresponders" if they failed to achieve improvement ≥50 % of the initial BASDAI. We selected candidate SNPs previously reported, associated with susceptibility or pathogenesis of AS and with other spondylarthropaties (SpAs). The predictors of nonresponse were modeled with multiple logistic regression. The predictive power of the genetic model of nonresponse to treatment was tested with AUC-ROC. One hundred and twenty-one (121) AS patients fulfilled the inclusion criteria. Of the candidate SNPs tested for association with treatment effectiveness, five independent predictors were identified: rs917997, rs755622, rs1800896, rs3740691, and rs1061622. The genetic model of nonresponse to treatment had a predictive power of 0.77 (95 % CI 0.68-0.86). Our study identified several polymorphisms which could be the useful genetic biomarkers in predicting nonresponse to anti-TNF-alpha therapy.


Asunto(s)
Antirreumáticos/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Área Bajo la Curva , Estudios de Cohortes , Etanercept , Femenino , Genotipo , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polimorfismo de Nucleótido Simple , Curva ROC , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondilitis Anquilosante/genética , Insuficiencia del Tratamiento
4.
Rheumatol Int ; 34(2): 165-70, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24390635

RESUMEN

To define and give priory to standards of care in patients with spondyloarthritis (SpA). A systematic literature review on SpA standards of care and a specific search in relevant and related sources was performed. An expert panel was established who developed the standards of care and graded their priority (high, mild, low, or no priority) following qualitative methodology and Delphi process. An electronic survey was sent to a representative sample of 167 rheumatologists all around the country, who also gave priority to the standards of care (same scale). A descriptive analysis is presented. The systematic literature review retrieved no article specifically related to SpA patients. A total of 38 standards of care were obtained-12 related to structure, 20 to process, and 6 to result. Access to care, treatment, and safety standards of care were given a high priority by most of rheumatologists. Standards not directly connected to daily practice were not given such priority, as standards which included a time framework. The standards generated for the performance evaluation (including patient and professionals satisfaction) were not considered especially important in general. This set of standards of care should help improve the quality of care in SpA patients.


Asunto(s)
Calidad de la Atención de Salud/normas , Reumatología/normas , Espondiloartritis/terapia , Nivel de Atención/normas , Consenso , Técnica Delphi , Humanos , Mejoramiento de la Calidad/normas , Espondiloartritis/diagnóstico
5.
Clin Exp Rheumatol ; 31(5): 739-48, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23899791

RESUMEN

OBJECTIVES: This study aims to assess the impact of a structured education and home exercise programme in daily practice patients with ankylosing spondylitis. METHODS: A total of 756 patients with ankylosing spondylitis (72% males, mean age 45 years) participated in a 6-month prospective multicentre controlled study, 381 of whom were randomised to an education intervention (a 2-hour informative session about the disease and the implementation of a non-supervised physical activity programme at home) and 375 to standard care (controls). Main outcome measures included Bath Ankylosing Spondylitis Disease Activity and Functional Index (BASDAI, BASFI). Secondary outcome measures were 0-10 cm visual analog scale (VAS) for total pain, nocturnal pain and global disease activity and quality of life (ASQoL), knowledge of disease (self-evaluation ordinal scale) and daily exercise (diary card). RESULTS: At 6 months, the adjusted mean difference between control and educational groups for BASDAI was 0.32, 95% confidence interval (CI) 0.10-0.54, p=0.005, and for BASFI 0.31, 95%CI 0.12-0.51, p=0.002. Significant differences were found also in VAS for total pain, patient´s global assessment and in ASQoL. Patients in the education group increased their knowledge about the disease and its treatments significantly (p<0.001) and practised more regular exercise than controls (p<0.001). CONCLUSIONS: A structured education and home exercise programme for patients with ankylosing spondylitis in daily practice was feasible and helped to increase knowledge and exercise. Although statistically significant, the magnitudes of the clinical benefits in terms of disease activity and physical function were poor.


Asunto(s)
Terapia por Ejercicio , Conocimientos, Actitudes y Práctica en Salud , Servicios de Atención de Salud a Domicilio , Educación del Paciente como Asunto , Espondilitis Anquilosante/terapia , Actividades Cotidianas , Adulto , Análisis de Varianza , Distribución de Chi-Cuadrado , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Recuperación de la Función , España , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/fisiopatología , Factores de Tiempo , Resultado del Tratamiento
6.
Ann Rheum Dis ; 71(5): 714-7, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22294640

RESUMEN

OBJECTIVE: To identify genomic variants in the 19q13 chromosome region associated with ankylosing spondylitis (AS) in human leucocyte antigen (HLA)-B27-positive populations. METHODS: High-throughput genotyping of 1536 haplotype-tag single nucleotide polymorphisms (SNPs) was performed in 249 patients with AS and 302 healthy controls. Some of the identified associations were validated by genotyping four SNPs in two additional cohorts consisting of 412 cases/301 controls and 144 cases/203 controls. All individuals selected (both cases and controls) were HLA-B27-positive. RESULTS: Two markers in two different genes (CNOT3 and LAIR2) showed significant association (p<10(-3)) with AS. In addition, sliding windows analysis showed association of groups of adjacent SNPs in regions located around CNOT3 (Chr19: 59347459-59356564, p=2.43 × 10(-4) to 6.54 × 10(-4)). The associations were validated by genotyping four SNPs from regions located near LAIR2 and CNOT3 genes (rs1055234, rs8111398, rs2287828 and rs4591276) in two additional cohorts. The CNOT3 polymorphism (rs1055234) remained associated with AS (combined p=9.73 × 10(-6)). One SNP, located downstream of KIR3DL1, was detected which, tested in combination with HLA-Bw4I80, was associated with AS. CONCLUSION: A novel significant association was detected between SNP rs1055234 and AS susceptibility.


Asunto(s)
Cromosomas Humanos Par 19 , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Espondilitis Anquilosante/genética , Factores de Transcripción/genética , Estudios de Cohortes , Genotipo , Antígeno HLA-B27/análisis , Antígeno HLA-B27/genética , Ensayos Analíticos de Alto Rendimiento , Humanos , Receptores Inmunológicos , Espondilitis Anquilosante/diagnóstico
7.
Rheumatology (Oxford) ; 51(8): 1471-8, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22495925

RESUMEN

OBJECTIVE: The aim of this study was to analyse if single nucleotide polymorphisms (SNPs) inside and outside the MHC region might improve the prediction of radiographic severity in AS. METHODS: A cross-sectional multi-centre study was performed including 473 Spanish AS patients previously diagnosed with AS following the Modified New York Criteria and with at least 10 years of follow-up from the first symptoms of AS. Clinical variables and 384 SNPs were analysed to predict radiographic severity [BASRI-total (BASRI-t) corrected for the duration of AS since first symptoms] using multivariate forward logistic regression. Predictive power was measured by the area under the receiver operating characteristic curve (AUC), specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: The model with the best fit measured radiographic severity as the BASRI-t 60th percentile and combined eight variables: male gender, older age at disease onset and six SNPs at ADRB1 (rs1801253), NELL1 (rs8176785) and MHC (rs1634747, rs9270986, rs7451962 and rs241453) genes. The model predictive power was defined by AUC = 0.76 (95% CI 0.71, 0.80), being significantly better than the model with only clinical variables, AUC = 0.68 (95% CI 0.63, 0.73), P = 0.0004. Internal split-sample analysis proved the validation of the model. Patient genotype for SNPs outside the MHC region, inside the MHC region and clinical variables account for 26, 38 and 36%, respectively, of the explained variability on radiographic severity prediction. CONCLUSION: Prediction of radiographic severity in AS based on clinical variables can be significantly improved by including SNPs both inside and outside the MHC region.


Asunto(s)
Complejo Mayor de Histocompatibilidad/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple/genética , Receptores Adrenérgicos beta 1/genética , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/genética , Adulto , Proteínas de Unión al Calcio , Estudios de Cohortes , Estudios Transversales , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Radiografía , Sensibilidad y Especificidad , Espondilitis Anquilosante/patología
8.
Arthritis Rheum ; 63(11): 3305-12, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21769851

RESUMEN

OBJECTIVE: To investigate the potential association of major histocompatibility complex (MHC) markers other than HLA-B27 with ankylosing spondylitis (AS). METHODS: A total of 603 patients with AS and 542 healthy control subjects, all of whom were HLA-B27 positive, were selected for this study based on clinical criteria. First, high-density genotyping across the MHC region (2,360 single-nucleotide polymorphisms [SNPs]) was performed in a cohort of 191 patients and 241 control subjects. After a fine-mapping study, 5 SNPs from the HLA-DPA1/DPB1 region were validated in a second cohort of 412 patients with AS and 301 healthy control subjects. RESULTS: Seventeen SNPs located within or near the HLA-DPA1 and HLA-DPB1 loci showed association with AS (P = 1.38 × 10⁻5 to 0.05). In addition, multimarker tests, both linkage disequilibrium and sliding windows, showed association of some groups of adjacent SNPs within the HLA-DPA1/DPB1 region with AS (P = 1.0 × 10⁻4 to 3.96 × 10⁻7). We validated the association by genotyping 5 SNPs from the DPA1/DPB1 region in an additional cohort and obtained P values from 6.42 × 10⁻5 to 0.01 in the analysis of the combined cohorts. Subtyping analysis of HLA-DPA1 and HLA-DPB1 showed that HLA-DPA1*01:03, A1*02:01, and B1*13:01 were the subtypes most susceptible to AS. CONCLUSION: HLA markers and linkage disequilibrium blocks near HLA-DPA1 and HLA-DPB1 are statistically associated with AS. We identified a region located around the HLA-DPA1 and HLA-DPB1 loci associated with AS, another region within the MHC that is different from HLA-B27.


Asunto(s)
Cadenas alfa de HLA-DP/genética , Cadenas beta de HLA-DP/genética , Complejo Mayor de Histocompatibilidad/genética , Espondilitis Anquilosante/genética , Adulto , Alelos , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple
9.
Arthritis Rheum ; 63(7): 1833-42, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21452291

RESUMEN

OBJECTIVE: The p38 MAPK is important in the pathogenic immune response in rheumatoid arthritis (RA). The p38 molecule can be activated through phosphorylation on Thr¹8°-Tyr¹8² by upstream MAPK kinases and via an alternative pathway through phosphorylation on Tyr³²³. We undertook this study to quantify the phosphorylation of Tyr³²³ p38 and of Thr¹8°-Tyr¹8² p38 on T cells from healthy controls and patients with RA or ankylosing spondylitis (AS) to identify variables associated with p38 phosphorylation and disease activity. METHODS: We measured p38 phosphorylation on Tyr³²³ and Thr¹8°-Tyr¹8² by flow cytometry and Western blotting on T cells from 30 control subjects, 33 AS patients, 30 patients with RA in remission, and 79 patients with active RA. We collected the clinical characteristics and analyzed correlations between clinical variables, the Disease Activity Score in 28 joints (DAS28), and p38 phosphorylation levels. Multivariate regression analysis was performed to identify variables associated with p38 phosphorylation on Tyr³²³ and Thr¹8°-Tyr¹8². RESULTS: Phosphorylation of p38 on Tyr³²³ was higher in T cells from patients with active RA (P = 0.008 versus healthy controls) than in patients with RA in remission or in patients with AS. Tyr³²³ p38 phosphorylation was associated with disease activity determined by the DAS28 (P = 0.017). Enhanced p38 phosphorylation was linked to Lck-mediated activation of the Tyr³²³-dependent pathway in the absence of upstream MAPKK activation. CONCLUSION: Our results indicate that phosphorylation status on Tyr³²³ p38 correlates with RA disease activity and suggest that the Tyr³²³-dependent pathway is an attractive target for down-regulation of p38 activity in RA patients.


Asunto(s)
Artritis Reumatoide/metabolismo , Tirosina/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Adulto , Artritis Reumatoide/inmunología , Western Blotting , Femenino , Citometría de Flujo , Humanos , Masculino , Análisis Multivariante , Fosforilación , Análisis de Regresión , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Proteínas Quinasas p38 Activadas por Mitógenos/inmunología
10.
Ann Rheum Dis ; 70(5): 827-30, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21242234

RESUMEN

OBJECTIVES: To evaluate the performance of a healthcare programme in early spondyloarthritis (SpA). METHODS: Based on previous analyses and expectations of a nominal group, the following were set: (1) minimum standards to create early SpA units; (2) standard operating procedures; and (3) eight performance indicators that can be measured in real time using a web-based platform. RESULTS: At the end of the evaluation of the programme the expected level of performance was achieved in three of the indicators: 'referral reliability' (standard (S) >50%, real value (RV) 92%), 'accessibility' (S >90%, RV=91%) and 'duration of first visit' (S >50%, RV=53%). The performance in the remaining indicators was inferior: 'success of referral criteria' (S >50%, RV=28%), 'clinical reports issued' (S >90%, RV=25%), 'feedback guarantee' (S >85%, RV=2%), 'missing data' (S <10%, RV=24%) and 'frequency of review' (S >90%, RV=84%). Explanations for the low performance are provided. CONCLUSIONS: It is possible to implement a large-scale programme that is measurable.


Asunto(s)
Implementación de Plan de Salud , Modelos Organizacionales , Programas Nacionales de Salud/organización & administración , Espondiloartritis/terapia , Atención a la Salud/organización & administración , Atención a la Salud/normas , Diagnóstico Precoz , Investigación sobre Servicios de Salud/métodos , Humanos , Evaluación de Programas y Proyectos de Salud , Indicadores de Calidad de la Atención de Salud , Derivación y Consulta/normas , España , Espondiloartritis/diagnóstico
11.
Rheumatology (Oxford) ; 50(1): 132-6, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20823095

RESUMEN

OBJECTIVE: To present the usefulness of a centralized system of data collection for the development of an international multicentre registry of SpA. METHOD: The originality of this registry consists in the creation of a virtual network of researchers in a computerized Internet database. From its conception, the registry was meant to be a dynamic acquiring system. RESULTS: REGISPONSER has two developing phases (Conception and Universalization) and gathers several evolving secondary projects (REGISPONSER-EARLY, REGISPONSER-AS, ESPERANZA and RESPONDIA). Each sub-project answered the necessity of having more specific and complete data of the patients even from the onset of the disease so, in the end, obtaining a well-defined picture of SpAs spectrum in the Spanish population. CONCLUSION: REGISPONSER is the first dynamic SpA database composed of cohorts with a significant number of patients distributed by specific diagnosis, which provides basic specific information of the sub-cohorts useful for patients' evaluation in rheumatology ambulatory consulting.


Asunto(s)
Bases de Datos Factuales/normas , Sistemas de Registros Médicos Computarizados/normas , Sistema de Registros/normas , Espondiloartritis/epidemiología , Humanos , Cooperación Internacional , España/epidemiología , Espondiloartritis/clasificación , Espondiloartritis/fisiopatología
12.
Rheumatology (Oxford) ; 50(11): 1969-75, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21865284

RESUMEN

OBJECTIVES: The aim of this study was to assess the involvement of the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene in AS susceptibility and functional severity in a Spanish population. METHODS: Eight single nucleotide polymorphisms (SNPs) spanning the ERAP1 gene were genotyped by allele-specific fluorescent PCR in 300 AS Spanish patients and 300 spondylarthritis-free controls. The influence of the ERAP1 SNPs on the functional severity of AS was analysed with the BASFI corrected for disease duration. Association analyses with AS susceptibility and functional severity were performed. RESULTS: Significant ERAP1 single marker association with AS susceptibility was found for five SNPs, namely rs30187 (allele T: P = 0.035), rs17482078 (allele C: P = 0.030), rs2287987 (allele T: P = 0.028), rs26653 (allele C: P = 0.041) and rs10050860 (allele C: P = 0.018). Three of the associated SNPs (rs17482078, rs2287987 and rs10050860) were in strong linkage disequilibrium. After imputing genotypes with the HapMap CEU data as reference, the strongest association was with rs41135 (P = 0.0046) in the 5'-upstream region of ERAP1. In addition, the SNP rs17481856 was found to be a risk factor for functional severity in AS and a borderline trend was observed for rs27044. CONCLUSIONS: These results suggest that the ERAP1 gene is associated with genetic predisposition to AS and influences the functional severity of the disease in a Spanish population.


Asunto(s)
Aminopeptidasas/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Espondilitis Anquilosante/genética , Estudios Transversales , Femenino , Antígeno HLA-B27/genética , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor , Índice de Severidad de la Enfermedad , España , Espondilitis Anquilosante/fisiopatología
13.
Rheumatology (Oxford) ; 50(10): 1828-37, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21700683

RESUMEN

OBJECTIVES: Etanercept 50 mg a week is approved in the treatment of AS. Increasing the etanercept dose to 100 mg/week improves efficacy in cutaneous psoriasis, a clinical manifestation related to the spondylarthritis family, while maintaining its safety profile. The purpose of this study was to evaluate the efficacy and safety of etanercept 100 vs 50 mg/week in patients with AS. METHODS: Adult patients with AS were randomized to receive etanercept 50 mg twice a week (biw), or etanercept 50 mg once a week (qw) for 12 weeks. The primary efficacy endpoint was Ankylosing Spondylitis Assessment Study (ASAS20) response at Week 12; secondary endpoints included ASAS40, ASAS50, ASAS70 and ASAS5/6 responses, partial remission and quality of life. Safety was assessed until 15 days after the last visit. RESULTS: A total of 108 patients were randomly selected and treated, 54 in each arm. At 12 weeks, ASAS20 response was achieved by 34 (71%) out of 48 patients of the etanercept 50 mg biw group and by 37 (76%) out of 49 patients of the etanercept 50 mg qw group (not statistically significant differences). Other efficacy variables improved significantly over time, but not between treatment groups. Fifty-six patients experienced at least one adverse event (generally, infections and infestations, gastrointestinal disorders and injection site reactions), most of them mild or moderate. CONCLUSIONS: High-dose (100 mg/week) etanercept in the treatment of AS for 12 weeks is as safe as the standard dose (50 mg/week). However, it does not significantly increase its efficacy. Trial Registration. Clinicaltrials.gov, http://clinicaltrials.gov/, NCT00873730.


Asunto(s)
Inmunoglobulina G/uso terapéutico , Inmunosupresores/uso terapéutico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Etanercept , Femenino , Estado de Salud , Humanos , Masculino , Calidad de Vida , Inducción de Remisión , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/fisiopatología , Resultado del Tratamiento
14.
Clin Exp Rheumatol ; 29(5): 822-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22011437

RESUMEN

OBJECTIVES: To analyse potential differences in disease phenotype between patients with familial ankylosing spondylitis (AS) and sporadic AS. METHODS: A cross-sectional study was conducted on all patients with definite AS registered at the internet database REGISPONSER. Sociodemographic data, clinical features, spinal mobility measurements, the Bath AS disease activity index (BASDAI), functional index (BASFI) and radiology index (BASRI), laboratory data (ESR, CRP, HLA-B27), overall patient assessment of the disease (VAS), and treatments used were obtained. Familial AS was considered when the patient was confirmed to have first-degree relatives with spondyloarthropathy. The Chi-square test and Mann-Whitney U-test were used for the statistical analysis. RESULTS: A total of 1316 AS patients (990 males, 326 females; mean age 48.2 ± 12.6 years), with mean age at symptom onset 26.1 ± 8.5 years, were evaluated. The prevalence of familial AS was 20% (n=263). Familial and sporadic AS groups presented differences (p<0.05) in the following parameters: female (34.6% vs. 22%), mean age at symptom onset (25.0±9.2 years vs. 27.3 ± 10.0 years), disease duration (23 ± 13 years vs. 21 ± 12 years), uveitis (27.5% vs. 19.3%), presence of HLA-B27+ (93% vs. 83%), VAS for overall patient assessment (5.0 cm vs. 4.4 cm), BASDAI (4.4 cm vs. 4.0 cm) and response to NSAID (82% vs. 74%). CONCLUSIONS: Patients with familial AS were younger at symptom onset and had poorer VAS for overall patient assessment and BASDAI than the other group. There was a higher prevalence of females, uveitis, positive HLA-B27, hip prostheses and a better response to NSAID in the familial AS group.


Asunto(s)
Salud de la Familia/estadística & datos numéricos , Antígeno HLA-B27/genética , Sistema de Registros/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/genética , Adulto , Antiinflamatorios no Esteroideos/uso terapéutico , Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Prevalencia , Distribución por Sexo , España/epidemiología , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/cirugía , Uveítis/epidemiología
15.
Arthritis Care Res (Hoboken) ; 73(6): 856-860, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32100954

RESUMEN

OBJECTIVE: To describe the radiographic phenotype of axial spondyloarthritis (SpA) according to the presence of HLA-B27. METHODS: An international collaboration compared the radiographic phenotype of axial SpA according to HLA-B27 status. Patients with ankylosing spondylitis (AS) and axial psoriatic arthritis (PsA) were collected. Radiographs were read centrally, blinded to clinical details. The symmetry of the sacroiliac joints and lumbar syndesmophytes and the morphology of syndesmophytes (typical marginal versus atypical chunky), together with the modified Stoke Ankylosing Spondylitis Spine Score and the Psoriatic Arthritis Spondylitis Radiographic Index, were recorded. RESULTS: A total of 244 patients with PsA and 198 patients with AS were included. In PsA, 60 patients (25%) were HLA-B27 positive while in AS, 148 patients (75%) were HLA-B27 positive. Patients with HLA-B27 were younger and more often male and had a longer duration of disease. In multivariable logistic regression, HLA-B27 was significantly associated with syndesmophyte symmetry (odds ratio [OR] 3.02 [95% confidence interval (95% CI) 1.38, 6.61]) and marginal syndesmophytes (OR 1.97 [95% CI 1.16, 3.36]) but not with sacroiliac symmetry. Mean radiographic scores were higher for patients with HLA-B27. CONCLUSION: Patients with axial SpA who are positive for HLA-B27 have more severe radiographic damage, more marginal syndesmophytes, and more frequent syndesmophyte symmetry compared to patients who are negative for HLA-B27.


Asunto(s)
Artritis Psoriásica/diagnóstico por imagen , Antígeno HLA-B27/análisis , Articulación Sacroiliaca/diagnóstico por imagen , Espondilitis Anquilosante/diagnóstico por imagen , Adulto , Anciano , Artritis Psoriásica/inmunología , Canadá , Estudios Transversales , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/inmunología
17.
Rheumatology (Oxford) ; 49(1): 73-81, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19605374

RESUMEN

OBJECTIVES: Although clinicians recognize hip involvement, which frequently leads to hip replacement surgery, as an important feature of AS, data on the epidemiology, nature of the disease and therapeutic strategies are scarce. We aimed to describe the epidemiology of clinical and radiological hip involvement and define the risk factors for the hip replacement surgery in AS patients. METHODS: Data from 3 datasets were merged, including 847 Belgian (ASPECT database), 1405 Spanish (REGISPONSER database) and 466 Ibero-American (RESPONDIA database) AS patients. The ASPECT and REGISPONSER database (Dataset A) are used for exploratory analysis; the RESPONDIA database (Dataset B) is used for confirmative analysis. Factors associated with hip involvement and the hip replacement surgery were analysed. RESULTS: Twenty four (REGISPONSER) to 36% (RESPONDIA) of AS patients under rheumatologist's care presented clinical hip involvement, including the 5% (Dataset A) of AS patients who needed hip replacement surgery. Patients with hip involvement had significantly worse overall Bath Ankylosing Spondylitis Functional Index (BASFI) scores compared with patients without hip involvement (mean difference = 1.6, P < 0.001) (Dataset A, confirmed in B). Corrected for disease duration, patients with early disease onset, enthesial and axial disease needed most frequently hip replacement surgery (Dataset A, confirmed in B). CONCLUSION: Hip involvement is commonly recognized by rheumatologists in AS patients, and involves about one out of the three to four patients with AS and is associated with impaired functioning reflected by higher overall BASFI scores. Early onset of disease, axial and enthesial disease are associated with the hip replacement surgery in AS.


Asunto(s)
Artroplastia de Reemplazo de Cadera/estadística & datos numéricos , Articulación de la Cadera/patología , Espondilitis Anquilosante/patología , Adulto , Edad de Inicio , Bélgica/epidemiología , Métodos Epidemiológicos , Femenino , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Radiografía , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/epidemiología , Espondilitis Anquilosante/cirugía
18.
Rheumatology (Oxford) ; 49(3): 458-66, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20032229

RESUMEN

OBJECTIVE: To develop a model to predict RA outcome based on biochemical variables and single nucleotide polymorphisms (SNPs). METHODS: We collected baseline data from RA patients. SNP genotyping was performed using an oligonucleotide microarray. Remission and severe disability were investigated as outcomes of the study. Logistic regression models and receiver operating characteristic (ROC) curves were used to determine sensitivity (S), specificity (Sp) and likelihood ratio (LR). RESULTS: Six hundred and thirty-two patients (375 in the study and 257 in the validation) were included. Twenty-two out of 152, and 19 out of 208 patients had an HAQ > 2. The model obtained to predict disability included levels of the anti-cyclic citrullinated peptide (anti-CCP) antibodies, ESR and SNP rs2070874 in the IL-4 gene. Homozygous and heterozygous carriers of the IL-4 33T allele had a decreased risk of severe disability. The discriminative power had an area under the curve (AUC) of 0.792 (95% CI 0.694, 0.889), with S 41%, Sp 95% and LR +7.6. Twenty-one out of 268 and 17 out of 211 patients were in remission in the study and validation cohorts, respectively. The model included absence of anti-CCP antibodies and the SNP rs2476601 on the PTPN22 gene. Homozygous and heterozygous carriers of the PTPN22 1858T allele had a decreased probability of remission. The discriminative power had an AUC of 0.842 (95% CI 0.756, 0.928), with S 76%, Sp 86% and LR + 5.4. Predictive ability was confirmed on the validation cohort. CONCLUSIONS: We have developed two models based on laboratory variables that are associated with relevant outcomes for RA patients at disease onset.


Asunto(s)
Artritis Reumatoide/diagnóstico , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Artritis Reumatoide/genética , Artritis Reumatoide/fisiopatología , Artritis Reumatoide/terapia , Autoanticuerpos/sangre , Biomarcadores/sangre , Evaluación de la Discapacidad , Métodos Epidemiológicos , Femenino , Marcadores Genéticos , Genotipo , Humanos , Interleucina-4/genética , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Péptidos Cíclicos/inmunología , Pronóstico , Inducción de Remisión
19.
Reumatol Clin (Engl Ed) ; 16(5 Pt 1): 333-338, 2020.
Artículo en Inglés, Español | MEDLINE | ID: mdl-30193774

RESUMEN

OBJECTIVE: To develop a consensus to standardize the use of Spanish terms, abbreviations and acronyms in the field of spondyloarthritis (SpA). METHODS: An international task force comprising all native Spanish-speaking Assessment of SpondyloArthritis International Society (ASAS) members, the executive committee of Grupo para el estudio de la Espondiloartritis de la Sociedad Española de Reumatología (GRESSER), two methodologists, two linguists from the Real Academia Nacional de Medicina de España (RANM) and two patients from the Spanish Coordinator of Spondylitis Associations (CEADE) was established. A literature review was performed to identify the conflicting terms/abbreviations/acronyms in SpA. This review examined written sources in Spanish including manuscripts, ICF and ICD, guidelines, recommendations and consensuses. This was followed by a nominal group meeting and a three-round Delphi. The recommendations from the RANM based on the Panhispanic dictionary were followed throughout the process. RESULTS: Consensus was reached for 46 terms, abbreviations or acronyms related to the field of SpA. A Spanish translation was accepted for 6 terms and 6 abbreviations to name or classify the disease, and for 6 terms and 4 abbreviations related to SpA. It was agreed not to translate 15 acronyms into Spanish. However, when mentioning them, it was recommended to follow this structure: type of acronym in Spanish and acronym and expanded form in English. With regard to 7 terms or abbreviations attached to acronyms, it was agreed to translate only the expanded form and a translation was also selected for each of them. CONCLUSIONS: Through this standardization, it is expected to establish a common use of the Spanish nomenclature for SpA. The implementation of this consensus across the community will be of substantial benefit, avoiding misunderstandings and time-consuming processes.


Asunto(s)
Espondiloartritis/clasificación , Espondiloartritis/diagnóstico , Terminología como Asunto , Abreviaturas como Asunto , Técnica Delphi , Humanos , Cooperación Internacional , Investigación Cualitativa , España
20.
Rheumatology (Oxford) ; 48(4): 404-9, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19208685

RESUMEN

OBJECTIVE: To determine the first signs and symptoms, and the clinical, biological and radiological characteristics of patients with early SpA. METHODS: A total of 150 SpA patients were selected from 2367 listed in REGISPONSER (Registro Español de Espondiloartritis de la Sociedad Española de Reumatología). The inclusion criterion was a disease course of

Asunto(s)
Espondiloartritis/diagnóstico , Adulto , Edad de Inicio , Análisis de Varianza , Artritis/diagnóstico , Artritis/diagnóstico por imagen , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/diagnóstico por imagen , Dolor de Espalda/diagnóstico , Dolor de Espalda/diagnóstico por imagen , Estudios de Cohortes , Femenino , Humanos , Síndrome del Colon Irritable/diagnóstico , Síndrome del Colon Irritable/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Prohibitinas , Radiografía , Articulación Sacroiliaca/diagnóstico por imagen , Espondiloartritis/diagnóstico por imagen , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/diagnóstico por imagen
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