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BACKGROUND: Inborn errors of immunity (IEI) with dysregulated JAK/STAT signaling present with variable manifestations of immune dysregulation and infections. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but initially reported outcomes were poor. JAK inhibitors (JAKi) offer a targeted treatment option that may be an alternative or bridge to HSCT. However, data on their current use, treatment efficacy and adverse events are limited. OBJECTIVE: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers. METHODS: We conducted a multicenter retrospective study on patients with a genetic disorder of hyperactive JAK/STAT signaling who received JAKi treatment for at least 3 months. RESULTS: Sixty-nine patients (72% children) were evaluated (45 STAT1 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 1 JAK1-GOF). Ruxolitinib was the predominantly prescribed JAKi (80%). Overall, treatment resulted in improvement (partial or complete remission) of clinical symptoms in 87% of STAT1-GOF and in 90% of STAT3-GOF patients. We documented highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 91% overall survival. CONCLUSIONS: Our study suggests that JAKi may be highly effective to treat symptomatic JAK/STAT IEI patients. Prospective studies to define optimal JAKi dosing for the variable clinical presentations and age ranges should be pursued.
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Síndromes de Inmunodeficiencia , Inhibidores de las Cinasas Janus , Niño , Humanos , Inhibidores de las Cinasas Janus/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Síndromes de Inmunodeficiencia/terapia , Resultado del TratamientoRESUMEN
OBJECTIVES: To analyse changes over time in the treatment with disease modifying anti-rheumatic drugs and biological therapies prescribed to patients from an early arthritis register and whether these changes had an impact on their outcome. METHODS: This was a longitudinal retrospective 2-year study based on data collected in the PEARL study. The population was clustered in three groups depending on year of symptoms onset (2000-2004, 2005-2009, 2010-2014). Intensity of disease-modifying anti-rheumatic drug treatment was calculated and the percentage of patients receiving biological therapy during the first 2-year follow-up was collected. Disease activity and remission at the end of follow-up, as well as radiological progression were the outcomes analysed. Multivariable analyses were fitted to determine which variables including the three period times were associated with the outcomes. RESULTS: A significant increase in treatment intensity was observed in patients with undifferentiated arthritis, getting closer to that prescribed to patients fulfilling the 1987 RA criteria at the last period studied (2010-2014). This finding was associated with a significantly higher percentage of patients in remission and lower progression of the erosion component of the Sharp van der Heijde score. CONCLUSIONS: During the last 15 years, the treatment of patients with early arthritis in our hospital has been progressively increased and it has been associated with significantly better outcomes.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Planificación de Atención al Paciente , Pautas de la Práctica en Medicina/normas , Reumatólogos/normas , Adulto , Anciano , Artritis Reumatoide/diagnóstico por imagen , Progresión de la Enfermedad , Intervención Médica Temprana/normas , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud , Radiografía , Estudios Retrospectivos , Factores de TiempoRESUMEN
To study the predictive value of clinical remission definitions and ultrasound (US) examination on X-ray progression in rheumatoid arthritis (RA). This was an observational prospective multicenter 1-year follow-up cohort of RA patients with moderate disease activity (3.2 < DAS28 ≤ 5.1) who started anti-TNF therapy. DAS28ESR, DAS28CRP, SDAI, CDAI, and ACR/EULAR remission criteria were applied and reduced 12-joint US examination was performed at baseline and at 6 and 12 months. At baseline and month 12, radiographs of hands and feet were obtained in a subset of patients. A blind independent reader scored radiographs. X-ray progression was defined as Sharp van der Heijde change score >1 and no progression was defined as ≤0. 319 of 357 patients completed the study; patients had a mean (SD) age of 53.5 (13.1) years, with a disease duration of 7.5 (7.1) years. Laboratory, clinical, and US values significantly improved at month 6, except CRP, with additional improvement at month 12. Remission and low disease activity rates increased at follow-up. In the subset of 115 patients with radiological studies, clinical remission by any definition was not significantly associated with X-ray progression. Patients without PD signal at baseline and month 6 were a lower risk of X-ray progression than patients with PD signal, OR 0.197 (95% CI 0.046-0.861) and 0.134 (95% CI 0.047-0.378), respectively. Absence of PD signal, but not clinical remission predicts lack of X-ray progression. A feasible 12-joint US examination may add relevant information to RA remission criteria.
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Antiinflamatorios/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Articulaciones del Pie/efectos de los fármacos , Articulaciones de la Mano/efectos de los fármacos , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anciano , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/fisiopatología , Progresión de la Enfermedad , Femenino , Articulaciones del Pie/diagnóstico por imagen , Articulaciones de la Mano/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Radiografía , Inducción de Remisión , UltrasonografíaRESUMEN
OBJECTIVES: To assess the mortality rate (MR) and the mortality risk of a rheumatoid arthritis (RA) inception cohort, with and without biologic agents (BAs). Other factors associated to mortality were also investigated. METHODS: Retrospective longitudinal study of RA patients, attending the rheumatology outpatient clinic of a tertiary Hospital (Madrid), collected over 5 years (2000-2004), and followed from the diagnosis of RA up to the patients' death, lost to follow-up or September 2013. The dependent variable was death and the independent variable was exposure to BAs. Covariables: sociodemographic, clinical and therapy variables. MR was expressed per 1,000 patient-years with the 95% confidence interval [CI]. BA influence on MR was analysed by multivariable Cox models. Clinical and therapy variables were used in a time-dependent manner. The results are expressed in hazard ratio (HR) and [CI]. RESULTS: We included 576 patients and 711 courses of therapy. 19.6% were taking BA, 86% disease-modifying anti-rheumatic drugs (DMARDs) (70% on methotrexate - MTX), and 12% were untreated. There were 133 deaths during 4,981.64 patient-years at risk. The MR for BA was 12.6 [6-26], for DMARDs was 22.3 [18.4-27.1], and for those without treatment was 89.1 [61.9-128.2]. The adjusted HR for mortality in those exposed to BA versus those not exposed was 0.75 [0.32-1.71]). Other variables independently associated with mortality were: age, rheumatoid factor, hospital admissions, Health Assessment Questionnaire (HAQ), and MTX use (HR: 0.44 [0.29-0.66]). CONCLUSIONS: BAs and standard DMARDs are more effective in decreasing mortality compared to no therapy. Patients exposed to Bas were not associated with a significant increase or decrease in mortality when compared to patients with non-biological DMARDs. The use of MTX remains the only drug that has independently shown a beneficial effect on mortality.
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Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/mortalidad , Factores Biológicos/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Femenino , Humanos , Estudios Longitudinales , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVE: The aim of this research was to investigate the relationship between disease activity and health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE) considering the increased interest in the management of this disease. MATERIALS AND METHODS: HRQoL was measured at clinic visits during a 12-month follow-up period using questionnaires on fatigue (FACIT-FATIGUE); quality of life, EuroQol 5-dimension (EQ-5D-5L) health questionnaire with 5 levels; disability, Health Assessment Questionnaire (HAQ), and a Global Health Status (GHS) scale. Disease activity, organ damage and other clinical factors that could affect HRQoL were recorded. The association between disease activity and HRQoL was assessed using Bayesian linear regression models with monotonic effects. RESULTS: Data from 70 patients at the baseline visit and 42 patients with 1 year of follow-up were analyzed. At baseline, 28.57% of patients presented Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)>6. In the 70 baseline patients, disease activity was associated with HRQoL in all four parameters. In the 42 patients with 12 months of follow-up, the positive association of disease activity with GHS, FACIT-FATIGUE and EQ-5D-5L and the negative association with HAQ was maintained. Patients who are smokers and those receiving immunosuppressant therapy presented low GHS and FACIT-FATIGUE scores. Moreover, older age at inclusion was significantly associated to low GHS, while low leucocyte and 25-OH-vitamin D levels were associated to fatigue perception in SLE patients. CONCLUSION: Our results showed a statistically significant association between disease activity and HRQoL parameters.
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Lupus Eritematoso Sistémico , Calidad de Vida , Humanos , Teorema de Bayes , Índice de Severidad de la Enfermedad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Encuestas y Cuestionarios , Fatiga/etiologíaRESUMEN
OBJECTIVES: To evaluate the aspects of the basal bone health status in prostate cancer patients. Furthermore, to evaluate in a real-world setting the effect of different schemes (intermittent or continuous) of androgen deprivation therapy (ADT) and the effect of denosumab in bone mass density (BMD). METHODS: Observational, retrospective study of a cohort of prostate cancer patients in treatment with luteinizing hormone-releasing hormone (LH-RH) agonists, evaluated in the rheumatology department of a tertiary center. Demographics, FRAX score, LH-RH treatment scheme, osteoporosis treatment, laboratory data and BMD were collected. Mixed effect regression models to analyze the interaction between LH-RH treatment scheme, denosumab and BMD evolution were used. RESULTS: Eighty-three patients (mean age 71±8years) were included. At the basal evaluation, 16% of patients presented densitometric osteoporosis and 27% of patients presented high fracture risk. Eighty percent of patients had inadequate vitaminD levels. VitaminD >30ng/mL was correlated with higher T-scores. There was no association between LH-RH treatment scheme and BMD evolution, however there was a positive association with denosumab. CONCLUSION: A high proportion of patients presented elevated fracture risk or inadequate vitaminD levels, not previously recognized. Bone health assessment and fracture risk evaluation are convenient in these patients. In a real-world setting, the effect of denosumab in BMD is detected, however the effect of intermittent LH-RH schema treatment is less evident.
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Fracturas Óseas , Osteoporosis , Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Anciano , Neoplasias de la Próstata/tratamiento farmacológico , Densidad Ósea , Antagonistas de Andrógenos/efectos adversos , Andrógenos , Denosumab/uso terapéutico , Denosumab/farmacología , Estudios Retrospectivos , Osteoporosis/inducido químicamente , Hormona Liberadora de GonadotropinaRESUMEN
INTRODUCTION AND OBJECTIVE: Belimumab is a monoclonal antibody targeting BLyS approved for Systemic Lupus Erythematosus (SLE), with recent indication for lupus nephritis (LN). To analyze effectiveness of Belimumab in LN patients. METHODS: Retrospective and cross-sectional study including SLE patients (SLICC/ACR 2012 criteria) with LN demonstrated by kidney biopsy, treated with Belimumab. A clinical history review was made and serological data, kidney function and urine sediment were collected. RESULTS: Eight patients with LN demonstrated by kidney biopsy were included. Median age was 37.56 (7.03) years, with 15.13 (8.71) years since SLE diagnosis was made and 4.61 (2.64) years since onset of belimumab. Proteinuria was reduced to normal values in 6 patients, and renal function was stable from the beginning of treatment in all cases. There was a reduction in the anti-DNA level and normalization of complement in those cases in which it was reduced. One patient presented an increase in anti-DNA titer, with normal complement. CONCLUSIONS: In clinical practice, belimumab can improve LN in terms of serological activity, kidney function and urine sediment.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Adulto , Anticuerpos Antinucleares , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Estudios Transversales , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
OBJECTIVE: The aim of this study was to analyze which are the main factors that could influence the result of a CT guided biopsy in vertebral osteomyelitis (VO) patients. METHODS: A single center retrospective observational study was performed including adult patients who had been diagnosed with VO and undergone CT guided needle biopsy from January 2010 to January 2020. Demographical features, concurrent diseases, laboratory findings, microbiological diagnosis, radiological data, medical complications, antibiotic exposure were compiled. Multivariate analysis was performed with a logistic regression comparing the patients depending on the culture result. RESULTS: Seventy-seven patients were included in the study. Baseline characteristics were comparable between groups. Sample culture was positive in 43 cases (56%). Microorganism isolated were gram+(72%), gram-(14%), mycobacteria (7%) and fungi (7%). Delay in the procedure, antibiotic exposure and blood culture positivity were also similar among both groups. The biopsy results were not influenced by the CRP value, the presence of fever nor antibiotic exposure. The longer duration of back pain was associated to a lower probability of a positive culture. CONCLUSIONS: In conclusion, our study displays an acceptable reliability of CT guided needle biopsy in VO patients, even in cases under antibiotic treatment. The presence of fever or CRP values did not predict a positive culture. Delay in diagnosis could impact negatively on culture yield.
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Biopsia Guiada por Imagen , Osteomielitis , Adulto , Biopsia con Aguja , Humanos , Osteomielitis/diagnóstico , Reproducibilidad de los Resultados , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND/OBJECTIVE: To assess the effectiveness and safety of Baricitinib and Tofacitinib in rheumatoid arthritis (RA) patients in "real world" conditions. METHODS: A single centre retrospective study was performed including RA patients who had initiated treatment with Baricitinib or Tofacitinib from September-2017 to January-2020. Demographic, clinical, laboratory, efficacy and safety variables were collected from baseline and at months 1, 3, 6, 12, 18 and 24. Effectiveness was evaluated by changes from the baseline in DAS28, SDAI, HAQ and acute phase reactants. Safety analysis included adverse events due to any cause, including infection or intolerance. Infection was considered severe if it implied hospitalization. Statistical analysis consisted in Bayesian mixed ordinal regression models including the monotonic effect of each visit and Kaplan-Meier survival curves. RESULTS: Overall, 98 patients were included. A significant reduction of disease activity scores was noted in both groups. No difference between either treatment was detected in terms of effectiveness even in first line, after bDMARD failure, in monotherapy nor combined therapy. A total of 54 adverse events were recorded of which 18 were considered relevant. The incidence of infection, including Herpes Zoster, was similar in both groups. No patients in either group suffered any tuberculosis, thromboembolic event, malignancy, death or cardiovascular adverse events. Survival analysis did not show any difference between groups. CONCLUSION: Baricitinib and Tofacitinib are both comparable in terms of effectiveness and safety in real world conditions.
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Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Humanos , Inhibidores de las Cinasas Janus/efectos adversos , Antirreumáticos/efectos adversos , Teorema de Bayes , Estudios Retrospectivos , Pirroles/efectos adversos , Artritis Reumatoide/tratamiento farmacológicoRESUMEN
Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA). Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The "Hospital Universitario La Princesa Index" (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R 2 parameter and the quasi-likelihood under the independence model criterion. Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R 2 = 0.351) and SDAI ones (R 2 = 0.329). For serum IL-6 levels, the SDAI (R 2 = 0.208) followed by the HUPI model (R 2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R 2 = 0.034) and the DAS28 models (R 2 = 0.026) performed best whereas the DAS28 (R 2 = 0.030) and HUPI models (R 2 = 0.023) did so in PEARL. Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.
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INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease that particularly affects young women during their second and third decades. Events attributed to SLE itself and others related to the disease may impact negatively on the quality of life, employment and disability. However, there are not many studies focused on the impact that the disease may have on patients regarding those aspects. In Spain, the evaluation of disability and the assignation of a pension is given by the National Social Security Institute of Spain, INSS ("Instituto Nacional de la Seguridad Social"). OBJECTIVE: To assess the relationship between cumulative damage regarding the affected organ and the percentage of disability recognised by the National Social Security Institute of Spain (INSS) in SLE patients. METHODS: Cross-sectional prospective study of SLE patients according to the SLICC-2012 criteria, from the Rheumatology Service of two Spanish hospitals. We collected clinical and demographic data through personal interview and the SLICC/ACR questionnaire, and classified patients regarding a recognised disability or not. RESULTS: 142 patients were evaluated; 30% had some percentage of official disability. We found a positive correlation between percentage of recognised disability and the SLICC/ACR index score. Musculoskeletal system is the most affected system, without differences between both groups; but we found a higher proportion of damage in nervous system, renal and vasculitis in patients with a recognised disability. CONCLUSION: There is a positive correlation between percentage of recognised disability in Spain and the cumulative damage in SLE.
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INTRODUCTION: To determine patient and rheumatologist preferences for rheumatoid arthritis (RA) treatment attributes in Spain and to evaluate their attitude towards shared decision-making (SDM). METHODS: Observational, descriptive, exploratory and cross-sectional study based on a discrete choice experiment (DCE). To identify the attributes and their levels, a literature review and two focus groups (patients [P] = 5; rheumatologists [R] = 4) were undertaken. Seven attributes with 2-4 levels were presented in eight scenarios. Attribute utility and relative importance (RI) were assessed using a conditional logit model. Patient preferences for SDM were assessed using an ad hoc questionnaire. RESULTS: Ninety rheumatologists [52.2% women; mean years of experience 18.1 (SD: 9.0); seeing an average of 24.4 RA patients/week (SD: 15.3)] and 137 RA patients [mean age: 47.5 years (SD: 10.7); 84.0% women; mean time since diagnosis of RA: 14.2 years (SD: 11.8) and time in treatment: 13.2 years (SD: 11.2), mean HAQ score 1.2 (SD: 0.7)] participated in the study. In terms of RI, rheumatologists and RA patients viewed: time with optimal QoL: R: 23.41%/P: 35.05%; substantial symptom improvement: R: 13.15%/P: 3.62%; time to onset of treatment action: R: 16.24%/P: 13.56%; severe adverse events: R: 10.89%/P: 11.20%; mild adverse events: R: 4.16%/P: 0.91%; mode of administration: R: 25.23%/P: 25.00%; and added cost: R: 6.93%/P: 10.66%. Nearly 73% of RA patients were involved in treatment decision-making to a greater or lesser extent; however, 27.4% did not participate at all. CONCLUSION: Both for rheumatologists and patients, the top three decision-making drivers are time with optimal quality, treatment mode of administration and time to onset of action, although in different ranking order. Patients were willing to be more involved in the treatment decision-making process.
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Artritis Reumatoide/terapia , Prioridad del Paciente/estadística & datos numéricos , Relaciones Médico-Paciente , Pautas de la Práctica en Medicina/estadística & datos numéricos , Reumatólogos/normas , Adulto , Artritis Reumatoide/tratamiento farmacológico , Actitud del Personal de Salud , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reumatología/métodos , España , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Polymyalgia rheumatica (PR) can be associated with large vessel vasculitis (LVV). We evaluate the diagnostic role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and its impact on the treatment of LVV associated with PR. MATERIALS AND METHODS: Retrospective study of patients diagnosed with PR. Data was collected from health records. Blood analysis included acute-phase reactants (APR), C-reactive protein (CRP) and erythrocyte sedimentation rate. An 18F-FDG PET/CT scan was performed in those patients whose symptoms persisted, in those with elevated APR, those who required higher doses of steroids or those who had atypical features of PR (low-grade fever, weight loss, among others). RESULTS: Twenty-three were eligible; 48% (n = 11) of the patients were diagnosed with LVV associated with PR. The site was heterogeneous, but mostly involved the aorta. In 80% of the patients with LVV, a disease-modifying antirheumatic drug was added to their treatment. Elevated CRP values were associated with the likelihood of presenting LVV. CONCLUSIONS: LVV is not uncommon, clinical features and elevated CRP levels should raise suspicion of LVV associated with PR. 18F-FDG PET/CT is useful in identifying LVV associated with PR.
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Fluorodesoxiglucosa F18 , Polimialgia Reumática/complicaciones , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Vasculitis Reumatoide/diagnóstico por imagen , Proteínas de Fase Aguda/análisis , Anciano , Aortitis/diagnóstico por imagen , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Femenino , Arteritis de Células Gigantes/sangre , Arteritis de Células Gigantes/complicaciones , Humanos , Masculino , Polimialgia Reumática/sangre , Polimialgia Reumática/tratamiento farmacológico , Estudios Retrospectivos , Vasculitis Reumatoide/sangre , Vasculitis Reumatoide/tratamiento farmacológico , Vasculitis Reumatoide/etiologíaRESUMEN
The study aims to analyze the association between the bone and cartilage/periarticular components of the radiographic joint damage and disability over the course of disease, in a cohort of rheumatoid arthritis (RA) patients from a day-to-day clinical practice. The secondary aim is to study the role of demographic and disease-related variables in this association. We performed a retrospective longitudinal study including 736 RA patients. Disability was assessed with the health assessment questionnaire (HAQ), and radiographic joint damage of hands and wrists with the Sharp van-der-Heijde score (total (SHS), erosion (ES), and narrowing/(sub)luxation (NSLS) components]. Generalized estimating equations models, adjusted by disease activity, demographic and disease-related variables, were used to test the relationship between SHS and medium-term (median value of the HAQs performed in the following year after each radiograph) and long-term (set of HAQ measures performed during follow-up, at least 1 year apart from the first x-ray) disability. Interaction terms between the SHS and demographic and disease-related variables were introduced in the models. To account for multiple testing, Bonferroni correction was applied. NSLS was independently associated with medium-term disability, even after Bonferroni correction. We observed significant and positive interactions between NSLS and age at x-ray, and with the ES. SHS showed no association with long-term disability. The cartilage/soft tissue component of the radiographic joint damage seems to exert a much more important role in medium-term disability than the erosive component. This association could be modulated by the age at the x-ray and by the magnitude of the erosive damage.
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Artritis Reumatoide/fisiopatología , Huesos/fisiopatología , Cartílago Articular/fisiopatología , Articulaciones de la Mano/fisiopatología , Adulto , Anciano , Artritis Reumatoide/diagnóstico por imagen , Huesos/diagnóstico por imagen , Cartílago Articular/diagnóstico por imagen , Estudios de Cohortes , Femenino , Articulaciones de la Mano/diagnóstico por imagen , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Radiografía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Evaluate the relationship between structural damage assessed by radiography or ultrasonography in the hands of patients with psoriatic arthritis (PsA) with loss of strength together with functional disability. METHODS: A cross-sectional study was conducted in patients with PsA involving the hands. Erosions and loss of radiographic joint space were measured in the dominant hand using a modified Sharp van der Heijde method and an ultrasound assessment. Hand strength was assessed with a dynamometer and disability was assessed using the Health Assessment Questionnaire (HAQ). The statistical analysis was performed using multiple linear regression models. FINDINGS: 76 patients were included with a mean age of 57⯱â¯9.9â¯years, with 56.6% women. A statistically significant relationship was found between presence of erosions and reduction in lateral (pâ¯=â¯0.027) and tip (pâ¯=â¯0.030) pinch strength in the hand. This was also the case for loss of joint space and reduction in lateral (pâ¯=â¯0.012) and tip (pâ¯=â¯0.006) pinch strength. There was an association between total ultrasound (US) alterations and reduction in lateral pinch strength (pâ¯=â¯0.03). An association was also observed between erosions, loss of joint space and total US alterations and disability measured by the HAQ (pâ¯<â¯0.001; <0.001; 0.012, respectively). HAQ scores were associated with a decrease in mean lateral (pâ¯<â¯0.001) and tip (pâ¯<â¯0.001) pinch strength. INTERPRETATION: In patients with PsA involving the hands, structural alterations of the dominant hand assessed by conventional x-ray and ultrasound are associated with loss of strength measured objectively with dynamometry and greater disability also studied subjectively using the HAQ.
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Artritis Psoriásica/fisiopatología , Artritis Reumatoide/fisiopatología , Fuerza de la Mano , Mano/fisiopatología , Adulto , Anciano , Estudios Transversales , Personas con Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dinamómetro de Fuerza Muscular , Radiografía , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Ultrasonografía , Rayos XRESUMEN
BACKGROUND AND OBJECTIVE: to analyse the association between interferon-1α (INF1α), interleukin-10 (IL-10) and BLyS concentrations and clinical activity in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: A cross-sectional, observational study of 142 SLE patients and 34 healthy controls was performed, through a complete blood and urine test and review of their medical history. Serum concentration of INF1α, IL-10 and BLyS was determined by colorimetric methods. A biostatistical analysis was performed with R (3.3.2.). RESULTS: 69% of our SLE patients showed at least one cytokine increased. INF1α, IL-10 and BLyS are higher in SLE patients than in healthy controls (P<.001, P=.005 and P=.043, respectively), being INF1α the most frequent. Patients were categorised according to low or high concentrations of the three cytokines. We found a significant association between increased IL-10/INF1α concentrations and a higher clinical activity measured by SELENA-SLEDAI (P<.0001) and, to a lesser extent, an association with increased INF1α/IL-10/BLyS concentrations. Elevated levels of IL-10/INF1α and INF1α/IL-10/BLyS related to increased C3-C4 consumption (P<.001 and P=.001 respectively) and anti-dsDNA titres (P=.001 and P=.002 respectively). Elevated INF1α/BLyS related to higher anti-dsDNA titres (P=.004) and ENA positivity (P<.001). Increased levels of INF1α/IL-10/BLyS related to positivity of ANAs (P<.001) and APL (P=.004). CONCLUSIONS: INF1α, IL-10 and BLyS are higher in SLE patients than in healthy controls. Increased IL-10 levels, regardless of whether or not there were also increased levels of BLyS and/or INF1α, was the cytokine that best fit with clinical activity in SLE measured with classic methods.
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Factor Activador de Células B/sangre , Interferón-alfa/sangre , Interleucina-10/sangre , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Adulto , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVES: To describe the mortality rate (MR) and standardized MR (SMR) of an incident cohort of rheumatoid arthritis (RA) patients followed up for 20 years, and to analyze the influence on morality risk of different demographic and clinical variables, including radiographic joint damage. METHODS: Retrospective longitudinal study that included 2271 RA patients attending the rheumatology outpatient clinic of the Hospital Clínico San Carlos (Madrid, Spain), enrolled from January 1994 to February 2013 and followed up from RA diagnosis to patients׳ death or September 2013. Disability and disease activity were measured as the averaged value of the Heath Assessment Questionnaire and the erythrocyte sedimentation rate, respectively, of the first 2 years after RA diagnosis. Radiographic joint damage of hands and wrists was assessed with the Sharp/van der Heijde score. Indirect SMRs with a 95% of confidence interval (95% CI) were calculated. Cox bivariate and multivariate regression models were performed to assess risk factors for death. RESULTS: A total of 431 patients died (19%) during the observation time (18,482 person-years), resulting in a MR of 23 subjects per 1000 patient-years [95% CI: 21-26]. SMR was 1.89 (1.72-2.08). In the multivariate analysis, men, older age at diagnosis, the presence of rheumatoid factor, higher number of hospital admissions, greater disease activity, and greater radiographic joint damage were independently associated with greater mortality risk. CONCLUSIONS: RA patients have an excess mortality compared with the general population. Radiological joint damage and early disease activity are independent mortality risk factors. A tighter control at early stages may be necessary to reduce mortality.
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Artritis Reumatoide/mortalidad , Articulaciones de la Mano/diagnóstico por imagen , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factores Sexuales , España/epidemiología , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Prostaglandin E receptor 4 (PTGER4) is implicated in immune regulation and bone metabolism. The aim of this study was to analyze its role in radiological joint damage in rheumatoid arthritis (RA). METHODS: Six independent cohorts of patients with RA of European or North American descent were included, comprising 1789 patients with 5083 sets of X-rays. The Hospital Clínico San Carlos Rheumatoid Arthritis, Princesa Early Arthritis Register Longitudinal study, and Hospital Universitario de La Paz early arthritis (Spain) cohorts were used as discovery cohorts, and the Leiden Early Arthritis Clinic (The Netherlands), Wichita (United States), and National Databank for Rheumatic Diseases (United States and Canada) cohorts as replication cohorts. First, the PTGER4 rs6896969 single-nucleotide polymorphism (SNP) was genotyped using TaqMan assays and available Illumina Immunochip data and studied in the discovery and replication cohorts. Second, the PTGER4 gene and adjacent regions were analyzed using Immunochip genotyping data in the discovery cohorts. On the basis of pooled p values, linkage disequilibrium structure of the region, and location in regions with transcriptional properties, SNPs were selected for replication. The results from discovery, replication, and overall cohorts were pooled using inverse-variance-weighted meta-analysis. Influence of the polymorphisms on the overall radiological damage (constant effect) and on damage progression over time (time-varying effect) was analyzed. RESULTS: The rs6896969 polymorphism showed a significant association with radiological damage in the constant effect pooled analysis of the discovery cohorts, although no significant association was observed in the replication cohorts or the overall pooled analysis. Regarding the analysis of the PTGER4 region, 976 variants were analyzed in the discovery cohorts. From the constant and time-varying effect analyses, 12 and 20 SNPs, respectively, were selected for replication. Only the rs76523431 variant showed a significant association with radiographic progression in the time-varying effect pooled analysis of the discovery, replication, and overall cohorts. The overall pooled effect size was 1.10 (95 % confidence interval 1.05-1.14, p = 2.10 × 10(-5)), meaning that radiographic yearly progression was 10 % greater for each copy of the minor allele. CONCLUSIONS: The PTGER4 gene is a candidate risk factor for radiological progression in RA.
Asunto(s)
Artritis Reumatoide/genética , Artritis Reumatoide/patología , Predisposición Genética a la Enfermedad/genética , Subtipo EP4 de Receptores de Prostaglandina E/genética , Artritis Reumatoide/diagnóstico por imagen , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Genotipo , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Polimorfismo de Nucleótido Simple , Radiografía , Factores de RiesgoRESUMEN
INTRODUCTION: The severity of joint damage progression in rheumatoid arthritis (RA) is heritable. Several genetic variants have been identified, but together explain only part of the total genetic effect. Variants in Interleukin-6 (IL-6), Interleukin-10 (IL-10), C5-TRAF1, and Fc-receptor-like-3 (FCRL3) have been described to associate with radiographic progression, but results of different studies were incongruent. We aimed to clarify associations of these variants with radiographic progression by evaluating six independent cohorts. METHODS: In total 5,895 sets of radiographs of 2,493 RA-patients included in six different independent datasets from the Netherlands, Sweden, Spain and North-America were studied in relation to rs1800795 (IL-6), rs1800896 (IL-10), rs2900180 (C5-TRAF1) and rs7528684 (FCRL3). Associations were tested in the total RA-populations and in anti-citrullinated peptide antibodies (ACPA)-positive and ACPA-negative subgroups per cohort, followed by meta-analyses. Furthermore, the associated region C5-TRAF1 was fine-mapped in the ACPA-negative Dutch RA-patients. RESULTS: No associations were found for rs1800795 (IL-6), rs1800896 (IL-10) and rs7528684 (FCRL3) in the total RA-population and after stratification for ACPA. Rs2900180 in C5-TRAF1 was associated with radiographic progression in the ACPA-negative population (P-value meta-analysis = 5.85 × 10(-7)); the minor allele was associated with more radiographic progression. Fine-mapping revealed a region of 66Kb that was associated; the lowest P-value was for rs7021880 in TRAF1. The P-value for rs7021880 in meta-analysis was 6.35 × 10(-8). Previous studies indicate that the region of rs7021880 was associated with RNA expression of TRAF1 and C5. CONCLUSION: Variants in IL-6, IL-10 and FCRL3 were not associated with radiographic progression. Rs2900180 in C5-TRAF1 and linked variants in a 66Kb region were associated with radiographic progression in ACPA-negative RA.