RESUMEN
OBJECTIVES: Investigating the association between different definitions of axial involvement and syndesmophytes development over 2 years in patients with psoriatic arthritis (PsA). METHODS: Patients from a prospective multicentre cohort (Belgian Epidemiological Psoriatic Arthritis Study) involving 17 Belgian rheumatology practices were recruited between December 2012 and July 2014 and included when fulfilling the Classification Criteria for Psoriatic Arthritis. Axial involvement included six clinical and two radiographic oriented definitions.Two calibrated central readers evaluated radiographic damage by assessing the modified Stoke Ankylosing Spondylitis Spinal Score and modified New York criteria. New syndesmophytes after 2 years were described conditional on axial involvement at baseline. Logistic regression analyses were used to investigate the association between syndesmophyte development and axial involvement. All definitions of axial involvement were evaluated separately. RESULTS: From 150 patients, a 2-year follow-up of spinal radiographs was obtained. There are 11 patients with new syndesmophytes after 2 years. For the clinical definitions of axial involvement 'global assessment', 'detailed assessment', 'back pain (BP)' and 'inflammatory BP (IBP)' the probabilities of developing syndesmophytes ranged between 0.06 and 0.08 and were similar for the presence or absence of the definition. When including elevated C reactive protein (CRP) to the definitions the probability of developing syndesmophytes over 2 years increased two times for CBP and seven times for IBP.With radiographic axial involvement a similar trend was seen; radiographic sacroiliitis as definition showed a probability three times higher. When combined with elevated CRP there would be a 14 times higher chance to develop syndesmophytes in 2 years. The ORs varied from 0.83 to 13.80, though none of them were statistically significant. CONCLUSIONS: The likelihood of syndesmophyte formation in PsA is low. The probability of developing syndesmophytes is much higher when axial involvement is determined radiographically rather than clinically, particularly in the context of high CRP.
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Artritis Psoriásica , Sacroileítis , Espondilitis Anquilosante , Humanos , Artritis Psoriásica/diagnóstico por imagen , Artritis Psoriásica/complicaciones , Estudios Prospectivos , Columna Vertebral , Espondilitis Anquilosante/complicaciones , Sacroileítis/complicacionesRESUMEN
BACKGROUND: To examine radiographic axial damage of the sacroiliac joints and spine in patients with psoriatic arthritis (PsA) and spondyloarthritis (SpA) in private and academic Belgian practices. METHODS: Patients with PsA with clinical diagnosis of PsA and fulfilling the Classification Criteria for Psoriatic Arthritis from the prospective Belgian Epidemiological Psoriatic Arthritis Study and patients with SpA fulfilling the Assessment of SpondyloArthritis international Society classification criteria for SpA originate from the Ghent and BelGian Inflammatory Arthritis and spoNdylitis cohorTs were included in this study. Baseline pelvic and spinal radiographs were analysed by two calibrated readers. Blinded for the origin of the cohort or clinical data readers assessed the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and modified New York criteria on spinal and pelvic radiographs, respectively. Data were compared between both patient groups. RESULTS: Of the 525 patients included (312 PsA and 213 SpA), most patients showed normal spinal radiographs: 87.5% of the patients with PsA and 92.0% of the patients with SpA. Patients with SpA with spinal damage show higher mSASSS than the patients with PsA (p<0.05). In patients with PsA, cervical spine is more often affected; 24/33 patients (72.7%) compared with lumbar spine 11/33 (33.3%). While in patients with SpA, syndesmophyte location was more evenly distributed; cervical 9/14 (64.3%) and lumbar 10/14 (71.4%). CONCLUSION: Minimal radiographic spinal damage was observed in Belgian patients with PsA or SpA. Patients with SpA tend to have higher mSASSS values and more syndesmophytes compared with PsA. Syndesmophytes were more often located in the cervical spine of patients with PsA, while the location was equally distributed in axSpA.
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Artritis Psoriásica , Espondiloartritis , Espondiloartropatías , Espondilitis Anquilosante , Humanos , Artritis Psoriásica/complicaciones , Artritis Psoriásica/epidemiología , Estudios Prospectivos , Espondiloartritis/complicaciones , Espondiloartritis/diagnóstico , Espondiloartritis/epidemiología , Espondilitis Anquilosante/complicaciones , Espondilitis Anquilosante/epidemiología , Vértebras LumbaresRESUMEN
OBJECTIVES: The aim of the study is to report a series of 17 cases of ankle bi-arthritis that occurred shortly after coronavirus disease 2019 RNA vaccination, and to discuss the potential role of these vaccines in the pathogenesis of this rheumatological manifestation. METHODS: All patients were examined in the same department and received a full work-up to investigate the usual causes of ankle bi-arthritis. No rheumatic inflammatory disease occurred after 9 months of follow-up. A post-vaccination serological follow-up in search of anti-Spike antibodies was requested for all patients. RESULTS: All patients recovered with low dose of prednisolone within <2 months, except one who could not be weaned off CS. The level of antibodies found was very high in all patients. CONCLUSION: The ankle bi-arthritis occurrence chronology, the follow-up and the similar clinical presentation might suggest a pathogenic role of RNA vaccination.
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Artritis Reactiva , Vacunas contra la COVID-19 , COVID-19 , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Enfermedades Reumáticas , ARN , Vacunación/efectos adversosRESUMEN
OBJECTIVES: Psoriatic arthritis (PsA) is a chronic inflammatory disease, frequently associated with cardiovascular (CV) comorbidities. Our aim was to compare the prevalence of CV comorbidities between two groups of PsA patients from different European countries: Belgium and Italy. METHODS: This is a cross-sectional analysis of two longitudinal cohorts in which 803 PsA patients were enrolled (463 from Belgium and 340 from Italy). All enrolled patients were ≥18 years old and fulfilled the ClASsification criteria for Psoriatic Arthritis (CASPAR criteria). For each patient, demographics, clinical assessments, smoking habits, the presence of arterial hypertension (AH), obesity (BMI ≥30), type 2 diabetes (T2D), CV diseases (acute myocardial infarction, stroke or transient ischaemic attack), dyslipidaemia (Italy only) and hypercholesterolaemia (Belgium only) were collected. RESULTS: The most prevalent comorbidities among Italian patients with PsA were: AH (45.1%), dyslipidaemia (38.6%) and obesity (30.8%), and among Belgian patients were: hypercholesterolaemia (30.9%), obesity (27%) and AH (26.4%). Moreover, the prevalence of T2D and CV diseases was respectively 14.2% and 7.1% among Italian patients and 7.6% and 3.5% among Belgian patients. When comparing the two groups, AH, T2D and CV diseases were significantly more prevalent in Italian PsA patients. After controlling for different confounders, Italian patients, regardless of age, sex, smoking habits, PsA duration, other CV comorbidities, therapy, disease activity and function, had a higher risk to be hypertensive (OR 2.00, p=0.007). Instead of the country in which patients lived was not a predictor for the risk of T2D and CV diseases. Obesity prevalence was not different between the two groups. The lipid profile was unfavourable in both populations (even if not comparable between the two groups, due to the different way of collection), as is often the case in PsA. CONCLUSIONS: The prevalence of AH, T2D and CV diseases were higher in Italian patients rather than Belgians. Moreover, among patients with PsA, the risk of AH was higher in the Italian cohort compared to the Belgian cohort. These results suggest that further research is needed to evaluate potential extrinsic factors (geography and sociocultural aspects) that may contribute to CV risk.
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Artritis Psoriásica , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Hipertensión , Enfermedades Cardiovasculares/epidemiología , Humanos , Artritis Psoriásica/complicaciones , Artritis Psoriásica/epidemiología , Factores de Riesgo , Prevalencia , Bélgica/epidemiología , Italia/epidemiología , Estudios Transversales , Obesidad/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Hiperlipidemias/epidemiología , Hipertensión/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , AncianoAsunto(s)
Abuso Sexual Infantil , Fibromialgia , Delitos Sexuales , Niño , Fibromialgia/genética , Humanos , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To characterize the frequency of PsA subtypes, estimate the severity based on damage and inflammation and estimate the impact of PsA on patients' health-related quality of life. METHODS: We conducted a longitudinal observational study in 17 academic and non-academic centres in Belgium. Patients with PsA fulfilling Classification Criteria for Psoriatic Arthritis were recruited. Three visits were scheduled: at baseline (T0), at 1 year (±1 month; T1) and at 2 years (±1 month; T2) of follow-up. Demographics, clinical data and patient-reported outcome measures were collected at T0, T1 and T2. X-rays of the hands and feet were collected yearly (T0, T1 and T2). X-rays of the spine were collected at T0 and T2. Here we report on the burden of disease based on the clinical data and patient-reported outcomes. RESULTS: A total of 461 patients were recruited; 73.5% had combined peripheral and axial involvement and 13.7% had hip involvement. Plaque psoriasis was predominant (83.9%). At inclusion, 42.7% and 58.8% had no tender or swollen joints, respectively. Dactylitis and enthesitis were still present in 13.7% and 24.1% of the patients, respectively. Patients was treated with DMARDs (68%) and/or anti-TNF (44.2%). Forty-three per cent of the patients had a state of minimal disease activity and 62% considered the actual state as satisfactory. The mean HAQ score was 0.7%, with 32.5% of patients having a normal score (<0.3). CONCLUSION: Despite the availability of different treatment options, including biologics (anti-TNF), a substantial number of patients have active disease and have a high disease burden.
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Artritis Psoriásica/epidemiología , Productos Biológicos/uso terapéutico , Estudios Epidemiológicos , Medición de Resultados Informados por el Paciente , Calidad de Vida , Adulto , Anciano , Anciano de 80 o más Años , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Bélgica/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
OBJECTIVE: To determine which patients with ankylosing spondylitis (AS) have radiographic spinal damage and to investigate the relation between radiographic spinal changes and limitations in physical function. METHODS: A cross-sectional nationwide study in Belgium of patients with AS under the care of a rheumatologist. The treating physician completed a questionnaire including clinical disease manifestations and laboratory findings (HLA-B27 and C-reactive protein), and classified spinal radiographs into 3 categories: (1) no AS-related spinal abnormalities; (2) syndesmophytes; and (3) spinal ankylosis. Patients completed the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI). Ordinal regressions were performed to quantify the relationship between clinical manifestations and spinal radiographic changes. Generalized linear models were computed to quantify relationships among clinical manifestations, radiographic spinal changes, and functioning (BASFI). RESULTS: A total of 619 patients fulfilled modified New York criteria for definite AS and had evaluable radiographic data; 68% were male and disease duration was 17.5 (SD 12.2) years. Male sex, younger age at symptom onset, and hip involvement were associated with radiographic changes; but HLA-B27, peripheral arthritis, and extraarticular disease status (uveitis, psoriasis, and inflammatory bowel disease) were not. Older age, BASDAI, hip involvement, and spinal change contributed to BASFI; but sex, disease duration, peripheral arthritis, and extraarticular manifestations did not. CONCLUSION: Radiographic spinal changes in patients with AS are seen more often in men and those with hip involvement. BASFI status indicates the influence of radiographic changes and hip involvement, but does not reflect the presence of peripheral arthritis and does not differ between men and women.
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Estado de Salud , Índice de Severidad de la Enfermedad , Columna Vertebral/diagnóstico por imagen , Espondilitis Anquilosante/diagnóstico por imagen , Espondilitis Anquilosante/fisiopatología , Adolescente , Adulto , Edad de Inicio , Anquilosis/diagnóstico por imagen , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía , Columna Vertebral/patología , Espondilitis Anquilosante/patología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To investigate the expression and localization of aquaporin 5 (AQP5) in salivary glands and salivary gland function in the NOD mouse. METHODS: All experiments were performed using NOD and BALB/c mice (ages 8 weeks and 24 weeks). Real-time reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical analysis were used to study the expression and distribution of AQP5 in salivary glands. In addition, salivary gland function was determined. RESULTS: Compared with the levels in BALB/c mice, relative AQP5 messenger RNA levels were not significantly modified in the parotid glands from NOD mice of both ages but were significantly increased in the submandibular glands from NOD mice of both ages. Western blot analyses of both salivary gland membranes revealed that the level of AQP5 protein was increased in 24-week-old NOD mice. Important inflammatory infiltrates were observed in the submandibular glands, but not in the parotid glands, from 24-week-old NOD mice. The 8-week-old and 24-week-old BALB/c mice and the 8-week-old NOD mice showed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, in acini from the submandibular glands (but not the parotid glands) from 24-week-old NOD mice, AQP5 staining was reduced at the apical membrane but was increased at the basal membrane. A moderately statistically significant decrease in pilocarpine-stimulated salivary flow was observed in 24-week-old NOD mice compared with that in age-matched BALB/c mice. CONCLUSION: Submandibular glands from 24-week-old NOD mice displayed inflammatory infiltrates, increased AQP5 protein expression, and impaired AQP5 distribution. However, the moderately statistically significant decrease in the salivary flow rate in these mice did not match the extent of AQP5 misdistribution.
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Acuaporina 5/genética , Expresión Génica , Síndrome de Sjögren/genética , Glándula Submandibular/metabolismo , Animales , Acuaporina 5/metabolismo , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Glándula Parótida/efectos de los fármacos , Glándula Parótida/metabolismo , Glándula Parótida/patología , Glándula Parótida/fisiopatología , Pilocarpina/farmacología , ARN Mensajero/metabolismo , Saliva/metabolismo , Síndrome de Sjögren/metabolismo , Síndrome de Sjögren/patología , Glándula Submandibular/efectos de los fármacos , Glándula Submandibular/patología , Glándula Submandibular/fisiopatologíaRESUMEN
OBJECTIVES: This study aimed to describe the epidemiology of ankylosing spondylitis (AS) in rheumatology practice at the beginning of the anti-TNF (tumour necrosis factor) era, and to evaluate the initiation of anti-TNF therapy in a clinical setting where prescription is regulated by the authority's imposed reimbursement criteria. METHODS: Between February 2004 and February 2005, all Belgian rheumatologists in academic and non-academic outpatient settings were invited to register all AS patients who visited their practice. A random sample of these patients was further examined by an in-depth clinical profile. In a follow-up investigation, we recorded whether patients initiated anti-TNF therapy and compared this to their eligibility at baseline evaluation. RESULTS: 89 rheumatologists participated and registered 2141 patients; 1023 patients were clinically evaluated. These 847 fulfilled the New York modified criteria for definite AS and 176 for probable AS. The profile of AS in rheumatology practice is characterised by longstanding and active disease with a high frequency of extra-articular manifestations and metrological and functional impairment. At a median of 2 months after the clinical evaluation, anti-TNF therapy was initiated in 263 of 603 (44%) evaluable patients with definite AS and in 22 of 138 (16%) evaluable patients with probable AS (total 38%). More than 85% of the patients who started anti-TNF therapy had an increased Bath Ankylosing Spondylitis Disease Activity Index despite previous NSAID (non-steroidal anti-inflammatory drug) use. CONCLUSIONS: Of a representative cohort of 1023 Belgian AS patients seen in daily rheumatology practice, about 40% commenced anti-TNF therapy. Decision factors to start anti-TNF therapy may include disease activity and severity.
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Antirreumáticos/uso terapéutico , Pautas de la Práctica en Medicina , Reumatología , Espondilitis Anquilosante/epidemiología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Anticuerpos Monoclonales/economía , Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/economía , Bélgica/epidemiología , Estudios de Cohortes , Costos de los Medicamentos , Etanercept , Femenino , Adhesión a Directriz , Humanos , Inmunoglobulina G/economía , Inmunoglobulina G/uso terapéutico , Infliximab , Modelos Logísticos , Masculino , Persona de Mediana Edad , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Sistema de Registros , Índice de Severidad de la Enfermedad , Espondilitis Anquilosante/tratamiento farmacológicoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of celecoxib in patients with ankylosing spondylitis (AS). METHODS: This was a 12-week randomized, double-blind, placebo-controlled study with 4 treatment arms: celecoxib 200 mg qd, celecoxib 400 mg qd, naproxen 500 mg bid, and placebo. Patients (age 18-75 yrs) requiring daily treatment with nonselective nonsteroidal antiinflammatory drugs, and with a pain intensity on visual analog scale (VAS) > or = 50 mm worsening by 30% compared with a preinclusion visit (14 days prior) were studied. Primary endpoints were least-squares mean changes from baseline in pain intensity, disease activity (patient global assessment VAS), and functional impairment [Bath Ankylosing Spondylitis Functional Index (BASFI)]. Adverse events were monitored throughout the study. RESULTS: Of 611 randomized patients, 137 were allocated to celecoxib 200 mg, 161 to celecoxib 400 mg, 157 to naproxen, and 156 to placebo. Improvements in least-squares mean pain intensity, disease activity, and BASFI scores were significantly greater in the celecoxib 200 mg, celecoxib 400 mg, and naproxen groups than in the placebo group (p < or = 0.001) at Week 12 and the interim timepoints, Weeks 1, 3, and 6. Celecoxib 400 mg was as effective as naproxen; however, naproxen was more effective than celecoxib 200 mg. Celecoxib was well tolerated, with an adverse event profile similar to placebo. However, 3 naproxen-treated patients experienced serious treatment-related gastrointestinal (GI) adverse events (one severe gastric ulcer, one moderate GI hemorrhage, one severe GI hemorrhage). CONCLUSION: In this 12-week study, celecoxib 200 mg qd and 400 mg qd were efficacious and well tolerated in treating signs and symptoms of AS.
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Pirazoles/administración & dosificación , Espondilitis Anquilosante/diagnóstico , Espondilitis Anquilosante/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Celecoxib , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Masculino , Efecto Placebo , Pirazoles/efectos adversos , Sulfonamidas/efectos adversos , Resultado del TratamientoRESUMEN
B cells play an important role in the pathogenesis of many autoimmune diseases. Different approaches targeting the B cell compartment are under investigation. Selective modulation of B cells has been recently achieved using a humanised monoclonal antibody against the B cell surface marker CD22. This antibody (epratuzumab) was originally developed for the treatment of non-Hodgkin's lymphoma and was found to be effective, with a very good safety profile. Recent studies have demonstrated the efficacy and safety of epratuzumab in several autoimmune diseases, including systemic lupus erythematosus and primary Sjögren's syndrome.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Lectina 2 Similar a Ig de Unión al Ácido Siálico/inmunología , Síndrome de Sjögren/tratamiento farmacológico , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Antineoplásicos/administración & dosificación , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Esquema de Medicación , Interacciones Farmacológicas , Quimioterapia Combinada , Humanos , Lupus Eritematoso Sistémico/inmunología , Linfoma no Hodgkin/inmunología , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome de Sjögren/inmunologíaRESUMEN
This open-label, phase I/II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sjögren's syndrome (pSS). Sixteen Caucasian patients (14 females/2 males, 33-72 years) were to receive 4 infusions of 360 mg/m2 epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG) was devised to provide a clinically meaningful assessment of response, defined as a > or = 20% improvement in at least two of the aforementioned parameters, with > or = 20% reduction in ESR and/or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human (epratuzumab) antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response (at > or = 20% improvement level) at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%-50% responded at the > or = 30% level, while 10%-45% responded at the > or = 50% level for 10-32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted.
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Anticuerpos Monoclonales/uso terapéutico , Síndrome de Sjögren/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Linfocitos B/inmunología , Linfocitos B/patología , Sedimentación Sanguínea , Regulación hacia Abajo , Esquema de Medicación , Fatiga/etiología , Fatiga/fisiopatología , Femenino , Humanos , Inmunoglobulina G/sangre , Infusiones Intravenosas , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Saliva/metabolismo , Lectina 2 Similar a Ig de Unión al Ácido Siálico/inmunología , Lectina 2 Similar a Ig de Unión al Ácido Siálico/metabolismo , Síndrome de Sjögren/sangre , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/metabolismo , Resultado del TratamientoAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Linfocitos B/inmunología , Lupus Eritematoso Sistémico/terapia , Linfoma no Hodgkin/terapia , Lectina 2 Similar a Ig de Unión al Ácido Siálico/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales Humanizados , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Linfocitos B/patología , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/patología , Depleción Linfocítica , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , RoedoresRESUMEN
Salivary glands are involved in secretion of saliva, which is known to participate in the protection and hydratation of mucosal structures within the oral cavity, oropharynx and oesophagus, the initiation of digestion, some antimicrobial defence, and the protection from chemical and mechanical stress. Saliva secretion is a watery fluid containing electrolytes and a mixture of proteins and can be stimulated by muscarinic and adrenergic agonists. Since water movement is involved in saliva secretion, the expression, localization and function of aquaporins (AQPs) have been studied in salivary glands. This review will focus on the expression, localization and functional roles of the AQPs identified in salivary glands. The presence of AQP1, AQP5 and AQP8 has been generally accepted by many, while the presence of AQP3, AQP4, AQP6 and AQP7 still remains controversial. Functionally, AQP5 seems to be the only AQP thus far to be clearly playing a major role in the salivary secretion process. Modifications in AQPs expression and/or distribution have been reported in xerostomic conditions.
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Acuaporinas/fisiología , Glándulas Salivales/fisiología , Envejecimiento , Animales , Acuaporina 5/metabolismo , Acuaporina 5/fisiología , Acuaporinas/metabolismo , Transporte Biológico Activo , Línea Celular , Diabetes Mellitus/metabolismo , Neoplasias de Cabeza y Cuello/fisiopatología , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Transporte de Proteínas , Glándulas Salivales/metabolismo , Glándulas Salivales/efectos de la radiación , Síndrome de Sjögren/metabolismo , Agua/metabolismo , Xerostomía/metabolismo , Xerostomía/fisiopatologíaRESUMEN
OBJECTIVE: Adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody, was evaluated for its safety and efficacy compared with placebo in the treatment of active psoriatic arthritis (PsA). METHODS: Patients with moderately to severely active PsA and a history of inadequate response to nonsteroidal antiinflammatory drugs were randomized to receive 40 mg adalimumab or placebo subcutaneously every other week for 24 weeks. Study visits were at baseline, weeks 2 and 4, and every 4 weeks thereafter. The primary efficacy end points were the American College of Rheumatology 20% improvement (ACR20) response at week 12 and the change in the modified total Sharp score of structural damage at week 24. Secondary end points were measures of joint disease, disability, and quality of life in all patients, as well as the severity of skin disease in those patients with psoriasis involving at least 3% of body surface area. RESULTS: At week 12, 58% of the adalimumab-treated patients (87 of 151) achieved an ACR20 response, compared with 14% of the placebo-treated patients (23 of 162) (P < 0.001). At week 24, similar ACR20 response rates were maintained and the mean change in the modified total Sharp score was -0.2 in patients receiving adalimumab and 1.0 in those receiving placebo (P < 0.001). Among the 69 adalimumab-treated patients evaluated with the Psoriasis Area and Severity Index (PASI), 59% achieved a 75% PASI improvement response at 24 weeks, compared with 1% of the 69 placebo-treated patients evaluated (P < 0.001). Disability and quality of life measures were also significantly improved with adalimumab treatment compared with placebo. Adalimumab was generally safe and well-tolerated. CONCLUSION: Adalimumab significantly improved joint and skin manifestations, inhibited structural changes on radiographs, lessened disability due to joint damage, and improved quality of life in patients with moderately to severely active PsA.
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Anticuerpos Monoclonales/administración & dosificación , Artritis Psoriásica/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Artritis Psoriásica/inmunología , Artritis Psoriásica/patología , Evaluación de la Discapacidad , Método Doble Ciego , Femenino , Humanos , Inyecciones Subcutáneas , Articulaciones/patología , Masculino , Persona de Mediana Edad , Placebos , Calidad de Vida , Índice de Severidad de la Enfermedad , Piel/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA-4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy. METHODS: This was a 12-month, multicenter, randomized, double-blind, placebo-controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial. RESULTS: A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted. CONCLUSION: Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.
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Artritis Reumatoide/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Abatacept , Formación de Anticuerpos , Artritis Reumatoide/fisiopatología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Estado de Salud , Humanos , Inmunoconjugados/administración & dosificación , Inmunoconjugados/efectos adversos , Inmunoconjugados/inmunología , Inducción de Remisión , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
OBJECTIVE: There is no effective treatment for patients with primary Sjögren's syndrome (SS). Since tumor necrosis factor alpha (TNF alpha) could be a key element in the pathogenesis of primary SS, we conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of infliximab in primary SS. METHODS: A total of 103 patients with primary SS were randomly assigned to receive infliximab infusions (5 mg/kg) or placebo at weeks 0, 2, and 6 and were followed up for 22 weeks. All patients fulfilled the new American-European Consensus Group criteria for SS and had active disease as assessed by values >50 mm on 2 of 3 visual analog scales (VAS) (0-100 mm) that evaluated joint pain, fatigue, and buccal, ocular, skin, vaginal, or bronchial dryness. A favorable overall response was defined as the patient having > or =30% improvement between weeks 0 and 10 in the values on 2 of the 3 VAS. Secondary end points were values on each VAS separately, the number of tender and swollen joints, the basal salivary flow rate, results of the Schirmer test for lacrimal gland function, the focus score on labial salivary gland biopsy, the level of C-reactive protein, and the erythrocyte sedimentation rate evaluated at weeks 0, 10, and 22, as well as quality of life evaluated by use of the generic Short Form 36 questionnaire administered at weeks 0, 10, and 22. RESULTS: At week 10, 26.5% of patients receiving placebo and 27.8% of patients treated with infliximab had a favorable overall response (P = 0.89), and at week 22, 20.4% of the placebo group and 16.7% of the infliximab group had a favorable response (P = 0.62). In addition, the 2 groups did not differ in any of the secondary end points over the 22 weeks of the trial. Severe adverse events reported in the infliximab group did not differ from those observed in previous studies. CONCLUSION: This randomized, double-blind, placebo-controlled study of an anti-TNF agent did not show any evidence of efficacy of infliximab in primary SS.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Antirreumáticos/administración & dosificación , Síndrome de Sjögren/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/efectos adversos , Antirreumáticos/efectos adversos , Método Doble Ciego , Humanos , Inmunoglobulina G/sangre , Infliximab , Persona de Mediana Edad , Calidad de Vida , Síndrome de Sjögren/inmunología , Insuficiencia del TratamientoRESUMEN
BACKGROUND: Effective new therapies are needed for rheumatoid arthritis. Current therapies target the products of activated macrophages; however, T cells also have an important role in rheumatoid arthritis. A fusion protein--cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis. CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells, blocking the engagement of CD28 on T cells and preventing T-cell activation. A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis. METHODS: We randomly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig per kilogram of body weight (105 patients), 10 mg of CTLA4Ig per kilogram (115 patients), or placebo (119 patients) for six months. All patients also received methotrexate therapy during the study. The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology (ACR), which define the response according to its extent: 20 percent (ACR 20), 50 percent (ACR 50), or 70 percent (ACR 70). Additional end points included measures of the health-related quality of life. RESULTS: Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo (60 percent vs. 35 percent, P<0.001). Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group. The group given 10 mg of CTLA4Ig per kilogram had clinically meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey. CTLA4Ig was well tolerated, with an overall safety profile similar to that of placebo. CONCLUSIONS: In patients with active rheumatoid arthritis who were receiving methotrexate, treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life. CTLA4Ig is a promising new therapy for rheumatoid arthritis.
Asunto(s)
Artritis Reumatoide/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Activación de Linfocitos/efectos de los fármacos , Linfocitos T/efectos de los fármacos , Abatacept , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos/sangre , Artritis Reumatoide/inmunología , Método Doble Ciego , Femenino , Humanos , Inmunoconjugados/efectos adversos , Inmunoconjugados/inmunología , Inmunoconjugados/farmacología , Masculino , Persona de Mediana Edad , Linfocitos T/inmunologíaRESUMEN
Sjögren's syndrome (SS) is a common autoimmune disease characterized by destruction and dysfunction of the salivary and lachrymal glands. Systemic manifestations occur in almost one third of patients with SS. Treatment of SS has been long considered as disappointing, being mainly restricted to local management with artificial tears and oral lubricants or to the use of immunosuppression-based therapies for systemic disease. Better knowledge of the pathogenesis of SS, including the role of retroviruses and cytokines and the discovery of aquaporins, provides new perspectives for the local and systemic management of this disease. Our goal is to focus on these recent therapeutic progresses.