Role of Carotid Ultrasound and Systematic Coronary Risk Evaluation Charts for the Cardiovascular Risk Stratification of Patients with Psoriatic Arthritis.

OBJECTIVE: The assessment of the cardiovascular (CV) risk is recommended in patients with chronic inflammatory rheumatic diseases. The objectives of this study were to assess the CV risk profile in a cohort of patients with psoriatic arthritis (PsA), to determine the presence of subclinical cardiovascular disease by carotid ultrasound (US), and to study the association of CV disease to PsA characteristics. METHODS: This was a cross-sectional multicentric descriptive study. The clinical CV risk was calculated with Systematic Coronary Risk Evaluation (SCORE) charts. Common carotid US was conducted to evaluate the carotid wall intima-media thickness and the presence of atheroma plaques. Patients were reclassified upon US results. Multivariate analyses were performed to identify associations of US carotid abnormalities with the classical CV risk factors and PsA characteristics. RESULTS: The study included 176 patients with PsA. The SCORE-estimated CV risk was intermediate in 65.3% of the patients. In the US study, 32% of the patients had abnormalities, and 30.8% of the patients were upgraded and reclassified as very high risk owing to the presence of atheroma. Subclinical CV disease was associated with age and dyslipidemia but not with other risk factors. It was associated with axial disease in the subgroup with intermediate risk, and with C-reactive protein levels in patients with high risk. CONCLUSION: Many patients with PsA have clinical estimated intermediate or high risk of a fatal CV event. A carotid US study detects subclinical vascular disease and may be useful to depict the real risk. The presence of atheroma is only partially explained by the classic CV risk factors.

Clinical relevance of monitoring serum levels of adalimumab in patients with rheumatoid arthritis in daily practice.

OBJECTIVES: The aim of this paper is to assess the usefulness of measuring serum levels of adalimumab (ADL) and anti-ADL antibodies in 57 patients with rheumatoid arthritis (RA) treated with ADL for at least 3 months in daily practice. METHODS: All patients received concomitant disease-modifying anti-rheumatic drug (DMARD). Receiver-operator characteristics (ROC) analysis was used to obtain the cut-off value of ADL for low disease activity (DAS28-ESR ≤3.2). RESULTS: Anti-ADL antibodies were detected in 4 (7%) patients with a mean (SD) DAS28 score of 4.6 (0.9). Patients with positive anti-ADL antibodies had significantly lower levels of ADL and higher DAS28 scores than those with negative antibodies. Patients with DAS28 ≤3.2 as compared with patients with DAS28 >3.2 showed significantly better SDAI score, higher serum concentrations of ADL and none of them showed anti-ADL antibodies. The cut-off of serum level of ADL for DAS28 <3.2 was 4.3 mg/L. According to serum levels of ADL, patients were grouped into group 1 (low level) <5.5 mg/L, group 2 (medium level) 5.5-11.3 mg/L and group 3 (high level) >11.3 mg/L. Patients in the medium group were closed to clinical remission (median DAS28 2.7) and patients in the high group were on clinical remission (DAS28 2.1). CONCLUSIONS: Serum levels of ADL should be maintained >4.3 mg/L. In patients with ADL levels >11.3 mg/L, a decrease of the dose of ADL or an increase in the interval between doses may be planned. The presence of anti-ADL antibodies was associated with a loss of clinical efficacy of ADL.

Practical application of acid dissociation in monitoring patients treated with adalimumab.

Patients treated with adalimumab (ADL) can induce anti-ADL antibodies (AAA) formation that is associated with low drug levels and clinical non-response. But, in the majority of the assays, the measurement of AAA is hampered by the presence of the drug itself. In support of immunogenicity assessment in clinical samples with subtherapeutic ADL levels, we proved acid pre-treatment for AAA detection with the Promonitor-enzyme-linked immunosorbent assay (ELISA). Were measured AAA after acidification in 32 serum samples with a subtherapeutic ADL trough level. ADL and AAA concentrations were measured by ELISA (Promonitor). The impact of drug concentration on AAA recovery (with or without acidification) was also evaluated by mixing known amounts of ADL (0.25, 0.5 and 1 mg/L) and AAA (100, 200, 300 and 400 AU/mL) from clinical samples in pooled serum. The drug significantly inhibited the detection of AAA in untreated samples. And progressively higher levels of ADL cause increasing inhibition of signal. Acid pre-treatment carried a significant increase in assay response, particularly at lower free ADL concentrations. AAA were detected in the 53 % of the samples after acid dissociation. In seven patients, the positive AAA after dissociation was detected in the first monitoring of ADL and five patients were positive 3 months later for AAA with the standard assay. Monitoring AAA using acid dissociation in patients with subtherapeutic circulating level of ADL could detect precocious problems of bioavailability, assess the immunogenicity of ADL and may be used to optimise dose regimens, thereby preventing prolonged use of inadequate therapy and guide change of treatment.

Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis.

To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn's disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept therapy in patients with ankylosing spondylitis.

Impact of the use of musculoskeletal ultrasound by rheumatologists in patients with shoulder and hand complaints compared with traditional clinical care.

OBJECTIVES: To compare the routine use of musculoskeletal ultrasonography (MSUS) with traditional clinical care in daily practice at shoulder and hand level. METHODS: An observational study was performed in four rheumatology departments. Within each department, 2 rheumatologists were selected; one rheumatologist used MSUS, and the other followed traditional rheumatology care. Consecutive patients with nontraumatic pain, hand numbness or disability, or pain and/or limitations in the shoulder were selected. We collected information regarding the clinical and MSUS diagnoses, changes in diagnosis and treatment following MSUS, local injections, the rheumatologist's satisfaction and the use of health care resources. A descriptive analysis was performed. RESULTS: A total of 168 patients were analysed, with 104 and 64 patients in the MSUS and traditional care groups, respectively. MSUS led to a diagnosis and therapeutic change in 53 (52%) and 55 patients (54%), respectively. The rate of local injection was 47% in the MSUS group (73% unexpected, 61% performed using US) compared with 21% in the traditional group (p=0.001). According to the rheumatologists, MSUS was useful in 72 cases (71%) and extremely useful in 20 cases (20%), and the rheumatologists reported a higher satisfaction with their patient evaluations (p<0.001). The MSUS group required fewer additional tests (38% vs. 81%, respectively, p<0.001), fewer medical visits (46% vs. 84%, p<0.001), and lower direct costs (11 vs. 30 euros, p<0.001) than the traditional care group. CONCLUSIONS: Compared with traditional care, the routine use of MSUS in rheumatology practice at hand and shoulder level can lead to important improvements in care, thereby reducing the number of additional tests and medical visits.

Duración del tratamiento con etanercept y razones de discontinuación en una cohorte de pacientes con patología reumática / Duration of treatment with etanercept and motives for discontinuation in a cohort of patients with rheumatic disease

Objetivos. Evaluar la supervivencia del tratamiento con etanercept (ETN) y las causas de discontinuación en una cohorte local de pacientes en tratamiento biológico (TB). Comparar con la supervivencia general del resto de TB. Pacientes y métodos. Estudio observacional prospectivo de cohortes. Se han analizado los datos de diagnóstico, fecha de inicio y fin de tratamiento, así como la causa de interrupción de nuestro registro de TB. Mediante el método de Kaplan-Meier se ha estimado la supervivencia de ETN al año, a los 2 años y a los 5 años. Resultados. De un total de 205 pacientes que recibieron TB, 92 (45%) iniciaron tratamiento con ETN. En el 48% el diagnóstico fue artritis reumatoide, 33% espondilitis anquilosante, 11% artritis psoriásica y 8% otros diagnósticos (artritis idiopática juvenil, espondiloartritis asociada a enfermedad inflamatoria intestinal y síndrome SAPHO). Continúan con ETN 48 pacientes (52%). Las causas de discontinuación fueron: ineficacia (65%), acontecimiento adverso (33%), pérdida de seguimiento (2%). En 2 pacientes el tratamiento se retiró por remisión clínica. Los acontecimientos adversos fueron: infección (4 pacientes), reacción cutánea post-inyección (3), uveítis (3), neoplasia (2) y otros (3). La supervivencia estimada de ETN al año de tratamiento fue del 64% (IC del 95%, 54-74), a los dos años del 59% (48-69) y a los 5 años del 43% (30-52), y la del resto de TB fue del 61% (51-68), el 47,5% (40-55) y el 23% (10,5-32), respectivamente. Los tests estadísticos revelaron diferencias significativas (log-rank: p=0,024; Breslow: p=0,068; Tarone-Ware: p=0,040). Conclusiones. En nuestra cohorte de pacientes la supervivencia estimada de ETN en el primero, segundo y quinto de año de tratamiento es superior a la obtenida con el resto de TB, siendo la diferencia significativa a los 5 años (AU)

Objective. To evaluate the duration of etanercept (ETN) treatment and motives for discontinuation in our local cohort of patients with rheumatic pathology and compare them to the group with other biological treatments. Patients and methods. Prospective observational cohort study. Disease diagnosis, start and end date and motive for discontinuation were recorded. Survival estimation was explored using Kaplan-Meier analysis with remaining patients censored at 1-year, 2-years and 5-years follow-up. Results. Ninety-two (45%) out of 205 patients started ETN treatment. Disease diagnoses recorded were: 48% rheumatoid arthritis, 33% ankylosing spondylitis, 11% psoriatic arthritis, 8% others (juvenile idiopathic arthritis, inflammatory bowel disease related spondylitis, SAPHO syndrome). 52% of patients are still on the drug. The motives for discontinuation were: inefficacy (65%), adverse events (33%) and lack of compliance (2%). Two patients discontinued ETN due to prolonged disease control. Adverse events were: infection (4 patients), post-injection skin reaction (3), uveitis (3), neoplasia (2) and others (3). Using a Kaplan–Meier analysis, at 1-year 64% (CI95% 54-74) of patients with ETN treatment had not experienced treatment failure, at 2-years, 59% (48-69) and at 5-years, 43% (30-52). With the rest of biologicals estimated survival was 61% (51-68), 47,5% (40-55) and 23% (10,5-32) respectively. Statistical analysis revealed significant differences (log-rank: P=.024; Breslow: P=.068; Tarone-Ware: P=.040). Conclusions. In our cohort of patients treated with ETN the estimated survival was better than patients treated with other biological drugs at 1-year, 2-years and 5-years (AU)

[Duration of treatment with etanercept and motives for discontinuation in a cohort of patients with rheumatic disease]. / Duración del tratamiento con etanercept y razones de discontinuación en una cohorte de pacientes con patología reumática.

OBJECTIVE: To evaluate the duration of etanercept (ETN) treatment and motives for discontinuation in our local cohort of patients with rheumatic pathology and compare them to the group with other biological treatments. PATIENTS AND METHODS: Prospective observational cohort study. Disease diagnosis, start and end date and motive for discontinuation were recorded. Survival estimation was explored using Kaplan-Meier analysis with remaining patients censored at 1-year, 2-years and 5-years follow-up. RESULTS: Ninety-two (45%) out of 205 patients started ETN treatment. Disease diagnoses recorded were: 48% rheumatoid arthritis, 33% ankylosing spondylitis, 11% psoriatic arthritis, 8% others (juvenile idiopathic arthritis, inflammatory bowel disease related spondylitis, SAPHO syndrome). 52% of patients are still on the drug. The motives for discontinuation were: inefficacy (65%), adverse events (33%) and lack of compliance (2%). Two patients discontinued ETN due to prolonged disease control. Adverse events were: infection (4 patients), post-injection skin reaction (3), uveitis (3), neoplasia (2) and others (3). Using a Kaplan-Meier analysis, at 1-year 64% (CI(95%) 54-74) of patients with ETN treatment had not experienced treatment failure, at 2-years, 59% (48-69) and at 5-years, 43% (30-52). With the rest of biologicals estimated survival was 61% (51-68), 47,5% (40-55) and 23% (10,5-32) respectively. Statistical analysis revealed significant differences (log-rank: P=.024; Breslow: P=.068; Tarone-Ware: P=.040). CONCLUSIONS: In our cohort of patients treated with ETN the estimated survival was better than patients treated with other biological drugs at 1-year, 2-years and 5-years.

Manejo de las manifestaciones extraglandulares del síndrome de Sjögren primario / Management of the extraglandular manifestations of primary Sjögrens syndrome

El síndrome de Sjögren primario (SSp) es una enfermedad sistémica autoinmune, de progresión lenta y etiología desconocida, que se caracteriza por la infiltración linfocitaria de las glándulas exocrinas, provocando especialmente xeroftalmia y xerostomía. Puede afectar a cualquier órgano o sistema, provocando manifestaciones extraglandulares, que incluso pueden preceder a las típicas manifestaciones glandulares y retrasar el diagnóstico. En los últimos años el mayor conocimiento de la enfermedad ha inducido también mejoras en su manejo terapéutico (AU)

Primary Sjögren′s syndrome (pSS) is a chronic systemic autoimmune disease, of slow progression, characterized by lymphocytic infiltration of the exocrine glands, that leads to sicca symptoms, mainly xerophtalmia and xerostomia. It may involve any organ and lead to extraglandular manifestations, which also can precede typical glandular manifestations and delay the diagnosis of pSS. In the past years, better knowledge of the disease has led to improvement in treatment management (AU)

[Management of the extraglandular manifestations of primary Sjögrens syndrome]. / Manejo de las manifestaciones extraglandulares del síndrome de Sjögren primario.

Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease, of slow progression, characterized by lymphocytic infiltration of the exocrine glands, that leads to sicca symptoms, mainly xerophtalmia and xerostomia. It may involve any organ and lead to extraglandular manifestations, which also can precede typical glandular manifestations and delay the diagnosis of pSS. In the past years, better knowledge of the disease has led to improvement in treatment management.

Susceptibilidad de la población española a los efectos adversos por sulfasalazina: revisión sistemática / Susceptibility of the spanish population to adverse effects by sulfasalazine: systematic review

Introducción: La experiencia clínica hace sospechar que la población española pudiera sufrir más efectos adversos por la sulfasalazina (SSZ). Se realizó una revisión sistemática de la literatura existente con el objetivo de analizar la susceptibilidad a desarrollar eventos adversos producidos por la SSZ en la población española. Material y método: Se definió una estrategia de búsqueda bibliográfica sensible en EMBASE, IBECS y MEDLINE desde 1973 hasta marzo de 2007. En los artículos seleccionados se buscó la descripción de los efectos adversos, tanto en el texto como en las tablas, así como los motivos de retirada, la población estudiada y la discusión sobre la opinión de las diferencias en los efectos adversos de los diferentes grupos de tratamiento. Resultados: De un total de 106 artículos rescatados se seleccionaron 36 para realizar un análisis detallado de los 34 artículos seleccionados en MEDLINE y EMBASE y de los 2 de IBECS. No se encontró ningún estudio que evidencie que la población española sea más susceptible a los efectos adversos por SSZ. Conclusiones: Los efectos adversos por SSZ varían según el patrón de acetilación. En la población española la prevalencia de acetiladores lentos es mayor que en otros grupos étnicos; por tanto, cabría inferir que la incidencia de efectos adversos secundarios a la SSZ podría ser mayor en la población española que en otros grupos. No encontramos evidencia en la literatura de que la población española sea más susceptible a los efectos adversos por la SSZ (AU)

Background: Clinical experience raises suspicion that the spanish population could suffer higher rates of side effects of sulfasalazine (SSZ) therapy. We conducted a systematic review of existing literature to analyze the susceptibility to developing adverse events produced by SSZ in the Spanish population. Material and method: A literature search was conducted in EMBASE, IBECS, and MEDLINE from 1973 to March 2007. The items sought were those describing adverse effects, both in text and tables, and reasons for withdrawal, the population under study and discussion of differences in side effects of the different treatment groups. Results: Of the 106 retrieved articles, 36 were selected for review and detailed analysis. 34 articles were selected from MEDLINE and EMBASE and 2 from IBECS. We did not find any study that showed that the Spanish population was more susceptible to SSZ. Conclusions: The adverse effects of SSZ vary with the pattern of acetylation. Thus, in slow-acetylators, depending on the dosage of SSZ, the side effects increase significantly. In the Spanish population slow-acetylators prevalence is higher than in other ethnic groups. Therefore, one could infer that the incidence of adverse side effects by SSZ could be higher in the Spanish population than in others different ethnic groups. We found no evidence that the Spanish population was more likely to suffer adverse effects by SSZ than other ethnic groups (AU)

[Susceptibility of the spanish population to adverse effects by sulfasalazine: systematic review]. / Susceptibilidad de la población española a los efectos adversos por sulfasalazina: revisión sistemática.

BACKGROUND: Clinical experience raises suspicion that the spanish population could suffer higher rates of side effects of sulfasalazine (SSZ) therapy. We conducted a systematic review of existing literature to analyze the susceptibility to developing adverse events produced by SSZ in the Spanish population. MATERIAL AND METHOD: A literature search was conducted in EMBASE, IBECS, and MEDLINE from 1973 to March 2007. The items sought were those describing adverse effects, both in text and tables, and reasons for withdrawal, the population under study and discussion of differences in side effects of the different treatment groups. RESULTS: Of the 106 retrieved articles, 36 were selected for review and detailed analysis. 34 articles were selected from MEDLINE and EMBASE and 2 from IBECS. We did not find any study that showed that the Spanish population was more susceptible to SSZ. CONCLUSIONS: The adverse effects of SSZ vary with the pattern of acetylation. Thus, in slow-acetylators, depending on the dosage of SSZ, the side effects increase significantly. In the Spanish population slow-acetylators prevalence is higher than in other ethnic groups. Therefore, one could infer that the incidence of adverse side effects by SSZ could be higher in the Spanish population than in others different ethnic groups. We found no evidence that the Spanish population was more likely to suffer adverse effects by SSZ than other ethnic groups.