Cambios en la masa ósea en una población infantil con diabetes mellitus tipo 1. Estudio longitudinal / Changes in bone mass in a paediatric population with type 1 diabetes mellitus. Longitudinal study

Objetivo: Evaluar, a lo largo de un seguimiento de 79,2 meses, el comportamiento de la densidad mineral ósea (DMO) determinada mediante Densitometría Axial Computarizada (DXA), la densidad mineral ósea volumétrica (DMOvol) y su relación con los datos antropométricos, junto con los parámetros relativos al metabolismo óseo (calcio, fósforo, fosfatasa alcalina, parathormona (PTH) y vitamina D (25-OH-D3)) en una población infantil con Diabetes Mellitus Tipo 1 (DM1) sin complicaciones microvasculares y un grupo control de referencia de similares características.Material y métodos: Inicialmente, se realizó un estudio transversal en 40 niños diabéticos (edad media 9,4±2,8 años) y 108 controles (9,3±1,5 años) para valorar las posibles diferencias entre ambas poblaciones. 26 pacientes del grupo diabético inicial, fueron reevaluados tras 79,2 meses de seguimiento.Resultados: Se observó que, al inicio, la masa ósea fue similar en los diabéticos y controles. Después del seguimiento, la DMO de los niños diabéticos era muy inferior a la esperada en población infantil no diabética.El peso, la altura y el Índice de Masa Corporal (IMC) siguieron el mismo patrón que la DMO. Los valores de calcio, fósforo, fosfatasa alcalina, PTH y vitamina D, aunque en rango de normalidad, fueron más bajos que en los controles. La fosfatasa alcalina no se incrementó en el periodo puberal.Conclusiones: El presente estudio demuestra que los niños y adolescentes con un diagnóstico reciente de DM1 tienen una DMO normal. Sin embargo, con el paso del tiempo, y sobre todo durante la adolescencia, muestran una menor ganancia de masa ósea y alteraciones en los parámetros de recambio óseo. (AU)

Differences in clinical manifestations and increased severity of systemic lupus erythematosus between two groups of Hispanics: European Caucasians versus Latin American mestizos (data from the RELESSER registry).

BACKGROUND: Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. OBJECTIVES: This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. METHODS: This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. RESULTS: A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). CONCLUSION: SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

OBJECTIVES: To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. METHODS: This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. RESULTS: Mean age (years) ±â€¯S.D. at diagnosis was 14.2 ±â€¯2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ±â€¯S.D. was 1.27 ±â€¯1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P < 0.001); Cluster 2 (14.5% of patients) was characterized by renal damage in 60% of patients, significantly more than Clusters 1 and 3 (P < 0.001), in addition to increased more ocular, cardiovascular and gonadal damage; Cluster 3 (12.7%) was the only group with musculoskeletal damage (100%), significantly higher than in Clusters 1 and 2 (P < 0.001). The overall mortality rate in Cluster 2 was 2.2 times higher than that in Cluster 3 and 5 times higher than that in Cluster 1 (P < 0.017 for both comparisons). CONCLUSIONS: In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement.

The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB).

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. METHODS: The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. RESULTS: Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100 mg/dl (34%) and a high-density lipoprotein (HDL) level of <50 mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (p=0.001) and with TC (p=0.005) and TGs (p<0.001) at the end of the follow-up period. CONCLUSION: Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity.

Multicenter longitudinal study of B-lymphocyte depletion in refractory systemic lupus erythematosus: the LESIMAB study.

OBJECTIVE: This study aimed to investigate the effectiveness and safety of single and repeated courses of rituximab in patients with refractory lupus. METHODS: LESIMAB is a multicenter, retrospective, longitudinal study of lupus patients who have not responded to standard therapy and have been treated with rituximab. Response rates at six months and at follow-up were defined as efficacy outcomes. Complete response was defined as a SELENA-SLEDAI score ≤ two and a SELENA-SLEDAI Flare Index of zero. Partial response was defined as a reduction in the SELENA-SLEDAI score of ≥four points with no new or worsening of symptoms. Adverse events were collected. RESULTS: Seventy-three (62.9%) of 116 patients achieved a response at six months (complete in 22 and partial in 51). Ninety-seven (77.6%) of 128 patients achieved a response after a mean follow-up of 20.0 ± 15.2 months (complete in 50 and partial in 47). High baseline SLEDAI score, previous treatment with ≥100 mg/day prednisone, and no history of severe hematologic flare were associated with response after the first treatment course. The median time to response was 6.5 months (95% CI, 5.0-8.0). Thirty-seven patients (38.1%) relapsed after the first infusion. The flare was severe in seven cases and mild to moderate in 29 cases. Serious infection rate was 12.6/100 patient-years. A schedule of four weekly doses was associated with more serious infections. Six patients died: two of infection and four of lupus complications. CONCLUSION: Rituximab can be an effective treatment option for patients who have refractory lupus with severe or life-threatening disease with an acceptable tolerance profile.

Dose escalation of the anti-TNF-alpha agents in patients with rheumatoid arthritis. A systematic review.

OBJECTIVE: To estimate the proportion of rheumatoid arthritis (RA) patients on anti-tumour necrosis factor (anti-TNF) who require dose escalation. METHODS: Systematic review of the scientific literature. Infliximab, etanercept and adalimumab studies in RA were considered. Primary outcome was the proportion of patients requiring dose escalation. American College Rheumatology (ACR) and Disease activity score (DAS) responses post-escalation were assessed when available. RESULTS: From 1801 references, 16 studies with 8510 patients were included. Of all the infliximab patients, 53.7% underwent dose escalation. Fourty-four per cent of the infliximab patients experienced dose increase and 8.3%, frequency increase. The ACR20 response to dose escalation ranged from 27 to 36% and DAS28 improved from 5.2 to 4.5 in one study and from 4.1 to 3.7 in another. Of the etanercept patients, 17.5% experienced a dose increase but changes on the mean dose were not statistically significant. CONCLUSIONS: Dose escalation is common in patients treated with infliximab, and less frequent with etanercept. In a proportion of patients, the dose escalation seems effective. The design and evidence level of the available studies limit the strength of the conclusions.

[Effectiveness and safety of adalimumab and etanercept for rheumatoid arthritis in a third-level hospital]. / Efectividad y seguridad de adalimumab y etanercept en artritis reumatoide en un hospital de tercer nivel.

OBJECTIVE: To assess the effectiveness of adalimumab and etanercept at 6 and 12 months after therapy onset using DAS28, EULAR (European League Against Rheumatism), and ACR (American College of Rheumatology) criteria, and to analyze safety. METHOD: A prospective, 12-month, observational study of a patient cohort diagnosed with rheumatoid arthritis who were started on adalimumab or etanercept at the Rheumatology Department between January 2003 and December 2004. DAS28, EULAR, and ACR criteria were examined at 6 and 12 months. An intention-to-treat analysis was performed, and adverse reactions were quantitized. RESULTS: Ninety-nine patients were included - 50 on adalimumab and 49 on etanercept. Of these, 30 and 20%, respectively, received monotherapy. No differences in effectiveness were seen between both drugs during the studied periods of time according to DAS28. EULAR response to adalimumab at 6 and 12 months was: good 28 and 38%; moderate 40 and 36%; nil 10 and 4%; regarding etanercept at 6 and 12 months: good 29 and 43%; moderate 31 and 24%; nil 18 and 10%. As regards adalimumab at 6 and 12 months: ACR20: 64 and 62%; ACR50: 44 and 46%; ACR70: 22 and 26%; as regards etanercept at 6 and 12 months: ACR20: 61 and 65%; ACR50: 41 and 45%; ACR70: 16 and 24%. Eleven patients discontinued therapy in each group. CONCLUSIONS: Adalimumab and etanercept had a similar effectiveness in our population. Criteria of use may condition results, and thus awareness of other hospitals experience is encouraged.

Efectividad y seguridad de adalimumab y etanercept en artritis reumatoide en un hospital de tercer nivel / Effectiveness and safety of adalimumab and etanercept for rheumatoid arthritis in a third-level hospital

Objetivo: Valorar la efectividad de adalimumab y etanercept alos 6 y 12 meses de tratamiento mediante DAS28, criteriosEULAR (European League Against Rheumatism) y ACR (AmericanCollege of Rheumatology) y analizar la seguridad.Método: Estudio observacional, prospectivo, durante 12meses, de una cohorte de pacientes diagnosticados de artritis reumatoide,que iniciaron tratamiento con adalimumab o etanercepten el servicio de reumatología entre enero de 2003 y diciembrede 2004. Se determinaron criterios DAS28, EULAR y ACR a los6 y 12 meses. Se analizó por intención de tratar y se cuantificaronlas reacciones adversas.Resultados: Se incluyeron 99 pacientes, 50 con adalimumaby 49 con etanercept, de ellos el 30 y 20% en monoterapia. Nohubo diferencia de efectividad según DAS28 entre ambos fármacosen los periodos estudiados. La respuesta EULAR para adalimumaba los 6 y 12 meses fue: buena 28 y 38%, moderada 40 y36%, y ninguna 10 y 4% y para etanercept: buena 29 y 43%,moderada 31 y 24% y ninguna 18 y 10%. Para adalimumab a los6 y 12 meses: ACR20: 64 y 62%; ACR50: 44 y 46%; ACR70:22 y 26% y para etanercept a los 6 y 12 meses: ACR20: 61 y65%; ACR50: 41 y 45%; ACR70: 16 y 24%. Cesaron tratamientoen cada grupo 11 pacientes.Conclusiones: Adalimumab y etanercept presentan similarefectividad en nuestra población. Los criterios de utilización puedencondicionar los resultados, por ello es interesante conocer laexperiencia de otros hospitales

Objective: To assess the effectiveness of adalimumab and etanerceptat 6 and 12 months after therapy onset using DAS28,EULAR (European League Against Rheumatism), and ACR (AmericanCollege of Rheumatology) criteria, and to analyze safety.Method: A prospective, 12-month, observational study of apatient cohort diagnosed with rheumatoid arthritis who were startedon adalimumab or etanercept at the Rheumatology Departmentbetween January 2003 and December 2004. DAS28,EULAR, and ACR criteria were examined at 6 and 12 months.An intention-to-treat analysis was performed, and adverse reactionswere quantitized.Results: Ninety-nine patients were included – 50 on adalimumaband 49 on etanercept. Of these, 30 and 20%, respectively,received monotherapy. No differences in effectiveness were seenbetween both drugs during the studied periods of time according toDAS28. EULAR response to adalimumab at 6 and 12 months was:good 28 and 38%; moderate 40 and 36%; nil 10 and 4%; regardingetanercept at 6 and 12 months: good 29 and 43%; moderate31 and 24%; nil 18 and 10%. As regards adalimumab at 6 and 12months: ACR20: 64 and 62%; ACR50: 44 and 46%; ACR70: 22and 26%; as regards etanercept at 6 and 12 months: ACR20: 61and 65%; ACR50: 41 and 45%; ACR70: 16 and 24%. Elevenpatients discontinued therapy in each group.Conclusions: Adalimumab and etanercept had a similar effectivenessin our population. Criteria of use may condition results, andthus awareness of other hospitals experience is encouraged

Adaptación transcultural y validación de una versión en español de un instrumento específico para medir calidad de vida relacionada con la salud en pacientes con espondilitis anquilosante: el ASQoL / Cross-cultural adaptation and validation of a Spanish version of a specific instrument to measure health-related quality of life in patients with ankylosing spondylitis

Objetivo: Adaptación transcultural y validación de la versión en español del Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL). Pacientes y métodos: Estudio transversal con prueba testretest. Se incluyeron pacientes con espondilitis anquilosante (EA). Se realizó adaptación transcultural de la versión original del ASQoL mediante traducción y retrotraducción. Se estudiaron validez de constructo, consistencia interna, reproducibilidad y factibilidad. El análisis estadístico se realizó con el coeficiente de correlación de Spearman, la pruebas U de Mann- Whitney y Kruskal-Wallis, el coeficiente alfa de Cronbach y el estadístico kappa. Resultados: Se incluyeron 54 pacientes, 37 (68,5%) varones, con edad (promedio ± DE) 40,5 ± 10,5 años. El ASQoL tuvo una puntuación de 6,8 ± 4,7 (mediana, 7; intervalo, 0-17) y presentó correlaciones altas con los componentes globales físico (rho = 0,79) y mental (0,69) del SF-36 y con los dominios de dolor (0,82), vitalidad (0,75) y rol físico (0,68), así como con la mayoría de variables representativas de la EA. Las puntuaciones del ASQoL fueron significativamente diferentes entre los pacientes con distintos niveles de respuesta en el perfil de salud del EuroQol. El ASQoL tuvo un coeficiente alfa de Cronbach de 0,86. La prueba test-retest se realizó en 10 pacientes con un intervalo de 24 h y tuvo una kappa entre 1 (12 preguntas) y 0,57 (1 pregunta) con rho de 0,98 para las puntuaciones globales. El tiempo empleado osciló entre 2 y 5 min. Conclusiones: La versión en español del ASQoL es válida, fiable y factible de aplicar en nuestro medio para medir la calidad de vida de los pacientes con EA(AU)

Objective: To make a cross-cultural adaptation and validation of a version in Spanish of the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) for assessing the health-related quality of life (HRQL) of patients with Ankylosing Spondylitis (AS). Patients and methods: A cross-sectional study with test-retest. AS patients (modified New York criteria) were included. Cross-cultural adaptation was done. Construct validity was assessed comparing the ASQoL scores with the SF-36 and EuroQol scores and diseaserelated variables. Internal consistency and reliability (test-retest) were assessed. Feasibility was assessed by the time spent to complete the questionnaire and the number of items without answer. Spearman correlation coefficient, Mann-Whitney U test, and Kruskal-Wallis test were used in the statistical analysis. Cronbach´alpha coefficient and statistic kappa were used for assessing internal consistency and reliability. Results: Fifty-four patients, 37 males (68.5%), with age (mean±SD) 40.5 ± 10.5 years, were included. The ASQoL global score was 6.8 ± 4.7 (median, 7; range, 0-17). The ASQoL scores had high correlations with physical (rho = 0.79) and mental (0.69) SF-36 components, the SF-36 domains pain (0.82), vitality (0.75), and role-physical (0.68), and the most of the disease-related variables. The ASQoL scores were significantly different between patients with different response levels in the health profile of the EuroQol. The Cronbach´alpha coefficient was 0.86. The reliability had kappa = 1 in 12 items and rho = 0.98. The time spent to complete the ASQoL was from 2 to 5 minutes and there only was a missing answer in one patient. Conclusion: The Spanish ASQoL is valid, reliable, and feasible instrument for assessing the HRQL of the AS patients(AU)

[Cross-cultural adaptation and validation of a Spanish version of a specific instrument to measure health-related quality of life in patients with ankylosing spondylitis]. / Adaptación transcultural y validación de una versión en español de un instrumento específico para medir calidad de vida relacionada con la salud en pacientes con espondilitis anquilosante: el ASQoL.

OBJECTIVE: To make a cross-cultural adaptation and validation of a version in Spanish of the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) for assessing the health-related quality of life (HRQL) of patients with Ankylosing Spondylitis (AS). PATIENTS AND METHODS: A cross-sectional study with test-retest. AS patients (modified New York criteria) were included. Cross-cultural adaptation was done. Construct validity was assessed comparing the ASQoL scores with the SF-36 and EuroQol scores and diseaserelated variables. Internal consistency and reliability (test-retest) were assessed. Feasibility was assessed by the time spent to complete the questionnaire and the number of items without answer. Spearman correlation coefficient, Mann-Whitney U test, and Kruskal-Wallis test were used in the statistical analysis. Cronbach́alpha coefficient and statistic kappa were used for assessing internal consistency and reliability. RESULTS: Fifty-four patients, 37 males (68.5%), with age (mean±SD) 40.5±10.5 years, were included. The ASQoL global score was 6.8±4.7 (median, 7; range, 0-17). The ASQoL scores had high correlations with physical (rho = 0.79) and mental (0.69) SF-36 components, the SF-36 domains pain (0.82), vitality (0.75), and role-physical (0.68), and the most of the disease-related variables. The ASQoL scores were significantly different between patients with different response levels in the health profile of the EuroQol. The Cronbach́alpha coefficient was 0.86. The reliability had kappa = 1 in 12 items and rho = 0.98. The time spent to complete the ASQoL was from 2 to 5 minutes and there only was a missing answer in one patient. CONCLUSION: The Spanish ASQoL is valid, reliable, and feasible instrument for assessing the HRQL of the AS patients.

Análisis de costes en una cohorte de enfermos con artritis reumatoide atendidos en área especializada de reumatología en España / Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units in Spain

Objetivo: Conocer los costes generados durante un año por pacientes con artritis reumatoide (AR) atendidos en unidades de reumatología de hospitales públicos españoles. Métodos: Estudio observacional, multicéntrico, longitudinal y prospectivo, de un año de duración, realizado en unidades de reumatología de hospitales públicos españoles seleccionados de forma probabilística. Los pacientes con AR se seleccionaron aleatoriamente en cada hospital. Se realizaron 4 visitas (basal y cada 4 meses). Se registró la utilización de recursos y costes mediante diarios y entrevistas estructuradas. Resultados: Se incluyó a 301 pacientes y completaron 190 (83% mujeres), con edad (media ± DE) de 59 ± 13 años y duración de la enfermedad de 10 ± 10 años. El coste mediano anual por paciente fue de 3.845 euros (318- 36.783). El coste global anual estimado para la AR atendida en unidades de reumatología de hospitales públicos españoles es de 590.110.000 euros. De los costes globales, el 74% correspondió a costes directos y el 26% a costes indirectos. El 81% del coste directo fue por gasto médico y, de éste, el 56%, por fármacos y el 11%, por hospitalización, el 21% correspondió a visitas médicas y el 12%, a pruebas de laboratorio y complementarias. El principal componente del coste indirecto fue la invalidez, que supuso el 66% del total. Conclusión: El coste directo de la AR fue sustancialmente mayor que el indirecto. El coste por medicamentos fue el principal componente del coste. El coste anual por paciente tuvo un rango muy amplio debido a la gran variabilidad en la utilización de recursos(AU)

Objective: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. Methods: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. Results: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59 ± 13 years and the mean disease duration was 10 ± 10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. Conclusions: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient(AU)

Adalimumab for treating rheumatoid arthritis.

BACKGROUND: Adalimumab is a fully human anti-TNFalpha monoclonal antibody. Published studies indicate that its use in patients with RA can be effective and safe. OBJECTIVES: The aim of this review was to assess the efficacy and safety of adalimumab in the treatment of RA. SEARCH STRATEGY: Electronic databases were searched up to August, 2004: MEDLINE, CINAHL, EBM Reviews (CDSR, ACP Journal Club, DARE and CENTRAL) and Health STAR. Conference proceedings were hand searched and pharmaceutical companies were contacted to obtain additional unpublished data from published trials. Adalimumab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. SELECTION CRITERIA: All randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing adalimumab alone or in combination with DMARDs to placebo or other DMARDs. DATA COLLECTION AND ANALYSIS: Two reviewers independently collected the data in a standardized form and assessed the methodological quality of the trial using validated criteria. Outcome measures included ACR and EULAR responses, DAS 28 and components of ACR response and radiographic data. Safety data were also included. Continuous data were reported as weighted mean difference (WMD) with 95% confidence interval (95%CI), absolute benefit (AB) and relative difference (RD). Dichotomous outcomes were reported as relative risk (RR) with 95% CI, absolute risk difference (ARD) or risk difference (RDiff) with 95%CI and number needed to treat (NNT) or to harm (NNH). When significant heterogeneity was not found, data were pooled. MAIN RESULTS: Six studies with 2381 patients were included in this review. Two comparisons were done: A. adalimumab subcutaneously (sc) + methotrexate (or DMARDs) versus placebo sc + methotrexate (or DMARDs). B. adalimumab sc in monotherapy versus placebo sc. In the comparison A, with adalimumab 40 mg every other week (e.o.w.), the RR to achieve an ACR 20 response at 24 weeks ranged in the included studies from 1.52 to 4.63, and the NNT ranged from 1.9 to 5.4. The RR (95%CI) to achieve an ACR 50 response was 4.63 (3.04-7.05), and the NNT was 3.0 (95%CI 2.0-6.0). The RR (95%CI) to achieve an ACR 70 response was 5.14 (3.14-8.41) and the number needed to treat was 7.0 (95%CI 5.0-13.0). At 52 weeks, the RRs (95%CI) to achieve an ACR 20, 50, and 70 response were 2.46 (1.87-3.22), 4.37 (2.77-6.91), and 5.15 (2.60-10.22), with NNTs of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg e.o.w. and 20 mg every week (e.w.) significantly slowed the radiological progression including Sharp modified index, erosion score, and joint space score (only with 40 mg e.o.w.). In the comparison B, with adalimumab 40 mg e.o w. , the RRs to achieve an ACR 20, 50, and 70 response at 24/26 weeks were 1.91 (1.17-3.10), 2.84 (1.58-5.12), and 7.33 (2.25-33.90) with NNTs of 5.0 (95%CI 3.0-9.0), 7.0 (4.0-20.0), and 9.0 (3.0-38.0), respectively. In most of the analysed studies and comparisons, there were not significant differences in safety outcomes between adalimumab and control groups. The development of positive antinuclear antibodies was significantly more frequent in adalimumab patients than in placebo patients. Serious infections were significantly more frequent in adalimumab patients in only one study (Keystone 2004) with a RR (95%CI) of 7.64(1.02-57.18) and a NNH of 30.2. AUTHORS' CONCLUSIONS: On the basis of the studies reviewed here, adalimumab in combination with methotrexate is efficacious and safe in the treatment of the rheumatoid arthritis. Adalimumab 40 mg sc e.o.w. and 20 mg e.w. slows the radiographic progression at 52 weeks. Adalimumab in combination with DMARDs other than methotrexate is also efficacious and safe, even though data from one only study are available and the number of patients in each group is low. Adalimumab in monotherapy is efficacious and safe in the treatment of the rheumatoid arthritis but the effect size is lower than with combined therapy.

[Resource utilization in a cohort of rheumatoid arthritis patients attended in rheumatology units in Spain]. / Utilización de recursos en una cohorte de pacientes con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To determine resource use over a 1-year period in patients with rheumatoid arthritis (RA) attended in rheumatology units in hospitals within the Spanish public health system. PATIENTS AND METHODS: An observational, longitudinal, prospective, multicenter, 1-year study was performed in randomly selected rheumatology units in hospitals of the Spanish public health system. Patients with RA were randomly selected in each hospital. Four visits (at baseline and every 4 months) were conducted by a rheumatologist not routinely involved in the care of the patient. Demographic and disease-related variables were collected. Patient diaries and systematic interviews were used to gather data on resource use. RESULTS: A total of 301 patients were included and 190 (83% females) completed the study. The mean age was 59 ± 13 years and the mean disease duration was 10 ± 10 years. The resources most heavily used were medical. All of the patients made medical visits with a median of four visits to rheumatologists (1-13). Ninetynine percent of the patients took at least one drug. The most frequent drugs were paracetamol (41%), deflaza-cort (32%), and methotrexate (24%). Laboratory tests were performed in all patients, and x-rays were performed in 59%. Sixty-one patients (32%) were hospitalized; 75% of these patients were non-surgical. The most frequently used non-medical direct resources were meals and home visits by non-medical staff (39%). Thirtyone patients (16%) had some type of work disability. CONCLUSIONS: AR is associated with substantial utilization of medical and non-medical resources related to the disease and work disability.

[Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units in Spain]. / Análisis de costes en una cohorte de enfermos con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. METHODS: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. RESULTS: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59±13 years and the mean disease duration was 10±10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. CONCLUSIONS: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient.

[Rofecoxib versus non-steroidal anti-inflammatory drugs in arthrosis treatment: cost-effectiveness analysis for Spain]. / Rofecoxib frente a antiinflamatorios no esteroideos en el tratamiento de la artrosis: análisis coste-efectividad para España.

OBJECTIVE: Analyze the efficiency of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) versus rofecoxib prescription for arthrosis treatment in Spain through a theoretical model of cost-effectiveness. METHODOLOGY: A theoretical model of decision that evaluates the efficiency of the use of non-selective NSAIDs and rofecoxib in the treatment of patients > 65 years with arthrosis who were nonrespondent to the administration of acetaminophen 4 g/day. The analysis focuses on the estimate of the impact derived from the gastrointestinal (GI) adverse effects. Two alternative analysis contexts are considered: "customary clinical practice" and "rational use of GI drugs" with possible preventive use of gastroprotective (GP) drugs in both groups. The time horizon is 1 year. Direct expenses are estimated from the Spanish Health System perspective. The effectiveness parameter used is the number of severe GI complications prevented. RESULTS: Under the assumptions of the first context, with a 55% estimated combinated prescription of non-selective GP with NSAID, and 6% with rofecoxib, the percentage of cost compensation of rofecoxib is 72%. Under the assumptions of the second context, the cost of rofecoxib is totally compensated when the percentage of combinated prescription of GP with NSAIDs is 59%. CONCLUSION: The use of rofecoxib can be a cost-effective alternative with regard to the traditional non-selective NSAID in the arthrosis treatment, especially in context of higher preventive use of CI drugs.

La versión española del BASDAI es fiable y se correlaciona con la actividad de la enfermedad en pacientes con espondilitis anquilosante / The Spanish version of the BASDAI is reliable and correlates with disease activity in patients with ankylosing spondylitis

Objetivo: Estudiar la fiabilidad, validez de constructo y factibilidad de una versión en español del Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) para medir la actividad de la enfermedad en pacientes con espondilitis anquilosante (EA).Métodos: Estudio transversal. Se incluyeron pacientes con EA (criterios de Nueva York modificados). El mismo reumatólogo evaluó a todos los pacientes. Se registraron variables demográficas y relacionadas con la EA, incluyendo valoraciones globales del médico y el paciente, valoración del dolor por el paciente, BASDAI, BASFI (Bath Ankylosing Spondylitis Functional Index), BASMI (Bath Ankylosing Spondylitis Metrology Index) y cuestionarios de calidad de vida SF-36 y EuroQol. El BASDAI fue adaptado al español. Se estudiaron la fiabilidad (consistencia interna y reproducibilidad test-retest), validez de constructo y factibilidad (tiempo empleado y comprensión).Resultados: Se incluyeron 92 pacientes, 69 varones (75 por ciento), con edad (X +/- DE [media +/- desviación estándar]) de 40,7 +/- 9,1 años y duración de la enfermedad (X +/- DE) de 11 +/- 7,8 años. La puntuación del BASDAI mostró correlación estadísticamente significativa con r de Pearson mayores de 0,6 con a valoración del dolor por el paciente (VGP), valoración del dolor por el paciente y medido por el SF-36, función física medida por el BASFI y por el SF-36, calidad de vida medida por el SF-36 y Euro Qol y vitalidad medida por el SF-36. VGP, valoración del dolor por el paciente, BASFI y vitalidad mantuvieron asociación independiente con el BASDAI, en el modelo de regresión y explicaron el 73 por ciento de las variaciones en su puntuación. El coeficiente alfa de Cronbach fue de 0,87 y la prueba test-retest tuvo una rho de Spearman de 0,92, p<0,0001. El tiempo promedio fue de 60 segundos y la comprensión buena. Conclusiones: La versión en español del BASDAI mostró fiabilidad, validez de constructo y factibilidad, por lo que puede ser utilizada para medir la actividad de la enfermedad en pacientes españoles con EA (AU)

Costes calidad de vida-artritis reumatoide. Estudio económico y de la calidad de vida de los pacientes con artritis reumatoide en España. Resultados preliminares / The costs and quality of life in rheumatoid arthritis study in Spain. Preliminary results

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Calidad de vida de los pacientes con osteoporosis. Validación de la versión en español de un instrumento específico: el OPTQoL / Quality of life in patients with osteoporosis. Validation of the Spanish version of the Osteoporosis-Targeted Quality of Life Questionnaire

Objetivo: Estudiar la validez y confiabilidad de una versión española del Osteoporosis-Targeted Quality of Life Questionnaire (OPTQoL), un instrumento específico para medir calidad de vida relacionada con la salud (CVRS) en pacientes con osteoporosis (OP).Pacientes y métodos: Estudio transversal. Se incluyó a las pacientes con OP primaria (posmenopáusica o senil) definida por densidad mineral ósea (DMO) en columna lumbar o cuello femoral con T-score < -2,5 desviaciones estándar (DE). Se registraron variables demográficas y de enfermedad y se aplicaron los instrumentos OPTQoL (de 0 a 10, mejor a peor CVRS), SF-36 (de 0 a 10, mejor a peor CVRS), EuroQoL-pefil de salud (de 0 a 2, mejor a peor CVRS) y EuroQol-escala visual (de 0 a 10, mejor a peor estado de salud). Se estudió validez de constructo del OPTQoL (análisis de correlación y regresión con SF-36 y otras variables), capacidad discriminativa entre pacientes con y sin fractura vertebral (prueba de la U de Mann-Whitney), coherencia interna ( de Cronbach), reproducibilidad (prueba test-retest), tiempo empleado y comprensión. Para los análisis de correlación se utilizaron el doble producto momento de Pearson y el coeficiente de correlación de Spearman (test-retest). Se consideró significativo un valor de p < 0,05, sin ajuste para comparaciones múltiples. Resultados: 45 pacientes (43 mujeres) con edad (media ñ DE), 66,3 ñ 6,8 años; tiempo desde la menopausia (mujeres), 20,1 ñ 8,5 años, y T-score en columna lumbar, -3,42 ñ 0,9 DE; 20 (44 por ciento) con fracturas vertebrales. OPTQoL global, 7 ñ 2,1; correlación con SF-36 global, r = 0,69, p < 0,0001. OPTQoL- función física, 6,7 ñ 2,5; correlación con SF-36 función física, r = 0,74, p < 0,0001. OPTQoL adaptaciones, 7,1 ñ 2,1; correlación con SF-36escala física global, r = 0,66, p < 0,0001. OPTQoL miedos, 7,1 ñ 2,1. OPTQoL en pacientes con fracturas, mediana 8,2 frente a 6,3 en pacientes sin fractura, p = 0,0068. Coherencia interna y reproducibilidad test-retest: OPTQoL función física: alfa, 0,84 y rho, 0,95; adaptaciones, 0,85 y 0,98; miedos, 0,82 y 0,96. Tiempo: 5-10 min. Comprensión: buena. Conclusiones: La versión española del OPTQoL es válida, confiable y factible para medir CVRS en pacientes con OP. El deterioro de CVRS en la muestra de pacientes estudiada es importante (AU)

Purified protein derivative reaction in systemic lupus erythematosus patients. Indirect study of cellular immunity.

Cutaneous anergy in SLE patients results from disease activity and/or immunosuppressive treatment (IT). The aim of this study was to evaluate purified protein derivative (PPD) reaction in SLE patients. A total of 145 patients and 20 controls were studied. Five units of PPD were applied on day 0, and skin reaction was measured after 3 (PPD1) and 6 (PPD2) days. A booster was applied (day 14), and the reaction was measured after 3 (PPD3) and 6 (PPD4) days. Non-parametric ANOVA test and unpaired Student's t-test were performed. Forty patients (group I) were inactive (MexSLEDAI < 3), receiving no IT (at least 3 months previous to the PPD test); 39 (group II) were inactive receiving IT; 24 (group III) were active without IT, and 42 (group IV) were active with IT. Active patients had lower PPD1 (group III, 1.4 +/- 0.9; group IV, 0.6 +/- 0.5) than inactive patients (group I, 8.4 +/- 2.3; group II, 5.1 +/- 1.9) and than controls (9.4 +/- 3; P < or = 0.001). Group IV had lower delayed response (PPD2 = 0.3 +/- 0.3) than inactive groups (group I, 2.6 +/- 0.9; group II, 3.1 +/- 0.8) and than controls (7.9 +/- 2.5; P < or = 0.001). Group III had lower delayed reaction (PPD2 = 1.2 +/- 0.8) than controls (P < or = 0.001). Active SLE patients, receiving or not receiving IT, had lower skin response to PPD than inactive patients and controls.