Jordi Gratacós

Significant loss of bone mass in patients with early, active ankylosing spondylitis : A followup study

OBJECTIVE To analyze whether inflammatory disease activity plays a substantial role in the loss of bone mass observed in ankylosing spondylitis (AS) patients who have not yet developed ankylosis. METHODS A longitudinal cohort study of 34 patients with early AS (duration <10 years) without ankylosis was conducted. The mean followup was 19 months. Loss of bone mass in defined regions of the lumbar spine and femoral neck was analyzed by dual x-ray absorptiometry. Patients were grouped according to biologic parameters of disease activity (erythrocyte sedimentation rate or C-reactive protein level). Group 1 consisted of 14 patients with active disease; group 2 comprised 20 patients with inactive disease. Serum levels of interleukin-6 (IL-6) and of hormones (sex, thyroid, and calciotropic), vertebral mobility (Schober test), daily physical activity, and treatment administered were recorded every 6 months for all patients. RESULTS At the end of the followup period, patients with active AS showed a significant reduction in bone mass in the lumbar spine (mean 1.01 gm/cm2 at study entry versus 0.961 gm/cm2 at followup [P = 0.005]) and femoral neck (0.849 gm/cm2 versus 0.821 gm/cm2 [P = 0.015]), which represented losses of 5% and 3%, respectively. In contrast, no significant reduction in bone mass was observed in patients with inactive AS. As expected, serum IL-6 levels were significantly higher in patients with active AS than in those with inactive disease (mean +/- SD 8.3 +/- 9 pg/ml versus 2.8 +/- 5 pg/ml [P = 0.008]). No significant differences were observed between the 2 groups in any of the other variables analyzed. CONCLUSION The observation that loss of bone mass in AS occurred only in patients with persistent active disease strongly suggests that inflammatory activity of the disease itself plays a major role in the pathophysiology of the early bone mineral disorders observed in these patients.

Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients

Objectives: To evaluate the prevalence and incidence of antimalarial myopathy in patients with rheumatic diseases treated with antimalarial drugs. Methods: Over a three year period, all patients with rheumatic diseases who were taking antimalarial drugs were studied. Serum muscle enzymes were assessed at the time of inclusion and every six months thereafter. Muscle strength, electromyography (EMG), and muscle biopsy were assessed in patients with a persistent muscle enzyme disturbances. Results: 119 patients were included (111 chloroquine, eight hydroxychloroquine). Of these, 22 (18.5%) had a persistent muscle enzyme disturbance: lactate dehydrogenase 19/22 (86%); creatine kinase 7/22 (32%), and aldolase 3/22 (14%). Findings of antimalarial myopathy were detected in 3/15 biopsied patients (20%) by light microscopy and in all 15 by electron microscopy. Eleven patients had myopathy at the time of inclusion (prevalence 9.2%) and four patients developed muscle injury during follow up (annual incidence 1.2%). Muscle weakness was observed in 8 of 15 patients with biopsy proven myopathy, giving a prevalence of clinical antimalarial myopathy of 6.7%. All these patients also had a myopathic pattern on electromyography. Conclusions: The prevalence of antimalarial myopathy is higher than previously recognised when muscle enzyme determination is used as a screening method. When a persistent muscle enzyme disturbance is observed, clinical and electromyographic studies should be undertaken periodically to detect the development of clinical myopathy. In cases of clinical myopathy, an anatomical-pathological tissue study, including an ultrastructural study, is mandatory to confirm the diagnosis.

Prevalence of Vertebral Fractures by Semiautomated Morphometry in Patients with Ankylosing Spondylitis

Objective. Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the axial skeleton and characterized by ossification of the spinal disc, joints, and ligaments leading to progressive ankylosis. Vertebral osteoporosis is a recognized feature of AS. Studies have confirmed a moderate to high prevalence of vertebral fractures with extremely varying ranges in patients with AS. Our objective was to estimate the prevalence of vertebral fractures in a representative Spanish population of patients with AS using a validated semiquantitative method, MorphoXpress®. Methods. Patients were randomly selected from the 10 initial participating centers of the Spanish National Registry of Spondyloarthropathies (REGISPONSER) by consecutive sampling. All patients fulfilled the New York modified criteria for AS and had a baseline thoracolumbar radiograph. A prevalent vertebral fracture was defined according to the Genant classification criteria. Results. The estimated prevalence of vertebral fractures was 32.4% (95% CI 25.5%–39.3%). The majority of fractures were localized in the thoracic segment (n = 100; 82.%) and were mild (n = 79; 64.8%). In logistic regression analysis, age (odds ratio per year 1.05, 95% CI 1.03–1.08, p < 0.001), disease duration (OR per year 1.03, 95% CI 1.01–1.06, p = 0.011), Bath Ankylosing Spondylitis Functional Index score (OR per score 1.16, 95% CI 1.03–1.30, p = 0.015), Bath Ankylosing Spondylitis Radiographic Index-TS (OR per score 1.25, 95% CI 1.12–1.39, p < 0.001), and wall-occiput distance (OR per cm 1.15, 95% CI 1.08–1.23, p < 0.001) were all associated with prevalent fracture. Conclusion. Semiquantitative methods are needed to improve the diagnosis of vertebral fractures in AS in order to start early treatment and to avoid complications arising from osteoporosis.

Work Disability in Patients with Ankylosing Spondylitis

Objective. To determine the prevalence of work disability in Spanish patients with ankylosing spondylitis (AS) and to identify factors related to it. Methods. A cross-sectional study based on data from Regisponser (National Spanish Registry of Patients with Spondyloarthropathy). Demographic and disease-related variables were collected. AS patients were classified as work-disabled according to the Spanish Social Security System criteria. Variables that discriminated between AS patients with and those without work disability were identified using chi-square test or unpaired t test when appropriate. Multiple logistic regression was performed. Results. In total 699 AS patients, age 48.7 ± SD 12.7 years and with disease duration 14.1 ± 10.1 years, were analyzed; 179 patients (25.6%) had permanent work disability. Several variables had significantly different values in patients with compared to those without work disability. In the regression model (pseudo R2 = 0.26, p < 0.0001), age (p = 0.001), sex (p = 0.04), disease duration (p = 0.006), total Bath AS Radiological Index (p = 0.007), Bath AS Functional Index (BASFI; p = 0.007), and chest expansion (p = 0.03) retained an independent association with work disability. When BASFI was excluded from the model the independent association with sex did not remain, and a significant association with finger to floor distance was found (p = 0.040). Conclusion. The prevalence of permanent work disability in Spanish patients with AS is significant, and the main factors related to it are age, disease duration, structural damage, and physical functioning. Longitudinal studies are needed to confirm these results.

Prevalencia de hipovitaminosis D en una población anciana institucionalizada. Valoración del tratamiento sustitutivo

Fundamento La osteoporosis senil es una enfermedad grave y prevalente, uno de cuyos mecanismos causantes mas importantes parece ser el deficit de vitamina D. La hipovitaminosis D es probablemente frecuente entre la poblacion anciana, en especial en la institucionalizada. El objetivo de este trabajo fue determinar la prevalencia de hipovitaminosis D en una poblacion anciana institucionalizada. Sujetos y metodo Estudio transversal en el que se incluyo de forma aleatoria 100 ancianos institucionalizados. Se valoro la prevalencia de hipovitaminosis D, asi como las posibles repercusiones sobre el metabolismo fosfocalcico y la presencia de hiperparatiroidismo secundario. Se recogieron ademas el grado de exposicion solar y la presencia de comorbilidad. Estudio longitudinal (6 meses) en el que se incluyeron los individuos con hipovitaminosis D y se valoro la eficacia de dos pautas terapeuticas distintas con calcidiol (16.000 UI a la semana o 16.000 UI cada tres semanas). Resultados El 87% de los individuos presentaron hipovitaminosis D. El 21,8% de ellos presentaron ademas un hiperparatiroidismo secundario. La poblacion estudiada tuvo tambien un bajo grado de exposicion solar y una alta prevalencia de comorbilidad. Las dos dosis de calcidiol consiguen normalizar las concentraciones de 25-OHD 3 y compensar el hiperparatiroidismo secundario, si bien con la administracion semanal se consiguieron concentraciones sanguineas mas elevadas. Conclusiones En la poblacion anciana institucionalizada y con elevada comorbilidad, la prevalencia de hipovitaminosis D es muy alta. El aporte de calcio y calcidiol consigue normalizar la 25-OHD 3 , mejorar la absorcion de calcio y compensar el hiperparatiroidismo secundario. En la poblacion geriatrica institucionalizada deberia considerarse la necesidad de la suplementacion con calcio y vitamina D.

The burden of ankylosing spondylitis in Spain.

OBJECTIVE To investigate the burden of ankylosing spondylitis (AS) in Spain, as baseline for economic evaluation of the use of biological agents. METHODS A cross-sectional retrospective observational study was performed in 601 patients with AS in Spain, using a methodology developed in studies in the United Kingdom and Canada. Patients were mailed a questionnaire asking about their health-care consumption, out-of-pocket expenses, work capacity, need for informal care during the past 3 months, as well as quality of life. Patients current functional status and disease activity level was assessed using the Bath functional and disease activity indexes (BASFI and BASDAI). RESULTS The mean age (median) was 47.8 (12.4) years, and the mean disease duration was 18.8 years. Eighty percent of patients were male, and slightly more than half of patients below 65 years of age were working. The mean (median) BASDAI and BASFI scores were 4.3 (2.5) and 3.8 (2.9),respectively, and all levels of disease severity were represented. The mean (median) total annual cost per patient is estimated at euro 20,328 (euro 7920). Direct health care represented 22.8%, investments (adaptations of house and devices) and informal care 43.5%, and productivity losses 33.7%. Costs increased significantly with worsening disease, in particular diminishing physical function, covering a range between euro 5000 and euro 75,000 per patient and year. The mean (median) utility was 0.59 (0.30). Utility showed a significant inverse relation with BASFI and BASDAI, covering a range from 0.80 for patients with BASFI/BASDAI below 3 to 0.25 for patients with BASFI/BASDAI greater than 7. CONCLUSIONS As in studies in other countries, all types of costs accelerate steeply with worsening disease while utility decreases significantly, indicating the need to prevent disease progression.

Prediction of major clinical response (ACR50) to infliximab in psoriatic arthritis refractory to methotrexate

Objectives: To determine the predictive factors of clinical response to infliximab in patients with refractory psoriatic polyarthritis. Methods: A multicentre open study which included 69 patients with psoriatic polyarthritis refractory to methotrexate (15 mg/week at least for 8 weeks). Patients were treated with infliximab 5 mg/kg every 8 weeks in addition to their stable doses of methotrexate. A major clinical response was defined by the ACR50 at week 38. Logistic regression analysis was performed to analyse which of the following measures at the start of treatment were associated with an ACR50 response: demographic and clinical characteristics, duration of disease, tender and swollen joint counts, involvement of large joints (knee or hip, or both), erythrocyte sedimentation rate, C reactive protein (CRP), Health Assessment Questionnaire disability index, axial involvement, and the presence of erosions at baseline. Results: In an intention to treat analysis 30/69 (44%) patients achieved an ACR50 response. In the univariate analysis both the presence of large joint involvement and severe disability were associated with a poor clinical response. In a multivariate logistic regression analysis high CRP values were independently associated with a good therapeutic response (odds ratio (OR) = 18.7; 95% confidence interval (CI) 1.8 to 181.6; p = 0.011). In contrast, large joint involvement and severe disability were associated with a poor response, which reached significance for large joint involvement (OR = 29.3; 95% CI 3.2 to 266.3; p = 0.003). Conclusion: A lower disability and, in particular, the absence of large joint involvement and higher CRP serum levels at the start of infliximab treatment are factors that seem to influence the probability of achieving a good therapeutic response in patients with psoriatic arthritis.

Actualización del Consenso de la Sociedad Española de Reumatología sobre el uso de antagonistas del TNFα en las espondiloartritis, incluida la artritis psoriásica

.Hay poca evidencia cientifica de que los denominadosfarmacos modificadores de enfermedad (FAME),como el metotrexato, la sulfasalazina, la leflunomida,las sales de oro, los antimalaricos, etc., sean eficaces enla EA. La sulfasalazina se ha demostrado efectiva enestudios controlados, aunque de forma modesta, en lasmanifestaciones perifericas de la EA

High-dose etanercept in ankylosing spondylitis: results of a 12-week randomized, double blind, controlled multicentre study (LOADET study)

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

Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

IntroductionEvidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.MethodsSamples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.ResultsWith cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.ConclusionsCFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.