Baseline serum RANKL levels may serve to predict remission in rheumatoid arthritis patients treated with TNF antagonists.

AIMS: The objective of this study was to investigate whether baseline receptor activator for nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) serum (s) levels can predict the therapeutic response to TNF antagonists (a-TNF). METHODS: We studied 75 rheumatoid arthritis patients (81% female) with a longstanding refractory disease. The variables of disease activity, physical function and sRANKL and sOPG levels were determined before and after both 12-14 and 28-30 weeks of a-TNF therapy (65 adalimumab, 10 infliximab). Remission was defined by a 28 joint count disease activity score (DAS28) /=1.2 at both 3- and 7-month follow-up visits. RESULTS: In most patients, disease activity was severe, as reflected by a baseline DAS28 score of 5.9+/-1 (mean+/-SD), an HAQ of 1.6 (1.1 to 2.1) (median (interquartile range (IQR))) and a CRP 15 mg/l (IQR: 9 to 24). The sRANKL levels and RANKL/OPG ratio in patients that achieved remission were significantly lower at baseline than in the remaining patients at both 3 and 7 months of follow-up. The sOPG levels correlated with the HAQ and the physician's disease assessment and diminished significantly after a-TNF treatment. However, no significant association was detected between the therapeutic response profile and sOPG levels. CONCLUSIONS: These data suggest that in patients receiving a-TNF treatment, lower serum levels of RANKL and RANKL/OPG ratio may serve to predict remission.

Reproducibility of metacarpophalangeal bone mass measurements obtained by dual-energy X-ray absorptiometry in healthy volunteers and patients with early arthritis.

The prognostic value of measuring hand bone mineral density (BMD) in patients with early arthritis (EA) has been recently assessed. In this work, we evaluate the reproducibility of measuring juxta-articular BMD by dual-energy X-ray absorptiometry (DXA) at the second to fifth metacarpophalangeal (MCP) joints. We obtained whole hand (WH) and MCP joint BMD measurements from 16 healthy subjects and from 22 patients with EA. The coefficient of variation, intraclass correlation coefficient (ICC), and smallest detectable difference (SDD) were calculated. The coefficient of variation ranged from 1.3% to 0.7% at MCP joints and from 1.4% to 0.9% in the WH measurements, respectively. The intra- and interobserver ICC for both WH and MCP joints ranged from 0.97 to 0.99. The SDD at the different anatomical locations analyzed ranged from 0.006 to 0.022 g/cm2 in healthy controls and from 0.005 to 0.010 g/cm2 in EA. Interestingly, patients who fulfilled rheumatoid arthritis criteria showed a lower bone mass than those with undifferentiated arthritis. Therefore, BMD measurements obtained by DXA at MCP joints were reproducible and it might be useful in the study of patients with EA.

Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator.

OBJECTIVE: To assess the effects of the prescription formulation of glucosamine sulfate (1,500 mg administered once daily) on the symptoms of knee osteoarthritis (OA) during a 6-month treatment course. METHODS: Three hundred eighteen patients were enrolled in this randomized, placebo-controlled, double-blind trial in which acetaminophen, the currently preferred medication for symptomatic treatment of OA, was used as a side comparator. Patients were randomly assigned to receive oral glucosamine sulfate 1,500 mg once daily (n = 106), acetaminophen 3 gm/day (n = 108), or placebo (n = 104). The primary efficacy outcome measure was the change in the Lequesne index after 6 months. Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and response according to the Osteoarthritis Research Society International criteria. These outcome measures were assessed using an intent-to-treat analysis. RESULTS: At baseline, the study patients had moderately severe OA symptoms (mean Lequesne index approximately 11 points). Glucosamine sulfate was more effective than placebo in improving the Lequesne score, with a final decrease of 3.1 points, versus 1.9 with placebo (difference between glucosamine sulfate and placebo -1.2 [95% confidence interval -2.3, -0.8]) (P = 0.032). The 2.7-point decrease with acetaminophen was not significantly different from that with placebo (difference -0.8 [95% confidence interval -1.9, 0.3]) (P = 0.18). Similar results were observed for the WOMAC. There were more responders to glucosamine sulfate (39.6%) and acetaminophen (33.3%) than to placebo (21.2%) (P = 0.004 and P = 0.047, respectively, versus placebo). Safety was good, and was comparable among groups. CONCLUSION: The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating knee OA symptoms. Although acetaminophen also had a higher responder rate compared with placebo, it failed to show significant effects on the algofunctional indexes.

CD69 expression on lymphocytes and interleukin-15 levels in synovial fluids from different inflammatory arthropathies.

OBJECTIVE: The aim was to study a possible relationship between CD69 expression on lymphocytes and interleukin-15 (IL-15) levels in synovial fluid (SF) from patients with different inflammatory arthropathies. METHODS: CD69 expression was assessed by two-color flow cytometry on different subsets of synovial fluid lymphocytes (SFL) obtained from patients with diagnoses of rheumatoid arthritis (RA), seronegative spondyloarthropathy (SSd), and crystal-associated arthritis (CAA). The IL-15 levels in synovial fluid supernatants were measured by enzyme-linked immunoassay (ELISA). RESULTS: No significant differences between the three groups of arthropathies were observed in the distribution of synovial fluid lymphocyte subsets. CD69-positive SFL were mainly CD3-, CD45RO-, and CCR5-positive cells. Although no significant differences in the percentage of CD69-positive lymphocytes were observed between the three groups of patients, the highest level of CD69 expression on lymphocytes was observed in RA patients (mean fluorescence intensity 37.9 +/- 5.2 compared to 17.5 +/- 3.3 in SSd and 12.4 +/- 2.6 in CAA, P = 0.007 and P < 0.001, respectively). In addition, the expression of CD69 on SFL from RA correlated with their respective IL-15 levels measured in SF supernatants. CONCLUSION: Our data provide in vivo evidence of the putative role that IL-15 can play in the high expression of CD69 on SFL from RA patients.

Mecanismos de acción de fármacos modificadores de la evolución de la artritis reumatoide / Mechanisms of action of dugs modifying the evolution of rheumatoid arthritis

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Proyecto EPISER 2000: prevalencia de enfermedades reumáticas en la población española / EPISER 2000: prevalence of rheumatic diseases in the Spanish population. Methodology, recruitment results, and population characteristics

Fundamento: El objetivo del estudio EPISER 2000 es de estimar la prevalencia de lumbalgia, artrosis de manos y rodilla, artritis reumatoide, fibromialgia, y osteoporosis en la población española, así como realizar un pilotaje de un estudio de prevalencia de lupus eritematoso sistémico. Métodos: Encuesta poblacional a 2.998 sujetos mayores de 20 años de edad, seleccionados mediante muestreo polietápico, aleatorio y estratificado por edad y sexo, de los padrones de 20 municipios españoles. La encuesta fue realizada por reumatólogos entrenados e incluía una densitometría de manos. Durante la misma visita, los sujetos positivos para el cribado de las enfermedades objeto de estudio eran examinados detalladamente siguiendo un protocolo estandarizado. Para la definición de los casos se utilizaron criterios validados del American College of Rheumatology y de la OMS. A los sujetos que rechazaron acudir a la entrevista, se les facilitaba un cuestionario básico, por teléfono o por correo. Resultados: La tasa de reclutamiento obtenida fue del 73 por ciento (2.192), siendo la mayoría de los fallos debidos a la imposibilidad de localizar a los sujetos seleccionados (390; 13 por ciento). En 203 (6,7 por ciento) casos la no participación se debió a errores censales manifiestos. El 7 por ciento (213) rechazó participar. La participación fue mayor en el medio rural (84 por ciento) y entre las mujeres (76 por ciento). No se encontraron diferencias relevantes en la características sociodemográficas y en el perfil de salud entre los sujetos que rechazaron y los que aceptaron participar. Conclusiones: El estudio EPISER 2000 presenta validez para la generalización de los resultados sobre prevalencia de las principales enfermedades reumatológicas en la población española. Se discute la efectividad del diseño frente a estudios similares (AU)