Rheumatoid Arthritis: Rodriguez-Valverde V

Martinez-Taboada VM, Blanco R, Fito C, Pacheco MJ, Delgado-Rodriguez M, Rodriguez-Valverde V. · Rheumatology Division, Hospital Universitario "Marqués de Valdecilla," Facultad de Medicina, Universidad de Cantabria, Santander, Spain. · Semin Arthritis Rheum. · Pubmed #11182026 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: During the last few years, there have been several studies on T cell subsets in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), with conflicting results. Whereas some authors have found normal values of circulating CD8+ T cells, others have found a decreased number. Furthermore, in some studies, the level of CD8+ cells was found to be related to disease activity, and it has been proposed that a decrease of CD8+ T cells be used as a diagnostic criterion for PMR. The purpose of our study was to determine the value of assessing T cell subsets in PMR and GCA. METHODS: T lymphocyte subsets were determined by flow cytometry using a whole blood lysis technique in the following groups: 28 PMR and 6 GCA patients before corticosteroid treatment, 20 PMR and 12 GCA patients in clinical remission with steroid treatment, 55 PMR patients in remission without steroid treatment, 17 rheumatoid arthritis (RA) patients before treatment, and 18 age-matched controls with noninflammatory conditions. Total white cell, lymphocyte, and platelet counts, hemoglobin, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured by routine techniques. Comparisons were made by the Student's t-test and the Mann-Whitney test. A MEDLINE database search for studies published between 1983 and 1997 was performed. RESULTS: Compared with noninflammatory controls, CD8+ T cells were not reduced before steroid treatment in patients with active PMR/GCA in proportion (P =.7) or absolute numbers (P =.1). Patients with active disease had significantly lower hemoglobin levels and higher platelet counts, CRP, and ESR than noninflammatory controls (P <.05). When compared with active RA, CD8+ T cells were not reduced in patients with active PMR in proportion (P =.5) or absolute numbers (P =.2). Between these two groups, RA patients were significantly younger (P =.003) and had lower ESR values (P =.003). We did not find significant differences between patients with active PMR/GCA and those in remission with steroid therapy, except for the lower hemoglobin levels and higher platelet count, CRP, and ESR in the active disease group (P <.05). The same results were found when patients with active disease were compared with PMR in remission and no longer on steroid therapy, the only significant differences were those parameters reflecting the acute phase response (hemoglobin levels, platelet count, CRP and ESR). CONCLUSIONS: This study does not confirm the previous findings that the proportion or number of circulating CD8+ T cells are reduced in patients with active PMR/GCA. The utility of the determination of CD8+ T cells for diagnostic and prognostic purpose should be evaluated in a large multicenter study.

Smolen JS, Breedveld FC, Burmester GR, Combe B, Emery P, Kalden JR, Klareskog L, Maini RN, Numo R, van De Putte LB, van Riel PL, Rodriguez-Valverde V. · University of Vienna, Berlin. · Ann Rheum Dis. · Pubmed #10873957 links to  free full text

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Alvarez-Rodriguez L, Carrasco-Marin E, Lopez-Hoyos M, Mata C, Fernandez-Prieto L, Ruiz-Soto M, Calvo J, Rodriguez-Valverde V, Ruiz T, Blanco R, Corrales A, Martinez-Taboada VM. · Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Fundación Marqués de Valdecilla-Instituto de Formación e Investigación Margués de Valdecilla, Spain. · Hum Immunol. · Pubmed #19026700 No free full text.

Abstract: The objective of this study was to investigate whether there is an association between IL1RN polymorphism and disease susceptibility for three age-related inflammatory conditions: polymyalgia rheumatica (PMR), giant cell arteritis (GCA), and elderly-onset rheumatoid arthritis (EORA). A tandem-repeat polymorphism within IL1RN intron 2 was analyzed in 139 PMR, 69 GCA, and 156 RA patients (75 with EORA) as well as in 437 healthy subjects, together with the in vitro production of IL-1beta. Our results showed that the IL1RN*2/2 genotype was more frequent in PMR patients compared with controls (p = 0.032, odds ratio = 1.785, 95% confidence interval = 1.047-3.044) and GCA patients (p = 0.008, odds ratio = 4.661, 95% confidence interval = 1.352-16.065). We found no difference in the distribution of genotypes between PMR and EORA or between EORA and controls. However, the frequency of the IL-1RN*2/2 genotype had a tendency to be higher in patients with EORA compared with young onset RA. The presence of IL1RN*1 or IL1RN*2 allele was not associated with severity of the disease in PMR and GCA patients and did not influence the production of IL-1beta. In conclusion, the IL1RN*2 polymorphism in a homozygous state was associated with an increased susceptibility to PMR and may give some clues for a differential therapy with GCA.

van der Heijde D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H, Melo-Gomes J, Tornero-Molina J, Wajdula J, Pedersen R, Fatenejad S, Anonymous00372. · Department of Rheumatology, University Hospital, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #16572441 links to  free full text

Abstract: OBJECTIVE: To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. METHODS: Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. RESULTS: A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P<0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P<0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P<0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P<0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. CONCLUSION: Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.

Klareskog L, Gaubitz M, Rodriguez-Valverde V, Malaise M, Dougados M, Wajdula J, Anonymous00057. · Department of Medicine, Karolinska Institutet at Karolinska University Hospital, Stockholm 17176, Sweden. · Ann Rheum Dis. · Pubmed #16540554 No free full text.

Abstract: OBJECTIVE: To evaluate the long-term safety and efficacy of etanercept in patients with rheumatoid arthritis. METHODS: 549 patients entered this 5-year, open-label extension study and received etanercept 25 mg twice weekly. All patients showed inadequate responses to disease-modifying antirheumatic drugs before entry into the double-blind studies. Safety assessments were carried out at regular intervals. Primary efficacy end points were the numbers of painful and swollen joints; secondary variables included American College of Rheumatology (ACR) response rate, Disease Activity Score and acute-phase reactants. Efficacy was analysed using the last-observation-carried-forward approach. RESULTS: Of the 549 patients enrolled in the open-label trial, 467 (85%), 414 (75%) and 371 (68%) completed 1, 2 and 3 years, respectively; 363 (66%) remained in the study at the time of this analysis. A total exposure of 1498 patient-years, including the double-blind study, was accrued. In the open-label trial, withdrawals for efficacy-related and safety-related reasons were 11% and 13%, respectively. Frequent adverse events included upper respiratory infections, flu syndrome, rash and injection-site reactions. Rates of serious infections and malignancies remained unchanged over the course of the study; there were no reports of patients with central demyelinating disease or serious blood dyscrasias. After 3 years, ACR20, ACR50 and ACR70 response rates were 78%, 51% and 27%, respectively. The Disease Activity Score score was reduced to 3.0 at 3 months and 2.6 at 3 years from 5.1. A sustained improvement was found in Health Assessment Questionnaire scores throughout the 3-year time period. CONCLUSION: After 3 years of treatment, etanercept showed sustained efficacy and a favourable safety profile.

Lopez-Hoyos M, Ruiz de Alegria C, Blanco R, Crespo J, Peña M, Rodriguez-Valverde V, Martinez-Taboada VM. · Immunology Service, Hospital Universitario Marqués de Valdecilla, Facultad de Medicina, Universidad de Cantabria, Santander, Spain. · Rheumatology (Oxford). · Pubmed #14970400 links to  free full text

Abstract: BACKGROUND: In a significant number of patients the differential diagnosis between elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) is very difficult because of the lack of specific serum markers. Anti-cyclic citrullinated peptide antibodies (anti-CCP Abs) have recently been shown to be highly specific for rheumatoid arthritis (RA). This is the first study addressing the utility of these antibodies in the differential diagnosis between EORA and PMR. METHODS: Serum samples from 57 EORA patients and 49 PMR patients were studied for the presence of anti-CCP Abs and rheumatoid factor (RF). As controls, samples from 41 RA patients (age at onset <60 yr) and 24 aged healthy subjects were analysed. RESULTS: Sixty-five per cent of EORA patients had anti-CCP Abs, whereas none of the PMR patients or the aged healthy subjects was positive for those antibodies. Ten of the EORA patients started with polymyalgic symptoms and two of them were positive for anti-CCP Abs. Interestingly, there was a significant correlation between anti-CCP Abs and RF in EORA but not in young RA patients. CONCLUSIONS: The presence of anti-CCP Abs in a patient with clinical symptoms of PMR must be interpreted as highly suggestive of EORA.

Calvo-Alén J, Corrales A, Sánchez-Andrada S, Fernández-Echevarría MA, Peña JL, Rodriguez-Valverde V. · Hospital Universitario 'M Valdecilla', Division of Rheumatology, Av Valdecilla s/n, 39006 Santander, Cantabria, Spain. · Clin Rheumatol. · Pubmed #12740668 No free full text.

Abstract: The aim of this study was to study the short-term functional and anatomical prognosis of rheumatoid arthritis (RA) in a series of Spanish patients and to identify different subsets of patients as well as possible baseline factors associated with specific outcomes. All patients seen in our division who met the ACR criteria for RA and with disease duration between 2 and 7 years were eligible for the study. Available patients were further evaluated at the clinic for disease activity using biological tests and joint indices as joint counts and Thompson's index, functional capacity using the ACR functional classification (ACR-FC) and the modified Health Assessment Questionnaire (M-HAQ) and radiologic damage by the Sharp's radiologic scoring method. Cluster analysis was used to identify different clinical subsets of patients. One hundred and sixty-three patients were eligible for the study, 13 could not be located or refused to participate and 12 had died. Mean (+/-SD) age at disease onset and mean disease duration were, respectively, 56(+/-14) years and (55+/-20) months. Median (interquartile range) of M-HAQ was 0.4 (0.1-1.1) and 41% of patients were in III or IV ACR-FC. The majority of patients (93%) showed radiologic lesions and 65% had erosions. Cluster analysis identified three subsets: cluster I (70% of patients) was characterised by a good prognosis, cluster II (13%) by a high level of disease activity, and cluster III (17%) by a greater anatomic damage and longer disease duration. No baseline predictive markers were found for these different outcomes. We concluded that RA portends an overall poor short-term prognosis in a relative large percentage of our patients with significant anatomic and functional sequelae. Aggressive management is specially indicated in this subgroup of patients, although definitive prognostic markers for its early identification are still lacking.

Alonso-Bartolomé P, Martínez-Taboada VM, Blanco R, Rodriguez-Valverde V. · Division of Radiology, Hospital Universitario Marques de Valdecilla, Facultad de Medicina, Universidad de Cantabria, Santander, Spain. · Semin Arthritis Rheum. · Pubmed #10406409 No free full text.

Abstract: OBJECTIVE: Insufficiency fractures (IF) occur when normal or physiological muscular activity stresses a bone that is deficient in mineral or elastic resistance. IF of the tibia and fibula are probably less common than IF of the ribs, vertebrae, hip, pelvis, and distal ulna, and therefore they are frequently underrecognized and mistaken for other conditions. Our aim was to analyze the main features and outcome of IF of the tibia and fibula in patients attending our Rheumatology Service. METHODS: IF was considered when occurring spontaneously or with minimal trauma. Between January 1984 and July 1997, 25 patients were diagnosed as having IF of the tibia and fibula. The main predisposing factors, clinical features, therapy, and outcome were retrospectively reviewed. RESULTS: All the patients except four were women (mean age, 66+/-12 years). Three cases were diagnosed between 1984 and 1990 (0.42 cases/year) and 22 between 1991 and 1997 (three cases/year). Eighteen patients had an underlying CONDITION: rheumatoid arthritis (RA, 13 cases), psoriatic arthritis (2), systemic lupus erythematosus (SLE) (1), kidney transplant (1), and Crohn's disease (1). Eleven patients had osteoporotic fractures in other locations. Risk factors for osteoporosis were corticosteroids (13 cases), prolonged immobilization (10), early menopause (2), and methotrexate therapy (10). All patients had pain on weight bearing and marked functional impairment, 16 had local inflammatory signs, and 10 had deformity. In only five patients the diagnosis of IF was considered at the first examination. The diagnostic delay was 76+/-117 days (median, 21). The initial radiograph was diagnostic in 20 patients, and in the remaining the diagnosis was made by computed tomography (CT) scan (three cases), magnetic resonance imaging (MRI) (1), and bone scan (1). IF were located as follows: tibia (10 cases), fibula (seven), tibia and fibula (eight). Nineteen patients were treated with conservative management, four received no specific treatment, and two required surgery. Sixteen patients were hospitalized for a mean period of 12+/-8 days. Most patients had complete recovery. The high frequency of IF seen in RA patients is probably due to the severe disease in patients treated by our Service and that such patients have a higher risk for osteoporosis and its complications. CONCLUSIONS: IF of the tibia and fibula are probably more common than previously thought. They usually occur in patients with underlying rheumatic diseases, mainly RA, and are frequently mistaken for other joint and bone conditions. Despite a frequent delay in diagnosis, they have a good prognosis with conservative management. Nonetheless, a higher index of suspicion may avoid unnecessary investigations and treatments.

Martinez-Taboada VM, Rodriguez-Valverde V, Gonzalez-Vilchez F, Armijo JA. · No affiliation provided · Rheumatology (Oxford). · Pubmed #15501999 links to  free full text

This publication has no abstract.