Emilio Martín-Mola

Hospital Universitario La Paz, Madrid, Madrid, Spain

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Publications (110)547.19 Total impact

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    ABSTRACT: Chinese translation Many patients with rheumatoid arthritis (RA) do not achieve adequate and safe responses with disease-modifying antirheumatic drugs (DMARDs). Tofacitinib is a novel, oral, Janus kinase inhibitor that treats RA. To evaluate the efficacy and safety of tofacitinib in combination with nonbiologic DMARDs. 1-year, double-blind, randomized trial (ClinicalTrials.gov: NCT00856544). 114 centers in 19 countries. 792 patients with active RA despite nonbiologic DMARD therapy. Patients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice daily. Primary end points were 20% improvement in American College of Rheumatology (ACR20) criteria; Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6; DAS28-4(ESR)-defined remission, change in Health Assessment Questionnaire Disability Index (HAQ-DI) score, and safety assessments. Mean treatment differences for ACR20 response rates (month 6) for the 5-mg and 10-mg tofacitinib groups compared with the combined placebo groups were 21.2% (95% CI, 12.2% to 30.3%; P < 0.001) and 25.8% (CI, 16.8% to 34.8%; P < 0.001), respectively. The HAQ-DI scores (month 3) and DAS28-4(ESR) less than 2.6 response rates (month 6) were also superior in the tofacitinib groups versus placebo. The incidence rates of serious adverse events for patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3, or 10.9 events per 100 patient-years of exposure, respectively. In the tofacitinib groups, 2 cases of tuberculosis, 2 cases of other opportunistic infections, 3 cardiovascular events, and 4 deaths occurred. Neutrophil counts decreased, hemoglobin and low- and high-density lipoprotein cholesterol levels increased, and serum creatinine levels had small increases in the tofacitinib groups. Placebo groups were smaller and of shorter duration. Patients received primarily methotrexate. The ability to assess drug combinations other than tofacitinib plus methotrexate was limited. Tofacitinib improved disease control in patients with active RA despite treatment with nonbiologic DMARDs, primarily methotrexate. Pfizer.
    Annals of internal medicine 08/2013; 159(4):253-61. · 13.98 Impact Factor
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    ABSTRACT: Anti-TNF drugs have proven to be effective against Spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF is related to the previous development of ADA to the first anti-TNF drug in SpA patients. Forty two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF. Clinical activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the 1st and 2nd anti-TNF) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration. All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF. Out of 42 patients, 11 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first (3.52 +/- 1.03 without ADA vs 3.14 +/- 0.95 with ADA, P=0.399) and to the second (3.36 +/- 0.94 without ADA vs 3.09 +/- 0.91 with ADA, P=0.466) anti-TNF. At 6 months after switching, patients with previous ADA had lower disease activity (1.62 +/- 0.93 with ADA vs 2.79 +/- 1.01 without ADA, P=0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs 3 out of 11 (27.3%) with ADA, P=0.002). In SpA, the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.
    Arthritis research & therapy 07/2013; 15(4):R79. · 4.27 Impact Factor
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    ABSTRACT: Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. INTRODUCTION: To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. METHODS: A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. RESULTS: PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. CONCLUSIONS: Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.
    Osteoporosis International 06/2013; · 4.04 Impact Factor
  • Annals of the rheumatic diseases 06/2013; · 8.11 Impact Factor
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    ABSTRACT: BACKGROUND: Calprotectin is potentially a more sensitive biomarker of disease activity in rheumatoid arthritis (RA) than conventional acute-phase proteins such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) because it directly reflects inflammation in the synovium and synovial fluid rather than systemic inflammatory activity. OBJECTIVE: The aim of this study was to evaluate relationships between serum calprotectin levels, disease activity, and response to treatment. Calprotectin was also investigated as a predictive marker of clinical response. METHODS: This observational study included selected cohorts of patients with RA treated at La Paz University Hospital, Madrid, Spain. Associations between serum calprotectin levels and clinical and laboratory parameters were analyzed in a cross-sectional cohort of 60 patients with varying disease activity, and changes in calprotectin levels in response to treatment with infliximab were analyzed at baseline and after 3 and 6 months of treatment in a longitudinal cohort of 20 patients with very active disease. RESULTS: In the cross-sectional cohort, calprotectin levels correlated with rheumatoid factor levels (r = 0.25; p < 0.05) but not with titers of antibodies to cyclic citrullinated peptide. Significant correlations were also observed between calprotectin levels and the 28 swollen joint count (28-SJC), Disease Activity Score based on a 28-joint count (DAS28), Simplified Disease Activity Index (SDAI), ESR, and CRP levels. In the longitudinal cohort, calprotectin levels at baseline were not predictive of response to treatment but significantly decreased during treatment in responders (p < 0.0001). CONCLUSION: Calprotectin levels strongly correlate with clinical and laboratory assessments of joint inflammation and also decrease in response to treatment, indicating that calprotectin is a promising marker for assessment and monitoring of disease activity in patients with RA. Investigations are required to further evaluate its diagnostic, prognostic, and therapeutic potential.
    Molecular diagnosis & therapy 01/2013; · 1.69 Impact Factor
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    ABSTRACT: Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤-1.5 standard deviations. Subjects received 20 µg/day teriparatide (n=45) or 35 mg/week risedronate (n=47) for 18 months. Primary objective was to compare lumbar spine (L1-L3) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high resolution QCT (HRQCT) at the 12(th) thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/day and 6.4 years, respectively. 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% vs 3.8%; p=0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/TV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0%-34.0%; risedronate: 4.2%-6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 <p <0.015). Adverse events were similar between groups. None of the patients on teriparatide but 5 (10.6%) on risedronate developed new clinical fractures (p=0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate. © 2013 American Society for Bone and Mineral Research.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2013; · 6.04 Impact Factor
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    ABSTRACT: The first biological therapeutics in rheumatology are approaching patent expiration, encouraging development of 'follow-on' versions, known as 'biosimilars'. Biological agents range from simple replacement hormones to complex monoclonal antibodies and soluble receptors: large, intricate proteins with unique tertiary and quaternary structures that are inherently difficult to replicate. Post-translational modifications, such as glycosylation, may occur from changes in cell lines and/or manufacturing processes, resulting in products that are highly similar, but not identical, to approved 'reference' agents, hence, the term 'biosimilar', rather than 'bioidentical'. Even minor modifications in manufacturing processes, which iteratively occur with reference products due to improvements in efficiency, scale up to meet commercial demands or changes in manufacturing sites, may alter biological function and/or immunogenicity, potentially changing their safety and efficacy profile. As biosimilars are now in randomised controlled trials for treatment of rheumatic diseases, rheumatologists face decisions regarding equipoise and will need to consider their clinical use versus reference products. A clear understanding of the inherent differences between reference antibodies and biosimilars, their clinical implications and the processes governing regulation, approval and clinical use of biosimilars, is paramount. A panel of international experts in the field of rheumatology recently convened to evaluate and discuss these issues.
    Annals of the rheumatic diseases 12/2012; · 8.11 Impact Factor
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    ABSTRACT: BACKGROUND: Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion. METHODS: Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement. RESULTS: The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise. CONCLUSIONS: The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.
    Annals of the rheumatic diseases 11/2012; · 8.11 Impact Factor
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    ABSTRACT: Objective. To examine the frequency and phenotype of Th17 cells in the peripheral blood of patients with early non-radiographic axial SpA (early nrSpA).Methods. CD4(+) T cells were isolated from the peripheral blood of 30 early nrSpA patients, 11 AS patients and 41 age- and sex-matched healthy controls by Ficoll-Hypaque gradient and magnetic negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells and of cells producing TNF-α or IL-10 was determined by cytometry and concentrations of IL-17, IL-22, IFN-γ, TNF-α, IL-10 and IL-4 were measured by ELISA.Results. Early nrSpA but not AS patients demonstrated a significantly lower percentage of circulating Th17, Th1 and Th17/Th1 cells, together with lower CD4-derived IL-17 and IFN-γ secretion, as compared with controls. In contrast, the percentage of circulating cells producing IL-10 or TNF-α, and the secretion of CD4-derived IL-10, TNF-α, IL-22 and IL-4 in early nrSpA were not different from controls. All Th17 cells were CD45RO(+)CD45RA(-) and CCR6(+). The frequency of circulating Th17, Th1 and Th17/Th1 was negatively correlated with BASDAI, BASFI, ASDAS-CRP, ASDAS-ESR, AS quality of life (ASQOL) and patient's global assessment in HLA-B27(+) but not in HLA-B27(-) early nrSpA patients. A positive correlation between circulating Th17 cells and BASDAI was observed in AS.Conclusion. A decreased percentage of Th17, Th1 and Th17/Th1 cells is apparent in peripheral blood CD4(+) T cells from early nrSpA. Th17, Th1 and Th17/Th1 cell numbers are related to disease activity indices in HLA-B27(+), but not in HLA-B27(-), early nrSpA patients.
    Rheumatology (Oxford, England) 10/2012; · 4.24 Impact Factor
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    ABSTRACT: OBJECTIVES: The goal of this study was to investigate the usefulness of a short ultrasound (US) assessment in gout. METHODS: Patients with gout, confirmed by urate crystal identification, and having at least one symptomatic flare in the last three months were included. Standardised US examinations of sixteen joints and eight tendons in the lower limbs were carried out. Six lesions were studied: hyperechoic spots in the synovial fluid, hyperechoic cloudy areas (HCA), bright stippled aggregates (BSA), the double contour sign (DCS), erosions and the Doppler signal. For reliability, inter-reader analyses were performed by five rheumatologists. With the results, a short US assessment was created. RESULTS: Twenty-nine consecutive patients were included (93% men). The Doppler signal, HCAs and BSAs appeared in 100%, 97% and 93% of the patients, respectively. The DCS was found in 69% of patients. The locations that were most affected were the first metatarsophalangeal joint (MTP) and the knee joints, both of which are in 93% of patients. Reliability analyses showed consistent results for erosions, the Doppler signal, HCAs and the DCS in the 1st MTP (k=0.818, k=0.958, k=0.739 and k= 0.697, respectively) and for the DCS in the knees (k=0.779). A six-minute US examination of four joints (knees and the 1st MTPs) detected HCAs or DCS in 97% of cases. CONCLUSIONS: A US examination of four joints for two elemental lesions (the DCS and HCAs) is feasible, reliable and has face and content validity as a diagnostic test in patients with crystal-proven gout.
    Clinical and experimental rheumatology 09/2012; · 2.66 Impact Factor
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    ABSTRACT: Enthesitis is the hallmark of spondyloarthritis and is observed in all subtypes. Namely, a wide information on spondyloarthritis abnormalities, including synovitis, bursitis, tendinitis, enthesitis and cortical bone abnor malities (erosions and enthesophytes), can be effi - ciently perceived by ultrasound power Doppler. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect pathology at asymptomatic enthesis. Vascularized enthesitis detected by ultrasound power Doppler appears to be a valuable diagnostic tool to confirm spondyloarthritis diagnosis. This article focuses on the validity and reliability of ultrasound enthesitis assessment in the management of spondyloarthritis patients.
    Acta reumatologica portuguesa 07/2012; 37(3):217. · 0.70 Impact Factor
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    ABSTRACT: OBJECTIVE: To estimate the Minimum Clinically Important Improvement (MCII) and Patient Acceptable Symptomatic State (PASS) values for 4 generic outcomes in 5 rheumatic diseases and 7 countries. METHODS: We conducted a multinational (Australia, France, Italy, Lebanon, Morocco, Spain, The Netherlands), 4-week cohort study involving 1,532 patients which were prescribed NSAISDs for ankylosing spondylitis, chronic back pain, hand osteoarthritis, hip and/or knee osteoarthritis or rheumatoid arthritis. The MCII and PASS values were estimated with the 75(th) percentile approach for 4 generic outcomes: pain, patient global assessment, functional disability and physician global assessment, all normalized to a 0-100 score. RESULTSA: For the whole sample, the estimated MCII values for absolute change at 4 weeks (95% confidence interval [95% CI]) were -17 (-18, -15) for pain; -15 (-16, -14) for patient global assessment; -12 (-13, -11) for functional disability assessment; and -14 (-15, -14) for physician global assessment. For the whole sample, the estimated PASS values were 42 (40, 44) for pain; 43 (41, 45) for patient global assessment; 43 (41, 44) for functional disability assessment; and 39 (37, 40) for physician global assessment. Estimates were consistent across diseases and countries (for subgroups ≥20 patients). CONCLUSION: This work allows for promoting the use of values of MCII (15/100 for absolute improvement, 20% for relative improvement) and PASS (40/100) in reporting the results of trials of any of the 5 involved rheumatic diseases with pain, patient global assessment, physical function or physician global assessment used as outcome criteria. © 2012 by the American College of Rheumatology.
    Arthritis care & research. 06/2012;
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    ABSTRACT: BACKGROUND: Infliximab (IFX) is a monoclonal antibody against tumour necrosis factor α that is effective for treating spondyloarthritis (SpA). However, after initial success of the drug some patients lose responsiveness or develop infusion reactions, which may be related to the development of antibodies against the drug.OBJECTIVE: To investigate the clinical relevance of antibodies to infliximab (ATI) formation in patients with SpA undergoing IFX treatment over a prolonged period.METHODS: 94 patients with SpA treated with IFX from 1999 to 2010 were studied. Their clinical characteristics, serum trough IFX levels and ATI status were evaluated for a mean of 6.99 (95% CI:6.28 to 7.7) years. Clinical activity and improvement were measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS): inactive <1.3, moderate ≥1.3 and <2.1, high ≥2.1-≤3.5, and very high >3.5 at three time points (6 months, 12 months and >4 years).RESULTS: ATI were detected in 24 (25.5%) patients. The patients with ATI had higher ASDAS scores than those without ATI (2.55±0.89 vs 1.79±1.04, p=0.038 at 6 months; 1.95±0.67 vs 1.67±0.71, p=0.042 at 1 year; 2.52±0.99 vs 1.53±0.81, p=0.024 at >4 years). Eleven patients (12%) developed infusion-related reactions, and of these, ATI were present in eight patients (73%). The patients with infusion-related reactions had higher ATI titres (median 12 931 AU/ml, IQR 853-82 437) vs median 2454 AU/ml, IQR 449-7718, p=0.028) and shorter survival (4.25 years vs 8.19 years, p<0.001). ATI development occurred more frequently in the patients not receiving methotrexate (20/58 (34.5%) vs 4/36 (11.1%), p=0.011).CONCLUSION: In patients with SpA treated with IFX, ATI formation is associated with a poor clinical response, the appearance of infusion reactions and the discontinuation of treatment.
    Annals of the rheumatic diseases 05/2012; · 8.11 Impact Factor
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    ABSTRACT: To explore the sensitivity to change of colour Doppler ultrasound (CDUS) in giant cell arteritis (GCA). This was a blind, prospective study composed of 30 consecutive patients diagnosed with GCA. In 25 of the cases this was their first episode of GCA, and 13 of the cases were relapses. All participants had presented with at least 1 branch involvement in the basal sonography, and steroid treatment had been initiated. A CDUS was performed every 2 weeks during the first month, and every 4 weeks thereafter, until halo disappearance was observed in the bilateral parietal and frontal branches of the temporal superficial artery. Thirty-eight episodes of GCA in 30 different patients (19 women and 11 men; mean age, 79.24±4.76 years; range 70-88) were followed. Dark halo disappearance occurred in 95% of cases. The mean time until halo disappearance was observed was around 11 weeks, with 50% of cases showing halo disappearance within the first 8 weeks. The relapse cases appeared to have less arterial wall affectation than the primary GCA cases, reduced erythrocyte sedimentation rate ESR and an earlier loss of the halo sign. Patients with a smaller number of affected branches required less time for halo disappearance. CDUS shows a sensitività to change in GCA. Halo disappearance is rare before two weeks, and it frequently persists during the first two months after initiating steroid therapy. Our data emphasise the advantages of using CDUS to monitor GCA activity.
    Clinical and experimental rheumatology 03/2012; 30(1 Suppl 70):S34-8. · 2.66 Impact Factor
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    ABSTRACT: BACKGROUND: Infliximab (IFX) is a monoclonal antibody against tumour necrosis factor alpha that is effective for treating spondyloarthritis (SpA). However, after initial success of the drug some patients lose responsiveness or develop infusion reactions, which may be related to the development of antibodies against the drug. OBJECTIVE: To investigate the clinical relevance of antibodies to infliximab (ATI) formation in patients with SpA undergoing IFX treatment over a prolonged period. METHODS: 94 patients with SpA treated with IFX from 1999 to 2010 were studied. Their clinical characteristics, serum trough IFX levels and ATI status were evaluated for a mean of 6.99 (95% CI:6.28 to 7.7) years. Clinical activity and improvement were measured using the Ankylosing Spondylitis Disease Activity Score (ASDAS): inactive <1.3, moderate >/=1.3 and <2.1, high >/=2.1-</=3.5, and very high >3.5 at three time points (6 months, 12 months and >4 years). RESULTS: ATI were detected in 24 (25.5%) patients. The patients with ATI had higher ASDAS scores than those without ATI (2.55+/-0.89 vs 1.79+/-1.04, p=0.038 at 6 months; 1.95+/-0.67 vs 1.67+/-0.71, p=0.042 at 1 year; 2.52+/-0.99 vs 1.53+/-0.81, p=0.024 at >4 years). Eleven patients (12%) developed infusion-related reactions, and of these, ATI were present in eight patients (73%). The patients with infusion-related reactions had higher ATI titres (median 12 931 AU/ml, IQR 853-82 437) vs median 2454 AU/ml, IQR 449-7718, p=0.028) and shorter survival (4.25 years vs 8.19 years, p<0.001). ATI development occurred more frequently in the patients not receiving methotrexate (20/58 (34.5%) vs 4/36 (11.1%), p=0.011). CONCLUSION: In patients with SpA treated with IFX, ATI formation is associated with a poor clinical response, the appearance of infusion reactions and the discontinuation of treatment.
    01/2012: pages 1955-60;
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    ABSTRACT: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib) IL-15 expression on B cell survival. Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001). IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05). Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.
    PLoS ONE 01/2012; 7(7):e40620. · 3.73 Impact Factor
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    ABSTRACT: To examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients. CD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-γ, TNF-α and IL-10 were measured by ELISA in cell-free supernatants. When all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-γ, TNF-α and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC. Decreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate.
    PLoS ONE 01/2012; 7(8):e42189. · 3.73 Impact Factor
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    Annals of the rheumatic diseases 09/2011; 71(1):157-8. · 8.11 Impact Factor
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    ABSTRACT: To evaluate the ability of ultrasound (US) to detect the presence and change of Achilles erosions in spondyloarthritis (SpA). A blind prospective two-dimensional (2D) and three-dimensional (3D) US study of Achilles enthesis erosions in early SpA was undertaken. US examinations were performed at baseline and at 6 and 12 months of follow-up. Clinical outcomes measures were collected. Bilateral Achilles entheses of 68 patients (35 women) were investigated. The mean Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (CRP) levels were 4.58 ± 2.05 and 5.97 ± 9.91 mg/l, respectively. The κ values for intrareader agreement for 2D and 3D images were 0.84 and 0.85 for two readers. 2D US visualised 10 erosions (7.4%) and 3D US visualised 13 erosions (9.6%) in 10 patients (14.7%). At 6 and 12 months of follow-up, 25% and 50% of basal erosions had disappeared, respectively and, of the new erosions that appeared at 6 months, 40% had disappeared 6 months later. A statistically significant association between erosion and CRP levels, entheseal Doppler signals and the number of tender and swollen joints was found. US examination of Achilles erosions is reliable and sensitive to change. An association was found between Achilles erosions and objective activity-based measurements of SpA outcomes.
    Annals of the rheumatic diseases 08/2011; 70(11):2008-10. · 8.11 Impact Factor
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    ABSTRACT: To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity. A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10 recommendations. A 4-point Likert scale (never, not very often, very often, always) assessed the degree to which each recommendation was being applied in current daily practice. If respondents answered 'never' or 'not very often', they were asked whether they would change their practice according to the particular recommendation. A total of 1901 physicians representing 34 countries participated. Both agreement with and application of recommendations was high. With regard to application of recommendations in daily practice, the majority of responses were 'always' and 'very often'. A significant percentage of participants who were currently not applying these recommendations in clinical practice were willing to change their practice according to the recommendations. The results of this survey demonstrated great support of 'Treating RA to Target' recommendations among the international rheumatology community. Additional efforts may be needed to encourage application of the recommendations among certain clinicians who are resistant to changing their practice.
    Annals of the rheumatic diseases 07/2011; 70(11):1999-2002. · 8.11 Impact Factor

Publication Stats

4k Citations
547.19 Total Impact Points

Institutions

  • 1990–2013
    • Hospital Universitario La Paz
      • Servicio de Reumatología
      Madrid, Madrid, Spain
  • 2012
    • Paris Diderot University
      Lutetia Parisorum, Île-de-France, France
    • New University of Lisbon
      • Faculty of Medical Sciences
      Lisbon, Lisbon, Portugal
    • Hospital General Universitario Gregorio Marañón
      Madrid, Madrid, Spain
    • Medical University of Vienna
      Wien, Vienna, Austria
  • 2011
    • Government of Quebec
      Québec, Quebec, Canada
  • 2008–2010
    • Hospital Universitario Infanta Sofía
      Madrid, Madrid, Spain
  • 2009
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
  • 1999–2008
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain
  • 2005
    • University of Nottingham
      • Division of Academic Rheumatology
      Nottingham, ENG, United Kingdom
  • 2004
    • Royal Cornwall Hospitals NHS Trust
      Truro, England, United Kingdom