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Dive into the research topics where Rosa Merino is active.

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Featured researches published by Rosa Merino.


The New England Journal of Medicine | 2012

Randomized Trial of Tocilizumab in Systemic Juvenile Idiopathic Arthritis

Fabrizio De Benedetti; Hermine I. Brunner; Nicolino Ruperto; Andrew Kenwright; Stephen Wright; Inmaculada Calvo; Ruben Cuttica; Angelo Ravelli; Rayfel Schneider; Patricia Woo; Carine Wouters; Ricardo Machado Xavier; Lawrence S. Zemel; E. Baildam; Ruben Burgos-Vargas; Pavla Dolezalova; Stella Garay; Rosa Merino; R. Joos; Alexei A. Grom; Nico Wulffraat; Zbigniew Zuber; Daniel J. Lovell; Alberto Martini

BACKGROUND Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. METHODS We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension. RESULTS At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range. CONCLUSIONS Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00642460.).


Arthritis & Rheumatism | 2011

High Incidence of NLRP3 Somatic Mosaicism in Patients With Chronic Infantile Neurologic, Cutaneous, Articular Syndrome: Results of an International Multicenter Collaborative Study

Naoko Tanaka; Kazushi Izawa; Megumu Saito; Mio Sakuma; Koichi Oshima; Osamu Ohara; Ryuta Nishikomori; Takeshi Morimoto; Naotomo Kambe; Raphaela Goldbach-Mansky; Ivona Aksentijevich; Geneviève de Saint Basile; Bénédicte Neven; Marielle van Gijn; Joost Frenkel; Juan I. Aróstegui; Jordi Yagüe; Rosa Merino; Mercedes Ibañez; Alessandra Pontillo; Hidetoshi Takada; Tomoyuki Imagawa; Tomoki Kawai; Takahiro Yasumi; Tatsutoshi Nakahata; Toshio Heike

OBJECTIVE Chronic infantile neurologic, cutaneous, articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID), is a dominantly inherited systemic autoinflammatory disease. Although heterozygous germline gain-of-function NLRP3 mutations are a known cause of this disease, conventional genetic analyses fail to detect disease-causing mutations in ∼40% of patients. Since somatic NLRP3 mosaicism has been detected in several mutation-negative NOMID/CINCA syndrome patients, we undertook this study to determine the precise contribution of somatic NLRP3 mosaicism to the etiology of NOMID/CINCA syndrome. METHODS An international case-control study was performed to detect somatic NLRP3 mosaicism in NOMID/CINCA syndrome patients who had shown no mutation during conventional sequencing. Subcloning and sequencing of NLRP3 was performed in these mutation-negative NOMID/CINCA syndrome patients and their healthy relatives. Clinical features were analyzed to identify potential genotype-phenotype associations. RESULTS Somatic NLRP3 mosaicism was identified in 18 of the 26 patients (69.2%). Estimates of the level of mosaicism ranged from 4.2% to 35.8% (mean ± SD 12.1 ± 7.9%). Mosaicism was not detected in any of the 19 healthy relatives (18 of 26 patients versus 0 of 19 relatives; P < 0.0001). In vitro functional assays indicated that the detected somatic NLRP3 mutations had disease-causing functional effects. No differences in NLRP3 mosaicism were detected between different cell lineages. Among nondescript clinical features, a lower incidence of mental retardation was noted in patients with somatic mosaicism. Genotype-matched comparison confirmed that patients with somatic NLRP3 mosaicism presented with milder neurologic symptoms. CONCLUSION Somatic NLRP3 mutations were identified in 69.2% of patients with mutation-negative NOMID/CINCA syndrome. This indicates that somatic NLRP3 mosaicism is a major cause of NOMID/CINCA syndrome.


Arthritis & Rheumatism | 2014

Clinical Features, Treatment, and Outcome of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis: A Multinational, Multicenter Study of 362 Patients

Francesca Minoia; Sergio Davì; AnnaCarin Horne; Erkan Demirkaya; Francesca Bovis; Caifeng Li; Kai Lehmberg; Sheila Weitzman; Antonella Insalaco; Carine Wouters; Susan Shenoi; Graciela Espada; Seza Ozen; Jordi Anton; Raju Khubchandani; Ricardo Russo; Priyankar Pal; Ozgur Kasapcopur; Paivi Miettunen; Despoina Maritsi; Rosa Merino; Bita Shakoory; Maria Alessio; Vyacheslav Chasnyk; Helga Sanner; Yi Jin Gao; Zeng Hua-song; Toshiyuki Kitoh; Tadej Avcin; Michel Fischbach

To describe the clinical, laboratory, and histopathologic features, current treatment, and outcome of patients with macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (JIA).


Annals of the Rheumatic Diseases | 2014

The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry

Helen J. Lachmann; Riccardo Papa; K. Gerhold; Laura Obici; Isabelle Touitou; Luca Cantarini; Joost Frenkel; Jordi Anton; Isabelle Koné-Paut; Marco Cattalini; Brigitte Bader-Meunier; Antonella Insalaco; Véronique Hentgen; Rosa Merino; Consuelo Modesto; N Toplak; Rainer Berendes; Seza Ozen; Rolando Cimaz; Annette Jansson; Paul A. Brogan; Philip N. Hawkins; N Ruperto; Alberto Martini; P Woo; Marco Gattorno

Objective To evaluate the genetic findings, demographic features and clinical presentation of tumour necrosis factor receptor-associated autoinflammatory syndrome (TRAPS) in patients from the Eurofever/EUROTRAPS international registry. Methods A web-based registry collected retrospective data on patients with TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals included paediatric rheumatology centres and adult centres with a specific interest in autoinflammatory diseases. Cases were independently validated by experts in the disease. Results Complete information on 158 validated patients was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for 39% of sequence variants. A family history was present in 19% of patients with R92Q and 64% of those with other variants. The median age at which symptoms began was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were recurrent in 88% and the commonest features associated with the pathogenic variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and eye manifestations (45%). Disease associated with R92Q presented slightly later at a median of 5.7 years with significantly less rash or eye signs and more headaches. Children were more likely than adults to present with lymphadenopathy, periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%) patients at a median age of 43 years. Conclusions In this, the largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation. Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation.


Rheumatology | 2015

Blau syndrome: cross-sectional data from a multicentre study of clinical, radiological and functional outcomes

Carlos D. Rose; Steven Pans; Ingele Casteels; Jordi Anton; Brigitte Bader-Meunier; Philippe Brissaud; Roland Cimaz; G Espada; Jorge Fernandez-Martin; E. Hachulla; Miroslav Harjacek; Raju Khubchandani; Friederike Mackensen; Rosa Merino; Antonio Naranjo; Sheila Oliveira-Knupp; Christine Pajot; Ricardo Russo; Christine Thomee; Sebastiaan J. Vastert; Nico Wulffraat; Juan I. Aróstegui; Kevin Foley; John Bertin; Carine Wouters

OBJECTIVE To report baseline articular, functional and ocular findings of the first international prospective cohort study of Blau syndrome (BS). METHODS Three-year, multicentre, observational study on articular, functional (HAQ, Childhood HAQ and VAS global and pain), ophthalmological, therapeutic and radiological data in BS patients. RESULTS Baseline data on the first 31 recruited patients (12 females and 19 males) from 18 centres in 11 countries are presented. Of the 31 patients, 11 carried the p.R334W NOD2 mutation, 9 the p.R334Q and 11 various other NOD2 missense mutations; 20 patients were sporadic and 11 from five BS pedigrees. Median disease duration was 12.8 years (1.1-57). Arthritis, documented in all but one patient, was oligoarticular in 7, polyarticular in 23. The median active joint count was 21. Functional capacity was normal in 41%, mildly impaired in 31% and moderate-severe in 28% of patients. The most frequently involved joints at presentation were wrists, ankles, knees and PIPs. On radiographs, a symmetrical non-erosive arthropathy was shown. Previously unknown dysplastic bony changes were found in two-thirds of patients. Ocular disease was documented in 25 of 31 patients, with vitreous inflammation in 64% and moderate-severe visual loss in 33%. Expanded manifestations (visceral, vascular) beyond the classic clinical triad were seen in 52%. CONCLUSION BS is associated with severe ocular and articular morbidity. Visceral involvement is common and may be life-threatening. Bone dysplastic changes may show diagnostic value and suggest a previously unknown role of NOD2 in bone morphogenesis. BS is resistant to current drugs, suggesting the need for novel targeted therapies.


Rheumatology International | 2015

Clinical management algorithm of uveitis associated with juvenile idiopathic arthritis: interdisciplinary panel consensus

Rosa Bou; Alfredo Adán; Fátima Borrás; Beatriz Bravo; Inmaculada Calvo; Jaime de Inocencio; Jesús Díaz; Julia Escudero; Alex Fonollosa; Carmen García de Vicuña; Victoria Hernández; Rosa Merino; Jesús Peralta; María-Jesús Rúa; Pilar Tejada; Jordi Anton

Uveitis associated with juvenile idiopathic arthritis (JIA) typically involves the anterior chamber segment, follows an indolent chronic course, and presents a high rate of uveitic complications and a worse outcome as compared to other aetiologies of uveitis. Disease assessment, treatment, and outcome measures have not been standardized. Collaboration between pediatric rheumatologists and ophthalmologists is critical for effective management and prevention of morbidity, impaired vision, and irreparable visual loss. Although the Standardization of Uveitis Nomenclature Working Group recommendations have been a great advance to help clinicians to improve consistency in grading and reporting data, difficulties arise at the time of deciding the best treatment approach in the individual patient in routine daily practice. For this reason, recommendations for a systematized control and treatment strategies according to clinical characteristics and disease severity in children with JIA-related uveitis were developed by a panel of experts with special interest in uveitis associated with JIA. A clinical management algorithm organized in a stepwise regimen is here presented.


Journal of Aapos | 2013

Adalimumab therapy for refractory childhood uveitis.

Luciano Bravo-Ljubetic; Jesús Peralta-Calvo; Susana Noval; Natalia Pastora-Salvador; José Abelairas-Gómez; Rosa Merino

PURPOSE To report the results of adalimumab therapy in a cohort of children with refractory noninfectious uveitis. METHODS The medical records of patients diagnosed with uveitis and treated with biweekly adalimumab injections for a period of at least 3 months at the University Hospital of La Paz from 2007-2012 were retrospectively reviewed. Improvement in inflammatory activity was graded according to grading schema of the Standardization of Uveitis Nomenclature Working Group. RESULTS A total of 15 patients participated in the study (12 girls; mean patient age, 12 years). Diagnoses included juvenile idiopathic arthritis in 10 patients, idiopathic uveitis in 4, and familial juvenile systemic granulomatosis or Blau syndrome in 1. Mean follow-up was 32 months (median, 36; range, 15-58 months). Improvement in inflammatory activity was initially observed in 12 (86%) of 14 children, with a mean time to achieve response of 6 weeks (median, 4; range, 1-18). Treatment was effective in 9 patients (60%), mildly effective in 2 (13%), ineffective in 2 (13%), and resulted in worsening in 2 (13%). In the juvenile idiopathic arthritis patients, response was effective in 6 cases (60%), mildly effective in 2 (20%), and ineffective in 2 (20%). Adalimumab therapy was discontinued in 4 patients. CONCLUSIONS Adalimumab was effective in most patients in the initial control of acute inflammatory activity in children with refractory uveitis, although therapy appears to become less effective in the long term.


Rheumatology | 2013

Reduced joint assessment vs comprehensive assessment for ultrasound detection of synovitis in juvenile idiopathic arthritis

Paz Collado; Esperanza Naredo; Cristina Calvo; Mari Luz Gamir; Inmaculada Calvo; Maria Luz García; Rosa Merino; Jenaro Graña; Sagrario Bustabab; Jesús Garrido

OBJECTIVE To propose a reduced joint power Doppler US (PDUS) assessment and provide preliminary evidence of its validity, feasibility, reliability and sensitivity to change compared with a comprehensive (i.e. 44 joints) PDUS assessment in evaluating synovitis in JIA. METHODS This multicentre study included 42 children with active JIA with ≥4 clinically involved joints requiring modified therapy. At each visit, clinical and PDUS assessments were performed blinded. Each joint was scored for greyscale (GS) synovitis and power Doppler signal according to a 4-point semiquantitative scale with calculation of US composite indices and US composite joint counts. A process of data reduction based on the frequency of US joint involvement was performed to obtain a reduced PDUS assessment. The relationship between the comprehensive and the reduced PDUS assessments was investigated by Spearmans coefficient at all visits, as well as the relationship between changes in the two PDUS assessments during follow-up. In addition, the metric properties of the comprehensive and the reduced PDUS assessments were tested. RESULTS The 10-joint PDUS assessment, including bilateral knee, ankle, wrist, elbow and the second MCP joints, detected 100% of children with GS synovitis and power Doppler signal. The two PDUS assessments were highly correlated at all visits. The reduced model had a higher responsiveness than the comprehensive model. Intraobserver and interobserver agreement was good for both US findings. CONCLUSION The 10-joint PDUS assessment is valid and feasible for assessment of synovitis in JIA in clinical practice.


The Journal of Rheumatology | 2010

Discontinuation of Etanercept After Successful Treatment in Patients with Juvenile Idiopathic Arthritis

Agustín Remesal; Jaime de Inocencio; Rosa Merino; Julia García-Consuegra

To the Editor: Etanercept (ETN) has been used to treat patients with juvenile idiopathic arthritis (JIA) with demonstrated efficacy and safety1,2. However, few studies have addressed the appropriate time and the way to discontinue the drug once the disease is inactive. We analyzed the progress of patients with JIA after discontinuation of ETN and the clinical response to reintroduction of the drug in those who relapsed. A retrospective chart review 2004 to 2009 revealed that therapy with ETN had been discontinued in 26 patients with JIA due to inactive disease (16 female, 10 male). The mean age at discontinuation of drug was 11 ± 2 (range 2.6–18.8) years. The clinical subtypes of JIA were 11 cases of enthesitis-related arthritis, 7 rheumatoid factor-negative polyarthritis, 2 systemic JIA with polyarticular involvement, 1 psoriatic arthritis, and 1 persistent oligoarticular arthritis. Inactive disease was defined according to the criteria of Wallace, et al 3, which required no joints with active arthritis, no … Address correspondence to Dr. Remesal; E-mail: agusremesal{at}hotmail.com


Anales De Pediatria | 2015

Documento de consenso SEIP-SERPE-SEOP sobre el tratamiento de la osteomielitis aguda y artritis séptica no complicadas

J. Saavedra-Lozano; Cristina Calvo; R. Huguet Carol; Carlos Rodrigo; E. Núñez; I. Obando; P. Rojo; Rosa Merino; C. Pérez; F.J. Downey; E. Colino; J.J. García; María José Cilleruelo; F. Torner; L. García

This is a Consensus Document of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediatrica), Spanish Society of Paediatric Rheumatology (Sociedad Española de Reumatología Pediátrica) and the Spanish Society of Paediatric Orthopaedics (Sociedad Española de Ortopedia Pediátrica), on the treatment of uncomplicated acute osteomyelitis and septic arthritis. A review is presented on the medical and surgical treatment of acute osteoarticular infection, defined as a process with less than 14 days of symptomatology, uncomplicated and community-acquired. The different possible options are evaluated based on the best available scientific knowledge, and a number of evidence-based recommendations for clinical practice are provided.

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Jordi Anton

University of Barcelona

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Consuelo Modesto

Autonomous University of Barcelona

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Carine Wouters

Katholieke Universiteit Leuven

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Inmaculada Calvo

Instituto Politécnico Nacional

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Ricardo Russo

University of Buenos Aires

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Alberto Martini

Istituto Giannina Gaslini

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