42 research outputs found
The Castilian Spanish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)
No full textThe Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Castilian Spanish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability and construct validity (convergent and discriminant validity). A total of 526 JIA patients (8.6% systemic, 49.4% oligoarticular, 18.2% RF negative polyarthritis, 23.8% other categories) and 78 healthy children, were enrolled in six centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Castilian Spanish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practise and clinical research
Validity and Reliability of Four Parent/Patient–Reported Outcome Measures for Juvenile Idiopathic Arthritis Remote Monitoring
Get PDFObjective: The aim of this work was to provide evidence of validity and reliability for 4 parent/child-reported outcome measures included in the Outcome Measures in Rheumatology juvenile idiopathic arthritis core domain set: the evaluation of the child's pain and level of disease activity, the assessment of morning stiffness duration, and an active joint count for proxy/self-assessment. Methods: Patients were included in the multinational study Epidemiology Treatment and Outcome of Childhood Arthritis. Criterion validity was assessed by examining the correlation of the 4 tested measures with physician measures and the clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10) in the whole sample and after grouping patients by International League of Associations for Rheumatology (ILAR) category, geographic area, and education level. Reliability was assessed comparing 2 visits 7-14 days apart with intraclass correlation coefficients (ICCs). Results: A total of 8,643 parents and 6,060 patients had all the evaluations available. Correlations of tested measures were moderate (0.4-0.7) with physician-reported measures. The level of correlation with the cJADAS10 remained stable after grouping patients by ILAR category, geographic areas, and level of education of the parent filling the questionnaire. In 442 parents and 344 children, ICCs ranged between 0.79 and 0.87 for parents and 0.81 and 0.88 for children. Conclusion: The 4 tested parent/child-reported outcomes showed good criterion validity and excellent reliability. These tools can be considered for remote patient assessment, when in-person evaluation might not be possible
Una adolescencia americana. Las ciudades del Nuevo Mundo hispánico hasta 1600. Historias. Revista de la Dirección de Estudios Históricos Num. 71 (2008) septiembre-diciembre
No full textFray Antonio de Remesal, Historia general de las Indias occidentales y particular de la gobernación de Chiapas y Guatemala, México, Porrúa, 1988 [1615], t. II, pp. 17-18.Francisco Cervantes de Salazar, Túmulo imperial de la gran ciudad de México, México, Antonio de Espinosa, 1560.Thomas Calvo, L’Amérique Ibérique de 1570 à 1910, París, Nathan, 1994, pp. 128-153Luis Weckman, La herencia medieval de México, México, FCE, 1994, pp. 427-428Anne Colin Delavaud, “L’héritage colonial et les problemes d’aménagement des centre-villes”, en Cahiers des Amèriques Latines, núm. 18, 1994, pp. 65-79.José Luis Romero, Latinoamérica: las ciudades y las ideas, México, Siglo XXI, 1984, p. 48.Fray Bartolomé de las Casas, Historia de las Indias, Saragosse, 1552, fol. 23v.Francisco de Solano, Normas y leyes de la ciudad hispanoamericana. 1492-1600, Madrid, CSIC, pp. 31-39.Ernesto Lemoine, Valladolid-Morelia, 450 años. Documentos para su historia (1537-1828), Morelia, Morevallado, 1993, pp. 54-55.Fray Toribio de Benavente (Motolinía), Historia de los indios de la Nueva España, Madrid, Alianza, 1988 [1585], p. 59.Francisco de la Maza, San Miguel de Allende, México, Frente de Afirmación Hispanista, 1972, pp. 15-17.Eloy Méndez Sáinz, Urbanismo y morfología de las ciudades novohispanas. El diseño de Puebla, México, 1988, pp. 189-198P. Sánchez Ochoa, Los hidalgos de Guatemala: realidad y apariencia en un sistema de valores, Sevilla, Universidad de Sevilla, 1976, p. 25.Francisco de Toledo, Disposiciones gubernativas para el Virreinato del Perú, 1569-1580, Sevilla, CSIC, 1986, t. II, p. 167.Jorge González Ángulo, “El criollismo y los símbolos urbanos”, en Historias, núm. 26, abril-septiembre de 1991, p. 73.Francisco de Burgoa, Palestra historial, México, Porrúa, 1989 [1670], pp. 193-195.Jorge Enrique Hardoy y Carmen Aranovich, “Urbanización en América hispánica entre 1580 y 1630”, en Boletín del Centro de Investigaciones Históricas y Estéticas, núm. 11, mayo 1969, p. 76.Bernardo Balbuena, Grandeza mexicana y fundamentos del Siglo de Oro y El Bernardo, prólogo de Francisco Monterde, México, UNAM, 1992 [1604], p. 15.V. Fraser, The Architecture of Conquest. Building in the Viceroyalty of Peru, 1535-1635, Cambridge, Cambridge University Press, 1990, p. 4.Jorge González Ángulo, “El criollismo y los símbolos urbanos”, en Historias, núm. 26, abril-septiembre de 1991, p. 73.Juan López de Velasco, Geografía y descripción universal de las Indias, Madrid, Biblioteca de Autores Españoles, 1971, p. 2.J. E. Hardoy, “Sistemas sociopolíticos y urbanización. Una selección de ejemplos históricos y contemporáneos”, en J. E. Hardoy y R.P. Schaedel, Las ciudades de América Latina y sus áreas de influencia a través de la historia, Buenos Aires, SIAP, 1978, pp. 85-91.Pedro López de Villaseñor, Cartilla vieja de la nobilísima ciudad de Puebla (1781), México, UNAM, 1961, p. 75.Claude Perrault y Galiani (eds.), Les diz livres d’architecture de Vitruve corrigez et traduits nouvellement en François, París, 1673, p. 18.Chantal Cramaussel, Poblar la frontera. La provincia de Santa Bárbara en Nueva Vizcaya durante los siglos xvi y XVII, Zamora, El Colegio de Michoacán, 2006, pp. 85-134.Manuel Toussaint, Federico Gómez de Orozco y Justino Fernández, Planos de la ciudad de México, México, DDF, 1990 [1938], pp. 120-146.Planos de ciudades iberoamericanas y filipinas existentes en el archivo de Indias, Madrid, Instituto de Estudios de Administración Local, planos número 17-19, pp. 374-379.Fundación de la ciudad de Buenos Aires, por D. Juan de Garay, con otros documentos de aquella época, Buenos Aires, Imprenta del Estado, 1836.Alain Musset, De l’eau vive a l’eau morte. Enjeux techniques et culturels dans la vallée de Mexico (xvie- s.), París, ERC, 1991.Inmaculada Alva Rodríguez, Vida municipal en Manila, siglos XVI-XVII, Córdoba, Universidad de Córdoba, 1997, pp. 129-133.Luis Chávez Orozco, Defensa de don Núñez de Villavicencio y efemérides de la alhóndiga y pósito de la ciudad de México (1578-1599), México, Almacenes Nacionales de Depósito, 1966, p. 102.G. Foster, Cultura y conquista. La herencia española de América, Xalapa, Universidad Veracruzana, 1962.“Carta al príncipe Felipe”, en Mariano Cuevas, S. J., Documentos inéditos del siglo xvi para la historia de México, 2a. ed. facs., México, Porrúa, 1975 [1914], pp. 184-186.P. Sanz Camañes, Las ciudades en la América hispana. Siglos XVI al XVIII, Madrid, Silex, 2004, p. 352.A. Yáñez Salazar, “El edificio de cabildo de la ciudad de México”, en R. Gutiérrez et al., Cabildos y ayuntamientos en América, México, UAM/Tilde, 1990, p. 96.Amédée Frezier, Voyage de a mer du Sud. Aux côtes du Chili et du Pérou, París, Utz, 1995, p. 216.Domingo Amunategui Solar, El cabildo de La Serena (1678-1890), Santiago de Chile, 1928, p. 9.Javier Ortiz de la Tabla Ducasse, Los encomenderos de Quito, 1534-1660, Sevilla, 1993, p. 16.E. E. Calnek, “Conjunto urbano y modelo residencial en Tenochtitlan”, en E. E. Calnek, W. Borah, A. Moreno Toscano, K. A. Davies y L. Unikel (eds.), Ensayos sobre el desarrollo urbano de México, México, Sepsetentas, 1974, pp. 11-59.James Lockhart, Los nahuas después de la Conquista. Historia social y cultural de los indios del México central del siglo xvi al xviii, México, FCE, 1999, pp. 43-44Esperanza Ramírez Romero, Catálogo de monumentos y sitios de la región lacustre, t. I, Pátzcuaro, Morelia, Gobierno del Estado de Michoacán, 1986, pp. 57-58 y 61-65.J.E. Casariego, El municipio y las cortes en el imperio español de Indias, Madrid, Biblioteca Moderna de Ciencias Históricas, 1946.Mario Góngora, El estado de derecho indiano. Época de fundación 1492-1570, Santiago de Chile, Instituto de Investigaciones Histórico-Culturales- Universidad de Chile, 1951, pp. 79-82.Francisco Xavier Tapia, Cabildo abierto colonial, Madrid, Cultura Hispánica, 1966.Pedro A. Porras Arboledas, “Las ordenanzas municipales. Algunas propuestas para su estudio y un ejemplo”, en Espacio, tiempo y forma, Madrid, UNED-serie III/7, 1994, pp. 49-64. Para el mundo americano, Francisco Domínguez Compañy, “Ordenanzas municipales hispanoamericanas”, en Revista de Historia de América, núm. 86, julio-diciembre 1978, pp. 9-60.P. Sánchez Ochoa, Los hidalgos de Guatemala: realidad y apariencia en un sistema de valores, Sevilla, Universidad de Sevilla, 1976, pp. 58-59; Tamar Herzog, Defining Nations. Inmigrants and Citizens in Early Modern Spain and Spanish America, New Haven, Yale University Press, 2003.José Enciso Contreras, Epistolario de Zacatecas, 1549-1599, Zacatecas, H. Ayuntamiento de Zacatecas, 1996, p. 47.Margarita Menegus, “El gobierno de los indios. Señores o cabildo”, en Enrique Florescano y Virginia García Acosta, Mestizajes tecnológicos y culturales en México, México, CIESAS, 2004, p. 327.Javier Ortiz de la Tabla Ducasse, Los encomenderos de Quito 1534-1560: origen y evolución de una elite colonial, Sevilla, Escuela de Estudios Hispano-Americanos, 1993, pp. 98-99.Gregorio Salinero, Une ville entre deux mondes. Trujillo d’Espagne et les Indes au xvie siècle, Madrid, Casa de Velázquez, 2006, p. 229.Para 1600 las ciudades americanas combinan tradición y modernidad; pero quedarse en ello sería poco original. La idea de una síntesis alcanzada nos retendría más si no fuera una idea peligrosa, porque desliza la impresión de una facilidad casi natural que está lejos de coincidir con los hechos; como veremos, mil veces ha sido preciso que la obra volviera al bastidor, a punta de fracasos y tanteos. Pero es una síntesis a pesar de todo, posible quizá porque ha sabido relegar las nociones (y la cronología) de antiguo y de moderno: que intenta revivir ciertas tradiciones, de sobrepasar ciertas modernidades.To consider urban landscapes from an American perspective is only possible until 1600, after a century of conquest and colonization, after hundreds of attempts, many of them unsuccessful, to found cities. At this point, around 250 cities were definitely established and thousands of native centers had been transformed, destroyed, renewed or moved.</p
Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes.
Get PDFBACKGROUND: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares. METHODS: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. The primary outcome was complete response (resolution of flare and no flare until week 16). In the subsequent phase up to week 40, patients who had a complete response underwent a second randomization to receive canakinumab or placebo every 8 weeks. Patients who underwent a second randomization and had a subsequent flare and all other patients received open-label canakinumab. RESULTS: At week 16, significantly more patients receiving canakinumab had a complete response than those receiving placebo: 61% vs. 6% of patients with colchicine-resistant familial Mediterranean fever (P<0.001), 35% versus 6% of those with mevalonate kinase deficiency (P=0.003), and 45% versus 8% of those with TRAPS (P=0.006). The inclusion of patients whose dose was increased to 300 mg every 4 weeks yielded a complete response in 71% of those with colchicine-resistant familial Mediterranean fever, 57% of those with mevalonate kinase deficiency, and 73% of those with TRAPS. After week 16, an extended dosing regimen (every 8 weeks) maintained disease control in 46% of patients with colchicine-resistant familial Mediterranean fever, 23% of those with mevalonate kinase deficiency, and 53% of those with TRAPS. Among patients who received canakinumab, the most frequently reported adverse events were infections (173.3, 313.5, and 148.0 per 100 patient-years among patients with colchicine-resistant familial Mediterranean fever, those with mevalonate kinase deficiency, and those with TRAPS, respectively), with a few being serious infections (6.6, 13.7, and 0.0 per 100 patient-years). CONCLUSIONS: In this trial, canakinumab was effective in controlling and preventing flares in patients with colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, and TRAPS. (Funded by Novartis; CLUSTER ClinicalTrials.gov number, NCT02059291 .)
The phenotype and genotype of mevalonate kinase deficiency: A series of 114 cases from the Eurofever Registry
Get PDFOBJECTIVES:
Mevalonate kinase deficiency (MKD) is a rare metabolic disease characterized by recurrent inflammatory episodes. This study aimed to describe the genotype, phenotype and the response to treatment in an international cohort of MKD patients.
METHODS:
All MKD cases were extracted from the Eurofever registry (EAHC Project No. 2007332), an international, multicenter registry that retrospectively collects data on children and adults suffering from autoinflammatory diseases.
RESULTS:
One hundred and fourteen MKD patients were included in this study. The median age of onset was 0.5 years. Patients had on average 12 episodes per year. Most patients had gastrointestinal symptoms (n=112), mucocutaneous involvement (n=99), lymphadenopathy (n=102) or musculoskeletal symptoms (n=89). Neurological complaints included headache (n=43), but also cerebellar syndrome (n=2) and mental retardation (n=4). AA-amyloidosis was noted in five patients, almost twice as many as expected from previous cohorts. Macrophage activation syndrome occurred in one patient. Between attacks patients were generally well, but 10-20% patients suffered from constitutional symptoms, such as fatigue, between febrile attacks. Patients with p.V377I/p.I268T compound heterozygosity suffered significantly more often from AA-amyloidosis. Patients without a p.V377I mutation suffered more often from severe musculoskeletal involvement. Treatment with NSAIDs could relieve symptoms. Steroids given during attacks, anakinra and etanercept appeared to improve symptoms and could induce complete remission in MKD patients.
CONCLUSION:
This study described the clinical and genetic characteristics of 114 MKD patients, which is the largest cohort studied so far. The clinical manifestations confirm earlier reports. However, the prevalence of AA-amyloidosis was far higher than expected. This article is protected by copyright. All rights reserved
Real-world psychosocial impact among patients with juvenile idiopathic arthritis and families in Spain
Get PDFChildren; Family; PsychosocialNiños; Familia; PsicosocialNens; Família; PsicosocialBackground
To assess the psychosocial impact of moderate-severe juvenile idiopathic arthritis (JIA) on patients and their families, among those who had been treated with at least one anti-tumor necrosis factor (anti-TNF-α), according to routine clinical practice in Spain.
Patients and methods
A 24-month observational, multicentric, cross-sectional and retrospective study was performed. Children diagnosed with JIA were enrolled at three tertiary-care Spanish hospitals. The study included children treated with biologic disease-modifying antirheumatic drugs (bDMARD) who participated in a previous study, the ITACA, and who continued follow-up in these pediatric rheumatology units. Patient health-related quality of life (HRQoL) was assessed using the Pediatric Quality of Life Inventory (PedsQL™). Caregivers completed an interview to gather information about school attendance, their children’s participation in school and social activities, its impact on their jobs and social life and perceived psychosocial support.
A descriptive statistical analysis of all the variables was performed. The Mann–Whitney-U test or Kruskall-Wallis H test were used to compare quantitative variables and Fisher’s exact tests was used for qualitative variables. Tests were two-tailed with a significance level of 5%. The data were analyzed using SPSS V18.0 statistical software.
Results
One hundred and seven patients were included. Overall, patients were on inactive disease or low disease activity according to JADAS-71 score and had very low functional disability according to CHAQ score. Up to 94.4% of patients were receiving drug treatment, mainly with bDMARD in monotherapy (84.5%). Based on PedsQL, patients and parents referred a high HRQoL. School Functioning PedsQL domain achieved the lowest score. Work and social impact due to the child´s disease was greater for mothers than for fathers. The understanding of the disease was lower at school than in the with family and friends’ environments.
Conclusion
Most of the patients had a high HRQoL and had controlled disease activity, despite having a negative psychosocial impact on some of them and their families, mainly on school functioning. Children’s disease seems to involve greater work and psychosocial impacts for mothers than for fathers of children affected by JIA.This study is funding by Pfizer
Corpore Et Animo Praepurgata La Teología Mariana de la Inmaculada Concepción en un Sermón Inédito del Siglo XVIII
Get PDFEn el Archivo Histórico de la Provincia de San Luis Bertrán de Colombia (AHPSBC), se encuentran diversos sermones predicados por los frailes dominicos de la Nueva Granada durante el siglo XVIII. Tomando como base los métodos histórico–crítico y teológico, se hace aquí un análisis mariológico del sermón De Concepción: Beatus venter qui te portavit (Lc 11, 27), predicado en 1797; mediante la identificación de categorías teológicas basadas tanto en fuentes bíblicas y patrísticas como de los demás escritores eclesiásticos propuestos por el autor. Debido a que estos textos gozan de un lenguaje icónico y apologético, se brindan los aportes a la Historia de la Teología a través del análisis paleográfico, archivístico, diplomático y codicológico del documento.Several sermons preached by the Dominican friars of New Granada during the 18th century can be found in the Historical Archives of the Province San Luis Bertrán of Colombia (AHPSBC). Based on the historical-critical and theological method, a mariological analysis of the sermon De Concepción: Beatus venter qui te portavit (Lc 11, 27), preached in 1797, is made by identifying theological categories based on biblical and patristic sources, as well as the other ecclesiastical writers proposed by the author. Since these texts have been endowed with an iconic and apologetic language, contributions to the History of Mariology are provided through the paleographic, archival, diplomatic and codicological analysis of the sermon selected.Teólogohttp://unidadinvestigacion.usta.edu.coPregrad
Characterization of the efficiency and uncertainty of skimmed milk flocculation for the simultaneous concentration and quantification of water-borne viruses, bacteria and protozoa
Get PDF[EN] In this study, the use of skimmed milk flocculation (SMF) to simultaneously concentrate viruses, bacteria and protozoa was evaluated. We selected strains of faecal indicator bacteria and pathogens, such as Escherichia coli and Helicobacter pylori. The viruses selected were adenovirus (HAdV 35), rotavirus (RoV SA-11), the bacteriophage MS2 and bovine viral diarrhoea virus (BVDV). The protozoa tested were Acanthamoeba, Giardia and cryptosporidium. The mean recoveries with q(RT)PCR were 66% (HAdV 35), 24% (MS2), 28% (RoV SA-11), 15% (BVDV), 60% (E. coli), 30% (H. pylori) and 21% (Acanthamoeba castellanii). When testing the infectivity, the mean recoveries were 59% (HAdV 35), 12% (MS2), 26% (RoV SA-11) and 0.7% (BVDV). The protozoa Giardia lamblia and Cryptosporidium parvum were studied by immunofluorescence with recoveries of 18% and 13%, respectively. Although q(RT)PCR consistently showed higher quantification values (as expected), q(RT)PCR and the infectivity assays showed similar recoveries for HAdV 35 and RoV SA-11. Additionally, we investigated modelling the variability and uncertainty of the recovery with this method to extrapolate the quantification obtained by q(RT)PCR and estimate the real concentration. The 95% prediction intervals of the real concentration of the microorganisms inoculated were calculated using a general non-parametric bootstrap procedure adapted in our context to estimate the technical error of the measurements. SMF shows recoveries with a low variability that permits the use of a mathematical approximation to predict the concentration of the pathogen and indicator with acceptable low intervals. The values of uncertainty may be used for a quantitative microbial risk analysis or diagnostic purposes. (C) 2017 The Author(s). Published by Elsevier B.V.This study was funded by the Water Challenges for a Changing World Joint Programming Initiative (W2013-095-C03-01), the Spanish Ministry of Economy and Competitiveness (MINECO - AGL2014-55081-R) and the Grup de Recerca Consolidat: Virus, bacteris i protozous d'interes en salut publica, aigua y aliments (Generalitat de Catalunya, Virbap - 2014-SGR-914). Eloy Gonzales-Gustavson would like to acknowledge the Presidente de la República scholarship from the Peruvian Government, which supported a PhD grant.Gonzales-Gustavson, E.; Cárdenas-Youngs, Y.; Calvo, M.; Figueira, M.; Hundesa, A.; Amoros, I.; Moreno Trigos, MY.... (2017). Characterization of the efficiency and uncertainty of skimmed milk flocculation for the simultaneous concentration and quantification of water-borne viruses, bacteria and protozoa. Journal of Microbiological Methods. 134:46-53. https://doi.org/10.1016/j.mimet.2017.01.006S465313
Abatacept Improves Health-Related Quality of Life, Pain, Sleep Quality, and Daily Participation in Subjects With Juvenile Idiopathic Arthritis
No full textObjective. To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA). Methods. In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to >= 1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined ""responders"") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children`s Sleep Habits Questionnaire, and a daily activity participation questionnaire. Results. A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents` usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents` usual activity days/month, respectively, in abatacept-versus placebo-treated subjects). Conclusion. Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.Bristol-Myers Squib
Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial
Get PDFBACKGROUND: The anti-interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years. METHODS: Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2-17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing < 30 kg (n = 38) who received tocilizumab 12 mg/kg IV Q2W in the previous trial (control group). RESULTS: Eleven patients (mean age, 1.3 years) received tocilizumab during the main evaluation period. The primary end point was met: tocilizumab exposures for patients younger than 2 were within the range of the control group (mean [±SD] μg/mL concentration at the end-of-dosing interval [Cmin]: 39.8 [±14.3] vs 57.5 [±23.3]; maximum concentration [Cmax] postdose: 288 [±40.4] vs 245 [±57.2]). At week 12, pharmacodynamic measures were similar between patients younger than 2 and the control group; mean change from baseline in Juvenile Arthritis Disease Activity Score-71 was - 17.4 in patients younger than 2 and - 28.8 in the control group; rash was reported by 14.3 and 13.5% of patients, respectively. Safety was comparable except for the incidence of serious hypersensitivity reactions (27.3% in patients younger than 2 vs 2.6% in the control group). CONCLUSIONS: Tocilizumab 12 mg/kg IV Q2W provided pharmacokinetics, pharmacodynamics, and efficacy in sJIA patients younger than 2 comparable to those in patients aged 2 to 17 years. Safety was comparable except for a higher incidence of serious hypersensitivity events in patients younger than 2 years. CLASSIFICATION: Juvenile idiopathic arthritis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01455701 . Registered, October 20, 2011, Date of enrollment of first participant: October 26, 2012.sponsorship: This study was funded by F. Hoffmann-La Roche Ltd. Funding for manuscript preparation was provided by F. Hoffmann-La Roche Ltd. (F. Hoffmann-La Roche Ltd.)status: Publishe
