Real-world persistence of initial targeted therapy strategy in monotherapy versus combination therapy in patients with chronic inflammatory arthritis

Objective: The persistence of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real-life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. Methods: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. Results: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00-2.50; p = .049), PsA (HR 2.48; 95% CI 1.65-3.72) and AS (HR 16.77; 95% CI 7.37-38.16; p < .001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05-1.21). Conclusions: In this real-life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients.This research is supported by the Research Unit of the Spanish Society of Rheumatology. BIOBADASER is supported by the Spanish Agency of Drugs and Medical Devices (AEMPS), Biogen, Bristol-Myers and Squibb (BMS), Celltrion, Janssen, Lilly, Merck Sharp and Dohme (MSD), Novartis, Pfizer, Regeneron, and Samsung Bioepis.S

Una perspectiva multidisciplinaria

Derivado de la necesidad de fomentar la investigación multidisciplinaria, la Facultad de Economía de la Universidad Autónoma del Estado de México llevó a cabo los días 8 y 9 de septiembre de 2016, el VIII Coloquio de Investigación intitulado “Desarrollo económico, regional y sustentable”. En este magno evento se presentaron 36 ponencias agrupadas en cinco mesas de trabajo: sectores productivos, crecimiento económico y mercado de trabajo; tecnología, innovación y organizaciones; desigualdad regional, pobreza y migración; economía financiera e internacional; y medio ambiente y sociedad. Del material expuesto en el VIII Coloquio, se eligieron 16 investigaciones, mismas que integran este libro. Los estudios presentados en cada uno de los subsiguientes capítulos fueron seleccionados de acuerdo a un proceso de rigurosidad científica, siendo sometidos a dictamen por pares ciegos a partir de la integración de un Comité Académico de expertos. Lo anterior con la finalidad de proporcionar al lector un material de investigación de calidad y solidez científica respecto a temas de trascendencia vinculados con los sectores productivos, la innovación, las organizaciones, la responsabilidad social, la desigualdad, la educación y el medioambiente.Consecuencia de la apertura de los mercados y los preceptos competitivos dictados por la globalización, se manifiesta la necesidad de vincular los diversos saberes provenientes de las ciencias naturales y sociales, con el fin de complementar el conocimiento y generar nuevas formas de visualizar el entorno. A raíz de ello, la investigación multidisciplinaria asume un papel cada vez más importante en los círculos académicos, empresariales y gubernamentales. En este marco, entra en desuso la visualización del individuo como un sujeto atomístico desvinculado del medio ambiente que le rodea. El objetivo de este libro es otorgar una visión multidisciplinaria al estudio de temas económicos incorporando visiones teóricas y empíricas procedentes de las ciencias sociales y naturales. La obra está compuesta por 16 capítulos agrupados en cuatro secciones. La primera parte, conglomera cinco capítulos en torno a los tópicos sectores productivos y crecimiento económico.Facultad de Economía. Universidad Autónoma del Estado de Méxic

Vascular smooth muscle cell-specific progerin expression in a mouse model of Hutchinson-Gilford progeria syndrome promotes arterial stiffness: Therapeutic effect of dietary nitrite

Vascular stiffness is a major cause of cardiovascular disease during normal aging and in Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder caused by ubiquitous progerin expression. This mutant form of lamin A causes premature aging associated with cardiovascular alterations that lead to death at an average age of 14.6 years. We investigated the mechanisms underlying vessel stiffness in LmnaG609G/G609G mice with ubiquitous progerin expression, and tested the effect of treatment with nitrites. We also bred LmnaLCS/LCS Tie2Cre+/tg and LmnaLCS/LCS SM22αCre+/tg mice, which express progerin specifically in endothelial cells (ECs) and in vascular smooth muscle cells (VSMCs), respectively, to determine the specific contribution of each cell type to vascular pathology. We found vessel stiffness and inward remodeling in arteries of LmnaG609G/G609G and LmnaLCS/LCS SM22αCre+/tg , but not in those from LmnaLCS/LCS Tie2Cre+/tg mice. Structural alterations in aortas of progeroid mice were associated with decreased smooth muscle tissue content, increased collagen deposition, and decreased transverse waving of elastin layers in the media. Functional studies identified collagen (unlike elastin and the cytoskeleton) as an underlying cause of aortic stiffness in progeroid mice. Consistent with this, we found increased deposition of collagens III, IV, V, and XII in the media of progeroid aortas. Vessel stiffness and inward remodeling in progeroid mice were prevented by adding sodium nitrite in drinking water. In conclusion, LmnaG609G/G609G arteries exhibit stiffness and inward remodeling, mainly due to progerin-induced damage to VSMCs, which causes increased deposition of medial collagen and a secondary alteration in elastin structure. Treatment with nitrites prevents vascular stiffness in progeria.Ministerio Ciencia, Innovacion y Universidades, Grant/Award Number: SAF2016-79490-R, SAF2016-8035-P, SEV-2015-0505, SVP-2014-068334; European Regional Development Fund; NIH grants, Grant/Award Number: AG047373, T32-GM008076, F31HL142160; NSF grant, Grant/Award Number: CMMI 1548571; Red de Investigacion Cardiovascular (RETIC Program, Instituto de Salud Carlos III; ProCNIC FoundationS