To examine disease activity and physical function after implementation of treat-to-target (T2T) strategy in patients with established rheumatoid arthritis (RA) over a long-term period. Patients with RA were started on a T2T strategy in 2005 and followed through 2014. Patients were seen every 3-4 months until remission/low disease activity was achieved and every 6 months thereafter. Disease activity was measured by the DAS28 and CDAI, and physical function by the HAQ-DI. Results were presented as all observed data, without imputation for missing values. Changes in disease activity and physical function were evaluated by generalized estimating equations (GEE). Two hundred and twenty-nine patients were included, with a mean (SD) disease duration of 10.6 (7.4) years. Significant improvements were seen in both composite scores during the follow-up period, as demonstrated by DAS28 (β coefficient = 0.19; 95% CI = 0.16-0.21; p < 0.01) and by CDAI (β coefficient = 1.59; 95% CI = 1.84-1.34; p < 0.01). Physical function also improved, as demonstrated by HAQ-DI (β coefficient = 0.03; 95% CI = 0.02-0.04; p < 0.01). Biological therapy was associated with improvement in disease activity and in physical function. Leflunomide was only associated with improvement in physical function. Clinically meaningful reductions of DAS28, CDAI and HAQ-DI were observed in patients with established rheumatoid arthritis from 2005 to 2014. Implementation of new therapeutic options, in the scenario of T2T strategy, was associated with improvement in disease activity and physical function.
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Background HLA-G may exert long-term immunotolerogenic effects through the generation of suppressor cells [reviewed in [1]]. Such features render HLA-G an attractive candidate gene for susceptibility to immune mediated diseases. Indeed, our group has observed a positive association of a 3’UTR haplotype encompassing the 14bp locus and the +3142C/G (rs1063320) and disease susceptibility in patients with systemic lupus erythematosus [2]. Objectives To investigate the genetic influence of the two HLA-G 3’UTR polymorphisms – the 14 bp insertion/deletion (rs1704) and the +3142C>G (rs1063320) – in the susceptibility to rheumatoid arthritis in a double-center study comprising a Southern-Brazilian cohort from Porto Alegre and Northern-Brazilian cohort from the city of Belém. Methods A total number of 546 RA patients and 531 controls was PCR genotyped for the two polymorphisms. Results Haplotype frequencies differed significantly between control groups from the Northern and Southern cohorts. After adjusting for city of origin and gender, we observed that female patients presented a higher frequency of the deletion-G (D/G) haplotype (OR=1.634, 95% CI=1.128–2.368, P=0.009). After stratifying for RF positivity, only the female RF+ group of patients presented statistical significance (OR=1.829, 95%C.I =1.243–2.690, P=0.002) - Table 1. Table 1.HLA-G D/G carrier frequencies in patients and comparison with controls AllFemalesMales N/Total (freq)N/Total (freq)N/Total (freq) Porto Alegre (South) Controls0.206 (59/287)0.133 (16/120)a,b0.257 (43/167) Patients (all)0.235 (80/340)0.242 (67/277)a0.206 (13/63) RF+0.238 (67/281)0.247 (56/227)b0.204 (11/54) RF–0.232 (13/56)0.234 (11/47)0.222 (2/9) Belém (North) Controls0.338 (75/222)0.302 (38/126)c0.385 (37/96) Patients (all)0.360 (71/197)0.374 (68/182)0.200 (3/15) RF+0.405 (60/148)0.414 (58/140)c0.250 (2/8) RF–0.242 (8/33)0.286 (8/28)0.0 (0/5) aP=0.015, bP=0.017, cP=0.072. Conclusions Our results suggest a differential influence of HLA-G 3’UTR polymorphisms in disease susceptibility, with the D/G haplotype as a risk factor for RA in RF+ females. References Carosella ED, HoWangYin K-Y, Favier B, LeMaoult J. Hla-g-dependent suppressor cells: Diverse by nature, function, and significance. Human immunology 2008;69:700-7. Consiglio CR, Veit TD, Monticielo OA, et al. Association of the hla-g gene +3142c>g polymorphism with systemic lupus erythematosus. Tissue Antigens 2011;77:540-5. Disclosure of Interest None Declared
Cerumen is a bee product produced exclusively by stingless bees, resulting from a mixture of beeswax and plant resins. The antioxidant activity of bee products has been investigated since oxidative stress is associated with the onset and progression of several diseases that can lead to death. In this context, this study aimed to investigate the chemical composition and antioxidant activity of cerumen produced by the Geotrigona sp. and Tetragonisca fiebrigi stingless bees, in vitro and in vivo. The chemical characterization of cerumen extracts was performed by HPLC, GC, and ICP OES analyses. The in vitro antioxidant potential was evaluated by DPPH• and ABTS•+ free radical scavenging methods, and in human erythrocytes subjected to oxidative stress with AAPH. In vivo, the antioxidant potential was evaluated in Caenorhabditis elegans nematodes subjected to oxidative stress with juglone. Both cerumen extracts presented phenolic compounds, fatty acids, and metallic minerals in their chemical constitution. The cerumen extracts showed antioxidant activity by capturing free radicals, reducing lipid peroxidation in human erythrocytes, and reducing oxidative stress in C. elegans, observed by the increase in viability. The results obtained indicate that cerumen extracts from Geotrigona sp. and Tetragonisca fiebrigi stingless bees may be promising against oxidative stress and associated diseases.
BackgroundTreating rheumatoid arthritis (RA) to a target has become a landmark strategy to be pursued in every patient. Compared to usual care, treat to target (T2T) has decreased radiographic progression and improved quality of life and physical function1. Nonetheless, few studies have addressed the true long-term impact of a T2T strategy in a real-world setting with established RA patients2,3.ObjectivesTo examine the long-term effectiveness of a treat-to-target strategy in patients with established rheumatoid arthritis in daily practice.MethodsRheumatoid arthritis patients previously treated under usual care condition were started on a T2T strategy between March 2005 and February 2007 and followed through December 2014. Participants were seen every 3 months until remission/low disease activity was reached and every 6 months afterwards. After DMARD change, participants were assessed monthly for three consecutive months. Treatment escalation followed a step-up strategy, according to national recommendations. Disease activity was measured by DAS28 and CDAI, and physical function by HAQ. Data were extracted by standardized chart and research forms review. Change in disease activity and physical function was compared using Wilcoxon's test and Generalized estimate equations.ResultsSignificant improvements were seen in both composite scores during follow-up period. There was a significant reduction in DAS28 (4.6±0.1 vs. 3.1±0.1; p<0.001) and in CDAI (21.2±1.0 vs. 7.9±0.7; p<0.001). Physical function also improved, as demonstrated by reduction in HAQ-DI (1.3±0.05 vs 1.0±0.1; p<0.001). The reduction in DAS28, CDAI and HAQ-DI was nonlinear. The percentage of participants in remission increased significantly from 11% to 35% by DAS28 and from 6% to 19% by CDAI (p<0.001). Likewise, there was an improvement in LDA from 10% to 28% by DAS28 and from 22% to 52% by CDAI (p≤0.001). At the end of follow up, 62% of the cohort achieved the target by DAS28 and 71% by CDAI. As well as 30% of participants reached HAQ≤0.5 and DAS≤3.2.ConclusionsTreat-to-target strategy aiming for remission or low activity disease is effective in patients with established RA. The access to biologic DMARDs might have contributed to achieve disease activity control in a substantial proportion of the patients.ReferencesGrigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): A single-blind randomised controlled trial. Lancet. 2004;364:263–9.Fransen J, Moens HB, Speyer I, van Riel PLCM. Effectiveness of systematic monitoring of rheumatoid arthritis disease activity in daily practice: a multicentre, cluster randomised controlled trial. Ann Rheum Dis. 2005;64:1294–8.Pope JE, Haraoui B, Rampakakis E, Psaradellis E, Thorne C, Sampalis JS. Treating to a Target in Established Active Rheumatoid Arthritis Patients Receiving a Tumor Necrosis Factor Inhibitor: Results From a Real-World Cluster-Randomized Adalimumab Trial. Arthritis Care Res. 2013;65(9):1401–9.Disc...
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