BackgroundRheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by joint destruction, deformity, lower functional status and decrease in life expectancy. Wnt signaling pathway recently it has been implicated in bone homeostasis. Studies suggest that overexpression of inhibitors of the way, like the Dickkopf 1 protein (DKK1) has been implicated in bone destructionObjectivesTo compare circulating levels of DKK1 in patients with RA to their disease activity and functional statusMethods379 consecutive patients with early and established RA were evaluated at the Hospital Militar Central in Bogota-Colombia, between March 2015 and November 2016. A complete medical history related to RA was obtained. Disease activity was evaluated by DAS28-CRP, CDAI, SDAI and RAPID3. functional status was measurement using MDHAQ and the Steinbrocker functional classification. DKK1 levels measured by ELISA using an Abcam® kitResultsThe mean age was 60,7±13,1 years, disease duration 13,1±10,9 years, 80,4% were female. Higher levels of DKK1 were not associated with higher disease activity by CDAI (p=0,70), SDAI (p=0,84), DAS28 with CRP (p=0,80) or RAPID3 (p=0,70). Interestingly Higher levels of DKK1 were significantly associated to greater disability and lower functional status according to the Steinbrocker functional grading (p=0.013) and with severe disability by MDHAQ (p=0.004), Table 1.Other variables associated with joint destruction were osteoporosis, elevated rheumatoid factor, smoking, and hospitalizationConclusionsHigher levels of DKK1 were found in patients with lower functional status. This association was not found in patients with greater disease activity according to CDAI, SDAI, DAS28 and RAPID3. This could be explaining by greater structural damage though more studies would be needed to explore this possibilityReferences Huizinga TW, Pincus T. In the Clinic. Rheumatoid arthritis. Ann Intern Med. 2010 Jul 6;153(1):ITC1–1-ITC-15. Disclosure of InterestNone declared
Objectives: Biologics represent major advances in the treatment of rheumatoid arthritis (RA) with eight agents available on the market by 2010. In the Medicare program, 3 agents are Part B covered infusibles, while the remaining five are Part D covered self-injectables. This study examines the association between cost sharing and the initiation and choice of RA biologic (Part D vs. Part B) in Medicare beneficiaries. MethOds: Fee-for-service beneficiaries with continuous Part D coverage and RA (ICD-9-CM 714.xx) in the 2010 Medicare 5% files (N= 12,923) were examined. Dependent variables included initiation of any biologic among all RA patients and the use of a Part D (vs. Part B) biologic among biologic users. To isolate the effect of the specialty tier cost-sharing (from that of the donut hole) we further identified whether a Part D biologic was first initiated in the initial coverage limit (ICL) phase or not. The key independent variable was the beneficiary's low income subsidy (LIS) status i.e. non-LIS vs. full-LIS as a proxy for higher (initially 25% to 35% coinsurance followed by donut hole) vs. lower cost-sharing ($3-$5 copay), respectively. Multivariate logistic regressions with robust clustered standard errors at the plan level were estimated. Results: Overall RA biologic use was 17% in the sample (10 % Part B and 7% Part D biologics). Compared to full-LIS patients, non-LIS patients had lower odds of initiating any RA biologic in the year (OR 0.84, 95% CI 0.75-0.94). Among biologic users, non-LIS patients were less likely to use a Part D biologic in the entire year (OR 0.19, 95% CI 0.15-0.24) and in the ICL-phase (OR 0.22, 95% CI 0.17-0.28). cOnclusiOns: High cost sharing due to specialty tiers and the coverage gap under Part D may be associated with non-LIS patients foregoing use of any RA biologic or substituting with infusible biologics under Part B.
BackgroundA main challenge in spondyloartritis (SpA) management was the availability of reliable biomarkers related with disease activity, or predicting joint damage and the response to treatment. Although erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are currently used as biomarkers for disease activity, they lack sensitivity, specificity and reproducibility. With the understanding of SpA pathogenesis, additional biomarkers like metalloproteinase 3 (MMP-3), interleukin (IL)-1a, IL-6, lipopolysaccharide-binding protein (LBP), tumour necrosis factor a (TNFa), macrophage colony stimulating factor (M-CSF), interferon gamma (INF-g), IL-17 and IL-23, had been proposedObjectivesWe aimed to evaluate the associations of MMP-3, IL-1a, IL-6, M-CSF, LPB, IL-17 and IL-23 levels in SpA patients positive for HLA-B27 or HLA-B15Methods178 patients (100 men and 78 women) with SpA according to ASAS criteria were included in the study. HLA typing was performed by PCR using the Biorad® HLA-SSP ABDR plates. The levels of TNFa, IL-1a, IL-6, INF-g and IL-17 were measured by a cytometric bead-array (CBA Flex Set) using a FACS Canto II Flow CytometerÔ. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of IL-23, M-CSFand MMP-3. CRP and LBP levels were measured by chemiluminescence. Statistical analysis was made with SPSS v19. For comparison of quantitative variables with a normal distribution we used the Student's t-test. Categorical variables were presented in frequency charts and percentages, and the Chi-squared test and Fisher's exact test were used when necessary, for comparing groups. Two-tailed P-value <0.05 was considered statistically significantResultsOf the 178 patients, 70 were positive for HLA-B27, 34 for HLA-B15 and 74 had other HLA-B. According to ASAS classification criteria, 152 patients had axial SpA (axSpA) manifestations, 161 had peripheral SpA (pSpA) manifestations, and 148 patients had mixed axial and peripheral manifestations. Figure 1 shows the mean levels of inflammatory serologic biomarkers in these subgroups of patientsConclusionsHigh levels of IL-17 and IL-23 were associated with the presence of HLA-B27, which mainly correlates with an axial presentation of the disease as compared to HLA-B15 patients. Accordingly, the genotype (presence of HLA-B27 or HLA-B15) and phenotype (axial or peripheral involvement) may help physicians when considering a targeted therapy of SpA patients with IL-17 inhibition in a context of personalized medicineDisclosure of InterestNone declared
BackgroundSince 1973, the association of HLA-B27 and spondyloarthritis (SpA) is well known, however in Colombian population it is present in only 40% of patients and HLA-B15 is present almost in 25%. A mechanism of polygenic mechanism has been proposed as an explanation for the development of SpA. Endoplasmic reticulum aminopeptidase (ERAP) genes 1 and 2 have been implicated. ERAP1 is strongly associated with HLA-B27 positive patients and ankylosing spondylitis, but not with ERAP2ObjectivesTo determine the association between ERAP polymorphisms and HLA-B27 or HLA-B15 positive SpA patientsMethods178 patients with SpA according to ASAS criteria were included in the study. HLA typing was performed by the PCR technique using the Biorad® HLA-SSP plates. The polymorphisms were determined by the RT-PCR technique using Roche® probes for ERAP1 rs27044, rs17482078, rs10050860, and rs30187. For ERAP2 the probes used were rs2910686, rs2248374 and rs2549782. The allele and genotype frequencies polymorphisms were obtained by direct counting. In each group the Hardy-Weinberg equilibrium was evaluated using the 2 test. Associations were assessed using odds ratio (OR). Stata v.12.0 program was used to analyse data. The construction and analysis of haplotypes was performed using Haploview v.4.2ResultsIn total 70 patients were HLA-B27 positive and 34 were HLA-B15 positive. 78 were women and 100 were men. Linkage disequilibrium map of the ERAP gene is depicted in figure 1. When analysed by ERAP2 haplotype it is observed that there is a statistically significant association with the combinations described in table 1. No associations were observed between ERAP1 haplotypes and HLA-B15 or B27Table 1.ERAP2 Haplotypes in HLA-B15 and B27 PatientsHaplotypesHLA B15HLA B27OR p n (AF)n (AF)(CI 95%) TGT 0.201 0.0782.943 (1.264–6.585)0.009*TGC0.055 0.227 4.483 (1.524–13.187)0.003*CAT0.021 0.119 9.014 (1.181–68.807)0.009*CAC0.6430.4991.750 (0.968–3.162)0.077CGC0.0160.0350.465 (0.053–4.056)0.672CGT0.0310.0132.406 (0.332–17.45)0.584TAT0.0190.0131.185 (0.106–13.29)1.00TAC0.0130.0151.185 (0.106–13.29)1.00ERAP: endoplasmic reticulum aminopeptidase; AF: allelic frequency; OR: odds ratio.ConclusionsIn the group of patients analysed, a statistically significant association was found between patients with SpA HLA-B15 positive and the haplotype TGT of ERAP2. Also HLA-B27 positive SpA patients were associated with haplotype TGC and CAT of ERAP2 with statistical significanceDisclosure of InterestNone declared
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