BackgroundRheumatoid Arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Müllerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyze the relationship between fertility in RA women patients and AMH.ObjectivesThe aim of present study is to determine the AMH serum concentrations in a long-standing RA patients and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs.MethodsSerum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by ELISA (Gen II Beckman Coulter Inc.) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student’s t-test or Mann-Whitney U test for continuous variables and Fisher’s exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. P value <0.005 were considered significant.ResultsThe median age was similar in AR and control groups (37.4±6.23 vs 37.3±6.27 P=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was <3 in 71.7% of patients and ≥3 in 28.3%. Disease activity measured by DAS28 was 2.89± 1.54. The age-adjusted mean serum concentration of HAM was 1.27 ng/ml [IQR 0.42; 2.24] in RA patients and 1.31 ng/ml [IQR 0.46; 3.09] in controls (P=0.608). Neither disease activity (P=0.862), nor current or previous bDMARDs treatments (P=0.871) were associated with HAM levels. However, a negative linear correlation was observed between HAM and IL-10 levels (P= 0.033).ConclusionOur study shows that ovarian reserve determined by HAM serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, HAM levels were not affected by disease activity however a significant correlation was observed between HAM and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have be recommended in RA pregnant patients.References[1] Brouwer J, Fleurbaaij R, Hazes JM, Dolhain RJ, Laven JS. Subfertility in rheumatoid arthritis is often unexplained or caused by anovulation. Arthritis Care Res (Hoboken). 2016.[2] Brouwer J,...
Background The patient with fibromyalgia (FM) is, according to many publications, a major consumer of health resources with a significant increase in emergency assistance, hospitalization and complementary tests. The Spanish guidelines for FM since 2006 define very strictly which tests are necessary for these patients and follow up consultations in primary care. Rheumatoid arthritis (RA) is a complex disease that may require considerable hospital resources and whose follow up tend to be in the hospital (in our environment), which is why it has been selected for cost comparison. Objectives We propose to study the hospital costs represented by patients with FM over a one year period compared to the cost of RA. Methods We selected all the patients with the previous diagnosis of FM or RA who were attending the rheumatology consultation between the first until the 30 June 2012 We reviewed the one year expenses incurred from hospital visits, interconsultations and complementary tests. Surgery and the consumption of pharmaceutical drugs were excluded from the study. New patients were analyzed independently from those attending follow ups consultations. Results We recruited 48 FM and 53 RA, 1 man in the FM group and 8 in the RA group. The average age was 51 years for FM and 62 for RA. The patients affected by RA made up 56% more visits/year than FM to Rheumatology. The number of visits to other Units was similar in both groups: 229 versus 234. The number of imaging tests was 52 for FM and 115 in the RA. Laboratory tests (blood analysis, urinalysis, blood cultures) were 46 for FM versus 181 in RA and the number of hospitalization days was 5 times greater for RA group. On the other hand the cost of other tests such as MRI, CT-guided blocks, EEG, endoscopy or ultrasound is double in the case of FM. The average annual cost of FM was € 1100 per patient/ year and the RA €1600/year. Analytical tests and hospitalization make up 41% of the Hospital cost of FM and 24% of RA. For FM, 41% of the cost is attributed to other consults different than Rheumatology, whereas 24% for RA. No differences were detected between groups of new patients and those currently being treated (whether by biological treatment or not). Conclusions We note that in rheumatology spending is much lower in FM than in RA but not in the diagnostic tests that seem to correlate with the number of visits in other Departments that rheumatology which is similar in both groups, which could be due to the guidelines for FM it’s not know for other specialties. The RA group was older than FM and that may have caused a bias in the measurement of the cost. The annual cost is far from the published ranges of € 9500-10500 per year for FM and € 2055-5634 per year for RA, but in that studies drug expenditure and the cost of employee absence are included. The implementation of treatment guidelines of the FM in other areas than the Rheumatology might be important in reducing costs. Disclosure of Interest None Declared
Background:Abatacept (CTLA4-Ig) is an approved biological therapy for the treatment of rheumatoid arthritis (RA). Similar to other biological agents, most patients (60%) respond significantly to this therapy. To date, however, the biological mechanisms underlying the lack of efficacy for this drug are unknown.Objectives:The objectives of the present study were to characterize the biological processes underlying the lack of efficacy of abatacept and to evaluate the blood transcriptome as a valid source for drug response prediction.Methods:A total of n=57 patients diagnosed with RA were recruited for this study from 16 rheumatology departments in Spain. All patients were >18 years old and, had >6 months of disease evolution. The primary clinical response to abatacept was defined at week 12 using the EULAR criteria. Good and moderate responders were aggregated into a single response group, and compared to the no response group of patients. Blood RNA was collected from all patients at baseline. From a subgroup of patients (n=31), blood RNA was also obtained at weeks 12, 24 and 48 of treatment with abatacept. Gene expression levels were determined using paired-end RNA-seq (Illumina). Differential gene expression, association to biological processes, longitudinal association analysis and building of the multigenic predictor were performed using the R software and the specialized Bioconductor libraries. The the prediction accuracy was evaluated using the ROC AUC.Results:From the 57 patients treated with abatacept, n=10 (17.5%) were good EULAR responders, n=24 (42%) moderate EULAR responders and n=23 (40.5%) non-responders at week 12 of therapy. Biological process analysis identified two significantly distinct biological profiles between responders and non-responders. In responders, we found an association to pathways associated with the effector phase of T cells (e.g. interleukin-15 and 2 signalling, P < 0.05). Non-responder patients showed instead a strong association to biological processes associated with antigen presentation and activation of T cells (P < 0.005). Using the baseline gene expression profiles, we built a multigenic predictor of response to abatacept with an AUC = 75%. In the longitudinal cohort, patients were stratified based on reaching an inactive state (i.e. DAS28 < 3.2). Using this endpoint measure, the longitudinal analysis of the 4 time points corroborated the association of response with antigen presentation (P < 0.01).Conclusion:The analysis of blood RNA profiles of RA patients has enabled the identification of specific biological processes associated with the lack of response to abatacept. Also, we demonstrate that blood expression profiles can be predictive of the response to the drug at week 12 of therapy.Disclosure of Interests:Antonio Julià: None declared, Maria Lopez Lasanta: None declared, Antonio Gómez: None declared, Raimon Sanmarti Grant/research support from: Research support: Bristol-Myers Squibb, Speakers bureau: Speakers bureau: Bristol-Myers Squibb, Carlos Marras Fernandez Cid: No...
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