High Clinical Disease Activity Research Articles

P007 Neutrophil function in lesional biopsies is a strong determinant of IBD severity and may relate to an altered functional state already present in circulating cells

Abstract Background Neutrophils clear luminal bacteria from the intestinal lamina propria and have a protective role in Inflammatory Bowel Disease (IBD). However, their production of inflammatory cytokines, matrix metalloproteases and radical oxygen species causes irreversible tissue damage. Histological assessment of infiltrating neutrophils and indirect measurement of neutrophil-derived calprotectin in feces are used to assess disease severity in patients. Since IBD is a heterogeneous disease in terms of presentation, severity and course, we hypothesize that different patients have a different composition of their neutrophil compartment that leads to a different balance between protection and damage. We aim to study the variability in neutrophil phenotype and function and relate it to patient heterogeneity. Methods We analyzed endoscopic biopsies and peripheral blood samples from children diagnosed with IBD within the PIBD-SETQ cohort. Paired biopsies obtained at diagnosis were scored by a pathologist and analyzed by IHC and RNAseq. RNAseq was also performed on purified circulatory neutrophil at diagnosis and their phenotype was analyzed by whole-blood flow cytometry. Results At diagnosis, high numbers of infiltrating neutrophils in intestinal tissue differentiated IBD patients with high clinical disease activity, more severe endoscopic and histological disease and high plasma concentrations of IL-17. RNA sequencing of lesional intestinal biopsies revealed differential expression of genes linked to neutrophil degranulation and IL-17 signaling in the colon of IBD patients with high neutrophil infiltration. Moreover, these biopsies had high mRNA expression for Oncostatin M, a neutrophil product known to associate with therapy resistance. To assess whether circulating neutrophils were altered in IBD before entering the intestinal tissue, we performed bulk RNAseq analysis of purified circulating neutrophils from non-IBD and CD patients. Neutrophils from CD patients had increased expression of genes related to granule formation and filling (MMP9, S100A8, S100A9) and pathogen sensing (TLR5, NLRC4) but not cytokine production (IL1B, OSM), relative to non-IBD patients. Expression of CD10 was decreased in circulating neutrophils from UC and CD patients while CD16 expression was lower in UC-derived neutrophils, suggesting these cells have a more immature state. Conclusion We have detected changes in the maturity of neutrophils in the circulation of some IBD patients that could have functional consequences in terms of bacterial clearance and tissue damage in the intestinal mucosa. Uncovering different functional profiles in neutrophils may help dissect patient heterogeneity and provide novel targets for therapy.

Early use of high efficacy therapies in pediatric forms of relapsing-remitting multiple sclerosis: A real-life observational study.

Pediatric forms of multiple sclerosis are more active than those in adults. Yet, the effectiveness of different therapeutic approaches is not well studied in this population. Our objective was to compare the effectiveness of the early use of high efficacy therapies (HETs) with the effectiveness of moderate efficacy therapies (METs) in children with MS. This observational study included patients diagnosed with pediatric MS, at 4 hospital centers in France, during a 10-year period. METs included: interferon β-1a, glatiramer acetate, dimethyl fumarate, teriflunomide; HETs included: fingolimod, natalizumab, ocrelizumab, alemtuzumab. The primary endpoint was the occurrence of a new relapse, the secondary endpoint was EDSS worsening. Sixty-four patients were included in the analysis (80% women; mean age 15.5 years, 81% treated with MET) with a median follow-up of 22.5 months. At baseline, 52 patients were on MET (interferon β-1a, glatiramer acetate, dimethyl fumarate, teriflunomide) and 12 patients were on HET (natalizumab, ocrelizumab). The cumulative probability of being relapse-free at 6.5 years was 23.3% on MET, vs 90.9% on HET (p=0.013). The cumulative probability of no EDSS worsening did not differ between the 2 groups. Patients starting with METs had much higher clinical disease activity than those starting early with HETs. Rapid initiation of more aggressive treatment may allow better disease control; however, the data on EDSS worsening are not conclusive.

Clinical features of patients with ankylosing spondylitis with inefficacy of two or more biological disease modifying antirheumatic drugs

The “Treat-to-target” (T2T) strategy for axial spondyloarthritis (axSpA) has made it possible to optimize therapy in most patients, but in some of them the treatment goals are not achieved.Objective: to analyze the clinical features of patients with ankylosing spondylitis (AS) with inefficacy of two or more biological disease modifying antirheumatic drugs (bDMARDs).Material and methods. From February 2020 to March 2022 458 patients with AS, who met the modified New York criteria of 1984, were admitted to V.A. Nasonova Research Institute of Rheumatology. From this group, 30 (6.6%) patients with high clinical disease activity and inefficacy of at least two bDMARDs were selected. The control group consisted of 139 (30.5%) patients with AS, who either had no history of bDMARDs use, or had previously received only one of them. All patients were examined in accordance with generally accepted methods and underwent a double expert control.Results and discussion. Men predominated in the main and control groups (67 and 60%, respectively). In patients of the main group, there was a higher laboratory activity of the disease, especially ESR (p=0.002), more often peripheral arthritis was detected. In both groups, there was a high incidence of coxitis (69.2 and 69.7%, respectively), while in the main group there were significantly more patients who underwent total joint arthroplasty, and the frequency of detected syndesmophytes was 2 times lower compared to the control. Differences in the features of AS onset were also established: in the main group, the disease often began with reactive arthritis (ReA), while in the control group, with inflammatory back pain.Conclusion. The T2T strategy in axSpA does not always lead to the achievement of the intended goals, and, according to our data, among inpatients with AS, the number of people with a history of inefficacy of two or more bDMARDs reaches 6%. In these patients, compared with the control, the following features of the disease can be distinguished: frequent onset with ReA, a significant incidence of peripheral arthritis and joint arthroplasty, and a higher ESR.

Anaemia is associated with higher disease activity in axial spondyloarthritis but is not an independent predictor of spinal radiographic progression: data from the Swiss Clinical Quality Management Registry

ObjectiveAs anaemia represents a biomarker for increased radiographic damage in rheumatoid arthritis, we aimed to investigate whether it independently predicts spinal radiographic progression in axial spondyloarthritis (axSpA).MethodsAxSpA patients with available haemoglobin levels from the prospective Swiss Clinical Quality Management Registry were included for comparison of patients with and without anaemia. Spinal radiographic progression was assessed according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in patients with ankylosing spondylitis (AS) if ≥ 2 sets of spinal radiographs were available every 2 years. The relationship between anaemia and progression (defined as an increase ≥ 2 mSASSS units in 2 years) was analysed with generalized estimating equation models after adjustment for the Ankylosing Spondylitis Disease Activity Score (ASDAS) and potential confounding, as well as after multiple imputations of missing values.ResultsA total of 212/2522 axSpA patients presented with anaemia (9%). Anaemic patients had higher clinical disease activity, higher acute phase reactants and more severe impairments in physical function, mobility and quality of life. In the subgroup of patients with AS (N = 433), a comparable mSASSS progression was found in anaemic and non-anaemic patients (OR 0.69, 95% CI 0.25 to 1.96, p = 0.49). Age, male sex, baseline radiographic damage and ASDAS were associated with enhanced progression. The results were confirmed in complete case analyses and with progression defined as the formation of ≥ 1 syndesmophyte in 2 years.ConclusionAlthough anaemia was associated with higher disease activity in axSpA, it did not additionally contribute to the prediction of spinal radiographic progression.Key Points• Anaemia is associated with higher disease activity and more severely impaired physical function, mobility and quality of life in axSpA.• Anaemia does not provide an additional value to ASDAS for prediction of spinal radiographic progression.

Serum immune profiling in pediatric Crohn's disease demonstrates stronger immune modulation with first-line infliximab than conventional therapy and pre-treatment profiles predict clinical response to both treatments.

Despite its efficacy, rational guidance for starting/stopping first-line biologic treatment in individual pediatric Crohn's disease (CD) patients is needed. We assessed how serum immune profiles before and after first-line infliximab (FL-IFX) or conventional (CONV) induction therapy associate with disease remission at week 52. pre- (n=86), and 10-14 week post-treatment (n=84) sera were collected from patients with moderate-to-severe paediatric CD in the TISKids trial, randomised to FL-IFX (n=48; five 5mg/kg infusions over 22 weeks) or CONV (n=43; exclusive enteral nutrition or oral prednisolone); both groups received azathioprine maintenance. The relative concentrations of 92 inflammatory proteins were determined with Olink Proteomics; fold changes (FC) with |Log2FC|>0.5 after FDR adjustment were considered significant. FL-IFX modulated a larger number of inflammatory proteins and induced stronger suppression than CONV; 18/30 proteins modulated by FL-IFX were not regulated by CONV. Hierarchical clustering based on IFX-modulated proteins at baseline revealed two clusters of patients: CD-hi patients had significantly higher concentrations of 23/30 IFX-modulated proteins (including oncostatin-M, TNFSF14, HGF, TGF-α) and higher clinical disease activity, CRP and blood neutrophils at baseline than CD-lo patients. Only 24% of CD-hi FL-IFX-treated patients maintained remission without escalation at week 52 vs 58% of CD-lo FL-IFX-treated patients. Similarly, 6% of CD-hi CONV-treated patients achieved remission vs 20% of CONV-treated CD-lo patients. Clustering based on immune profiles post-induction therapy did not relate to remission at week 52. FL-IFX leads to stronger reductions and modulates more immune proteins than CONV. Stratification on pre-treatment profiles of IFX-modulated proteins directly relates to maintenance of remission without treatment escalation.

Clinical disease activity is a major determinant of plasma D-dimer elevation in outpatients with rheumatoid arthritis: A hospital-based cross-sectional study.

To identify factors associated with plasma D-dimer levels in outpatients with rheumatoid arthritis (RA). We consecutively recruited 460 RA patients who visited our hospital for routine follow-ups between June and October 2021. Plasma D-dimer, RA-related characteristics, comorbidities, and cardiovascular and venous thromboembolism (VTE) risk factors were examined at enrolment. Patients with elevated D-dimer levels underwent whole-leg venous ultrasonography to diagnose deep vein thrombosis (DVT). Participants had no DVT signs or symptoms. Among them, 252 (54.8%) were positive for plasma D-dimer (≥0.5 μg/ml) and 40 (8.7%) had high D-dimer levels (≥3 μg/ml). The mean was 1.07 μg/ml. After adjustments, age [odds ratio (OR) 1.88 per additional 10 years, P = .003], high and moderate clinical disease activity index (OR 8.79, P < .001), and the presence of comorbidities or cardiovascular/VTE risk factors (OR 2.94, P = .017) were identified as the factors independently associated with high D-dimer levels. Among patients with D-dimer levels ≥3 μg/ml, 10 (25%) had DVT in their lower limbs, and D-dimer levels were significantly higher in patients with DVT compared with those without it (mean 6.0 vs. 4.1 μg/ml, P < .001). Clinical disease activity is a major contributor to plasma D-dimer elevation in RA outpatients.

Association of - 717 A > G (rs2794521) CRP polymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease where genetic factors have been related to SLE susceptibility and disease severity. CRP polymorphisms have been associated with high C-reactive protein (CRP) serum levels, cardiovascular disease (CVD), and high clinical disease activity in SLE patients; however, the evidence is still inconclusive. This study was aimed to assess the association of the - 717 A > G, - 409 G > A, + 1444 C > T, and + 1846 C > T CRP polymorphisms with genetic susceptibility, clinical disease activity, and CVD risk in Mexican-mestizo SLE patients. A comparative cross-sectional study was conducted on 369 unrelated women: 183 with SLE according to the 1997 SLE-ACR criteria and 186 healthy subjects (HS). The clinical disease activity was assessed by the Mex-SLEDAI score; CRP and lipid profile were quantified by turbidimetry and colorimetric-enzymatic assays, respectively. The CRP polymorphisms genotyping was carried out by allelic discrimination. SLE patients with - 717 AA genotype had higher CRP serum levels than SLE carriers of AG and GG genotypes (AA = 5mg/L vs. AG = 3.2mg/L vs. GG = 2.4mg/L; p = 0.01), and the AA genotype was associated with high CVD risk by CRP in SLE patients (OR = 3; CI: 1.2-7.6; p < 0.01). The - 717 A > G CRP polymorphism is a risk factor for high CRP levels and high CVD risk in Mexican-mestizo SLE patients. Key Points • Cardiovascular disease is one of the major causes of death in SLE patients due to the higher prevalence of traditional and non-traditional cardiovascular risk factors. • C-reactive protein is a liver-derived acute-phase protein suggested as one powerful independent risk predictor factor for cardiovascular disease. • Single nucleotide polymorphisms in CRP have been suggested as genetic susceptibility factors that could modify the SLE pathophysiology outcomes. • Mexican-mestizo SLE patients carrying the -717 A>G CRP AA genotype had 3-fold high cardiovascular disease risk than SLE patients with AG or GG genotypes.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI&nbsp;VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Rebound of clinical disease activity after fingolimod discontinuation? A nationwide cohort study of patients in Denmark

ObjectiveWe investigated whether clinical rebound occurred after fingolimod discontinuation in a complete population of patients with relapsing-remitting multiple sclerosis (RRMS) in Denmark. We further identified clinical and demographical factors associated...

Clinical, radiological, and magnetic resonance imaging characteristics of axial spondyloarthritis with late onset.

We aimed to investigate the clinical, diagnostic, and imaging features of patients with late onset axial spondyloarthritis (SpA) with initial symptom manifestation aged over 45 years.Participants with axial SpA were consecutively recruited. Clinical, demographic, blood, and imaging parameters were compared between the groups with early (≤45 years) and late onset (>45 years) at a cross-sectional level. Logistic regressions were used to determine the independent associations with axial SpA with late onset.A total of 455 participants were recruited. Among them, 70 (15.4%) had late onset disease. Multivariate analyses showed that axial SpA with late onset was associated with higher C-reactive protein based ankylosing spondylitis disease activity index (ASDAS-CRP) (B = 0.10; P = .04), higher intensity of spinal inflammation as measured by maximum apparent diffusion coefficient (spinal ADC max) (B = 0.27; P = .03) and mean ADC (spinal ADC mean) (B = 0.30; P = .004), lower modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) (B = –0.12; P = .02), more tender joint count (B = 0.12; P = .02), and fewer inflammatory back pain (IBP) (OR = 0.26; P < .001).Axial SpA with late onset had higher clinical disease activity, higher intensity of spinal MRI inflammation, less radiographic damage, and more tender joint count. There was also less inflammatory back pain, which could make the diagnosis more difficult.

CRP Serum Levels Are Associated with High Cardiometabolic Risk and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) patients have a higher frequency of cardiovascular risk factors such as high C-reactive protein (CRP) levels than the general population. CRP is considered a cardiovascular disease marker that could be related to SLE clinical disease activity. This study aimed to assess the association between CRP with cardiometabolic risk and clinical disease activity in SLE patients. A comparative cross-sectional study was conducted in 176 female SLE patients and 175 control subjects (CS) with median ages of 38 and 33 years, respectively; SLE patients were classified by the 1997 SLE-ACR criteria, and the clinical disease activity by the Mexican-SLEDAI (Mex-SLEDAI). CRP and lipid profile (triglycerides, cholesterol, HDL-C, and LDL-C) were quantified by turbidimetry and colorimetric-enzymatic assays, respectively. SLE patients had higher CRP levels than CS (SLE: 5 mg/L vs. CS = 1.1 mg/L; p < 0.001). In SLE patients, CRP levels ≥ 3 mg/L were associated with a higher risk of cardiometabolic risk status assessed by LAP index (OR = 3.01; IC: 1.04–8.7; p = 0.04), triglycerides/HDL-C index (OR = 5.2; IC: 2.1–12.8; p < 0.001), Kannel index (OR = 3.1; IC: 1.1–8.1; p = 0.03), Castelli index (OR = 6.6; IC: 2.5–17.8; p < 0.001), and high clinical disease activity (OR = 2.5: IC: 1.03–6.2; p = 0.04; and β coefficient = 5.8; IC: 2.5–9.4; R2 = 0.15; p = 0.001). In conclusion, high CRP levels were associated with high cardiometabolic risk and clinical disease activity in SLE patients.

Treatment of rheumatoid arthritis after regression of lymphoproliferative disorders in patients treated with methotrexate: a retrospective, multi-center descriptive study.

To identify the optimal treatment for rheumatoid arthritis (RA) after the regression of lymphoproliferative disorders (LPDs). The subjects were 232 patients with RA who developed LPD between 2000 and 2017 at seven hospitals participating in the LPD-WG study. Kaplan-Meier and Cox proportional regression analyses were performed to determine the factors associated with the rate of LPD relapse and the retention of biological disease-modifying antirheumatic drugs (bDMARDs). Treatment for RA was resumed in 138 patients after spontaneous regression of LPD after the discontinuation of methotrexate and in 52 patients after chemotherapy for LPD (persistent-LPD). LPD relapses occurred in 23 patients. Not DMARDs use but Hodgkin's lymphoma was identified as a risk factor for LPD relapse. In 88 RA patients treated with bDMARDs [tocilizumab, 39 patients; abatacept 20 patients; tumor necrosis factor inhibitor, 29 patients], the one-year retention rate was 67.8%. The risk factors for discontinuation of bDMARDs were persistent-LPD, non-diffuse large B-cell lymphomas (non-DLBCL), and a high clinical disease activity index (CDAI). Tocilizumab showed the highest retention rate among bDMARDs, particularly in DLBCL. Although any bDMARD could be used in patients after LPD regression, effectiveness and risk for relapse should be carefully assessed for each LPD subtype.

Clinico-radiological dissociation of disease activity in MS patients: frequency and clinical relevance.

To investigate the prevalence and clinical relevance regarding disability progression in multiple sclerosis patients with a dissociation in clinical and radiological disease expression. We prospectively selected patients with early relapsing-remittingmultiple sclerosis (MS) or a clinically isolated syndrome (CIS) from the Amsterdam MS cohort. Patients underwent clinical examination at baseline, after 2years, 6years and a subset also after 11years, including the Expanded Disability Status Scale (EDSS), 25-foot walk test (25-FWT) and 9-hole peg test (9-HPT). Brain and spinal cord MRI scans were obtained at baseline and after 2years. Two years after baseline, patients with dissociation in their clinical and radiological disease progression were identified as: (1) patients with high clinical disease activity (defined by relapses) and low radiological disease activity (defined by white-matter lesions on T2-weighted imaging); or (2) patients with low clinical disease activity and high radiological disease activity. Binary logistic regression analyses were performed to predict disability progression after 6 and 11years of follow-up. Patients with low clinical and low radiological disease activity were used as the reference group. The prevalence of clinico-radiological dissociation was low (6.4% had high clinical and low radiological disease activity and 5.1% had a combination of low clinical and high radiological disease activity) compared to 88.5% of patients without a dissociation. Patients with a dissociation of clinical and radiological disease activity did not show a statistically significant difference in risk of disability progression after 6 and 11years. A clinico-radiological dissociation is rather a rare phenomenon in MS patients. The clinical relevance of such a dissociation regarding the prediction of disability progression is questionable.

P825 The impact of a SNP-dose–response effect on course of inflammatory bowel disease: a numerical analysis of SNP distribution within the Swiss IBD Cohort Study

Abstract Background Several large genome wide association studies have identified an increasing number of IBD risk loci with currently more than 240 established loci and generated robust data on disease association. However, knowledge remains limited on distinctive associations to specific clinical characteristics. The Swiss IBD Cohort Study (SIBDCS) represents a large prospective cohort study with clinically and phenotypically sound data collection since 2006 including genotyping. In this study, we aimed to determine individual associations of known risk loci with clinical features of patients in the SIBDCS, as well as their combined effect on clinical outcomes. Methods Based on 158 analysed SNPs, we investigated the numerical distribution of risk alleles and determined an individual SNP risk score (defined as percentage of risk alleles; i.e. number of risk alleles divided by twice the number of given SNPs multiplied with 100). We then performed linear regression modelling to investigate, whether relevant clinical disease characteristics associate with this SNP risk score. Further, for each given clinical outcome, a model was run with all SNPs as potential predictors, and the number of significant associations per SNP counted. Results In a total of 2304 genotyped patients, we observed a median number of risk alleles of 167, 168 and 167 for IBD overall, CD and UC/IC, respectively with a narrow inter quartile range [11 (q25 = 162, q75 = 173) for IBD and CD; 12 (q25 = 161, q75 = 173) for UC/IC]. A higher SNP risk score was significantly associated with any complications (defined as a composite of any or more of colorectal cancer, colon dysplasia, intestinal lymphoma, osteopenia/-porosis, anaemia, deep venous thrombosis, pulmonary embolism, nephro- or cholelithiasis, malabsorption syndrome, massive haemorrhage, perforation/peritonitis, pouchitis), stenosis in CD patients; pancolitis, conversion to CD, female sex in UC patients; higher clinical disease activity in both CD &amp; UC. Regarding individual SNPs, we identified substantial differences in terms of the frequency of associations to disease-related outcomes with up to 11 for rs4899554 in CD and 7 for rs9557195 in UC, respectively. Conclusion In our large population of IBD patients there is high per patient frequency of hetero- and homozygous SNP risk alleles. The association of higher SNP risk score with several disease-related outcomes indicates a potential interplay of per patient given SNP risk alleles.

User stories as lightweight requirements for agile clinical decision support development.

ObjectiveWe sought to demonstrate applicability of user stories, progressively elaborated by testable acceptance criteria, as lightweight requirements for agile development of clinical decision support (CDS).Materials and MethodsUser stories employed the template: As a [type of user], I want [some goal] so that [some reason]. From the “so that” section, CDS benefit measures were derived. Detailed acceptance criteria were elaborated through ensuing conversations. We estimated user story size with “story points,” and depicted multiple user stories with a use case diagram or feature breakdown structure. Large user stories were split to fit into 2-week iterations.ResultsOne example user story was: As a rheumatologist, I want to be advised if my patient with rheumatoid arthritis is not on a disease-modifying anti-rheumatic drug (DMARD), so that they receive optimal therapy and can experience symptom improvement. This yielded a process measure (DMARD use), and an outcome measure (Clinical Disease Activity Index). Following implementation, the DMARD nonuse rate decreased from 3.7% to 1.4%. Patients with a high Clinical Disease Activity Index improved from 13.7% to 7%. For a thromboembolism prevention CDS project, diagrams organized multiple user stories.DiscussionUser stories written in the clinician’s voice aid CDS governance and lead naturally to measures of CDS effectiveness. Estimation of relative story size helps plan CDS delivery dates. User stories prove to be practical even on larger projects.ConclusionsUser stories concisely communicate the who, what, and why of a CDS request, and serve as lightweight requirements for agile development to meet the demand for increasingly diverse CDS.

Are key cytokines genetic and serum levels variations related to rheumatoid arthritis clinical severity?

This study evaluated the possible association between SNPs in cytokines coding genes, namely IL10, IL6 and IFNG, cytokines serum levels and clinical assessment' scores in patients with Rheumatoid Arthritis(RA). SNPs genotyping was performed in 126 RA patients and 177 healthy individuals with Taqman probes specific for IL10 -1082 (T>C, rs1800896);INFG -1616 (A>G, rs2069705) and IL6 -174 (G>C, rs1800795) variants,positioned in regulatory regions. Cytokine Bead Array (CBA) was used to measure cytokine levels. We found association between INFG -1616 G allele(p = 0.0210; OR = 1.605) and INFG -1616 GG genotype (p = 0.0268; OR =2.609) and RA susceptibility. We also observed association between IL10 -1082 TT genotype and high clinical disease activity index (CDAI) values (p = 0.026; OR = 1.906; 95% CI = 1.082 - 3.359), IL10 -1082 CC genotype and low CDAI values (p = 0.016; OR = 0.256) and INFG -1616 AA and high CDAI values (p = 0.025; OR = 2.919). IL10 -1082 CC also exhibited the lowest IL-10 levels than IL10 -1082 TT (p = 0.020) and IL10 -1082 TC (p = 0.032). Finally, we verified higher IL-6 value in the RA patients than healthy control group (p = 0.007) and an association between high IL-6 levels and increased CDAI (r = 0.4648, p = 0.0015); DAS 28 (r = 0.3933, p= 0.0091), presence of bone erosions (r = 0.3170, p = 0.0361), ESR levels(r = 0.3041, p = 0.0448) and IFN-γ levels (r = 0.3049, p = 0.0468).Altogether, we suggest that IL10 -1082 (T>C, rs1800896) and INFG -1616(A>G, rs2069705) polymorphisms as well as IL-6 levels alterations may play a role for prognostic and disease follow-up.

The Efficacy and Safety of Infliximab in Pediatric Crohnʼs Disease in China

BACKGROUND: Few studies have examined the efficacy and safety of infliximab (IFX) in pediatric Crohn's disease (CD) in China. This study aimed to investigate the response and remission rate of IFX, as well as the associated adverse events. METHODS: We collected data from CD patients who had received IFX 2 or more times from three hospitals in Shanghai from January 2007 to December 2016. The efficacy of IFX was observed, as well as the adverse events, relapse rate and retreatment efficacy. The overall risk factors related to IFX were also evaluated. RESULTS: Eighty-six patients participated in the study. With treatment, the patients demonstrated improved growth and nutrition indices and decreased disease activity. The clinical response rate was 91.9% and 88.2% at weeks 10 and 34, respectively. The sustained remission rates were 69.8% and 67.6% at weeks 10 and 34, respectively. The mucous healing rate was 19.3% at week 10 and 25.7% at week 34. Finally, 45 patients (66.2%) demonstrated durable responses, and 23 (33.8%) showed complete LOR. Adverse events related to IFX occurred in 55.8% of the patients, including allergic reactions in 17.4% and infections in 41.9%. Univariate analysis showed that a high pediatric clinical disease activity index score prior to IFX administration was a risk factor for IFX LOR. Continuation of concomitant azathioprine beyond induction was a protective factor for durable response. CONCLUSION(S): IFX is an effective treatment for CD in Chinese children; however, adverse events can occur. A comprehensive evaluation must be performed before each IFX infusion.

Correlation Between the Oral Manifestations of Rheumatoid Arthritis Patients on Different Treatments with The Clinical Disease Activity

Objective:Toevaluate the oral findings and correlating the oral findings with the clinical disease activity index. Subjects, Materials and Methods:This cross- sectional studyincludedeighty-five rheumatoid arthritis patients. Twenty-five patients were on Methotrexate, thirty patients on Etanercept and thirty patients were on a combination of Methotrexate and Etanercept. Each patient was examined to calculate the clinical disease activity index and to detect any oral finding. Results: The highest summation of rheumatoid arthritis patients was presented with a high clinical disease activity index, while the number of those with low disease activity index was the lowest. Oral dryness showed to be the most common oral findings (60%) followed by tempromandibular joint disorders (31.8%) then aphthous ulcerations (9.4%) and glossitis (5.8%), while the lichenoid drug reaction, angular chelitis and geographic tongue were the less commonly seen findings (1.1% for each). Most of the oral findings were seen in patients treated with Etanercept or Methotrexate alone, while the patients treated with a combination of them had less oral side effects. A higher number of rheumatoid arthritis patients with oral findings were showing high and moderate disease activity. Conclusions: The oral dryness, tempromandibular joint disorders and aphthous ulcerations were the main oral manifestations found in rheumatoid arthritis patients. Angular chelitis positively correlate with the increasing in

The management of multiple sclerosis by reference centers in south of Italy: a 2011 survey on health demands and needs in Campania region.

This cross-sectional study has investigated the diagnostic and therapeutic management of patients suffering from multiple sclerosis (MS) in the Campania Region (Italy). A survey involving all the reference centers for MS in Campania Region was conducted from March to August 2011. Centers responded to a web-administered questionnaire on management and clinical characteristics of MS patients. In the study period, 3263 patients (mean age 37 years, 66 % females) accessed the centers. Patients received a first diagnosis of MS in 161 cases (4.9 %). About 37 % of the subjects without a previous diagnosis came to the centers on their own initiative. All patients underwent a complete neurological examination and expanded disability status scale. The other most common investigations were magnetic resonance imaging (44.0 %) and evoked potentials (22.1 %). The number of treated patients was 2797 (87.1 %). The most used drugs were interferon β and glatiramer acetate. The time between diagnosis and initiation of therapy exceeded 6 months in 32 % of cases. Second-line drugs were under-used: 16 % of patients who might benefit from them show high clinical and radiological disease activity despite treatment with immunomodulant drugs. The MS care management of the surveyed centers showed consistent margins for improvement in 2011. Even though these data do not represent the current situation, they can be used to monitor improvements in MS care.

SAT0116 What Drives the RAPID Increase in Risk of Acute Coronary Syndrome following RA Diagnosis?

BackgroundThe risk of cardiovascular disease (CVD) is increased in RA patients. We have previously reported a rapid increase in risk of acute coronary syndromes (ACS) following RA diagnosis. Despite known...