miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1

Antimicrobial responses play an important role in maintaining intestinal heath. Recently we reported that miR-511 may regulate TLR4 responses leading to enhanced intestinal inflammation. However, the exact mechanism remained unclear. In this study we investigated the effect of miR-511 deficiency on anti-microbial responses and DSS-induced intestinal inflammation. miR-511-deficient mice were protected from DSS-induced colitis as shown by significantly lower disease activity index, weight loss and histology scores in the miR-511-deficient group. Furthermore, reduced inflammatory cytokine responses were observed in colons of miR-511 deficient mice. In vitro studies with bone marrow-derived M2 macrophages showed reduced TLR3 and TLR4 responses in miR-511-deficient macrophages compared to WT macrophages. Subsequent RNA sequencing revealed Wdfy1 as the potential miR-511 target. WDFY1 deficiency is related to impaired TLR3/TLR4 immune responses and the expression was downregulated in miR-511-deficient macrophages and colons. Together, this study shows that miR-511 is involved in the regulation of intestinal inflammation through downstream regulation of TLR3 and TLR4 responses via Wdfy1.

Baseline predictors of different types of treatment success in rheumatoid arthritis

ObjectiveTo perform a comprehensive analysis on predictors of achieving disease activity outcomes by change, response and state measures.MethodsWe used data from three rheumatoid arthritis (RA) trials (one for main analysis, two for validation) to analyse the effect of patient and disease characteristics, core set measure and composite indices on the achievement of different outcomes: response outcomes (% of patients achieving a relative response margin); state outcomes (remission or low disease activity, LDA) and change outcomes (numerical change on metric scales).ResultsWe included patients from the ASPIRE trial (for analysis) and from the ATTRACT and GO-BEFORE trials (for validation). While lower disease activity components at baseline—except acute phase reactants—were associated with achievement of state outcomes (such as LDA by the Simplified Disease Activity Index, SDAI), higher baseline values were associated with change outcomes (such as SDAI absolute change). A multivariate analysis of the identified predictors of state outcomes identified best prediction by a combination of shorter disease duration, male gender and lower disease activity. For prediction of response, no consistently significant predictors were found, again, with exception of C reactive protein, for which higher levels at baseline were associated with better responses.ConclusionPrediction of treatment success is limited in RA. Particularly in early RA, prediction of state targets can be achieved by lower baseline levels of diseases activity. Gender and disease duration may improve the predictability of state targets. In clinical trials, included populations and choice of outcomes can be coordinated to maximise efficiency from these studies.

Medication adherence and persistence of psoriatic arthritis patients treated with biological therapy in a specialty pharmacy in Brazil: a prospective observational study

Background: Pharmaceutical services in Brazil provide access, supply, and rational use of drugs for all population and an effort has been made to improve the quality of these services. Biological drugs are high-cost drugs supplied in Brazil that can inhibit disease progression and improve the quality of life of psoriatic arthritis (PsA) patients. However, some patients did not achieve therapeutic goals. Objective: To evaluate the medication adherence and persistence of PsA patients treated with tumor necrosis factor inhibitors (anti-TNF) drugs and their associated factors. Methods: A prospective observational study was performed at a single-specialty pharmacy in Belo Horizonte, Brazil. Medication adherence, persistence, and clinical outcomes were evaluated at 12 months of follow-up. Medication persistence was historically compared to overall PsA patients treated in Brazil. Associated factors were identified through log-binomial regression. Results: One hundred ninety-seven PsA patients were included in the study, of whom 147 (74.6%) and 142 (72.1%) had medication adherence and persistence, respectively. Patients treated with infliximab presented the highest adherence (90.5%) and persistence rate (95.2%) in comparison to patients treated with other drugs, except for adalimumab versus infliximab for adherence outcome. All clinical measures significantly improved in patients with medication adherence and persistence. Medication persistence was higher for patients attended by specialty pharmacy than other PsA patients in Brazil. The associated factors to higher medication adherence were lower disease activity by BASDAI, being non-white race, and intravenous drug use. The associated factors to higher medication persistence were lower disease activity by Bath Ankylosing Spondylitis Activity Index (BASDAI), intravenous drug use, non-use of corticoids and non-steroidal anti-inflammatory drugs, and comorbidity. Conclusions: Patients with medication adherence and persistence had significant improvements in clinical measures, functionality, and quality of life. High medication adherence and persistence to biological therapy were observed and associated with lesser disease activity at baseline. Also, medication persistence to PsA patients attended in specialty pharmacy was higher than the overall PsA population in Brazil, which indicates the importance of pharmaceutical services to provide health care and promote the effectiveness and safety of biological therapies.

The effects of pregnancy on relapse rates, disability and peripartum outcomes in women with multiple sclerosis: a systematic review and meta-analysis

Background: Although previous cohort studies of women with multiple sclerosis (MS) yielded a reduction in relapse rate during pregnancy, the effect size has not been quantified in a comprehensive manner. In addition, the effects on disability progression and peripartum outcomes have been controversial. The purpose of this work is to assess the effect of pregnancy on disease activity, and to assess the effects of MS on pregnancy as well. Materials & methods: We searched in PubMed, Cochrane Library and EMBASE for cohort studies dealing with the effects of pregnancy on relapse rates, disability progression and peripartum outcomes in women with MS. The evaluated outcomes were: changes in the annualized relapse rate (ARR) in pregnancy and puerperium, disability worsening compared with the year before pregnancy, and peripartum outcomes, which were compared with the ones of non-MS women. In the majority of cohorts included here, the women were not under disease modifying therapies during pregnancy. Results: We found 23 cohort studies measuring changes in the ARR during pregnancy and puerperium; 12 were prospective and 11 retrospective. In 17 cohorts there was significant reduction in the ARR during pregnancy compared with prepregnancy period. The pooled mean reduction in the ARR was -0.5 (95% CI: 0.67–0.38), p < 0.001, from 15 cohorts included in meta-analysis. In 18 cohorts the ARR increased in the 3-month puerperium relative to prepregnancy year period; the pooled mean increase in the ARR was 0.22 (95% CI: 0.11–0.33), p < 0.001, from 14 cohorts included in meta-analysis. Disability worsening was addressed in 18 cohorts, and in 14 of them there were no significant changes. Peripartum complications and obstetrical outcomes were assessed in 16 cohorts, of whom 13 were retrospective, without finding significant differences. Conclusion: Pregnancy is associated with lower disease activity, and puerperium with higher disease activity. Disability does not change significantly after pregnancy. The obstetrical outcomes are not very different from those of non-MS women in most cohorts.

Youth with multiple sclerosis have low levels of fitness

Background: Moderate and vigorous physical activity is associated with improved outcomes in youth with multiple sclerosis (MS). Physical fitness may also influence disease and health outcomes in this population. Objectives: To determine if there were differences in physical fitness between youth with MS and healthy controls (HC). To examine relationships between physical fitness, physical activity (PA) level, fatigue, depression and disease activity in youth with MS and HC. Methods: Youth with MS ( n = 19) and HC ( n = 21) completed tests establishing cardiorespiratory-fitness (VO2peak), endurance via 2-minute walk test, and musculoskeletal strength via grip strength (GS). Questionnaires determined fatigue, depression, and PA levels. Weekly PA level was determined by accelerometry. Tests of differences and correlational analyses were used to evaluate physical fitness. Results: Youth with MS had lower VO2peak ( U = 279, p < 0.0001), endurance ( t = 2.6, p = 0.02), and higher body mass index (BMI) ( t = -5.9, p = 0.001) than HC. Higher VO2peak was associated with higher moderate to vigorous PAaccelerometer in HC (Spearman-Rho = 0.5, p = 0.03), but not in youth with MS (Spearman-Rho = 0.5, p = 0.06). Lower VO2peak and GS were associated with higher disability (Spearman-Rho = -0.6, p = 0.03) and relapses in MS (Spearman-Rho = -0.52, p = 0.04). Conclusions: Youth with MS have lower levels of fitness, compared with HC. Higher levels of fitness were associated with lower disease activity and disability in youth with MS.

Combination therapy in rheumatoid arthritis

The therapeutic armamentarium available for treatment of rheumatoid arthritis (RA) has changed significantly over the past 30 years, transforming the therapeutic landscape and prognosis for a substantial proportion of patients with RA. Combination therapies represent an important therapeutic paradigm for management of rheumatoid arthritis. The rationale for combination therapies is clear and demonstrated to bring treatment benefit to patients achieving lower disease activity scores and reduced radiologic progression according to ‘treat-to-target’ principles. A rigorous evidence-based debate is required involving not only parameters related to disease activity scores and radiologic progression, but related to the cost-effectiveness analysis of using many of these newer agents compared to older csDMARDs. This chapter addresses the evidence related to the utilization of combination strategies for the management of RA as compared to monotherapy.

Treatment preferences in patients with axial spondyloarthritis

Background: One of the premises of the Treat to Target (T2T) is the shared treatment decision between the rheumatologist and the patient. For this reason, patient preferences play a fundamental role in the success of treatment in the short and long term. The aims of this study were to evaluate the treatment preferences of patients with Axial Spondyloarthritis (axSpA) and to identify the factors associated with their choice. Material and methods: Cross sectional study. Patients ≥18 years old that fulfilled the ASAS 2009 criteria for axSpA were included. Sociodemographic data, comorbidities, disease characteristics, and treatments received were recorded. A specially designed questionnaire in both, multiple choice modality and response mode listed in order of priority of the statements was administered. Statistical analysis: Descriptive statistics. Student’s T-test, Chi2 test and multiple logistic regression analysis. A value of p <0.05 was considered significant. Results: Seventy patients were included with a median age (m) of 46.5 years (IQR: 38-57), 55 males (78.6%) and a median disease duration of 13.5 years (IQR: 7.75-23.25). The relevant aspects for choosing a treatment were: the ability to improve the quality of life (32.9%), followed by improvement in joint inflammation (22.9%), pain (21. 4%) and physical function (14.3%). The chosen administration routes in decreasing order of frequency were: oral (51.4%), subcutaneous (SC) (41.4%), intramuscular (IM) 4.3% and intravenous (IV) 2.9%. The preferred frequency of oral administration was one tablet per week (61.1%) and SC administration, once a month (34.5%). The choice of oral route was associated with: preference for self-administration, preference for receiving the medication at home and higher level of education. The choice of the SC route was independently associated with the type of axSpA (AS) and a lower educational level. The patients under biological SC treatment and with lower disease activity, showed higher level of treatment satisfaction. Conclusion: The most preferred way of administration by patients with axSpA was the oral route. Lower disease activity and SC biological treatment were associated with treatment greater compliance.

High Levels of Psychological Resilience Associated With Less Disease Activity, Better Quality of Life, and Fewer Surgeries in Inflammatory Bowel Disease

Background Stress and depression are risk factors for inflammatory bowel disease (IBD) exacerbations. It is unknown if resilience, or one’s ability to recover from adversity, impacts disease course. The aim of this study was to examine the association between resilience and IBD disease activity, quality of life (QoL), and IBD-related surgeries. Methods We performed a cross-sectional study of IBD patients at an academic center. Patients completed the Connor-Davidson Resilience Scale questionnaire, which measures resilience (high resilience score ≥ 35). The primary outcome was IBD disease activity, measured by Mayo score and Harvey-Bradshaw Index (HBI). The QoL and IBD-related surgeries were also assessed. Multivariate linear regression was conducted to assess the association of high resilience with disease activity and QoL. Results Our patient sample comprised 92 patients with ulcerative colitis (UC) and 137 patients with Crohn disease (CD). High resilience was noted in 27% of patients with UC and 21.5% of patients with CD. Among patients with UC, those with high resilience had a mean Mayo score of 1.54, and those with low resilience had a mean Mayo score of 4.31, P &lt; 0.001. Among patients with CD, those with high resilience had a mean HBI of 2.31, and those with low resilience had a mean HBI of 3.95, P = 0.035. In multivariable analysis, high resilience was independently associated with lower disease activity in both UC (P &lt; 0.001) and CD (P = 0.037) and with higher QoL (P = 0.016). High resilience was also associated with fewer surgeries (P = 0.001) among patients with CD. Conclusions High resilience was independently associated with lower disease activity and better QoL in patients with IBD and fewer IBD surgeries in patients with CD. These findings suggest that resilience may be a modifiable factor that can risk-stratify patients with IBD prone to poor outcomes.

Inflammatory hallmarks of lesser prominence in psoriatic arthritis patients starting biologics: a Nordic population-based cohort study

Objectives To assess secular trends in baseline characteristics of PsA patients initiating their first or subsequent biologic DMARD (bDMARD) therapy and to explore prescription patterns and treatment rates of bDMARDs from 2006 to 2017 in the Nordic countries. Methods PsA patients registered in the Nordic rheumatology registries initiating any treatment with bDMARDs were identified. The bDMARDs were grouped as original TNF inhibitor [TNFi; adalimumab (ADA), etanercept (ETN) and infliximab (IFX)]; certolizumab pegol (CZP) and golimumab (GOL); biosimilars and ustekinumab, based on the date of release. Baseline characteristics were compared for the five countries, supplemented by secular trends with R2 calculations and point prevalence of bDMARD treatment. Results A total of 18 089 patients were identified (Denmark, 4361; Iceland, 449; Norway, 1948; Finland, 1069; Sweden, 10 262). A total of 54% of the patients were female, 34.3% of patients initiated an original TNFi, 8% CZP and GOL, 7.5% biosimilars and 0.3% ustekinumab as a first-line bDMARD. Subsequent bDMARDs were 25.2% original TNFi, 9% CZP and GOL, 12% biosimilars and 2.1% ustekinumab. From 2015 through 2017 there was a rapid uptake of biosimilars. The total of first-line bDMARD initiators with lower disease activity increased from 2006 to 2017, where an R2 close to 1 showed a strong association. Conclusion Across the Nordic countries, the number of prescribed bDMARDs increased from 2006 to 2017, indicating a previously unmet need for bDMARDs in the PsA population. In recent years, PsA patients have initiated bDMARDs with lower disease activity compared with previous years, suggesting that bDMARDs are initiated in patients with a less active inflammatory phenotype.

AB0349 EFFICACY OF TOFACITINIB THERAPY, DEPENDING ON THE USE OF DMARDS IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A REAL CLINICAL PRACTICE IN RUSSIAN FEDERATION.

Background:Objectives:To evaluate how disease-modifying antirheumatic drugs (DMARDs) affects efficacy of tofacitinib (TOFA) therapy in patients with rheumatoid arthritis (RA).Methods:We analyzed the history of 107 patients (mean age 51,4±12,1 yrs) with RA according to the 2010 ACR/EULAR criteria, from 11 regions Russian Federation, including patients who were treated at the V.A. Nasonova Research Institute of Rheumatology. These patients were non-responders to DMARDs, previously biologic therapy and were treated with TOFA in combination with DMARDs or without. 107 patients (77 woman (72%),tested positive for ACCP (76.5%)/RF (87.3%), the median disease duration was 7,5±6,6 years; the mean DAS28 score was 5,8±1,0, mean SDAI and CDAI score was 35,6±13,4 and 32,1±12,4 respectively) received TOFA for 12 months. TOFA therapy was started in all patients in dose 5 mg BID per os with escalation to 10 mg BID in 17,6% pts.Results:The use of TOFA was accompanied by a decrease in the disease activity after 6 and 12 months of therapy. All patients were divided into 3 groups, depending on DMARDs therapy: TOFA+ methotrexate (MTX), TOFA+ another DMARDs (leflunomide, hydroxychloroquine, azathioprine), mono-therapy of TOFA. The dynamic of the disease activity in 3 groups is presenting on the table below:Table 1.AOutcome of contributory AEs/SAE at close of follow-up.BSAEs classified as ‘expected’. DLT: dose limiting toxicity; N+V: nausea, vomiting.ParametersWeeksTOFA+MTX(n=69)TOFA+ another DMARDs (n=20)TOFA monotherepy (n=18)DAS28 (ESR)baseline5,9 ±1,05,6±1,16,0±0,86 months3,5±1,2*4,1±1,1*4,2±1,6*12 months3,3±1,0*3,5±1,3*3,8±1,2*SDAIbaseline36,2±14,232,6±9,535,3± 10,36 months14,4± 10,7*16,7± 10,2*27,3±19,1*12 months9,5±8,0*12,9± 8,6*15,3±10,2*CDAIbaseline32,4±12,129,7±8,933,2±9,86 months13,3±10,2*15,6±9,8*22,4±16,8*12 months8,7±7,6*12,6±8,2*14,4±9,6**p<0,05Patients who received TOFA with MTX had lower disease activity during the therapy. Patients on mono-therapy of TOFA had higher disease activity according to DAS28, SDAI, CDAI.Conclusion:Tofacitinib is effective ts-DMARDs for active rheumatoid arthritis on the Russian population. It shows better efficacy in combination with methotrexate, than in combination with another DMARDs (leflunomide and other) or in mono-therapy.Disclosure of Interests:None declared