Low Disease Activity Score Research Articles

B-103 Correlation of Novel Markers, Anti-Sa (Citrullinated Vimentin) and Anti-CarP (Carbamylated Protein), with High Vectra® DA Disease Activity Scores in Rheumatoid Arthritis (RA)

Abstract Background Citrullination and carbamylation are post-translational modifications where autoantibodies against citrullinated and carbamylated proteins in RA have been associated with more aggressive disease. At the same time, Vectra® DA is blood test that yields a RA disease activity score from 1 to 100. Here, 120 patient samples were analyzed to assess the relationship of disease activity as measured by Vectra® score and the presence of Anti-Sa (Citrullinated Vimentin) and Anti-CarP (Carbamylated Protein). Methods Serum samples were analyzed for Vectra® DA (which is validated for adults with RA) where 12 biomarker measurements (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, YKL-40, Leptin, Resistin, SAA, CRP) together with patient age, gender and adiposity are used to generate a score where established categories are low for 1 to 29, moderate for 30 to 44, and high for 45 to 100. Anti-Sa and Anti-CarP were by ELISA lab-developed tests (LDT) with a cut-off for positive of >20 Units (U). Results Anti-Sa and Anti-CarP for 40 samples from each Vectra® DA category are reported. Patients with the highest Vectra® scores (mean 58.2, range 46.8 - 87.5) had highest rates of positivity for Anti-Sa (52.5%) and Anti-CarP (35%). In contrast, the group with the lowest Vectra® scores (mean 11.8, range 3.8 - 18.1) were infrequently positive for Anti-Sa (17.5%) and Anti-CarP (0%). Frequencies with moderate Vectra® scores (mean 37.1, range 32.4 - 41.8) were mid-range: Anti-Sa (25%) and 7.5% for Anti-CarP (7.5%). Of note, positivity of Anti-Sa was analytically stronger, i.e. higher titer, in patients with moderate or high Vectra® (mean 90.0U or 81.7U), compared to values seen in those with low Vectra® (mean 60.4 U). Conclusions Our analysis of 120 patient samples demonstrates that high disease activity as determined by Vectra® DA corresponds to higher positivity of novel autoantibody markers, Anti-Sa and Anti-CarP. High Vectra® DA scores (>44) are associated with a 20% 1-year risk of radiographic progression while low scores (<30) carry only a 1% risk. Here, we found that patients with high Vectra® scores were 3 times more likely to test positive for Anti-Sa than those with low disease activity scores. At the same time, Anti-CarP occurred in high frequency (35%) with high Vectra® in contrast to zero positivity observed with low Vectra® scores. Thus, our findings support Anti-CarP’s reported association with more active disease with higher risk of developing joint erosions. Also of note, patients with high Vectra® scores had particularly high Anti-Sa positivity - both a 52.5% positivity rate as well as higher Anti-Sa levels (titers) than the group with lower Vectra® scores. These data corroborate other studies where Anti-Sa not only predicted more aggressive, rapid disease progression, but its titers correlated with clinical measures of disease activity. Taken together, our data support the consistency and clinical usefulness of the Vectra® score along with novel autoantibody markers, Anti- Anti-Sa and Anti-CarP, in order to assess RA severity, prognosis, and patient-specific treatment strategies.

Inhibition of influenza virus infection in mice by pulmonary administration of a spray dried antiviral drug

Increasing resistance to antiviral drugs approved for the treatment of influenza urges the development of novel compounds. Ideally, this should be complemented by a careful consideration of the administration route. 6′siallyllactosamine-functionalized β-cyclodextrin (CD-6′SLN) is a novel entry inhibitor that acts as a mimic of the primary attachment receptor of influenza, sialic acid. In this study, we aimed to develop a dry powder formulation of CD-6′SLN to assess its in vivo antiviral activity after administration via the pulmonary route. By means of spray drying the compound together with trileucine, a dispersion enhancer, we created a powder that retained the antiviral effect of the drug, remained stable under elevated temperature conditions and performed well in a dry powder inhaler. To test the efficacy of the dry powder drug against influenza infection in vivo, infected mice were treated with CD-6′SLN using an aerosol generator that allowed for the controlled administration of powder formulations to the lungs of mice. CD-6′SLN was effective in mitigating the course of the disease compared to the control groups, reflected by lower disease activity scores and by the prevention of virus-induced IL-6 production. Our data show that CD-6′SLN can be formulated as a stable dry powder that is suitable for use in a dry powder inhaler and is effective when administered via the pulmonary route to influenza-infected mice.

Spirituality is associated with immune parameters and disease activity in primary Sjögren’s syndrome: a cross-sectional study

The role of spirituality in health and disease is a complex and emerging area of research. Incorporating spirituality into the bio-psycho-social model of health and disease leading to the bio-psycho-social-spiritual model provides a more comprehensive framework. In this context, chronic disorders like primary Sjögren’s syndrome (pSS) are of interest due to their intricate interactions between biological, psychological, and spiritual factors. This study explored the relationship between spirituality, immune parameters, and disease activity in pSS patients. Data from 108 patients were analyzed, including self-assessed spirituality (answering to direct questions and completing the Spiritual Transcendence Scale), immunological parameters and disease activity scores. The findings revealed several associations. Individuals with spiritual attitudes or engaged in regular prayer/meditation showed lower serum levels of autoantibodies specific to pSS and lower disease activity scores. Spiritual engagement was also linked to decreased perceived skin and tracheal dryness, suggesting potential benefits for physical symptoms. These findings suggest that spirituality may play a significant role in modulating immune responses and disease activity in pSS patients. The study underscores the importance of considering spirituality as an integral part of the holistic approach to health and disease, further expanding the understanding of the interconnectedness of biological, psychological, and spiritual dimensions.

Baixo estado de atividade da doença e avaliação de dano permanente em pacientes ambulatoriais com lúpus eritematoso sistêmico

ObjectiveVerify the association between low disease activity and damage accrual in Systemic Lupus Erythematosus patients.MethodsWe evaluated 60 patients following the Rheumatology Out patient Clinic with American College of Rheumatology and European League Against Rheumatism of Systemic Lupus Erythematosus diagnostic criteria. We evaluated clinical and demographic data like gender, age, and disease duration. We evaluated disease activity using the Systemic Lupus Erythematosus Low disease activity score, and damage accrual we evaluated using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. The Chi-Square test realized statistical analysis, and a level of 0.05 was considered significant.ResultsOn 60 patients studied, we found lupus low disease activity state in 45 (75%) and 15 (25%) were in disease activity. Concerning damage accrual, we found that 11 (42.3%) had damage, and 40 (66,6%) did not have damage. Five patients with damage did not have disease activity, and 40 with no activity did not have damage. Of patients with disease activity, 11 we found with damage, and no damage was found in nine. Females predominate in this population with 98.3% of patients; the mean age was 43.4 years old, and the mean disease duration was 12.8 years. The statistical analysis results showed an association between low disease activity and no damage accrual in SLE patients (p<0.005).ConclusionOur results demonstrated an association between low disease activity and no damage accrual in systemic lupus erythematosus patients.

P873 Ustekinumab Real World Evidence Study (UndieS): Assessing the suitability of patients treated in routine clinical care for participation in the pivotal phase 3 clinical trial

Abstract Background Phase 3 randomised controlled trials (RCTs) are recognised as the gold standard for measuring the efficacy of new medicines and are essential for licensing new products. To maximise internal validity, RCTs recruit a highly selected, carefully defined group of participants, whereas patients treated in routine practice are much more heterogeneous. We set out to describe the real-world use of ustekinumab and assess the proportion of treated patients who would have been eligible for the relevant registration studies. Methods UndieS is a UK-based, multicentre, prospective, observational study investigating the effectiveness of ustekinumab in 593 Crohn’s disease patients. Objective evidence of active Crohn’s disease (biochemical or endoscopic) and/or failure or intolerance to another therapy were the only entry criteria. Within the limits of the study, we compared participants’ characteristics with the eligibility requirements of the UNITI clinical trial programme. The pragmatic modified Harvey-Bradshaw Index (mHBI), shown to correlate to CDAI score, was used in UndieS. No endoscopic follow up information was collected. Results 82% of patients treated in this real-world study would not have been eligible for participation in the UNITI programme. Eight RCT eligibility criteria would each be expected to exclude at least 10% of the real-world patient population (figure 1). A low disease activity score was the eligibility criterion most frequently expected to render UndieS participants ineligible for the UNITI programme with 61% of predicted CDAI scores (i.e. estimated from mHBI) falling below the threshold for RCT eligibility, despite 80% of those treated having objective evidence of inflammation and 55% failed/ were intolerant to an alternative therapy. Only 13% of participants were using corticosteroids at baseline. 59% of UndieS participants had previously failed or been intolerant to at least one anti-TNFα medication. For those who would have been ineligible for the RCT based on laboratory tests, an elevated ALT was the commonest abnormality among UndieS participants. The requirements for multiple venepunctures and pregnancy avoidance were the most relevant impediments for UndieS patients, with 28% of females of childbearing potential not willing to agree to the specified conditions. Conclusion Within the limitations of this study, we have demonstrated a significant disparity between participants in phase 3 RCTs and patients treated in routine clinical care. This questions the applicability of efficacy studies to real world clinical practice. Data from high quality, observational studies should complement findings from RCTs to support decision makers. Future work will investigate whether outcomes differ according to RCT eligibility.

Non-Medical Switching from Tocilizumab to Sarilumab in Rheumatoid Arthritis Patients with Low Disease Activity, an Observational Study.

Tocilizumab and sarilumab are IL-6-receptor antagonists registered for rheumatoid arthritis (RA), with equal effectiveness and safety. Switching from tocilizumab to sarilumab could be a strategy to reduce injection burden, in case of drug shortages, and to reduce costs. This study therefore aims to investigate the effectiveness and safety of switching patients with RA with well-controlled disease under tocilizumab treatment to sarilumab. Patients with RA with low Disease Activity Score 28 (DAS28;-CRP < 2.9 or < 3.5 with clinical judgment), on stable dose tocilizumab (> 6 months) were offered to switch to sarilumab. Patients who switched and consented were followed for 6 months. Sarilumab was started at 200 mg and double the last tocilizumab interval. Co-primary outcomes at 6 months were (i) the 90% confidence interval (CI) of DAS28-CRP change from baseline compared with the non-inferiority margin of 0.6 and (ii) the 90% CI of the proportion of patients persisting with sarilumab, compared with a prespecified minimum of 70%. Of 50 invited patients, 25 agreed to switch to sarilumab, and 23 patients switched and were included. One patient was lost to follow-up immediately after inclusion, therefore 22 patients are included in the analyses. At 6 months, mean change in DAS28-CRP was 0.48 (90% CI: 0.11-0.87), compared with the non-inferiority margin of 0.6. Sarilumab persistence was 68% (90% CI: 51-82%, 15 out of 22 patients), compared with the prespecified minimum of 70%. Non-medical switching from tocilizumab to sarilumab in patients doing well on tocilizumab failed to show non-inferiority regarding disease activity and drug persistence.

Clinical validation of a multi-protein, serum-based assay for disease activity assessments in multiple sclerosis

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients.

Altered Circulating Follicular T Helper Cell Subsets and Follicular T Regulatory Cells Are Indicators of a Derailed B Cell Response in Lupus, Which Could Be Modified by Targeting IL-21R.

Systemic lupus erythematosus (SLE) is characterized by the breakdown of self-tolerance, the production of high-affinity pathogenic autoantibodies and derailed B cell responses, which indicates the importance of central players, such as follicular T helper (TFH) subsets and follicular T regulatory (TFR) cells, in the pathomechanism of the disease. In this study, we aimed to analyze the distribution of the circulating counterparts of these cells and their association with disease characteristics and B cell disproportions in SLE. We found that the increased percentage of activated circulating TFH (cTFH) and cTFR cells was more pronounced in cutaneous lupus; however, among cTFH subsets, the frequency of cTFH17 cells was decreased in patients with lupus nephritis. Furthermore, the decreased proportion of cTFH17 cells was associated with low complement C4 levels and high disease activity scores. We also investigated whether the blocking of the IL-21 receptor (IL-21R) with an anti-IL-21R monoclonal antibody inhibits the B cell response, since IL-21 primarily produced by TFH cells potentially promotes humoral immunity. We observed that anti-IL-21R inhibited plasmablast generation and immunoglobulin production. Our study demonstrated that, besides cTFR/cTFH imbalance, cTFH17 cells play a crucial role in SLE pathogenesis, and modulating cTFH-B cell interaction through the IL-21/IL-21R pathway may be a promising therapeutic strategy to suppress the pathological B cell response.

Impact of a hybrid medical care model in the rheumatoid arthritis patient-reported outcomes: A non-inferiority crossover randomized study

Objective Patients and physicians can naturally adopt hybrid healthcare models that combine face-to-face consultations with telemedicine. The study's objective was to compare the impact of two healthcare interventions, hybrid care modality and face-to-face consultation, on the patient-reported outcomes of rheumatoid arthritis patients, during the COVID-19 pandemic. Methods Consecutive outpatients reincorporated to a clinic previously in lockdown were invited to a non-inferiority, randomized study (October 2020–-May 2022). Patients were randomized to 6 months of face-to-face consultation or hybrid care modality (intervention period-1) and then the converse modality (intervention period-2). The primary outcome was disease activity/severity behavior (Routine Assessment of Patient Index Data 3). Additional patient-reported outcomes were disability (Health Assessment Questionnaire Disability Index), quality-of-life (World Health Organization quality of life questionnaire-brief version), adherence and satisfaction with medical care, and treatment recommendation. Sample size calculation established 55 patients/healthcare interventions. Results There were 138 patients invited to participate, 130 agreed and 121 completed their study participation. Sixty-one and 60 patients respectively, received face-to-face consultation and hybrid care modality over intervention period-1. Patients were primarily middle-aged females (90.1%), with (median, IQR) 12 (9–16) years of education, long-standing disease, working (62.8%), receiving disease-modifying anti-rheumatic drugs (96.7%), and corticosteroids (61.2%). Patients had low disease activity (median Routine Assessment of Patient Index Data 3: 2.7) and Health Assessment Questionnaire Disability Index score that translated into the absence of disability, while quality of life was compromised. Baseline characteristics were similar between patients assigned to each healthcare intervention. Differences in Routine Assessment of Patient Index Data 3 behavior were below the non-inferiority margin. Results considered the order in which patients received the intervention and baselines scores, and extended to the patient-reported outcomes left. Conclusions Hybrid care modality was non-inferior to in-person consultations in achieving patient-reported outcomes during the COVID-19 pandemic in rheumatoid arthritis patients.

Probability of Medication Intensifications in Rheumatoid Arthritis Patients With Low Disease Activity Scores on Their Patient-Reported Outcomes: A Medical-Records Review Study.

Patients with rheumatoid arthritis require frequent consultations to monitor disease activity and intensify medication when treatment targets are not met. However, because most patients are in remission during follow-up, it should be possible to reduce the number of consultations for them. Electronic patient-reported outcomes (ePROs) could be used to identify patients who meet their treatment goal and who could therefore be eligible to skip their visit. The aim of this study was to assess the probability that patients with low disease activity scores on their ePROs do not need a disease-modifying antirheumatic drug (DMARD) or steroid intensification in the first 2 weeks after completion of the ePROs. This medical-records review study compared results of ePROs answered during routine care with DMARD or steroid intensifications collected from anonymized electronic medical record at Reade. The primary outcome was the positive predictive value (PPV) of having a low disease activity score on an ePRO for not receiving a DMARD or steroid intensifications within 2 weeks. The 3 studied ePROs (and respective low disease activity outcome) were the Routine Assessment of Patient Index Data 3 (RAPID3) (score <2), Patient Acceptable Symptom State (PASS) (yes), and the flare question (no). The secondary aim of the study was to assess which combination of ePROs resulted in the best PPV for DMARD or steroid intensifications. Of the 400 randomly selected records, ultimately 321 were included (302 unique patients). The PPV of a RAPID3 <2, being in PASS, and a negative answer on the flare question were, respectively, 99%, 95%, and 83% to not receive a DMARD or steroid intensification within 2 weeks. The combination of a RAPID3 <2 and a negative flare question resulted in a PPV of 100%; this combination was present in 29% (93/321) of the total study population. The RAPID3, PASS, and flare question have a high diagnostic accuracy to identify individuals who will not receive a DMARD or steroid intensification in the following 2 weeks. The combination of the RAPID3 and flare question yielded the best combination of diagnostic accuracy and highest percentage of patients who could be eligible to skip a visit. These results suggest that accurate identification of patients who meet their treatment goal with ePROs is possible.

Does herpes simplex virus have a role in the pathogenesis of systemic lupus erythematosus in Egyptians?

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune mediated tissue damage affecting a wide range of organs. The pathogenesis of SLE is complex. Infectious agents, including viruses, can act as environmental triggers, inducing or promoting onset and exacerbations of autoimmune disease in genetically predisposed individuals. Viral infections may be involved in the pathogenesis of SLE. To date, there is no published data about role of herpes simplex virus (HSV) in pathogenesis of SLE in Egyptian population. This study was designed to investigate a possible role of HSV in pathogenesis of SLE and its relation to disease activity. This study included 90 SLE female patients and 83 apparently healthy age-matched female subjects. SLE disease activity was assessed using SLEDAI-2K score. Qualitative assessment of anti-HSV antibodies (HSV1/2 IgM and IgG) was performed using ELISA kits. There was no statistically significant difference in frequency of HSV1/2 IgG positive test between SLE patients (97.6%) and control subjects (94.4%). There was a statistically significant increase in frequency of HSV1/2 IgM positive test in SLE patients compared to control subjects (P < 0.001). There was no difference in the frequency of HSV1/2 IgM and HSV1/2 IgG positive test results between SLE patients with higher disease activity score (60% and 95.6%, respectively) and those with lower disease activity score (60% and 93.3%, respectively). High prevalence of HSV1/2 IgG antibodies was observed among Egyptians. The lack of significant difference in frequency of HSV1/2 IgG between SLE patients and control subjects may indicate that HSV is not involved in SLE pathogenesis. Also, HSV infection may have no role in SLE disease exacerbation due to the absence of significant difference in the frequency of HSV1/2 IgM and HSV1/2 IgG antibodies in SLE patients with higher disease activity compared to those with lower disease activity.

A4 HELMINTH-DERIVED METABOLITES INDUCE A TOLEROGENIC PROFILE IN DENDRITIC CELLS AND ALLEVIATE EXPERIMENTAL COLITIS

BackgroundInflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by abdominal pain, bloody diarrhea, fatigue, weight loss, and diminished quality of life. The morbidity associated with IBD is a result of loss of tolerance towards the gastrointestinal commensal microbiota. The high incidence of IBD in Western societies is inversely correlated with the low incidence of intestinal helminth parasite infections, potentially due to the ability of the helminth parasite to induce tolerance by inducing tolerogenic dendritic cells (tolDC) polarization. Although macromolecules from helminth such as proteins and polysaccharides have been shown to polarize tolDCs, to characterize a novel pathway, in this study we focused on small molecules such as metabolites in the helminth secretome. We hypothesized that helminth-derived metabolites (HDMs) polarize DCs towards a tolerogenic phenotype, which alleviates colitis.AimsTo evaluate and characterize the tolerogenic response induced by HDMs in DCs, and its ability to alleviate colitis.Methods Heligmosomoides polygyrus worms were culture for 24 h and HDMs were isolated from conditioned media by chromatography. Bone marrow dendritic cells (BMDCs) were differentiated with GM-CSF for 8 days and then incubated with HDM for 4 h before LPS stimulation for 20 h. Cytokine secretion was measured by ELISA. The transcriptome of DCs treated with HDMs was assessed by RNAseq. Colitis was induced by giving 3% DSS in drinking water for 5 days followed by 3 days of tap water. The anti-colitic effect of HDMs was assessed by daily treatment with HDM or DCs treated with HDM in the 3 days of tap water.ResultsPre-treatment with HDM decreased LPS-induced TNF and increased IL-10 release by BMDCs, compared to control BMDCs. Colitic mice treated with HDM presented lower disease activity scores, less colon shortening, decreased weight loss, and healthier histopathology compared to vehicle-treated colitic mice. Importantly, there was an increased frequency of CD11c+ CD103+ DCs in the colon of HDM-treated mice, suggesting that HDM alleviates colitis by increasing the abundance of tolDCs in the colon. Adoptive transfer of HDM-treated DCs also reduced the severity of colitis compared with vehicle-treated mice or mice that received naïve DCs. These results indicate that HDM induced tolerogenic DCs, which in turn ameliorates DSS colitis. RNAseq showed that HDM upregulated 183 and downregulated 76 genes. These differentially expressed genes may indicate a novel mechanism by which helminths induce a tolerogenic profile in DCs.ConclusionsHDMs induce tolerogenic DCs and alleviate DSS-induced colitis.Funding AgenciesNSERC and FRQNT

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis

Rheumatoid arthritis is a severe chronic autoimmune disorder that results from pathological activation of immune cells and altered cytokine/chemokine network. The aim of our study was to evaluate concentrations of chosen cytokines and chemokines in blood sera and synovial fluid samples isolated from low disease activity rheumatoid arthritis (RA) patients and osteoarthritis (OA) sufferers. Blood sera and synovial fluid samples have been obtained from 24 OA and 14 RA patients. Cytokines/chemokines levels have been determined using a Milliplex® Map 38-plex human cytokine/chemokine magnetic bead-based panel (Merck Millipore, Germany) and Luminex® MAGPIX® platform (Luminex USA). Low disease activity RA patients showed altered concentration of numerous cytokine/chemokine when compared to OA controls—they were characterized by, inter alia, increased: eotaxin/CCL11 (p = 0.037), GRO/CXCL1 (p = 0.037), IL-2 (p = 0.013), IL-4 (p = 0.017), IL-7 (p = 0.003), IL-8 (p = 0.0007) and GM-CSF (p = 0.037) serum levels, whilst MDC/CCL22 concentration was decreased in this group (p = 0.034). Eotaxin/CCL11 (p = 0.001), GRO/CXCL1 (p = 0.041), IL-10 (p = 0.003), GM-CSF (p = 0.01), IL-1RA (p = 0.0005) and VEGF (p = 0.01) concentrations in synovial fluid of RA females were also increased. Even with low disease activity score, RA patients exhibited increased concentrations of cytokines with pro- and anti-inflammatory activities, as well as numerous chemokines, growth factors and regulators of angiogenesis. Surprisingly, RA subjects also shown decreased concentration of CCL22 chemokine. The attempt to restore cytokine balance and tolerogenic environment is ineffective in RA sufferers even with good disease management. Distinguished factors could serve as possible indicators of disease progression even in low disease activity patients.

Methotrexate Disposition, Anti-Folate Activity, and Metabolomic Profiling to Identify Molecular Markers of Disease Activity and Drug Response in the Collagen-Induced Arthritis Mouse Model.

Methotrexate (MTX) is widely used in the treatment of autoimmune arthritis but is limited by its unpredictable and variable response profile. Currently, no biomarkers exist to predict or monitor early therapeutic responses to MTX. Using a collagen-induced arthritis (CIA) mouse model, this study aimed to identify biochemical pathways and biomarkers associated with MTX efficacy in autoimmune arthritis. Following arthritis disease induction, DBA/1J mice were treated with subcutaneous MTX (20 mg/kg/week) and disease activity was assessed based on disease activity scores (DAS) and paw volume (PV) measurements. Red blood cell (RBC) and plasma samples were collected at the end of the study and were assessed for folate and MTX content. Plasma samples were analyzed by semitargeted global metabolomic profiling and analyzed by univariate and multivariate analysis. Treatment with MTX was associated with significant reductions in disease activity based on both DAS (p = 0.0006) and PV (p = 0.0006). MTX therapy resulted in significant reductions in 5-methyltetrahydrofolate (5mTHF) levels in plasma (p = 0.02) and RBCs (p = 0.001). Reductions in both RBC and plasma 5mTHF were associated with lower DAS (p = 0.0007, p = 0.01, respectively) and PV (p = 0.001, p = 0.005, respectively). Increases in RBC MTX were associated with lower DAS (p = 0.003) but not PV (p = 0.23). Metabolomic analysis identified N-methylisoleucine (NMI) and quinolone as metabolites significantly altered in disease mice, which were corrected towards healthy control levels in mice treated with MTX. Reductions in plasma NMI were associated with lower DAS (p = 0.0002) and PV (p = 9.5 × 10−6). Increases in plasma quinolone were associated with lower DAS (p = 0.02) and PV (p = 0.01). Receiver-operating characteristic curve analysis identified plasma NMI (AUC = 1.00, p = 2.4 × 10−8), RBC 5mTHF (AUC = 0.99, p = 2.4 × 10−5), and plasma quinolone (AUC = 0.89, p = 0.01) as top discriminating metabolites of MTX treatment. Our data support a relationship between MTX efficacy and its effect on circulating folates and identified 5mTHF, NMI, and quinolone as potential therapeutic biomarkers of disease activity and MTX response in the CIA mouse model of autoimmune arthritis.

Demographic and Clinical Characteristics of Patients with Sustained and Switching Treatments Using Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs: A Multicenter, Observational Cross-Sectional Study for Rheumatoid Arthritis.

IntroductionRheumatoid arthritis is a chronic inflammatory disease with different disease activity grades. Several registries have been designed to determine the appropriate regimens of disease-modifying antirheumatic drugs to obtain sustained clinical remission. We examined epidemiological and clinical characteristics of rheumatoid arthritis patients using a clinical registry database (BioSTaR) and analyzed the differences in patients with sustained and switched therapies.MethodsA multicenter, observational cross-sectional study for rheumatoid arthritis was performed between February 2019 and September 2020 using the BioStaR-RA registry.Demographic and clinical characteristics were prospectively recorded into a specifically designed electronic database. The patients were divided into three groups due to the heterogeneity of the study cohort. Patients were grouped as Group I (Initial; within the first 6 months of treatment with biological/targeted synthetic drugs), Group ST (Sustained Treatment; any first drug lasting for at least 6 months without any change), and Group S (Switch; any switching to another drug). Comparative analysis was performed between sustained treatment (Group ST) and drug switching (Group S) groups.ResultsThe study included a total of 565 patients. The mean age was 53.7 ± 12.8 years, and the majority were female (80.4%). There were 104, 267, and 194 patients in Groups I, ST, and S, respectively. Erosive arthritis and hematological extra-articular involvement were more frequently detected in Group S than Group ST (p = 0.009 and p = 0.001). The patients in Group S had significantly higher disease activity scores (DAS28-CRP, CDAI, and SDAI) (p = 0.025, p = 0.010, and p = 0.003). There were significantly more patients with moderate disease activity in Group S (p < 0.05).ConclusionsThe groups with sustained treatment and switching included patients with different disease activity status, although higher disease activity was determined in switchers. Overall, moderate disease activity and remission were the most common disease activity levels. Lower disease activity scores, lower hematologic manifestations, better functional status, and lesser radiographic damage are associated with sustained treatment.

Work participation in patients with systematic lupus erythematosus: a systematic review.

ObjectivesThis systematic review assessed which variables are associated with or are predictors for work participation outcomes in patients with systematic lupus erythematosus (SLE).MethodsA literature search using MEDLINE, The Cochrane Library, Embase and CINAHL was conducted to identify all studies published from inception (1947) to June 2021 on factors related to and/or predicting employment status, absenteeism and/or presenteeism in SLE patients aged ≥18 years. The quality of included articles was assessed using the QUIPS tool. Narrative summaries were used to present the data.ResultsFifteen studies (nine on associations, four on predictions, and two assessing both) were included, encompassing data of 3800 employed patients. Younger age, Caucasian ethnicity, higher educational level, lower disease activity score, shorter disease duration, absence of specific disease manifestations, higher levels of physical functioning and less physical job demands and higher levels of psychological/cognitive functioning were associated with or predicted favorable work outcomes. Older age, non-Caucasian ethnicity, female gender, never being married, poverty, lower educational level, higher disease activity score, longer disease duration, specific disease manifestations, lower levels of physical functioning, more physical job demands and low job control, less job tenure and lower levels of cognitive functioning were associated with or predicted an unfavorable work outcome. Limitations of the evidence were the quality of the studies and the use of heterogeneous outcome measures, applied statistical methods and instruments used to assess work participation.ConclusionWe recommend applying the EULAR points to consider for designing, analysing and reporting on work participation in inflammatory arthritis also to SLE studies on work participation, to enhance the quality and comparability between studies and to better understand the impact of SLE on work participation.Trial registrationregistration in PROSPERO (CRD42020161275; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=161275).

Glucocorticoid discontinuation in patients with early rheumatoid and undifferentiated arthritis: a post-hoc analysis of the BeSt and IMPROVED studies

ObjectivesTo evaluate the success rate of glucocorticoid discontinuation and to study which factors are associated with successful discontinuation.MethodsData from two treat-to-target studies, BeSt (target Disease Activity Score (DAS) ≤2.4) and...

OP0293 OPTIMIZING A TOOL TO IDENTIFY LUPUS FLARES IN DAILY CLINICAL PRACTICE: SLE-DAS FLARE VERSUS SELENA FLARE INDEX

Background:In the management of patients with Systemic Lupus Erythematosus (SLE), it is of utmost importance to accurately identify lupus flares. There is a conceptual consensus definition of lupus flares [1]; however, the instruments used to identify flares in clinical trials, such as the SELENA Flare Index (SFI) are too cumbersome to apply in daily clinical practice. The SLE disease activity score (SLE-DAS) is a validated continuous measure of disease activity with higher sensitivity to change and validity in predicting damage accrual when compared to SLEDAI-2K. SLE-DAS is quickly scored with its online calculator. An increase in SLE-DAS ≥1.72 was validated as a clinically meaningful worsening of SLE disease activity. [2]Objectives:To compare the performance of SLE-DAS, classic SFI (c-SFI), revised SFI (r-SFI) and SLEDAI-2K in the identification of lupus flares in a real-life clinical setting.Methods:We included patients with SLE fulfilling classification criteria [ACR (1997) and/or SLICC and/or EULAR/ACR], followed at an academic lupus clinic from January 2017 to June 2020, and presenting with lupus low disease activity score (LLDAS) at baseline.Flares occurring after baseline were identified as fulfillment of the conceptual definition of flare, as assessed by the senior lupus expert at time of each outpatient visit. For each flare event, we evaluated the fulfillment of flare criteria according to c-SFI, r-SFI, SLEDAI-2K (score increase ≥4 points from baseline), and SLE-DAS (score increase ≥1.72 from baseline). As control visits without flare, we considered the first visit after baseline, where we assessed the four tools, excluding those where a flare was identified by the gold-standard expert evaluation. Sensitivity and specificity of the four flare tools were estimated and McNemar’s test applied to assess differences with the gold-standard flare definition. The inter-instrument agreement with the gold-standard was assessed through Cohen’s Kappa.Results:We included 297 patients (female: 86.2%; mean age: 48.9±14.6 years, mean disease duration: 12.5±9.0 years). At baseline, all patients were in LLDAS, receiving ongoing antimalarials, immunosuppressants, and/or glucocorticoids in 91.0%, 43.8% and 33.6%, respectively. During follow-up, 22.2% developed flares. The analysis included 92 flares [musculoskeletal (40.2%); renal (23.9%), mucocutaneous (18.5%), haematological (5.9%), serositis (3.3%); multisystemic (8.7%)], with increase or change of treatment in 80.4% of these episodes, and 292 visits without flare considered as control.There was no statistically significant difference between either SLE-DAS flare or c-SFI and the gold-standard expert flare definition (p=0.41 and p=0.82, respectively), while r-SFI and SLEDAI-2K flare were different from the gold-standard (Table 1). There was a strong agreement between SLE-DAS flare, c-SFI, r-SFI and the expert definition (Cohen’s kappa, Table 1).Table 1.Performance of the flare tools for the gold-standard flare definition.Sensitivity (%)Specificity (%)McNemar’s§§Kappa§SLE-DAS flare90.195.0n.s.0.836c-SFI flare91.196.5n.s.0.869r-SFI flare93.492.9p&lt;0.010.820SLEDAI-2K flare51.698.6p&lt;0.00010.590§§ McNemar’s test: significant difference from gold-standard if p&lt;0.05; § Cohen’s kappa agreement (0-1) with the gold-standard flare definition; n.s.: non-significantConclusion:The c-SFI and SLE-DAS showed the best performance in identifying SLE flares. The SLE-DAS flare definition is easier to apply and hence might be considered as an optimal tool to be used in daily clinical practice.

Systematic review with meta-analysis: effectiveness of hyperbaric oxygenation therapy for ulcerative colitis.

Background and aims:Hyperbaric oxygenation therapy has been used in the treatment of ulcerative colitis in the past few years. However, its efficacy still remains unclear. The aim of the study was to investigate the efficacy of hyperbaric oxygen combination therapy in patients with ulcerative colitis.Methods:We conducted a comprehensive study search up to September 2020, from the online databases Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, WanFang and VIP.Results:Thirteen studies comprising 780 patients were included. We found that compared with conventional therapy, hyperbaric oxygen combination therapy was superior in reaching clinical remission [risk ratio (RR)=1.62; 95% confidence interval (CI) 1.42 to 1.84; p < 0.001] and clinical response (RR=1.29; 95% CI 1.21 to 1.38; p < 0.001), with lower disease activity scores [standard mean difference (SMD)= −1.19; 95%CI −1.74 to −0.65; p < 0.001]. An obvious reduction of serum levels of tumor necrosis factor-α (SMD= −1.96; 95%CI −2.50 to −1.41; p < 0.001) and interleukin (IL)-6 (SMD= −2.49; 95% CI −2.84 to −2.15; p < 0.001), and elevation of IL-10 level (SMD=2.40; 95% CI 0.68 to 4.12; p = 0.006) were also observed.Conclusion:Hyperbaric oxygen combination therapy was effective in patients with ulcerative colitis, and has potential as a complementary method for its treatment.

Shared epitope and polymorphism of MICA and NKG2D encoding genes in Greek and Polish patients with rheumatoid arthritis.

The present study aimed to analyse and compare the distribution of MICA (rs1051792) and NKG2D/KLRK1 (rs1154831, rs1049174, rs2255336) polymorphisms in 61 Greek and 100 Polish patients with rheumatoid arthritis in relation to the presence of the HLA-DRB1 shared epitope and clinical parameters. Genotyping of selected polymorphism was performed using real-time PCR. HLA-DRB1 shared epitope alleles segregated differently in Greek and Polish patients but in both populations were detected in over 60% of cases. The rs1051792-A variant was more common among SE-positive Polish patients (p = 0.003) while the rs1049174-G allele was more frequently observed in Greeks than in Poles (p < 0.001). Moreover, among Greek patients, the rs1051792-GG homozygotes more frequently presented with anti-CCP antibodies and rheumatoid factor (RF), while carriers of the rs1049174-G variant and rs1154831-CC homozygotes were characterized by lower disease activity scores (p < 0.05 in all cases). These results imply that, in addition to the HLA-DRB1 SE alleles, MICA and NKG2D polymorphisms may also play a role in rheumatoid arthritis.