csDMARD Treatment Research Articles

Biologic and targeted synthetic disease-modifying anti-rheumatic drugs improve body composition in rheumatoid arthritis patients more than conventional synthetic disease-modifying anti-rheumatic drugs: Results from the PRESENT study.

The effects of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on body composition and muscle function in rheumatoid arthritis (RA) patients requiring treatment enhancement were compared. This multicenter, prospective, observational study (PRESENT Study) divided RA patients non-randomly into a csDMARD group (n = 100) and a b/tsDMARD group (n = 100). Changes in body composition and muscle function were examined in 80 patients in each group followed for 52 weeks. The percentages of new-onset and improved sarcopenia over 1 year were investigated. Patients in the b/tsDMARD group were divided into three groups by drug type: TNF inhibitors (n = 30), non-TNF inhibitors (n = 23), and JAK inhibitors (n = 27). Baseline median age and disease duration were 70.0 and 4.0 years, respectively. Changes in weight (24 and 52 weeks) and muscle mass (52 weeks) were significantly higher in the b/tsDMARD group (p = .035, p < .001, and p = .002, respectively). On multivariate logistic regression analysis, b/tsDMARD treatment (OR 3.21, p = .002), DAS28-ESR (OR 0.65 p = .011), and muscle mass (OR 0.90, p = .023) were independently associated with increased muscle mass at 52 weeks. The percentages of new-onset and improved sarcopenia were almost equal. There were no significant differences in the time-dependent changes (52 weeks) of clinical status, body composition, muscle function, and status of sarcopenia among TNF inhibitors, non-TNF inhibitors, and JAK inhibitors. Weight and muscle mass increased significantly more with b/tsDMARD than with csDMARD treatment. There were no differences in body composition changes by mode of action with b/tsDMARDs.

The effects of sarilumab as monotherapy and in combination with non-methotrexate disease-modifying anti-rheumatic drugs on unacceptable pain in patients with rheumatoid arthritis: a post-hoc analysis of the HARUKA phase 3 study.

To investigate unacceptable pain (UP; visual analogue scale [VAS] >40 mm) and uncontrolled inflammation (C-reactive protein [CRP] ≥1.0 mg/dL) in patients with active rheumatoid arthritis (RA) receiving sarilumab (SAR) as monotherapy or in combination with non-methotrexate conventional synthetic disease-modifying antirheumatic drugs (SAR+csDMARDs). In the HARUKA phase 3 study (NCT02373202), Japanese patients received either SAR monotherapy (n=61) or SAR+csDMARDs (n=30). In this post-hoc analysis, changes in the proportions of patients with/without UP and controlled/uncontrolled inflammation were assessed over 52 weeks. At baseline, 80.3% (49/61) of patients receiving SAR monotherapy had UP and this proportion decreased with treatment to 55.9% (33/59) at Week 4 and 15.5% (9/58) at Week 52. The SAR+csDMARDs group achieved a reduction in UP from 73.3% (22/30) at baseline to 34.5% (10/29) at Week 4 and 0% (0/24) by Week 52. At baseline, 34.4% (21/61) and 50% (15/30) of patients had both UP and uncontrolled inflammation in the SAR monotherapy and SAR+csDMARDs groups; by Week 2, the proportions decreased to 6.6% (4/61) and 3.3% (1/30), respectively; and 0% in both groups by Week 52. UP and inflammation were reduced in patients with active RA in Japan in both SAR monotherapy and SAR+csDMARDs treatment groups.

Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis

ObjectiveThere are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. MethodsPatients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. ResultsSix hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2–21.2) compared to double therapy (9.6 months; 95%CI: 7.03–12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005). ConclusionPatients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.

The changes of intestinal flora and its relevance with memory Tfh and B cells in rheumatoid arthritis patients treated with csDMARDs and csDMARDs + bDMARDs

BackgroundA growing body of experimental and clinical evidence has implicated gut microbiota in the onset and course of rheumatoid arthritis (RA). The imbalance of intestinal flora in RA patients may lead to abnormal expression of immune cells and related cytokines. PurposeConventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and conventional synthetic disease-modifying antirheumatic drugs combined with biological disease-modifying antirheumatic drugs (csDMARDs + bDMARDs) are widely used to treat RA, but the characteristics of gut microbiota before and after treatment and their relationship with memory Tfh/B cells and cytokines remain unclear. MethodsStool samples were collected from 50 RA patients and 25 healthy controls (HCs) for 16SrRNA gene sequencing. We examined the proportion of lymphocyte subsets in healthy controls and RA patients. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of related cytokines in serum. The α and β diversity of intestinal flora, and the correlation between intestinal flora and clinical indicators, lymphocyte subsets, cytokines were analyzed. ResultAt the genus level, Ruminococcaceae_Ruminococcus was decreased in the csDMARDs and csDMARDs + bDMARDs treatment group, whereas Faecalibacterium was reduced in the csDMARDs treatment group, compared to untreated group. CD4+CD45RO+CCR7+CXCR5+central memory Tfh cells and CD4+CD45RO+CCR7-CXCR5+effector memory Tfh cells were significantly lower in the csDMARDs + bDMARDs treatment group than in untreated group. CD19+CD27+IgD+pre-switched memory B cells were higher in the csDMARDs and csDMARDs + bDMARDs treatment groups, whereas CD19+CD27+IgD-switched memory B cells were significantly lower than in untreated group. Ruminococcaceae_Ruminococcus was negatively correlated with CD19+CD27+IgD+ pre-switched memory B cells but positively correlated with CD4+CD45RO+CCR7-CXCR5+effector memory Tfh and CD19+CD27+IgD-switched memory B cells in patients with RA treated with DMARDs. ConclusionThe gut microbiota, memory Tfh cells, memory B cells, and cytokines of patients with RA changed significantly under different treatment regimens and had certain correlations with the clinical indicators of RA.

COVID-19 infection characteristics, risk factors and its potential impacts on Takayasu arteritis: a web-based survey in a large cohort.

To investigate the characteristics of COVID-19 and its impact on patients with Takayasu's arteritis (TAK). A web-based survey was administered to a TAK cohort and their co-residents in China during January 2023. Infection symptoms, post-acute sequelae of COVID-19 (PASC), potential impacts of COVID-19 on patients' disease condition, treatment and immune-related parameters were analyzed. In addition, risk factors for COVID-19 and disease relapse after infection were explored. The infection rate was significantly lower in patients with TAK than in co-residents (79.13% vs 90.67%, p=0.025). TAK patients were more prone to gastrointestinal symptoms (17.78% vs 5.88%, p=0.024), sleep problems (25.15% vs 10.29%, p=0.011), and symptoms involving more than 2 organs (58.90% vs 35.29%, p=0.001) after infection. Although only 2.45% of TAK patients were hospitalized and none progressed to life-threatening conditions, they were more likely to suffer from PASC (26.38% vs 13.24%, p=0.029), especially active patients. Active disease after the pandemic was significantly lower in infected patients than uninfected patients (21/163, 12.88% vs. 11/43, 25.58%, p=0.041). The presence of multiple system symptoms was a risk factor for active TAK after infection [OR: 3.62 (95% CI 1.06-12.31), p=0.040]. Moreover, csDMARDs treatment was a risk factor for COVID-19 infection [OR: 3.68 (95% CI 1.56-8.66), p=0.002]. Although TAK patients with COVID-19 have more acute and post-acute symptoms, there is no adverse outcome and the risk of disease relapse does not increase. Patients treated with csDMARDs may be at higher risk of infection and deserve more clinical attention.

Proof-of-Concept Double-Blind Placebo-Controlled Trial Measuring Cartilage Composition in Early Rheumatoid Arthritis under TNF-α-Inhibitor Therapy

Low levels of delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) values are indicative of cartilage degeneration. Patients with early rheumatoid arthritis are known to have low dGEMRIC values due to inflammatory activity. The additional effect of biological disease-modifying antirheumatic drug (bDMARD) and conventional synthetic disease-modifying antirheumatic drug (csDMARD) treatment on cartilage status is still unclear. In this prospective, double-blinded, randomized proof-of-concept clinical trial, patients with early rheumatoid arthritis (disease duration less than 12 months from symptoms onset) were treated with methotrexate + adalimumab (10 patients: 6/4 (f/m)). A control group with methotrexate alone (four patients: 2/2 (f/m)) was used. Cartilage integrity in the metacarpophalangeal joints was compared using dGEMRIC at baseline, 12, and 24 weeks after treatment initiation. A statistically significant increase in dGEMRIC levels was found in the adalimumab group considering the results after 12 and 24 weeks of therapy (p < 0.05) but not in the control group (p: non-significant). After 24 weeks, a tendency towards increased dGEMRIC values under combination therapy was observed, whereas methotrexate alone showed a slight decrease without meeting the criteria of significance (dGEMRIC mean change: +85.8 ms [-156.2-+346.5 ms] vs. 30.75 ms [-273.0-+131.0 ms]; p: non-significant). After 24 weeks of treatment with a combination of methotrexate and adalimumab, a trend indicating improvement in cartilage composition is seen in patients with early rheumatoid arthritis. However, treatment with methotrexate alone showed no change in cartilage composition, as observed in dGEMRIC sequences of metacarpophalangeal joints.

Using Treg, Tr1, and Breg Expression Levels to Predict Clinical Responses to csDMARD Treatment in Drug-naive Patients With Rheumatoid Arthritis.

Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping. We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05). Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients.

Establishment and verification of a nomogram and a preliminary study on predicting the clinical response of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is an autoinflammatory disease, its core treatment principle is to achieve remission as soon as possible. There is no good prediction model that can accurately predict the remission rate of patients to choose a good treatment scheme. Here, we aimed to verify the prognostic value of some inflammatory indicators in RA and establish a prediction model to predict the remission rate after treatment. A total of 223 patients were enrolled at Qilu Hospital from June 2014 to June 2020. Baseline clinical data were collected and plasma was obtained to detect the inflammatory indicators. All patients were treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). All patients were followed up and were recorded the time to reach the disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR) of <2.6. A total of 156 patients were randomly assigned to the development cohort, and 67 patients were assigned to the validation cohort. Inflammatory indicators in plasma were detected by enzyme-linked immunosorbent assay (ELISA). The predictive factors were screeded by using least absolute shrinkage and selection operator (LASSO) and Cox regression. The model was created and verified by using the standard method. A total of 6 independent risk factors were analyzed to construct a nomogram to predict the remission rate in 3, 6 and 12 months. The remission rates after treatment in 3, 6 and 12 months were 38.76%, 58.91%, and 81.40%, respectively. Patient age, C-reactive protein (CRP), interleukin (IL)-6, galectin-9 (Gal-9), health assessment questionnaire (HAQ), and DAS28-ESR were included in the prognostic model to predict the remission rate. The resulting model had good discrimination ability in both the development cohort (C-index, 0.729) and the validation cohort (C-index, 0.710). Time-dependent receiver operating characteristic (ROC) curve, calibration analysis, and decision curve analysis (DCA) showed that the model has significant discriminant power and clinical practicability in predicting the remission rate. We established a new predictive model and validated it. The model can predict the remission rate in 3, 6 and 12 months after receiving csDMARDs treatment. By using this model, we can facilitate the identification of high-risk patients early and intervene with them as soon as possible.

Determinants of health-related quality of life in spondyloarthritis and rheumatoid arthritis - data from the COMOSPA and COMORA studies

ObjectivesTo assess the hierarchy of outcomes contributing to health-related quality of life (HRQoL) in spondyloarthritis (SpA) and rheumatoid arthritis (RA). MethodsData from the international cross-sectional COMOSPA and COMORA studies were used. HRQoL was assessed using the EuroQOL 5-dimension 3-level (EQ-5D-3 L). First, multivariable linear regression models were used to identify associations between EQ-5D-3 L (dependent variable) and several demographic and clinical variables (independent variables). Second, a decision tree was built using Chi-square Automatic Interaction Detector, a method of unbiased hierarchical multivariable analysis (dependent variable: EQ-5D-3 L). ResultsIn total, 3984 patients with SpA and 3920 patients with RA were included. In SpA, HRQoL was associated with BASFI (adjusted B=-0.006; 95%CI=-0.007 to -0.005), ASDAS (-0.052; -0.071 to -0.033), work productivity loss score (-0.002; -0.003 to -0.002), NSAID treatment (-0.052; -0.083 to -0.020), bDMARD treatment (-0.051; -0.082 to -0.021), university education (-0.051; -0.075 to -0.027) and radiographic sacroiliitis (0.035; 0.004 to 0.030). In RA, HRQoL was associated with modified Health Assessment Questionnaire (MHAQ) (-0.220, -0.253 to -0.188), DAS28-CRP-3v (-0.027, -0.036 to -0.018), work productivity loss score (-0.003, -0.003 to -0.002), presence of erosions (-0.042, -0.065 to -0.020), alcohol consumption ≥3 units/day (0.012, 0.001 to 0.024)) and csDMARD treatment (0.034, 0.001 to 0.066). The decision tree revealed BASFI and MHAQ as first variables with the most discriminative power on EQ-5D-3 L, followed by work productivity loss and disease activity, in both SpA and RA cohorts. ConclusionIn SpA and RA, physical function is the main contributor to HRQoL measured by EQ-5D-3 L, followed by disease activity and work productivity loss.

Iguratimod versus salazosulfapyridine in rheumatoid arthritis patients with an inadequate response to methotrexate: Adjusted with propensity score matching.

Methotrexate (MTX) is recommended as a first-line conventional synthetic disease-modifying antirheumatic drug (csDMARD) for treating rheumatoid arthritis (RA). This retrospective study sought to identify an add-on csDMARD treatment strategy for RA patients with MTX-inadequate response (IR). We collected the cases of RA patients treated with salazosulfapyridine (SASP) or iguratimod (IGU) as the additional csDMARD for MTX-IR during a 24-month follow-up. We performed propensity score matching to evaluate the retention rate, clinical efficacy, and safety profile (n = 54, each group). The retention rates at 24 months were 38.5% (MTX+SASP group) and 67.8% (MTX+IGU group). At 3 and 6 months, the MTX+IGU group's 28 joint-disease activity score (DAS28) was significantly decreased versus the MTX+SASP group, and at 3 months the MTX+IGU group's good-responder percentage (22.9%) was significantly higher versus the MTX+SASP group's good-responder percentage (10.7%). Conversely, compared to the MTX+SASP group, the MTX+IGU group showed a greater reduction in the estimated glomerular filtration rate from baseline during follow-up. IGU is a useful add-on csDMARD for RA patients with MTX-IR; its high retention rate and good clinical response make it a useful combination therapy for controlling RA disease activity. However, the renal function should be monitored during follow-up.

POS0691 EMULATING A TARGET TRIAL OF ADALIMUMAB VERSUS TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: A COMPARATIVE EFFECTIVENESS ANALYSIS USING THE OPAL REAL-WORLD DATASET

BackgroundThere is increasing recognition of the complementary role for real-world evidence (RWE) in health care and regulatory decision-making (1). However, careful analysis is required when drugs are compared using observational data to account for differences between treatment groups. Electronic medical records (EMR) are an important source of real-world data (RWD), but outcomes are often recorded incompletely.We emulated a target trial of adalimumab (ADA) versus tofacitinib (TOF) in patients with rheumatoid arthritis (RA) using the OPAL dataset to illustrate the application of methodologies to address the challenges of non-random treatment assignment and incomplete data. The OPAL dataset is derived from EMR of 112 community-based rheumatologists around Australia, where practitioners have discretion to prescribe whichever b/tsDMARD they consider most clinically appropriate.ObjectivesTo estimate the average treatment effect (ATE) of TOF compared to ADA at 3 and 9 months, defined as the difference in mean disease activity score (DAS28CRP), in patients with RA who are new users of a b/tsDMARD. This is equivalent to aiming to estimate the intention-to-treat effect in a randomised controlled trial.MethodsOPAL patients diagnosed with RA were included if they initiated ADA or TOF between 1 October 2015 and 1 April 2021, were new b/tsDMARD users (no prior recorded b/tsDMARD, at least 6 months of prior csDMARD treatment), and had at least 1 component of DAS28CRP recorded at baseline or during follow-up. Data were also extracted on baseline characteristics. Baseline characteristics were DAS28CRP, patient demographics, regional location, disease duration, prescriber characteristics (including gender, experience), prior recorded comorbidities, and prior and concomitant treatment with csDMARDs and oral corticosteroids.We used random forest multiple imputation to impute missing baseline and follow-up DAS28CRP components (2). Stable balancing weights (SBW) were then used to balance the treatment groups in terms of their baseline characteristics, including DAS28CRP (3). For each imputed dataset, the ATE at 3 months was estimated as the difference between the mean outcome in the two treatment groups after balancing (i.e. weighting) the sample, and then these estimates were averaged across the 10 imputed datasets. The ATE at 9 months was estimated similarly. The whole procedure was subsequently performed in 1000 bootstrap samples to estimate a 95% confidence interval (CI) for the ATEs using the percentile method (4).Results842 patients were identified including n=569 treated with ADA and n=273 treated with TOF. After applying the SBW, the maximum difference between the mean of each baseline characteristic in the ADA and TOF groups was less than 0.03% of the corresponding standard deviation in the whole sample, indicating reasonable balance was achieved in this complex dataset. After weighting, mean DAS28CRP reduced from 5.3 at baseline (both ADA and TOF groups) to 2.6 and 2.3 at 3 and 9 months for ADA, and 2.4 and 2.3 at 3 and 9 months for TOF.The estimated ATE was -0.22 (95% CI -0.36, -0.03; p=0.02) at 3 months, indicating a modest but significant reduction in disease activity for patients on TOF. The estimated ATE was -0.03 (95% CI -0.19, 0.1; p=0.56) at 9 months, indicating no difference between groups.ConclusionDAS28CRP was significantly lower at 3 months for patients treated with TOF compared to ADA. However, 3 months of treatment with either drug led to substantive average reductions in mean DAS28CRP, consistent with remission. There was no difference between drugs at 9 months. Future work will estimate a per-protocol effect.

TNF inhibitors for the prevention of Alzheimer’s disease: Preliminary findings from the rheumatoid arthritis medication and memory study (RESIST)

AbstractBackgroundA raised level of serum TNFα observed in patients with Alzheimer’s disease has been associated with an increased rate of neurodegeneration and risk of conversion from mild cognitive impairment (MCI) to AD dementia. This led to the hypothesis that reduction in peripheral TNFα via TNF inhibitors (TNFi) may reduce the rate of neurodegeneration and may protect against development of AD.MethodThe rheumatoid arthritis medication and memory study (RESIST) is an 18‐month observational study which aims to compare the rate of cognitive decline between TNFi and conventional synthetic disease modifying anti‐rheumatic drugs (csDMARDs) in patients with both rheumatoid arthritis (RA) and MCI. Participants ≥ 55 years of age were recruited from rheumatology clinics in both Northern Ireland and Southampton and were cognitively assessed using the Free and Cued Selective Reminding Test (FCSRT) and Montreal Cognitive Assessment (MoCA). At the time of analysis n=130 participants had completed a 6‐month assessment and n=69 had completed a 12‐month assessment. ANCOVA analysis was conducted to calculate the difference in mean (and 95% CI) FCSRT and MoCA scores at both 6‐ and 12‐month timepoints between TNFi and csDMARD treatment groups, adjusting for baseline cognitive scores. Further adjustments were made for age, gender, RA disease activity and other confounding variables.ResultThere was no evidence of a difference between TNFi and csDMARD treatment in cognitive outcomes measured by FCSRT (6‐month cohort (mean difference 0.58, 95% CI ‐ 1.40, 2.56, p = 0.565); 12‐month cohort (mean difference ‐1.09, 95% CI ‐3.57, 1.38, p = 0.381)) or MoCA (6‐month cohort (mean difference ‐1.09, 95% CI ‐3.57, 1.38, p = 0.381); 12‐month cohort (mean difference ‐0.04, 95% CI ‐1.06, 0.98, p = 0.940)) after adjustment for baseline cognitive scores nor was there a difference in cognitive outcomes between treatment groups after adjustment for additional confounders.ConclusionThis preliminary analysis found little evidence of a relationship between TNFi and better cognitive performance however analysis was limited by lack of power and short follow‐up periods. This analysis will be repeated once RESIST has ended to determine if there is any statistically significant cognitive benefit of TNFi treatment after 18‐months.

A cross-sectional study on clinical characteristics of Saudi axial spondylarthritis: preliminary results.

To describe Spondyloarthritis (SpA) patients in a single center (preliminary phase), Build connections to establish local cohorts, Saudi Registry, and publication in Gulf and Arab database. This prospective observational cohort consists of patients with spondylarthritis (SpA) diagnosed by a rheumatologist. Patients with AS were defined as those who met the modified New York criteria for Ankylosing Spondylitis (AS) 1984. All other patients with axial SpA who did not meet the radiology criteria of modified New York criteria for Ankylosing Spondylitis were classified as having non-radiographic axial SpA based on Assessment of SpondyloArthritis International Society (ASAS) diagnostic criteria for axial spondyloarthropathy. The study group comprised 106 patients with SpA (49 patients with AS and 57 patients with non-radiographic axial SpA). Patients with non-radiographic axial SpA and patients with AS who had previously been treated with biologic disease-modifying drugs (DMARDs) were 66.67 percent and 83.67 percent, respectively. In patients with AS, CRP and age significantly impact disease activities (p<0.05). The overall mean ASDAS score was 2.3 ± 0.7. This study has shown a more detailed description of the largest Saudi cohort reported yet. Interestingly, both disease groups, Ankylosing spondylitis and non-radiographic spondyloarthritis showed a lower prevalence of HLA-B27 is lower in the general Saudi population compared to other nations including Caucasians, thus, limiting its use as a diagnostic tool. The majority of both groups, nearly three-quarters of all patients (74.53%) in biologic DMARD treatment, and only (22.64%) used csDMARD treatment, which may help control disease activity and showing easier access and availability of these therapies to the patient. Patients with non-radiographic axial SpA showed slightly higher Extra-articular Manifestations comparing with AS patients.

Circulating and Synovial Pentraxin-3 (PTX3) Expression Levels Correlate With Rheumatoid Arthritis Severity and Tissue Infiltration Independently of Conventional Treatments Response.

AimsTo determine the relationship between PTX3 systemic and synovial levels and the clinical features of rheumatoid arthritis (RA) in a cohort of early, treatment naïve patients and to explore the relevance of PTX3 expression in predicting response to conventional-synthetic (cs) Disease-Modifying-Anti-Rheumatic-Drugs (DMARDs) treatment.MethodsPTX3 expression was analyzed in 119 baseline serum samples from early naïve RA patients, 95 paired samples obtained 6-months following the initiation of cs-DMARDs treatment and 43 healthy donors. RNA-sequencing analysis and immunohistochemistry for PTX3 were performed on a subpopulation of 79 and 58 synovial samples, respectively, to assess PTX3 gene and protein expression. Immunofluorescence staining was performed to characterize PTX3 expressing cells within the synovium.ResultsCirculating levels of PTX3 were significantly higher in early RA compared to healthy donors and correlated with disease activity at baseline and with the degree of structural damages at 12-months. Six-months after commencing cs-DMARDs, a high level of PTX3, proportional to the baseline value, was still detectable in the serum of patients, regardless of their response status. RNA-seq analysis confirmed that synovial transcript levels of PTX3 correlated with disease activity and the presence of mediators of inflammation, tissue remodeling and bone destruction at baseline. PTX3 expression in the synovium was strongly linked to the degree of immune cell infiltration, the presence of ectopic lymphoid structures and seropositivity for autoantibodies. Accordingly, PTX3 was found to be expressed by numerous synovial cell types such as plasma cells, fibroblasts, vascular and lymphatic endothelial cells, macrophages, and neutrophils. The percentage of PTX3-positive synovial cells, although significantly reduced at 6-months post-treatment as a result of global decreased cellularity, was similar in cs-DMARDs responders and non-responders.ConclusionThis study demonstrates that, early in the disease and prior to treatment modification, the level of circulating PTX3 is a reliable marker of RA activity and predicts a high degree of structural damages at 12-months. In the joint, PTX3 associates with immune cell infiltration and the presence of ectopic lymphoid structures. High synovial and peripheral blood levels of PTX3 are associated with chronic inflammation characteristic of RA. Additional studies to determine the mechanistic link are required.

PSY12 Experience with Apremilast in Treatment of Psoriatic Arthritis in US Clinical Practice; Assessments from Trio Health and the American Rheumatology Network (ARN)

As a PDE4 inhibitor, apremilast is a unique agent in the treatment armamentarium for psoriatic arthritis (PsA). It is the one targeted immune modulating (TIM) treatment that may be combined with csDMARDs, biologic therapies, or used as a monotherapy. Here we examined care for PsA in a large network of community rheumatologists focusing on use of apremilast relative to TNF inhibitors. This study analyzed patients diagnosed with PsA receiving apremilast monotherapy or TNF inhibitor monotherapy as initial targeted treatment between Jan 2014 to Nov 2019 with ≥6 months follow-up. Disease Assessment Scores (DAS) were calculated using CDAI or Rapid 3. As a surrogate for clinical effectiveness, we examined time from monotherapy initiation to modification or discontinuation, defined as either drug discontinuation or addition of a csDMARD or TIM, via KM analyses. Of 817 apremilast-treated patients, 378 (46%) had no prior observed PsA treatment, 205 (25%) had previous csDMARDs treatment alone, and 234 (29%) previously received other TIM therapies. 329 apremilast-treated patients and 2438 TNFi-treated patients were identified as receiving monotherapy with no prior TIM therapy. From the TNFi-group, a subset of 658 patients were selected based on propensity score matching. Characteristics for the apremilast monotherapy and TNFi monotherapy groups differed significantly for gender and age group but not for baseline disease severity. Median time from monotherapy initiation to initial modification or discontinuation was significantly different between apremilast (17.0 months) and TNFi (34.4 months, p=0.002). In subset analyses, these differences persisted among females (p = 0.03), males (p <0.001) and patients with severe baseline DAS (p=0.009), but not different among non-severe baseline DAS. Time to apremilast modification or discontinuation was significantly less than the matched TNFi group. However, when stratified by baseline DAS, those with low DAS had no difference in time to modification between apremilast and TNFi.

Discontinuation of biologic DMARDs in a real-world population of patients with rheumatoid arthritis in remission: outcome and risk factors.

Data from randomized controlled trials have shown the feasibility of discontinuation of bDMARD therapy in patients with RA that have reached remission. Criteria for selecting patients that are likely to remain in remission are still incompletely defined. We aimed to identify predictors of successful discontinuation of bDMARD therapy in the Swiss Clinical Quality Management (SCQM) registry, a real-world cohort of RA patients. RA patients in DAS28-ESR remission who stopped bDMARD/tsDMARD treatment were included. Loss of remission was defined as a DAS28-ESR > 2.6 or restart of a bDMARD/tsDMARD. Time to loss of remission was the main outcome. Kaplan-Meier methods were applied and Cox regression was used for multivariable analyses adjusting for confounding factors. Missing data were imputed using multiple imputation. A total of 318 patients in a bDMARD/tsDMARD-free remission were followed between 1997 and 2017. In total, 241 patients (76%) lost remission after a median time of 0.9 years (95% CI: 0.7, 1.0). The time to loss of remission was shorter in women, in patients with a longer disease duration >4yrs and in patients who did not meet clinical disease activity index (CDAI) remission criteria at baseline. Remission was longer in patients with csDMARD therapy during b/tsDMARD free remission [hazard ratio (HR) 0.8, P =0.05, 95% CI: 0.6, 1.0]. In a real-world patient population, the majority of patients who discontinued b/tsDMARD treatment lost remission within <1 year. Our study confirms that fulfilment of more rigorous remission criteria and csDMARD treatment increases the chance of maintaining b/tsDMARD-free remission.

The efficacy, safety and cost-effectiveness of hydroxychloroquine, sulfasalazine, methotrexate triple therapy in preventing relapse among patients with rheumatoid arthritis achieving clinical remission or low disease activity: the study protocol of a randomized controlled clinical Trial (ESCoRT study)

BackgroundTumor necrosis factor α inhibitors (TNFi) is effective for rheumatoid arthritis (RA) patients who fail to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Because of high cost, the discontinuation is common but often lead to disease relapse. The study aims to investigate, if the combination therapy of csDMARDs is more effective in reducing disease relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi and MTX.MethodsIt will be a two-stage trial. In the first stage, all RA patients who failed to csDMARDs treatment [disease activity score 28 (DAS28)-CRP > 3.2] will receive MTX plus TNFi for no more than 12 weeks. Patients achieving DAS28-CRP < 3.2 during the first stage will be randomized into three groups at 1:1:1 ratio: (A) add hydroxychloroquine (HCQ) and sulfasalazine (SSZ) for the first 12 weeks and then remove TNFi but continue other treatments for the next 48 weeks; (B) maintain TNFi + MTX for 60 weeks; and (C) maintain TNFi + MTX for the first 12 weeks and then remove TNFi but continue MTX monotherapy for the next 48 weeks. The primary outcome will be disease relapse (DAS28-CRP increases by at least 0.6 and > 3.2). Secondary outcomes will include the incremental cost per reducing 1 case of relapse; patient reported intolerance to the treatment; adverse events; change of mean disease activity measured by DAS28, clinical disease activity index (CDAI) and simplified disease activity index (SDAI); the proportion of modified Sharp score increase < 0.3; ultrasound-detected remission in hands; Health Assessment Questionnaire Disability Index (HAQ-DI) and health related quality of life [the five-level EuroQol-5D (EQ-5D-5L) and short form-6D (SF-6D)].DiscussionThe aim of this trail will be to seek effective treatment options of preventing relapse of RA. The results of the current study may provide an instructive recommendation for more economical application of TNFi treatment in RA.Trial registration NCT, NCT02320630. Registered on 16 December 2014. https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=3&cx=-jg9qo2.

Comparative Cost-Effectiveness of Tofacitinib With Continuing Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs for Active Rheumatoid Arthritis in South Korea.

IntroductionThe objective of this study was to evaluate the cost-effectiveness of initiating treatment with tofacitinib and subsequently incorporating it into a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) treatment sequence and to compare the cost-effectiveness of this sequence with that of continuing csDMARDs alone in patients with active rheumatoid arthritis (RA).MethodsA cohort-based Markov model was used to evaluate the cost-effectiveness of two tofacitinib treatment sequences compared with that of continuing the csDMARD treatment sequence over a lifetime. Of the two tofacitinib sequences, the first consisted of initial tofacitinib treatment followed by biologic DMARDs (bDMARDs) and the second consisted of csDMARD treatments followed by tofacitinib. A third treatment sequence, continuing the csDMARD treatment sequence before starting bDMARDs, was used as a comparator. Efficacy was assessed using the American College of Rheumatology (ACR) response rates (ACR 20, ACR 50, and ACR 70) after 6 months, which were converted to changes in the health assessment questionnaire-disability index (HAQ-DI) score. Utility was estimated by mapping from the HAQ-DI score, costs were analyzed from a Korean societal perspective, and outcomes were considered in terms of quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model.ResultsThe incremental cost-effectiveness ratios over a lifetime for starting with tofacitinib and incorporating tofacitinib into the csDMARD treatment sequence versus continuing csDMARDs only were US$14,537 per QALY and US$7,086 per QALY, respectively. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robustness of these results.ConclusionStarting with tofacitinib and incorporating it into a csDMARDs treatment sequence is cost-effective compared to continuing csDMARDs alone in patients with RA.

Concomitant beta-blocker use is associated with a reduced rate of remission in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs: a post hoc multicohort analysis.

Background:Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with increased risk of cardiovascular disease (CVD). Treatment for CVD may involve pharmacological agents that antagonise beta adrenergic receptors. These receptors may play an important role in immunology, and the effects of beta-blockers (BB) in RA is unknown. The aim of this study was to investigate the association between BB use and remission in patients with RA initiating tocilizumab +/− conventional synthetic (cs-) DMARD therapy.Methods:Data was pooled from five randomised trials investigating tocilizumab and/or csDMARD treatment in RA (primarily methotrexate). The association between BB use and remission according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) was assessed by Cox proportional hazard analysis. Sensitivity analysis in patients with pre-existing CVD and an exploratory analysis of the impact of other CVD drugs were conducted.Results:Data were available from 5502 participants, 594 (10.8%) of whom were using systemic BB. BB use was associated with less frequent SDAI remission in the total [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.57–0.87, p = 0.001] and CVD cohort [adjusted HR 0.72 (0.57–0.90, p = 0.005)]. The association was consistent between trials (interaction p = 0.44) and treatment arms (interaction p = 0.06). No significant association between remission and β1-receptor selectivity was identified (p = 0.16), and the association was independent from other cardiovascular drug use. Similar associations between BB use and CDAI remission were observed.Conclusion:In a large, pooled cohort of RA patients initiating csDMARDs and/or tocilizumab, BB use was independently associated with less frequent remission.

Clinical characteristics, disease activity, functional status, and quality of life results of patients with psoriatic arthritis using biological and conventional synthetic disease-modifying antirheumatic drugs.

Objectives This study aims to compare the clinical characteristics, disease activity, and quality of life (QoL) of patients with psoriatic arthritis (PsA) who use biological and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in a nationwide cohort throughout Turkey.Patients and methods A total of 961 patients (346 males, 615 females; mean age 46.9±12.2 years; range, 18 to 81 years) with PsA according to the classification criteria for PsA were included in the study. The patients’ demographic and clinical characteristics, physical examination results, Disease Activity Score 28, Disease Activity Index for Psoriatic Arthritis and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Psoriasis Area and Severity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, Psoriatic Arthritis Quality of Life (PsAQoL), and short form-36 scores were all recorded.Results Of the patients, 23% underwent biological DMARD (bDMARD) monotherapy, 42% underwent conventional synthetic DMARD (csDMARD) monotherapy, 10% underwent a csDMARD combination therapy, and 10% underwent a combination bDMARD and csDMARD treatment. The visual analog scale (VAS pain), patient global assessment, physician global assessment, and BASDAI scores were found to be lower among patients using combination treatment of csDMARD and bDMARD, while the swollen joint count was found to be lower among patients using bDMARD. The PsAQoL score was found to be the lowest among patients not using any medication and the highest among those using bDMARD.ConclusionIn our study, patients with PsA were successfully treated with both csDMARD and bDMARD monotherapy. When the biological treatments used for PsA were compared with csDMARD, it was found that biological treatments had a positive effect on both disease activity and the QoL. Combinations of csDMARDs and bDMARDs were preferred in cases in which the disease activity was still high or increased. Because of the highest efficacy of the combined treatment, we highly suggest increasing the number of patients on combined treatment.