Moderate High Disease Activity Research Articles

Single-cell RNA-seq analysis reveals cell subsets and gene signatures associated with Rheumatoid Arthritis Disease Activity.

Rheumatoid arthritis (RA) management lean toward achieving remission or low-disease activity. In this study, we conducted single-cell RNA sequencing (scRNAseq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals (18 RA patients and 18 matched controls, accounting for age, sex, race, and ethnicity), to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity. Our analysis revealed 18 distinct PBMC subsets, including an IFITM3 overexpressing Interferon-activated (IFN-activated) monocyte subset. We observed an increase in CD4+ T effector memory cells in patients with moderate to high disease activity (DAS28-CRP ≥ 3.2), and a decrease in non-classical monocytes in patients with low disease activity or remission (DAS28-CRP < 3.2). Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA and matched controls, with a downregulation of pro-inflammatory genes in the gamma-delta T cells subset, alteration of genes associated with RA predisposition in the IFN-activated subset, and non-classical monocytes. Additionally, we identified a gene signature associated with moderate-high disease activity, characterized by upregulation of pro-inflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, G0S2, and downregulation of genes including HLA-DQB1, HLA-DRB5, TNFSF13B. Notably, cell-cell communication analysis revealed an upregulation of signaling pathways, including VISTA, in both moderate-high and remission-low disease activity contexts. Our findings provide valuable insights into the systemic cellular and molecular mechanisms underlying RA disease activity.

Effectiveness and safety of treat-to-target strategy for methotrexate-naïve rheumatoid arthritis patients >75 years of age.

To identify differences in effectiveness and safety of a treat-to-target (T2T) strategy comparing late-onset MTX-naïve RA patients (LORA) ≥75 or <75 years of age. Treatment was adjusted to target low disease activity with conventional synthetic DMARDs followed by biologic DMARDs (bDMARDs) in LORA ≥75 years (n = 98, mean age 80.0 years) and LORA <75 years (n = 99) with moderate-high disease activity. Achievement of Simplified Disease Activity Index (SDAI) remission at week 156 by non-responder imputation analysis was evaluated as a primary outcome. LORA ≥75 years had more comorbidities than LORA <75 years, but SDAI and ACPA positivity were similar at baseline. Of the LORA ≥75 years, 70.4% started MTX and 34.1% and 37.1% received a bDMARD at week 52 and 156, respectively (very similar to the LORA <75 years). Glucocorticoid use was more frequent in the LORA ≥75 years than in the LORA <75 years. Comorbidities/adverse events more frequently contributed to the reasons for non-adherence to T2T in the LORA ≥75 than in the LORA <75. At week 156, 32.7% of the LORA ≥75 and 66.7% of the LORA <75 achieved SDAI remission (P < 0.001). The cumulative incidence of serious adverse events (SAEs) over 156 weeks was 42.8% in the LORA ≥75 and 22.1% in the LORA <75. Multivariable analysis indicated an increased risk of SDAI non-remission at week 156 in the LORA ≥75 [odds ratio 2.82 (95% CI 1.29. 6.14)] after adjusting for comorbidities at baseline, non-adherence to T2T and SAEs. It was more difficult to achieve remission in the LORA ≥75 patients than in the LORA <75 patients due to both poor treatment response and safety issues.

Carotid atherosclerosis in the first five years since rheumatoid arthritis diagnosis: a cross sectional study

BackgroundSystemic inflammation, documented before rheumatoid arthritis (RA) diagnosis, is associated with accelerated atherosclerosis. We aimed to compare the prevalence of carotid plaque (CP) in RA patients in the first five years since diagnosis and healthy controls, and to determine disease characteristics associated with the presence of subclinical atherosclerosis in RA patients.MethodsThis was a cross-sectional study. We recruited 60 RA patients in the first five years since diagnosis and 60 matched healthy controls. Carotid ultrasound was performed to detect the presence of CP and measure carotid-intima media thickness (cIMT). Subclinical atherosclerosis was considered as the presence of CP and/or increased cIMT. Distribution was evaluated with the Kolmogorov-Smirnov test. Comparisons were made with Chi-square or Fisher’s exact test for qualitative variables and Student’s t or Mann-Whitney’s U test for quantitative variables. A p-value < 0.05 was considered significant.ResultsThere were no differences in the demographic characteristics between RA patients and controls. The mean disease duration was 2.66 ± 1.39 years. A higher prevalence of CP (30.0% vs. 11.7%, p = 0.013), bilateral CP (18.3% vs. 3.3%, p = 0.008), increased cIMT (30.0% vs. 6.7%, p = 0.001), and subclinical atherosclerosis (53.3% vs. 18.3%, p = < 0.001) was found in RA patients. RA patients with subclinical atherosclerosis were older (56.70 years vs. 50.00 years, p = 0.002), presented a higher prevalence of dyslipidemia (53.1% vs. 14.3%, p = 0.002), and higher prevalence of classification in moderate-high disease activity category measured by DAS28-CRP (68.8% vs. 35.7%, p = 0.010). The latter variable persisted independently associated with subclinical atherosclerosis in the binary logistic regression (OR 6.11, 95% CI 1.51–24.70, p = 0.011).ConclusionsIn the first five years since diagnosis, higher prevalence of subclinical atherosclerosis, including CP was found in RA patients. Carotid ultrasound should be considered part of the systematic CVR evaluation of RA at the time of diagnosis.

Moderate-High Disease Activity in Patients with Recent-Onset Psoriatic Arthritis-Multivariable Prediction Model Based on Machine Learning.

The aim was to identify patient- and disease-related characteristics predicting moderate-to-high disease activity in recent-onset psoriatic arthritis (PsA). We performed a multicenter observational prospective study (2-year follow-up, regular annual visits) in patients aged ≥18 years who fulfilled the CASPAR criteria and had less than 2 years since the onset of symptoms. The moderate-to-high activity of PsA was defined as DAPSA > 14. We trained a logistic regression model and random forest-type and XGBoost machine learning algorithms to analyze the association between the outcome measure and the variables selected in the bivariate analysis. The sample comprised 158 patients. At the first follow-up visit, 20.8% of the patients who attended the clinic had a moderate-to-severe disease. This percentage rose to 21.2% on the second visit. The variables predicting moderate-high activity were the PsAID score, tender joint count, level of physical activity, and sex. The mean values of the measures of validity of the machine learning algorithms were all high, especially sensitivity (98%; 95% CI: 86.89-100.00). PsAID was the most important variable in the prediction algorithms, reinforcing the convenience of its inclusion in daily clinical practice. Strategies that focus on the needs of women with PsA should be considered.

Increased prevalence of Staphylococcus aureus nasal carriage in rheumatoid arthritis patients with moderate/high disease activity

BackgroundStaphylococcus aureus (S. aureus) nasal carriage is a well-known risk factor for surgical site infection (SSI) after total joint arthroplasty. This study aimed to compare the prevalence of S. aureus nasal carriage between patients with osteoarthritis (OA), a degenerative joint disease, and those with rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease, who underwent total joint arthroplasty, and to investigate the influence of RA disease activity on nasal carriage rate. MethodsThis retrospective study targeted 508 OA and 107 RA patients who underwent S. aureus nasal screening prior to primary total knee and/or hip arthroplasty. RA patients were divided into two groups based on disease activity: the remission/low disease activity (REM/LDA) group and the moderate/high disease activity (MDA/HDA) group. Factors associated with S. aureus nasal carriage were assessed with multivariate logistic regression models. ResultsOf all 615 patients, 155 (25%) carried S. aureus in their nares. Compared to OA patients, RA patients had a significantly higher rate of S. aureus nasal carriage (24% vs. 33%, p = 0.049). Compared to the REM/LDA group (n = 39), the MDA/HDA group (n = 58) had a significantly higher rate of S. aureus nasal carriage (21% vs. 41%, p = 0.032). Multivariate analysis revealed that the MDA/HDA group, but not the REM/LDA group, had a significantly higher odds of S. aureus nasal carriage compared to the OA group (odds ratio: 2.76, 95% confidence interval: 1.07–7.12). ConclusionPreoperative nasal screening for S. aureus is beneficial, especially in RA patients with moderate/high disease activity.

"From Where I Stand": using multiple anchors yields different benchmarks for meaningful improvement and worsening in the rheumatoid arthritis flare questionnaire (RA-FQ).

The Rheumatoid Arthritis Flare Questionnaire (RA-FQ) is a patient-reported measure of disease activity in RA. We estimated minimal and meaningful change from the perspective of RA patients, physicians, and using a disease activity index. Data were from 3- to 6-month visits of adults with early RA enrolled in the Canadian Early Arthritis Cohort. Participants completed the RA-FQ, the Patient Global Assessment of RA, and the Patient Global Change Impression at consecutive visits. Rheumatologists recorded joint counts and MD Global. Clinical Disease Activity Index (CDAI) scores were computed. We compared mean RA-FQ change across categories using patients, physicians, and CDAI anchors. The 808 adults were mostly white (84%) women (71%) with a mean age of 55 and moderate-high disease activity (85%) at enrollment. At V2, 79% of patients classified their RA as changed; 59% were better and 20% were worse. Patients reporting they were a lot worse had a mean RA-FQ increase of 8.9 points, whereas those who were a lot better had a -6.0 decrease. Minimal worsening and improvement were associated with a mean 4.7 and -1.8 change in RA-FQ, respectively, while patients rating their RA unchanged had stable scores. Physician and CDAI classified more patients as worse than patients, and minimal and meaningful RA-FQ thresholds differed by group. Thresholds to identify meaningful change vary by anchor used. These data offer new evidence demonstrating robust psychometric properties of the RA-FQ and offer guidance about improvement or worsening, supporting its use in RA care, research, and decision-making.

POS0680 PHYSICIANS’ REASONS FOR PRESCRIBING JANUS KINASE INHIBITORS (JAKi) IN PATIENTS WITH RHEUMATOID ARTHRITIS (RA), AND ASSOCIATED ALIGNMENT BETWEEN PHYSICIANS AND PATIENTS IN A REAL-WORLD CLINICAL SETTING

BackgroundShared decision making, a cornerstone of RA management1, allows physicians and their patients to make informed decisions about their treatment goals and choice of care. As new treatments become available, it is important to understand rheumatologists’ reasons for choosing JAKi.ObjectivesThis survey evaluated rheumatologists’ clinical and patient centric reasons for choosing JAKi, in addition to exploring alignment between rheumatologists and RA patients in terms of treatment choice and satisfaction.MethodsThe Adelphi RA Disease Specific Programme™2 is a large, multinational, point-in-time survey conducted amongst rheumatologists and their consulting patients with RA in Europe (Belgium, France, Germany, Italy, Spain, UK) between January and October 2020. Physicians completed record forms for up to 10 consecutive RA patients, collecting demographic, clinical and treatment data, and reasons for current treatment choice. Patients were invited to complete a patient questionnaire to assess their satisfaction with ongoing treatment (5-point scale), and perceptions of shared decision making for the current treatment.Results316 rheumatologists provided data for 3121 patients, of whom 1130 (36.2%) completed patient reported questionnaires. Overall, 67% were female, mean age was 53 years (SD 14), 23% had moderate-high disease activity score (DAS28: &gt;3.2). 68% of patients were currently receiving either a biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD; defined here as advanced therapy, AT), 72% were on first line AT. Overall, physicians and their patients were aligned that a conversation took place about a treatment decision (n=855, 79% net alignment), and this was a shared treatment decision (n=814, 75% net alignment). 15% of patients not taking an AT were reported to have a clinical condition warranting one; reasons for not taking AT included patients’ concerns about infection (24%), conventional synthetic DMARDs were tolerable and safe in the patient (18%), and patient dislike of infusions/injections (17%). Of 2143 patients receiving AT, 19% were prescribed JAKi; 57% as monotherapy, 43% as combination therapy. For physician stated reasons for choice of JAKi, factors were driven by both perceptions of clinical efficacy and onset of action, as well as factors relating to patient acceptability such as method of delivery and ease of use (Table 1). With respect to JAKi treatment (n=135 patient-physician pairs), 62% of physicians and their patients were aligned on satisfaction, however 30% of patients reported less satisfaction than their consulting physician (Figure 1).Table 1.Physician stated clinical and patient centric reasons for prescribing a JAKi in their patients with RA (data are percentage of patients; n=397)Reasons for prescribing JAKiPatients (%)Top 5 clinical reasonsStrong overall efficacy74Fast onset of action49Inhibition of disease progression42Strong efficacy as monotherapy39Achievement of clinical remission37Top 5 patient centric reasonsAcceptability of method of delivery for the patient39Enabling patient to perform everyday tasks/activities36Ease of product use (for the patient)33Improvement or maintenance of quality of life30Improving patient’s mood/state of mind14ConclusionCommunicating the choice of pharmacological therapy to patients with RA has become increasingly complex for physicians with expansion of approved treatments. In this subgroup of patients on JAKi, the drug attributes considered as reasons for prescribing were driven by clinical factors as well as by patient centric attributes. Although communications between patients and physicians were largely aligned, better understanding of patient expectations might serve to improve messaging about treatment options and resulting satisfaction.

Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis

ObjectivesTo evaluate if baricitinib, a Janus kinase inhibitor, further enhances disease-modifying effects by uncoupling the link between disease activity and structural damage progression in patients with rheumatoid arthritis (RA) using...

Subclinical Atherosclerosis Measure by Carotid Ultrasound and Inflammatory Activity in Patients with Rheumatoid Arthritis and Spondylarthritis

Objective: To compare the effect of inflammation on subclinical atherosclerosis using carotid ultrasound in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Methods: Cross-sectional study including 347 participants (148 RA, 159 SpA, and 40 controls). We measured the carotid intima media thickness (cIMT) and detection of atheromatous plaques using carotid ultrasound. We recorded disease activity (DAS28-CRP/ASDAS-CRP) and traditional cardiovascular risk factors. We performed descriptive, bivariate, and linear multivariate analyses (dependent variable: cIMT) to evaluate the influence of diagnosis on cIMT in all patients. Two additional multivariate analyses were performed by stratifying patients according to their inflammatory activity. Results: cIMT correlated with the mean CRP during the previous 5 years in RA, but not with CRP at the cut-off date. We did not find such differences in patients with SpA. The first multivariate model revealed that increased cIMT was more common in patients with RA than in those with SpA (β coefficient, 0.045; 95% confidence interval (95% CI), 0.0002–0.09; p = 0.048) after adjusting for age, sex, disease course, and differential cardiovascular risk factors (arterial hypertension, smoking, statins, and corticosteroids). The second model revealed no differences in cIMT between the 2 groups of patients classified as remission–low activity (β coefficient, 0.020; 95% CI, −0.03 to 0.080; p = 0.500). However, when only patients with moderate–high disease activity were analysed, the cIMT was 0.112 mm greater in those with RA (95% CI, 0.013–0.212; p = 0.026) than in those with SpA after adjusting for the same variables. Conclusions: Subclinical atherosclerosis measured by carotid ultrasound in patients with RA and SpA is comparable when the disease is well controlled. However, when patients have moderate–high disease activity, cIMT is greater in patients with RA than in those with SpA after adjusting for age, sex, disease course, and cardiovascular risk factors. Our results point to greater involvement of disease activity in subclinical atherosclerosis in patients with RA than in those with SpA.

Is Serum C- Reactive Protein to Albumin Ratio Be A New Biomarker for Assessing Disease Activity and Quality of Life in Rheumatoid Arthritis?

The C-reactive protein (CRP)/albumin ratio is a biomarker that has gained importance in recent years in demonstrating systemic inflammation. The aim of this study was to evaluate the relationship of CRP/albumin ratio with disease activity and quality of life in patients with rheumatoid arthritis (RA). Fifty RA patients were included in this cross-sectional study. The CRP/albumin ratio was calculated from the blood of the individuals included in the study. The disease activity score-28 (DAS-28) measurement scale was used to determine disease activity. The Health Assessment Questionnaire (HAQ) was used to assess functional status, and the Short-form health survey 36 (SF-36) was used to assess the quality of life. When the patients were evaluated according to the disease activity level, the CRP/albumin ratio was statistically significantly higher in patients with moderate-high disease activity compared to those in remission in post-hoc analyses (p=0.006). In correlation analyzes, moderate and positive correlation (p=0.002, rs= 0.426; p<0.001, rs= 0.536, respectively) was observed between CRP/albumin ratio and erythrocyte sedimentation rate (ESR) and DAS 28-ESR scores. When the patients were evaluated according to the drug treatments they received, no significant difference was observed between conventional DMARD and biological DMARD users in terms of CRP/albumin ratio, SF-36, and HAQ scores (p>0.05). Our results suggest that CAR may be used in clinics to determine inflammation and disease activity as an inexpensive and easily applicable biomarker.

Preliminary Data on Post Market Safety Profiles of COVID 19 Vaccines in Rheumatic Diseases: Assessments on Various Vaccines in Use, Different Rheumatic Disease Subtypes, and Immunosuppressive Therapies: A Two-Centers Study.

An increased risk of developing severe infections has been evidenced in rheumatic disease (RD) patients, and anti-COVID-19 vaccination is strictly recommended for RD patients. However, up to now, no data are available on safety, immunogenicity and efficacy of COVID-19 vaccinations in RD patients. The possible development of adverse events (AEs), including the flare-up of underlying RD, represents a matter of growing importance. The aim of our study is to assess, in RD patients, the safety profile of different types of approved vaccines and the possible influence of immunosuppressive therapies and clinical or demographic characteristics of RD patients on development of AEs. Participants (n = 185; 30.7%) received anti-COVID-19 vaccinations, 137 with autoimmune/chronic inflammatory RD (Au/cIn-RD) and 48 with nonautoimmune/chronic inflammatory RD (no-Au/cIn-RD). AEs were recorded in 42% of patients after the first dose of vaccine, and in 26% of patients after the second dose. The most common reported AEs after anti-COVID 19 vaccines were site injection pain (17%), headache (12%), fever (12%), myalgia (10%) and fatigue (10%). Relapses of the underlying Au/c-In-RD were recorded in 2.2% of patients after the first dose of vaccine. In Au/c-In-RD the risk of developing AEs after the first dose of vaccine was lower in older patients (OR = 0.95; p = 0.001), and in the group of patients with complete control of RD (OR: 0.2; p = 0.010). A lower percentage of AEs was observed in patients with complete control of their Au/cIn-RD (29%) compared to those with low (57%) or moderate-high disease activity (63%) (p = 0.002 and p = 0.006 respectively). In this study all types of COVID-19 vaccines in use in Italy seemed safe in RD patients. The results of this study might provide reassuring information for Au/cIn RD patients and clinicians and could strengthen the data on vaccine safety to guide the use of COVID-19 vaccines in Au/cIn-RD on immunosuppressive agents.

Doppler enthesitis: a potential useful outcome in the assessment of axial spondyloarthritis and psoriatic arthritis.

To analyse the frequency of power Doppler (PD) enthesitis in active axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients and its potential usefulness in clinical practice. A prospective multicentre cross-sectional study in patients with axSpA and PsA with active disease was undertaken. Patients underwent bilateral ultrasound (US) examination of the peripheral entheses according to the Madrid Sonographic Enthesis Index (MASEI). The MASEI and Outcome Measures in Rheumatology (OMERACT) PD enthesitis definitions were checked. An inter-reader analysis of recorded videos was performed to determine reliability. Sixty-four consecutive patients were included. The mean DAS28 (3.9 ± 1.3) for peripheral involvement, mean BASDAI (5.6 ± 2.2) for axial involvement, and CRP values (10 ± 10.9) reflected moderate-high disease activity at baseline. The mean global MASEI score was 29.4 (± 11.4), and 55 patients (86%) scored ≥ 18 (proposed cut-off point to diagnose SpA). At the patient level, abnormal US findings consistent with at least one enthesis showing a PD signal were observed in 52 (81.3%) patients using the MASEI PD definition and 48 (75%) using the OMERACT PD definition, without significant variation between axSpA and PsA. The inter-reader reliability was excellent (kappa = 0.92 for MASEI PD and 0.86 for OMERACT PD). PD enthesitis was found in the majority of patients with active axSpA and PsA, independent of axial or peripheral affectation. Both MASEI and OMERACT PD definitions were useful in detecting active enthesitis. These findings support the usefulness of a PD US evaluation of entheses in the assessment of axSpA and PsA. Key Points • PD enthesitis is a very common finding in patients with active axSpA and PsA • Both MASEI and OMERACT PD definitions are useful to detect active enthesitis • US enthesitis may reveal information in axSpA and PsA.

The Effect of Anti-TNF Therapy on Cardiac Function in Rheumatoid Arthritis: An Observational Study.

Congestive heart failure (CHF) is the second most prevalent cause of death in rheumatoid arthritis (RA). The systemic inflammatory state in RA patients is deemed responsible for this finding. Anti-inflammatory treatment with anti-tumor necrosis factor (anti-TNF) therapy decreases CV risk and subsequently might improve the cardiac function by lowering the overall inflammatory state. This study investigated the effect of anti-TNF on the cardiac function in RA patients. Fifty one RA patients were included, of which thirty three completed follow-up. Included patients were >18 years, had moderate–high disease activity and no history of cardiac disease. Patients were assessed at baseline and after six months of anti-TNF treatment. Patients underwent conventional Speckle tracking and tissue Doppler echocardiography in combination with clinical and laboratory assessments at baseline and follow-up. The left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) showed no changes during follow-up, LVEF 63% (±9) to 62% (±8) p = 0.097 and GLS −20 (±4) to −20 (±3) p = 0.79, respectively. Furthermore, E/e’ nor E/A changed significantly between baseline and follow-up, respectively 8 (7–9) and 8 (7–9) p = 0.17 and 1.1 (±0.4) and 1.1 (±0.4) p = 0.94. Follow-up NT-proBNP decreased with 23%, from 89 ng/L (47–142) to 69 ng/L (42–155), p = 0.10. Regression analysis revealed no association between change in inflammatory variables and cardiac function. Echocardiography showed no effect of anti-TNF treatment on the cardiac function in RA patients with low prevalence of cardiac dysfunction. Moreover, NT-proBNP decreased, possibly indicating (subtle) improvement of the cardiac function.

Increased Serum Interleukin-2 Levels Are Associated with Abnormal Peripheral Blood Natural Killer Cell Levels in Patients with Active Rheumatoid Arthritis.

Objective To investigate the relationship between serum interleukin-2 (IL-2) levels and disease activity, absolute numbers of peripheral lymphocyte subsets, autoantibodies, and associated cytokines in patients with rheumatoid arthritis (RA). Methods This study included 106 patients with RA, evaluated their disease activity (DAS28 score), and divided them into disease remission (DAS28 ≤ 2.6), low disease activity (DAS28 ≤ 3.2), and moderate-high disease activity (DAS28 > 3.2) groups. Flow cytometry was used to detect the absolute numbers of peripheral lymphocyte subpopulations and CD4+ T cell subsets in each group, and serum cytokine levels were measured using cytometric bead array. Results Serum IL-2 levels in RA patients were positively correlated with disease activity and rheumatoid factor titers (p < 0.001 and p = 0.045, respectively), and multiple regression analysis revealed that serum IL-2 levels were an independent factor affecting disease activity. Serum IL-2 levels were positively correlated with Th17/Treg ratios (p = 0.013). Compared with the remission group, peripheral lymphocyte and CD4+ T lymphocyte subsets in patients with active RA decreased to varying degrees; however, the numbers of peripheral natural killer (NK) cells were significantly higher in the moderate-high disease activity group than in the remission (p = 0.046) and low disease activity (p = 0.020) groups; the percentages of NK cells had the same trend. In addition, the number and percentage of NK cells were positively correlated with serum IL-2 levels (p = 0.018 and p = 0.006, respectively). Conclusions In RA patients, serum IL-2 levels were not only correlated with patients' disease activity and autoantibody levels but were also involved in their Th17/Treg immune imbalance. In addition, in patients with active RA, NK cell levels were abnormally elevated, possibly due to high serum levels of IL-2.

Disease Activity and Anticitrullinated Peptide Antibody Positivity Predict the Worsening of Ventricular Function in Rheumatoid Arthritis.

ObjectiveThis prospective study was designed to analyze the incidence and the factors associated with impairment in left ventricular systolic function (LVSF) overtime in patients with rheumatoid arthritis (RA) without overt cardiac disease. In particular, we verified the hypothesis that a relationship between worsening of LVSF and markers of RA disease activity exists.MethodsOne hundred forty outpatients with RA without overt heart disease underwent clinical, laboratory, and echocardiographic evaluation at baseline and after 35 (interquartile range [IQR] 23‐47) months of follow‐up. A clinical Disease Activity Index (CDAI) score greater than 10 indicated the presence of moderate‐high RA disease activity; data on anticitrullinated peptide antibody (ACPA) positivity were recorded at baseline. Stress‐corrected midwall fractional shortening (sc‐MFS) was used as a measure of LVSF and was considered impaired if less than 86.5%.ResultsAt 36 (IQR 23‐47) months follow‐up, impaired sc‐MFS was detected in 60 of 140 (43%) patients, compared with 80 patients with normal sc‐MFS. Disease duration and activity, ACPA positivity, inflammatory markers, cardiovascular and antirheumatic therapies, and sc‐MFS were similar between the two groups at baseline. A multiple logistic regression analysis showed ACPA positivity, moderate‐high disease activity (CDAI greater than 10), and disease duration as independent predictors of impaired sc‐MFS at follow‐up. Finally, a simple clinical score to predict worsening of LVSF at midterm was built (area under the curve of 0.80, with a sensibility and specificity of 78% and 82%, respectively).ConclusionDisease duration, ACPA positivity, and moderate‐high disease activity are independent prognosticators of LVSF impairment in RA. Adverse changes in heart function could be prevented by good control of inflammation and modulation of autoimmunity.

The Relationship Between Disease Activity, Demographic and Characteristic Features in Individuals with Rheumatoid Arthritis

In the analysis of the data, significant difference between remission and moderate-high disease activity was observed in morning stiffness, presence of deformity, presence of nodule, osteoporosis and exertional dyspnea; whereas statistically significant difference between low and moderate-high disease activity was observed in osteoporosis and dyspnea at rest (p < 0.05).

Responsiveness of the Persian health assessment questionnaire measures in differentiating among disease activity levels in rheumatoid arthritis patients

ObjectivesEvidence suggests that inflammation has a harmful effect on muscle strength as well as on functional disability. The purpose of the present study was to examine the association of objectively measured disease activity levels and functional disability among Iranian patients with Rheumatoid Arthritis (RA), and to analyse whether a Persian version of the health assessment questionnaire-disability index (PHAQ-DI) can distinguish between RA patients at different stages of the disease progression. Materials & methods198 RA patients were requested to complete the PHAQ-DI. The disease activity score for each patient was evaluated using the disease activity score (DAS-28). The association analysis between the PHAQ-DI scores and the four levels of disease activity was measured using a Spearman correlation coefficient. A Kruskal-Wallis analysis was utilized to determine differences in PHAQ-DI scores among the levels of disease activity. The Receiver operating characteristic (ROC) curve was also utilized to determine the PHAQ-DI total score cut-off for predicting the level of disease activity. ResultsSpearman's correlation coefficients between the PHAQ-DI and the disease activity level ranged between 0.59 and 0.75. There were significant differences in the PHAQ-DI total score among known groups with various disease activity levels (P = 0.001); However, HAQ-DI total score could not differentiate the remission phase from low disease activity levels in patients with RA (p = 0.37). The PHAQ-DI total score cut-off for distinguishing remission-low disease activity from moderate-high disease activity was 1.19, with a specificity of 0.91 and a sensitivity of 0.615. ConclusionThe present findings provide evidence for the degree to which the PHAQ-DI measures identify and distinguish disease activity levels in patients with rheumatoid arthritis. The PHAQ-DI questionnaire, as a patient-administered, non-invasive, fast, inexpensive and available tool, can be used in the rheumatologist's office as a substitute for determining disease activity in patients with active RA.

Clinical and therapeutic management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: RADAR study.

To describe the clinical and therapeutic management of rheumatoid arthritis (RA) patients with biological disease-modifying antirheumatic drugs (bDMARDs), alone or in combination with conventional synthetic DMARDs (csDMARDs), as well as analysing changes over time in bDMARD use. An observational, retrospective, multicentre study was conducted in the rheumatology departments of 10 public Spanish hospitals. Patients with RA treated with bDMARDs at baseline who had medical records available in the data collection period 2013-2016 were included. All visits to rheumatology departments recording any type of bDMARD modification (dose, etc.) were collected. Clinical characteristics, concomitant treatment, resource use, work productivity and quality of life (QoL) were recorded. 128 patients were included: 81 received first-line bDMARD treatment, 28 second-line bDMARD treatment and 19 received third or later lines. Mean study follow-up was 4.1years. Assessment of DAS28 was available in 54.6% of visits. At baseline, 48.7% of patients had moderate-high disease activity. At final observation, 69.5% of patients continued with the first bDMARD. Tumour necrosis factor blockers were administered to 85.2% of patients in first line, 45.7% in second line and 18.1% in third or later lines. At final observation, 80.2% of patients still felt pain/discomfort. As expected, those with higher disease activity had higher loss of work productivity and lower QoL, as assessed by DAS28, than patients with lower disease activity. Drugs represented 82.6% of the total cost. In this Spanish cohort of 128 patients, most patients remained on the first prescribed bDMARD, despite remaining signs and symptoms.

Long-Term Radiographic and Patient-Reported Outcomes in Patients with Rheumatoid Arthritis Treated with Tofacitinib: ORAL Start and ORAL Scan Post-hoc Analyses.

IntroductionHere we examine the relationship between achieving different levels of disease activity with tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis), long-term structural progression, and patient-reported physical function.MethodsThis was a post hoc analysis of two 24-month, phase III randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder (IR) patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily as either monotherapy or with background MTX. The modified total Sharp score (mTSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were analyzed at month 24 according to disease activity at month 6 defined by the Clinical Disease Activity Index (CDAI) or the Disease Activity Score in 28 joints, C-reactive protein (DAS28CRP).ResultsMean changes from baseline in mTSS at month 24 were less in patients with CDAI remission at month 6 than in those with CDAI moderate/high disease activity (MDA/HDA) at month 6. A DAS28CRP of < 1.9 most closely approximated CDAI remission (≤ 2.8). Tofacitinib appeared to inhibit joint damage in the presence of persistent inflammation compared with MTX. More patients receiving tofacitinib or MTX with CDAI remission or low disease activity (LDA) at month 6 reported normative HAQ-DI scores (< 0.5) at month 24 than did those with CDAI MDA/HDA.ConclusionRegardless of treatment, in both MTX-naïve and MTX-IR patients, remission or LDA at month 6 was associated with successful long-term outcomes: inhibition of structural progression and normative HAQ-DI scores. Long-term outcomes were similar when patients achieved CDAI remission or a DAS28CRP of < 1.9, confirming that this is an appropriate cut-off for remission with DAS28CRP. Tofacitinib potentially inhibits joint damage even with persistent inflammation.FundingPfizer Inc.Trial registrationClinicaltrials.gov identifiers: NCT01039688 and NCT00847613.Electronic supplementary materialThe online version of this article (10.1007/s40744-018-0113-7) contains supplementary material, which is available to authorized users.

SAT0333 The Influence of Golimumab Levels on Clinical Response in Spondyloarthritis Patients at 52 Weeks of Follow-Up

BackgroundPreviously an association has been demonstrated between drug levels and clinical activity in Spondyloarthritis (SpA) patients treated with Infliximab, Adalimumab or Etanercept. Until now, there is not enough evidence about...