Classification Criteria For RA Research Articles

Subjective Symptoms and Disease Activity Related to Serum Zinc Concentration in Primary Sjögren's Syndrome.

Background/Objectives: We examined the frequency of zinc deficiency in patients with Sjögren's syndrome (SS) and the relationship between zinc deficiency and each of the subjective symptoms and disease activity. Methods: We enrolled 164 patients aged ≥ 20 years with primary SS (pSS) based on the revised diagnostic criteria of the Ministry of Health, Labor and Welfare (1999) and 144 patients with RA diagnosed according to the ACR/EULAR classification criteria for RA (2010) as a comparison group. Subjective symptoms were confirmed using an original questionnaire, and disease activity was determined using the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI). The serum zinc concentrations were measured in both SS and RA patients. Results: The rate of zinc deficiency in the SS group was 26.1%, significantly higher than that in the RA group (7.6%). The rate of zinc deficiency was significantly higher in the pSS group compared with Japanese health checkup recipients reported in the literature. The mean serum zinc concentration in primary SS was 60.6 ± 7.3 µmol/L in the high disease activity group with an ESSDAI of ≥5 points, which was significantly lower than the concentration of 69.7 ± 10.2 µmol/L in patients with an ESSDAI of ≤4 points. Conclusions: The frequency of zinc deficiency was higher in patients with pSS than in patients with RA. Disease activity was also higher in patients with zinc deficiency, suggesting an association between zinc concentration and organ involvement in pSS.

Effectiveness and tolerability of antifibrotics in rheumatoid arthritis-associated interstitial lung disease

ObjectiveOur aim was to investigate the effectiveness and tolerability of antifibrotics in a real-world cohort of patients with rheumatoid arthritis-associated interstitial lung diseases (RA-ILD). MethodsIn this retrospective cohort study, we identified RA-ILD patients initiating antifibrotics at Mass General Brigham Integrated Health Care System, a large multi-hospital healthcare system in Boston, MA, USA. We used electronic query to identify all patients with at least 2 RA diagnosis codes and a prescription for either nintedanib or pirfenidone (2014–2023). All analyzed patients met 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for RA and had definite RA-ILD according to Bongartz criteria. Data regarding pulmonary function test (PFT) results, adverse events (AEs), tolerability, and clinical data were collected. A linear mixed model with random intercept was used to compare the within-patient trajectory of the percent predicted forced vital capacity (FVCpp) within 18-months before to 18-months after antifibrotic initiation among those with these PFT data. Lung transplant-free survival and drug retention was estimated in a Kaplan-Meier analysis and a Cox regression analysis was performed to identify independent baseline factors associated with lung transplant or mortality. ResultsWe analyzed 74 patients with RA-ILD that initiated antifibrotics (mean age 67.8 years, 53 % male); 40 patients initiated nintedanib and 34 initiated pirfenidone. Median follow-up was 89 weeks (min 4, max 387). There was a significant improvement in the estimated slope of FVCpp after antifibrotic initiation (−0.3 % per year after initiation compared to −6.2 % per year before antifibrotic initiation, p = 0.03). Nintedanib and pirfenidone had similar FVCpp trajectory. Twenty-six patients (35 %) died and 4 (5 %) had undergone lung transplantation during follow-up. Male sex and heavy smoking were each associated with the composite outcome of lung transplant or mortality. AEs were reported in 41 (55 %) patients, with gastrointestinal (GI) AEs being most common (n = 30). The initial antifibrotic was discontinued in 34 (46 %) patients mostly due to GI AEs (n = 19). The median drug retention time was 142 weeks (95 %CI 56, 262) with no difference between nintedanib and pirfenidone (p = 0.68). ConclusionIn this first real-world study of antifibrotic use dedicated to RA-ILD, antifibrotic initiation was associated with a modestly improved trajectory of FVCpp. AEs were frequently reported, particularly GI, and discontinuation was common. However, lung transplant and mortality rates were still high, emphasizing the need for further therapeutic strategies in patients with severe RA-ILD. These real-world data complement previous trial data that investigated efficacy and safety.

THE PREVALENCE OF EYE INVOLVEMENTS IN RHEUMATOID ARTHRITIS AND THEIR CORRELATION WITH ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY IN SULAIMANI GOVERNORATE/IRAQ

BackgroundRheumatoid arthritis is a common autoinflammatory disease that affects the joints and causes several extra-articular problems, including ocular involvement, which typically manifests in the anterior ocular region. The anti-CCP has a sensitivity comparable to the rheumatoid factor and higher specificity for identifying the disease.
 ObjectivesTo estimate the prevalence of eye involvements in Rheumatoid arthritis and their correlation to the anti-cyclic citrullinated peptide antibody.
 Patients and MethodsA cross-sectional study of 121 patients who satisfied the 2010 ACR/EULAR RA Classification Criteria (6/10 or more points) were between 18 and 60. After establishing a patient’s medical history and physical examination, blood samples were collected to test for anti-CCP antibodies, and an eye exam was conducted.
 ResultsThere were significantly more females than males;104 (86%) were female, and 17 (14%) were males. The median age was 47(42−53.5) years. The median disease duration was 4(2−10) years. The mean disease activity was 3.86 ±1, and the median anti-cyclic citrullinated antibody titers were 29.18(16.75−133.35) U/ml. The overall eye complications typical of Rheumatoid arthritis were observed in 37 (30.6%) and 84 (69.4%) without eye involvement. Dry eyes were the most frequent eye complaint (29.8%). One instance with episcleritis (0.8%). One with filamentary keratitis (0.8%). Anterior uveitis was detected in two cases (1.7%). Eye involvement correlated with anti-cyclic citrullinated peptide antibody (P- value 0.004).
 ConclusionEye manifestations of rheumatoid arthritis were a prominent part of extra-articular manifestation. The dry eye was the most apparent manifestation, and they correlated to the anti-CCP antibody.

Is symptom duration before DMARD therapy a determinant of direct and indirect costs in DMARD-naïve RA patients? A systematic review.

Early treatment of RA improves clinical outcomes; however, the impact on health economic outcomes is unclear. This review sought to investigate the relationship between symptom/disease duration and resource utilization/costs and the responsiveness of costs following RA diagnosis. A systematic search was performed on Pubmed, EMBASE, CINAHL and Medline. Studies were eligible if patients were DMARD-naïve and fulfilled 1987 ACR or 2010 ACR/EULAR RA classification criteria. Studies had to report symptom/disease duration and resource utilization or direct/indirect costs as health economic outcomes. The relationships between symptom/disease duration and costs were explored. Three hundred and fifty-seven records were identified in a systematic search; nine were eligible for analysis. The mean/median of symptom/disease duration in studies ranged between 25 days and 6 years. Annual direct costs of RA following diagnosis showed a U-shaped distribution in two studies. Longer symptom duration before starting a DMARD (>180 days) was associated with lower health-care utilization in the first year of RA diagnosis in one study. Annual direct and indirect costs 6 months before RA diagnosis were higher in patients with shorter symptom duration (<6 months) in one study. Given the clinical and methodological heterogeneities, the association between symptom/disease duration and costs after diagnosis was not computed. The association between symptom/disease duration at the time of DMARD initiation and resource utilization/cost in patients with RA remains unclear. Health economic modelling with clearly defined symptom duration, resource utilization and long-term productivity is vital to address this evidence gap.

Single-cell RNA transcriptomic and plasma Lipidomic reveal the potential mechanisms of a Methotrexate-based therapy against Rheumatoid Arthritis

ObjectiveTo assess whether a Methotrexate-based therapy could achieve more clinical benefit, we arranged a Simon 2-Stage Phase 1 Trial. Single-cell RNA sequencing and lipidomic profiling were performed to reveal the potential mechanisms. MethodsPatients were enrolled in an open-label, Simon 2-stage, single-center, single-arm trial at Guangdong Provincial Hospital of Chinese Medicine. Main inclusion criteria were defined as follows: Aged 18 to 70, low to medium disease activity, fulfilled the RA classification criteria of EULAR/ACR 2010. Patients received the oral medication of MTX 10–15 mg weekly and natural product granules twice a day. Primary outcome was the American College of Rheumatology (ACR) 20% preliminary definition of improvement. Single-cell RNA sequencing(scRNA-seq) on peripheral blood mononuclear cells (PBMCs) was used to show the aberrant metabolism before and after the trial. Plasma lipidomic profiling quantified the lipid changes caused by this MTX-based therapy. Finally, post-hoc analysis on responders and non-responders were used for further analysis. ResultsBetween October 2020 and June 2022, 46 patients received treatment, while 42 finished follow-ups. 27 of 46 (58.70%) patients achieved ACR20, and significant changes were observed in several secondary outcomes. Comparative scRNA-seq analysis before and after the treatment revealed that lipidomic metabolism was broadly downregulated. Plasma lipidomic profiling reveals that 40 lipids were observed significantly changed. Post-hoc analysis showed the lipid changes were separately linked to clinical parameters in responders and non-responders. ConclusionThe study reveals that the combination therapy of HQT+MTX is effective and has a certain correlation with lipid metabolism, but more rigorous study design is still needed to confirm this speculation.

The frequency and factors affecting anxiety and depression in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Anxiety and depression are important problems in patients with RA. The aim of this study was to determine the frequency and the factors affecting depression and anxiety in patients with RA. One hundred and eighty-two patients with RA, aged 18-85 years, were included in this study. The diagnosis of RA was established according to ACR/EULAR RA classification criteria from 2010. Psychosis, pregnancy, breastfeeding and malignancy were exclusion criteria. The demographic data as well as disease duration, educational status, Disease Activity Score with 28-joint counts (DAS28), Health Assessment Questionnaire (HAQ) score and the Hospital Anxiety and Depression Scale (HADS) were the parameters used in the analysis. Depression symptoms were present in 50.3%, anxiety in 25.3% of the studied patients. In patients with depression and/or anxiety HAQ and DAS28 scores were higher than other studied RA patients. Depression was determined at significantly higher rates in females, housewives and those with a low education level. Anxiety was determined significantly more often in blue-collar workers. In the present study, depression and anxiety were observed at high rates in patients with RA. These results confirm the real problem in RA patients in comparison to the general population. This points to the relationship between inflammation and depression and anxiety. Psychiatric evaluations and mental status assessment should not be forgotten together with physical examinations of RA patients.

The validity and reliability of the Turkish version of the Arthritis Impact Measurement Scale 2-Short Form (AIMS2-SF) for rheumatoid arthritis.

The objective of this study is to investigate the validity and reliability of the Turkish version of the Arthritis Impact Measurement Scale 2-Short Form (AIMS2-SF). Subjects fulfilling the ACR 2010 classification criteria for RA were enrolled into the study. Scale reliability was investigated using test-retest reliability (intra-class correlation coefficient-ICC) and internal consistency approaches (Cronbach's α). Spearman's rank correlation coefficients evaluated relationships between quantitative parameters and validity. Construct validity was assessed by correlating AIMS2-SF with clinical parameters and functional parameters including, Nottingham Health Profile (NHP), Health Assessment Questionnaire (HAQ), Beck Depression Inventory (BDI) and Duruöz Hand Index (DHI). One hundred and sixteen patients (105 females and 11 males) were recruited. The mean age ± standard deviation (SD) was 52.45 ± 11.48years. Cronbach's α was 0.88 and the ICC was 0.91. There were significant correlations (rho and p values) with parameters directly related to health-related quality of life (HRQoL); NHP subscales (energy levels: 0.54, pain: 0.62, emotional reaction: 0.50, sleep 0.44, social interaction: 0.51, physical activity: 0.61; p < 0.0005), HAQ (0.60, p < 0.0005), BDI (0.63, p < 0.001) and DHI (0.63, p < 0.0005). Poor or non-significant correlations were found for parameters not directly related to QoL, such as age (0.07, p = 0.45) and disease duration (0.12, p = 0.21); however, disease activity (0.43, p < 0.0005) and NRS pain (0.46, p < 0.0005) were correlated with AIMS2-SF as moderate. The Turkish AIMS2-SF version is a reliable and valid tool that may be used to evaluate QoL for RA. The scale can be easily used in daily practice.

Anti-protein arginine deiminase antibodies are distinctly associated with joint and lung involvement in rheumatoid arthritis.

RA is a chronic inflammatory disease in which possible interstitial lung disease (ILD) is an extra-articular manifestation that carries significant morbidity and mortality. RF and ACPA are included in the RA classification criteria but prognostic and diagnostic biomarkers for disease endotyping and RA-ILD are lacking. Anti-protein arginine deiminase antibodies (anti-PAD) are a novel class of autoantibodies identified in RA. This study aimed to assess clinical features, ACPA and anti-PAD antibodies in RA patients with articular involvement and ILD. We retrospectively collected joint erosions, space narrowing, clinical features and lung involvement of a cohort of 71 patients fulfilling the 2010 ACR/EULAR RA classification criteria. Serum samples from these patients were tested for ACPA IgG (QUANTA Flash CCP3), and anti-PAD3 and anti-PAD4 IgG, measured with novel assays based on a particle-based multi-analyte technology (PMAT). Anti-PAD4 antibodies were significantly associated with radiographic injury (P = 0.027) and erosions (P = 0.02). Similarly, ACPA levels were associated with erosive disease (P = 0.014). Anti-PAD3/4 double-positive patients displayed more joint erosions than patients with anti-PAD4 antibodies only or negative for both (P = 0.014 and P = 0.037, respectively). RA-ILD (15.5%, 11/71 patients) was associated with older age (P < 0.001), shorter disease duration (P = 0.045) and less erosive disease (P = 0.0063). ACPA were elevated in RA-ILD, while anti-PAD4 were negatively associated (P = 0.043). Anti-PAD4 and anti-PAD3 antibodies identify RA patients with higher radiographic injury and bone erosions. In our cohort, ILD is associated with lower radiographic and erosive damage, as well as low levels of anti-PAD4 antibodies.

Stage-specific roles of microbial dysbiosis and metabolic disorders in rheumatoid arthritis

ObjectiveRheumatoid arthritis (RA) is a progressive disease including four stages, where gut microbiome is associated with pathogenesis. We aimed to investigate stage-specific roles of microbial dysbiosis and metabolic disorders in...

Are SMAD2/4/7 genetic variants associated with rheumatoid arthritis susceptibility and severity?

SMADs play one of the key roles in the TGFβ signalling pathway. Therefore, through their involvement in the immune response as well as in the fibrosis process, these proteins appear to take on one of the essential functions in the pathogenesis of autoimmune connective tissue diseases such as RA. This study aimed to investigate the association of selected SNPs in SMAD2/4/7 with RA risk in the Caucasian population and disease course in RA patients. The study was conducted on 647 patients with established RA and 496 unrelated healthy controls (HCs). All patients fulfilled the American College of Rheumatology Diagnostic classification criteria for RA (ACR 1987). The analysis has been conducted using TaqMan genotyping assay. Transcript-inferred pathogenicity score (TraP-score) has been evaluated by TrapScore. PredictSNP.2 has been used to predict the effect of amino acid substitutions. The present study revealed in SMAD4 a significantly higher frequency of AG rs12456284 (under codominant model OR=0.62 p=0.027 and overdominant model OR=0.59 p=0.016) and GA rs10502913 (under codominant model OR=0.65 p=0.050 and overdominant OR=0.64 p=0.033) genotypes in healthy subjects in comparison to RA patients. Additionally, very strong LD has been noted between these two genetic variants (D'=0.95 r2=0.90). Moreover, bioinformatic analysis classified rs12456284 as deleterious change with 94% prediction accuracy. SMAD2 rs1792666 and SMAD7 rs3736242 showed to have the highest association with disease course. SMAD4 rs10502913, SMAD7 rs3736242, and SMAD7 rs4464148 were associated with the concentration of creatinine. Our results suggested that rs12456284 and rs10502913 in SMAD4 may have a potential protective effect against RA. Particularly, SMAD2 rs1792666 and SMAD7 rs3736242 seem to be significantly associated with diseases course in RA patients in the Caucasian population.

AB0169 EARLY REMISSION AT 6 MONTHS AS A PREDICTOR OF LONGTERM REMISSION IN NEW ONSET RHEUMATOID ARTHRITIS

BackgroundEarly therapeutic intervention is crucial for patients with early rheumatoid arthritis (ERA). The goal of remission is achievable in a large proportion of ERA patients.ObjectivesTo evaluate the rate of patients in remission at 6 months and to correlate the 36 and 60 months remission rate in the Belgian CAP48 cohort and the UCLouvain Brussels cohort. To identify baseline characteristics differences between patients achieving remission or not.MethodsWe included patients with ERA from the CAP48 cohort and from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 RA classification criteria. All patients were naïve to csDMARDs therapy. We collected patient characteristics at baseline and clinical response was analysed at 6, 36 and 60 months.Results287 RA patients from our UCLouvain Brussels Cohort and the CAP48 cohort were analysed (211 Females, 76 Males, mean age 46.2 years, 43.4% with baseline erosion, 70.1% with ACPA, 70.3% with Rheumatoid Factor, mean HAQ 1.16, mean DAS28-CRP 4.67, mean SDAI 24.9 and mean CDAI 24.1).Table 1.The clinical results are summarized in the Table.DAS28-CRPMean(±SD)SDAIMean(±SD)CDAIMean(±SD)Remission(DAS28-CRP), %HAQMean(±SD)Baseline n=2874.67 (±1.38)26.5 (±15.5)24.1 (±14.4)/1.16 (±0.70)Months 6 n=2872.97 (±1.34)11.3(±12.3)10.5 (±11.8)44,9%0.60 (±0.62)Months 36 n=2872.24 (±1.04)7.5(±8.6)6.2 (±7.8)71,1%0.52 (±0.59)Months 60 n=1962.41 (±1.00)6.4(±6.5)5.7 (±6.2)66,3%0.56 (±0.63)We divided the patients according to whether they achieved remission DAS28-CRP &lt; 2.6 (group 1), or not (group 2) at 6 months.Patient baseline characteristics were similar in the two groups respectively: age (46.7 vs 45.4 yrs); female (68.5 vs 77.3%); smoker (25.6 vs 27.0%); ACPA positive (70.1 vs 75.4%); baseline X-ray erosion (45.0 vs 54.7%).DAS28-CRP, SDAI and CDAI at 6 months could predict long-term remission at 36 and 60 months, Figure:Figure 1.In group 1 global remission (DAS28-CRP&lt;2.6, HAQ&lt;0.5 and no X-ray progression) was observed in 75.6% at 60 months. The majority of these patients (69.4%) are still treated with Methotrexate, the others were treated with combination therapy.ConclusionEarly and long term remission is an achievable goal in our two cohorts. Early diagnosis is critical in standard of care. At 6 months, all remission index criteria are good predictor for long term remission and could be used in daily care.Disclosure of InterestsNone declared

Hematological markers and ultrasound 7-joint inflammation score as add-on tools in the assessment of inflammation in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction that eventually induces severe disability. Inflammation is the key determinant and primary underlying mechanism leading to disability and increased mortality in patients with RA. This study aimed to correlate the hematological markers and ultrasound 7-joint inflammation score to disease activity in rheumatoid arthritis patients.ResultsThe current study involved 54 RA patients diagnosed according to the 2010 ACR/EULAR classification criteria for RA and thirty healthy control subjects. There were 48 females (88.9%) and 6 males (11.1%). The age of patients ranged from 32 to 60 years, with a mean of 46.04 ± 5.65 years. Using disease activity score 28-ESR, total white blood cell count and absolute lymphocytic count were significantly lower in RA patients with high disease activity. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, mean platelet volume, ESR, and CRP were significantly higher in patients with high disease activity using disease activity score 28 CRP. Also, a statistically significant positive correlation was detected between neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and both clinical disease activity scores. Red cell distribution width but not platelet distribution width was significantly higher in RA patients but both parameters had no association or correlation with clinical disease activity scores. Neutrophil-to-lymphocyte ratio was found to have a statistically significant positive correlation with the tenosynovitis score by powered Doppler ultrasound. There were statistically significant positive correlations between disease activity score 28 ESR and CRP and synovitis and tenosynovitis scores by greyscale and powered Doppler ultrasound using the ultrasound 7 score.ConclusionNeutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume could be potential inflammatory markers for follow-up of disease activity in RA patients. The ultrasound 7 score is a simple and practical scoring system for use in the detection of inflammation, even subclinically in RA patients, which may help the physician in his clinical decisions. The combined use of both hematological markers and the ultrasound 7 score may be of great value.

Potential Benefit of Rituximab in Rhupus Patients From a Single-Center: A Series of 16 Cases.

Rhupus syndrome is better characterized, but uncertainties remain, and therapeutic management must be defined. The objective was to analyze therapeutic procedures with a focus on biologic disease-modifying antirheumatic drugs (bDMARDs). This 10-year medical records review was based on diagnosis codes (rheumatoid arthritis [RA] and systemic lupus erythematosus [SLE]) and biological data (anti-CCP testing, anti-dsDNA, and anti-RNP antibodies). Patients fulfilling 2010 ACR/EULAR and 2012 SLICC and/or 2019 ACR/EULAR classification criteria for RA and SLE, respectively, were included. Sixteen patients were identified. Rheumatoid arthritis most often preceded rhupus, with predominant articular pattern; 11 of them had erosive arthropathy. Skin involvement was the most frequent associated manifestation (n = 12). Serious events were reported, including active glomerulonephritis (n = 3), ischemic stroke (n = 1), and myocardial infarction (n = 1). Immunological profiles showed positivity for antinuclear (n = 16), anti-dsDNA (n = 9), and anti-CCP (n = 9). Ten patients required bDMARDs. All types of RA-approved bDMARDs were used. Abatacept was considered effective in 3 of the 4 patients, with 1 primary failure, 1 secondary escape, and 2 therapeutic maintenances, whereas primary or secondary failure was observed under tocilizimub and TNF-blocking agents. Rituximab was the most prescribed (n = 9) and the most effective with a sustained response in 6 patients. In rhupus refractory to conventional treatment, T or B lymphocytes targeted therapies, and particularly rituximab, seem to be a relevant therapeutic option unlike anticytokine biologics.

Hand and foot MRI in contemporary undifferentiated arthritis: in which patients is MRI valuable to detect rheumatoid arthritis early? A large prospective study.

ObjectivesIdentifying patients that will develop RA among those presenting with undifferentiated arthritis (UA) remains a clinical dilemma. Although MRI is helpful according to EULAR recommendations, this has only been determined in UA patients not fulfilling 1987 RA criteria, while some of these patients are currently considered as RA because they fulfil the 2010 criteria. Therefore, we studied the predictive value of MRI for progression to RA in the current UA population, i.e. not fulfilling RA classification criteria (either 1987 or 2010 criteria) and not having an alternate diagnosis. Additionally, the value of MRI was studied in patients with a clinical diagnosis of UA, regardless of the classification criteria.MethodsTwo UA populations were studied: criteria-based UA as described above (n = 405) and expert-opinion-based UA (n = 564), i.e. UA indicated by treating rheumatologists. These patients were retrieved from a large cohort of consecutively included early arthritis patients that underwent contrast-enhanced MRI scans of hand and foot at baseline. MRIs were scored for osteitis, synovitis and tenosynovitis. Patients were followed for RA development during the course of 1 year. Test characteristics of MRI were determined separately for subgroups based on joint involvement and autoantibody status.ResultsAmong criteria-based UA patients (n = 405), 21% developed RA. MRI-detected synovitis and MRI-detected tenosynovitis were predictive for progression to RA. MRI-detected tenosynovitis was independently associated with RA progression (odds ratio (OR) 2.79; 95% CI 1.40, 5.58), especially within ACPA-negative UA patients (OR 2.91; 95% CI 1.42, 5.96). Prior risks of RA development for UA patients with mono-, oligo- and polyarthritis were 3%, 19% and 46%, respectively. MRI results changed this risk most within the oligoarthritis subgroup: positive predictive value was 27% and negative predictive value 93%. Similar results were found in expert-opinion-based UA (n = 564).ConclusionThis large cohort study showed that MRI is most valuable in ACPA-negative UA patients with oligoarthritis; a negative MRI could aid in preventing overtreatment.

Prevalence and impact of fibromyalgia on disease activity in a sample of Iraqi patients with rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease. Fibromyalgia (FM) is a common diffuse pain syndrome in several rheumatic diseases. This study aimed to find the prevalence of FM in RA patients and to explore its impact on the disease activity of RA patients.Material and methodsA total of 170 RA patients diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA were enrolled in this cross-sectional study. Age, gender, body mass index, marital status, educational level, occupation, smoking history, disease duration, and medications used were reported. Fibromyalgia was diagnosed by using the fibromyalgia criteria 2016 revision. The disease activity of RA patients was measured by using the clinical disease activity index (CDAI) and disease activity score-28 (DAS28).ResultsThe mean age of fibromyalgia syndrome (FMS) patients was 51.263 ±11.531 years, and for non-FMS patients it was 48.469 ±13.932 years. FM was present in 57 (42.7%) RA patients, among whom the prevalence of FMS among female patients was 36.4%, which was significantly higher than that among male patients, at 6.3% (p = 0.015). FM significantly increased the disease activity measured by DAS28 ( = 0.241, p = 0.001) and by CDAI ( = 0.359, p &lt; 0.001). Female gender and functional class of patients with RA positively increase the disease activity DAS28 ( = 0.142, p = 0.032;  = 0.396, p &gt; 0.001), while only functional class increased the disease activity measured by CDAI ( = 0.373, p &gt; 0.001).ConclusionsThe occurrence of FM in RA patients was common, and there was significant positive correlation between FMS severity and RA disease activity.

DAS28‐CRP Cutoffs for High Disease Activity and Remission Are Lower Than DAS28‐ESR in Rheumatoid Arthritis

ObjectiveGuidelines do not specify how cutoffs for high disease activity differ between the Disease Activity Score 28‐joint count indices DAS28–erythrocyte sedimentation rate (ESR) and DAS28–C‐reactive protein (CRP). Studies that compare DAS28‐CRP and DAS28‐ESR depend on data from clinical trials, registries, or practices with multiple providers. Existing studies use data from patients who received immunosuppressive therapy. This study compared the DAS28‐ESR and DAS28‐CRP values from immunosuppressive treatment–naïve patients in a single physician practice.MethodsA retrospective electronic medical chart review was conducted for new diagnoses of rheumatoid arthritis (RA; International Classification of Diseases [ICD]‐9 714), based on the American College of Rheumatology/European League against Rheumatology 2010 RA classification criteria. The number of patients with high disease activity (>5.1) was compared using ESR and CRP data to calculate the proportion of discordance. A receiver operator curve and Youden index was used to calculate the DAS28‐CRP high disease activity cutoff estimation that corresponds with DAS28‐ESR of more than 5.1.ResultsThere were 171 patients included in this study. The baseline mean DAS28‐ESR was higher than the baseline mean DAS‐28 CRP: 5.1 ± 1.2 versus 4.1 ± 1.0 (P < 0.001); 48.5% of patients met criteria for high disease activity (score >5.1) compared with only 14.6% when measured by DAS28‐CRP. Discordance was 33.9%. κ coefficient was only .307. Receiver operator curve and Youden index analysis suggested that the cutoff point for high disease activity of DAS28‐CRP greater than 4.1, which corresponds to DAS28‐ESR greater than 5.1. Similarly, DAS28‐ESR posttreatment scores were significantly higher than DAS28‐CRP. When measured by DAS28‐ESR, patients in remission had higher scores as measured by DAS28‐ESR (1.81) than DAS28‐CRP (1.45).ConclusionThere is a difference between DAS28‐ESR and DAS28‐CRP, even when calculated for immunosuppressive treatment–naïve patients. DAS28‐CRP is significantly lower than DAS28‐ESR.

Effectiveness of TOcilizumab in comparison to Prednisone In Rheumatoid Arthritis patients with insufficient response to disease-modifying antirheumatic drugs (TOPIRA): study protocol for a pragmatic trial

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, predominantly affecting joints, which is initially treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). In RA patients with insufficient response to csDMARDs, the addition of prednisone or tocilizumab, a biological DMARD (bDMARD), to the medication has been shown to be effective in reducing RA symptoms. However, which of these two treatment strategies has superior effectiveness and safety is unknown.MethodsIn this multicenter, investigator-initiated, open-label, randomized, pragmatic trial, we aim to recruit 120 RA patients meeting the 2010 ACR/EULAR classification criteria for RA, with active disease defined as a Clinical Disease Activity Index (CDAI) > 10 and at least one swollen joint of the 28 assessed. Patients must be on stable treatment with csDMARDs for ≥ 8 weeks prior to screening and must have been treated with ≥ 2 DMARDs, of which a maximum of one tumor necrosis factor inhibitor (a class of bDMARDs) is allowed. Previous use of other bDMARDs or targeted synthetic DMARDs is not allowed. Patients will be randomized in a 1:1 ratio to receive either tocilizumab (subcutaneously at 162 mg/week) or prednisone (orally at 10 mg/day) as an addition to their current csDMARD therapy. Study visits will be performed at screening; baseline; and months 1, 2, 3, 6, 9, and 12. Study medication will be tapered in case of clinical remission (CDAI ≤ 2.8 and ≤ 1 swollen joint at two consecutive 3-monthly visits) with careful monitoring of disease activity. In case of persistent high disease activity at or after month 3 (CDAI > 22 at any visit or > 10 at two consecutive visits), patients will switch to the other strategy arm. Primary outcome is a change in CDAI from baseline to 12 months. Secondary outcomes are additional clinical response and quality of life measures, drug retention rate, radiographically detectable progression of joint damage, functional ability, and cost utility. Safety outcomes include tocilizumab-associated adverse events (AEs), glucocorticoid-associated AEs, and serious AEs.DiscussionThis will be the first randomized clinical trial comparing addition of oral prednisone or of tocilizumab head to head in RA patients with insufficient response to csDMARD therapy. It will yield important information for clinical rheumatology practice.Trial registrationThis trial was prospectively registered in the Netherlands Trial Register on October 7, 2019 (NL8070). The Netherlands Trial Register contains all items from the World Health Organization Trial Registration Data Set.

P240 Can ultrasound alone predict the need to treat ACPA positive individuals without synovitis?

Abstract Background In anti-cyclic citrullinated peptide antibody-positive (ACPA+) individuals without clinical synovitis (at-risk), to define the critical ultrasound (US) features sufficiently predictive for inflammatory arthritis (IA) to enable logical initiation of therapy. Methods In a single centre prospective cohort, at risk ACPA+ individuals with a new musculoskeletal symptoms underwent an US scan of 38 joints and 18 tendons at first visit. The predictive value of US abnormalities (Power Doppler (PD), Grey Scale (GS), erosion or tenosynovitis (TSV)) for progression to IA was analysed and the best predictive joints determined by Multivariable Cox Regression, adjusted for confounders. The US results were combined with clinical symptoms/findings to produce predictive models. Results Consecutive at-risk ACPA+ individuals (n = 457, mean age 50.3 years old, 74.2% women) were followed up for median of 15.4 months (range 0.1-127.4), a complete dataset with follow-up of at least 6 months was available for 319 of them. 135 (29.5%) developed IA after a median of 11.3 months (range 0.1-111.7). The negative predictive value of a US scan without any abnormality was 82%. In multivariable Cox regression, both PD and TSV were predictive of progression, with respectively hazard ratios of 1.2 (9=0.026) and 1.13 (p = 0.025). All US abnormalities had a high specificity (spec) but only moderate sensitivity (sens), PD was the most specific with a spec/sens of 0.94/0.23, followed by TSV with a spec/sens of 0.91/0.26 but the best area under the curve (AUC) of 0.599 (P = 0.0015). The addition ACPA titre (high compared to low), but not GS, improved spec/sens up to 0.92/0.34 and AUC to 0.964 (p &amp;lt; 0.001). A selection of US and clinical data of 14 joints also improved prediction, with an AUC of 0.670 (p &amp;lt; 0.001) and a spec/sens of 0.65/0.62. A selection of the 34 most predictive features reached the same sens/spec as the ACR/EULAR 2010 classification criteria for RA, showing a spec/sens of 0.80/0.56. Conclusion In at-risk ACPA+ individuals, the presence of sub-clinical US abnormalities are highly specific for progression to IA. The only moderate sensitivity can be improved by using joints or features selection in combination with clinical examination. These results are the first step in providing guidance for which at-risk ACPA+ individuals to treat. Disclosures L.M. Duquenne None. K. Mankia None. L. Garcia Montoya None. A. Di Matteo None. J. Nam None. P. Emery None.

O37 Utility of RA classification criteria in early inflammatory arthritis referral prioritisation

Abstract Background Early arthritis clinics are increasingly utilised as a method of ensuring patients suspected of disease are assessed promptly to enable suitable treatment. Early recognition with treat to target has been demonstrated in systematic reviews to significantly improve mortality and morbidity outcomes. The United Kingdom’s National Institute for Health and Care Excellence (NICE) recommend potentially affected patients are referred from primary care within 3 days and seen in secondary care within 3 weeks. We hypothesised that utilising the ACR/EULAR 2010 rheumatoid arthritis classification criteria we could identify variables within the primary care referral which make an early arthritis more or less likely. Methods A retrospective study of all the patients seen in early inflammatory arthritis (EIA) Clinic from September 2017 to August 2018 in Aneurin Bevan University Health Board. EULAR scores of 145 patients were calculated based on the data provided in the primary care referral. These scores and their components were then compared to the eventual diagnosis. Results EULAR score of ≥ 5 had specificity of &amp;gt; 78% and sensitivity of &amp;lt; 30% in predicting EIA. EULAR score of 8 or more was 100% specific for EIA with positive likelihood ratio of infinity. Whereas EULAR score &amp;lt; 3 had a specificity of &amp;gt; 70% and sensitivity of &amp;lt; 45% for Non EIA with a positive likelihood ratio of 1.59. Considering individual EULAR components a high positive Rheumatoid Factor (RF) or Anti-citrullinated peptide antibody (ACPA) and involvement of greater than 10 joints had a positive likelihood ratio of ≥ 3.00 for EIA. A low positive RF or ACPA had a specificity of 66.67% and sensitivity of 27.59% for EIA with a positive likelihood ratio of 0.83. Surprisingly involvement of 4-10 small joints or 2-10 large joints or just 1 large joint had a specificity of ≥ 75% for EIA and a positive likelihood ratio of greater than 1.00. A positive ESR or CRP had a specificity of 36.84% and sensitivity of 67.92% with a positive likelihood ratio for EIA of 1.08. A negative ESR and CRP had a specificity of 67.92% and a sensitivity of 35.00% for Non EIA with a positive likelihood ratio of 1.09. The duration of symptoms of &amp;lt; 6 weeks had a specificity of 77.55% and sensitivity of 24.39% with positive likelihood ratio for Non EIA of 1.08, however duration of &amp;gt; 6 weeks had a positive likelihood ratio of 0.97 for EIA with a lower specificity of 22.45% . Conclusion The total EULAR score and individual components can be used to prioritize primary care referrals. A EULAR score of less than 3, duration of symptoms of &amp;lt; 6 weeks, a negative ESR and CRP, a low positive RF or ACPA makes EIA less likely. Disclosures S.M. Imaduddin None. P. O'Biern None.

Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients.

To identify serum sphingolipids that could act as candidate biomarkers in RA. We performed lipidomic analyses in the serum of 82 participants: 19 established RA patients, 18 untreated early RA patients, 13 untreated early arthritis patients not fulfilling the classification criteria for RA, 12 established SpA patients and 20 controls. We compared the lipid levels from the different patient groups with the control group through multiple-regression analyses controlling for age at diagnosis, gender and medication (cDMARDs and corticoids). Established RA patients had significantly increased levels of sphingosine, monohexosylceramide and ceramide compared with controls, when controlling for age and gender. Monohexosylceramide levels remained significantly increased when additionally controlling for medication. On the contrary, SpA patients had significantly decreased levels of ceramide, in both analyses. We observed a detectable increase in the levels of certain sphingolipids in the serum of established RA patients when compared with controls, in line with previous observations in the synovial fluid. Such findings provide further evidence that sphingolipids may play a key role in the pathophysiology of RA.