Disease Activity Score 28-CRP Research Articles

Multidimensional biomarker approach integrating tumor markers, inflammatory indicators, and disease activity indicators may improve prediction of rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis (RA) often leads to interstitial lung disease (ILD), significantly affecting patient outcomes. This study explored the diagnostic accuracy of a multi-biomarker approach to offer a more efficient and accessible diagnostic strategy for RA-associated ILD (RA-ILD). Patients diagnosed with RA, with or without ILD, at Beijing Tiantan Hospital from October 2019 to October 2023 were analyzed. A total of 125 RA patients were included, with 76 diagnosed with RA-ILD. The study focused on three categories of indicators: tumor markers, inflammatory indicators, and disease activity measures. The heatmap correlation analysis was employed to analyze the correlation among these indicators. Logistic regression was used to determine odds ratios (OR) for indicators linked to RA-ILD risk. Receiver-operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic potential of these indicators for RA-ILD. The results of logistic regression analysis showed that tumor markers (carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1)), as well as inflammatory indicators (neutrophil, neutrophil-to-lymphocyte ratio (NLR), platelet, C-reactive protein (CRP)) and disease activity measures (disease activity score-28-CRP (DAS28-CRP), rheumatoid factor (RF), and anti-cyclic peptide containing citrulline (anti-CCP)), were significantly associated with RA-ILD. The correlation coefficients among these indicators were relatively low. Notably, the combination indicator 4, which integrated the aforementioned three categories of biomarkers, demonstrated improved diagnostic accuracy with an AUC of 0.857. The study demonstrated that combining tumor markers, inflammatory indicators, and disease activity measures significantly enhanced the prediction of RA-ILD. Key Points • Multidimensional strategy: Integrated tumor markers, inflammatory indicators, and disease activity measures to enhance early detection of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). • Diagnostic accuracy: Employed heatmap correlation and logistic regression, identifying significant associations and improving diagnostic accuracy with a multidimensional biomarker combination. • Superior performance: The combined multidimensional biomarker strategy demonstrated higher diagnostic precision compared to individual or dual-category indicators. • Clinical relevance: Offers a promising, accessible approach for early detection of RA-ILD in clinical settings, potentially improving patient outcomes.

Vatari Guggulu, Hingvashtaka Churna, and Brihat Saindhavadya Taila in the management of rheumatoid arthritis: An open-label, prospective, single-arm multi-center study

Abstract Background: Despite significant advances in the diagnosis and treatment of rheumatoid arthritis (RA), the clinical outcomes remain unsatisfactory in a significant proportion of patients. Ayurveda management for RA (Amavata) has shown promising clinical outcomes in routine clinical practice and as per published research studies. Objective: The study was designed to assess the therapeutic effect and safety of Ayurveda interventions, Vatari Guggulu (VG), Hingvashtaka Churna (HC), and Brihat Saindhavadya Taila (BS) in the management of RA. Materials and Methods: An open-label, prospective, single-arm multicenter study was conducted at Ayurveda Research Institutes in Patna, Bhubaneswar, and Guwahati with a sample size of 180 participants. Patients of any gender aged 20–60 years with clinically diagnosed RA as per the revised American College of Rheumatology criteria and willing to provide written informed consent to participate in the study were included in the study. Ayurveda interventions, VG, HC, and BS, were administered to the study participants for 12 weeks, with a follow-up at four weeks without intervention. The primary outcome measure was a change in the Disease Activity Score-28 (DAS28) from baseline. The other outcome measures included change in the Indian Health Assessment Questionnaire Disability Index score (HAQ-DI), changes in the acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and change in the quality of life parameters (assessed through the SF-36 questionnaire). Results: A total of 180 participants were enrolled in the study, and data of 179 participants were considered for the final analysis. A statistically significant difference was observed in the outcome parameters, such as a mean change in the DAS28 score, HAQ-DI score, SF-36 score, and ESR and CRP levels (P < 0.001) after 12 weeks of treatment. The mean DAS28 score changed from 6.50 ± 0.790 at baseline to 4.21 ± 1.286 on week 16 follow-up (P < 0.001). No participant withdrew from the study due to adverse events. The trial interventions were well-tolerated and safe. Conclusion: The study outcomes provide preliminary evidence of the safety and potential benefits of the Ayurveda interventions in the management of RA. Further, randomized controlled studies may be planned to generate robust evidence on the therapeutic potential of these interventions so that they can be recommended for use in routine clinical practice. Trial registration: CTRI/2014/12/005242.

Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept

BackgroundTo compare a treat-to-target (T2T) approach and routine care (RC) in adults with active to severely active rheumatoid arthritis (RA) initiating subcutaneous abatacept.MethodsA 12-month cluster-randomized trial in active RA patients treated with abatacept was conducted. Physicians were randomized to RC or T2T with a primary endpoint of achieving sustained Clinical Disease Activity Index (CDAI) low disease activity (LDA) at two consecutive assessments approximately 3 months apart. Additional outcomes included Simple Disease Activity Index (SDAI), Disease Activity Score 28-CRP (DAS28-CRP), Routine Assessment of Patient Index Data 3 (RAPID3), and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Time to achieve therapeutic endpoints was assessed with survival analysis.ResultsAmong the 284 enrolled patients, 130 were in the T2T group and 154 in RC. Primary endpoint was achieved by 36.9% and 40.3% of patients in T2T and RC groups, respectively. No significant between-group differences were observed in the odds of achieving secondary outcomes, except for a higher likelihood of CDAI LDA in the T2T group vs. RC (odds ratio [95% confidence interval]: 1.33 [1.03–1.71], p = 0.0263). Compared with RC, patients in the T2T group achieved SDAI remission significantly faster (Kaplan–Meier-estimated mean [standard error]: 14.0 [0.6] vs. 19.3 [0.8] months, p = 0.0428) with a trend toward faster achievement of CDAI LDA/remission, DAS28-CRP remission, and HAQ-DI minimum clinically important difference.ConclusionsPatients managed per T2T and those under RC experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with higher odds of CDAI LDA and a shorter time to achieving therapeutic endpoints.Trial registrationName of the registry: ClinicalTrials.gov.Trial registrations: NCT03274141.Date of registration: September 6, 2017.

Is the Level of Pentraxin-3 a Valid Biomarker in Axial Spondyloarthritis?

Abstract Background Pentraxin-3 (PTX-3) is essential in inflammation, remodelling and regulation of inflammation in various rheumatic diseases. This study aimed to determine whether serum PTX-3 levels indicate increased inflammation and disease activity in patients with axial spondyloarthritis (AxSpA). Material and Methods The study comprised 50 AxSpA patients and 20 healthy controls (HC). Serum PTX-3, interleukin (IL)-17 and IL-23 levels were compared between AxSpA patients and the control group. The relationship between PTX-3 levels and acute-phase reactants and disease activity was examined. Disease activity was scored using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP). Patients with AxSpA were also separated into two subgroups – non-radiographic AxSpA (nr-AxSpA) and radiographic AxSpA (r-AxSpA) – and compared based on their PTX-3 levels. PTX-3, IL-17 and IL-23 levels were measured using the enzyme-linked immunosorbent assay method. Results PTX-3 levels were higher in patients with AxSpA compared with the HC (2.69±2.03 vs 1.84±1.03 ng/mL, p=0.025). When patients were divided into nr-AxSpA and r-AxSpA subgroups, this difference was found to be only due to patients with r-AxSpA. The r-AxSpA group had significantly higher PTX-3 levels than the nr-AxSpA and HC groups (p=0.020 and p=0.016, respectively). There was no statistically significant difference in PTX-3 levels between the nr-AxSpA and HC groups (p=0.961). There was no correlation between PTX-3 levels and acute-phase reactants, IL-17, IL-23 and disease activity scores (BASDAI and ASDAS-CRP). Conclusion These findings support the hypothesis that PTX-3 levels are higher in patients with r-AxSpA, where chronic inflammation and structural progression are more pronounced and can be used as an inflammation marker. However, they demonstrate that this relationship does not exist in nr-AxSpA and that there is no correlation between disease activity and PTX-3 levels. Thus, PTX-3 levels may be associated with structural changes.

Assessment of Vitamin D3 level in patients of rheumatoid arthritis and its relationship with disease activity using DAS 28-CRP in tertiary care center of Bihar, India

Background: Rheumatoid arthritis (RA) is most common type of inflammatory arthritis. It is chronic autoimmune disease that affects joints as well as extra-articular structures. The prevalence of this condition could be due to both genetic and non-genetic factors (e.g., environmental, viral, and hormonal). Aims and Objectives: The aim of the study was to determine and correlate 25(OH) D level with disease severity in patients of RA. Materials and Methods: The prospective observational study consists of 70 patients of RA and 70 healthy controls. Assessed level of 25(OH) D, C-reactive protein (CRP), anti-cyclic citrullinated peptide (CCP), erythrocyte sedimentation rate (ESR), and Disease Activity Score (DAS) 28-CRP score were compared in both cases and controls. Correlation of Vitamin D level with parameters such as CRP, Anti-CCP, and ESR was performed. Correlation between Vitamin D level deficiency and disease activity among the RA patients was assessed. Results: The mean age of patients in the RA group was 37.77±13.31 years. The mean CRP in cases was 40.57±25.94 mg/L and in controls was 3.26±1.95 mg/L with significant intergroup difference (P<0.001). The mean anti-CCP in cases was 62.18±27.21 U/mL and in controls was 4.99±1.52 U/mL with significant intergroup difference (P<0.001). The mean 25(OH) D level in cases was 12.65±5.88 and in controls was 32.18±10.22. The 25(OH) D was significantly decreased in cases than controls (P<0.001). A significant inverse relationship between serum 25(OH) D levels and DAS28 was observed. Receiver operating characteristic (ROC) curves results showed that 25(OH) D<11.7 ng/mL indicates severe disease activity (Area under ROC curve=84%, Sensitivity 77.78%, and specificity 83.33%,). 25(OH) D between 11.7 ng/mL and 19.83 ng/mL indicates moderate disease activity. 25(OH) D˃19.83 ng/mL indicates low disease activity value below 4.13 is alarming situation. Conclusion: The study reveals high prevalence of Vitamin D deficiency and insufficiency in RA patients. There is also significant inverse correlation exist between serum Vitamin D levels and RA disease activity. Vitamin D level is good disease activity predictor in patients of RA.

Serum BMP-2 and BMP-4 levels and their relationship with disease activity in patients with rheumatoid arthritis and ankylosing spondylitis.

This study aims to investigate the levels of bone morphogenic proteins (BMPs), one of the pathways affecting bone turnover in these diseases, and to investigate their relationship with disease activity. Between September 2013 and July 2015, a total of 100 ankylosing spondylitis (AS) patients (53 males, 48 females; median age: 40 years; range, 18 to 62 years), 58 rheumatoid arthritis (RA) patients (25 males, 33 females; median age: 40.5 years; range, 26 to 59 years), and 102 age- and sex-matched healthy controls (55 males, 47 females; median age: 38 years; range, 18 to 55 years) were included in the study. In all groups, serum BMP-2 and BMP-4 levels were measured using enzyme-linked immunosorbent assay (ELISA). Demographic data (age, sex, duration of disease) and acute phase reactants of the patients at the final visit were recorded. Disease activity was assessed through the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (ASDAS-CRP) for AS patients and through the Disease Activity Score-28-CRP (DAS-28-CRP) for RA patients. The median BMP-2 values were found to be significantly higher in the RA group compared to the other groups and in the control group compared to the AS group (p<0.001 for both). There was no significant difference between the groups in terms of median BMP-4 values (p>0.05). No significant relationship was found between serum BMP-2 and BMP-4 levels and disease activity in both AS and RA patients, while there was a weak positive correlation between erythrocyte sedimentation rate and CRP levels with BMP-2 level in RA patients (p=0.014, r=0.320 and p=0.029, r=0.287, respectively). Our study results suggest that the BMP pathway may have different dual effects in AS and RA patients depending on the underlying pathogenesis, and that local effects are more prominent than serum levels.

Disease activity correlates and functionality in patients with rheumatoid arthritis - real-world experience from a South Asian country.

IntroductionThere is a lack of data assessing disease activity in patients with rheumatoid arthritis from Pakistan. We sought to determine the correlation between Disease Activity Score 28 (DAS28) and disease activity parameters and the modified Health Assessment Questionnaire (mHAQ). Secondarily, we evaluated the concordance of acute phase reactants with disease activity.Material and methodsWe prospectively studied 132 patients with rheumatoid arthritis (RA) as per the 2010 American College of Rheumatology/European League Against Rheumatism criteria, not in clinical remission. Based on the DAS28 score, the patients were divided into low, moderate, and high activity groups. The patients were also categorized according to the elevation of acute phase reactants to determine concordance and discordance with DAS28–ESR and DAS28–CRP. Descriptive statistics and Pearson’s correlation were computed.ResultsComplete demographics was available for 132 participants. The mean age was 46.2 ±12.8 years; there were 85.6% (n = 113) females. The mean disease duration was 5.7 ±6.4 years. The (Rephrase as mean ±SD) DAS28 and mHAQ scores were 3.4 ±1.8 and 0.77 ±0.68, respectively. A significant correlation was observed between DAS28 and tender and swollen joint count (r = 0.64; p < 0.001); DAS28 and mHAQ (r = 0.47; p-value < 0.001), DAS28 and patient’s global assessment (PGA) (r = 0.45; p-value < 0.001). A weak correlation was observed between mHAQ and CRP and ESR, with r = 0.242 and 0.225, respectively, p-value < 0.001. In comparison, no correlation of DAS28 with the rheumatoid factor (r = –0.035) or ACPA antibody (r = –0.094) was noted. A positive concordance between ESR and CRP was observed in severely active RA.ConclusionsFrom an outpatient setting in a South Asian country, DAS28–ESR emerged as the preferred choice for an accurate assessment of disease severity in RA when combined with the mHAQ. Acute phase reactants increase positively in concordance with severely active RA, although discordant in low to moderately active disease.

Consideration of differences in drug usage between young-onset and elderly-onset rheumatoid arthritis with target of low disease activity

Objectives Elderly-onset rheumatoid arthritis (EORA) is reported to differ from young-onset rheumatoid arthritis (YORA) with regard to patient background and drug treatment. We examined the amount of drug administered to patients who achieved low disease activity (LDA) for rheumatoid arthritis at our hospital. Methods Demographics, clinical history, and treatments were compared between patients with EORA (n = 70) and YORA (n = 190). Results There was a significant difference in the average age (73.8 vs. 57.8 years), disease duration (6.66 vs. 14.7 years), and sex (62.9% males vs. 83.7% females), but no difference in rheumatoid factor positivity (85.3% vs. 80.7%), anti-citrullinated peptide antibody positivity (86.5% vs. 87.7%), simplified disease activity index (4.28 vs. 4.59), or disease activity score 28-CRP (1.99 vs. 2.04) in the EORA and YORA groups, respectively. There were also no significant differences in prednisolone use (37.1% vs. 36.3%), amount of methotrexate administered (MTX) (1.45 vs. 1.41 mg), and MTX use (55.7% vs. 65.3%). However, the MTX dose (2.89 vs. 4.09 mg/week, p = .011) and overall biologics use (32.9% vs. 56.3%, p = .0012) were significantly lower in patients with EORA than in those with YORA. Conclusion Patients with EORA may be able to achieve LDA with lower drug dosage than those with YORA.

Sustainable positive effects of Ramadan intermittent fasting in rheumatoid arthritis.

The short-term positive effects of intermittent fasting during the month of Ramadan on rheumatic inflammatory diseases have been previously evaluated. The objective of this study was to assess the sustainability of these effects on rheumatoid arthritis (RA) activity. This prospective study included 35 patients with RA, who observed fasting during Ramadan 2019. The disease activity was assessed and compared between three time points: T1 (6months before the beginning of Ramadan), T2 (during the month between the 7th day of fasting and the 7th day after Ramadan), and T3 (averagely 3.4months after fasting). The disease activity score 28 (DAS28) was used to evaluate the disease activity. After a significant decrease of all disease activity parameters between T1 and T2, a gradual increase of clinical and biological outcomes was seen between T2 and T3. Except for CRP, which was significantly higher at T3 (p = 0.02), the changes of the other disease activity parameters were not statistically significant. By reference to baseline data (T1), the decrease of ESR, DAS28 CRP, and DAS28 ESR induced after Ramadan fast was maintained until T3, with statistically significant differences. We can therefore conclude that this study has been conducted at the beginning of the fading-out of the effects of Ramadan fast, and that the duration of 3months may be the recommended interval between fasting periods to maintain the positive effects of intermittent fasting on RA activity. Key Points • Intermittent fasting can induce a rapid improvement of rheumatoid arthritis activity. • The positive effects of this model of fasting can last up to 3months. • The recommended interval between fasting periods may be estimated at 3months.

Yisaipu® Provide AS Patients With an Economical Therapeutic Option While Original Biologicals are More Advantageous in the COVID-19 Epidemic Situation.

Objectives: Anti-tumor necrosis factor (TNF) agents have been regarded as the most effective treatment for ankylosing spondylitis (AS) so far. However, economic factors limited the prescription of original biologicals in China. Yisaipu® is a biosimilar for etanercept as pre fill syringes (PFS), which has entered China’s national medical insurance catalog for more than 10 yr and was widely used because it greatly reduced the economic burden of AS patients. Yisaipu® is provided subcutaneous injection in hospital setting only. We collected clinical data of AS patients before, during and after COVID-19 epidemic, in an attempt to investigate the advantages and disadvantages of original biologicals and Yisaipu® during regular follow up and COVID-19 epidemic.Methods: AS patients who received original biologicals or Yisaipu® in our department for more than 1 yr were included in our study. General data, demographic characteristics, disease activity, quality of life and medical compliance were collected from regular visits. The patients were followed up through telephone interviews from April 20th to 27th, 2020 about the overall impact of the COVID-19 epidemic.Results: There was no significant difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP) between the two groups. Health Assessment Questionnaire for Spondyloarthropathies (HAQ-s) showed that Yisaipu® group was superior to original biological group in terms of eating, gripping and driving. In addition, the medical cost of Yisaipu® was lower than that of original biologicals. The overall impact of the COVID-19 epidemic on patients of original biological group was comparatively smaller than that on Yisaipu® group.Conclusions: Yisaipu® provided AS patients with an economical selection during regular follow-up, while original biologicals had certain advantages in the COVID-19 epidemic setting, including a longer time interval between two drug administrations and the self-injection dose form of medication.

Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT

BackgroundTo investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex.MethodsThe phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex.ResultsEfficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P < 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27− subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively.ConclusionsSecukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/−) and/or MRI (+/−) status, HLA-B27 (+/−) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (−) subgroups. Male patients had higher relative responses than female patients.Trial registrationClinicalTrials.gov, NCT02696031. Registered on 02 March 2016

The Effect of Etanercept in Nonradiographic Axial Spondyloarthritis by Stratified C-Reactive Protein Levels.

ObjectiveBiological agents have shown markedly different response rates by baseline C‐reactive protein (CRP). Here, we determine the response of patients with nonradiographic axial spondyloarthritis (nr‐axSpA) to etanercept stratified by their baseline CRP level.MethodsThe EMBARK trial was a phase 3, randomized, double‐blind, placebo‐controlled study of etanercept in nr‐axSpA. The primary endpoint was Assessment of Spondyloarthritis International Society (ASAS) 40 at Week 12, the conclusion of the double‐blind phase. It recruited patients who met the ASAS criteria for axial spondyloarthritis, and sacroiliac joint magnetic resonance scans were completed on all patients. In this post hoc analysis, we analyzed outcomes by baseline C‐reactive protein (CRP) level of less than 5 mg/L, 5 mg/L to 10 mg/L, and greater than 10 mg/L. The clinical trial outcome data were accessed via the Vivli platform.ResultsIn the less than 5 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, Ankylosing Spondylitis Disease Activity Score‐CRP (ASDAS‐CRP), and ASDAS‐ESR (erythrocyte sedimentation rate) outcomes were 49% (P = 0.84), 26% (P = 0.14), 42% (P = 0.002), and 44% (P = 0.006), respectively. In the 5 to 10 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, ASDAS‐CRP, and ASDAS‐ESR outcomes were 56% (P = 0.99), 31% (P = 0.40), 56% (P = 0.16), and 50% (P = 0.11), respectively. In the greater than10 mg/L CRP group treated with etanercept, the ASAS20 response, ASAS40 response, ASDAS‐CRP, and ASDAS‐ESR outcomes were 74% (P = 0.02), 68% (P = 0.003), 82% (P = 0.005), and 50% (P = 0.001), respectively.ConclusionAlthough there are reduced ASAS20 and ASAS40 response rates in the groups with baseline CRP less than 10 mg/L, there remain clinically relevant responses when the composite outcome measures ASDAS‐CRP or ASDAS‐ESR were used, and this should be considered when deciding on thresholds for reimbursement.

Factors associated with remission at 5-year follow-up in recent-onset axial spondyloarthritis: results from the DESIR cohort.

ObjectiveThe factors contributing to long-term remission in axial SpA (axSpA) are unclear. We aimed to characterize individuals with axSpA at the 5-year follow-up to identify baseline factors associated with remission.MethodsWe included all patients from the DESIR cohort (with recent-onset axSpA) with an available Ankylosing Spondylitis Disease Activity Score–CRP (ASDAS-CRP) at 5-year follow-up. Patients in remission (ASDAS-CRP < 1.3) were compared with those with active disease by demographic, clinical, biological and imaging characteristics. A logistic model stratified on TNF inhibitor (TNFi) exposure was used.ResultsOverall, 111/449 patients (25%) were in remission after 5 years. Among those never exposed to TNFi, 31% (77/247) were in remission compared with 17% (34/202) of those exposed to TNFi. Patients in remission after 5 years were more likely to be male, HLA-B27+, have a lower BMI, and a higher education level. Baseline factors associated with 5-year remission in patients never exposed to TNFi included lower BASDAI [adjusted odds ratio (ORa) 0.9, 95% CI: 0.8, 0.9) and history of peripheral arthritis (ORa 2.1, 95% CI: 1.2, 5.3). In those exposed to TNFi, remission was associated with higher education level (ORa 2.9, 95% CI: 1.6, 5.1), lower enthesitis index (ORa 0.8, 95% CI: 0.7, 0.9), lower BASDAI (ORa 0.9, 95% CI: 0.9, 0.9) and lower BMI (ORa 0.8, 95% CI: 0.7, 0.9).ConclusionThis study highlights the difficulty in achieving 5-year remission in those with recent-onset axSpA, especially for the more active cases, despite the use of TNFi. Socio-economic factors and BMI are implicated in the outcome at 5 years.

O13 Which composite measure best reflects disease activity and predicts treatment change in psoriatic arthritis?

Abstract Background/Aims Multiple composite measures of disease activity are available and used in psoriatic arthritis (PsA) research; however, poor agreement remains amongst clinicians on the optimal measure of disease activity. Research to date has focused on polyarticular PsA, despite oligoarticular disease accounting for around half of cases in clinical practice. We aim to compare the ability of Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), Disease Activity score for PSoriatic Arthritis (DAPSA), GRAppa Composite scorE (GRACE) and Disease Activity Score 28 CRP (DAS28-CRP) to assess disease activity and predict treatment change, amongst usual care patients with oligoarticular and polyarticular psoriatic disease. Methods The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise (GRACE) dataset was utilised. Oligoarthritis was defined as &amp;lt; 5 active joints. Reference measures were clinician and patient opinions on disease control and whether treatment was escalated. Patients with baseline data for all composite measures were included. The ability of each composite measure to predict treatment change and capture disease activity was compared using the Mann-Whitney U test. Results Data were available for 271 patients (152 oligoarthritis, 119 polyarthritis). The mean age, duration of PsA and psoriasis were similar for both groups. A higher proportion of oligoarticular patients were male. Patients with polyarticular disease had higher disease activity in skin, enthesitis and dactylitis. Using both patient and physician definitions of disease control, all composite measures were able to differentiate between patients with active and quiescent disease, regardless of disease subtype (p &amp;lt; 0.05). PASDAS demonstrated the largest differentiation in score. Differences between active and inactive disease scores were more pronounced in oligoarticular disease. PASDAS demonstrated the greatest ability to predict treatment change in both oligoarticular and polyarticular disease. Interestingly, DAPSA could not predict treatment change in polyarticular patients, p = 0.074 (Table 1). Conclusion This is the first study to compare composite measures, in oligoarticular and polyarticular PsA in a multinational cohort. All composite measures of disease activity were able to differentiate between active and inactive disease in both subtypes. PASDAS demonstrated the largest discrimination in both polyarticular and oligoarticular disease, suggesting greatest clinical and research utility. Disclosure L. Tucker: None. P. Helliwell: None. L. Coates: None.

THU0138 AGEING IN RA PATIENTS DETERIORATED MODIFIED HEALTH ASSESSMENT QUESTIONNAIRE (MHAQ) OVER A 7-YEAR PERIOD INDEPENDENTLY FROM DISEASE ACTIVITY.

Background:Recent advances of treatment for rheumatoid arthritis (RA) realizes us to set the treatment goal as remission. As the results, health assessment questionnaire (HAQ) has been also becoming better in these years. On the other hand, progress in ageing has been a major issue in Japan, including the patients with RA. which is thought as one of the factors affecting HAQ.Objectives:To evaluate the impact of ageing on HAQ in RA patients.Methods:The data of 208 RA patients used in this study was collected over a 7-year period from 2010 to 2017 as part of a prospective cohort study (TOMORROW Study: UMIN000003876) that included RA patients and age- and sex-matched volunteers recruited through mass media as controls. The data of RA patients included anthropometric, blood test data, disease activity score28-CRP (DAS28) and modified HAQ (mHAQ), together with baseline (BL) characteristics. The course of mHAQ for 7 years were analyzed by repeated measure ANOVA, and association between the changes of mHAQ at year-7 from BL (ΔmHAQ) and BL factors were analyzed by multiple regression analysis.Results:Two hundred and eight RA patients (153 women; mean age 58.1 years) were enrolled in the present study. Modified HAQ decreased significantly over the 7-year study period in RA patients. When the patients were stratified into 3 groups (lower than 2.7, between 2.7 and 4.1, over 4.1) by DAS28 at BL, mHAQ of the patients with high disease activity (DAS28: over 4.1) at BL was significantly worse than other groups (p=0.018; repeated measure ANOVA). There was no interaction between time and 3 groups (p=0.118; repeated measure ANOVA). Multiple regression analysis with ΔmHAQ as the outcome variable and ACPA, age, BMI, CRP, DAS28, MMP-3 at BL as independent variables revealed that age (p=0.034) and DAS28 (p=0.042) were independently related with ΔmHAQ.Conclusion:Ageing in RA patients impacted worsening of mHAQ over a 7-year period independently from disease activity. On assessing mHAQ in elderly RA patients, we must consider the age as well as the disease activity.Disclosure of Interests:Kentaro Inui Grant/research support from: Janssen Pharmaceutical K.K., Astellas Pharma Inc., Sanofi K.K., Abbvie GK, Takeda Pharmaceutical Co. Ltd., QOL RD Co. Ltd., Mitsubishi Tanabe Pharma, Ono Pharmaceutical Co. Ltd., Eisai Co.,Ltd.,, Speakers bureau: Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma, Janssen Pharmaceutical K.K., Astellas Pharma Inc., Takeda Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Abbvie GK, Pfizer Inc., Eisai Co.,Ltd., Chugai Pharmaceutical Co., Ltd., Yuko Sugioka: None declared, Tadashi Okano Grant/research support from: AbbVie, Eisai, Mitsubishi Tanabe Pharma Corporation and Nipponkayaku, Speakers bureau: AbbVie, Asahikasei, Astellas Pharma Inc, Ayumi Pharmaceutical, Bristol-Myers Squibb, Chugai Pharmaceutical, Daiich Sankyo, Eisai, Janssen, Lilly, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Ono Pharmaceutical, Pfizer, Sanofi, Takeda Pharmaceutical, Teijin Pharma and UCB, Masahiro Tada: None declared, Kenji Mamoto: None declared, kazuki Orita: None declared, Hiroaki Nakamura Grant/research support from: Astellas Pharma Inc. and Asahi Kasei Pharma Co.

Filgotinib, a JAK1 Inhibitor, Modulates Disease-Related Biomarkers in Rheumatoid Arthritis: Results from Two Randomized, Controlled Phase 2b Trials.

IntroductionThe Janus kinase (JAK) inhibitor therapeutic class has shown significant clinical benefit in the treatment of rheumatoid arthritis (RA). We sought to gain insight into the mode of action and immunological effects of filgotinib, a JAK1 selective inhibitor, in active RA by analyzing secreted and cell-based biomarkers key to RA pathophysiology in two phase 2b trials of filgotinib in active RA.MethodsImmune cell subsets and 34 serum biomarkers were analyzed longitudinally over 12 weeks using blood samples collected from patients with active RA receiving filgotinib (100 or 200 mg once daily) or placebo (PBO) in the two phase 2b trials (DARWIN 1, on a background of methotrexate, and DARWIN 2, as monotherapy).ResultsConsistently across both studies, filgotinib treatment decreased multiple immune response biomarkers that have key roles in RA for immune response, and decreased markers that promote matrix degradation, angiogenesis, leukocyte adhesion, and recruitment. Filgotinib did not significantly modulate T and natural killer (NK) lymphoid subsets, but slightly increased B cell numbers after 12 weeks. Multiple correlations were observed for changes in biomarkers with disease activity score 28-CRP. MIP1β showed modest predictivity at baseline for ACR50 response at 12 weeks in the 100 mg filgotinib dose across both studies (AUROC, 0.65 and 0.67, p < 0.05).ConclusionsFilgotinib regulates biomarkers from multiple pathways, indicative of direct and indirect network effects on the immune system and the stromal response. These effects were not associated with reductions of major circulating lymphoid populations.Trial RegistrationClinicalTrials.gov, NCT01888874, NCT01894516.Electronic supplementary materialThe online version of this article (10.1007/s40744-019-00192-5) contains supplementary material, which is available to authorized users.

Correlation between serum il-17 level, disease activity and functional disability in premenopausal rheumatoid arthritis patients

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis in adults and is characterized by chronic, progressive, systemic inflammation. Interleukin-17 (IL-17) is a cytokine that is expressed in inflammatory and autoimmune diseases and is expected to play an important role in the pathogenesis of RA. Since many years, the measurement of disease activity in RA has been done by Disease Activity Score-28 (DAS-28). Regarding the correlation between serum level of IL-17 and disease activity, some authors found a good significant correlation between these parameters, while others stated that DAS-28 values for expressing disease activity in RA patients may be flawed by coexisting fibromyalgia lead to higher total scores. Disability assessment in RA patients has usually been assessed by Health Assessment Questionnaire - Disability Index (HAQ-DI) and it is one of the most widely used comprehensive, validated, patient-oriented outcome assessment instruments. The study included 25 premenopausal RA patients and 20 healthy subjects. Serum IL-17 was assessed by ELISA, disease activity by DAS-28 CRP and functional disability by HAQ-DI. Serum IL-17 is increased among RA patients but it has no correlation with disease activity and functional disability in premenopausal RA patients.

Normal serum matrix metalloproteinase-3 levels can be used to predict clinical remission and normal physical function in patients with rheumatoid arthritis

This study aimed to evaluate whether normal serum matrix metalloproteinase-3 (MMP-3) levels can be used to predict clinical remission and normal physical function at a single time point when treating patients with rheumatoid arthritis (RA) in daily practice settings. Subjects were all 1321 RA patients who were treated at our hospital. The accuracy of serum MMP-3 levels was larger than those of C-reactive protein (CRP) levels for predicting clinical remission [Simplified Disease Activity Index (SDAI) ≤3.3], normal function [Disability Index of the Health Assessment Questionnaire (HAQ-DI) ≤0.5], and both in clinical remission and with normal function (clinical remission + normal function) using receiver operating characteristic curve analysis. Serum MMP-3 levels were significantly correlated with CRP levels [r 0.229 (men), r 0.476 (women)] using Pearson's correlation coefficients. Among patients with normal CRP levels (n=807), the percentage of patients in clinical remission, with normal function, and with clinical remission + normal function having normal serum MMP-3 levels was significantly higher than those with abnormal serum MMP-3 levels. In addition, among patients with the 28-point count Disease Activity Score-CRP (DAS28-CRP) remission (DAS28-CRP <2.3), the percentage of patients in clinical remission, with normal function, and with clinical remission + normal function having normal serum MMP-3 levels was significantly higher than those with abnormal serum MMP-3 levels. Our findings suggest that normal serum MMP-3 levels, in combination with CRP levels or disease activity, are useful for predicting clinical remission and normal physical function in patients with RA.

Detection of synovial inflammation in rheumatic diseases using superb microvascular imaging: Comparison with conventional power Doppler imaging

Aim: Superb microvascular imaging (SMI), a novel ultrasonography, is based on the sensitivity of Doppler technology. This study evaluated power Doppler (PD) ultrasound signals in patients with rheumatic disease using SMI and conventional PD imaging (cPDI) and compared the correlations of these signals to clinical assessments.Methods: Thirty-nine patients with rheumatic disease (27 rheumatoid arthritis [RA] and 12 non-RA) were enrolled. We investigated SMI and cPDI signals in 26 joints using an Aplio 300. Individual scores were summed to calculate total SMI and cPDI scores.Results: Total SMI scores were significantly higher than total cPDI scores in patients with RA, but not in those with the non-RA disease. Total SMI score was associated with serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3; disease activity score 28-CRP and health assessment questionnaire disability index scores, and SMI were more sensitive to detect active synovitis than cPDI in RA patients. Among the joint regions, the wrists and metacarpophalangeal joints were more sensitive to the detection of synovial inflammation using SMI in patients with RA.Conclusion: SMI was more sensitive in detecting synovial inflammation than cPDI in patients with RA. SMI could be a potentially useful imaging modality for accurately diagnosing and monitoring the disease activity of RA.

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab

Objective: This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA).Methods: Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis.Results: DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382–0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002–1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively.Conclusion: Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.