DAS28 Remission Research Articles

Radiographic remission in rheumatoid arthritis quantified by computer-aided joint space analysis (CASJA): a post hoc analysis of the RAPID 1 trial

BackgroundThe reduction of finger joint space width (JSW) in patients with rheumatoid arthritis (RA) is strongly associated with joint destruction. Treatment with certolizumab pegol (CZP), a PEGylated anti-TNF, has been proven to be effective in RA patients. The computer-aided joint space analysis (CAJSA) provides the semiautomated measurement of joint space width at the metacarpal-phalangeal joints (MCP) based on hand radiographs. The aim of this post hoc analysis of the RAPID 1 trial was to quantify MCP joint space distance (JSD-MCP) measured by CAJSA between baseline and week 52 in RA patients treated with certolizumab pegol (CZP) plus methotrexate (MTX) compared with MTX/placebo.MethodsThree hundred twenty-eight patients were included in the post hoc analysis and received placebo plus MTX, CZP 200 mg plus MTX and CZP 400 mg plus MTX. All patients underwent X-rays of the hand at baseline and week 52 as well as assessment of finger joint space narrowing of the MCP using CAJSA (Version 1.3.6; Sectra; Sweden). The joint space width (JSW) was expressed as mean joint space distance of the MCP joints I to V (JSD-MCPtotal).ResultsThe MTX group showed a significant reduction of joint space of − 4.8% (JSD-MCPtotal), whereas in patients treated with CZP 200 mg/MTX and CZP 400 mg/MTX a non-significant change (JSD-MCPtotal + 0.6%) was observed. Over 52 weeks, participants with DAS28 remission (DAS28 ≤ 2.6) exhibited a significant joint space increase of + 3.3% (CZP 200 mg plus MTX) and + 3.9% (CZP pegol 400 mg plus MTX).ConclusionCZP plus MTX did not reduce JSD-MCPtotal estimated by CAJSA compared with MTX/placebo. Furthermore, clinical remission (DAS28 ≤ 2.6) in patients treated with CZP plus MTX was associated with an increasing JSD, indicating radiographic remission in RA.

Attainment of the Patient-acceptable Symptom State in 548 patients with rheumatoid arthritis: Influence of demographic factors.

To explore the clinical and socio-demographic factors associated with Patient Acceptable Symptom Status (PASS) in Rheumatoid Arthritis (RA). In a post-hoc analyses of a cross-sectional study, RA patients from 11 countries were included. PASS was assessed as acceptable/not acceptable status by the patient. Variables collected included socio-economic (gender, age and country gross domestic product (GDP) per capita) and clinical variables: DAS28-3vESR (28 joint counts and Erythrocyte Sedimentation Rate), the patient-reported Rheumatoid Arthritis Impact of Disease (RAID) score and its seven domains (scored 0 to 10). Patients in PASS or not were compared through univariable tests and factors associated with PASS assessed by multivariable forward conditional logistic regression. A similar analysis was performed in the subgroup patients in DAS28 remission (n=168). A total of 548 patients were included: 80.5% female, mean (±SD) age 55.8±12.8years, disease duration 13.6±10.6years, DAS28 3.6±1.5. Overall, 360 (65.7%) considered themselves to be in PASS. Independent factors positively associated with being in PASS were age>50years [odds ratio, OR 1.67; (95% confidence Interval: 1.04-2.67)], a lower DAS28 [OR: 1.28 (1.08-1.52)], lower pain [OR:1.45 (1.27-1.64)] and better emotional well-being [OR:1.28 (1.13-1.45)]. Among patients in remission, being in PASS was positively associated with less severe pain [OR: 2.50 (1.79-3.84)], age>50 years [OR 3.30 (1.03 to10.87)] and living in a country of the low GDP category [OR: 5.08; (1.34-19.23)]. Being in PASS is related to many factors besides disease activity, including age, perceived impact of the disease and national GDP.

OP0034 DOES THE RISK OF VENOUS THROMBOEMBOLISM VARY WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS?

Background:Patients with rheumatoid arthritis (RA) are at increased risk for venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) (1). Several established risk factors of VTE, such as age, immobilization and comorbid conditions, occur more often patients with RA (2). In addition, inflammation may in itself also increase VTE risk by upregulating procoagolatory factors and causing endothelial damage (3). Recent reports indicate an increased risk of VTE in RA patients treated with JAK-inhibitors (4), pointing to the need to better understand how inflammation measured as clinical RA disease activity influences VTE risk.Objectives:To investigate the relationship between clinical RA disease activity and incidence of VTE.Methods:Patients with RA were identified from the Swedish Rheumatology Quality Register (SRQ) between July 1st2006 and December 31st2017. Clinical rheumatology data for these patients were obtained from the visits recorded in SRQ, and linked to national registers capturing data on VTE events and comorbid conditions. For each such rheumatologist visit, we defined a one-year period after the visit and determined whether a VTE event had occurred within this period or not. A visit followed by a VTE event was categorized as a case, all other visits were used as controls. Each patient could contribute to several visits. The DAS28 score registered at the visit was stratified into remission (0-2.5) vs. low (2.6-3.1), moderate (3.2-5.1) and high (>5.1) disease activity. Logistic regression with robust cluster standard errors was used to estimate the association between the DAS28 score and VTE.Results:We identified 46,311 patients with RA who contributed data from 320,094 visits. Among these, 2,257 visits (0.7% of all visits) in 1345 unique individuals were followed by a VTE within the one-year window. Of these, 1391 were DVT events and 866 were PE events. Figure 1 displays the absolute probabilities of a VTE in this one-year window, and odds ratios for VTE by each DAS28 category, using DAS28 remission as reference. The one-year risk of a VTE increased from 0.5% in patients in DAS28 remission, to 1.1% in patients with DAS28 high disease activity (DAS28 above 5.1). The age- and sex-adjusted odds ratio for a VTE event in highly active RA compared to RA in remission was 2.12 (95% CI 1.80-2.47). A different analysis, in which each patient could only contribute to one visit, yielded similar results.Figure 1.Odds ratios (OR) comparing the odds of VTE for DAS28 activity categories versus remission. Grey estimates are from unadjusted logistic regression models, black estimates are from logistic regression models adjusted for age and sex. Absolute one-year risk of VTE are estimated from unadjusted models.Conclusion:This study demonstrates a strong association between clinical RA inflammatory activity as measured through DAS28 and risk of VTE. Among patients with high disease activity one in a hundred will develop a VTE within the coming year. These findings highlight the need for proper VTE risk assessment in patients with active RA, and confirm that patients with highly active RA, such as those recruited to trials for treatment with new drugs, are already at particularly elevated risk of VTE.

OP0019 STABLE VERSUS TAPERED AND WITHDRAWN TREATMENT WITH TUMOR NECROSIS FACTOR INHIBITOR IN RHEUMATOID ARTHRITIS REMISSION (ARCTIC REWIND): A RANDOMISED, OPEN-LABEL, PHASE 4, NON-INFERIORITY TRIAL

Background:Remission is the preferred treatment target in rheumatoid arthritis (RA), and many patients require biologic DMARDs to reach this state. It is debated whether tapering of tumor necrosis factor inhibitor (TNFi) treatment to discontinuation should be considered in RA patients who sustain remission on treatment (1).Objectives:The primary study objective was to assess the effect of tapering and withdrawal of TNFi on the risk of flares in RA patients in clinical remission.Methods:In the non-inferiority ARCTIC REWIND trial, RA patients in remission for at least 12 months on stable TNFi therapy were randomly assigned to continued stable TNFi or tapering (half-dose TNFi for 4 months, thereafter withdrawal of TNFi), with visits every four months. csDMARD co-medication was kept stable in both arms. Patients had to be in DAS remission at inclusion with 0/44 swollen joints. The primary endpoint was the proportion of patients with disease flare during the 12-month study period (defined as DAS>1.6, change in DAS>0.6 and 2 or more swollen joints, or the physician and patient agreed that a clinically significant flare had occurred). Full-dose TNFi was reinstated in case of flares in the tapering arm. The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. The inferiority null-hypothesis was tested in the per-protocol population by mixed effect logistic regression. Radiographs were scored by van der Heijde modified Sharp score (0 and 12 months, average of two readers, progression: ≥1 unit change). ClinicaltrialsNCT01881308.Results:We randomised 99 patients, 92 received the allocated treatment strategy, 84 were included in the per-protocol population. Baseline characteristics, clinical and ultrasound disease activity were balanced (Table). csDMARD co-medication was used by 93% in the stable and 88% in the tapering arm. In the primary analysis, 5% of patients in the stable TNFi arm experienced a flare during 12 months, compared to 63% in the tapering TNFi arm. The risk difference (95% CI) was 58% (42% to 74%, Fig 1), with stable treatment being deemed superior to tapering. 90% in the stable and 81% in the tapering arm did not show progression of radiographic joint damage, difference (95% CI) -9% (-24%, 6%). At 12 months, DAS scores, DAS remission and function were similar between groups (Fig 2). The numbers of adverse events (AE)/serious AE in the stable and tapering arm were 57/2 and 50/3, respectively, with 26 and 15 infections.Conclusion:In a randomised clinical trial assessing patients in prolonged and deep RA remission, we observed a large increase in the flare rate in patients who tapered and discontinued TNFi. Patients responded well to reinstated treatment and remission rates in the two study arms were comparable at 12 months.

Indicators of rheumatoid arthritis disease activity. An association with a patient’s psychological status

Objective: to study of the relationship between psychological factors and indicators of rheumatoid arthritis (RA) disease activity in patients who have been followed up for a long time after initiation of treat-to-target therapy.Patients and methods. The investigation enrolled 38 RA patients (29 women and 9 men) aged 33 to 80 years (mean age, 56.5±12.5 years) with a mean disease duration of 6.0±0.9 years. All the patients underwent clinical examination; the following parameters were recorded: patient global assessment; physician’s global assessment; pain visual analogue scale (VAS), by measuring in millimeters; number of painful joints (NPJ), and number of swollen joints (NSJ). The investigators determined functional status with the Health Assessment Questionnaire (HAQ), quality of life with the 36-Item Short Form Health Survey questionnaire (SF-36), the nature of pain by the painDETECT questionnaire (PDQ), and the presence of anxiety and depression with the Hospital Anxiety and Depression Scale (HADS). The patients also filled out the Resilience (Res) Questionnaire (RQ) and the General Self-Efficacy ((GSE) Scale. Disease activity was evaluated by DAS28, CDAI, and RAPID3 scores. Results and discussion. RA disease activity was high in 4 patients, moderate in 21, and low in 9, and 4 patients had DAS28 remission. The average scores of RQ, its individual components, and GSE scale were comparable with the corresponding population scores for this age group. The patients who had RQ scores below the average group ones were noted to have significantly higher scores of patient global assessment; physician’s global assessment, NPJ, NSJ, CDAI, and RAPID3 than in those who had moderate and higher RQ scores. The similar trend was traced for individual Res components, such as involvement (INV), control (CONT), and risk acceptance (RA). However, the revealed differences in these indicators failed to reach statistical significance. There was no correlation between the measures of inflammatory activity and the result of GSE. The patients with subclinical and clinical anxiety and depression had significantly lower RQ, INV, and CONT scores than those who did not have anxiety or depression, whereas RA and GSE did not differ significantly in these groups. There was a significant positive correlation of Res, INV, and CONT with the quality of life, as assessed by SF-36. The findings suggest that low RQ scores can decrease the efficiency of the therapy performed (due to the patient’s poor compliance), on the one hand, and can corrupt the result of inflammatory activity assessment (due to the impact on a patient’s perception of his/her illness), on the other hand.Conclusion. The findings may suggest that there is a need to assess the psychological status of a patient when determining the level of RA disease activity.

Dynamics of lymphocyte subpopulations, CD4+CD25+CD127- T regulatory cells in patients with rheumatoid arthritis during therapy with the rituximab biosimilar Acellbia

Objective: to evaluate the effect of the rituximab (RTM) biosimilar Acellbia on the peripheral blood levels of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, and CD4+CD25+CD127- lymphocytes in patients with rheumatoid arthritis (RA).Patients and methods. Examinations were made in 20 RA patients who received 2 RTM infusions at a total dose of 1200 mg. The levels of C-reactive protein, IgM rheumatoid factor, IgG, IgM, and IgA were measured by a nephelometric method. The relative and absolute contents of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, CD4+CD25+CD127- T regulatory cells (Tregs) were estimated by multicolor flow cytofluorometry.Results and discussion. At week 24 of RTM therapy, there was a good/satisfactory effect according to EULAR criteria in 17 (85%) patients; DAS28 remission in 4 (20%), and SDAI remission in 2 (10%). The use of RTM was accompanied by a significant increase in the relative content of CD4+CD25+CD127- T lymphocytes, the median of which at weeks 12 and 24 after therapy initiation increased from 6.8 [5.2; 7.6]% to 7.3 [6.1; 8.3] and 6.97 [6.4; 8.2]%, respectively (p<0.05). The absolute peripheral blood count of Tregs tended to increase at weeks 12 after the first infusion of the drug (up to 0.05 [0.04; 0.075] ⋅ 109 /l; p=0.05). At week 24 follow-up, the patients who achieved SDAI remission/low disease activity had significantly higher baseline relative Tregs levels (7.35 [6.8; 7.97]% than those with the moderate activity of the pathological process (5.8 [4.3; 7.22] %; p<0.05).Conclusion. The use of the RTM biosimilar is accompanied by the development of complete depletion of CD19+ lymphocytes and by an increase in CD3+ and CD3+CD4+ lymphocytes and Tregs. The larger baseline number of CD4+CD25+CD127- lymphocytes is associated with the higher efficiency of RTM therapy.

Modifiable Lifestyle Factors Associated With Response to Treatment in Early Rheumatoid Arthritis.

ObjectiveWe aimed to evaluate the associations between response to algorithm‐directed treat‐to‐target conventional synthetic disease‐modifying antirheumatic drug therapy and potentially modifiable lifestyle factors, including dietary fish oil supplementation, body mass index (BMI), and smoking history in a rheumatoid arthritis (RA) inception cohort.MethodsPatients with RA with a duration of less than 12 months were reviewed every 3 to 6 weeks to adjust therapy according to disease response. All patients received advice to take fish oil supplements, and omega‐3 status was measured as plasma levels of eicosapentaenoic acid (EPA). Lifestyle factors and other variables potentially prognostic for 28‐joint Disease Activity Score (DAS28) remission and DAS28 low disease activity (LDA) at the 12‐month visit were included in multivariable logistic regression models.ResultsOf 300 participants, 57.7% reached DAS28 LDA, and 43.7% were in DAS28 remission at 1 year. Increase in plasma EPA was associated with an increase in the odds of being in LDA (adjusted odds ratio [OR] = 1.27; P < 0.0001) and remission (adjusted OR = 1.21; P < 0.001). There was some evidence that the effect of BMI on LDA might be modified by smoking history. An increase in BMI was associated with a decrease in the odds of being in LDA in current and former smokers but had no impact on LDA in patients who had never smoked. There were no meaningful associations between BMI or smoking history and remission.ConclusionOmega‐3 status, BMI, and smoking history are potential predictors of outcome in early RA. The possibility of an effect modification by smoking on the predictive value of BMI merits further investigation.

Cumulative patient-based disease activity monitoring in rheumatoid arthritis – predicts sustained remission, flare and treatment escalation

ObjectivePatient-based Disease Activity Score 2 (PDAS2) had been developed for RA patients to self-assess and record disease activity in between clinic visits. This study explored the clinical utility of time-integrated cumulative PDAS2 (cPDAS2) on predicting sustained remission or low disease activity state (LDAS), flare and treatment escalation. MethodsWe recruited 100 patients to record PDAS2 at home fortnightly between two consecutive clinic visits. Rheumatologists adjusted treatment according to disease activity recorded during clinic consultation while blinded to home PDAS2 scores. cPDAS2 calculated from the area-under-curve of all PDAS2 scores were compared with disease activities at both visits. cPDAS2 and ΔcPDAS2 (change from PDAS2 at the first visit) were tested to determine their ability to predict ACR/EULAR remission, SDAI flare-up (from remission/LDAS to moderate/high disease activity) and treatment escalation. Optimal cut-points were determined by Receiver Operator Characteristic curve. ResultsMean age of the patients was 59 years, mean RA duration 14 years, 90% were female, 71% seropositive and 64% in remission/LDAS. The home PDAS2 completion rate was 92%. PDAS2 scores were done 7.5 times every 15 days over a 16-week follow-up (all medians). The sensitivity of cPDAS2 in predicting Boolean/SDAI remission at two visits, DAS28, SDAI and CDAI remission or LDAS were 93%, 84%, 73% and 80% respectively. cPDAS2 ≥ 0.29 predicted flare (P = 0.04), with specificity 79% and negative predicting value (NPV) 88%. Rheumatologists' decision to escalate treatment was predicted by (cPDAS2 ≥ 4.33 and ΔcPDAS2 ≥ 0.059) (P = 0.007) with specificity 88% and NPV 89%, and (cPDAS2 ≥ 4.33 or ΔcPDAS2 ≥ 0.059) (P = 0.02) with both sensitivity and NPV 100%. ConclusionPDAS2 monitoring at home is feasible. cPDAS2 is useful to predict flare and treatment escalation.

Use of rheumatoid arthritis impact of disease (RAID) in routine care; identification of DAS28 remission and unmet patient-reported outcomes.

ObjectiveThe aim was to assess how the patient-reported outcome RA impact of disease (RAID) relates to DAS28 categories in routine care, its utility in identifying patients in DAS28 remission (RDAS) or low disease activity (LDAS) and the burden of unmet patient-reported needs in those achieving RDAS/LDAS.MethodsDAS28 and RAID scores were collected from patients with established RA attending for routine review. The relationship between RAID and DAS28 was assessed with univariate pairwise correlation and mixed-effects linear regression analyses. RAID <2 was defined as a patient-acceptable state.ResultsOne hundred and ninety-eight patients were assessed, with 220 observations, using DAS28-CRP categories: 47.5% RDAS, 14.1% LDAS, 31.8% moderate DAS (MDAS) and 6.6% high DAS (HDAS). Both patient visual analog scale score and tender joint count exhibited a high statistical association with RAID using linear regression (P < 0.0001). The mean RAID score per DAS28-CRP category was RDAS 1.84, LDAS 4.78, MDAS 5.60 and HDAS 7.68, with a statistically significant increase in RAID per unit increase in DAS-CRP or DAS28-ESR on linear regression (P < 0.001). Of 66 patients with RAID <2, 64 (97%) were in RDAS and 65 (98.5%) in RDAS/LDAS. Of 134 patients in RDAS/LDAS, RAID was ≥2 in 69 (51.5%), with fatigue and sleep being the worst-scoring domains.ConclusionRAID functions well as a patient-reported outcome in routine care. Patients with RAID <2 have a high likelihood of being in RDAS/LDAS and, if pre-screened, could avoid a clinic visit. Analysis of RAID domains provides individualized targets for holistic care in RA management, with fatigue and sleep problems dominating unmet needs in those in RDAS/LDAS.

P62 Assessing the effect of increased body mass on response to DMARD treatment in rheumatoid arthritis: results from the METEOR database

Abstract Background Worldwide, &amp;gt;60% patients with rheumatoid arthritis (RA) are overweight/obese (body mass index, BMI≥25kg/m2). Studies demonstrate poorer disease outcomes and health-related quality of life in these patients. However, little is known about the effect of increased BMI on drug choice, dosing, or treatment response. Objective: To explore the effect of increased BMI on DMARD-prescribing, methotrexate (MTX)-dose, and disease activity over 12 months. Methods Participants registered on METEOR (international database of RA patients) were stratified into early (&amp;lt;1year post-diagnosis, eRA), and established RA (estRA). EULAR response and DAS28 remission (including components), and treatment regimens were recorded at baseline, 6, and 12 months. Increased BMI (defined overweight and obese) were explored in 1) eRA and 2) estRA, as predictors of good EULAR response, DAS28 remission, number of DMARDs prescribed, and MTX-dose. Logistic and linear regression models (controlling for age, gender, smoking, and baseline outcome values), subgroup analyses (by drug exposure), and sensitivity analyses, were performed. Results 1,313 patients (1056 female) were included, 582 eRA. In eRA, increased BMI was not significantly associated with remission outcomes. In estRA, obese patients on monotherapy were statistically significantly less likely to achieve good EULAR response [OR 0.4 (95%CI 0.23-0.7)] or DAS28 remission [OR 0.47 (95%CI 0.24-0.88)] at 6 months, compared to those of normal weight. A similar trend observed at 12 months did not reach significance. Obese estRA patients were more likely to be treated with combination conventional synthetic DMARDs (csDMARD) than monotherapy, compared with those of normal weight, significant at 6 months [OR 1.59 (95%CI 1.03-2.45)]. In early and established disease, no significant difference in remission outcomes was demonstrated for combination compared to monotherapy. However, overweight/obese individuals were less likely to achieve remission overall (non-significant). Regarding components of remission, tender joint count and ESR in estRA were higher in overweight/obese individuals at 6 months [β 1.05 (95%CI 0.05-2.06)] and 12 months [β 6.58 (95%CI 0.16-12.99)] respectively, compared to those of normal weight. Sensitivity analyses showed no difference in the above results. MTX-dose was available for 613 patients at sequential visits. Within this subgroup, overweight/obese patients with both eRA and estRA were exposed to higher doses of MTX (mono- and combination-therapy) at any time-point, compared to those of normal weight. eRA: overweight: β 5.33, 95%CI 3.10-7.56; obese: β 6.01, 95%CI 3.57-8.46. estRA: overweight: β 4.87, 95%CI 3.79-5.95; obese: β 2.69, 95%CI 1.56-3.83. An average weekly dose of 20mg was prescribed in overweight/obese patients, compared to 15mg in those of normal weight. Conclusion We observed that overweight/obese individuals require more intense csDMARD therapy to achieve the same treatment targets as those of normal weight. Awareness of this is particularly important given the increasing obesity prevalence in RA. Disclosures M. Dey None. S.S. Zhao None. E. Psarelli None. R.J. Moots None. R. Landewe Other; Member of METEOR board. N.J. Goodson None.

O14 Semi-quantitative assessment of synovial inflammation on US guided synovial membrane biopsy is contingent to disease phase, autoimmune profile and treatment response in RA: a large single center experience

Abstract Background Ultrasound (US)-guided minimally-invasive synovial tissue (ST) biopsy is a well-tolerated procedure for basic and translational studies on chronic inflammatory joint diseases as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). The aim of the study was to evaluate the utility of histopathologic criteria to differentiate US-guided ST biopsies in daily clinical care in relation to diagnosis, disease characteristics, US parameters and treatment response in a large single center ST biopsy unit. Methods 1,064 patients [545 RA, 167 PsA, 75 SpA, 199 undifferentiated peripheral inflammatory arthritis (UPIA), 18 crystal arthritis, 26 connective tissue diseases and 34 osteoarthritis (OA) respectively] who underwent US-guided ST biopsy were enrolled. US parameters (Synovial Hyperthrophy and Power Doppler signal respectively) were recorded for each biopsied joint. RA, PsA and SpA patients were stratified based on disease activity phase (naive to DMARDs, DMARDs resistant and in sustained remission, respectively). Clinical, demographic and immunological characteristics were recorded for each patient. All ST FFPE specimens were routinely processed and stained with H&amp;E and classified by a pathologist, blinded to clinical characteristics, using the Krenn score to assess the degree of ST inflammation. Moreover, the presence/absence of lymphocytes, plasmacells, granulocytes and oedema was assessed for each ST. All naive to treatment RA were treated according to the T2T scheme and followed for at least 12 months and DAS remission rate was recorded. Results In the cohort, the distribution of synovitis score was significantly different among patients with inflammatory chronic diseases (RA, PsA, SpA and UPIA respectively) compared to OA (ANOVA Test p &amp;lt; 0.001). Moreover, Krenn score directly correlated with synovial hyperthrophy (R = 0.36; p &amp;lt; 0.001) and Power Doppler signal (R = 0.40;p&amp;lt;0.001) of the biopsied joint. Considering the RA cohort, naive RA showed a higher Krenn score compared to resistant RA (p &amp;lt; 0.001) and RA in sustained clinical and US remission (p &amp;lt; 0.001), directly correlating with DAS28 (R = 0.51; p &amp;lt; 0.001). Moreover, ACPA and RF positivity was related to the Krenn score and to ST plasmacells presence at RA onset (p &amp;lt; 0.05 and p &amp;lt; 0.001, respectively) but not at the time of DMARDs-failure or sustained remission achievement (p &amp;gt; 0.05 for both). Stratifying naive RA based on disease duration at ST biopsy, naive RA with symptoms duration &amp;gt;1 year, showed higher Krenn score compared to those with symptoms duration &amp;lt;3 months (p &amp;lt; 0.001). Finally, logistic regression analysis revealed that Krenn score higher or equal to 4.5 at baseline is an independent factor of no DAS remission achievement within 12 months [OR(95%CI):0.37(0.20-0.67)p&amp;lt;0.001] in naive RA. Conclusion Krenn score is a reliable tool for the semi-quantitative assessment of ST inflammation on US-guided ST biopsies being differentially distributed among various chronic inflammatory joint diseases and contingent to disease phase, autoimmune profile and therapeutic response in RA. Disclosures S. Alivernini None. B. Tolusso None. M. Gessi None. M. Gigante None. L. Petricca None. C. Di Mario None. S. Perniola None. A. Fedele None. G. Peluso None. L. Bui None. A. Capacci None. F. Federico None. G. Ferraccioli None. E. Gremese None.

Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM)

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic...

Association between pain phenotype and disease activity in rheumatoid arthritis patients: a non-interventional, longitudinal cohort study

BackgroundIn well-controlled rheumatoid arthritis (RA) without significant joint damage, a substantial proportion of patients complain of persistent pain. Previous studies have identified different pain phenotypes in RA, in which non-nociceptive pain phenotypes are associated with higher concurrent disease activity scores. In this longitudinal study, we explored associations between pain phenotypes and long-term disease activity outcome in RA patients. Secondly, we explored whether pain phenotype is associated with comorbid conditions.MethodsOne hundred eighty established RA patients were classified with a nociceptive (61%) or a non-nociceptive (39%) pain phenotype, based on their responses to the painDETECT-questionnaire. Two years of clinical follow-up data on disease activity outcomes were collected. Information on comorbid diseases was derived from electronic patient files.ResultsPatients with a non-nociceptive pain phenotype showed higher mean disease activity scores (DAS28, 2.57; 95% CI, 2.37–2.77 vs. 2.11; 95% CI, 1.94–2.27; p < 0.001) and a twofold lower chance of achieving sustained DAS28 remission (OR = 0.49; 95% CI, 0.26–0.92; p = 0.020). Only the tender joint count and patient global health significantly differed between the pain phenotype groups. Patients with a non-nociceptive pain phenotype had more often been diagnosed with concurrent fibromyalgia (9.9% vs. 0.9%; p = 0.007) and other pain-associated comorbid diseases (52.1% vs. 35.8%; p = 0.030) compared with patients with a nociceptive pain phenotype.ConclusionThis longitudinal study showed consistently worse long-term disease activity outcomes in RA patients with a non-nociceptive pain phenotype which appeared to be mainly due to differences in the subjective components of the disease activity score.Trial registrationThe DREAM cohort study is registered in the Netherlands Trial Register: NTR578.

Comparative Effectiveness of Certolizumab Pegol, Abatacept, and Biosimilar Infliximab in Patients With Rheumatoid Arthritis Treated in Routine Care: Observational Data From the Danish DANBIO Registry Emulating a Randomized Trial.

Nationwide Danish guidelines regarding rheumatoid arthritis (RA) patients initiating biologic treatment (i.e., biologic disease-modifying antirheumatic drugs [DMARDs]) are issued on an approximately annual basis. For biologics-naive patients treated with concomitant methotrexate, mandatory medications included certolizumab pegol (CZP; year 2013-2014, recommended compliance 80%), abatacept (ABA; 2014-2015, 80%), and biosimilar infliximab (CT-P13; 2015-2016, 50%). We hypothesized that these guidelines could be perceived as a surrogate randomization tool in which calendar period rather than patient-specific factors defined the choice of the biologic DMARD. We undertook this study to assess compliance with guidelines (supporting the assumption of surrogate randomization) and to compare the effectiveness of CZP, ABA, and CT-P13 in patients treated according to guidelines. This was an observational cohort study emulating a randomized trial (using intent-to-treat analyses). RA patients compliant with the treatment guidelines were identified in DANBIO, and information on prior comorbidities was obtained by linking to national registries. Outcome measures included remission rates according to the Disease Activity Score in 28 joints (DAS28) (at 6 and 12 months) and treatment retention at 1 year, compared across treatment regimens. Comorbidity/confounder-adjusted multivariable logistic and Cox regression analyses were used. Seven hundred seventy-six patients were included in the study (336 receiving CZP, 215 receiving ABA, 225 receiving CT-P13). Compliance with treatment guidelines was high: 70%, 65%, and 59%, respectively. Six-month DAS28 remission rates were 35%, 33%, and 42%, and 12-month rates were 35%, 31%, and 35%, respectively. Compared to CZP, adjusted odds ratios for 6- and 12-month DAS28 remission rates were 0.96 (95% confidence interval [95% CI] 0.63-1.47) and 0.74 (95% CI 0.47-1.15) for ABA and 1.38 (95% CI 0.91-2.09) and 0.96 (95% CI 0.62-1.49) for CT-P13, respectively. Adjusted hazard ratios for withdrawal (during days 0-90 and days 91-365) were 0.70 (95% CI 0.39-1.27) and 1.16 (95% CI 0.84-1.60) for ABA and 0.58 (95% CI 0.33-1.10) and 0.83 (95% CI 0.59-1.17) for CT-P13, respectively, compared to CZP. The surrogate randomization procedure enabled head-to-head comparisons of CZP, ABA, and CT-P13. Although some differences in estimated effectiveness were observed across drugs, confidence intervals were wide and statistical significance was not reached.

The duration of remission and minimal disease activity after initiation and discontinuation of biological agents in patients with early psoriatic arthritis (data from the all-russian psoriatic arthritis registry)

Remission duration and minimal disease activity (MDA) during treatment with biological agents (BA) and after their discontinuation in patients with early psoriatic arthritis (PsA) have been insufficiently studied. Objective : to study the timing of the onset and duration of remission and MDA after BA initiation and discontinuation in patients with early PsA, followed up according to the Treat-to-Target (T2T) principles. Subjects and methods . The investigation enrolled 34 patients (18 men, 16 women) with early PsA who met the CASPAR criteria, had participated in the All-Russian Registry and followed up according to the T2T principles. The patients' mean age was 38±11 years; the duration of PsA and psoriasis was 12.0±10.0 and 89.8±91.1 months, respectively. At the beginning of the follow-up, the median DAS and DAPSA scores were 4.05 [3.72; 5.10] and 33.55[28.34; 41.77], respectively. All the patients were prescribed BAs (adalimumab (n=21), ustekinumab (n=8), certolizumab pegol (n=3) or etanercept (n=2)) in combination with methotrexate. The median therapy duration was 9 [6.5; 15] months. The activity of the disease and efficiency of PsA therapy were evaluated using DAS, DAPSA and the criteria for MDA (tender joint count of ≤1, swollen joint count of ≤1, PASI score ≤1 or BSA ≤3, pain intensity on visual analogue scale (VAS) ≤15 mm, patient's assessment of disease activity on VAS ≤20 mm; HAQ score ≤0.5; enthesitis index ≤1) at the beginning of the investigation and then every 3 months. The number of patients who had achieved remission (DAS <1.6; DAPSA ≤4) or MDA (5 of 7 criteria) during BA therapy at least once during the 24-month follow-up was determined. The absence of remission or MDA at the time of examination was considered to be an exacerbation. The duration of remission and MDA was estimated after BA discontinuation according to the activity indices at the time of examination by a physician every 3 months. Results and discussion . During the 24-month follow-up, DAS/DAPSA remissions were achieved at least once by 28 (82%)/27 (79%) patients, respectively; and MDA was seen in 28 (82%). The first DAS/DAPSA remission occurred after an average of 4.8±2.2/5.8±3.2 months; MDA – after 4.0±1.9 months. The average DAS/DAPSA remission duration was 9.1±5.0/8.3±5.0 months, respectively, and MDA – 11.0±5.5 months. Seven (21%) patients responded to therapy, but did not achieve neither DAPSA, nor DAS remission and 6 (18%) patients did not have MDA. 8 patients in remission continued to receive BAs until the end of the follow-up. Nineteen patients discontinued therapy for various reasons. After discontinuation of BAs, the physician recorded DAS exacerbation in 11 (55%) patients after an average of 6.5±2.3 months and DAPSA exacerbation in 12 (60%) after 5.8±2.3 months. According to the patient assessment, an exacerbation developed in an average of 3.5±3.4 months after BA discontinuation. A DAS/DAPSA exacerbation was observed in 5 (15%) patients during BA therapy after an average of 11.5±4.7/12.0±4.7 months. Conclusion . During BA therapy, the majority of patients with early PsA achieved remission and MDA following an average of 5 months after the start of treatment using the T2T strategy. After BA discontinuation, an exacerbation occurs in more than half of patients. Following BA discontinuation, the remission duration recorded by the physician according to the activity indices averages 6 months; the duration of subjective improvement according to the patient assessment was 3 months. With continued BA treatment, 15% were observed to have lost its efficiency after an average of 12 months.

Retention and response rates in 14 261 PsA patients starting TNF inhibitor treatment-results from 12 countries in EuroSpA.

To investigate TNF inhibitor (TNFi) retention and response rates in European biologic-naïve patients with PsA. Prospectively collected data on PsA patients in routine care from 12 European registries were pooled. Heterogeneity in baseline characteristics between registries were explored (analysis of variance and pairwise comparison). Retention rates (Kaplan-Meier), clinical remission [28-joint count DAS (DAS28) <2.6; 28 joint Disease Activity index for Psoriatic Arthritis ⩽4] and ACR criteria for 20% improvement (ACR20)/ACR50/ACR70 were calculated, including LUNDEX adjustment. Overall, 14 261 patients with PsA initiated a first TNFi. Considerable heterogeneity of baseline characteristics between registries was observed. The median 12-month retention rate (95% CI) was 77% (76, 78%), ranging from 68 to 90% across registries. Overall, DAS28/28 joint Disease Activity index for Psoriatic Arthritis remission rates at 6 months were 56%/27% (LUNDEX: 45%/22%). Six-month ACR20/50/70 responses were 53%/38%/22%, respectively. In patients initiating a first TNFi after 2009 with registered fulfilment of ClASsification for Psoriatic ARthritis (CASPAR) criteria (n = 1980) or registered one or more swollen joint at baseline (n = 5803), the retention rates and response rates were similar to those found overall. Approximately half of >14 000 patients with PsA who initiated first TNFi treatment in routine care were in DAS28 remission after 6 months, and three-quarters were still on the drug after 1 year. Considerable heterogeneity in baseline characteristics and outcomes across registries was observed. The feasibility of creating a large European database of PsA patients treated in routine care was demonstrated, offering unique opportunities for research with real-world data.

Efficacy and safety of original and biosimilar etanercept (SB4) in active rheumatoid arthritis – A comparison in a real-world national cohort

ObjectiveThe study aims to compare the efficacy and safety of biosimilar etanercept (SB4) to original etanercept (ETN) in a real-life national cohort of rheumatoid arthritis (RA). MethodsData from RA patients were retrieved electronically from the Romanian Registry of Rheumatic Diseases (RRBR), which contains all patients receiving biologics in the country. ResultsThe study included 242 patients with efficacy and safety data after 6 months of treatment: 123 (50.8%) with ETN, 119 (49.2%) with SB4. There were no significant differences after 6 months regarding composite scores of RA activity between patients on ETN and SB4 (e.g. DAS28 remission: 18.7% in ETN group and 17.6% in SB4 group, p = 0.823; Boolean remission: 11.4% in ETN group and 11.8% in SB4 group, p = 0.926). There were 11 adverse events (AE) in the ETN subgroup (including 3 severe AE: lower respiratory tract infection, enterocolitis and anaphylaxis) and 12 AE in SB4 subgroup (including 4 severe AE: lower respiratory tract infection, vasculitis, anaphylaxis and rash). ConclusionBiosimilar and original etanercept showed similar efficacy and safety after the first 6 months of treatment in RA patients from a national registry, which brings further evidence for biosimilarity in unselected patients in real-world setting.

Differences in disease activity measures in patients with rheumatoid arthritis who achieved DAS, SDAI, or CDAI remission but not Boolean remission

ObjectivesIn patients with rheumatoid arthritis (RA), remission may be assessed by various composite measures. We assessed achievement of remission as defined by Boolean criteria, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) and determined the components that limit patients in SDAI, CDAI, or DAS28(CRP) remission from achieving Boolean remission. MethodsThe proportions of patients achieving Boolean, SDAI, CDAI, or DAS28(CRP) remission were calculated for 3 trials: PREMIER and OPTIMA in patients with early RA and DE019 in patients with established RA. At the first visit that remission was recorded during the first 52 weeks of the trial, the following were assessed: swollen/tender joint count at 28 and 66/68 joints, CRP, Patient's/Physician's Global Assessment (PGA/PhGA), SDAI, DAS28(CRP), and Health Assessment Questionnaire-Disability Index. ResultsThe majority of patients (61–66%) who achieved SDAI or CDAI remission also attained Boolean remission. Although DAS28(CRP) remission was most frequently attained, 74–77% of patients in DAS28(CRP) remission did not achieve Boolean remission. Compared with patients in Boolean remission, patients in SDAI or CDAI remission but not Boolean remission had higher PGA scores, while patients with DAS28(CRP) remission but not Boolean remission had higher joint counts, and PGA and PhGA scores. ConclusionsDifferences in PGA limit patients in SDAI/CDAI remission from meeting the Boolean remission criteria, suggesting that these criteria otherwise can be used interchangeably. In contrast, patients in DAS28(CRP) remission are limited by differences in multiple disease activity measures from achieving Boolean remission.

Rheumatoid arthritis in real clinical practice: initiation of therapy with biological agents. Results of the «Computer Terminals of Self-Assessment for Patients with Rheumatic Diseases» («TERMINAL-II») project

Objective : to assess quality-of-life (QoL) dynamics in patients with rheumatoid arthritis (RA) when initiating therapy with biological agents (BAs) in real clinical practice. Patients and methods . The investigation enrolled patients with RA from the patient cohort participating in the TERMINAL-II multicenter Russian study, who newly initiated BA therapy. In the self-assessment terminal, the patient completed HAQ, EQ-5D, and RAPID-3 questionnaires. DAS28, SDAI, CDAI, and RAPID-3 were used to determine disease activity. The patient's functional status and QoL were assessed using the HAQ index and the EQ-5D questionnaire, respectively. The efficiency of the therapy was analyzed 6 months after the start of the study according to the standard procedures. Results and discussion . The investigation enrolled 156 RA patients: 79.6% females; mean age, 45.8±13.2 years; disease duration, 7.6±5.6 years. The patients had high RA activity (a mean DAS28 of 5.2±1.2, a mean SDAI of 39.5±16.4, a mean CDAI of 27.5±10.4, and a mean RAPID-3 of 15.1±3.6) and previous inefficacy of synthetic disease-modifying antirheumatic drugs (DMARDs) after at least 6 months of therapy. Only 1.2% of patients had a good functional status comparable to the population-based control (HAQ 40.5). 70% of patients needed to take non-steroidal anti-inflammatory drugs (NSAIDs). The first BA was chosen in accordance with the recommendations for administration of BAs and in terms of their availability in a specific region of the Russian Federation. The first prescribed BA was tumor necrosis factor-a (TNF-a) inhibitors in 112 (71.8%)patients, anti-B-cell therapy in 14 (9.0%), an interleukin-6 receptor inhibitor in 16 (10.3%), and a leukocyte costimulatory inhibitor in 14 (9.0%). Comparison of the patients receiving newly initiated therapy with TNF-a inhibitors and drugs with other mechanisms of action showed that the patients who had abatacept received higher doses of methotrexate (MTX), but lower doses of glucocorticoids (GCs) than those who were prescribed rituximab and tocilizumab. A statistically significant decrease in DAS28, SDAI, CDAI, and RAPID-3 scores was achieved after 6 months of therapy. Improvements of functional status and QoL in patients were also noted (p<0.0001). The patients continued to receive MTX. During the follow-up period, its dose remained almost unchanged: it averaged 15.7±3.8 and 15.7±3.7 mg/week at the beginning and the end of the study, respectively. Due to decreased inflammation, the dose of CS was reduced (on average, from 5.8±2.5 to 5.1±2.6 mg/day; p=0.02), the number of patients requiring NSAIDs declined (from 72.4 to 63.8%). DAS28, SDAI, and CDAI remission and low disease activity were achieved in 38.1, 16.5, and 20% of patients, respectively. The functional status improved in most patients with RA: 20, 50, and 70% improvements in HAQ were observed in 59.4, 46.9, and 28.7% of cases, respectively. QoL improvements were seen in two thirds of the patients: 30, 50, and 70% improvements in 58.3, 29.5, and in 23.7%. After 6-month follow-up, GC therapy was completely discontinued in 4.6% of patients; their dose was reduced in 5.3%, and 8.6% completely refused to take NSAIDs. Conclusion . Biologic therapy was shown to be effective in RA patients with an inadequate response to synthetic NSAIDs in real clinical practice. The patients preferred the subcutaneous injection of BAs. Biologic treatment in most patients was initiated with TNF-a inhibitors, mainly with adalimumab. Six-month therapy could reduce disease activity and improve functional status and health-related QoL in two thirds of severe patients.

Efficacy and retention rate of adalimumab in rheumatoid arthritis and psoriatic arthritis patients after first-line etanercept failure: the FEARLESS cohort.

Few studies have compared the efficacy of switching from etanercept to adalimumab in the real-life setting in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This study evaluated the 2-year retention rate and 12-month efficacy of adalimumab in RA and PsA patients, previously treated with etanercept. RA and PsA patients from 11 Italian Rheumatology Units received adalimumab after first-line etanercept failure. Two-year adalimumab retention rate was calculated by the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of drug persistence. Univariate and multivariate logistic regression analyses were developed to examine potential predictors of 12-month DAS-28 remission. The study population included 117 RA (disease duration of 10.1 ± 7.7years and baseline DAS28-ESR of 4.97 ± 1.3) and 102 PsA (disease duration of 7.1 ± 5.1years and baseline DAPSA of 24.6 ± 11.8). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients. Concomitant methotrexate treatment was not associated with increased drug survival in both groups. Similarly, cause of etanercept discontinuation or treatment duration was not associated with retention rate. 12-month remission and low disease activity were achieved, respectively, in 27.3% and 23.9% of RA patients and 27.4% and 23.5% PsA of patients. In multivariate models, etanercept discontinuation due to inefficacy (OR 0.27, 95% CI 1.03-0.73; p = 0.009) and baseline DAS-28 (OR 0.45, 95% CI 0.29-0.69; p < 0.001) remained significant negative predictors of remission in RA patients. No variable was associated with remission in PsA patients. Adalimumab after etanercept failure was highly effective and safe in both RA and PsA patients.