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Flare Assessment in Rheumatoid Arthritis (FLARE-RA) is a self-administered tool aiming to capture current or recent flares in rheumatoid arthritis (RA). We aimed to externally validate the FLARE-RA instrument and its existing cutoffs for flare detection within a bDMARD-tapering context in established RA. Data were analyzed from the Tapering Etanercept in Rheumatoid Arthritis (TapERA) trial, which studied the feasibility of tapering etanercept in patients with established RA in sustained remission. The English FLARE-RA was translated and cross-culturally adapted into Dutch, and internal consistency and test-retest reliability were evaluated with Crohnbach's alpha and intraclass correlation coefficient (ICC). Participants completed the FLARE-RA 3-monthly for 12 months. Accuracy and optimal cutoffs of FLARE-RA to detect DAS28-defined flares were assessed using area under the receiver operating characteristic curves (AUC). Association of FLARE-RA scores with current and future flares was studied using logistic generalized estimating equations (GEE). The Dutch FLARE-RA showed excellent internal consistency and test-retest reliability (Cronbach's alpha 0.96; ICC 0.96 [95% CI 0.70-1.00]). Discriminatory capacity of FLARE-RA to detect flares was acceptable (AUC 0.77, 0.80, and 0.72 for global, arthritis, and general symptoms subscales, respectively), with an optimal global score cutoff of 4/10. In GEE-models, higher FLARE-RA scores were associated with increased odds of both current and future flares. We successfully translated and cross-culturally adapted the FLARE-RA into a Dutch version and validated its capacity to detect flares in a bDMARD-tapering context in established RA. Finally, higher FLARE-RA scores might indicate an increased risk of future flares.Trial registration: EU Clinical Trials Register, https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004631-22/BE , EudraCT number 2012-004,631-22. Key Points • Translation and cross-cultural adaptation of the FLARE-RA resulted in a Dutch version with excellent internal consistency and test-retest reliability. • The FLARE-RA is a valid instrument to detect current OMERACT-defined flares within a bDMARD tapering setting, with an optimal global score cutoff of 4/10. • Higher scores on the FLARE-RA are associated with increased risk of future flares, which could be particularly relevant when considering DMARD tapering.

BackgroundRecent studies have identified important social inequalities in SARS-CoV-2 infection and related COVID-19 outcomes in the Belgian population. The aim of our study was to investigate the sociodemographic and socioeconomic characteristics associated with the uptake of COVID-19 vaccine in Belgium.MethodsWe conducted a cross-sectional analysis of the uptake of a first COVID-19 vaccine dose among 5,342,110 adults (≥18 years) in Belgium from December 28th2020 (official starting date of the vaccination campaign) until August 31st2021. We integrated data from four national data sources: the Belgian vaccine register (vaccination status), COVID-19 Healthdata (laboratory test results), DEMOBEL (sociodemographic/socioeconomic data), and the Common Base Registry for HealthCare Actors (individuals licensed to practice a healthcare profession in Belgium). We used multivariable logistic regression analysis for identifying characteristics associated with not having obtained a first COVID-19 vaccine dose in Belgium and for each of its three regions (Flanders, Brussels, and Wallonia).ResultsDuring the study period, 10% (536,716/5,342,110) of the Belgian adult population included in our study sample was not vaccinated with a first COVID-19 vaccine dose. A lower COVID-19 vaccine uptake was found among young individuals, men, migrants, single parents, one-person households, and disadvantaged socioeconomic groups (with lower levels of income and education, unemployed). Overall, the sociodemographic and socioeconomic disparities were comparable for all regions.ConclusionsThe identification of sociodemographic and socioeconomic disparities in COVID-19 vaccination uptake is critical to develop strategies guaranteeing a more equitable vaccination coverage of the Belgian adult population.

Although recommendations to manage women with rheumatoid arthritis (RA) during the reproductive phase have been established, there is further need for evidence-based information on drug treatment and safety during pregnancy.1 Registries are excellent data sources to address remaining questions. Therefore, a minimal core data set for registers studying pregnancy in rheumatology has been developed recently by an EULAR task force.2 We evaluated the feasibility of data collection according to this minimal core data set in the daily clinical management of pregnant women with RA within the rheumatology department of the University Hospital of Leuven (UHL). We performed a retrospective patient chart study in a population of 1072 patients (360 men and 712 women) with RA with a planned rheumatology outpatient visit at UHL between November 2019 and November 2020. Women were included if they were diagnosed with RA before getting pregnant, had a recorded pregnancy during the past 5 years and …

Background Shifts in treatment strategies for rheumatoid arthritis (RA) have made ambulatory care more labour-intensive. These developments have prompted innovative care models, including mobile health (mHealth) applications. This study aimed to explore the perceptions of mHealth-inexperienced stakeholders concerning these applications in RA care. Methods We performed a qualitative study by focus group interviews of stakeholders including RA patients, nurses specialised in RA care and rheumatologists. The qualitative analysis guide of Leuven (QUAGOL), which is based on grounded theory principles, was used to thematically analyse the data. In addition, the Persuasive Systems Design (PSD) model was used to structure recommended app-features. Results In total, 2 focus groups with nurses (total n = 16), 2 with patients (n = 17) and 2 with rheumatologists (n = 25) took place. Six overarching themes emerged from the analysis. Efficiency of care and enabling patient empowerment were the two themes considered as expected benefits of mHealth-use in practice by the stakeholders. In contrast, 4 themes emerged as possible barriers of mHealth-use: the burden of chronic app-use, motivational aspects, target group aspects, and legal and organisational requirements. Additionally, recommendations for an ideal mHealth-app could be structured into 4 domains (Primary Task Support, Dialogue Support, Social Support and System Credibility) according to the PSD-framework. Most recommended features were related to improving ease of use (Task Support) and System Credibility. Conclusions Although mHealth-apps were expected to improve care efficiency and stimulate patient empowerment, stakeholders were concerned that mHealth-app use could reinforce negative illness behaviour. For mHealth-apps to be successful in practice, challenges according to stakeholders were avoiding long-term poor compliance, finding the target audience and tailoring a legal and organisational framework. Finally, the ideal mHealth-application should above all be trustworthy and easy to use.

ObjectivesTo compare outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years.MethodsPatients with RA completing the 2-year CareRA randomised controlled trial were eligible for the 3-year observational CareRA-plus study. 5-year outcomes after randomisation to initial methotrexate (MTX) monotherapy with glucocorticoid bridging (COBRA-Slim) were compared with MTX step-up without glucocorticoids or conventional synthetic disease-modifying antirheumatic drug (DMARD) combinations with glucocorticoid bridging, per prognostic patient group. Disease activity (Disease Activity Score based on 28 joints calculated with C reactive protein (DAS28-CRP)) and functionality (Health Assessment Questionnaire (HAQ)) were compared between treatment arms using longitudinal models; safety and drug use were detailed.ResultsOf 322 eligible patients, 252 (78%) entered CareRA-plus, of which 203 (81%) completed the study. Treatments for high-risk patients resulted in comparable DAS28-CRP (p=0.539) and HAQ scores over 5 years (p=0.374). Low-risk patients starting COBRA-Slim had lower DAS28-CRP (p3 months and 17% for >6 months outside the bridging period.ConclusionsAll intensive treatments with glucocorticoids bridging demonstrated excellent 5 year outcomes. Initiating COBRA-Slim was comparably effective as more complex treatments for high-risk patients with early RA and more effective than initial MTX monotherapy for low-risk patients with limited need for biologics and chronic glucocorticoid use.

1.AbstractThe COVID-19 vaccination campaign in Belgium aimed to reduce disease spread and severity. We quantified the observed vaccine effectiveness (VE) against symptomatic infection (VEi) and hospitalization (VEh).Exhaustive data on testing and vaccination was combined with a clinical hospital survey. We estimated VEi using a test negative design and VEh using a proportional hazard analysis. We controlled for prior infection, age, sex, province of residence and calendar week of sampling. Variant of concern specific VE-estimates were obtained by time since vaccination from July 2021 to April 2022.We included 1,433,135 persons. VEi against Delta waned from an initial estimate of 81% (95%CI 80- 82) to 56% (95%CI 56-57) 100-150 days after primary-vaccination. Booster-vaccination increased initial VEi to 84% (95%CI 83-85). Against Omicron, an initial VEi of 37% (95%CI 34-40) waned to 18% (95%CI 17-20) 100-150 days after primary-vaccination. Booster-vaccination increased VEi to 52% (95%CI 51-53) and waned to 25% (95%CI 24-27) 100-150 days after vaccination. Hybrid immunity conferred by prior infection and booster-vaccination outperformed booster-vaccination only even if the infection was over one year ago, 67% (95%CI 66-68). Initial VEh for booster-vaccination decreased from 93% (95%CI 93-94) against Delta to 87% (95%CI 85-89) against Omicron. VEh for Omicron waned to 66% (95%CI 63-70) 100-150 days after booster-vaccination.In conclusion, we report significant immune-escape by Omicron. VEh was less affected than VEi and immune-escape was attenuated by booster-vaccination. Waning further reduced VEi- and VEh- estimates. Infection-acquired immunity offered additional protection against symptomatic infection in vaccinated persons which lasted at least one year.

The reliability and clinical usefulness of the different composite disease activity scores and their individual components in Rheumatoid Arthritis (RA) are still debated. This study investigated which measures of disease activity were preferred by rheumatologists. A mixed-method study was performed. First, ten Belgian rheumatologists were invited for individual interviews on their current practice and preferences for measurement of RA disease activity. Results of this qualitative study and evidence from literature served as input for developing a survey. This survey asked rheumatologists to rate preferred standard disease activity score(s), their individual components, ultrasound and related patient-reported outcomes (PROs), by maximum difference scaling. The relative importance score (RIS) for each indicator was calculated using hierarchical Bayes modeling. The qualitative study included 6/10 invited rheumatologists. Composite scores and components were perceived as useful, while PROs were found subjective. Interestingly, ultrasound was used to mediate discrepancies between physician and patient. The survey based on this was sent to 244 Belgian rheumatologists, 83/244 (34%) responded, including 66/83 (80%) complete and 17/83 (20%) incomplete surveys (two missing essential information). Most rheumatologists (75/81, 93%) used a disease activity score and 68/81 (84%) preferred the DAS28-CRP. Swollen joint count obtained the highest mean ± SD RIS (22.54 ± 2.64), followed by DAS28 ESR/CRP (20.61 ± 4.06), ultrasound (16.47 ± 7.97), CRP (13.34 ± 6.11) and physician's global assessment (12.59 ± 7.83). PROs including fatigue, pain, and patient's global assessment, and Health Assessment Questionnaire, obtained the lowest mean RIS (0.34-2.54). Rheumatologists place more faith in self-assessed disease activity components or in laboratory tests. Trust in PROs to evaluate disease activity is low in clinical practice. ispartof: RHEUMATOLOGY INTERNATIONAL vol:42 issue:5 pages:815-823 ispartof: location:Germany status: published

ObjectivesTo evaluate the cost-effectiveness of treat-to-target strategies among recently diagnosed patients with rheumatoid arthritis (RA) using methotrexate (MTX) and a step-down glucocorticoid (GC) scheme (COBRA Slim) compared with (1) this combination with either sulphasalazine (COBRA Classic) or leflunomide (COBRA Avant-Garde) in high-risk patients and (2) MTX without GCs (Tight-Step-Up, TSU) in low-risk patients.MethodsThe incremental cost-utility was calculated from a healthcare perspective in the intention-to-treat population (n=379) of the 2-year open-label pragmatic randomised controlled Care in early RA trial. Healthcare costs were collected prospectively through electronic trial records. Quality-adjusted life years (QALYs) were estimated using mapping algorithms for EuroQoL-5 Dimension. Multiple imputation was used to handle missing data and bootstrapping to calculate CIs. Robustness was tested with biological disease-modifying antirheumatic drugs at biosimilar prices.ResultsIn the high-risk group, Classic (∆k€1.464, 95% CI −0.198 to 3.127) and Avant-Garde (∆k€0.636, 95% CI −0.987 to 2.258) were more expensive compared with Slim and QALYs were slightly worse for Classic (∆−0.002, 95% CI −0.086 to 0.082) and Avant-Garde (∆−0.009, 95% CI −0.102 to 0.084). This resulted in the domination of Classic and Avant-Garde by Slim. In the low-risk group, Slim was cheaper (∆k€−0.617, 95% CI −2.799 to 1.566) and QALYs were higher (∆0.141, 95% CI 0.008 to 0.274) compared with TSU, indicating Slim dominated. Results were robust against the price of biosimilars.ConclusionsThe combination of MTX with a GC bridging scheme is less expensive with comparable health utility than more intensive step-down combination strategies or a conventional step-up approach 2 years after initial treatment.Trial registration numberNCT01172639.

Contains fulltext : 251456.pdf (Publisher’s version ) (Open Access) BACKGROUND: During the first half of 2021, we observed high vaccine effectiveness (VE) against SARS-CoV2-infection. The replacement of the alpha-'variant of concern' (VOC) by the delta-VOC and uncertainty about the time course of immunity called for a re-assessment. METHODS: We estimated VE against transmission of infection (VET) from Belgian contact tracing data for high-risk exposure contacts between 26/01/2021 and 14/12/2021 by susceptibility (VEs) and infectiousness of breakthrough cases (VEi) for a complete schedule of Ad26.COV2.S, ChAdOx1, BNT162b2, mRNA-1273 as well as infection-acquired and hybrid immunity. We used a multilevel Bayesian model and adjusted for personal characteristics (age, sex, household), background exposure, calendar week, VOC and time since immunity conferring-event. FINDINGS: VET-estimates were higher for mRNA-vaccines, over 90%, compared to viral vector vaccines: 66% and 80% for Ad26COV2.S and ChAdOx1 respectively (Alpha, 0-50 days after vaccination). Delta was associated with a 40% increase in odds of transmission and a decrease of VEs (72-64%) and especially of VEi (71-46% for BNT162b2). Infection-acquired and hybrid immunity were less affected by Delta. Waning further reduced VET-estimates: from 81% to 63% for BNT162b2 (Delta, 150-200 days after vaccination). We observed lower initial VEi in the age group 65-84 years (32% vs 46% in the age group 45-64 years for BNT162b2) and faster waning. Hybrid immunity waned slower than vaccine-induced immunity. INTERPRETATION: VEi and VEs-estimates, while remaining significant, were reduced by Delta and waned over time. We observed faster waning in the oldest age group. We should seek to improve vaccine-induced protection in older persons and those vaccinated with viral-vector vaccines.

Objective To unravel disease impact in early RA by separately quantifying patient-reported (PRF), clinical (CF) and laboratory (LF) factors. We propose a new indicator, the discordance score (DS), for early identification and prediction of patient’s unmet needs and of future achievement of sustained remission (SR) and RA-related quality of life (QoL). Methods Factor-scores obtained by factor analysis in the CareRA trial, allowed to compute DS, reflecting the difference between PRF and the mean of CF and LF. Improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time points per factor-score were calculated and compared between patients achieving/not achieving sustained (week 16–104) remission (DAS28CRP Results PRF, CF and LF scores improved rapidly within 8 weeks. PRF improved 57%, CF 90% and LF 27%, in those achieving SR, compared with 32% (PRF: P = 0.13), 77% (CF: P Conclusions All factor scores improved rapidly, especially in patients achieving sustained remission. Patient-reported burden improved less. Discordance scores could help predicting the need for additional non-pharmacological interventions to achieve sustained remission and decrease disease impact.

Objective: In patients with rheumatoid arthritis (RA) in sustained remission, tapering of biological disease-modifying anti-rheumatic drugs can be considered. Tapering has already been investigated, but its feasibility remains to be determined. Therefore, we explored the feasibility of tapering etanercept in RA in a setting close to practice. Method: Patients with RA in 28-joint Disease Activity Score (DAS28) remission (>= 6 months) and treated with etanercept 50 mg weekly (>= 1 year) were included in the pragmatic 1 year open-label multicentre randomized controlled TapERA (Tapering Etanercept in Rheumatoid Arthritis) trial. Patients were assigned to continue etanercept weekly or to taper to every other week (EOW). Patients who lost remission [DAS28-C-reactive protein (CRP) >= 2.6] were re-escalated to etanercept weekly. The primary outcome was the proportion of patients maintaining DAS28-CRP remission for 6 months. Results: Sixty-six patients were randomized to etanercept weekly (n = 34) or EOW (n = 32). After 6 months, 26/34 patients (76%) in the weekly and 19/32 (59%) in the EOW group maintained disease control (p = 0.136). In the EOW group, 20/32 patients (63%) remained on their tapered treatment during the trial. Two patients reintroduced weekly etanercept themselves. Ten patients were re-escalated to etanercept weekly by the rheumatologist, after a median (interquartile range) interval of 3.0 (2.0-6.0) months. Among these patients, 7/10 regained remission after re-escalation, four of them at the next study visit. Conclusions: Although non-inferiority could not be demonstrated, tapering of etanercept to EOW appeared feasible in patients in sustained remission.

ObjectiveTo unravel disease impact in early RA patients by separately quantifying patient reported (PRF), clinical (CF) and laboratory (LF) factors. We put forward a new indicator, the discordance score (DS), for early identification and prediction of unmet patient outcomes in terms of future achievement of sustained remission and RA-related quality of life (QoL).MethodsWe obtained factor scores via factor analysis in the CareRA trial, then calculated the DS between PRF and the mean of the other scores. We computed the improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time-points per factor score and compared these between patients achieving or not achieving sustained (week 16 to 104) remission (DAS28CRPResultsPRF, CF and LF scores improved rapidly within 8 weeks. In patients achieving SR; PRF improved 57%, CF 90% and LF 27%, compared to 32% PRF (p=0.13), 77% CF (pConclusionsAll factor scores improved rapidly, especially in patients achieving SR. Patient-reported burden improved less extensively. Discordance scores could help in predicting the need for additional non-pharmacological interventions to achieve SR and decrease disease impact.KEY MESSAGESWhat is already known about this subject?Early and intensive RA drug-treatment using disease activity as a target allows rapid disease control and prevents joint destruction.Including pain, fatigue and physical function when assessing patients with early RA broadens the evaluation of disease impact.What does this study add?Leveraging patient reported outcomes (pain, fatigue and physical function) and traditional disease activity measures, we introduce a new indicator (named discordance score) for unraveling disease impact and treatment efficacy.We show how the discordance score stands for current unmet patient reported outcomes and could be used to predict future sustained disease contol and quality of life (1 and 2 years after baseline).We demonstrate this effect both in patients with and without sustained remissionHow might this impact on clinical practice or future developments?The earlier detection of unmet needs despite good disease control could allow to perform timely interdisciplinary interventions other than medication adaptations and could promote psychosocial wellbeing for patients.

We thank Dr Dhir et al for their kind words and would like to address some of the points raised.1 First, in patients without markers of poor prognosis, the COBRA-Slim scheme with methotrexate (MTX) and prednisone bridging led to a more rapid response than initial MTX monotherapy in the first 16 weeks.2 Subsequently, remission rates did not differ until year 5, but patients starting a COBRA-Slim scheme had a lower disease activity and better functionality longitudinally over 5 years.3–5 This long-term effect of prednisone bridging seems counterintuitive to Dr Dhir, given the results of the 'BehandelStrategieen in Reumatoide Arthritis' (BeSt) study and the 'Treatment of Early Aggressive Rheumatoid Arthritis' (TEAR) trial, showing that long-term outcomes were essentially determined by treating-to-target.6 7 Unfortunately, differences in design and follow-up duration hamper direct comparisons of the Care in early Rheumatoid Arthritis (CareRA) study with these trials. The 2-year TEAR trial did not include a glucocorticoid bridging scheme in its MTX step-up arms, but 40% of patients were already on low-dose oral glucocorticoids at baseline, which was prohibited per protocol in the MTX-Tight-Step-Up (TSU) arm of CareRA. Moreover, only about one in …

ObjectivesRheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA) are chronic inflammatory rheumatic conditions with high levels of comorbidity requiring additional therapeutic attention. We aimed to compare the 3-year comorbidity incidence and pain medication prescription in patients diagnosed with RA, PsA or SpA versus controls.MethodsData between 1999 and 2012 were obtained from Intego, a general practitioner (GP) morbidity registry in Flanders, Belgium. Cases were identified by International Classification of Primary Care (ICPC-2) codes representing ‘rheumatoid/seropositive arthritis (L88)’ or ‘musculoskeletal disease other (L99)’. The registered keywords mapped to these ICPC-2 codes were further verified and mapped to a RA/SpA/PsA diagnosis. Controls were matched on age, gender, GP practice and diagnosis date. We analysed the 3-year comorbidity burden in cases and controls, measured by the Rheumatic Diseases Comorbidity Index (RDCI). All electronically GP-prescribed drugs were registered.ResultsIn total, 738, 229 and 167 patients were included with a diagnosis of RA, SpA or PsA, respectively. Patients with RA or PsA had comparable median RDCI scores at baseline, but higher scores at year 3 compared with controls (RA: p=0.010; PsA: p=0.008). At baseline, depression was more prevalent in PsA patients vs controls (pConclusionsThis study highlights the increasing comorbidity burden of patients with chronic inflammatory rheumatic conditions, especially for individuals with RA or PsA. The high opioid use in all populations was remarkable.

Objectives RA should be treated to target in a process of shared decision-making with patients. Person-centred care is essential to meeting specific patient needs. Nurse-led clinics, where a nurse is responsible for care, have demonstrated added value in some countries but are still not implemented widely. This study aimed to explore stakeholders’ perceptions of advantages, disadvantages and conditions for the implementation of nurse-led clinics for RA in Belgium. Methods We performed a cross-sectional qualitative study consisting of five semi-structured focus group interviews. Rheumatology nurses, patients with RA and rheumatologists were interviewed as stakeholders. The analysis was carried out by three researchers according to the Qualitative Analysis Guide of Leuven (QUAGOL), formulating a conceptual framework of overarching themes and deconstructing this into perceived advantages, disadvantages and conditions. Results Two focus groups with nurses (total n = 16), two with patients (n = 17) and one with rheumatologists (n = 9) were conducted. The interview synthesis resulted in five overarching themes across stakeholders: efficiency of care, disease management, legal and organizational requirements, the conventional role of the nurse and the extended role of the nurse. All stakeholders perceived additional education for nurses as essential, but rheumatologists debated nurses’ abilities to lead a rheumatology clinic. Furthermore, patients preferred care protocols to guide nurses, and care providers approached this reluctantly. Generally, patients with a well-controlled disease were perceived as the ideal candidates for nurse-led care. Conclusion Nurse-led clinics could provide many benefits but require additional nurse education and a legal and organizational framework before being implemented widely and successfully.

Objective.To explore the possibility of integrating patient-important outcomes like pain, fatigue, and physical function into the evaluation of disease status in early rheumatoid arthritis (ERA) without compromising correct disease activity measurement.Methods.Patients from the 2-year Care in Early Rheumatoid Arthritis (CareRA) trial were included. Pain and fatigue (visual analog scales), Health Assessment Questionnaire (HAQ), standard components of disease activity [swollen/tender joint counts (SJC/TJC), C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), physician (PhGH) and patient (PaGH) global health] were recorded at every visit (n = 10). Pearson correlation and exploratory factor analyses (EFA), using multiple imputation (15×) and outputation (1000×), were performed per timepoint and overall, on standard components of disease activity scores with and without pain, fatigue, and HAQ. Each of the 15,000 datasets was analyzed using EFA with principal component extraction and oblimin rotation to determine which variables belong together.Results.We included 379 patients. EFA on standard composite score components extracted 2 factors with no substantial cross-loadings. Still, pain (0.83), fatigue (0.65), and HAQ (0.59) were strongly correlated with PaGH. When rerunning the EFA with the inclusion of pain, fatigue, and HAQ, the 2-factor model had substantial cross-loadings between factors. However, a 3-factor model was optimal, with Factor 1: patient assessment, Factor 2: clinical assessment (PhGH, SJC, and TJC), and Factor 3: laboratory assessment (ESR/CRP).Conclusion.PaGH, pain, fatigue, and physical function represent a separate aspect of the disease burden of patients with ERA, which could be further explored as a target for care apart from disease activity. [ClinicalTrials.gov: NCT01172639].

ObjectiveTo explore non-steroidal anti-inflammatory drug (NSAID) and analgesic use in early rheumatoid arthritis (eRA) patients with a favourable risk profile initiating methotrexate (MTX) with or without glucocorticoid (GC) bridging.MethodsPatients with eRA (≤1 year) and favourable risk profile (no erosions, negative rheumatoid factor and anticitrullinated protein antibodiesor low disease activity) in the 2-year CareRA trial were randomised to MTX 15 mg with a step-down GC scheme (COBRA Slim), or MTX without oral GCs, Tight-Step-Up (TSU). Used analgesics were recorded, including frequency, start/end date and indication. Chronic intake (≥90 consecutive days in trial) of NSAIDs, acetaminophen, opioids including tramadol and antidepressants for the indication of musculoskeletal (MSK) pain was considered. Treatments were compared using χ2 and analysis of variance with Holm’s correction for multiple testing.ResultsIn total, 43 patients were randomised to COBRA Slim and 47 to TSU. At study inclusion, 33/43 (77%) of patients in the COBRA Slim and 32/47 (68%) in the TSU arm had been using analgesics (p=0.5). During the trial, 67 NSAID and analgesics were used for MSK pain in 26/43 (60%) COBRA Slim patients of which 9/43 (21%) daily chronically (DC), while 107 NSAID and analgesics were used in 43/47 (92%) TSU patients, of which 25/47 (53%) DC. The total number of patients on NSAID and analgesics at any time during the study (pConclusionIn eRA patients considered to have a favourable prognosis, initial oral GC bridging resulted in lower chronic NSAID and analgesic use.Trial registration numberNCT01172639.

INTRODUCTION/OBJECTIVES: Evidence regarding the effectiveness of step-down strategies for patients with well-controlled early rheumatoid arthritis (RA) on a combination of methotrexate (MTX) and leflunomide (LEF) is currently lacking. METHOD: The Care in early RA (CareRA) trial is a 2-year randomized pragmatic trial comparing different remission induction strategies in treatment-naïve patients with early RA. For this study, we included participants who achieved low disease activity (LDA) (DAS28-CRP ≤ 3.2) between 40 to 52 weeks after starting a combination of MTX, LEF, and a prednisone bridging scheme followed by a treat-to-target approach. Patients were re-randomized to a maintenance monotherapy of either MTX 15 mg weekly or LEF 20 mg daily. Remission rates (DAS28-CRP

To quantify the prevalence of co-morbidities in patients with early RA and determine their prognostic value for effectiveness outcomes in a randomized trial.We included patients from the 2-year pragmatic randomized CareRA trial, who had early RA (diagnosis 1 year), were DMARD naïve and then treated-to-target with different remission induction schemes. Prevalence of co-morbidities was registered at baseline and the Rheumatic Diseases Comorbidity Index (RDCI; range 0-9) was calculated. We tested the relation between baseline RDCI and outcomes including disease activity (DAS28-CRP), physical function (HAQ index), quality of life (SF-36 domains) and hospitalizations over 2 years, using linear mixed models or generalized estimating equations models.Of 379 included patients, 167 (44%) had a RDCI of minimum 1. RDCI scores of 1, 2 or ≥3 were obtained in 65 (17%), 70 (19%), and 32 (8%) participants, respectively. The most frequent co-morbidity was hypertension (22%). Patients with co-morbidities had significantly higher HAQ (β = 0.215; 95% CI: 0.071, 0.358), DAS28-CRP (β = 0.225; 95% CI: 0.132, 0.319) and lower SF-36 physical component summary scores (β =-3.195; 95% CI: -4.844, -1.546) over 2 years than patients without co-morbidities, after adjusting for possible confounders including disease activity and randomized treatment. Patients with co-morbidities had over time lower chances of achieving remission (OR = 0.724; 95% CI: 0.604, 0.867) and a higher risk of hospitalization (OR = 3.725; 95% CI: 2.136, 6.494).At disease onset, almost half of RA patients had at least one clinically important co-morbidity. Having co-morbidities was associated with worse functionality and disease activity outcomes over 2 years, despite intensive remission induction treatment.Clinical trials NCT01172639.

Introduction Drug therapy could alter fertility in patients with rheumatoid arthritis (RA). We aimed to perform a systematic review to evaluate if Disease-modifying antirheumatic drug (DMARD) therapy influences fertility as this is an important point to consider in shared decision making on RA therapy. Methods A search was conducted at 18/10/2019 in EMBASE, PubMed (including MEDLINE) and the Web of Science Core Collection. Our inclusion criteria were studies involving women or men diagnosed with RA, older than 18 years and on DMARD therapy, with as outcome a fertility parameter. Systematic reviews, meta-analyses, case reports, case series and animal studies were excluded. Studies not in English or Dutch or published before 2004 were excluded. Quality appraisal was performed by the CASP systematic review checklist. Results After duplicate removal, 9030 references were identified. After title/abstract screening, 82 articles remained. After full text screening, 4 articles could be retained. No studies were found through backward snowballing. Only studies involving women could be retained. The included studies investigated the effect of methotrexate, certolizumab pegol, etanercept and sulfasalazine on fertility. No detrimental effects of these DMARDs on time-to-pregnancy, anti-Mullerian hormone serum level or presence of a history of infertility, were reported. Conclusion This systematic review underlines the gap in knowledge regarding the effect of DMARDs on fertility in women and especially men with RA. DMARD treatment, contrary to general belief, seemed to have no harmful effect on fertility, possibly because it resulted in better controlled disease activity. More research is needed to improve guidance for patients with RA with a child wish.

ObjectivesTo identify and characterise a subgroup of patients with early rheumatoid arthritis (RA) reporting not feeling well 1 year after treatment initiation despite achieving optimal disease control according to current treatment standards.MethodsThis observational study included participants of the Care in early RA trial with a rapid and sustained response (DAS28CRPResultsAnalyses revealed three clusters. Of 140 patients, 77.9% were assigned to the ‘concordant to disease activity’ cluster, 9.3% to the ‘dominant fatigue’ cluster and 12.9% to the ‘dominant pain and fatigue’ cluster. Large differences in pain and fatigue reporting were found at week 16 when comparing the ‘concordant’ with the ‘dominant pain and fatigue’ or the ‘dominant fatigue’ cluster. Small differences in reporting were found for the other PROs. Illness perceptions and coping style also differed in the ‘concordant’ cluster.ConclusionsAlthough most patients reported PRO scores in concordance with their well-controlled disease activity, one in five persistent treatment responders reported not feeling well at year 1. These patients reported higher pain and fatigue, and different illness perceptions and coping strategies early in the disease course.

BackgroundThe Dutch-Flemish PROMIS® Upper Extremity (DF-PROMIS-UE) V2.0 item bank was recently developed using Item Response Theory (IRT). Unknown for this bank are: (1) if it is legitimate to calculate IRT-based scores for short forms and Computerized Adaptive Tests (CATs), which requires that the items meet the assumptions of and fit the IRT-model (Graded Response Model [GRM]);(2) if it is legitimate to compare (sub) groups of patients using this measure, which requires measurement invariance; and (3) the precision of the estimated patients’ scores for patients with different levels of functioning and compared to legacy measures. Aims were to evaluate (1) the assumptions of and fit to the GRM, (2) measurement invariance and (3) (comparative) precision of the DF-PROMIS-UE v2.0.MethodsCross-sectional data were collected in Dutch patients with upper extremity disorders. Assessed were IRT-assumptions (unidimensionality [bi-factor analysis], local independence [residual correlations], monotonicity [coefficient H]), GRM item fit, measurement invariance (absence of Differential Item Functioning [DIF] due to age, gender, center, duration, and location of complaints) and precision (standard error of IRT-based scores across levels of functioning). To study measurement invariance for language [Dutch vs. English], additional US data were used. Legacy instruments were the Disability of the Arm, Shoulder and Hand (DASH), the QuickDASH and the Michigan Hand Questionnaire (MHQ).ResultsIn total 521 Dutch (mean age ± SD = 51 ± 17 years, 49% female) and 246 US patients (mean age ± SD = 48 ± 14 years, 69% female) participated. The DF-PROMIS-UE v2.0 item bank was sufficiently unidimensional (Omega-H = 0.80, Explained Common Variance = 0.68), had negligible local dependence (four out of 1035 correlations > 0.20), good monotonicity (H = 0.63), good GRM fit (no misfitting items) and demonstrated sufficient measurement invariance. Precise estimates (Standard Error The DASH displayed better reliability than the DF-PROMIS-UE short form and standard CAT, the QuickDASH displayed comparable reliability. The MHQ-ADL displayed better reliability than the DF-PROMIS-UE short form and standard CAT for T-scores between 28 and 50. For patients with low function, the DF-PROMIS-UE measures performed better.ConclusionsThe DF-PROMIS-UE v2.0 item bank showed sufficient psychometric properties in Dutch patients with UE disorders.

OBJECTIVES To quantify the prevalence of co-morbidities in patients with early RA and determine their prognostic value for effectiveness outcomes in a randomized trial. METHODS We included patients from the 2-year pragmatic randomized CareRA trial, who had early RA (diagnosis

OBJECTIVE: Treating early, intensively, and to target leads to rapid disease control, preventing joint damage and loss of function in early rheumatoid arthritis (RA). We report the effect of such an approach on patient-reported outcomes and explore the contribution of rapid and persistent disease control to well-being after 1 year of treatment. METHODS: This study is part of the Care in Early RA trial, a prospective, 2-year, investigator-initiated, randomized controlled trial rooted in daily practice and implementing the treat-to-target principle. Short Form 36 (SF-36) health survey and Revised Illness Perception Questionnaire (IPQ-R) data were collected prospectively. We defined 4 clinical response profiles based on speed and consistency of the treatment response within the first year, defined as the Disease Activity Score in 28 joints using the C-reactive protein level

BackgroundPatients recently diagnosed with rheumatoid arthritis (RA) have specific educational and supportive needs. These could partly be addressed with mentoring by other patients living with RA. This qualitative study explores stakeholder perceptions towards peer mentoring in early RA care.MethodsTwo focus groups with patients with early RA (n=10), one with patient organisation representatives (n=5), one with rheumatologists (n=8) and one with rheumatology nurses (n=5) were held. Two patient research partners supported analysis and interpretation.ResultsFour overarching themes were found: added value, experience with peer mentoring, concerns and need in daily care. Patients and patient organisation representatives confirmed the potential of peer mentoring especially regarding sensitive topics not easily discussed with professionals. Patients felt it could provide additional understanding and recognition. Nurses and rheumatologists were less convinced of the added value of peer mentoring because patients never mentioned it and they were concerned about the loss of control over correct information provision. The need for peer mentoring was perceived as person and disease phase-dependent and should therefore be optional, rather than a care standard. The requirements for a peer mentorship programme remained challenging to define for stakeholders. However, all expressed the need for supervision by healthcare professionals and that peer mentors should be carefully selected, educated and matched to newly diagnosed patients.ConclusionPeer mentoring and its implementation remain vague concepts, especially for healthcare providers. However, patients are interested in mentoring by peers, and the current results may support in effectively implementing such programmes early in the disease.

Background:The treat-to-target Care in Early Rheumatoid Arthritis (CareRA) trial demonstrated that remission induction with csDMARD combinations and step-down glucocorticoids (GCs) was not superior over methotrexate (MTX) monotherapy with step-down GCs (Cobra Slim) in RA patients with a high-risk profile (1). Moreover, Cobra Slim showed benefit over a tight step-up with MTX in monotherapy (TSU) in RA patients with a low-risk profile.Objectives:To compare the long term outcomes up to 5 years of different initial intensive treatment strategies in participants of the CareRA-plus study.Methods:In the CareRA trial, patients with DMARD naïve early RA were stratified in a high- or low-risk group based upon the presence of serummarkers, disease activity and erosive status. High-risk patients were randomised to Cobra Classic (MTX+sulphasalazine with highly dosed GC remission induction scheme), Cobra Avant-Garde (MTX+leflunomide with moderately dosed GC scheme) or Cobra Slim. Low-risk patients were randomised to Cobra Slim or TSU. Patients completing this trial were eligible for the CareRA-plus observational study. Here, patients were evaluated 6-monthly over 3 years. Therapy adaptation was left to the treating physician. Efficacy was assessed by DAS28-CRP and HAQ and compared between the originally allocated treatment arms. The 5-year evolution from CareRA baseline of DAS28-CRP and HAQ was assessed via linear mixed models. All adverse events (AEs), considered to be clinically relevant by investigators, and DMARD/GCs therapy were registered.Results:Of 322 eligible patients, 252 (78%) were included in CareRA-plus, of which 203 (81%) completed the study. Characteristics and outcomes at the CareRA closing visit (year 2) did not differ between patients entering CareRA-plus or not. DAS28-CRP3 months).Conclusion:All intensive treatment strategies resulted in excellent long-term clinical outcomes. Initial Cobra Slim therapy showed comparable 5-year effectiveness as Cobra Classic and Avant-Garde in high-risk early RA patients and better efficacy and safety than conservative step up treatment in low-risk patients.Figure 1.Mean disease activity by DAS28-CRP or mean functionality by HAQ index scores for high-risk or low-risk patients.References:[1]Stouten, V. et al. Effectiveness of different combinations of DMARDs and glucocorticoid bridging in early rheumatoid arthritis: two-year results of CareRA. Rheumatology (Oxford). (2019)doi:10.1093/rheumatology/kez213.Disclosure of Interests: :Veerle Stouten: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Diederik De Cock: None declared, Sofia Pazmino: None declared, Johan Joly: None declared, Delphine Bertrand: None declared, Kristien Van der Elst: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

Objectives Timely treatment of patients with Early Rheumatoid Arthritis (ERA) favors a beneficial disease outcome. However, individuals often delay their contact with a healthcare professional (HCP) after ERA-related symptom onset. This study investigates the patients’ perspective on the patient’s journey from RA symptom onset until referral to a specialist. Methods A subgroup of patients with ERA from the Care in ERA (CareRA) trial were retrospectively interviewed to discuss their initial ERA-related experiences preceding diagnosis, using a bespoke assessment form. The form’s first section focused on initial symptoms and patients’ help-seeking behavior. The second part probed the consulted HCPs’ actions. Additional notes derived from the patient stories were thematically analyzed. Results Among 94 patients, pain (97%), swelling (73%) and stiffness (52%), typically in multiple joints, were reported as initial ERA-symptoms. The general practitioner (GP) was generally the first contacted HCP (87%). Frequently reported reasons to visit a HCP were too intense pain (90.4%) and difficulties in performing daily activities (69%). In 44.1% of patients, the HCP suspected ERA at the first visit. Approximately 25% of patients needed >5 visits before ERA detection. GPs mainly referred patients to rheumatologists (71%). Thematic analysis uncovered that often multiple HCPs were involved in the journey to RA detection and referral. Conclusion Pain is the most commonly reported initial symptom of ERA and the main reason to visit a HCP, mostly a GP. These GPs play a pivotal role in early detection and correct referral. Furthermore, the patient’s journey seems complex with often multiple HCPs involved.

Background Seronegative rheumatoid arthritis (RA) patients have been historically considered to have a milder disease. This confers a potential risk for under treatment. The quality of their response to early intensive therapies has not been thoroughly studied. Objectives To compare the disease course in seronegative and seropositive patients from the Care in early RA (CareRA) trial treated with COBRA Slim. Methods The CareRA trial included 379 patients with early RA (≤1 year) fulfilling 1987 or 2010 ACR criteria and naive to disease modifying anti-rheumatic drugs (DMARDs). Patients were randomized to one of four different intensive treatment strategies based on methotrexate (MTX) monotherapy or synthetic (cs)DMARD combinations with or without glucocorticoid (GC) bridging. Before randomization, stratification into a high- or low-risk group according to classical poor prognostic markers (presence of erosions, positivity to rheumatoid factor (RF) and/or anti-citrullinated protein antibody (ACPA), and elevated disease activity) was conducted. One of these strategies, COBRA Slim, a combination of MTX and a prednisone remission induction scheme stepping-down from 30 mg QD, was initiated in 141 patients from both risk strata, of which 38 were negative for both RF and ACPA (seronegative). Following the treat-to-target principle, using the disease activity score in 28 joints with C-reactive protein (DAS28CRP), treatment adaptations were steered at low disease activity (≤3.2), while aiming for remission ( The “as observed” population was analysed for differences in disease activity and radiographic progression between seronegative and seropositive patients at several time points during the 2-year study using independent sample t-test, Man Whitney-U or adjusted X2 (Yate’s correction for small samples). Survival analysis using Kaplan Meier was employed for time to first response to treatment. First response to treatment was defined as achieving first remission (DAS28CRP 1.2) after screening. Sensitivity analyses were applied on the complete CareRA cohort. Results Seronegative patients starting COBRA Slim (n=38), had similar age (53 vs 51 years, p=0.52), body mass index (25.5 vs 26.7, p=0.08), symptom duration (7.9 vs 7.2 months, p=0.23), presence of erosions (24% vs 23%, p=0.99) and gender distribution (82% vs 63%, p=0.06), compared to seropositive patients (n=103). However, parameters of disease activity were higher in seronegative patients at screening: DAS28CRP (5.1 vs 4.5, p=0.01), 28 swollen joint count (8.2 vs 5.7, p=0.02) and 28 tender joint count (10.3 vs 6.9, p=0.006). These results were corroborated when analysing the entire CareRA cohort. The mean disease activity was significantly higher in seronegative patients at the first stages (week 8 and 16), but became comparable by year 1 and 2 (Table 1). There was a significant difference in time to first treatment response between seronegative and seropositive patients, despite being treated with the same strategy, as depicted in the inverted Kaplan Meier plot (Figure 1). Conclusion In conclusion, CareRA participants with seronegative RA had a higher initial disease activity, longer time to experience a first treatment response, but achieve comparable remission status as seropositive patients with COBRA Slim, a combination of MTX with moderate dose GC bridging. This provides further evidence that, seronegative RA can no longer be considered a milder form of disease and requires an equally intensive initial treat-to-target therapy as seropositive RA. Disclosure of Interests Sofia Pazmino: None declared, Annelies Boonen: None declared, Veerle Stouten: None declared, Diederik De Cock: None declared, Delphine Bertrand: None declared, Kristien Van der Elst: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research

Background EULAR 2016 recommendations for the management of Rheumatoid Arthritis (RA) suggest to consider tapering of biological Disease-Modifying Antirheumatic Drugs (bDMARDs) in patients in sustained remission. More insight on the effect of tapering strategies is needed in daily practice. Objectives To investigate maintaining disease control after spacing dosages of etanercept 50mg from weekly to every other week (EOW) in a pragmatic randomized controlled trial (RCT). Methods Patients with RA who were in remission according to the disease activity score 28 (DAS28) remission criteria for at least 6 months and treated with etanercept 50mg weekly for at least a year were included in the one-year non-blinded multicentre TapERA (Tapering Etanercept in RA) RCT (EudraCTnumber 2012-004631-22). Patients were 1:1 randomly assigned to continue etanercept 50mg weekly or to taper to 50mg EOW. Patients who lost remission (DAS28 C-Reactive Protein (CRP) ≥ 2.6) received nonsteroidal anti-inflammatory drugs and if needed were re-escalated to etanercept weekly. If remission was still not reached, treatment had to be adapted, at the discretion of the treating rheumatologist. The outcomes were proportion of patients in DAS28 remission at 6 and 12 months, proportion in sustained remission and proportion regaining remission after reintroducing weekly etanercept (intention to treat analysis). Missing components of DAS28 were imputed using expectation maximization. Results In total, 69 patients (69.6% female) with a mean ± standard deviation (SD) age of 55.7 ± 11.3 years and a mean ± SD disease duration of 14.7 ± 8.0 years were included. The weekly and EOW group consisted of 35 and 34 patients respectively. At the month 6 visit 77.1% patients of the weekly and 76.5% of the EOW group were in remission (p=0.947) and 68.6% and 58.8% respectively maintained remission on every visit (p=0.400) (Table 1). Three (8.6%) patients of the weekly and 11 (32.4%) of the EOW group required a treatment adaptation, which was statistically significantly different (p=0.014). There was no difference between the weekly and EOW group in the mean ± SD DAS28 CRP at the first time of losing remission in patients flaring, namely 3.1 ± 0.6 and 3.1 ± 0.5 respectively (p=0.957). Eleven patients were re-escalated to a weekly treatment after a mean ± SD duration of 4.5 ± 3.1 months. Of these, 54.5% (6/11) regained remission after a mean ± SD duration of 4.7 ± 1.7 months. Of the 5 patients not regaining remission, 1 switched to a weekly regimen on the last trial visit, 1 required switching to another bDMARD and 3 patients had no additional treatment changes (mean ± SD DAS28 CRP at month 12: 3.4 ± 0.2). Two patients of the EOW group restarted weekly etanercept while still being in remission. Conclusion Approximately half of the EOW group was in sustained remission after 1 year and two thirds remained on their reassigned treatment. Furthermore, one in two patients were able to regain remission after reintroducing etanercept weekly. Therefore tapering of etanercept to EOW seems a feasible strategy in patients with RA in sustained remission, potentially leading to a beneficial cost-saving and safety profile. Disclosure of Interests Delphine Bertrand: None declared, Julie Mannaerts: None declared, Valerie Badot: None declared, Luk Corluy: None declared, Diederik De Cock: None declared, Kathleen De Knop: None declared, Isabelle de Wergifosse: None declared, Elke Geens: None declared, Ilse Hoffman: None declared, Johan Joly: None declared, Christine Langenaken: None declared, Jan Lenaerts: None declared, Joris Lenaerts: None declared, Sofia Pazmino: None declared, Veerle Stouten: None declared, Veerle Taelman: None declared, Mark Walschot: None declared, Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research

Background Patients with autoimmune inflammatory rheumatic diseases (AIIRD) have an increased risk for acquiring infections. Vaccines were developed to diminish the prevalence of vaccine-preventable infections. The EULAR recommendations for vaccination in adult patients with AIIRD emphasise the importance of assessing the vaccination status of patients with AIIRD. Objectives To determine the vaccination status of patients with AIIRD, the reason for non-vaccination and the proportion of patients that are vaccinated according to the EULAR recommendations. Methods The single-centre cross-sectional COLOSSeUM study was conducted in a tertiary referral centre. Between August and December 2018, all consecutive patients with AIIRD including Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS) and Juvenile Idiopathic Arthritis (JIA) who visited the outpatient clinic were included. The vaccination status (influenza winter season 2017-2018, pneumococcal, tetanus toxoid and hepatitis B vaccine) and history of varicella zoster virus infection was determined using a one-page questionnaire which was completed by the treating rheumatologist after discussion with the patient. The patients’ reason for non-vaccination was registered if applicable. Patients were classified as vaccinated according to the EULAR recommendations if they had a yearly influenza, an every-five-year pneumococcal and a decennial tetanus toxoid vaccine, the latter as recommended in the general population. Results The vaccination status of 633 consecutive patients was obtained. The group consisted of 489 (77.2%) patients with RA, 73 (11.5%) patients with PsA, 58 (9.2%) patients with AS and 13 (2.1%) patients with JIA with a mean ± standard deviation age of 59.8 ± 13.6, 55.8 ± 13.5, 45.2 ± 14.0 and 35.0 ± 13.9 respectively. Of all included patients with AIIRD, 69.2% were vaccinated for influenza, followed by vaccination rates of 55.0%, 32.1% and 30.5% for tetanus toxoid, pneumococcal and hepatitis B vaccination, respectively (Table 1). In addition, 70.6% of patients with AIIRD had a history of varicella zoster virus infection. Various reasons for non-vaccination were reported, of which ‘No specific reason’ was the most common, closely followed by non-awareness of the need for pneumococcal vaccination. The compliance with EULAR recommendations was 18.5%. Of the 429 patients with AIIRD not vaccinated according to the EULAR recommendations, 68 (15.9%) patients were not compliant with all three of the vaccines, 136 (31.7%) were not compliant with 2 vaccines (1: pneumococcal and 2: influenza or tetanus toxoid vaccine), 148 (34.5%) were not compliant with 1 vaccine (103 pneumococcal, 41 tetanus toxoid and 4 influenza vaccine) and 77 (17.9%) patients were unaware of their vaccination status for at least 1 vaccine. Conclusion In our patients with AIIRD, the highest vaccination rate for recommended vaccines was observed for influenza (nearly 70%). Not being vaccinated for pneumococcus was the main reason why patients did not comply with the EULAR recommendations. More attention is needed to determine and optimise the vaccination status of AIIRD patients and to increase the awareness regarding the pneumococcal vaccine. Disclosure of Interests: Delphine Bertrand: None declared, Sofie Coenen: None declared, Sofia Pazmino: None declared, Veerle Stouten: None declared, Diederik De Cock: None declared, Kristien Van der Elst: None declared, Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead, Marc Ferrante Grant/research support from: Janssen, Pfizer, Takeda, Consultant for: Abbvie, Boehringer-Ingelheim, Ferring, Janssen, Mitsubishi Tanabe, Takeda, MSD, Pfizer, Speakers bureau: Abbvie, Boehringer-Ingelheim, Chiesi, Ferring, Janssen, Lamepro, Mitsubishi Tanabe, MSD, Pfizer, Takeda, Tramedico, Tillotts, Zeria, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research DOI: 10.1136/annrheumdis-2019-eular.3060

Background: Management and support by an interdisciplinary rheumatology team are essential for achieving optimal disease outcomes in rheumatoid arthritis (RA). Nevertheless, health professionals generally do not experience the disease themselves, and patients may have specific educational needs that can only be provided by other patients having gone through the same experience. Furthermore, patients with RA may benefit most from such additional care interventions in the early disease stage when they are particularly faced with threats to their normal life. Peer mentoring has been studied and successfully implemented in other chronic conditions, however, this is rather a new care concept in the field of rheumatology. Objectives: Among four key stakeholders in the management of early RA, we aimed (1) to uncover the current experience with, need for and attitude towards implementing peer mentoring in the care for patients with early RA in Flanders; (2) to gather ideas for the content and format of a peer mentor program. Methods: We conducted an explorative qualitative focus group study. In total, five focus groups were organized to capture the perspective of each of the following stakeholders: patients with early RA (n=10), representatives of patient organizations (n=5), rheumatologists (n=10) and rheumatology nurses (n=5). Data were analyzed using the constant comparison method as presented in the Qualitative Analysis Guide of Leuven. Two patient research partners helped to analyze and interpret the data. Results: Most stakeholders perceived a potential need for peer mentoring in early RA. However, they underscored that this would be largely person and disease phase dependent suggesting that peer mentoring should be presented as an option to patients, rather than a standard of care. The additional value of peer mentors would be foremost situated in providing disease perspective and a sense of recognition to newly diagnosed patients. For some stakeholders, it was difficult to get a clear picture of such a program, which made it difficult for them to formulate an opinion on a specific format. The health professionals particularly mentioned the current lack of a formal framework for collaborating with patient experts, and the need for carefully selected and well-trained peer mentors. Stakeholders shared the view that the development of a peer mentor program and its integration within the current care context should ideally take place in co-operation with and under supervision of health professionals. Conclusion: Our results underline that peer mentoring in early RA holds potential for certain patients under certain circumstances, yet a clear framework for all stakeholders is a prerequisite to ensure a chance for success of this complex intervention. Future research should thus focus on unfolding the facilitators and barriers of collaborating with patient experts in the daily care of patients with early rheumatoid arthritis. Acknowledgement: This work was supported by Fonds Wetenschappelijk Reuma Onderzoek (FWRO). Disclosure of Interests: Kristien Van der Elst: None declared, Lore Bangels: None declared, Lianne Peerlings: None declared, Lies De Caluwe: None declared, Ilse Langers: None declared, Veerle Stouten: None declared, Diederik De Cock: None declared, Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research

Background Treating to a predefined target is a principle adopted in guidelines to treat rheumatoid arthritis (RA). It is currently the most efficient strategy to control disease activity, but its implementation in daily clinical practice remains challenging. Objectives To evaluate rheumatologists’ adherence to a treat-to-target (T2T) approach at a threshold of low disease activity (DAS28CRP≤3.2) in patients with early RA during the 2-year Care in early RA (CareRA) study. Methods CareRA is an investigator-initiated pragmatic multicentre trial, in which patients with early RA and naive to conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) were included (n=379). Participants were randomized to different remission induction schemes consisting of a csDMARD combination or methotrexate (MTX) monotherapy with and without a prednisone tapering down scheme. Following the T2T approach, specific treatment adaptations had to be performed in case of DAS28CRP>3.2 during the first study year, unless a predefined reason not to intensify treatment was provided. As first step, dose of MTX had to be increased from 15mg to 20mg weekly. As second step, dose of the other csDMARD was escalated in the combination arms and leflunomide was added in the MTX monotherapy arms. From week (w)52 onwards, further T2T was advised but type of treatment adaptation was left at the rheumatologists’ discretion. Adherence to this T2T approach was defined as performing a dose escalation or changing/adding DMARD medication in case of DAS28CRP>3.2 and was evaluated at every study visit during 2 years. Additionally, remission (DAS28CRP Results The proportion of patients with DAS28CRP>3.2 was 26% (93/365) at w8, but decreased to a stable average of 16% on the following visits and further diminished to 10% (30/303) at w104. The frequency of T2T adherence in these patients varied from 59% (55/93) at w8 to 17% (5/30) at w104 (Figure 1). The most frequent reason not to intensify treatment during the first study year was that rheumatologists considered the disease already well-controlled. This reason was reported in 50% of non-adherent cases at w8, in 15% at w16, 14% at w28, and 24% at w40. The second most frequently given reason for non-adherence during the first study year was that giving glucocorticoids or NSAIDs temporarily was preferred over changing DMARDs, as reported in 3% of cases at w8, 15% at w16, 27% at w28, and 35% at w40. T2T was applied at all visits in 41 out of 110 (37%) patients needing at least 1 adaptation during the 2-year trial. Of these 41 patients, 36 (88%) were in remission at w104, while of the 69 patients not always treated to the T2T principle, 40 (58%) were in remission at the end of the 2-year trial (p=0.001). Conclusion This study shows the difficulty of applying T2T strictly, both with and without a fixed protocol to follow. In less than half of patients theoretically in need of a treatment adaptation, treatment was intensified at all visits during the first 2 years of treatment. In the majority of cases rheumatologists gave as reason for overruling the T2T guidance that they estimated disease activity to be sufficiently controlled. However, patients in which the T2T principle was applied strictly, showed higher remission rates after 2 years of treatment. Disclosure of Interests Veerle Stouten: None declared, Diederik De Cock: None declared, Sofia Pazmino: None declared, Kristien Van der Elst: None declared, Johan Joly: None declared, Delphine Bertrand: None declared, Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research

Background In rheumatoid arthritis (RA), good disease control without major joint damage, loss of function or disability can be achieved. Still, a substantial number of patients report poor wellbeing. A better understanding is needed on why some patients still feel unwell despite good disease control. Specific attention to this mismatch, especially early in the disease, could help to further optimize the clinical course of new patients with RA. Objectives To identify and characterize patients with early RA treated optimally to current standards but reporting not feeling well after 1 year of treatment. Methods We included participants of the Care in early RA trial with an early and persistently favorable treatment response, defined as having a disease activity score (DAS28CRP) Results Analyses revealed 3 distinct clusters. Details are depicted in Table 1. Of 140 patients, 77.9% were assigned to the ‘concordant to disease activity’ cluster, 9.3% to the ‘dominant fatigue’ cluster and 12.9% to the ‘dominant pain and fatigue’ cluster. When comparing the concordant cluster with both discordant clusters, differences at BL and w16 were shown, with small effects on patients’ evaluation of their disease at year 1, such as more negative beliefs about the consequences of RA at w16 in patients reporting dominant pain and fatigue at year 1. Few differences with medium effects were identified, such as a moderately higher use of avoidance as a coping style at w16 and a stronger belief that symptoms can be explained by RA at w16, in patients reporting dominant fatigue at year 1 compared to patients in the concordant cluster. Large differences between patients in concordant and discordant clusters were found for pain and fatigue levels, which were already higher after 4 months of treatment for those patients reporting persistent pain and fatigue at year 1. Conclusion Three distinct groups of persistent responders with early RA were identified based on their 1-year PRO profile. The majority of patients were well-synchronized, reporting very low pain and fatigue levels in concordance with their well-controlled disease activity. One in 5 persistent responders, however, seemed to have unmet needs. In view of early identification of patients at risk of poor wellbeing despite good disease control, early pain and fatigue levels and certain coping behavior and illness perceptions were recognized as potential targets for future interventions. Disclosure of Interests Kristien Van der Elst: None declared, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research, Diederik De Cock: None declared, An De Groef: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Johanna Vriezekolk: None declared, Johan Joly: None declared, Philip Moons: None declared, Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead DOI: 10.1136/annrheumdis-2019-eular.3629

Background: Autoantibodies are present in the majority of rheumatoid arthritis (RA) patients and are used clinically as diagnostic serum biomarkers. Insight in their role in prediction of therapy response and disease progression would provide a useful tool for patient stratification and personalized selection of a suitable treatment. In a previous pilot experiment, autoantibody levels to the University of Hasselt (UH) peptide UH-RA.21 have been correlated with response to DMARD treatment. In patients continuing the same DMARD during a 17 month follow-up period, which was taken as a proxy for treatment success, persistently positive anti-RA.21 antibody levels showed an overall decrease in titers (p=0.0334). Objectives: Our aim is to determine the association between autoantibodies to the UH-RA.21 peptide and disease remission in early RA patients from the CareRA cohort. Methods: In the CareRA trial, different COBRA treatment regimens consisting of synthetic DMARDs combined with a step-down glucocorticoid treatment, have been studied. Disease remission was defined as a DAS28CRP Results: Antibodies to UH-RA.21 were found in 21% (47/223) of the baseline samples from the CareRA cohort. Compared to baseline levels, combination therapy induced a 50% reduction of anti-UH-RA.21 antibody levels in 30% of patients after 16 weeks and in 47% of patients after 52 weeks. Seroconversion was observed in 16% (7/44) of patients after 16 weeks and 30% (10/34) after 52 weeks. Seroconversion was not correlated with remission according to the DAS28CRP or SDAI remission indices. However, of those patients which were UH-RA.21 positive at baseline, more seroconversion occurred in patients reaching remission (5/14, 36%) than in patients remaining in active disease (2/30, 7%), according to CDAI remission criteria (p=0.025). Conclusion: A COBRA therapy induces a rapid decrease in anti-UH-RA.21 autoantibody levels in many patients. Moreover, early anti-UH-RA.21 seroconversion is associated with CDAI remission. Disclosure of Interests: Silke Loyens: None declared, Patrick Vandormael: None declared, Liesbeth De Winter: None declared, Veerle Stouten: None declared, Piet Geusens Grant/research support from: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Consultant for: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Research support, consultant and/or speaker fees from: Pfizer, Abbott, Eli Lilly, Amgen, MSD, Roche, UCB, BMS, Novartis, Will-Pharma, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Bio Minerals and Roche, Patrick Verschueren Grant/research support from: Unrestricted Pfizer Grant for Early RA research, Veerle Somers Grant/research support from: Research support from Bristol Myers-Squibb

Background:Rheumatoid arthritis (RA) can cause important bio-psychosocial burden. When exploring disease burden evolution in the 2-year Care in early RA (CareRA) trial, 3 factor scores were extracted via exploratory factor analysis (EFA).1 EFA uncovers the fact that multiple observed variables have similar patterns of responses because they are all associated with a latent, not directly observable, variable.Objectives:To validate in a population with established RA, the 3 factors scores and their individual components originally extracted in CareRA.Methods:Patients with established RA in sustained remission under treatment with etanercept (≥1 year) were enrolled in the TapERA (Tapering Etanercept in RA) trial between 2012 and 2014. Patients completed the Flare Assessment in RA (FLARE-RA) questionnaire.2Components of disease activity scores (swollen/tender joint count, physician and patient global health assessment, CRP and ESR), as well as pain (question 2) and fatigue evaluation (question 8), from the FLARE-RA questionnaire, and HAQ were recorded at every visit (v=5).Missingness on previously mentioned variables was handled with multiple imputation (100 imputations). Pain and fatigue were re-scaled from their original Likert scale of 1-6 to 0-100 to match CareRA data. Next, timepoint clustering was removed with multiple outputation (1000x) and each of the 100 000 datasets was analyzed by EFA with principal component extraction and oblimin rotation. The analyses were combined after re-ordering the factors by maximizing factor congruence.Results:Sixty-six patients with a mean disease duration of 14.8 years (SD 9.03), mean age of 55.21 years (SD12.87), 96% (63/66) positive to RF or ACPA, 77% (51/66) with erosions and 68% (45/66) female were included in this analysis.Table 1 provides the results of the EFAs from CareRA and TapERA. The factor structure and factor components remained the same in both datasets. The factor loadings, indicating how strongly a variable relates to its factor (correlation between observed and latent score), were also comparable. The HAQ, however; did have a stronger factor loading in TapERA (0.57 vs 0.92).Table 1.Results from the exploratory factor analyses in CareRA and TapERAVariableCareRATapERAPRFCFLFPRFCFLFFatigue0.900.80PaGH0.870.81Pain0.860.75HAQ0.570.92SJC280.920.82TJC280.890.84PhGH0.760.60CRP0.870.85ESR0.780.82Factor loadings presented (correlation between the observed score and the latent factor). Cross-loadings were negligible (PRF: patient-reported factor, CF: clinical factor, LF: laboratory factor, PaGH: patient’s global health assessment, HAQ: health assessment questionnaire, SJC28: 28 swollen joint count, TJC28: 28 tender joint count, PhGH: physician’s global health assessment, CRP: C-reactive protein, ESR: erythrocyte sedimentation rateConclusion:The latent factor structure for disease burden originally found in CareRA was successfully validated in the TapERA dataset, underlining the robustness of the PRF, CF and LF scores. HAQ seems to take “greater importance” on established RA. However, deviations in factor loadings (e.g., HAQ) could be attributed to differences between study populations (e.g., early vs. established RA, sample size). Apart from traditional clinical and laboratory factors, patient-reported pain, fatigue, functionality and overall well-being determine disease burden, both in early and established RA. Using these factor scores could facilitate detection and management of patient’s unmet needs.References:[1]Pazmino, et al. Does Including Pain, Fatigue, and Physical Function When Assessing Patients with Early Rheumatoid Arthritis Provide a Comprehensive Picture of Disease Burden? J Rheumatology 2020 Nov.[2]Berthelot JM, et al. A tool to identify recent or present rheumatoid arthritis flare from both patient and physician perspectives: the ‘FLARE’ instrument. Annals Rheumatic Diseases. 2012.Disclosure of Interests:None declared

Background:Current EULAR guidelines recommend treating RA early, intensively and to-target. A data-driven tool for planning the optimal moment for subsequent visits might adapt visit schedules more to the patient’s needs, without losing treatment quality.Objectives:To determine the optimal statistical model and clinical factors to predict the time to a treatment adaptation in early RA patients.Methods:This study included 379 patients from the treat-to-target Care in Rheumatoid Arthritis (CareRA) trial. The CareRA protocol included 2 predefined treatment adaptation steps for patients not reaching low disease activity (DAS28CRPResults:Factors selected to predict the first per protocol change included TJC, SJC, HAQ, CRP, pain and morning stiffness>15min. Factors selected to predict the second per protocol change included TJC, SJC, PGA, PhGA. Uno Concordance indices showed similar scores per different statistical model but higher scores at w4 and w8 compared to baseline indicating a better predictive performance (Table 1. next page).Table 1.Uno Concordance Scores. Format ‘mean (min-max)’.BaselineWeek 4Week 8Cox Proportional HazardsChange 10.63 (0.59-0.69)0.72 (0.68-0.80)0.75 (0.69-0.82)Change 20.58 (0.50-0.66)0.75 (0.65-0.87)0.78 (0.65-0.93)Linear Multi-Task RegressionChange 10.65 (0.62-0.68)0.72 (0.68-0.78)0.75 (0.69-0.79)Change 20.58 (0.51-0.68)0.72 (0.67-0.82)0.77 (0.68-0.89)Random Survival ForestChange 10.64 (0.58-0.67)0.71 (0.66-0.78)0.76 (0.68-0.80)Change 20.56 (0.50-0.68)0.72 (0.60-0.82)0.77 (0.64-0.92)Conclusion:Our data-driven approach identified predictive clinical factors with a high face validity including joint counts, functionality scores and global health indicators. The different model approaches did not seem to increase the predictive capacity performance. However, our results underline that not so much the baseline disease status but rather the early response to initial treatment reflected in the selected predictive factors can be used for prediction of the need for further treatment adaptation. These models will have to be enriched with patient reported outcomes to further improve predictive performance.Disclosure of Interests:None declared

Background:Treatment of Rheumatoid Arthritis (RA) has improved significantly based on early treat-to-target (T2T) strategies. Still, decreased health related quality of life (QoL), restricted ability to work and other unmet needs are reported by RA patients even in the absence of disease activity. We previously identified 3 factors representing the broader impact of RA using exploratory factor analysis: a patient-reported factor (patients global health, pain, fatigue and HAQ), a clinical factor (physician’s global health, tender and swollen joint count), and a laboratory factor (ESR and CRP)1.Objectives:To test whether the discordance between patient-reported (PRF) and clinical(CF)/laboratory(LF) measures can predict QoL, or has a mediating effect in predicting future disease burden based on disease activity (DAS28CRP).Methods:This is a post-hoc analysis of the 2-year CareRA trial. PRF, CF and LF scores were calculated as weighted (by factor loading) sum of their components at week 16, 52 and 104 after treatment initiation. A discordance score (DS) between PRF and the mean of the other two scores was also computed.Mediation analyses were fitted to test the hypothesis (Figure 1) that DS could be a mediator for predicting PRF, CF and LF at a future time point (week 16, 52 and 104) using DAS28CRP at a previous time point (baseline and week 16). Confidence intervals were estimated via 10 000 bootstraps. Finally, a linear regression was fitted for DS to predict future QoL (RAQoL questionnaire; range 0-30; higher values indicating worse QoL).Results:Patients with early RA (n=379) were included with a mean (SD) age of 53.9 (13.0), 77% seropositive and 69% women.The DS was shown to be mediating the effect of DAS28CRP on any future PRF (Table1). On the other hand, there was no mediation effect of the DS in the prediction of the CF and an inconsistent mediation effect when predicting the LF.Moreover, the DS at week 16 significantly predicted (p2 of 0.30 (CI 0.22-0.38). Similarly, it predicted RAQoL (p2 of 0.32 (CI 0.24-0.40).Table 1.Results of mediation analyses for prediction of future burden based on previous DAS28CRP and mediated by discordance.TimepointPredictor variablesDirect Effect95% CIsR2Mediation effect Patient-reported factorW16DAS28CRP at BL-0.0091-0.0240, 0.00580.1450PresentDS at BL0.0246*0.0169, 0.03310.1784W52DAS28CRP at W160.0215*0.0010, 0.04190.3394PartialDS at W160.0580*0.0442, 0.07390.2749W104DAS28CRP at W160.0101-0.0102, 0.03050.2798PresentDS at W160.0528*0.0396, 0.06860.2749Clinical factorW16DAS28CRP at BL0.0153*0.0074, 0.02320.0599AbsentDS at BL0.0019-0.0010, 0.00480.1784W52DAS28CRP at W160.0365*0.0267, 0.04630.1944AbsentDS at W160.0034-0.0031, 0.00950.2749W104DAS28CRP at W160.0115*0.0024, 0.02070.0409AbsentDS at W160.0033-0.0019, 0.00890.2749Laboratory factorW16DAS28CRP at BL0.0063*0.0015, 0.01110.0634PartialDS at BL0.0030*0.0012, 0.00500.1784W52DAS28CRP at W160.0003-0.0063, 0.00680.0305PresentDS at W160.0051*0.0012, 0.00960.2749W104DAS28CRP at W16-0.0007-0.0079, 0.00640.0014AbsentDS at W160.0013-0.0019, 0.00460.2749W: week BL: baseline DS: discordance scoreDAS28CRP: disease activity score in 28 joints with C-reactive protein*pConclusion:Early discordance between patient-reported and biological/clinical factors mediates the effect of disease activity on future patient-reported outcomes, but also predicts QoL. Paying attention to this early discordance might provide opportunities to prevent patient’s unmet needs by additional non-pharmacological interventions, hence broadening the scope of T2T.References:[1]Pazmino S, et al. Does Including Pain, Fatigue, and Physical Function When Assessing Patients with Early Rheumatoid Arthritis Provide a Comprehensive Picture of Disease Burden? J Rheumatol. 2020 Nov 15:jrheum.200758. doi: 10.3899/jrheum.200758. Ahead of print.Disclosure of Interests:None declared

Background:Fatigue is reported in up to 90% of patients with established Rheumatoid Arthritis (RA). Fatigue has a large impact on patient`s life and is perceived difficult to manage in many patients. The early disease course could constitute a window of opportunity to tackle fatigue.Objectives:To explore that, if RA can be controlled rapidly, complaints of fatigue could be less in the long run, even in patients considered at low risk to develop a severe disease course.Methods:Patients with a low risk profile recruited in the 2-year pragmatic Care in Early Rheumatoid Arthritis (CareRA) trial were used in this analysis. This low risk profile was based on the absence of erosions, rheumatoid factor, anti-citrullinated protein bodies or low disease activity status. The low-risk group was randomised to either a tight step-up starting with 15mg MTX weekly in monotherapy (MTX-TSU) or COBRA Slim, consisting of 15 mg MTX weekly and a prednisone step-down scheme starting at 30 mg. Fatigue was measured by the multi-dimensional fatigue inventory (MFI), a self-report instrument consisting of 20 questions with a Likert scale from 1-5 as answer. These 20 questions can be subdivided in five subscales (0-20) of four questions (higher scores indicating higher fatigue levels): general fatigue, mental fatigue, physical fatigue, reduced activity and reduced motivation. General fatigue means the general feeling of being tired. Mental fatigue implicates concentration and memory problems. Physical fatigue implicates a lack of energy and strength. Reduced activity means that patients can do less activities for example on one day. Reduced motivation means that patients don’t want to plan or do things due to lack of motivation. MFI was obtained at baseline, at week 16, week 52 and week 104. Cobra Slim was compared with MTX-TSU by Mann-Whitney-U test. The 5 domains of the MFI of the two groups were compared by a generalized estimating equation (GEE) over 2 years adjusting for baseline MFI domain score and DAS28.Results:Of the 90 patients recruited in the low-risk group, 80 (89%) patients completed the MFI at baseline. Randomisation was successful resulting in similar baseline characteristics and MFI levels between Cobra Slim (n=38) and MTX-TSU (n=42). After 2 years of treatment, DAS28CRP levels (Slim 1.9 ±0.8 - MTX-TSU 2.2 ±1.0, p=0.253) and DAS28CRP remission (Slim 81.5% - MTX-TSU 77.1%, p=0.677) did not differ between patients. However, general (Slim 9.8 ±4.1 – MTX-TSU 13.1 ±4.0, p=0.005) and mental (Slim 6.8 ±2.7 - MTX-TSU 10.0 ±4.9, p=0.022) fatigue levels on the MFI were lower in the Cobra Slim group at week 104. GEE analysis confirmed that groups differed in the general (p=0.026) and mental (p=0.013) fatigue scale over 2 years (Figure 1).Figure 1.DAS28CRP and MFI General Fatigue score over 2 years between groupsConclusion:Patients treated intensively have lower fatigue levels over 2 years compared to patients treated more conservatively, even if disease activity became similar in the two groups over time. This underlines the importance of initiating an optimal intensive treatment even in so called low-risk patients. Moreover, our results show that fatigue is a heterogeneous concept, with different interactions between treatment and type of fatigue. Although our study was limited by a small sample size, the data clearly shows how to improve fatigue levels significantly in early RA.Disclosure of Interests:Diederik De Cock: None declared, Amber Nooyens: None declared, Sofia Pazmino: None declared, Delphine Bertrand: None declared, Veerle Stouten: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

Background:The Flare assessment in rheumatoid arthritis (FLARE-RA) questionnaire has been developed to identify flares in patients with rheumatoid arthritis (RA). The first version was published by Berthelot et al. (2012) and consisted of 13 questions on a Likert-scale of 1-6 ranging from ‘completely untrue’ to ‘completely true’. When the FLARE-RA questionnaire was validated by Fautrel et al., 2 questions were removed, and it was rescaled to 0–10. The questionnaires’ usefulness has been tested in few studies. Further external validation in a well-defined cohort of patients with RA is needed.Objectives:To externally validate the FLARE-RA questionnaire and determine cut-offs for identifying a flare in an established RA population in which biologicals are tapered.Methods:Patients who were in remission according to the DAS28CRP or ESR (≥6 months) and treated with etanercept 50 mg weekly (≥1 year), were enrolled between 2012 – 2014 in the pragmatic 1-year open-label randomised controlled TapERA (Tapering Etanercept in RA) trial. Patients were randomised to continue etanercept 50 mg weekly or taper to 50 mg every other week. The FLARE-RA questionnaire (version of 2012) was completed every 3 months. Outcomes were based on 3 versions of the questionnaire (13 questions (13q), 11 questions (11q) and 11 questions rescaled (r11q)). Per time point, the average of the answers was calculated to obtain a total score of the FLARE-RA questionnaire. The total scores were compared between patients in remission (DAS28CRP 3.2 - ≤5.1) and high disease activity (DAS28CRP >5.1) using the Kruskal-Wallis test and between patients with and without a flare according to the OMERACT definition (increase in DAS28 >1.2 compared to baseline or increase in DAS28 >0.6 and current DAS28 ≥3.2) using the Mann-Whitney U test. The total FLARE-RA scores of the different time points were combined to determine the receiver operating characteristics (ROC) curves, the corresponding cut-off values and the area under the curve (AUC) for identifying an OMERACT flare. An AUC of 0.7 stands for having no, moderate and a good predictive value, respectively.Results:FLARE-RA questionnaires of 66 patients (68% female, mean ± standard deviation (SD) age of 55 ± 11 years) were collected. The FLARE-RA score (13q) did increase when disease activity increased at month (M) 3 and M12 (pTable 1.Comparison of the total FLARE-RA scores (13q) between the disease activity groups (DAS28CRP)RemissionLDAMDAHDAP-valueBLPatients (n)62310FLARE Q1.8 ± 0.81.5 ± 0.31.30.800M3Patients (n)501150FLARE Q2.1 ± 1.03.0 ± 0.93.5 ± 1.40.004M6Patients (n)52590FLARE Q2.1 ± 0.83.1 ± 1.33.1 ± 1.90.057M9Patients (n)481071FLARE Q2.1 ± 0.92.8 ± 1.13.3 ± 1.62.40.079M12Patients (n)52860FLARE Q2.1 ± 1.03.1 ± 0.83.2 ± 1.00.002Figure 1.ROC curves of the total FLARE-RA scores (13q, 11q and r11q version) for identifying a flare according to the OMERACT definition. FLARE Q is expressed in mean ± SD. M month, FLARE Q FLARE-RA questionnaire 13q, n number, LDA low disease activity, MDA moderate disease activity, HDA high disease activityConclusion:The FLARE-RA scores seem to reliably discern between patients with and without an OMERACT flare. A cut-off of 2.7 on the current questionnaire (r11q) had the optimal sensitivity and specificity to identify an OMERACT flare.Disclosure of Interests:Delphine Bertrand: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Diederik De Cock: None declared, Anneleen Moeyersoons: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Johan Joly: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

Background:Fatigue is mentioned as a symptom with high impact in many patients with Rheumatoid Arthritis (RA) and this symptom remains difficult to be managed by both the patient and the physician.Objectives:To investigate if rapid suppression of disease activity in early RA could impact fatigue complaints in the long run.Methods:For this study, we included patients from the 2-year pragmatic investigator-initiated Care in Early Rheumatoid Arthritis (CareRA) trial. Most patients were treated intensively, with different combinations of csDMARDs and glucocorticoid remission induction schemes, except one group without classic markers of poor prognosis that was treated with MTX weekly in monotherapy. Patients were followed up at least every 3 months, with more mandatory visits in the first 6 months of treatment. Clinical parameters including DAS28 components were registered at every visit. Fatigue was measured by the multi-dimensional fatigue inventory (MFI), a self-reported instrument consisting of 20 questions with a Likert scale from 1-5 as answer. These 20 questions can be subdivided in five subscales (0-20) of four questions (higher scores indicating higher fatigue levels): general fatigue, mental fatigue, physical fatigue, reduced activity and reduced motivation. General fatigue means the general feeling of being tired. Mental fatigue implicates concentration and memory problems. Physical fatigue implicates a lack of energy and strength. Reduced activity means that patients can do less activities for example on one day. Reduced motivation means that patients don’t want to plan or do things due to no motivation. MFI was obtained at baseline, at week 16, week 52 and week 104. Only patients with a filled-out MFI at baseline and available DAS28CRP at week 16 were included in this study.Patients were divided in 2 groups based on their response, defined as achieving or not achieving DAS28CRP remission (Results:Of the 379 patients recruited in the CareRA trial, 343 (90.5%) had a MFI score available at baseline and a DAS28CRP available at week 16 with 236 (68.8%) patients achieving remission, and 107 (31.2%) patients not achieving remission at week 16. After 2 years of treatment, the proportion of patients in DAS28CRP remission was still higher in the early responders versus controls (82.3% versus 63.5%, p=0.001). Every MFI domain after 2 years of treatment showed lower scores for early responders including general fatigue (p=0.017), physical fatigue (p=0.011), reduced activity (p=0.040) and mental fatigue (p=0.042) except reduced motivation (p=0.062) (see figure 1). GEE analysis demonstrated that all MFI domains differed over 2 years between patients in remission or not at week 16, including general fatigue (pFigure 1.MFI domain scores at baseline and at week 104 per groupConclusion:Patients reaching remission after 16 weeks of treatment achieve lower fatigue levels over 2 years compared to patients not reaching this early remission. This study underlines the importance of early disease control. Successful early intensive treatment improves in the long run not only clinical outcomes but also an important patient preferred outcome such as fatigue.Disclosure of Interests:Diederik De Cock: None declared, Amber Nooyens: None declared, Delphine Bertrand: None declared, Veerle Stouten: None declared, Sofia Pazmino: None declared, Johan Joly: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies