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Background/Objective Fatigue is common in patients with rheumatoid arthritis (RA). We assessed the relative impact of pain and disease activity on improvements in fatigue in 2 phase 3 baricitinib clinical trials. Methods RA-BEAM (NCT01710358) and RA-BEACON (NCT01721044) were randomized, double-blind, placebo-controlled studies in adults with moderate to severe RA. RA-BEAM assessed baricitinib + methotrexate (MTX) and adalimumab + MTX in patients with prior inadequate response/intolerance (IR) to MTX (MTX-IR). RA-BEACON assessed patients with IR to ≥1 biologic disease-modifying antirheumatic drug (bDMARD-IR). Measures included the Functional Assessment of Chronic Illness Therapy - Fatigue scale, Clinical Disease Activity Index (CDAI) for RA, and pain visual analog scale (VAS). Analyses were implemented separately for each study. Results Significant improvements were seen in disease activity and pain, which were greater with baricitinib versus adalimumab. A statistically significant improvement was seen in fatigue with both active treatments versus placebo. Moderate correlations were observed between improvements in disease activity and fatigue and between improvements in pain and fatigue in both MTX-IR and bDMARD-IR patients. Reductions in pain (≥50%) and remission or low disease activity (CDAI ≤10) had significant associations with fatigue improvement at week 24. In mediation analysis, improvements in fatigue attributable to CDAI and pain VAS in MTX-IR patients were 31% and 52%, respectively, for baricitinib, and 30% and 47%, respectively, for adalimumab. In bDMARD-IR patients, improvement in fatigue was attributed 48% to CDAI and 48% to pain VAS. Conclusions In both MTX-IR and bDMARD-IR patients, a large proportion of improvements in fatigue across treatment arms were accounted for by improvements in pain and disease activity.

Objective To evaluate the nature and burden of residual disease in rheumatoid arthritis (RA) in patients who meet treatment targets. Second, for those who did not meet targets, to evaluate how much is due to patient symptoms. Methods Prospective and retrospective studies were searched in Medline, Embase, and Cochrane Library in the English language from January 1, 2008 to April 18, 2018; conference abstracts (from January 2016 to April 2018) and reference lists of relevant studies were also screened. Results Of 8,339 records identified, 55 were included in the review; 53 were unique studies, including 10 randomized controlled trials. Of these, 48 reported on patients who achieved low disease activity (LDA) or remission. Studies varied in population, treatment goals, and outcome reporting. The proportions of patients with residual symptoms in these studies varied by the definitions used for LDA or remission and were more often reported in patients with LDA than those in remission. The most commonly reported outcome measures were functional disability (n = 34 studies), tender or swollen joints (n = 18), pain (n = 17), patient global assessment (n = 15), and fatigue (n = 14). However, few studies reported the percentage of patients achieving a specific threshold, which could then be used to easily define the presence of residual symptoms. Conclusion Residual symptoms are present in some patients despite their achieving LDA or remission, highlighting an unmet need, especially with respect to improving pain, fatigue, and function. Standardized reporting in future observational studies would facilitate better understanding of this issue in defined RA populations.

Objective As young people enter adulthood, the interchangeable use of child and adult outcome measures may inaccurately capture changes over time. This study aimed to use item response theory (IRT) to model a continuous score for functional ability that can be used no matter which questionnaire is completed. Methods Adolescents (ages 11-17 years) in the UK Childhood Arthritis Prospective Study (CAPS) self-completed an adolescent Childhood Health Assessment Questionnaire (CHAQ) and a Health Assessment Questionnaire (HAQ). Their parents answered the proxy-completed CHAQ. Those children with at least 2 simultaneously completed questionnaires at initial presentation or 1 year were included. Psychometric properties of item responses within each questionnaire were tested using Mokken analyses to assess the applicability of IRT modeling. A previously developed IRT model from the Pharmachild-NL registry from The Netherlands was validated in CAPS participants. Agreement and correlations between IRT-scaled functional ability scores were tested using intraclass correlations and Wilcoxon's signed rank tests. Results In 303 adolescents, the median age at diagnosis was 13 years, and 61% were female. CHAQ scores consistently exceeded HAQ scores. Mokken analyses demonstrated high scalability, monotonicity, and the fact that each questionnaire yielded reliable scores. There was little difference in item response characteristics between adolescents enrolled in CAPS and Pharmachild-NL (maximum item residual 0.08). Significant differences were no longer evident between IRT-scaled HAQ and CHAQ scores. Conclusion IRT modeling allows the direct comparison of function scores regardless of different questionnaires being completed by different people over time. IRT modeling facilitates the ongoing assessment of function as adolescents transfer from pediatric clinics to adult services.

Contains fulltext : 225847.pdf (Publisher’s version ) (Closed access) To re-evaluate the adherence to clinical practice guidelines recommended disease activity-based management of rheumatoid arthritis (RA) in daily clinical practice, among Dutch rheumatologists in the past decade. In 2007, disease activity was measured in only 16% of outpatient visits. All rheumatologists that participated in the 2007 study were invited to re-enter our study in 2016/2017. If necessary, data were supplemented with data from other rheumatologists. For all 26 rheumatologists who agreed to participate in our study, data were collected from 30 consecutive patients that visited the outpatient clinic. Per patient, data from four consecutive rheumatologist outpatient visits were collected. Since 2007, disease activity was measured more frequently in Dutch daily clinical practice, increasing from 16 to 79% of visits (2440/3081 visits). In addition, intensification of medication based on disease activity scores increased from 33 to 50% of visits (260/525 visits). DAS/DAS28 was the most frequently used disease activity measure (1596/2440 visits). There was a wide variation among rheumatologists in measuring disease activity and intensification of medication, 20-100% and 0-75% respectively. Over the past years, there has been a large improvement in disease activity assessment in daily clinical practice. Disease activity-based medication intensifications, also called tight control or treat to target, increased to a lesser extent. Large variation between different rheumatologists and clinics indicates that there is still room for improvement. Key Points • Following guideline dissemination disease activity is assessed more frequently (79%). • There is large variation between rheumatologists, indicating room for improvement. • Finding factors that explain variation is necessary to improve tight control in daily practice.

Contains fulltext : 251380.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To evaluate the effect of an intervention to improve disease activity-based management of RA in daily clinical practice by addressing patient level barriers. METHODS: The DAS-pass strategy aims to increase patients' knowledge about DAS28 and to empower patients to be involved in treatment (decisions). It consists of an informational leaflet, a patient held record and guidance by a specialized rheumatology nurse. In a Randomized Controlled Trial, 199 RA patients were randomized 1:1 to intervention or control group. Outcome measures were patient empowerment (EC-17; primary outcome), attitudes towards medication (BMQ), disease activity (DAS28) and knowledge about DAS28. RESULTS: Our strategy did not affect EC-17, BMQ, or DAS28 use. However it demonstrated a significant improvement of knowledge about DAS28 in the intervention group, compared to the control group. The intervention had an additional effect on patients with low baseline knowledge compared to patients with high baseline knowledge. CONCLUSION: The DAS-pass strategy educates patients about (the importance of) disease activity-based management, especially patients with low baseline knowledge. PRACTICE IMPLICATIONS: The strategy supports patient involvement in disease activity-based management of RA and can be helpful to reduce inequalities between patients in the ability to be involved in shared decision making.

© 2018, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology. Objective: The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. Methods: The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. Results: The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. Conclusion: We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.

Introduction This survey assessed the impact of rheumatoid arthritis (RA) on the lives of patients based on the perceptions of both patients and healthcare professionals (HCPs). Methods This is a cross-sectional survey of patients with RA. Data were collected from patients and HCPs who manage RA using a structured, closed-ended questionnaire in their local language. Respondents for the survey were recruited from survey panels of verified unique responses. The survey focused on the impact of disease on four domains: daily activities, relationships, work and aspirations. Results Overall, 1231 adult patients with RA and 270 rheumatologists or other HCPs were surveyed between November 2016 and February 2017. Almost one in three patients believed that the impact of RA is not well understood by people without the disease. Fifty-eight percent [95% confidence interval (CI) 55–61%] of patients felt frustrated when they were unable to undertake or complete daily activities because of their disease. Fifty-seven percent (95% CI 54–60%) of patients wished to be able to accept their life with RA. Forty-three percent (95% CI 40–46%) of patients hoped that the physical impact of RA will be better understood in future. Forty percent (95% CI 37–43%) of patients were forced to take long-term leave/retirement or experienced slow career progression since being diagnosed with RA. Twenty-three percent (95% CI 21–25%) of patients had difficulties in taking care of personal grooming, whereas 8% (95% CI 6–10%) of patients reported that RA ruined their life. Similar responses were observed among HCPs. Conclusion Patients and HCPs feel that the physical and emotional impact of RA is not well understood by people without the disease. In RA treatment decisions, patients’ personal goals and patient-reported outcomes should be taken into consideration along with clinical targets. Funding Eli Lilly and Company (Indianapolis, IN, USA). Electronic Supplementary Material The online version of this article (10.1007/s40744-019-00179-2) contains supplementary material, which is available to authorized users.

OBJECTIVE: To retrospectively compare the long-term clinical, functional, and cost outcomes for early RA patients (symptoms

Objective To assess psychometric properties and cross-language measurement equivalence of six versions of the Bristol Rheumatoid Arthritis Fatigue Scale (BRAF-MDQ) and the Rheumatoid Arthritis Impact of Disease Score (RAID in rheumatoid arthritis (RA). Methods Both questionnaires were completed by French (n = 206), German (n = 206), Dutch (n = 317), Spanish (n = 157), Swedish (n = 170) and UK (n = 210) RA patients. The presence of cross-language differential item functioning (DIF) was examined using the generalized partial credit model. The impact of DIF on the item and total scores was examined by comparing DIF unadjusted and DIF adjusted expected item and scale scores. IRT-based methods were used to assess psychometric properties of the instruments. Results 11 of the 20 BRAF-MDQ (55%) and 4 of the 7 RAID items (57%) exhibited significant DIF in at least one of the six countries. The mean number of items with DIF per country was 2.6 for BRAF-MDQ and 1.1 for RAID. However, the impact of DIF on the total RAID and BRAF-MDQ scores, as well as the BRAF subscales, was found to be negligible at the group level. Only for the BRAF physical subscale was there evidence of minor DIF. Marginal reliabilities of BRAF-MDQ (0.93) and RAID (0.89) were excellent, and precise scores could be obtained across the spectrum of disease impact and fatigue scores measured by these PROMs. Conclusion This study supports the cross-language measurement equivalence of BRAF-MDQ and RAID and provides further support for the psychometric properties of these measures in RA. Electronic supplementary material The online version of this article (10.1007/s11136-019-02188-8) contains supplementary material, which is available to authorized users.

Objective Inflammation-related symptoms such as pain, swelling and tenderness of the affected joint are frequently assessed using 5-point diary rating scales in gout clinical trials. Combining these into a single gout attack symptom intensity score may be a useful summary measure for these data, which is potentially more responsive to change compared with the individual components. The objective of this study was to develop a patient-reported gout flare intensity score, the Gout Attack Intensity Score (GAIS), for use in clinical studies, that includes components for gout-related pain, swelling and tenderness. Methods Data from a randomized controlled trial comparing anakinra to standard of care for the treatment of acute gout attacks were used for this study. A 7-day flare diary was completed by patients, including questions relating to intensity of pain, swelling and tenderness (5-point rating scales). Scalability of these items was assessed using Mokken Scale Analysis, and reliability using greatest lower bound reliability coefficients. Known-groups validity was evaluated, as well as the responsiveness to change and the presence of floor and ceiling effects. Results Scalability of the single items was supported, and GAIS scores were reliable (greatest lower bound >0.80). GAIS scores demonstrated responsiveness to change with high effect sizes (>0.8), and discriminated better between responders and non-responders compared with its single-item components. No floor and ceiling effects were found. Conclusion The GAIS seems to be a reliable and responsive instrument for assessing patient-reported gout attack intensity that may be used in gout clinical studies.

Contains fulltext : 238610.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The systematic development of an intervention to improve disease activity-based management of rheumatoid arthritis (RA) in daily clinical practice that is based on patient-level barriers. METHODS: The self-management strategy was developed through a step-wise approach, in a process of co-design with all stakeholders and by addressing patient level barriers to RA management based on disease activity. RESULTS: The resulting DAS-pass strategy consists of decision supportive information and guidance by a specialised rheumatology nurse. It aims to increase patients' knowledge on DAS28, to empower patients to be involved in disease management, and to improve patients' medication beliefs. The decision supportive information includes an informational leaflet and a patient held record. The nurse individualises the information, stimulates patients to communicate about disease activity, and offers the opportunity for questions or additional support. CONCLUSION: The DAS-pass strategy was found helpful by stakeholders. It can be used to improve RA daily clinical practice. Our systematic approach can be used to improve patient knowledge and self-management on other RA related topics. Also, it can be used to improve the management of other chronic conditions. We therefore provide a detailed description of our methodology to assist those interested in developing an evidence-based strategy for educating and empowering patients.

Objective To identify and describe health literacy profiles of patients with rheumatic diseases and explore whether the identified health literacy profiles can be generalized to a broader rheumatology context. Methods Patients with rheumatoid arthritis, spondyloarthritis, and gout from 3 hospitals in different regions in The Netherlands completed the Health Literacy Questionnaire (HLQ). Hierarchical cluster analysis was used to identify patients' health literacy profiles based on 9 HLQ domains. A multinomial regression model with the identified health literacy profiles as the dependent variable was fitted to assess whether patients with a given disease type or attending a given hospital were more likely to belong to a specific profile. Results Among 895 participating patients, the lowest mean HLQ domain scores (indicating most difficulty) were found for "critical appraisal," "navigating the health system," and "finding good health information." The 10 identified profiles revealed substantial diversity in combinations of strengths and weaknesses. While 42% of patients scored moderate to high on all 9 domains (profiles 1 and 3), another 42% of patients (profiles 2, 4, 5, and 6) clearly struggled with 1 or several aspects of health literacy. Notably, 16% (profiles 7-10) exhibited difficulty across a majority of health literacy domains. The probability of belonging to one of the profiles was independent of the hospital where the patient was treated or the type of rheumatic disease. Conclusion Ten distinct health literacy profiles were identified among patients with rheumatic diseases, independent of disease type and treating hospital. These profiles can be used to facilitate the development of health literacy interventions in rheumatology.

Objective The aim was to develop two disease- and treatment-related knowledge about RA (DataK-RA) short forms using item response theory-based linear optimal test design. Methods We used the open source Excel add-in solver to program a linear optimization algorithm to develop two short forms from the DataK-RA item bank. The algorithm was instructed to optimize precision (i.e. reliability) of the scores for both short forms, subject to a number of constraints that served to ensure that each short form would include unique items and that the short forms would have similar psychometric properties. Agreement among item response theory scores obtained from the different short forms was assessed using the Bland–Altman method and Student’s paired t-test. Construct validity and relative efficiency of the short forms was evaluated by relating the score to age, sex and educational attainment. Results Two short forms were derived from the DataK-RA item bank that satisfied all content constraints. Both short forms included 15 unique items and yielded reliable scores (r > 0.70), with low ceiling and floor effects. The short forms yielded statistically indistinguishable mean scores according to Student’s paired t-test and Bland–Altman analysis. Scores on short forms 1 and 2 were associated with age, sex and educational attainment to a similar extent. Conclusion In this study, we developed two DataK-RA short forms with unique items, yet similar psychometric properties, that can be used to assess patients pre- and post-test interventions aimed at improving disease-related knowledge in RA patients.

ObjectivesTo evaluate the efficacy and safety of anakinra in treating acute gout flares in a randomized, double-blind, placebo-controlled, active comparator, non-inferiority (NI) trial.MethodsPatients with a crystal-proven acute gout flare were randomized (1: 1) to treatment with anakinra or treatment as usual (free choice: either colchicine, naproxen or prednisone). The primary end point was the change in pain between baseline and the averaged pain score on days 2–4 measured on a five-point rating scale. NI of anakinra would be established if the upper bound of the 95% CI of the numeric difference in changed pain scores between treatment groups did not exceed the NI limit of 0.4 in favour of treatment as usual, in the per-protocol (PP) and intention-to-treat (ITT) populations, assessed in an analysis of covariance model. Secondary outcomes included safety assessments, improvement in pain, swelling, tenderness and treatment response after 5 days, assessed using linear mixed models and binary logistic regression models.ResultsForty-three patients received anakinra and 45 treatment as usual. Anakinra was non-inferior (mean difference; 95% CI) to treatment as usual in both the PP (–0.13; –0.44, 0.18) and ITT (–0.18; –0.44, 0.08) populations. No unexpected or uncommon (serious) adverse events were observed in either treatment arm. Analyses of secondary outcomes showed that patients in both groups reported similar significant reductions in their gout symptoms.ConclusionEfficacy of anakinra was shown to be non-inferior to treatment as usual for the treatment of acute gout flares, suggesting that anakinra is an effective treatment alternative for acute gout flares.Trial registrationHet Nederlands Trial Register, www.trialregister.nl, NTR5234

Purpose Generalized pain hypersensitivity is frequently observed in chronic pain conditions. Currently, identification is based on expert clinical opinion, and in very few cases combined with quantitative sensory testing. The objectives of this study were to develop and evaluate a short self-report measure of generalized pain hypersensitivity: a generalized pain questionnaire (GPQ). Methods Items for the GPQ were developed based on a literature review, followed by an interview study with ten rheumatic patients with suspected pain hypersensitivity. We examined the psychometric properties of the preliminary items in a sample of 212 outpatients suffering from either fibromyalgia (FM; n=98) or rheumatoid arthritis (n=114). Additionally, self-reported data were gathered on sociodemographics, fibromyalgia-survey criteria, health status, and neuropathic-like pain features. Results Mokken-scale analyses demonstrated a unidimensional seven-item scale with strong homogeneity (H=0.65) and high reliability (r=0.90). Correlations between total GPQ scores and relevant external measures, such as the FM-survey criteria and neuropathic-like pain features, were consistent with a priori expectations, supporting its external construct validity. Furthermore, the GPQ had good accuracy in distinguishing between patients with FM (generally assumed to be the result of central nervous system hypersensitization) and patients with RA (assumed to result mostly in local nociceptive or inflammatory pain), with an area under the receiver-operating characteristic curve of 0.89. A cutoff value >10 had the highest combination of sensitivity (82.7%) and specificity (77.2%). Conclusion The GPQ is psychometrically sound and appears promising for measuring the presence and severity of generalized pain hypersensitivity in chronic pain patients.

Purpose: Goal was to establish whether an intervention that aims to increase goal management competencies is effective in decreasing elevated levels of depressive symptoms and increasing well-being in patients with polyarthritis. Materials and methods: Eighty-five persons with polyarthritis and elevated levels of depressive symptoms participated in the goal management intervention consisting of six group-based meetings. A quasi-experimental design with baseline measurement, follow-up at 6 months and a reference group of 151 patients from an observational study was applied. Primary outcome was depression; secondary outcomes were anxiety, purpose in life, positive affect, satisfaction with participation, goal management strategies, and arthritis self-efficacy. A linear mixed model procedure was applied to evaluate changes in outcomes. Results: No improvement was found for depressive symptoms and no changes were found for the secondary outcomes, except for positive affect that improved in the intervention group. This increase was mediated by an increase in goal adjustment. Furthermore, goal maintenance decreased and self-efficacy for other symptoms increased in the intervention group. Conclusion: This study indicates that interventions designed to aid patients with arthritis with goal management skills are potentially helpful for increasing positive affect, although further studies are needed.Implications for rehabilitation People with polyarthritis have to manage their disease in combination with possibly conflicting roles and personal goals, resulting in an ongoing process of finding equilibrium in a constantly changing situation. Based on a person-focused view, the program Right on Target focused on coping with threatened activities and life goals due to arthritis. The program consisted of six group-based meetings led by a trained nurse and a personal trajectory wherein participants were stimulated to try out various behavioral options related to an own threatened activity in concordance with their personal goals. The program seemed effective in increasing flexible goal adjustment and self-efficacy and participants experienced more positive affect directly after the program and at 6-month follow-up.

Objective Recently we developed the Rasch Everyday Activity Limitations (REAL) generic item bank for measuring physical function. In this study we evaluate the REAL item bank in 209 RA patients and demonstrate how computerized adaptive testing (CAT) and Optimal Test Assembly methods can be used to derive measures from the REAL item bank with superior measurement performance compared with the HAQ Disability Index (HAQ-DI). Methods Structural validity of the item bank was assessed using confirmatory factor analysis. The validity of the REAL score metric in RA was evaluated by examining differential item functioning against the general population calibration sample. Besides the REAL-CAT, a 6-item short form (REAL-6) was developed using Optimal Test Assembly that was optimized with respect to common disability levels in RA, content and reading ease. Measurement precision of the different instruments was examined using item response theory methods. Construct validity was evaluated by testing hypothesized correlations with external measures. Results Good model-data fit was observed for a one-dimensional model and only two items showed differential item functioning of substantial magnitude. The REAL-CAT had superior measurement precision compared with HAQ-DI and REAL-6. REAL-6 outperformed HAQ-DI across all but the very lowest level of physical function. All three instruments demonstrated good construct validity (>75% of hypotheses affirmed) and only HAQ-DI had a ceiling effect (23.9%). Conclusion This study supports the validity of the REAL item bank and illustrates the potential of CAT and OTA applications based on the REAL item bank for assessing physical function in RA.

Objective: To determine the impact of stopping tumor necrosis factor inhibitor (TNFi) treatment on patient-reported outcomes (PROs) of physical and mental health status, health utility, pain, disability and fatigue in patients with established rheumatoid arthritis (RA). Methods: In the pragmatic 12-month POET trial, 817 RA patients with ≥6 months of remission or stable low disease activity were randomized 2:1 to stopping or continuing TNFi. In case of flare, TNFi was restarted at the discretion of the rheumatologist. PROs were assessed every 3 months. Results: TNFi was restarted within 12 months in 252/531 patients (47.5%) in the stop group. At 3 months, mean PRO scores were significantly worse in the stop group and a larger proportion of patients experienced a minimal clinically important difference (MCID) on all PROs. Effect sizes (ES) were strongest for health utility (ES = -0.24) and pain (ES = -0.30). Mean scores improved again after this point but disability scores remained significantly different at 12 months. After 12 months, the relative risk of experiencing a MCID ranged from 1.16 for mental health status to 1.58 for fatigue. Mean PRO scores for patients restarting TNFi within 6 months were no longer significantly different from those that did not restart TNFi at 12 months. Conclusion: Stopping TNFi had a significant negative short-term impact on a broad range of PROs. Long-term negative consequences appeared to be limited and outcomes in patients needing to restart TNFi within the first 6 months tended to be restored at 12 months. This article is protected by copyright. All rights reserved.

Objective: To develop a Disease and treatment associated Knowledge in RA item bank (DataK-RA) based on item response theory. Methods: Initial items were developed from a systematic review. Rheumatology professionals identified relevant content trough a RAND modified Delphi scoring procedure and consensus meeting. RA patients provided additional content trough a focus group. Patients and professionals rated readability, feasibility and comprehensiveness of resulting items. Cross-sectional data were collected to evaluate psychometric properties of the items. Results: Data of 473 patients were used for item reduction and calibration. Twenty items were discarded based on corrected item-total point biserial correlation

Objective Traditional patient-reported physical function instruments often poorly differentiate patients with mild-to-moderate disability. We describe the development and psychometric evaluation of a generic item bank for measuring everyday activity limitations in outpatient populations. Study design and setting Seventy-two items generated from patient interviews and mapped to the International Classification of Functioning, Disability and Health (ICF) domestic life chapter were administered to 1128 adults representative of the Dutch population. The partial credit model was fitted to the item responses and evaluated with respect to its assumptions, model fit, and differential item functioning (DIF). Measurement performance of a computerized adaptive testing (CAT) algorithm was compared with the SF-36 physical functioning scale (PF-10). Results A final bank of 41 items was developed. All items demonstrated acceptable fit to the partial credit model and measurement invariance across age, sex, and educational level. Five- and ten-item CAT simulations were shown to have high measurement precision, which exceeded that of SF-36 physical functioning scale across the physical function continuum. Floor effects were absent for a 10-item empirical CAT simulation, and ceiling effects were low (13.5%) compared with SF-36 physical functioning (38.1%). CAT also discriminated better than SF-36 physical functioning between age groups, number of chronic conditions, and respondents with or without rheumatic conditions. Conclusion The Rasch assessment of everyday activity limitations (REAL) item bank will hopefully prove a useful instrument for assessing everyday activity limitations. T-scores obtained using derived measures can be used to benchmark physical function outcomes against the general Dutch adult population. Electronic supplementary material The online version of this article (doi:10.1007/s11136-017-1627-0) contains supplementary material, which is available to authorized users.

Celine J Van De Laar,1 Martijn AH Oude Voshaar,1,2 Walid KH Fakhouri,3 Liliana Zaremba-Pechmann,3 Francesco De Leonardis,3 Inmaculada De La Torre,3 Mart AFJ Van De Laar1,2 1Transparency in Healthcare BV, Hengelo, the Netherlands; 2Department of Psychology and Communication of Health and Risk, Institute for Behavioural Research, University of Twente, Enschede, the Netherlands; 3Eli Lilly & Company, Indianapolis, IN, USACorrespondence: Celine J Van De Laar Tel +31 74-43032645Email c.vandelaar@tihealthcare.nlBackground: Baricitinib is a janus kinase (JAK1/JAK2) inhibitor developed for the treatment of patients suffering from rheumatoid arthritis (RA). Treating RA to the target of remission is current common practice. Cost-effectiveness of different treat-to-target (T2T) strategies, especially ones including new treatments is important for development and preference policy for treatment centers. European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) guidelines are currently unclear about preference between a JAK1/JAK2 versus a biological disease-modifying antirheumatic drug (bDMARD).Objective: The main goal of this paper was to evaluate the cost-effectiveness of baricitinib versus first biological for methotrexate inadequate responders in a T2T strategy using a Markov model that incorporates hospital costs as well as societal costs. Costs and utilities over five years were compared between the two strategies.Methods: A Monte Carlo simulation model was developed to conduct cost–utility analysis from the societal perspective over 5 years. Health states were based on the DAS28-erythrocyte sedimentation rate (ESR) categories. Effectiveness of baricitinib was retrieved from randomized controlled trials. Effectiveness of all other treatments, health state utilities, medical costs, and productivity loss were retrieved from the Dutch RhEumatoid Arthritis Monitoring (DREAM) cohorts. Annual discount rates of 1.5% for utility and 4% for costs were used. Probabilistic sensitivity analysis was employed to incorporate uncertainty and assess robustness of the results.Results: Probabilistic sensitivity analysis results showed the baricitinib strategy yielded lower costs and higher utility over a 5-year period. Scenario analyses showed the baricitinib strategy to be cost-effective in both the moderate and severe RA populations.Conclusion: Results suggest that the use of a JAK1/JAK2 inhibitor instead of a bDMARD in a T2T approach is cost-effective in csDMARD refractory RA patients.Keywords: Markov model, rheumatoid arthritis, baricitinib, cost-effectiveness, health economic model, treat-to-target

The next step in the treatment of immune diseases: jakinibs, inhibitors of the intracellular Janus kinase The intracellular Janus kinase (JAK) and the signal transduction and activator of transcription (STAT) proteins are involved in the whole spectrum of immune-mediated diseases. Currently, agents are developed that influence the JAK-STAT mechanism. JAK inhibitors (jakinibs) have only recently made their way into clinical practice. These agents exhibit both similarities and differences in terms of effectiveness and safety. In the coming years, results from basic and clinical research will improve our knowledge of these agents. For patients who suffer from immune-mediated diseases, their introduction appears to be a breakthrough that will offer new treatment options. One advantage over biologicals is that jakinibs can be taken orally. As with all new innovative medicines, with jakinibs one cannot escape a discussion over costs as well. The balance between the added value of jakinibs compared to biologicals, and the actual purchase prices for each of these treatment modalities, will influence the eventual positioning of jakinibs.

To re-evaluate the adherence to clinical practice guidelines recommended disease activity-based management of rheumatoid arthritis (RA) in daily clinical practice, among Dutch rheumatologists in the past decade. In 2007, disease activity was measured in only 16% of outpatient visits. All rheumatologists that participated in the 2007 study were invited to re-enter our study in 2016/2017. If necessary, data were supplemented with data from other rheumatologists. For all 26 rheumatologists who agreed to participate in our study, data were collected from 30 consecutive patients that visited the outpatient clinic. Per patient, data from four consecutive rheumatologist outpatient visits were collected. Since 2007, disease activity was measured more frequently in Dutch daily clinical practice, increasing from 16 to 79% of visits (2440/3081 visits). In addition, intensification of medication based on disease activity scores increased from 33 to 50% of visits (260/525 visits). DAS/DAS28 was the most frequently used disease activity measure (1596/2440 visits). There was a wide variation among rheumatologists in measuring disease activity and intensification of medication, 20-100% and 0-75% respectively. Over the past years, there has been a large improvement in disease activity assessment in daily clinical practice. Disease activity-based medication intensifications, also called tight control or treat to target, increased to a lesser extent. Large variation between different rheumatologists and clinics indicates that there is still room for improvement. Key Points • Following guideline dissemination disease activity is assessed more frequently (79%). • There is large variation between rheumatologists, indicating room for improvement. • Finding factors that explain variation is necessary to improve tight control in daily practice.

Background The aim of this retrospective study was to examine the longitudinal association between disease activity and radiographic damage in a cohort of patients with early RA (symptom onset Methods Baseline to 3-year follow-up data were used from patients included in the DREAM remission induction cohort. Patients received protocolized T2T treatment, aimed at 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR) remission. Disease activity (DAS28-ESR and C-reactive protein, CRP) were assessed at least every 3 months; X-rays of the hand and feet at inclusion, 6 months, and 1, 2, and 3 years were scored using modified Sharp/van der Heijde scoring (SHS). Between and within-person associations between time-integrated disease activity and radiographic progression over time were examined. Results A subset of 229 out of 534 included patients were available for analysis. At the between-patient level, time-integrated DAS28-ESR scores were not significantly correlated with progression at the 6 month and 2-year follow-up and only weakly at the 1-year (Pearson’s correlation coefficient r = 0.17, P r = 0.21, P r between 0.39 and 0.59; P values Conclusions In early RA patients treated according to T2T, radiographic progression appears to be an individually determined disease process, driven by factors other than consistent high disease activity. For individual patients, the intra-patient relation between disease activity and cumulative radiographic damage during the first 6 months is a good indicator for this relation in later years. Trial registration Netherlands Trial Register NTR578, 12 January 2006.

Background: Tofacitinib is an oral JAK inhibitor for the treatment of RA. Pain is the most common symptom reported by patients (pts) with RA,1,2 thus reduction of pain is an important treatment goal. Objectives: To evaluate the effect of tofacitinib monotherapy ± pain medication on pain in pts with RA. Methods: This pooled post hoc analysis included pts who received tofacitinib 5 mg BID monotherapy (ie without csDMARDs) in Phase (P)2 (NCT00550446), P3 (ORAL Solo; NCT00814307) and P3b/4 (ORAL Strategy; NCT02187055) studies. Pts were stratified by concomitant use of ‘any pain therapy’ (opioids, plain analgesics [eg acetaminophen], NSAIDs or glucocorticoids [GC; ≤10 mg of prednisone or equivalent per day]), ‘pure analgesics’ (opioids or plain analgesics) and ‘adjuvant analgesics’ (NSAIDs or GC). Pts receiving pain medication at baseline (BL) maintained a stable dose during the studies; opioid and/or acetaminophen dose could be increased as rescue therapy. Efficacy outcomes were assessed at Month (M)3 and M6: change from BL (δ) in Pt Assessment of Pain (Pain; visual analogue scale [VAS]) and δPain stratified by DAS28-4(ESR)-defined low disease activity (LDA; ≤3.2) status at M3 and M6. Results: Of 676 pts who received tofacitinib 5 mg BID monotherapy, 604 (89%) received ‘any pain therapy’, 141 (21%) received ‘pure analgesics’ and 589 (87%) received ‘adjuvant analgesics’. Demographics and BL disease characteristics, including disease activity and Pain VAS, were generally similar when stratified by use/type of pain medication. Reductions in pain (δPain VAS) at M3 and M6 were generally similar for pts who received tofacitinib with ‘any pain therapy’ vs those who did not receive ‘any pain therapy’ (Figure 1a). There was a trend for a numerically greater reduction in pain at M3 and M6 in pts who received tofacitinib with ‘any pain therapy’ and who achieved LDA at M3 and M6 vs those who received tofacitinib with ‘any pain therapy’ and did not achieve LDA (95% CI overlapped; Figure 1b). By contrast, pain reductions were similar for pts who received tofacitinib without ‘any pain therapy’, irrespective of LDA status. Similar trends were seen when pts were stratified by use of ‘pure analgesics’ and ‘adjuvant analgesics’ (data not shown). Conclusion: In this pooled post hoc analysis, pain reduction was similar in pts with RA receiving tofacitinib, regardless of pain medication use. Pain reduction was similar in pts receiving tofacitinib without ‘any pain therapy’, irrespective of LDA status. These results should be interpreted with caution, as pain medication could be used as rescue therapy, few pts received tofacitinib without ‘any pain therapy’, and confounding by indication cannot be excluded. Further analyses are required to explore the impact of tofacitinib on the relationship between reductions in pain and disease activity. References [1] Walsh DA, McWilliams DF. Curr Pain Headache Rep 2012; 16: 509-17. [2] American College of Rheumatology Pain Management Task Force. Arthritis Care Res (Hoboken) 2010; 62: 590-9. Acknowledgement: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Peter C. Taylor Grant/research support from: Celgene, Galapagos, Eli Lilly, UCB, Consultant for: AbbVie, Galapagos, Gilead, Eli Lilly, Pfizer Inc, Mart van de Laar Grant/research support from: AbbVie, Eli Lilly, Janssen-Cilag, Merck Inc, Pfizer Inc, Sanofi Genzyme, Speakers bureau: Eli Lilly, Pfizer Inc, Jeffrey R. Curtis Grant/research support from: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Consultant for: Abbvie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Crescendo Bioscience Inc., Valderilio F Azevedo Grant/research support from: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, GSK, Janssen, Merck Serono, Novartis, Pfizer Inc, UCB, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Palle Dahl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Noriko Iikuni Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Salim Benkhalifa Shareholder of: Pfizer SAS, Employee of: Pfizer SAS, Juan Jose Gomez-Reino Grant/research support from: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Consultant for: Biogen, Gilead, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, maxime dougados Grant/research support from: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma

Patient-reported outcome measures are commonly used in the assessment of patients with musculoskeletal diseases. The present review provides an overview of historic and recent developments, including core set recommendations for assessing patient-reported outcomes in patients with fibromyalgia, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. The evidence supporting commonly used patient-reported outcomes measures is reviewed. Furthermore, various methodological approaches that can be utilized to evaluate validity and measurement precision of patient reported outcomes are introduced. Commonly used methods based on the classical test theory as well as modern approaches based on item response theory will be discussed. The review finally describes the increasing use of item response theory-based approaches used in patient-reported outcomes assessment in the musculoskeletal diseases.

Background: Treating Rheumatoid Arthritis (RA) to an a priori defined disease activity target (T2T) is recommended in EULAR guidelines. This involves a step-up approach in which it is first attempted to achieve the target with a combination of conventional synthetic (cs) DMARDs. Baricitinib is a JAK1/JAK2-inhibitor approved for treatment of patients suffering from RA. EULAR and ACR guidelines currently position JAK1/JAK2-inhibitors and bDMARDs at the same level in the therapeutic treatment sequence for csDMARD Inadequate Responders (IR). Cost-effectiveness assessment of different T2T strategies, especially ones including new treatments, and integrating health economic considerations is of importance to the decision-making process as it incorporates the societal perspective in the longer run. Objectives: To compare the cost-effectiveness of the previously evaluated DREAM T2T strategy csDMARD combination therapy (csDMARDs)→ first bDMARD (adalimumab)→ next bDMARD (TNFi/non-TNFi) with the comparable strategy in which baricitinib is placed instead of adalimumab in csDMARDs IR using a Markov model. All analyses were performed from the societal perspective. Costs and effects over five years were compared between the two strategies to provide insight into the differences in economic considerations between treating patients with strategies including either JAK1/JAK2-inhibitor (baricitinib) or 1st bDMARD (adalimumab). Methods: A Monte Carlo microsimulation model was developed to conduct cost-utility analysis from the societal perspective over 5 years. Health states were based on the DAS28-ESR categories. Effectiveness of baricitinib was retrieved from clinical trials (1) and corrected for differences between RCT and real-world setting. Effectiveness of all other treatments, health state utilities, medical costs, and productivity loss were retrieved from DREAM cohorts (2) and the Dutch Institute for Health. Annual discount rates of 1.5% for utility and 4% for costs were used, as advised in Dutch guidelines. All analyses were run using probabilistic sensitivity analysis (PSA) to incorporate uncertainty around all parameters and assess result robustness. Results: PSA results showed the baricitinib strategy yielded lower costs and higher utility over a 5-year period and is cost-effective and dominant over the DREAM T2T strategy. Scenario analyses showed the baricitinib strategy to be cost-effective in both the moderate and severe at baseline RA populations analysed together and separately. CI= 95% Confidence Interval, QALY = Quality-Adjusted Life Year, ΔC = Cost difference, ΔE = Effect Difference, ICER = Incremental Cost-Effectiveness Ratio Conclusion: Results suggest the use of a JAK1/JAK2-inhibitor (baricitinib) instead of a 1st bDMARD (adalimumab) in a T2T strategy is cost-effective in treating RA patients. References: [1] Taylor, P. C., Keystone, E. C., van der Heijde, D., Weinblatt, M. E., del Carmen Morales, L., ... & Arora, V. (2017). Baricitinib versus placebo or adalimumab in rheumatoid arthritis. New England Journal of Medicine, 376(7), 652-662. [2] M., Versteeg, G. A., Vonkeman, H. E., Ten Klooster, P. M., Kuper, H. H., ... & van de Laar, M. A. (2016). Initial combination therapy versus step-up therapy in treatment to the target of remission in daily cl. Steunebrink, L. inical practice in early rheumatoid arthritis patients: results from the DREAM registry. Arthritis Research & Therapy, 18(1), 60. Disclosure of Interests: Celine van de Laar: None declared, Martijn Oude Voshaar: None declared, WALID FAKHOURI Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Liliana Zaremba-Pechmann Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Francesco de Leonardis Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Inmaculada De La Torre Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mart van de Laar Grant/research support from: Eli Lilly, Pfizer, Merck, AbbVie and Janssen Cilag, Consultant for: Sanofi Genzym, Eli Lilly, Pfizer, Merck, Abbvie and Janssen Cilag, Speakers bureau: Eli Lilly, Pfizer and Janssen Cilag

Background The ultimate goals for rheumatoid arthritis (RA) treatment are to achieve disease activity control and the best potential health state throughout the course of disease.1 In prior analyses of the Phase 3 trial, RA-BEAM (NCT01710358), baricitinib was associated with significant clinical improvements and patient-reported pain relief in RA patients (pts) who had had an inadequate response to methotrexate.2,3 The additional benefits of pain relief when inflammation is controlled are not well characterized. Objectives To quantify the contribution of pain relief to other PROs, fatigue, physical function, and quality of life, in pts who achieved control of inflammation, defined as swollen joint count (SJC) ≤1 and C-reactive protein (CRP) ≤1 mg/dL, at Week (Wk) 24 in a post hoc, pooled analysis of RA-BEAM. Methods Among pts with inflammation control, PROs were compared between pts who also achieved thresholds of pain relief at Wk 24 vs those who did not. Pain was measured with a visual analogue scale (VAS, range: 0-100 mm) and divided into ≤20, >20, ≤40, >40 mm.4,5 PROs included: the Health Assessment Questionnaire-Disability Index (HAQ-DI) normative value ( Results Of the total 1305 patients in RA-BEAM, 371 pts treated with adalimumab (121/330), baricitinib (187/487), or placebo (63/488) and background methotrexate achieved inflammation control at Wk 24. Among patients who achieved inflammation control, those who also achieved each pain relief threshold were statistically significantly more likely (p Conclusion When inflammation is controlled (SJC ≤1 and CRP ≤1 mg/dL), more pain relief is associated with better physical function, quality of life, and reduced fatigue. This may support consideration of pain relief as an additional goal of therapy, even when inflammation is controlled. Further investigation should evaluate this benefit with other patient populations and outcomes. Reference [1] Smolen, et al. ARD 2017; 76: 960-77; 2. Taylor, et al. NEJM 2017; 376: 652-62; 3. Taylor, et al. Arthritis Rheumatol 2017; 69 (Suppl 10); 4. Wolfe & Michaud, J Rheumatol 2007; 34: 1674-83; 5. Tubach, et al. Arthritis Care Res 2012; 64:1699-707. Disclosure of Interests Mart van de Laar Grant/research support from: Eli Lilly, Pfizer, Merck, AbbVie and Janssen Cilag, Consultant for: Sanofi Genzym, Eli Lilly, Pfizer, Merck, Abbvie and Janssen Cilag, Speakers bureau: Eli Lilly, Pfizer and Janssen Cilag, Janet Pope Consultant for: Eli Lilly and Company, Yvonne Lee Shareholder of: Express Scripts, Grant/research support from: Pfizer, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant for: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, Sanofi Genzyme, SOBI, UCB, Kei Ikeda: None declared, Amanda Quebe Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Xiang Zhang Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Carol Gaich Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Francesco de Leonardis Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jeffrey Lisse Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jennifer Workman Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Peter C. Taylor Grant/research support from: Celgene, Galapagos, Eli Lilly, UCB, Consultant for: AbbVie, Galapagos, Gilead, Eli Lilly, Pfizer Inc

Background: Rheumatoid Arthritis (RA) is a chronic inflammatory disorder that negatively affects the patients’ health-related quality of life (QOL).1 Despite much progress in addressing the burden of RA, a gap exists in terms of understanding ‘what really matters’ to patients with RA, and balancing patients’ QOL aspirations with clinical targets in key treatment decisions. Objectives: This international survey investigated how RA affects the lives of patients according to the perceptions of both patients and healthcare providers (HCPs), in order to help health professionals attune their care on the domains that really matter to patients. Methods: Data were collected from patients with RA, and rheumatologists or HCPs who treat RA in Canada, France, Germany, Italy, Netherlands, Spain, Sweden, and UK using a structured, closed-ended questionnaire in their local language. Respondents for the survey were recruited from survey panels of verified unique responses, as well as through social media. Data were summarized in terms of both frequency and percentages of patients to understand the experience of patients living with RA on daily activities, relationships, work, and aspirations. Results: Overall, 5400 adult patients (81% female; mean age 52 years), and 808 rheumatologists or HCPs participated in the survey between November 2016 and February 2017. Of these, the highest proportion of patient and HCP respondents were from the UK (n=1250) and France (n=230), respectively. Overall, 52% of patients and 62% of HCPs believed that the emotional impact of RA is not well understood by people without the disease; whereas 46% of patients and 52% of HCPs had a similar belief with regards to the physical impact of the disease. Patients who felt that the impact of RA is less well understood by others expressed more negative feelings about every aspect of their life with RA. Important relationships with spouse or partner, children, family, friends, and colleagues were generally affected negatively. Almost half of the patients (48%) who participated in the survey reported that they were forced to take long-term leave/retirement or experienced slow career progress since being diagnosed with RA; more than 3 in 5 patients found exercising to be difficult; and almost 1 in 4 patients found difficulties in taking care of personal grooming. Aching/stiff joints, pain, and fatigue were the key physical barriers to activities for patients, and 65% of patients felt frustrated when they were unable to undertake or complete daily activities due to their disease. Two-thirds of patients wished to be able to accept their life with RA and do what they can to cope with it in the future. Over half of the patients (52%) had a hope that the physical impact of RA will be better understood in the future. Conclusion: Despite major advancements in the treatment of RA, the chronic disease continues to significantly affect many aspects of patients’ lives, including relationships, career progression, daily activities, and ability to work. Both patients and HCPs felt that the physical and emotional impact of RA is not well understood by people without the disease. In line with a recently published study, pain, fatigue, and physical function remain primary barriers for patients to live a normal life and to participate fully.2 In RA treatment decisions, patients’ personal goals and patient-reported outcomes should be given greater consideration along with clinical targets. References [1] Wysocka-Skurska I, et al. Clin Interv Aging. 2016;11:1741-50. [2] Oude Voshaar MAH, et al. Arthritis Care Res (Hoboken). 2018Oct24. doi: 10.1002/acr.23799. [Epub ahead of print]. Disclosure of Interests: Rieke Alten Grant/research support from: Bristol-Myers Squibb, Speakers bureau: Bristol-Myers Squibb, Neil Betteridge Consultant for: Amgen, Eli Lilly, Grunenthal, GSK, Heart Valve Voice, Janssen, Roche, Sanofi Genzyme and Sanofi Regeneron, Speakers bureau: Amgen, Eli Lilly, Grunenthal, GSK, Heart Valve Voice, Janssen, Roche, Sanofi Genzyme and Sanofi Regeneron, Francesco de Leonardis Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Nicole Tietz Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mariana Guerreiro Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mart van de Laar Grant/research support from: Eli Lilly, Pfizer, Merck, AbbVie and Janssen Cilag, Consultant for: Sanofi Genzym, Eli Lilly, Pfizer, Merck, Abbvie and Janssen Cilag, Speakers bureau: Eli Lilly, Pfizer and Janssen Cilag

Background Delivery of rheumatological care is suggested to be compromised by patient health literacy. Prevalence of problematic health literacy in the Netherlands is estimated to be as high as 36%. “Health literacy represents the cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand and use information in ways which promote and maintain good health” (Nutbeam, 1998). A deeper understanding of diverse health literacy profiles of patients attending rheumatology clinics could facilitate development of interventions tailored to patients’ needs, in order to improve health outcomes and reduce inequities. Objectives To identify health literacy strengths and weaknesses among patients with Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA) attending a rheumatology clinic, and identify typical ‘health literacy profiles’ based on these strengths and weaknesses. Methods Consecutive RA and SpA patients attending the outpatient clinic at Maastricht UMC+, the Netherlands, were invited to participate. Health literacy was assessed using the Health Literacy Questionnaire (HLQ), which includes nine dimensions (Figure 1). Socio-demographics and health-related characteristics were also collected. Hierarchical cluster analysis following Ward’s method identified clusters based on HLQ scale scores. This method groups subjects into a predefined number of clusters, based on smallest differences to the mean of all scales, creating minimal variance within each cluster, and maximum variance between clusters. Three researchers jointly examined twenty cluster solutions for meaningfulness by interpreting HLQ scales and patient characteristics. Meaningful clusters are translated into health literacy profiles using HLQ patterns and demographic data. A patient representative confirmed the identified profiles. Results In total, 133 patients with RA and 106 with SpA completed the questionnaire. Of these, 61% (n=146) were female, mean age was 61.6 (±13.3), 27% (n=65) lived alone, 11% (n=26) did not speak Dutch at home, 28% (n=68) were employed, and 22% and 50% had received low and medium education, respectively. Figure 1 displays identified health literacy profiles and scale scores, with greener values representing strengths and red scores representing weaknesses. Overall, the pattern indicates RA and SpA patients have similar profiles, but some represent a clear majority of SpA or RA patients and could be considered disease-specific. For example, cluster 10 includes patients who typically feel comfortable in their relationship with their doctor (scales 1 and 6), and are rather confident in managing their health and getting the information they need (scale 3 and 7). However, they struggle in understanding health information (scale 9), and lack the social support needed to make health decisions and maintain good health (scale 4). This profile appeared restricted to RA patients. Conclusion This study identified potential typical health literacy profiles in patients with inflammatory arthritis in our clinic. Profiles reflected distinctive strengths and weaknesses on the nine health literacy dimensions. Some profiles appeared to be condition-specific, which warrants further investigation. Identified profiles will feed into co-design workshops with patients, professionals and other stakeholders, in order to develop interventions to tailor the care to patients’ needs. References [1] Nutbeam D. (1998). Health promotion glossary. Health Promotion International, 13, 349–364. Disclosure of Interests Mark Bakker: None declared, Polina Putrik: None declared, Jany Rademakers: None declared, Mart van de Laar Grant/research support from: AbbVie, Eli Lilly, Janssen-Cilag, Merck Inc, Pfizer Inc, Sanofi Genzyme, Speakers bureau: Eli Lilly, Pfizer Inc, Harald Vonkeman: None declared, Marc Kok: None declared, Hanneke Voorneveld: None declared, Sofia Ramiro Grant/research support from: MSD, Consultant for: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Maarten de Wit: None declared, Richard Osborne: None declared, Roy Batterham: None declared, Rachelle Buchbinder: None declared, Annelies Boonen: None declared

Background Despite advances in the treatment armamentarium for rheumatoid arthritis (RA) over the last decade, several unmet needs remain within RA management. Objectives To enhance scientific knowledge and improve patient care by providing practical tools and evidence-based awareness – in line with EULAR recommendations – on how to implement optimal RA management and address identified needs. Methods The eRA (evolving the management of RA) programme convened a Steering Committee (SC) of 17 European and International experts in RA, including representation from rheumatologists, nurses, health professionals and patients. Through literature search and assessment of expert opinion, 4 core areas of unmet need were identified: delays in referral and initiation of disease-modifying anti-rheumatic drugs, inconsistent application of treat-to-target strategy, sub-optimal identification and management of comorbidities, and a growing need to actively engage patients with their care. Several clinical and educational gaps associated with these unmet needs were also identified. To fill these gaps and support application of an optimal approach to RA management, practical and educational tools were developed. A cascade process engaging national leaders in rheumatology was then initiated to disseminate the tools to health professionals across Europe, with tools being updated in participating countries to ensure alignment with local practices and individual country needs. Broader programme dissemination is supported by congress activities and a digital communication plan. The eRA programme is funded by Sanofi Genzyme. Programme direction and content creation are driven by the SC. Results A suite of 12 educational tools was developed (Figure 1), including educational slides to raise awareness of unmet needs, self-reflection questionnaires to evaluate personal practice alongside EULAR recommendations, case scenarios outlining the optimal approach to management, and clinical checklists to support daily practice. The process to disseminate these tools commenced in November 2017 with a Multi-Country Workshop, which convened 43 national leaders in rheumatology from countries participating in the programme. Feedback on the eRA tools at this meeting was positive, and in 2018, additional countries were onboarded to the programme. Launch of a digital web-platform aims to further support dissemination of the eRA tools. Conclusion The content of the eRA programme has been well-received, largely due to the programme’s flexible approach, which is sympathetic to individual country needs. As the cascade process continues, it is anticipated that many more health professionals and patients will benefit from the eRA tools. References: Disclosure of Interests: Gerd Rudiger Burmester Consultant for: Roche, Sanofi-Genzyme, Speakers bureau: Roche, Sanofi-Genzyme, Mart van de Laar Grant/research support from: AbbVie, Eli Lilly, Janssen-Cilag, Merck Inc, Pfizer Inc, Sanofi Genzyme, Speakers bureau: Eli Lilly, Pfizer Inc, Jose-Maria Alvaro-Gracia Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer Inc, Roche, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer Inc, Roche, Sanofi, and UCB, Neil Betteridge Consultant for: Amgen, Eli Lilly, Grunenthal, GSK, Heart Valve Voice, Janssen, Roche, Sanofi Genzyme and Sanofi Regeneron, Speakers bureau: Amgen, Eli Lilly, Grunenthal, GSK, Heart Valve Voice, Janssen, Roche, Sanofi Genzyme and Sanofi Regeneron, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb, Bernard Combe Consultant for: Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Patrick Durez Speakers bureau: Bristol-Myers Squibb, Eli Lilly, Sanofi, Celltrion, Ricardo J.O Ferreira Consultant for: Sanofi Genzyme, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant for: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, Medac, MSD, NORDIC Pharma, Novartis, Pfizer, Roche, Sanofi-Aventis, Sanofi Genzyme, SOBI, UCB, Cem Gabay Grant/research support from: Roche, Pfizer, AB2 Bio Ltd, Consultant for: Roche, Pfizer, Lilly, AbbVie, Sanofi, Regeneron, Bristol-Myers Squibb, Novartis, UCB, AB2 Bio Ltd, Debiopharm, Annamaria Iagnocco: None declared, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB, Mikkel Ostergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Sofia Ramiro Grant/research support from: MSD, Consultant for: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, Lilly, MSD, Novartis, Pfizer, Sanofi, Andrea Rubbert-Roth Consultant for: Chugai, Eli Lilly, Roche, and Sanofi, Speakers bureau: AbbVie, Bristol-Myers Squibb, Chugai, Hexal/Novartis, Janssen, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, and Sanofi, Tanja Stamm Grant/research support from: TS has received grant support from AbbVie., Paid instructor for: TS has received speaker fees from AbbVie, Janssen, MSD, Novartis, and Roche., Zoltan Szekanecz Grant/research support from: Pfizer, UCB, Consultant for: Pfizer, Abbvie, Roche, Sanofi, Lilly, Novartis, Speakers bureau: Pfizer, Abbvie, Roche, Sanofi, Lilly, Novartis, Peter C. Taylor Grant/research support from: Celgene, Galapagos, Eli Lilly, UCB, Consultant for: AbbVie, Galapagos, Gilead, Eli Lilly, Pfizer Inc

Objective To further simplify the simple erosion narrowing score (SENS) by removing scored areas that contribute the least to its measurement precision according to analysis based on item response theory (IRT) and to compare the measurement performance of the simplified version to the original. Methods Baseline and 18-month data of the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial were modeled using longitudinal IRT methodology. Measurement precision was evaluated across different levels of structural damage. SENS was further simplified by omitting the least reliably scored areas. Discriminant validity of SENS and its simplification were studied by comparing their ability to differentiate between the COBRA and sulfasalazine arms. Responsiveness was studied by comparing standardized change scores between versions. Results SENS data showed good fit to the IRT model. Carpal and feet joints contributed the least statistical information to both erosion and joint space narrowing scores. Omitting the joints of the foot reduced measurement precision for the erosion score in cases with below-average levels of structural damage (relative efficiency compared with the original version ranged 35–59%). Omitting the carpal joints had minimal effect on precision (relative efficiency range 77–88%). Responsiveness of a simplified SENS without carpal joints closely approximated the original version (i.e., all Δ standardized change scores were ≤0.06). Discriminant validity was also similar between versions for both the erosion score (relative efficiency = 97%) and the SENS total score (relative efficiency = 84%). Conclusion Our results show that the carpal joints may be omitted from the SENS without notable repercussion for its measurement performance.

Objective.To examine whether different groups of fatigue trajectories can be identified among patients with early symptomatic osteoarthritis (OA) of the knee or hip, to describe the level of fatigue severity within each of these fatigue groups, and to investigate the involvement of age, sex, use of medication, comorbidity, and OA severity in relation to group membership.Methods.Six years of followup data on fatigue (Medical Outcomes Study Short Form-36 Vitality scale) came from the Cohort Hip and Cohort Knee (CHECK) cohort. Growth mixture modeling was applied to identify distinct fatigue trajectories as well as to take into account the effects of the patient characteristics.Results.Three fatigue trajectories were identified: low fatigue, low-to-high fatigue, and high fatigue. Latter trajectories showed considerable overlap from years 2 to 6, but differed in some patient characteristics in comparison with each other and in comparison with the low fatigue group. Comorbidity, medication use, and sex were significantly associated with the identified trajectories. Women, individuals with a comorbid disease, and those who used medication were more likely to follow a high fatigue trajectory.Conclusion.These findings suggest heterogeneous development of fatigue in the early OA population associated with varying patient characteristics. Further, this study shows that a considerable number of patients with OA already experience elevated levels of fatigue at an early stage of OA. While these findings need to be replicated, the identification of these trajectories with differing patient characteristics may warrant tailored psychosocial interventions for patients with elevated levels of fatigue.

Author(s): de Lautour, Hugh; Taylor, William J; Adebajo, Ade; Alten, Rieke; Burgos-Vargas, Ruben; Chapman, Peter; Cimmino, Marco A; da Rocha Castelar Pinheiro, Geraldo; Day, Ric; Harrold, Leslie R; Helliwell, Philip; Janssen, Matthijs; Kerr, Gail; Kavanaugh, Arthur; Khanna, Dinesh; Khanna, Puja P; Lin, Chingtsai; Louthrenoo, Worawit; McCarthy, Geraldine; Vazquez-Mellado, Janitzia; Mikuls, Ted R; Neogi, Tuhina; Ogdie, Alexis; Perez-Ruiz, Fernando; Schlesinger, Naomi; Ralph Schumacher, H; Scire, Carlo A; Singh, Jasvinder A; Sivera, Francisca; Slot, Ole; Stamp, Lisa K; Tausche, Anne-Kathrin; Terkeltaub, Robert; Uhlig, Till; van de Laar, Mart; White, Douglas; Yamanaka, Hisashi; Zeng, Xuejun; Dalbeth, Nicola | Abstract: To establish consensus for potential remission criteria to use in clinical trials of gout.Experts (n = 88) in gout from multiple countries were invited to participate in a web-based questionnaire study. Three rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed by a discrete-choice experiment using 1000Minds software. The exercises focused on identifying domains, definitions for each domain, and the timeframe over which remission should be defined.There were 49 respondents (56% response) to the initial survey, with subsequent response rates ranging from 57% to 90%. Consensus was reached for the inclusion of serum urate (98% agreement), flares (96%), tophi (92%), pain (83%), and patient global assessment of disease activity (93%) as measurement domains in remission criteria. Consensus was also reached for domain definitions, including serum urate (l0.36 mm), pain (l2 on a 10-point scale), and patient global assessment (l2 on a 10-point scale), all of which should be measured at least twice over a set time interval. Consensus was not achieved in the Delphi exercise for the timeframe for remission, with equal responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment, there was a preference towards 12 months as a timeframe for remission.These consensus exercises have identified domains and provisional definitions for gout remission criteria. Based on the results of these exercises, preliminary remission criteria are proposed with domains of serum urate, acute flares, tophus, pain, and patient global assessment. These preliminary criteria now require testing in clinical data sets.

Background The aim of this study was to identify predictors of prolonged disease control after discontinuation of tumor necrosis factor inhibitor (TNFi) treatment in patients with rheumatoid arthritis (RA). Methods Post-hoc analysis of 439 RA patients (67.3% rheumatoid factor positive) with longstanding RA in remission or with stable low disease activity, randomized to stopping TNFi treatment in the multicenter POET trial. Prolonged acceptable disease control was defined as not restarting TNFi treatment within 12 months after stopping. Baseline demographic and disease-related variables were included in univariate and multivariate logistic regression analysis for identifying predictors of relapse. Results One year after baseline, 220 patients (50.1%) had not restarted TNFi treatment. Use of an anti-TNF monoclonal antibody (versus a receptor antagonist, OR = 2.41; 95% CI: 1.58–3.67), ≤10 yrs. disease duration (OR = 2.15; 95% CI: 1.42–3.26) and low or moderate multi-biomarker disease activity (MBDA) scores (OR = 2.00; 95% CI: 1.10–3.64) at baseline were independently predictive of successful TNFi discontinuation (area under the receiver operating characteristic curve = 0.66; 95% CI: 0.61–0.71). Results were similar when using no physician-reported flare as the criterion. TNFi-free survival was significantly different for patient groups based on the number of predictors present, ranging from 21.4% of patients with no predictor present to 66.7% of patients with all three predictors present. Conclusion Patients using an anti-TNF monoclonal antibody, with shorter disease duration and low or moderate baseline MBDA score are most likely to achieve prolonged disease control after TNFi discontinuation. Trial registration Netherlands Trial Register NTR3112, 21 October 2011. Electronic supplementary material The online version of this article (10.1186/s41927-019-0071-x) contains supplementary material, which is available to authorized users.

Objectives To update the knowledge on employment and the role of mastery, a personal factor reflecting the level of control over life and disease, among Dutch patients with ankylosing spondylitis (AS) compared to general population subjects. Methods Data of persons ≤65 years participating in a Dutch cross-sectional multicentre study on social participation in AS were used. Being employed was the main outcome. Standardised employment ratios (SERs) were calculated using indirect standardisation after adjusting for age, gender and education and repeated after stratification by symptom duration tertiles. Modified Poisson regressions were performed to understand the role of mastery (Pearlin's scale) independent of sociodemographic and health-related factors. Results 214 patients and 470 controls (127 (59.3%) and 323 (68.7%) males; mean age 48.3 (SD 10.4) and 39.3 (SD 12.7) years, respectively) completed an online questionnaire. SER (95%CI) in patients was 0.83 (0.69-0.98); 0.84 (0.67-1.04) in males; 0.83 (0.59-1.07) in females. Adjusted absolute employment of patients compared to controls was 69% versus 84%; 73% versus 86% for males; 62% versus 78% for females. In multivariable analyses stratified for patients and controls, mastery was associated with being employed in patients, but only in those with low education. In controls, not mastery but higher education was associated with being employed. Conclusion Our study reveals that patients suffering from AS compared to population controls are less likely to be employed. Mastery is an important personal factor associated with employment in patients but not in controls. Interventions aimed at improving employment of patients with AS should likely account for mastery.