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The prevalence of multimorbidity among rheumatoid arthritis (RA) patients is increasing and associated with worse outcomes. Therefore, management of multimorbid patients requires a multidisciplinary approach. However, healthcare systems consist of mono-disciplinary subsystems, which limits collaboration across subsystems. To study the importance of a multidisciplinary, integrated approach, associations between expenditures and multimorbidity are assessed in real-life data. Retrospective data on RA patients from a Dutch single-hospital are analyzed and compared to the Dutch RA population data. The Elixhauser index is used to measure the multimorbidity prevalence. Regression analyses were conducted to derive the relationship between multimorbidity, healthcare costs and self-reported quality of life (e.g. EQ-5D). When analyzing the impact of multimorbidity within RA patients in context of a single-hospital context, multimorbidity is only partially captured: 13% prevalence versus 24% of the Dutch population. Multimorbidity is associated with higher care expenditures. Depending on the type of multimorbidity, expenditures are €43–€5821 higher in a single-hospital and from €2259–€9648 in population data. Finally, medication use associated with chronic diseases and self-reported aspects of well-being are associated with similar increases in healthcare expenditures as multimorbidity based on hospital care. Within RA, a single-hospital approach underestimates the association between multimorbidity and healthcare expenditures as 43% of healthcare utilization and expenditures are missed. To overcome a single-provider perspective in healthcare and efficiently coordinate multimorbid patients, besides providing holistic care, professionals also need to use data providing comprehensive pictures of patients.

Rheumatoid Arthritis (RA) is a chronic disease that impacts patients’ quality of life. Sophisticated organization of care delivery drives quality improvement. Therefore, the study objective was establishing a validated process map of the care cycle for RA patients. Hence, increasing transparency and optimizing care delivery and identifying areas of improvement. To map the RA care cycle, the care delivery value chain (CDVC) approach was used as framework to document activities and resources systematically. A mixed method study was conducted where quantitative data on activities were collected from health records and unstructured interviews with medical staff were held. Consequently, the process map was separately validated in a consensus meeting with a delegation of the medical staff and patient advisory board. At the start of the care cycle, the focus is predominantly on defining the treat-to-target strategy and examining disease activity. Towards the monitoring phase, tapering medication and managing the disease through patient-reported outcome measures are becoming increasingly important. Although patient’s functioning, quality of care and patient’s evaluation of received care are monitored, reflection of CDVC and engaging patients in the evaluation process resulted in improvement actions on outcome and process level. Mapping the RA care cycle following a systematic approach, provides insight and transparency in delivered activities, involved resources and the engagement of patients and caregivers at multiple levels, contributing to a system facilitating value-based care delivery. The CDVC framework and applied methodology is recommended in other conditions. Future research will focus at assigning outcomes and costs to activities and evaluating interventions to explore patient value.

ObjectiveRheumatologists play a pivotal role in the management of patients with psoriatic arthritis (PsA). Due to time constraints during clinic visits, the skin may not receive the attention needed for optimal patient outcome. Therefore, the aim of this study was to select a set of core questions that can help rheumatologists in daily rheumatology clinical practice to identify patients with PsA with a high skin burden.MethodsBaseline data from patients included in the Dutch South West Psoriatic Arthritis (DEPAR) cohort were used. Questions were derived from the Skindex-17 and Dermatology Life Quality Index (DLQI) questionnaires. Underlying clusters of questions were identified with an exploratory principal component analysis (PCA) with varimax rotation, after which a 2-parameter logistic model was fitted per cluster. Questions were selected based on their discrimination and difficulty. Subsequently, 2 flowcharts were made with categories of skin burden severity. Clinical considerations were specified per category.ResultsIn total, 413 patients were included. The PCA showed 2 underlying clusters: a psychosocial domain and a domain assessing physical symptoms. We selected these 2 domains. The psychosocial domain contains 3 questions and specifies 4 categories of skin burden severity. The physical symptoms domain contains 2 questions and categorizes patients in 1 out of 3 categories.ConclusionWe have selected a set with a maximum of 5 questions that rheumatologists can easily implement in their consultation to assess skin burden in patients with PsA. This practical guide makes the assessment of skin burden more accessible to rheumatologists and can aid in clinical decision making.

BACKGROUND: Time-driven activity-based costing (TDABC) can support value-based healthcare (VBHC) programs by providing insights into the actual relationships between time spent by the medical staff and the costs associated with specific care cycles. However, the robustness of time estimates (time variation) as well as the effort required to obtain these estimates are major challenges of the TDABC methodology, given the heterogeneity in patients' needs and the presence of (multi)morbidity. To allow for the variation in time estimates in an efficient manner, this study uses fuzzy logic (FL) to estimate the TDABC model parameters (FL-TDABC).METHODS: A standardized care path was used to calculate the annual costs (per patient) and cost drivers of the Rheumatoid arthritis (RA) care cycle following the FL-TDABC methodology. Cost information (2018) was derived from hospital reports concerning financial, human resource and business intelligence data from a Dutch top clinical research hospital, Maasstad Hospital. Time estimates of procedures were obtained by interviewing the medical staff and relevant care activities were extracted from electronic health records. For analytical and validation purposes, FL-TDABC estimates were compared with TDABC and ABC cost estimates.RESULTS: The RA care cycle annual costs totaled €1497 per patient (2018 prices) based on the FL-TDABC methodology. Maximum RA cycle costs (€1684) were some 22% higher than minimum costs (€1317) observed from FL-TDABC. Cost drivers explaining the cost variation are predominantly the number of consultations with rheumatologists and pharmacy costs related to RA. Based on TDABC and ABC, annual costs per patient were €1609 and €1604, respectively.CONCLUSIONS: The FL-TDABC methodology offers a more precise and efficient estimate of care cycle costs, allowing for the subjective (fuzzy) nature of healthcare time estimates made by the medical staff. As a result, the FL-TDABC provides insight into the practice variation, and hence it can promote the transition from a volume-based system to a VBHC system.

Objectives We studied discordance between health literacy of people with rheumatic and musculoskeletal diseases (RMDs) and assessment of health literacy by their treating health professionals, and explored whether discordance is associated with the patients’ socioeconomic background. Methods Patients with RA, spondyloarthritis (SpA) or gout from three Dutch outpatient rheumatology clinics completed the nine-domain Health Literacy Questionnaire (HLQ). Treating health professionals assessed their patients on each HLQ domain. Discordance per domain was defined as a ≥2-point difference on a 0–10 scale (except if both scores were below three or above seven), leading to three categories: ‘negative discordance’ (i.e. professional scored lower), ‘probably the same’ or ‘positive discordance’ (i.e. professional scored higher). We used multivariable multilevel multinomial regression models with patients clustered by health professionals to test associations with socioeconomic factors (age, gender, education level, migration background, employment, disability for work, living alone). Results We observed considerable discordance (21–40% of patients) across HLQ domains. Most discordance occurred for ‘Critically appraising information’ (40.5%, domain 5). Comparatively, positive discordance occurred more frequently. Negative discordance was more frequently and strongly associated with socioeconomic factors, specifically lower education level and non-Western migration background (for five HLQ domains). Associations between socioeconomic factors and positive discordance were less consistent. Conclusion Frequent discordance between patients’ scores and professionals’ estimations indicates there may be hidden challenges in communication and care, which differ between socioeconomic groups. Successfully addressing patients’ health literacy needs cannot solely depend on health professionals’ estimations but will require measurement and dialogue.

Objectives Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA. Methods We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA. Results In total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = Conclusions This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.

Objectives Rituximab (RTX) is a safe and effective treatment for RA. A dose-dependent infection risk was found in the REDO trial. Some studies associate RTX use with higher infection risks, possibly explained by low immunoglobulin levels and/or neutropenia. Additionally, a higher infection risk shortly after RTX infusion is reported. The objectives of this study were (i) to compare incidence rates of infections between doses and over time, and (ii) to assess B-cell counts, immunoglobulin levels, neutrophil counts and corticosteroid/disease modifying rheumatic drug use as mediating factors between RTX study dose and infection risk. Methods Post hoc analyses of the REDO trial were performed. Infection incidence rates between RTX dosing groups and between time periods were compared using Poisson regression. A step-wise mediation analysis was performed to investigate if any of the factors mentioned above act as a mediator in the observed dose-dependent difference in infection risk. Results The potential mediators that were investigated (circulating B-cell counts, immunoglobulin levels, neutrophil counts and drug use) did not explain the dose-dependent infection risk observed in the REDO trial. Additionally, a trend towards a time-dependent infection risk was found, with higher infection rates shortly after RTX infusion. Conclusions These secondary analyses of the REDO trial confirmed the observed dose-dependent infection risk. Additionally, we found that infection risks were higher shortly after RTX infusion. However, a mediating pathway was not found.

Objectives Psoriasis impacts health-related quality of life (HRQoL) in PsA patients. However, this is not adequately measured with a general HRQoL questionnaire. The aim of this study was to quantify the degree of psoriasis evolution in PsA patients over the first year of follow-up and to evaluate whether the impact of psoriasis on HRQoL can be adequately measured with a dermatology-specific HRQoL questionnaire. Methods Data were used from PsA patients in the Dutch south west Early Psoriatic Arthritis cohort. Psoriasis severity was measured with the Psoriasis Area and Severity Index (PASI). Dermatology-specific HRQoL was assessed with the Skindex-17 questionnaire. We used a Sankey diagram to illustrate the evolution of psoriasis severity during the first year of follow-up. To assess the association between psoriasis severity and the symptoms and psychosocial subscale of the Skindex-17, a linear regression analysis with hierarchical variable selection and zero-inflated negative binominal regression analysis were performed, respectively. Results We included 644 patients; 109 (17%) patients had no psoriasis (PASI = 0), 456 (71%) had mild psoriasis (PASI 12). Psoriasis severity did not fluctuate much during the first year. PASI was significantly associated with both subscales of the Skindex-17 at baseline and 12 months. Conclusion Psoriasis severity in PsA patients is mostly mild but impacts HRQoL when measured using a dermatology-specific HRQoL questionnaire. For optimal management of PsA patients, we recommend rheumatologists acquire information on skin burden by using a dermatology-specific HRQoL questionnaire.

Objectives The prevalence of psoriatic arthritis (PsA) is the same in men and women; however, the latter experience a higher burden of disease and are affected more frequently by polyarthritis. Here, we performed an early PsA cohort analysis to assess sex-related differences in demographics, disease characteristics, and evolution over 1 year including applied treatment strategies. Methods Our study is embedded in the Dutch south-west Early Psoriatic Arthritis cohoRt. We described patient characteristics and treatment decisions. For the comparison across sexes and baseline and 1 year follow-up, appropriate tests depending on the distribution were used. Results Two hundred seventy-three men and 294 women with no significant differences in age and ethnicity were included. Women reported significantly longer duration of symptoms before diagnosis and significantly higher tender joint count, a higher disease activity, higher levels of pain, and lower functional capacity. Although minimal disease activity (MDA) rates increased over time for both sexes, MDA remained significantly more prevalent among men at 1 year (58.1% vs 35.7%, p ). Initially, treatment strategies were similar in both sexes with methotrexate being the most frequently used drug during the first year. Women received methotrexate for a shorter period [196 (93–364) vs 306 (157–365), p ] and therefore received a lower cumulative dose compared to men. Retention time was shorter for all DMARDs, and women had a delayed start on b-DMARDs. Conclusion After 1 year of standard-of-care treatment, women did not surpass their baseline disadvantages. Despite the overall improvement, they still presented higher disease activity, higher levels of pain, and lower functional capacity score than men. The nature of these findings may advocate a need for sex specific adjustment of treatment strategies and evaluation in early PsA patients.

Achieving low disease activity (LDA) is important in patients with psoriatic arthritis. It is of value to know if health-related quality of life (HRQoL) of patients who reached musculoskeletal low disease activity can be further improved by additionally achieving remission of their psoriasis. So, the aim of this study was to assess HRQoL in patients with active psoriasis who reached disease activity in psoriatic arthritis (DAPSA) LDA after one year of follow-up.Data were collected from the Dutch south west Psoriatic Arthritis cohort. Musculoskeletal disease activity was measured using DAPSA. Patients who reached DAPSA-LDA after one year were divided based on reaching psoriasis remission (Psoriasis Area and Severity Index [PASI]1). HRQoL and work productivity were compared between both groups.After one year, 230 (44%) patients with active psoriasis at baseline reached DAPSA-LDA, of which 108 (47%) patients achieved psoriasis remission. The group of patients with active psoriasis (n=122, 53%) contained more men (p=0.023) and scored lower on the 12-item Psoriatic Arthritis Impact of Disease questionnaire (p=0.012). On the Skindex-17 psychosocial subscale, 31% experienced moderate to high impairment and on the symptoms subscale 28% experienced a lot of symptoms. Work productivity did not differ between both groups.The majority of patients with DAPSA-LDA and active psoriasis after one year has a good HRQoL. However, a proportion of these patients still experiences considerable skin burden. We recommend rheumatologists to continue assessing and treating psoriasis to reduce skin burden in PsA patients who achieved musculoskeletal low disease activity.

Lymphatic endothelial cells (LECs) line the lymphatic vasculature and play a central role in the immune response. LECs have abilities to regulate immune transport, to promote immune cell survival, and to cross present antigens to dendritic cells. Single-cell RNA sequencing (scRNA) technology has accelerated new discoveries in the field of lymphatic vascular biology. This review will summarize these new findings in regard to embryonic development, LEC heterogeneity with associated functional diversity, and interactions with other cells. Depending on the organ, location in the lymphatic vascular tree, and micro-environmental conditions, LECs feature unique properties and tasks. Furthermore, adjacent stromal cells need the support of LECs for fulfilling their tasks in the immune response, such as immune cell transport and antigen presentation. Although aberrant lymphatic vasculature has been observed in a number of chronic inflammatory diseases, the knowledge on LEC heterogeneity and functional diversity in these diseases is limited. Combining scRNA sequencing data with imaging and more in-depth functional experiments will advance our knowledge of LECs in health and disease. Building the case, the LEC could be put forward as a new therapeutic target in chronic inflammatory diseases, counterweighting the current immune-cell focused therapies.

Summary Background Rituximab is an effective treatment for rheumatoid arthritis, given as either two doses of 1000 mg (2 weeks apart) every 6 months (the dose recommended by the US Food and Drug Administration and European Medicines Agency) or two doses of 500 mg (2 weeks apart) or one dose of 1000 mg (a standard low dose) every 6 months. Findings of several small uncontrolled studies suggest that doses lower than the recommended dose or standard low dose might be sufficient for maintenance treatment, potentially improving safety and reducing costs. Therefore, we aimed to compare the efficacy of ultra-low doses of rituximab (one dose of 500 mg or 200 mg) with a standard low dose of rituximab (one dose of 1000 mg) for patients with rheumatoid arthritis who respond to standard doses of rituximab. Methods The REDO study is a randomised, double-blind, non-inferiority trial done at five centres in the Netherlands. Adults (aged ≥18 years) with rheumatoid arthritis responding well to rituximab were randomly allocated (1:2:2) to receive intravenous rituximab as one dose of either 1000 mg, 500 mg, or 200 mg, respectively. Volumes of all doses were equal to achieve masking. Randomisation lists were computer-generated and stratified by rheumatoid factor or anti-citrullinated protein antibody status (positive or negative) and concomitant use of conventional synthetic disease modifying antirheumatic drugs (yes or no). The primary analysis was a per-protocol hierarchical testing procedure comparing ultra-low doses with a standard low dose (500 mg vs 1000 mg at 3 months, followed by 500 mg vs 1000 mg at 6 months, 200 mg vs 1000 mg at 3 months, and 200 mg vs 1000 mg at 6 months), using a non-inferiority margin of 0·60 on change from baseline in the 28-joint disease activity score based on C-reactive protein levels (DAS28-CRP). The study is registered at www.trialregister.nl , NTR6117. Findings Between Dec 15, 2016, and Sept 20, 2018, 142 patients were randomly allocated to either 1000 mg rituximab (n=29), 500 mg rituximab (n=58), or 200 mg rituximab (n=55). The 500 mg dose was non-inferior to 1000 mg at 3 months (mean change from baseline in DAS28-CRP, −0·07, 95% CI −0·41 to 0·27) but not at 6 months (0·29, −0·08 to 0·65). Because of the hierarchical testing procedure, non-inferiority could not be tested for the 200 mg dose. 13 patients had serious adverse events, three (10%) in the 1000 mg group, six (10%) in the 500 mg group, and four (7%) in the 200 mg group. The most frequently reported serious adverse events were cardiovascular. No deaths occurred during the study. A significantly lower incidence of infections was seen in the ultra-low-dose groups compared with the standard dose group (1·24 infections per patient-year with the 1000 mg dose vs 0·52 per patient-year with the 500 mg dose and 0·55 per patient-year with the 200 mg dose; rate ratio 0·42, 95% CI 0·21–0·83; p=0·013 for 500 mg vs 1000 mg; 0·44, 0·22–0·88; p=0·019 for 200 mg vs 1000 mg). Interpretation Our study did not show non-inferiority of ultra-low doses of rituximab for continued treatment of patients with rheumatoid arthritis. Nonetheless, in clinical practice, a strategy with an ultra-low dose of rituximab might be considered after evaluation of risks and benefits, although further studies are needed to establish non-inferiority. Further analyses and a 2-year observational extension are ongoing and should provide further insight into efficacy and safety. Funding Menzis and Centraal Ziekenfonds.

ObjectivesThe impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems.MethodsWe performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak).ResultsIn total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31–40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years.ConclusionsThis is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed.

Medication adherence, which is the extent to which patients take their medication as prescribed, is essential in treating chronic inflammatory diseases such as rheumatoid arthritis (RA). Therefore, we nested a subproject in the two-year multicenter Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) trial to add a low-dose prednisolone (5 mg/day) or placebo to the standard care in older people (65+ years) with RA. Adherence was measured with an electronic monitoring cap that recorded bottle openings in all patients. In the subproject, we performed an adherence intervention with an advanced cap that could communicate with an application on the smart device via Bluetooth. We randomized patients with a smart device to receive or not to receive adherence reminders on the smart device for three months. Multiple problems emerged that precluded an answer to the research question: sample size (overly optimistic estimates of older patients with a smart device), logistic issues (availability of smartcaps, data extraction), randomization and treatment allocation errors (despite training of personnel), and low quality of the data in the intervention group (hardware failure, discovered too late because data was read in batches). For future trials planning to include a subproject, we recommend keeping it simple, starting with a field test before the actual study starts, and monitoring data from the beginning of the study.Keywords: medication adherence, electronic caps, rheumatoid arthritis, nested trial, randomization

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.

Objectives Suboptimal medication adherence is a serious problem in the treatment of chronic inflammatory diseases. To measure medication adherence, electronic monitoring is regarded as superior to pill count. GLORIA is an ongoing two-year trial on the addition of low-dose (5 mg/d) prednisolone or placebo to standard care in older people (65+ years) with RA. During the entire trial, adherence is measured with electronic caps, and with pill counts. The objective is to describe medication adherence patterns, and to compare the adherence results of the two methods. Methods The recorded adherence patterns of patients (blinded for treatment group) were classified according to descriptive categories. The cutoff for good adherence was set at 80% of prescribed pills taken. Results Trial inclusion closed in 2018 at 451 patients, but trial follow-up is ongoing; the current dataset contains adherence data of 371 patients. Mean number of recorded 90-day periods per patient was 4 (range 1–8). Based on pill count over all periods, 90% of the patients had good adherence; based on cap data, only 20%. Cap data classified 30% of patients as non-user ( Conclusion In our trial of older people with RA, the majority appeared to be adherent to medication according to pill count. Results from caps conflicted with those of pill counts, with patterns suggesting patients did not use the bottle for daily dispensing, despite specific advice to do so. Trial registration NCT02585258. ClinicalTrials.gov (https://www.clinicaltrials.gov/)

The rheumatology and clinical immunology care center at the Maasstad Hospital is one of the four larger rheumatology care centers in the Netherlands. In recent years, the journey of inflammatory arthritis patients was redesigned to enable value-based care. The initial results of this Joint Value program are promising.

Angiopoietin-2 (Ang-2), a ligand of the tyrosine kinase receptor Tie2, is essential for vascular development and blood vessel stability and is also involved in monocyte activation. Here, we examined the role of Ang-2 on monocyte activation in patients with systemic sclerosis (SSc). Ang-2 levels were measured in serum and skin of healthy controls (HCs) and SSc patients by ELISA and array profiling, respectively. mRNA expression of ANG2 was analyzed in monocytes, dermal fibroblasts, and human pulmonary arterial endothelial cells (HPAECs) by quantitative PCR. Monocytes were stimulated with Ang-2, or with serum from SSc patients in the presence of a Tie2 inhibitor or an anti-Ang2 neutralizing antibody. Interleukin (IL)-6 and IL-8 production was analyzed by ELISA. Ang-2 levels were elevated in the serum and skin of SSc patients compared to HCs. Importantly, serum Ang-2 levels correlated with clinical disease parameters, such as skin involvement. Lipopolysaccharide (LPS) LPS, R848, and interferon alpha2a (IFN-&alpha, ) stimulation up-regulated the mRNA expression of ANG2 in monocytes, dermal fibroblasts, and HPAECs. Finally, Ang-2 induced the production of IL-6 and IL-8 in monocytes of SSc patients, while the inhibition of Tie2 or the neutralization of Ang-2 reduced the production of both cytokines in HC monocytes stimulated with the serum of SSc patients. Therefore, Ang-2 induces inflammatory activation of SSc monocytes and neutralization of Ang-2 might be a promising therapeutic target in the treatment of SSc.

ObjectivesEarly initiation of effective treatment favours remission in rheumatoid arthritis, but it remains unknown if the same concept applies to psoriatic arthritis (PsA). Therefore, this study investigated whether the combination of golimumab plus methotrexate (MTX) as a first-line treatment is superior to MTX alone in inducing remission in PsA.MethodsThis investigator-initiated, multicentre, double-blind, randomised, placebo-controlled trial included 51 MTX and bDMARD-naive patients with PsA fulfilling the CASPAR criteria and with active disease at baseline (≥3 swollen joint count/tender joint count). Patients were randomised to golimumab (50 mg SC monthly)+MTX (n=26) (TNFi arm) or matched placebo+MTX (n=25) (MTX arm). MTX was started 15 mg/week and increased to 25 mg/week over 8 weeks. The primary endpoint was percentage of patients achieving Disease Activity Score (DAS) remission (ResultsThe primary efficacy endpoint was achieved by 81% in the TNFi arm versus 42 % in the MTX arm (p=0.004). This difference in DAS remission was already observed at week 8. A significant difference in favour of the golimumab+MTX arm at week 22 was also observed for other response criteria such as MDA, ACR20/50/70, disease measures and patient-reported outcomes. The occurrence rates of adverse event and treatment-emergent adverse event were similar in both arms.ConclusionsIn patients with early PsA, DAS remission at week 22 was almost doubled with golimumab+MTX versus MTX alone. This double-blind, randomised, placebo-controlled study supports the concept that early initiation of TNFi in patients with PsA favours remission.Trial registration numberNCT01871649.

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

Objective. To determine the symptom-modifying effect of hydroxychloroquine (HCQ) in hand osteoarthritis (OA).Methods. In this randomized, double-blind, multicenter trial, patients with symptomatic hand OA received either HCQ 400 mg once a day or placebo during 24 weeks. The primary outcome was change of pain measured on a 100-mm visual analog scale (VAS) at 24 weeks. Secondary outcomes included decrease of pain at weeks 6 and 12 and change in Australian Canadian Hand Osteoarthritis Index (AUSCAN) and Arthritis Impact Measurement Scale 2 short form (AIMS2-SF) total scores.Results. A total of 196 patients was included (placebo n = 98, HCQ n = 98). Mean +/- SD age was 58.0 +/- 7.6 years, and 86% were female. Baseline mean +/- SD pain VAS was 44.9 +/- 22.9 mm in the placebo group and 43.2 +/- 22.3 mm in the HCQ group. At 24 weeks, change in pain VAS was not significantly different between both groups (imputed mean VAS 42.7 in the HCQ group versus 45.3 in the placebo group after 24 weeks), as was the case in pain VAS at weeks 6 and 12. Changes in AUSCAN total score and AIMS2-SF total score in both groups were similar between the groups. In total, 24 patients in the placebo group and 21 patients in the HCQ group reported >= 1 adverse event. In the HCQ group, 3 patients reported a severe allergic reaction. Fifteen patients withdrew from the study (5 placebo, 10 HCQ group) due to adverse events.Conclusion. Treatment with HCQ at 24 weeks is not effective in reducing the symptoms of hand OA compared to placebo.

Vasodilator function is reported to be reduced in rheumatoid arthritis (RA), and is considered an early sign of vascular dysfunction, which is normalised by TNF inhibitors (TNFi). To optimise cost-effectiveness, tapering or interruption of TNFi therapy in established RA patients is advocated. We explored whether cessation of TNFi results in impaired vasodilator function and whether this relates to the development of a Disease Activity Score (DAS28)-based flare. Forty-one patients were assessed for eligibility as RA with at least 12 months of low disease activity (based on 28 joint counts); 35 enrolled into the randomised study: 8 were randomised to continue, 27 to stopping TNFi. Forearm vasodilation to acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed before cessation of TNFi therapy (visit 1) and 6 months after (dis)continuation of TNFi or at flare (based on DAS28) whichever came first (visit 2). None of the patients who continued their TNFi therapy flared. Eight out of 22 patients who stopped TNFi therapy flared. The vasodilator response to ACh and SNP was reduced significantly in patients who experienced a flare of RA: In patients who did not experience a flare, the vasodilator response to ACh or SNP was not significantly affected. Vasodilator function is reduced after cessation of TNFi, but only when RA reactivates, indicating that early vasodilator dysfunction is a consequence rather than a cause of systemic inflammation in RA and not specifically related to inhibition of TNFα signalling. Without close monitoring, microvascular damage can occur after TNFi interruption with potential devastating implications for cardiovascular health. Trial registration: NCT02130076

Objectives: We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison. Method: New and established PsA patients and healthy volunteers (aged 20–30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI. Results: The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10–22.5) in new PsA, 13.5 (9.5–18) in established PsA, and 3 (1–8.5) in healthy volunteers (p = 0.002). Conclusions: Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volunteers. After recoding of PD severity and excluding thickness of knee entheses, marked differences between PsA patients and healthy controls were observed.

Objective.Psoriatic arthritis (PsA) is a multifaceted disease. Affecting joints, skin, entheses, and dactylitis, its effect on health-related quality of life (HRQOL) could be substantial. We aim to assess HRQOL in patients newly diagnosed with PsA and analyze its associations with disease manifestations.Methods.Data collected at time of diagnosis from patients with PsA included in the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR) study were used. HRQOL was assessed using 8 domains of the Medical Outcomes Study Short Form-36 (SF-36) questionnaire. Patients were classified based on primary manifestation in arthritis subtypes (i.e., mono-, oligo-, or polyarthritis) and other subtypes (i.e., enthesitis, dactylitis, and axial disease). In all patients, presence of arthritis, enthesitis, dactylitis, psoriasis, and chronic inflammatory back pain was determined. Multivariable linear regression was used to determine associations of PsA manifestations with HRQOL.Results.Of 405 patients, primary manifestation was peripheral arthritis in 320 (78 monoarthritis, 151 oligoarthritis, and 91 polyarthritis), enthesitis in 37, axial disease in 9, and dactylitis in 39. Mean scores of SF-36 domains were lower than the Dutch reference population and similar across arthritis subtypes. A higher number of enthesitis locations and tender joints, and presence of chronic back pain, were independently associated with worse SF-36 scores. Psoriasis and dactylitis were not associated with worse scores.Conclusion.HRQOL was diminished in PsA at time of diagnosis compared to the Dutch reference population, and tender joints, enthesitis at clinical examination, and back pain as indicators of pain affected HRQOL.

Background:Although the prevalence of Psoriatic Arthritis (PsA) is the same in men and women, women experience a higher burden of disease (pain, disability, fatigue) (1).The persistent belief that women tend to over-report their symptoms compared to men may also contribute to under or delayed diagnosis in women. The clinical pattern of PsA also differs, with men presenting more commonly with peripheral and axial joint damage and women being affected more frequently by polyarthritis (2). Furthermore, most disease activity measures contain pain and quality of life measurement metrics that may perform differently by sex. As a result, this may affect the clinician’s perception of disease severity, influence management decisions and subsequently introduce sex bias in prescribing.Objectives:To assess sex-related differences in baseline demographics, disease characteristics and evolution over 1 year in patients with newly diagnosed PsA.Methods:Our study is embedded in the Dutch south-west Early Psoriatic Arthritis prospective cohort study. We described patient characteristics using simple descriptive analysis techniques. For the comparison across sexes and baseline and 1 year follow up, appropriate tests depending on the distribution were used.Results:273 men and 294 women with no significant differences in age and ethnicity were included. Women reported significantly longer duration of symptoms before diagnosis and significantly fewer of them were in paid employment at baseline. Oligoarthritis was the most common pattern of arthritis in both sexes. Polyarthritis and enthesitis were more prevalent in women who also presented at baseline a significantly higher tender joint count (Fig.1) than men but no difference in swollen joint count.Figure 1.Longitudinal evolution of TJC68, Pain, VAS global, BRAF for men and women in the first year of PsA.All composite indices (CPDAI, DAPSA, GRACE, MDA, Psoriatic ArthritiS Disease Activity Score) showed significantly worse results in women at baseline. Women also suffered more frequently from comorbid medical conditions, fatigue and anxiety, and reported more severe limitations in function and worse quality of life.At 12 months women, despite the improvement they made, reported significantly higher levels of pain compared to men. Although MDA rates increase over time for both sexes,(Fig.2), it remained significantly more prevalent among men (19.0% vs 11.1% at inclusion,p, and 58.1% vs 35.7%,p, at T12). DAPSA was significantly higher in women at both timepoints and a significantly higher percentage of men presented remission according to DAPSA score at 12 months.Figure 2.Longitudinal evolution of composite measures for men and women in the first year of PsA.Conclusion:After 1 year of follow-up women didn’t surpass their baseline disadvantages and despite the improvement, they still present higher disease activity, more pain and lower functional capacity than men. The nature of these findings may advocate a need for sex specific adjustment of treatment strategies and evaluation in psoriatic arthritis as sex-related difference in outcome persisted over time.References:[1]Eder L, Thavaneswaran A, Chandran V, Gladman DD. Gender difference in disease expression, radiographic damage and disability among patients with psoriatic arthritis. Annals of the rheumatic diseases. 2013;72(4):578-82.[2]Orbai AM, Perin J, Gorlier C, Coates LC, Kiltz U, Leung YY, et al. Determinants of Patient-Reported Psoriatic Arthritis Impact of Disease: An Analysis of the Association with Gender in 458 Patients from 14 Countries. Arthritis care & research. 2019.Disclosure of Interests:Evangelia Passia: None declared, Marijn Vis Grant/research support from: Novartis, Pfizer – grant/research support, Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Novartis, Pfizer – consultant, Laura C Coates: None declared, Anushka Soni Grant/research support from: Oxford-UCB prize fellowship, Speakers bureau: Janssen and Abbvie, Ilja Tchetverikov: None declared, Andreas Gerards: None declared, Lindy-Anne Korswagen: None declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Wiebo van der Graaff: None declared, Josien Veris-van Dieren: None declared, Natasja Denissen: None declared, F. Fodili: None declared, M. Starmans: None declared, Yvonne Goekoop-Ruiterman: None declared, M. van Oosterhout: None declared, Jolanda Luime: None declared

ObjectivesMethotrexate (MTX) is currently the recommended first-line therapy for treating psoriatic arthritis (PsA), despite lacking clear evidence. No estimates of efficacy of MTX in usual care and no clear MTX responsive clinical or laboratory variables are currently available. This study describes the response to MTX monotherapy in newly diagnosed patients with PsA in usual care. Second, we compared clinical variables and cytokine profiles in patients responding and not responding to MTX monotherapy.MethodsWe used data collected in the Dutch southwest Early Psoriatic Arthritis cohoRt study to select patients with PsA with oligoarthritis or polyarthritis, and at least 1 year follow-up. We analysed disease activity at 6 months of patients who started MTX monotherapy and still used MTX monotherapy 1 year after diagnosis. Cytokine profiles were determined at baseline and after 3 and 6 months with a bead-based multi-immunoassay.ResultsWe identified 219 patients of which 183 (84%) patients started MTX monotherapy within 6 months after diagnosis. 90 patients used MTX monotherapy throughout the first year of which 44 patients (24%) reached minimal disease activity(MDA) at 6 months, decreasing to 33 patients (18%) after 1 year. Non-responders had significantly higher concentrations of interleukin (IL) 23 and IL-10 before and during MTX therapy.ConclusionsOur results showed that only 18% of patients with PsA are in sustained MDA after 1 year of MTX monotherapy and non-responders more often had IL-23-driven disease. Our results indicate the need for more treat-to-target and personalised therapy strategies in PsA.

Recruitment of patients in randomized controlled trials is a well-known problem. Recruitment may be difficult and often takes more time than expected. Most trials adapt their recruitment target or ...

Background Rituximab (RTX) is an effective treatment for patients with Rheumatoid Arthritis (RA). 1000mg (1 × 1000mg or 2 × 500mg) has similar 6-month efficacy as the registered dose of 2 × 1000mg. Based on several case reports and a case series even lower doses might be sufficient for maintenance treatment, potentially improving safety and decreasing costs.(1) Objectives To compare effectiveness of RTX retreatment with ultra-low doses (1 × 500mg or 1 × 200mg) to standard low dose (1 × 1000mg). Methods A 6-month double-blind randomised controlled non-inferiority trial (REDO study (2)) was performed in 5 centres in the Netherlands. Patients with RA responding well to RTX (based on DAS28-CRP Results The projected inclusion was met (n=142, table 1a). In both ultra-low dose groups 2 patients received an extra dose of 1000mg RTX due to a flare. The 500mg dose was non-inferior to 1000mg at 3 months (-0.04 (95% CI -0.39 to 0.30)), but not at 6 months (0.31 (95% CI -0.05 to 0.68). The 200mg dose was non-inferior to 1000mg at both time points. Because of our pre-defined hierarchical testing, non-inferiority could not formally be inferred for the 200mg dose. Mean DAS28-CRP scores remained low in all groups throughout the study, and B-cell counts decreased similarly at 3 months (figure 1). In the 200mg group, more patients received intramuscular corticosteroid injection(s) compared to the 1000mg group (table 1b). Conclusion Non-inferiority of retreatment with 1 × 500mg or 1 × 200mg rituximab versus 1 × 1000mg after 6 months could not formally be established. However, ultra-low doses appear similarly effective in the majority of RA patients, judged by DAS28-CRP course over time and B-cell results, with use of slightly more co-medication. References [1] Shenoy et al. Arthritis Rheumatol 2015;67(suppl 10). [2] Den Broeder et al. Trials 2017;30;18(1):403. Disclosure of Interests L.M. Verhoef: None declared, Nathan den Broeder: None declared, R.M. Thurlings Grant/research support from: Congress invitations: Roche, Abbvie, Cellgene, W.H. van der Laan: None declared, W. van der Weele: None declared, Marc Kok: None declared, H.J. Bernelot Moens: None declared, Thasia Woodworth: None declared, Bart van den Bemt Grant/research support from: UCB, Pfizer, Abbvie, Bristol-Myers Squibb, Consultant for: UCB, Novartis and Pfizer, Speakers bureau: Pfizer, AbbVie, UCB, Biogen, Sandoz, Frank van den Hoogen Grant/research support from: Grants, speakers fee, advisory boards: AbbVie, Actelion, Amgen, Boehringer Ingelheim, Biogen, BMS, Celgene, Celltrion Healthcare, Corbus, Janssen, Eli Lilly, Mundipharma, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme., Alfons den Broeder Grant/research support from: Congress invitations: Roche, Cellgene, Abbvie, Biogen, Consultant for: Expert Witness for Fresenius, BI, BMS, Amgen

Background Switching patients from originator infliximab (IFX) to biosimilar IFX can reduce healthcare costs. Several studies have shown that switching does not affect the efficacy for rheumatoid arthritis (RA) patients(1,2), however prospectively collected data on pharmacokinetics, immunogenicity and quality of life (QoL) is scarce. Objectives We report data collected from RA patients in clinical remission enrolled in the SECURE study (IFX4501; registered at www.clinicaltrialsregister.eu 2014-004904-31). In SECURE we collected IFX serum concentrations, efficacy, quality of life (QoL) and safety data of patients switched from originator IFX to biosimilar IFX CT-P13 for up to 16 weeks. The IBD cohort of this study has been published elsewhere (3). Methods In this prospective, open-label, interventional, non-inferiority, multi-center, phase IV trial, adult RA patients in clinical remission >30 weeks (DAS Results Between July 2015 and December 2016, 34 RA patients were recruited. Two patients were excluded from the safety population (1 no IMP exposure; 1 no efficacy assessment) and two patients discontinued before week 16 (1 AE: renal colic; 1 personal reasons), leaving 30 patients in the intent to treat population. For 11 patients, blood samples were obtained at baseline and week 16. The IFX ratio at week 16 (biosimilar) compared to baseline (originator) was 107.40 (90% CI 90.35;127.66), indicating non inferiority. The number of included patients was too low for firm conclusions. The mean difference (95% CI) at week 16 compared to baseline was for the CRP -0.22 (-1.80,1.37); for DAS 0.12 (-0.06,0.30), for EQ5D thermometer -3.19 (-9.78,3.41) and EQ5D Health status -0.05 (-0.08,-0.01). These changes were not clinical relevant. In total 76 AEs were reported by 29 (90.6%) patients; 27 of these AEs were related to the study treatment. The most frequently reported AEs (≥5% subjects) were fatigue (9.4%), headache (6.3%), arthralgia (15.6%), back pain (9.4%), cough (6.3%), viral upper respiratory tract infection (15.6%) bursitis (6.3%) and pain in extremity (6.3%). Two non-related serious AEs were reported (ovarian cyst and benign parathyroid tumour). No ADA’s were detected by inclusion or during the follow-up period. Conclusion In this prospective, interventional study in RA patients in clinical remission there were no clinically relevant changes in clinical and biochemical efficacy, quality of life and tolerability 16 weeks after switching to the biosimilar IFX CT-P13 compared to the originator. This study is sponsored by Mundipharma Pharmaceuticals BV. References [1] Park, W. et al. Ann Rheum Dis76,346-354 (2017) [2] Jorgensen, K.K. et al. Lancet389, 2304-2316 (2017) [3] Strik, A.S. et al. Lancet Gastroenterol & Hepatol6(3),404-412 (2018) Disclosure of Interests Michael Nurmohamed Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Menarini, MSD, Mundipharma, Pfizer, Roche, Sanofi and UCB, Reinhard Bos Grant/research support from: SUN Pharma, Marc Kok: None declared, Lindy-Anne Korswagen: None declared, Petra Vos: None declared, Joanne Bloemsaat Employee of: Mundipharma Pharmaceuticals B.V, Theo Rispens Grant/research support from: Genmab, Speakers bureau: Pfizer, Abbvie, Regeneron, Yvonne van Megen Employee of: Mundipharma Pharmaceuticals B.V, Gerard D’Haens Consultant for: Abbvie, Ablynx, Amakem, Amgen, AM Pharma, Avaxia, Biogen, Bristol Meiers Squibb, Boerhinger Ingelheim, Celgene/Receptos, Celltrion, Cosmo, Covidien/Medtronics, Ferring, DrFALK Pharma, Eli Lilly, Engene, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Immunic, Johnson and Johnson, Lamepro, Lycera, Medimetrics, Millenium/Takeda, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Prometheus laboratories/Nestle, Protagonist, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant and Vifor; received speaker fees from Abbvie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts and Vifor.

Background: Methotrexate (MTX) is the preferred drug of most rheumatologists for treating psoriatic arthritis (PsA). Despite its widespread use in clinical practice, scientific evidence of methotrexate on the different manifestations of psoriatic disease is limited. Specifically, data of MTX use in usual care and in early PsA patients are lacking. Objectives: To describe the response to MTX for patients with PsA and an oligoarthritis or polyarthritis phenotype in usual care in the first year after diagnosis, and its impact on different aspects of the disease, including patients not achieving minimal disease activity (MDA) despite continuous exposure to MTX Methods: Data collected in the Dutch southwest Early Psoriatic Arthritis cohort (DEPAR) study were used. Patients with a new diagnosis of PsA who have not started disease-modifying antirheumatic drugs (DMARDs) for PsA were eligible to participate. In this analysis, only patients with a phenotype at time of diagnosis of oligoarthritis or polyarthritis (resp. 2-4 joints involved or 5 or more joints, as defined by the rheumatologist), and at least one year follow up were included. Research nurses collected clinical data and data on medication use every three months in the first year after diagnosis. The following outcomes were used to evaluate disease activity: MDA, EULAR active disease (at least one tender and swollen joint), disease activity index for PsA low disease activity (DAPSA-LDA: DAPSA≤14), and disease activity score 28 low disease activity (DAS28-LDA: DAS28≤3.2). Disease activity at six months of patients who started MTX within six months after diagnosis and have continued using MTX until one year after diagnosis was analyzed. Results: In April 2018, 219 patients had a phenotype of oligoarthritis (n=134, 61%) or polyarthritis (n=85, 39%) at time of diagnosis, and at least one year follow up. In 183 (84%) patients, MTX monotherapy was started within six months after diagnosis. Within the first year, 23 of these used MTX intermittently, 25 switched to a different DMARD, and 45 started a different DMARD while remaining on MTX therapy. The remaining 90 patients used MTX monotherapy throughout the first year and of these we assessed disease activity at 6 months after diagnosis. At 6 months, 38 patients out of these 90 were not in MDA despite continuous MTX treatment, while 44 achieved MDA. Major differences amongst the two groups included tender joint count, physical function, evaluation of pain and global disease activity and impact on health-related quality of life scores (Table 1). Conversely, 18% of all patients started MTX monotherapy were in sustained MDA at one year while continuing MTX monotherapy. Conclusion: The majority of patients with a new diagnosis of PsA with a phenotype of oligoarthritis or polyarthritis started MTX within a year after diagnosis. MTX is maintained as monotherapy in half of these patients, with 18% of them achieving sustained MDA using MTX monotherapy at one year. Interestingly, approximately half of the patients who had continued methotrexate monotherapy were not achieving MDA after six months and they report higher impact of disease on clinical and patient reported outcomes, suggesting need to consider improvement of therapy for these patients. Disclosure of Interests: Kim Wervers: None declared, Hannah den Braanker: None declared, Jolanda Luime: None declared, Ilja Tchetverikov: None declared, Andreas Gerards: None declared, Cathelijne Appels: None declared, Wiebo van der Graaff: None declared, Hans van Groenendael: None declared, Lindy-Anne Korswagen: None declared, Josien Veris-van Dieren: None declared, Johanna Hazes: None declared, Marc Kok: None declared, Marijn Vis Grant/research support from: Novartis

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:Rheumatologists play an important role in the management of patients with Psoriatic Arthritis (PsA). With PsA being a multifaceted disease, it can be challenging to assess the impact of psoriatic skin symptoms, next to the musculoskeletal complaints. We have previously shown that a dermatology-specific Health-related Quality of Life (HRQoL) questionnaire provides insight into the burden of skin symptoms, in contrast to a general HRQoL questionnaire.1 When treating PsA patients, specific questions on skin symptoms are necessary in order to assess the burden of psoriasis.Objectives:To create a set of questions that can easily identify PsA patients with a high psoriasis burden in daily rheumatology clinical practice.Methods:Data from patients receiving usual care were used from the Dutch south west Psoriatic Arthritis (DEPAR) cohort, consisting of newly diagnosed PsA patients included between July 2013 and March 2020. The two dermatology-specific HRQoL questionnaires used were the Skindex-17 and Dermatology Life Quality Index (DLQI), both with a one-week recall period.First, an exploratory principal component analysis (PCA) with varimax rotation was performed on both questionnaires combined, to identify underlying latent traits. Subsequently, items were dichotomized on their median frequencies. And a 2-parameter logistic (2PL) model was fitted for each latent trait. Item characteristic curves were plotted for each latent trait. Item selection took place based on the discrimination and difficulty of the items. Per latent trait, we selected 2 to 3 items distributed far apart across the latent trait. A flowchart was made with the selected questions.Results:In total, 413 patients with completed Skindex-17 and DLQI questionnaires at baseline were included. Mean (sd) age was 50.3 (13.4) years and median (IQR) Psoriasis Area and Severity Index (PASI) score 2 (0.5-4.2). The PCA gave the best fit with two underlying clusters of questions, namely psychosocial (n=20) questions and questions regarding physical symptoms (n=7). Three questions were selected to assess psychosocial impact and two for impact of physical symptoms (Figure 1). Questions should be asked in chronological order.Figure 1.Flowchart of questions assessing psoriasis burden.Cluster 1: PsychosocialThe first question is if the patient was embarrassed by their skin condition. If answered with “never”, the patient experienced the lowest burden. When answered with “rarely/sometimes” or “often/always”, continue to the second question. Ask the patient if they tended to stay at home because of their skin condition. If answered with “never”, they experienced a higher burden. If answered with “rarely/sometimes” or “often/always”, continue to the last question. Ask the patient if their skin condition has prevented them from working or studying. If not, the patient experienced a higher burden and if answered with “yes”, they experienced the highest burden in this domain.Cluster 2: Physical symptomsFirst ask the patient how itchy, sore, painful or stinging their skin was. If they answer with “not at all”, they experienced the lowest burden. If answered with “a little/a lot/very much”, continue to the second question. Ask if their skin was irritated. If answered with “never/rarely/sometimes”, they experienced a higher burden. If answered with “often/always”, the patient experienced the highest burden in this domain.Conclusion:We have created a practical guide for rheumatologists to distinguish PsA patients with a high psoriasis burden from those with a lower burden. With a minimum of two and a maximum of five questions, both psychosocial burden of psoriasis and burden of physical symptoms can be easily identified in daily clinical practice.References:[1]Kasiem FR, Kok MR, Tchetverikov I, Wervers K, Hazes J, Luime J, et al. AB0786 Impact of psoriasis severity on Health-Related Quality of Life in early psoriatic arthritis: results from real world data, the DEPAR study. Annals of the Rheumatic Diseases. 2020;79:1691-2.Disclosure of Interests:None declared

Background:Health literacy is increasingly recognised as a critical determinant of health. While care should be tailored to the health literacy needs of each patient [1], research in primary care shows that physicians often under- or overestimate their patients’ health literacy, with socioeconomic factors playing a role [2]. Evidence in a rheumatology setting is scarce.Objectives:-To investigate discordance between health literacy of patients with rheumatic and musculoskeletal diseases (RMDs) and assessment by their treating health professional, across the nine domains of the Health Literacy Questionnaire (HLQ).-To explore whether discordance is associated with the patient’s socioeconomic background.Methods:Patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), or gout from three Dutch outpatient rheumatology clinics completed the HLQ [3]. The treating health professional (rheumatologist, physician assistant, nurse (practitioner) or resident) assessed their patient’s level for each HLQ domain, or answered “I don’t know”. Discordance per domain was calculated as the patient’s score subtracted from the professional’s score (both on a 0-10 scale). Discordance was defined as a ≥2-point difference in either direction. Adjusted multilevel multinomial regression models (ref. = no discordance) with patients clustered by health professionals were computed to test the role of socioeconomic factors (age, gender, education level, immigration background, living alone and employment status) in negative (i.e. professional scored lower) and positive (i.e. professional scored higher) discordance.Results:Of 778 patients included, 41% had RA, 34% had SpA, and 25% had gout. We observed considerable discordance across all HLQ domains (Table 1). Professionals answered “I don’t know” most often for “Having social support for health” (19.4%, domain 4). Most discordance occurred for “Critically appraising information” (42.1%, domain 5). For all HLQ domains except “Having social support for health” (domain 4), discordance was associated with socioeconomic factors. In patients with a non-Western immigration background, professionals were likely to assign lower scores than patients’ HLQ scores in six domains. Education level was an important driver of discordance in seven domains, with the direction of the association being domain-dependent. Other factors associated with discordance in multiple domains were type of rheumatic disease, comorbidities, mastery, how well the professional knew the patient, type of professional, and disease impact.Table 1.Discordance per HLQ domain (n=778)HLQ domainProfessional scored lowerNo discordanceProfessional scored higherProfessional did not known (%)1. Healthcare provider support128 (16)514 (66)126 (16)10 (1)2. Having sufficient information100 (13)528 (68)143 (18)7 (1)3. Actively managing health95 (12)461 (59)208 (27)14 (2)4. Having social support for health55 (7)397 (51)175 (22)151 (19)5. Critically appraising information78 (10)448 (58)250 (32)2 (0)6. Actively engaging with providers205 (26)500 (64)70 (9)3 (0)7. Navigating the health system115 (15)544 (70)107 (14)12 (2)8. Finding health information163 (21)492 (63)98 (13)25 (3)9. Understanding health information145 (19)511 (66)110 (14)12 (2)Conclusion:Considerable discordance between patients’ health literacy and their treating health professionals’ assessment exists across health literacy domains. In eight out of nine domains, discordance was associated with the patient’s socioeconomic background, particularly education and immigration background. Understanding and addressing the reasons for discordance between patient-reported and professional-perceived health literacy has potential to improve responsiveness to patients’ needs, promote better communication and ultimately improve care outcomes.References:[1]Bakker et al., Arthrit Care Res (2021)[2]Storms et al., BMJ Open (2019)[3]Osborne et al., BMC Public Health (2013)Disclosure of Interests:None declared

Background:The effect of inflammatory arthritis (IA) on fertility has been mainly studied in women. Multiple factors associated with lower fertility rate in women can also be present in male patients with IA (1). The fertility rate in men with IA, however, has never been studied.Objectives:To describe the fertility rate (number of biological children per individual) of men with IA.Methods:We performed a multicenter cross-sectional retrospective study conducted in eight Dutch hospitals. Men with IA (Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA) and Spondyloarthritis (SpA)) who were over 40 years old and indicated that their family size was complete were invited to participate. Men who were still planning on having biological children were excluded. Participants completed a digital questionnaire that included fertility-related questions and questions regarding their demographic and clinical information. To analyze the impact of IA on male fertility rate, patients were divided into groups according to the age at the time of their diagnosis: age41 years.Results:In total 628 participants diagnosed with IA were included. The response rate 34.87%. Information regarding their age, age at diagnosis, clinical diagnosis and number of children is presented per group in Table 1. Regarding the total number of children per man, there was a statistically significant difference between the three groups (p=41 years (1.88 {SD 1.14}). Compared to men from the general population of the Netherlands, the total number of children of men diagnosed at age>41 years was not statistically different (1.88 vs 1.80, respectively).Table 1.Participants’ basic demographic and clinical characteristics, including the number of biological children per men.All patientsIA diagnosed at age IA diagnosed at age 31-40 yearsIA diagnosed at age >41 yearsTotal, n (%)628137 (21.82)149 (23.73)342 (54.46)Age, mean (SD)57.17 (9.98)53.01 (9.96)52.76 (7.35)61.06 (9.47)Diagnosis, n (%)•iRA297 (47.29)42 (30.66)67 (44.97)188 (55.32)•AJIA10 (1.59)10 (6.25)0 (0)0 (0)•ISpA (incl. PsA)320 (50.96)90 (65.69)83 (55.70)147 (42.98)Age at diagnosis, mean (SD)41.29 (13.08)26.27 (9.15)36.99 (5.66)49.98 (9.70)Disease duration, mean (SD)15.89 (11.88)26.48 (12.57)15.70 (8.52)11.30 (9.87)Number of biological children, mean (95% CI)1.71 (1.60-1.81)1.39 (1.15-1.63)a,b1.60 (1.38-1.82)a1.88 (1.75 -2.01)a p< 0.05 compared to those diagnosed age >41 yearsb p< 0.05 compared to those diagnosed age >31-40 yearsConclusion:This is the largest study ever conducted to evaluate the impact of IA on male fertility. We demonstrated that men diagnosed with IA before and during their reproductive years have a lower fertility rate than those men diagnosed with IA after their reproductive years. Multiple mechanisms (biological and non-biological) can be responsible for this association. More research is needed to identify the causes of these lower fertility rates in men with IA.References:[1]Perez-Garcia LF, Te Winkel B, Carrizales JP, Bramer W, Vorstenbosch S, van Puijenbroek E, et al. Sexual function and reproduction can be impaired in men with rheumatic diseases: A systematic review. Semin Arthritis Rheum. 2020;50(3):557-73.Figure 1.Total number of biological children (mean and SD) per group.Acknowledgements:The authors would like to acknowledge Ron Buijs, data manager of the Department of Rheumatology of the Erasmus MC, for his technical support with regards to data collection.Disclosure of Interests:Luis Fernando Perez-Garcia Consultant of: Galapagos, Esther Röder: None declared, Robbert Goekoop: None declared, Johanna Hazes: None declared, Marc R Kok Consultant of: Novartis, Grant/research support from: Novartis, Petra Kok: None declared, Hieronymus TW Smeele: None declared, Ilja Tchetverikov: None declared, J.H. van der Kaap: None declared, Annette van der Helm - van Mil: None declared, Bouwe Krijthe: None declared, Radboud Dolhain Speakers bureau: UCB, Roche, Abbvie, Genzyme, Novartis, Consultant of: Galapagos, Grant/research support from: UCB

Background:The need to involve patient reported outcomes (PROs) in the management of rheumatoid arthritis (RA) increases, since PROs quantify patient relevant outcomes. Although PROs have been incorporated in the core-outcome sets in clinical trials, knowledge about the treatment effects on these PROs is scarce. Therefore, we performed a systematic review on the effects of disease modifying anti-rheumatic drugs (DMARDs), of any type, on relevant PRO domains mentioned in the ICHOM standard set. This might support rheumatologists and RA patients during treatment decisions.Objectives:To get insight in the treatment effects of DMARDs of any type on three PRO domains that matter to patients (pain, activity limitations and fatigue).Methods:A systematic review was performed in Embase, Medline, Web of Science, Cochrane and Google Scholar. Included were all studies that were published before August 2019 and showed DMARD treatment effects in RA on PROs that are part of the ICHOM standard set. Three Bayesian network meta-analyses were performed for the PRO domains pain, activity limitations and fatigue. Preliminary results of DMARDs (in)directly compared to placebo were visualized by forest plots using R.Results:The search strategy yielded n=5974 articles. After selection was performed by 2 independent researchers, n=70 individual articles representing n=53 studies were extracted, over the three PRO domains; pain (n=31), activity limitations (n=41) and fatigue (n=21). In all RCTs, PROs were only reported as secondary or tertiary endpoints. In figure 1, we show the effects on PROs for any type of DMARD investigated compared to placebo. Overall, DMARDs show a greater reduction in pain (standardized mean difference (SMD); -0.97 – -0.22) and most of them in activity limitations (SMD; -0.81 – 0.56). In fatigue, this clear direction is lacking (SMD; -0.86 – 3.5). csDMARDs and anti-TNF seem to perform slightly, but nog significantly, worse than other bDMARDs and tsDMARDs in the first two domains.Conclusion:Within in this systematic review we report a reduction for DMARDs of any type on the domains of pain and activity limitations compared to placebo. However, results are still preliminary and should be interpreted with care. A more comprehensive network analysis might give a more definitive answer which DMARD performs best.Figure 1.Disclosure of Interests:None declared

Background:Treatment with low-dose glucocorticoids (GCs) (≤7.5 mg prednisolone) in combination with standard care is highly effective in rheumatoid arthritis (RA), but despite 70 years of clinical experience, evidence-based information on its balance of benefit and harm is incomplete. This leads to an ongoing debate, with under- and over-use of GCs as result. The GLORIA pragmatic trial was developed to assess harm, benefit and costs of low-dose GCs added to the standard treatment of older RA patients.Objectives:The objective of this abstract is to document the baseline status and frequency of comorbid conditions in the GLORIA study population. The results of the unblinded data will be submitted as late-breaking abstract.Methods:This double-blind, randomized, placebo-controlled, multicenter trial (1) was open for patients with RA according to the 1987 or 2010 (2) criteria, age ≥65 years, and disease activity score of 28 joints (DAS28) of ≥2.6. Patients were recruited from rheumatology clinics in Germany, Hungary, Italy, The Netherlands, Portugal, Romania and Slovakia. Eligible patients were randomized to two years of treatment with daily 5 mg prednisolone or matching placebo. All other medication was allowed, except for GCs. The presented data are blinded because the database is not closed yet.Results:The population consists of 451 patients with mean disease duration 10.6 (Q1-Q3: 3-15) years. The majority (70%) is female, mean age is 72.5 (Q1-Q3: 68-76, range: 65-88) years, 66% were positive for rheumatoid factor and 56% for ACPA. Patients had a mean of 4.3 (SD 2.8) comorbidities besides RA (3.4 active) and therefore used multiple concomitant medications (3.9 (SD 3.4)) (Table 1). The most common comorbidities (provisional data of 161 patients with complete coding) in this older population are: vascular disorders (58%), musculoskeletal and connective tissue disorders (57%) and a history of surgical and medical procedures (45%). Patients were most frequently on beta blocking agents (22%, mainly metoprolol) and HMG CoA reductase inhibitors (20%, mainly simvastatin). Most patients also have an extensive history of anti-rheumatic treatment. At the start of the trial most patients (82%) were on cDMARD treatment; 15% were on bDMARDs/tsDMARDs. Almost half of the patients previously had been treated with GCs, with a mean duration of 3.4 years and a mean last dose of 4.6 mg/day.Conclusion:The baseline data shows that we have an older study population who have relatively many other comorbidities next to RA and who are almost all treated with multiple concomitant medications in addition to the study medication. Therefore, we expect to report a high adverse event rate. Research among older patients is urgently needed, but the frailty of this population as represented by the multiple comorbidities and concomitant medications have to be taken into account in the analyses and interpretation of the results.References:[1]Hartman L, Rasch LA, Klausch T, Bijlsma HWJ, Christensen R, Smulders YM, et al. Harm, benefit and costs associated with low-dose glucocorticoids added to the treatment strategies for rheumatoid arthritis in elderly patients (GLORIA trial): study protocol for a randomised controlled trial. Trials. 2018;19:67.[2]Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-81.Table 1.Comorbidities and concomitant medications at baseline in the GLORIA trial.MeanSDRangeComorbidities 4.32.8 0-15 Active 3.4 Past 1.9Concomitant medications (count) 3.93.4 0-15 Beta blocking agents (%)22 HMG CoA reductase inhibitors (%)20 Platelet aggregation inhibitors (%)16 ACE inhibitors (%)12 Angiotensin II antagonists (%)11DAS28 4.521.05DAS28CRP 4.060.97HAQ (0-3) 1.20.7RA treatmentCurrent (%)Previous (%) cDMARD8492 bDMARD/tsDMARD1522 NSAID5129 Glucocorticoids 049Acknowledgements:The GLORIA project is funded by the European Union’s Horizon 2020 research and innovation programme under the topic ‘’Personalizing Health and Care’’, grant agreement No 634886.Disclosure of Interests:None declared

Background:The effect of inflammatory arthritis (IA) on pregnancy outcomes has been studied mainly in women. Paternal older age, sperm DNA integrity and certain genetic defects have been associated with worse pregnancy outcomes (1). However, pregnancy outcomes of partners of men with IA have never been studied.Objectives:To describe the pregnancy characteristics and outcomes of partners of men diagnosed with IA.Methods:We performed a multicenter cross-sectional retrospective study conducted in eight Dutch hospitals. Men with IA (Rheumatoid Arthritis (RA), Juvenile Idiopathic Arthritis (JIA) and Spondyloarthritis (SpA)) who were over 40 years old and indicated that their family size was complete were invited to participate. Participants completed a digital questionnaire that included pregnancy-related questions and questions regarding their demographic and clinical information. To analyze the impact of IA on pregnancy outcomes, pregnancies were classified into two groups; pregnancies that occurred after diagnosis of IA and before the diagnosis of IA.Results:In total 628 male participants diagnosed with IA were included. 408 men reported 897 singleton pregnancies that resulted in 794 live births. Regarding pregnancy characteristics, pregnancies conceived after diagnosis of IA had a higher mean paternal and maternal age at conception and a lower rate of spontaneous pregnancies (90.91 vs 96.60%, p=Table 1.Pregnancy characteristics and outcomes.AllpregnanciesPregnancy afterdiagnosis of IAPregnancy before diagnosis of IAP valuePregnancy characteristicsTotal number of pregnancies897220677Maternal age at conception, mean (SD)29.00 (5.00)30.69 (5.16)28.45 (4.83)pPaternal age at conception, mean (SD)31.31 (5.72)34.27 (6.08)30.49 (5.34)pSpontaneous pregnancy, n (%)854 (95.21)200 (90.91)654 (96.60)pPregnancy duration-months, median (IQR)39 (38-40)39 (38-40)39 (38-40)p=0.928Pregnancy outcomesLive births, n (%)794 (88.52)190 (86.36)604 (89.22)p=0.053Miscarriage, n (%)78 (8.70)27 (12.27)51 (7.53)pAbortion, n (%)25 (2.78)3 (1.36)22 (3.25)p=0.128*Medical indication5 (20.00)0 (0)5 (22.73)*Personal reasons20 (80.00)3 (100.00)17 (77.27)Pre-term birth149 (16.61)31 (14.09)118 (17.43)p=0.248Pregnancy complicationsNo complications during pregnancy, n (%)754 (84.34)184 (83.64)570 (84.57)p=0.741Hypertensive disorders(hypertension, pre/eclampsia), n (%)41 (4.57)8 (3.64)33 (4.87)p=0.445Gestational Diabetes Mellitus11 (1.28)2 (0.94)9 (1.38)p=0.619Growth restriction12 (1.34)1 (0.45)11 (1.65)p=0.193Conclusion:This is the largest study to describe the pregnancy characteristics and outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Prospective studies are needed to corroborate these findings.References:[1]Ibrahim Y, Johnstone E. The male contribution to recurrent pregnancy loss. Translational andrology and urology. 2018;7(Suppl 3):S317-S27.Acknowledgements:The authors would like to acknowledge Ron Buijs, data manager of the Department of Rheumatology of the Erasmus MC, for his technical support with regards to data collection.Disclosure of Interests:Luis Fernando Perez-Garcia Consultant of: Galapagos, Esther Röder: None declared, Robbert Goekoop: None declared, Marc R Kok Consultant of: Roche, Grant/research support from: Roche, Petra Kok: None declared, Hieronymus TW Smeele: None declared, Ilja Tchetverikov: None declared, Annette van der Helm - van Mil: None declared, J.H. van der Kaap: None declared, Bouwe Krijthe: None declared, Radboud Dolhain Speakers bureau: Abbvie, UCB, Genzyme, Novartis, Consultant of: Galapagos, Grant/research support from: UCB

Background:The prevalence of limited health literacy (i.e. cognitive and social resources of individuals to access, understand and apply health information to promote and maintain good health) in the Netherlands is estimated to be over 36% [1]. Access to and outcomes of rheumatological care may be compromised by limited patient health literacy, yet little is known about how to address this, thus action is required. As influencing individual patients’ health literacy in the rheumatology context is often unrealistic, it is paramount for the health system to be tailored to the health literacy needs of its patients. The OPtimising HEalth LIteracy and Access (Ophelia) process offers a method to inform system change [2].Objectives:Following the Ophelia approach:a. Identify health literacy profiles reflecting strengths and weaknesses of outpatients with RA, SpA and gout.b. Use the health literacy profiles to facilitate discussions on challenges for patients and professionals in rheumatological care and identify possible solutions the health system could offer to address these challenges.Methods:Patients with RA, SpA and gout attending outpatient clinics in three centres in the Netherlands completed the Health Literacy Questionnaire (HLQ) and questions on socio-demographic and health-related characteristics. Hierarchical cluster analysis using Ward’s method identified clusters based on the nine HLQ domains. Three researchers jointly examined 24 cluster solutions for meaningfulness by interpreting HLQ domain scores and patient characteristics. Meaningful clusters were translated into health literacy profiles using HLQ patterns and demographic data. A patient research partner confirmed the identified profiles. Patient vignettes were designed by combining cluster analyses results with qualitative patient interviews. The vignettes were used in two two-hour co-design workshops with rheumatologists and nurses to discuss their perspective on health literacy-related challenges for patients and professionals, and generate ideas on how to address these challenges.Results:In total, 895 patients participated: 49% female, mean age 61 years (±13.0), 25% lived alone, 18% had a migrant background, 6.6% did not speak Dutch at home and 51% had low levels of education. Figure 1 shows a heat map of identified health literacy profiles, displaying the score distribution per profile across nine health literacy domains. Figure 2 shows an excerpt of a patient vignette, describing challenges for a patient with profile number 9. The workshops were attended by 7 and 14 nurses and rheumatologists. Proposed solutions included health literacy communication training for professionals, developing and improving (visual) patient information materials, peer support for patients through patient associations or group consultations, a clear referral system for patients who need additional guidance by a nurse, social worker, lifestyle coach, pharmacist or family doctor, and more time with rheumatology nurses for target populations. Moreover, several system adaptations to the clinic, such as a central desk for all patient appointments, were proposed.Conclusion:This study identified several distinct health literacy profiles of patients with rheumatic conditions. Engaging with health professionals in co-design workshops led to numerous bottom-up ideas to improve care. Next steps include co-design workshops with patients, followed by prioritising and testing proposed interventions.References:[1]Heijmans M. et al. Health Literacy in the Netherlands. Utrecht: Nivel 2018[2]Batterham R. et al. BMC Public Health 2014, 14:694Disclosure of Interests:Mark Bakker: None declared, Polina Putrik: None declared, Jany Rademakers Speakers bureau: In March 2017, Prof. Dr. Rademakers was invited to speak about health literacy at the “Heuvellanddagen” Conference, hosted by Janssen-Cilag., Mart van de Laar Consultant of: Sanofi Genzyme, Speakers bureau: Sanofi Genzyme, Harald Vonkeman: None declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Hanneke Voorneveld: None declared, Sofia Ramiro Grant/research support from: MSD, Consultant of: Abbvie, Lilly, Novartis, Sanofi Genzyme, Speakers bureau: Lilly, MSD, Novartis, Maarten de Wit Grant/research support from: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Consultant of: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Speakers bureau: Dr. de Wit reports personal fees from Ely Lilly, 2019, personal fees from Celgene, 2019, personal fees from Pfizer, 2019, personal fees from Janssen-Cilag, 2017, outside the submitted work., Richard Osborne Consultant of: Prof. Osborne is a paid consultant for pharma in the field of influenza and related infectious diseases., Roy Batterham: None declared, Rachelle Buchbinder: None declared, Annelies Boonen Grant/research support from: AbbVie, Consultant of: Galapagos, Lilly (all paid to the department)

Background:Adherence is a serious problem in treatment of inflammatory diseases. To measure adherence, caps that record medication bottle openings may be superior to capsule counts (1). In the ongoing two-year GLORIA trial on the addition of low-dose (5 mg) prednisolone or placebo to standard of care in elderly patients (65+ years) with rheumatoid arthritis, adherence was measured in both ways during the whole trial.Objectives:To describe adherence patterns, and to compare adherence as assessed with adherence caps and with capsule counts in the GLORIA trial.Methods:The recorded adherence patterns of patients (blinded for treatment group) were classified according to descriptive categories. Overall adherence according to number of bottle openings was compared with adherence according to the capsule count. Good adherence was defined as 80%: i.e. for caps 80% of days one opening recorded, and for counts less than 20% of prescribed tablets returned at the subsequent visit. Each patient has a maximum of 8 periods of 90 days.Results:Trial inclusion has closed in 2018 at 452 patients; the current dataset contains adherence data of 385 patients. Mean number of recorded 90-day periods per patient was 4 (range 1-8). Based on capsule counts over all periods, 90% of the patients met the 80% threshold of adherence; based on cap data only 31% met this criterion.The four adherence patterns are shown in a calendar matrix, with yellow for zero, green for one and blue for ≥two openings on a day (Figure 1). Bottles were supposed to be opened once a day.Patients were categorized according to the opening pattern seen in at least 50% of assessed periods:32% non-use(26% stable use(≥80% of the days 1 opening);40% irregular use(different adherence patterns, in or between periods);2% weekly use(1 opening per week).Conclusion:In our trial of elderly rheumatoid arthritis patients, patients appeared to be mostly adherent according to conventional capsule counts. Results from adherence caps were highly discrepant with the capsule counts, with patterns suggesting patients did not use the bottle for daily dispensing, despite specific advice to do so.References:[1] El Alili M, Vrijens B, Demonceau J, Evers SM, Hiligsmann M. A scoping review of studies comparing the medication event monitoring system (MEMS) with alternative methods for measuring medication adherence. Br J Clin Pharmacol 2016;82:268-79.Acknowledgments:The GLORIA project is funded by the European Union’s Horizon 2020 research and innovation programme under the topic ‘’Personalizing Health and Care’’, grant agreement No 634886.Disclosure of Interests:Linda Hartman: None declared, Sabrina Paolino: None declared, Reinhard Bos: None declared, Daniela Opris-Belinski Speakers bureau: as declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Hanneke Griep-Wentink: None declared, Ruth Klaasen: None declared, Cornelia Allaart: None declared, George Bruyn: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Nuno Gomes: None declared, Rui Pinto: None declared, Thomas Klausch: None declared, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Maarten Boers: None declared

Background:Medication adherence in the GLORIA trial, among elderly patients with rheumatoid arthritis, is measured with caps that register openings of the medication bottle. At each study visit, one or two medication bottles with cap (kits) are dispensed, each containing 90 capsules. Multiple steps are needed to come to a workable dataset to describe adherence.Objectives:To describe the steps that are needed to come from raw data to a workable dataset to analyze adherence data that are recorded by electronic caps.Methods:The medication bottle contains a cap with the ability to register cap openings. The raw dataset from the caps consist of an excel file with one opening event per row, recorded as date and time. One cap yields approximately 90 rows. First, the kit numbers were matched to the corresponding patient numbers, that are recorded in another excel file. Instances where two kits were dispensed were recorded with two kit numbers in one cell and need to be copied to two cells with one kit number. Second, the VLOOKUP function was used to combine dates and kit numbers. One row now contains all openings from one kit. Then, the number of days between first opening and each next opening date was calculated. A range of 90 days was made to calculate how many times the bottle was opened on each day of the 90-days period. The results were color-coded to visualize instances of zero, one or ≥two openings on a day.Results:The colored calendar matrix (Figure 1) can now be used to categorize adherence patterns.Conclusion:A monitoring cap seems a simple instrument to measure adherence. However, multiple steps and a lot of time are needed to come to a workable dataset for the study of adherence patterns.Acknowledgments:The GLORIA project is funded by the European Union’s Horizon 2020 research and innovation programme under the topic ‟Personalizing Health and Care’’, grant agreement No 634886.Disclosure of Interests:Linda Hartman: None declared, Elisa Alessandri: None declared, Reinhard Bos: None declared, Daniela Opris-Belinski Speakers bureau: as declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Hanneke Griep-Wentink: None declared, Ruth Klaasen: None declared, Cornelia Allaart: None declared, George Bruyn: None declared, Hennie Raterman Grant/research support from: UCB, Consultant of: Abbvie, Amgen, Bristol-Myers Sqibb, Cellgene and Sanofi Genzyme, Marieke Voshaar Grant/research support from: part of phd research, Speakers bureau: conducting a workshop (Pfizer), Nuno Gomes: None declared, Rui Pinto: None declared, Thomas Klausch: None declared, WIllem Lems Grant/research support from: Pfizer, Consultant of: Lilly, Pfizer, Maarten Boers: None declared

Background:Psoriasis is an important feature of psoriatic arthritis (PsA). Psoriasis itself is known to have a significant impact on Health-related Quality of life (HRQoL)1, however its role within PsA is less well understood. In daily practice, assessment of psoriasis may not always be a priority for rheumatologists, having been trained to focus on articular involvement. In order to assess whether psoriasis deserves more attention from rheumatologists, the aim of this study is to evaluate the influence of psoriasis on HRQoL in early PsA patients.Objectives:To describe the evolution of psoriasis severity during the first year of follow up in patients with early PsA and to evaluate the impact of psoriasis severity on HRQoL.Methods:Real world data were used from the Dutch south west Psoriatic Arthritis cohort (DEPAR) study, consisting of newly diagnosed PsA patients included between July 2013 and February 2019. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI) and categorized in: no psoriasis (PASI 0), mild psoriasis (PASI12). Musculoskeletal disease severity was measured with the Disease Activity in PSoriatic Arthritis (DAPSA) score as contrast for psoriasis severity. DAPSA was categorized in: remission (REM[DAPSA≤4]), low disease activity (LDA[DAPSA≤14]), moderate disease activity (MDA[DAPSA≤28]) and high disease activity (HDA[DAPSA>28]).2General HRQoL was assesed with the Short-Form 36 (SF-36[Physical component scale and Mental component scale]). Skin-specific HRQoL was measured with the Skindex-17 (psychosocial scale and symptoms scale).Results:In total, 435 patients were included. Mean (sd) age was 49.7 (13.4) years and 53% (n=229) was male. Psoriasis severity does not fluctuate much over the course of the first year and the majority of patients had mild psoriasis (Figure 1). HRQoL worsened with increasing psoriasis severity, when measured by the Skindex17. This reduction in HRQoL was not seen when measured with the SF-36 (Figure 2).Figure 1.Psoriasis severity categories during the first year of follow up. No psoriasis (PASI 0), mild psoriasis (PASI12).Figure 2.A, B: Median Skindex17 psychosocial score and symptoms score per psoriasis severity category and DAPSA category at baseline. C,D: Mean SF36 Physical component scale (PCS) score and Mental component scale (MCS) score per psoriasis severity category and DAPSA category at baseline. No psoriasis (PASI 0), mild psoriasis (PASI12). REM (DAPSA28)Conclusion:In early PsA patients, psoriasis severity is mostly mild, but considerably impacts HRQoL when measured using a skin specific questionnaire. For optimal management of PsA patients, we therefore recommend rheumatologists to additionally acquire information on the degree of psoriatic involvement. In our opinion, this information is valuable for the adequate assessment of HRQoL.References:[1]Strober B, Greenberg JD, Karki C, Mason M, Guo N, Hur P, et al. Impact of psoriasis severity on patient-reported clinical symptoms, health-related quality of life and work productivity among US patients: real-world data from the Corrona Psoriasis Registry. BMJ Open. 2019;9(4):e027535.[2]Schoels MM, Aletaha D, Alasti F, Smolen JS. Disease activity in psoriatic arthritis (PsA): defining remission and treatment success using the DAPSA score. Ann Rheum Dis. 2016;75(5):811-8.Disclosure of Interests:Fazira R. Kasiem: None declared, Marc R Kok Grant/research support from: BMS and Novartis, Consultant of: Novartis and Galapagos, Ilja Tchetverikov: None declared, Kim Wervers: None declared, Johanna Hazes: None declared, Jolanda Luime: None declared, Marijn Vis Grant/research support from: Novartis, Pfizer – grant/research support, Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Novartis, Pfizer – consultant