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Objectives Anti-nucleocapsid (NC) antibodies are produced in response to SARS-CoV-2 infection. Therefore, they are well suited for the detection of a previous infection. Especially in the case of seroprevalence studies or during the evaluation of a novel in-vitro diagnostic test, samples have been stored at Methods The preanalytical impact of short-term storage (84 [58–98] days) on Results After short-term storage, the observed changes did not exceed the extent that could be explained by analytical variability. In contrast, results after long-term storage were approximately 20% higher and seemed to increase with storage duration. This effect was independent of the biobank from which the samples were obtained. Accordingly, the sensitivity increased from 92.6 to 95.3% (p=0.008). However, comparisons with data from Anti-Spike protein assays, where these deviations were not apparent, suggest that this deviation could also be explained by the analytical variability of the qualitative Anti-NC assay. Conclusions Results from anti-NC antibodies are stable during short-term storage at

BackgroundAn understanding vaccine-dependent effects on protective and sustained humoral immune response is crucial to planning future vaccination strategies against coronavirus disease 2019 (COVID-19).MethodsIn this multicenter, population-based, cohort study including 4601 individuals after primary vaccination against COVID-19 ≥ 4 months earlier we compared factors associated with residual antibody levels against severe acute respiratory syndrome coronavirus-2 receptor-binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1).ResultsOur main model including 3787 individuals (2 × BNT162b2, n = 2271; 2 × mRNA-1273, n = 251; 2 × ChAdOx1, n = 1265), predicted significantly lower levels of anti-RBD antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.7 binding antibody units per milliliter [BAU/mL]) compared with those vaccinated with BNT162b2 (1179.5 BAU/mL) or mRNA-1273 (2098.2 BAU/mL). Vaccine-dependent association of antibody levels was found for age with a significant predicted difference in BAU/ml per year for BNT162b2 (−21.5; 95% confidence interval [CI], −24.7 to −18.3) and no significant association for mRNA-1273 (−4.0; 95% CI, −20.0 to 12.1) or ChAdOx1 (1.7; 95% CI, .2 to 3.1). The predicted decrease over time since full immunization was highest in mRNA-1273 (−23.4; 95% CI, −31.4 to −15.4) compared with BNT162b2 (−5.9; 95% CI, −7 to −4.8).ConclusionsOur study revealed population-based evidence of vaccine-dependent effects of age and time since full immunization on humoral immune response. Findings underline the importance of individualized vaccine selection, especially in elderly individuals.

ObjectiveTo assess the humoral response to messenger RNA (mRNA) vaccine of patients with systemic autoimmune rheumatic disease (SARD) and the effect of immunosuppressive medication in a matched cohort study.MethodsPatients with SARD were enrolled and matched 1:1 for sex and age with healthy control (HC) subjects. Differences in humoral response to two doses of an mRNA vaccine in terms of seroconversion rate (SCR) and SARS-CoV-2 antibody level between the two groups and the impact of treatment within patients with SARD were assessed.ResultsWe enrolled 82 patients with SARD and 82 matched HC. SCR after the first dose was lower among the patient group than that of HC (65% compared with 100% in HC, pConclusionsPatients with SARD showed a good response after the second vaccination with an mRNA vaccine. However, the choice of immunosuppressive medication has a marked effect on both SCR and overall antibody level, and the number of different immunomodulatory therapies determines vaccination response.

BackgroundPolymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing agents are still needed.MethodsIn this double-blind, multi-centre phase 2/3 clinical trial, we randomly assigned 36 patients with new onset polymyalgia rheumatica from three centres to receive subcutaneous tocilizumab (162 mg per week) or placebo for 16 weeks (1:1 ratio). All patients received oral prednisone, tapered from 20 mg to 0 mg over 11 weeks.The primary endpoint was the proportion of patients in glucocorticoid-free remission at week 16; key secondary endpoints, including time to first relapse and cumulative glucocorticoid dose at weeks 16 and 24, were evaluated.ResultsFrom 20 November 2017 to 28 October 2019 39 patients were screened for eligibility; 19 patients received tocilizumab and 17 placebo. Glucocorticoid-free remission at week 16 was achieved in 12 out of 19 patients on tocilizumab (63.2%) and 2 out of 17 patients receiving placebo (11.8%, p=0.002), corresponding to an OR of 12.9 (95 % CI: 2.2 to 73.6) in favour of tocilizumab. Mean (±SD) time to first relapse was 130±13 and 82±11 days (p=0.007), respectively, and the median (IQR) cumulative glucocorticoid dose was 727 (721–842) mg and 935 (861–1244) mg (p=0.003), respectively. Serious adverse events were observed in five placebo patients and one tocilizumab patient.ConclusionIn patients with new onset polymyalgia rheumatica undergoing rapid glucocorticoid tapering, tocilizumab was superior to placebo regarding sustained glucocorticoid-free remission, time to relapse and cumulative glucocorticoid dose.Trial registration numberNCT03263715

ObjectivesTo assess the kinetics of humoral response after the first and second dose of messenger RNA (mRNA) vaccines in patients with inflammatory joint diseases compared with healthy controls (HC). To analyse factors influencing the quantity of the immune response.MethodsWe enrolled patients with rheumatoid arthritis (RA) and seronegative spondyloarthritis (SpA), excluding those receiving B-cell depleting therapies and assessed the humoral response to mRNA vaccines after the first and the second dose of the vaccine in terms of seroconversion rate and titre. We compared the results to a HC group and analysed the influence of therapies as well as other characteristics on the humoral response.ResultsSamples from 53 patients with RA, 46 patients with SpA and 169 healthy participants were analysed. Seroconversion rates after the first immunisation were only 54% in patients with inflammatory arthritis compared with 98% in the HC group. However, seroconversion rates were 100% in all groups after second immunisation. Patients developed reduced antibody titres after the first vaccination compared with HC, but there was no difference after the second dose. While disease modifying anti-rheumatic drug (DMARD) monotherapy did not affect antibody levels, seroconversion rates as well as titre levels were reduced in patients receiving a combination of DMARDs compared with HC.ConclusionsPatients with inflammatory joint diseases under DMARD therapy show impaired humoral responses to the first vaccine dose but excellent final responses to vaccination with mRNA vaccines. Therefore, the full course of two immunisations is necessary for efficient vaccination responses in patients with inflammatory arthritis under DMARD therapy.

ObjectivesEvidence suggests that B cell-depleting therapy with rituximab (RTX) affects humoral immune response after vaccination. It remains unclear whether RTX-treated patients can develop a humoral and T-cell-mediated immune response against SARS-CoV-2 after immunisation.MethodsPatients under RTX treatment (n=74) were vaccinated twice with either mRNA-1273 or BNT162b2. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein and neutralisation tests. SARS-CoV-2-specific T-cell responses were quantified by IFN-γ enzyme-linked immunosorbent spot assays. Prepandemic healthy individuals (n=5), as well as healthy individuals (n=10) vaccinated with BNT162b2, served as controls.ResultsAll healthy controls developed antibodies against the SARS-CoV-2 RBD of the spike protein, but only 39% of the patients under RTX treatment seroconverted. Antibodies against SARS-CoV-2 RBD significantly correlated with neutralising antibodies (τ=0.74, p+ peripheral B cells (n=36) did not develop specific antibodies, except for one patient. Circulating B cells correlated with the levels of antibodies (τ=0.4, pConclusionsThe data suggest that vaccination can induce SARS-CoV-2-specific antibodies in RTX-treated patients, once peripheral B cells at least partially repopulate. Moreover, SARS-CoV-2-specific T cells that evolved in more than half of the vaccinated patients may exert protective effects independent of humoral immune responses.

To investigate immunogenicity and safety of BNT162b2 booster vaccination with and without a tetravalent influenza vaccine.A prospective, open-label cohort study on immunogenicity and safety of COVID-19 booster vaccination with or without a tetravalent influenza vaccine was performed. 838 health care workers were included in the following study arms: BNT162b2 booster-only, influenza-vaccine-only or combination of both. Levels of antibodies against SARS-CoV-2 spike receptor binding domain (RBD), and haemagglutinine inhibition (HAI) tested for four different influenza strains (A(H1N1)pdm09, A(H3N2), B/Victoria, B/Yamagata) were measured at time of vaccination and four weeks later.After four weeks, median [IQR] anti-RBD antibody levels and relative change from baseline were higher in individuals who received BNTb162b2 booster vaccination only (absolute: 16,600 [10,980-24,360] vs. 12,630 [8,198-18,750] BAU/mL (p0·0001); relative increase: 49% [23·6-95·3] vs. 40% [21·9-80·6](p = 0·048); booster-only n=521 vs. combination-arm n=229 respectively). Results were confirmed after matching for sex, age, BMI, baseline antibody levels and vaccine compound received for primary immunization (absolute: 13,930 [10,610 - 22,760] vs. 12,520 [8,710 - 17,940]; p = 0·031); relative increase: 55·7% [27·8-98·5] vs. 42·2% [22·9-74·5]; p = 0·045). Adverse events were almost identical in the booster-only and the combination-arm, but numerically lower in the influenza arm (525/536[97·9] % vs.235/240 [97·9%] vs. 26/33 [78·8 %]).While no safety concerns occurred, our study provides evidence on reduced immunogenicity of a BNT162b2 booster vaccination in combination with a tetravalent influenza vaccine. Further studies investigating new influenza variants as well as potential differences vaccine effectiveness are needed.

Patients with rheumatoid arthritis (RA) have come to experience a tremendous increase in therapeutic options with disease-modifying antirheumatic drugs (DMARDs).1 After decades of dissatisfying drug therapy results with conventional synthetic DMARDs (csDMARDs) only, the introduction of the first tumor necrosis factor inhibitors in the late 1990s has revolutionized RA treatment.2.

ObjectivesA third COVID-19 vaccination is recommended for immunosuppressed patients. However, data on immunogenicity and safety of a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are sparse and therefore addressed within this clinical trial.Methods60 immunosuppressed patients and 48 healthy controls (HCs) received a third vaccination with an mRNA vaccine. The primary endpoint was defined as the presence of antibody levels against the receptor-binding domain (RBD)>1500 BAU/mL in patients with IMIDs versus HCs. Further endpoints included differences in neutralising antibodies and cellular immune responses after the third vaccination. Reactogenicity was recorded for 7 days, and safety was evaluated until week 4.ResultsRate of individuals with anti-RBD antibodies>1500 BAU/mL was not significantly different after the third vaccination between patients with IMIDs and HCs (91% vs 100% p=0.101). Anti-RBD and neutralising antibody levels were significantly lower in patients with IMIDs after the third vaccination than in HCs (p=0.002 and p=0.016, respectively). In contrast, fold increase in antibody levels between week 0 and 4 was higher in patients with IMIDs. Treatment with biological (b) disease-modifying anti-rheumatic drugs (DMARD) or combination of bDMARDs and conventional synthetic DMARDs was associated with reduced antibody levels. Enhanced cellular immune response to wild type and Omicron peptide stimulation was observed after the third vaccination. No serious adverse event was attributed to the third vaccination.ConclusionOur clinical trial data support the immunogenicity and safety of a third COVID-19 vaccination in patients with IMIDs. However, effects of DMARD therapy on immunogenicity should be considered.Trial registration numberEudraCT No: 2021-002693-10.

Understanding vaccine-dependent effects on protective and sustained humoral immune response are crucial to plan further vaccination strategies against COVID-19. Population-based data comparing different vaccination strategies are lacking.This multicenter, population-based cohort study included 4,601 individuals ≥18 years of age after primary vaccination against COVID-19 at least four months ago (full immunization). We compared factors associated with residual antibody levels against SARS-CoV-2 receptor binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 [ChAdOx1]).Our main model including 3,787 individuals (2xBNT162b2 n = 2,271, 2xmRNA-1273 n = 251, 2xChAdOx1 n = 1,265) predicted significantly lower levels of anti-RBD-antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.7 BAU/ml) compared to those vaccinated with BNT162b2 (1179.5 BAU/ml) or mRNA-1273 (2098.2 BAU/ml). Vaccine-dependent association of antibody levels was found for age with a significant predicted difference in BAU/ml per year for BNT162b2 (-21.5 [95%CI -24.7 to -18.3]) and no significant association for mRNA-1273 (-4.0 [95%CI -20.0 to 12.1]) or ChAdOx1 (1.7 [95%CI 0.2 to 3.1]). The predicted decrease over time since full immunization was highest in mRNA-1273 (-23.4 [95%CI -31.4 to -15.4]) compared to BNT162b2 -5.9 [95%CI -7 to -4.8]). Higher antibody levels were observed for individuals with systemic adverse events upon vaccination and current smoking (BNT162b2), for days between first and second vaccination (BNT162b2 and ChAdOx1) and for absence of comorbidities (all).Our study revealed population-based evidence of vaccine-dependent effects of age and time since full immunization on humoral immune response. Findings underline the importance of an individualized vaccine selection, especially in elderly individuals.

ObjectivesPatients under rituximab therapy are at high risk for a severe COVID-19 disease course. Humoral immune responses to SARS-CoV-2 vaccination are vastly diminished in B-cell-depleted patients, even after a third vaccine dose. However, it remains unclear whether these patients benefit from a fourth vaccination and whether continued rituximab therapy affects antibody development.MethodsIn this open-label extension trial, 37 rituximab-treated patients who received a third dose with either a vector or mRNA-based vaccine were vaccinated a fourth time with an mRNA-based vaccine (mRNA-1273 or BNT162b2). Key endpoints included the humoral and cellular immune response as well as safety after a fourth vaccination.ResultsThe number of patients who seroconverted increased from 12/36 (33%) to 21/36 (58%) following the fourth COVID-19 vaccination. In patients with detectable antibodies to the spike protein’s receptor-binding domain (median: 8.0 binding antibody units (BAU)/mL (quartiles: 0.4; 13.8)), elevated levels were observed after the fourth vaccination (134.0 BAU/mL (quartiles: 25.5; 1026.0)). Seroconversion and antibody increase were strongly diminished in patients who received rituximab treatment between the third and the fourth vaccination. The cellular immune response declined 12 weeks after the third vaccination, but could only be slightly enhanced by a fourth vaccination. No unexpected safety signals were detected, one serious adverse event not related to vaccination occurred.ConclusionsA fourth vaccine dose is immunogenic in a fraction of rituximab-treated patients. Continuation of rituximab treatment reduced humoral immune response, suggesting that rituximab affects a second booster vaccination. It might therefore be considered to postpone rituximab treatment in clinically stable patients.Trial registration number2021-002348-57.

Abstract: Systemic Lupus Erythematosus (SLE) is an autoimmune disease, which affects a wide range of organs with variable clinical features. Involvement of the nervous system is a challenging and multifaceted manifestation of the disease, presenting with a broad range of symptoms. Neuropsychiatric lupus (NPSLE) encompasses seven syndromes of the peripheral and 12 of the central nervous system, associated with a high disease burden. Despite advances in the management of SLE, NP manifestations still pose a challenge to clinicians. First, diagnosis and attribution to SLE is difficult due to the lack of specific biomarkers or imaging modalities. Second, therapeutic options are limited, and evidence is mainly based on case reports and expert consensus, as clinical trials are sparse. Moreover, no validated outcome measure on disease activity exists. Current recommendations for treatment include supportive as well as immunosuppressive medication, depending on the type and severity of manifestations. As NPSLE manifestations are increasingly recognized, a broader spectrum of therapeutic options can be expected.

ObjectivesSARS‐CoV‐2-induced COVID-19 has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination.MethodsIn this blinded randomised clinical trial, we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford–AstraZeneca). Patients were stratified according to the presence of peripheral B cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week 4. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at week 1 and week 4.ResultsSeroconversion rates at week 4 were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccines (p=0.6). Overall, 27% of patients seroconverted; specific T cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. 3/37 (8%) of patients without and 12/18 (67%) of the patients with detectable peripheral B cells seroconverted. No serious adverse events, related to immunisation, were observed.ConclusionsThis enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

ObjectivesIdentification of trajectories of radiographic damage in rheumatoid arthritis (RA) by clustering patients according to the shape of their curve of Sharp-van der Heijde scores (SHSs) over time. Developing models to predict their progression cluster from baseline characteristics.MethodsPatient-level data over a 2-year period from five large randomised controlled trials on tumour necrosis factor inhibitors in RA were used. SHSs were clustered in a shape-respecting manner to identify distinct clusters of radiographic progression. Characteristics of patients within different progression clusters were compared at baseline and over time. Logistic regression models were developed to predict trajectory of radiographic progression using information at baseline.ResultsIn total, 1887 patients with 7738 X-rays were used for cluster analyses. We identified four distinct clusters with characteristic shapes of radiographic progression: one with a stable SHS over the whole 2-year period (C0/lowChange; 86%); one with relentless progression (C1/rise; 5.8%); one with decreasing SHS (C2/improvement; 6.9%); one going up and down (C3/bothWays; 1.4%) of the SHS. Robustness of clusters were confirmed using different clustering methods. Regression models identified disease duration, baseline C-reactive protein (CRP) and SHS and treatment status as predictors for cluster assignment.ConclusionsWe were able to identify and partly characterise four different clusters of radiographic progression over time in patients with RA, most remarkably one with relentless progression and another one with amelioration of joint damage over time, suggesting the existence of distinct patterns of joint damage accrual in RA.

Aims:Line immune-assays (LIA) for the detection of myositis-specific antibodies (MSA) are used widely for characterization of idiopathic inflammatory myopathies (IIM). Their current use and significance for the diagnosis of IIM remains unclear.Methods:In this retrospective analysis, we retrieved clinical diagnoses of patients tested for MSA and myositis-associated antibodies (MAA) Jo-1, Mi-2α, Mi-2β, TIF1γ, SRP, MDA-5, NXP-2, SAE, PL-7, PL-12, EJ, OJ, PM-Scl100, PM-Scl75 and Ku. We calculated clinical specificity, clinical sensitivity, negative- and positive predictive values (PPV) as well as positive and negative likelihood ratios.Results:In total, we analyzed 3167 samples. After exclusion of repeated measurements and patients with insufficient clinical information, data of 1118 patients were available for analysis. A total of 242 patients tested positive for at least one antibody, of which 45 patients had a diagnosis of IIM; 25 IIM patients were negative for all MSA/MAA. Clinical specificity of MSA/MAA for the diagnosis of IIM ranged between 94.2% and 99.9%. Clinical sensitivity and PPV across all antibodies tested ranged from 0.0% to 12.9% and 0.0% to 72.7%, respectively.Conclusion:In clinical practice MSA/MAA are used widely for diagnostic work-up of IIM, resulting in a low pre-test probability. Clinicians should be aware that PPVs for most MSA/MAA are low.

Rheumatoid arthritis (RA) affects approximately 1% of the adult population. It is currently considered a chronic disease for which there is no cure, but remission has become an achievable goal with optimal treatment. Both disability and enormous cost are functions of the disease over time. It is therefore crucial to treat RA early and persistently until remission is present. The challenge of treatment of early RA is not the lack of effective medicine, but rather the ethical and economic considerations related to risk-benefit and cost-benefit. Overtreating patients with disease-modifying antirheumatic drugs (DMARDs) is often feared, but the potential undertreatment of patients with RA can have accelerated structural consequences. This chapter covers diagnosis of RA, from the initial evaluation of patients with new-onset arthritis to important differential diagnoses. Critical diagnostic features are explained, and the 2010 European League Against Rheumatism (EULAR) classification criteria are described and rationalized. The importance of distinction between classification and diagnosis is highlighted.

Objective In 2011 an ACR/EULAR collaboration developed new remission definitions for RA. In the present study, we evaluated the prevalence and predictive validity of these new ACR/EULAR remission criteria in 4 different European early rheumatoid arthritis cohorts. Method Data from a tot al of 722 patients with early RA were analysed. Presence of remission at 6 months, as defined by one of the 4 proposed ACR/EULAR remission definitions was used to predict good functional and radiological outcome between 1 and 2 years of follow-up. Results Remission rates at 6 months ranged from 2-17% (Boolean definition) between the four cohorts. The level of HAQ and radiological damage varied between cohorts. Patients in remission at 6 months have an increased likelihood of long-term good outcome in terms of HAQ stability, but not radiographic stability. The performance of the practice definitions of remission was highly similar to the trial definitions. CRP status seems to add little information to the classification of remission in early RA. Conclusion In clinical practice, a minority of patients with early RA achieves remission in the first 6 months of treatment. Remission at 6 months is predictive for good HAQ outcome between year 1 and 2 after inclusion, but not radiographic stability.

Objective To estimate prevalence and incidence of cardiovascular (CV) risk factors of hypertension, diabetes mellitus, hyperlipidemia, and obesity in patients with rheumatoid arthritis (RA), psoriasis, or psoriatic arthritis (PsA). Methods Patients with RA, psoriasis, or PsA were identified based on medical and pharmacy claims from the MarketScan claims databases from January 1, 2002 through December 31, 2014. Primary outcomes included age- and sex-standardized prevalence of CV risk factors during the 12 months preceding diagnosis date and incidence rates per 1,000 patient-years, with 95% confidence intervals (95% CIs) during followup. Results Prevalence for RA, psoriasis, and PsA cohorts for hypertension was 18.6% (95% CI 18.3–18.8), 16.6% (95% CI 16.3–17.0), and 19.9% (95% CI 19.4–20.4), respectively; for diabetes mellitus 6.2% (95% CI 6.1–6.4), 6.3% (95% CI 6.0–6.5), and 7.8% (95% CI 7.4–8.2); for hyperlipidemia 9.9% (95% CI 9.7–10.1), 10.4% (95% CI 10.2–10.7), and 11.6% (95% CI 11.2–12.0); and for obesity 4.4% (95% CI 4.2–4.6), 3.8% (95% CI 3.5–4.0), and 6.0% (95% CI 5.6–6.5). Incidence rates per 1,000 patient-years during followup for RA, psoriasis, and PsA cohorts, respectively, for hypertension were 74.0 (95% CI 72.5–75.5), 68.2 (95% CI 65.9–70.4), and 79.8 (95% CI 76.3–83.3); for diabetes mellitus 10.6 (95% CI 10.1–11.1), 13.0 (95% CI 12.1–13.8), and 14.7 (95% CI 13.5–16.0); for hyperlipidemia 40.3 (95% CI 39.4–41.3), 47.1 (95% CI 45.4–48.7), and 52.0 (95% CI 49.6–54.3); and for obesity 24.4 (95% CI 23.4–25.4), 26.4 (95% CI 25.0–27.8), and 32.9 (95% CI 30.6–35.2). Conclusion Patients with RA, psoriasis, and PsA have high prevalence and incidence of CV risk factors, suggesting the need for risk factor monitoring of these patients.

Objective Treat-to-target (TTT) is an accepted paradigm for the management of rheumatoid arthritis (RA), but some evidence suggests poor adherence. The purpose of this study was to test the effects of a group-based multisite improvement learning collaborative on adherence to TTT. Methods We conducted a cluster-randomized quality-improvement trial with waitlist control across 11 rheumatology sites in the US. The intervention entailed a 9-month group-based learning collaborative that incorporated rapid-cycle improvement methods. A composite TTT implementation score was calculated as the percentage of 4 required items documented in the visit notes for each patient at 2 time points, as evaluated by trained staff. The mean change in the implementation score for TTT across all patients for the intervention sites was compared with that for the control sites after accounting for intracluster correlation using linear mixed models. Results Five sites with a total of 23 participating rheumatology providers were randomized to intervention and 6 sites with 23 participating rheumatology providers were randomized to the waitlist control. The intervention included 320 patients, and the control included 321 patients. At baseline, the mean TTT implementation score was 11% in both arms; after the 9-month intervention, the mean TTT implementation score was 57% in the intervention group and 25% in the control group (change in score of 46% for intervention and 14% for control; P = 0.004). We did not observe excessive use of resources or excessive occurrence of adverse events in the intervention arm. Conclusion A learning collaborative resulted in substantial improvements in adherence to TTT for the management of RA. This study supports the use of an educational collaborative to improve quality.

Objective To quantify differences and determine the factors contributing to the difference in patient global assessment of rheumatoid arthritis (RA) disease activity (PtGA) between RA patients with multiple morbidities (RA-MM) and those with RA only. Methods We compared the PtGA between RA-MM patients and those with RA only, followed up in a longitudinal cohort (n = 1,040). In analyses performed on RA-MM patients (n = 575) and those with RA only (matched for swollen joint count, tender joint count, evaluator global assessment, and disease duration), the mean difference in PtGA (ΔPtGA) between the 2 groups was assessed. The contribution of patient characteristics to the explained variation of ΔPtGA in the matched cohort was calculated as semipartial R2 and summarized as the percentage of the total R2 in linear regression models. Results RA-MM patients reported higher (or worse) PtGA, with an increased PtGA associated with more morbidities (P for linear trend

Comorbidities are highly prevalent in patients with rheumatoid arthritis (RA), yet clinical care for such patients is often of inferior quality, even in rheumatology clinics. Suggestions for good clinical practice interventions from an expert panel aim to improve the quality of care for patients with RA who have associated comorbidities.

Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care.

Background The introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) revolutionized the treatment of rheumatoid arthritis (RA) and made remission (REM) or low disease activity (LDA) a realistic goal for most patients. It was shown that the discontinuation of bDMARDs in patients in REM or LDA is feasible (1,2) and that the physician’s opinion plays an important part in the decision to discontinue (3). However, there is no reliable way of identifying patients who would benefit from bDMARD discontinuation after reaching REM or LDA. Objectives To identify the preference of rheumatologists regarding different parameters while discontinuing a bDMARD in their patients. Methods A systematic literature review was conducted with the aim of identifying predictors of successful bDMARD discontinuation in RA patients in REM or LDA. These predictors were then adapted into general parameters and sorted into different categories: patient demographics (n=6), disease activity (n=6), patient reported outcomes (n=6), treatment related parameters (n=5), laboratory parameters (n=6) and imaging parameter (n=5). Those parameters were reviewed by an expert panel and then distributed to rheumatologists in Europe. Rheumatologists were asked to state whether they find the presented parameter important to support their decision to discontinue bDMARD therapy or not. They also had the opportunity to state parameters they consider important. Results 313 rheumatologists from 29 different European countries responded. Most of the participants have been practicing for 10 to 20 years and see 10 to 25 RA patients per week. The majority of the parameters were considered important by the participants, with 19 out of the 34 presented parameters being considered important by ≥ 70%. The most commonly considered parameters were (percentage of participants who considered the parameter important): Time in REM or LDA (99%), c-reactive protein (96%), swollen joint count (93%), concomitant conventional synthetic DMARD therapy (93%) and disease activity score – 28 joints (90%). The least commonly considered parameters were: simplified disease activity score (48%), gray scale positivity (47%), rheumatoid factor (41%), smoking status (35%), gender (13%), interleukin-6 (9%) and shared epitope (8%). An overview of responses is given in figure 1 and figure 2. The most frequently mentioned parameter in the comments was the patient’s opinion on discontinuation (n=28). Conclusion Rheumatologists appear to be very diligent in the things they consider when discontinuing bDMARDs in their patients. 19 of the 34 parameters have been considered important by ≥ 70% of participants. This might be because the presented parameters were based on predictors of successful discontinuation. This data gives insight into the current state of bDMARD discontinuation and can be used in further research to help identifying patients who would benefit from bDMARD discontinuation. References [1] van den Broek M, Klarenbeek NB, Dirven L, van Schaardenburg D, Hulsmans HM, Kerstens PJ, et al. Discontinuation of infliximab and potential predictors of persistent low disease activity in patients with early rheumatoid arthritis and disease activity score-steered therapy: subanalysis of the BeSt study. Annals of the rheumatic diseases. 2011;70(8):1389-94. [2] Tanaka Y, Yamanaka H, Ishiguro N, Miyasaka N, Kawana K, Kimura J, et al. Low disease activity for up to 3 years after adalimumab discontinuation in patients with early rheumatoid arthritis: 2-year results of the HOPEFUL-3 Study. Arthritis Res Ther. 2017;19(1):56. [3] Strand V, Miller P, Williams SA, Saunders K, Grant S, Kremer J. Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry. Rheumatol Ther. 2017;4(2):489-502. Disclosure of Interests Lukas Schlager: None declared, Michaela Loiskandl: None declared, Daniel Aletaha Grant/research support from: AbbVie, Bristol-Myers Squibb, and MSD, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medac, Merck, MSD, Pfizer Inc, Roche, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Medac, Merck, MSD, Pfizer Inc, Roche, and UCB, Helga Radner: None declared

Objectives To examine how comorbidities cluster in axial spondyloarthritis (axSpA) and whether these clusters are associated with quality of life, global health and other outcome measures. Methods We conducted a cross-sectional study of consecutive patients meeting ASAS criteria for axSpA in Liverpool, UK. Outcome measures included quality of life (EQ5D), global health and disease activity (BASDAI). We used hierarchical cluster analysis to group patients according to 38 pre-specified comorbidities. In multivariable linear models, the associations between distinct comorbidity clusters and each outcome measure were compared, using axSpA patients with no comorbidities as the reference group. Analyses were adjusted for age, gender, symptom duration, BMI, deprivation, NSAID-use and smoking. Results We studied 419 patients (69% male, mean age 46 years). 255 patients (61%) had at least one comorbidity, among whom the median number was 1 (range 1–6). Common comorbidities were hypertension (19%) and depression (16%). Of 15 clusters identified, the most prevalent clusters were hypertension-coronary heart disease and depression-anxiety. Compared with patients with no comorbidities, the fibromyalgia-irritable bowel syndrome cluster was associated with adverse patient-reported outcome measures; these patients reported 1.5-unit poorer global health (95%CI 0.01, 2.9), reduced quality of life (0.25-unit lower EQ5D; 95%CI −0.37, −0.12) and 1.8-unit higher BASDAI (95% CI 0.4, 3.3). Similar effect estimates were found for patients in the depression-anxiety cluster. Conclusion Comorbidity is common among axSpA patients. The two most common comorbidities were hypertension and depression. Patients in the depression-anxiety and fibromyalgia-IBS clusters reported poorer health and increased axSpA severity.

Objective To systematically review possible predictors of successful discontinuation of biologic or targeted synthetic DMARDs (b/tsDMARDs) in RA patients in remission or low disease activity. Methods MEDLINE database and Cochrane Library were scanned for studies that discontinued b/tsDMARDs in remission/low disease activity and searched for predictors of successful discontinuation. Additionally, EULAR and ACR meeting abstracts were hand searched. Results Thirty-four studies with a total of 5724 patients were included. Predictors of successful b/tsDMARD discontinuation were (number of studies): low disease activity (n = 13), better physical function (n = 6), low or absence of rheumatoid factor (n = 5) or ACPA (n = 3), low levels of CRP (n = 3) or ESR (n = 3), shorter disease duration (n = 3), low signals of disease activity by ultrasound (n = 3). Only one study with high risk of bias was identified on tsDMARD discontinuation. Conclusion Several predictors of successful bDMARD discontinuation were identified. Although studies are heterogeneous, these predictors may inform clinical decision making in patients who are considered for a potential bDMARD discontinuation.

Background:Joint damage is a defining feature of rheumatoid arthritis (RA), a major driver of functional impairment and of reduction of quality of life. Many factors are associated with damage accrual however, the course of structural damage of individual patients over time and factors associated with such trajectories have not been investigated.Objectives:Identification of trajectories of radiographic damage in RA by clustering patients according to the shape of their curve of Sharp-van der Heijde scores (SHS) over time. Developing models to predict their progression cluster from baseline characteristics.Methods:Patient-level data over a two-year period from 5 large randomized controlled trials on TNF-inhibitors in RA (ERA, PREMIER, TEMPO, GO-BEFORE and GO-FORWARD) were used. SHSs were clustered in a shape-respecting manner to identify distinct clusters of radiographic progression. Characteristics of patients within different progression clusters were compared at baseline and over time. Logistic regression models were developed to predict trajectory of radiographic progression using information at baseline.Results:In total 1887 patients with 7738 x-rays were used for cluster analyses. We identified 4 distinct clusters with characteristic shapes of radiographic progression: one with a stable SHS over the whole 2-year period (C0/lowChange; 86%); one with relentless progression (C1/rise; 5.8%); one with decreasing SHS (C2/improvement; 6.9%); and one going up and down (C3/bothWays; 1.4%) of the SHS. Robustness of clusters and shapes of progression over time were confirmed using different clustering methods and cut-offs to define radiographic progression (Figure 1). Regression models identified disease duration, baseline CRP and SHS and treatment status as predictors for cluster assignment (Table 1), showing good performance (PCC 87.5%; Nagelkerke r2 0.36).Conclusion:We were able to identify 4 different clusters of radiographic progression over time in patients with RA, most remarkably one with relentless progression and another one with amelioration of joint damage over time, suggesting the existence of distinct patterns of joint damage accrual in RA. The nature of the identified trajectories is mostly explained by inflammatory load, disease duration and especially type of treatment.Figure 1.Representations of the major three clusters of radiologic progression curves. (A) shows the curves of all patients with a SHS-range >= 10, colored by their cluster. Values between visits were linearly interpolated. Big dotted line is the median of particular cluster, thinner lines represent single patient values. Cluster C0 /lowChange are patients without enough variation in SHS to be seen as a curve, therefor not shown in the diagrams.Table 1.Simple logistic regression models to predict assignment to clusters of radiologic progression using information at baseline. Variables entered but not selected by a stepwise approach were: rheumatoid factor, age, gender, tender joint count;c0/low change vs:C1/rise ClusterC2/improve ClusterparametersOR95%CIOR95%CIX-ray Score1.021.01-1.031.031.02-1.03CRP (mg/dl)1.121.07-1.160.980.90-1.07Duration (years)0.870.80-0.951.091.05-1.12TreatmentCombinationREFREFREFREFcsDMARD4.982.88-8.630.050.01-0.23bDMARD Mono2.281.29-4.040.640.38-1.08Disclosure of Interests:Stephan Blüml Speakers bureau: Novartis, MSD, Abvie, Pfizer, Consultant of: MSD, Lilly, Novartis, Alexander Platzer: None declared, Farideh Alasti: None declared, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Consultant of: Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB., Consultant of: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB., Grant/research support from: Dr Smolen received grants to his institution from Abbvie, AstraZeneca, Janssen, Lilly, Merck Sharpe & Dohme, Pfizer, and Roche, Helga Radner: None declared

Background/purpose Treat-to-target (TTT) is a recommended strategy in the management of rheumatoid arthritis (RA), but various data sources suggest that its uptake in routine care in the US is suboptimal. Herein, we describe the design of a randomized controlled trial of a Learning Collaborative to facilitate implementation of TTT. Methods We recruited 11 rheumatology sites from across the US and randomized them into the following two groups: one received the Learning Collaborative intervention in Phase 1 (month 1–9) and the second formed a wait-list control group to receive the intervention in Phase 2 (months 10–18). The Learning Collaborative intervention was designed using the Model for Improvement, consisting of a Change Package with corresponding principles and action phases. Phase 1 intervention practices had nine learning sessions, collaborated using a web-based tool, and shared results of plan–do–study–act cycles and monthly improvement metrics collected at each practice. The wait-list control group sites had no intervention during Phase 1. The primary trial outcome is the implementation of TTT as measured by chart review, comparing the differences from baseline to end of Phase 1, between intervention and control sites. Results All intervention sites remained engaged in the Learning Collaborative throughout Phase 1, with a total of 38 providers participating. The primary trial outcome measures are currently being collected by the study team through medical record review. Conclusions If the Learning Collaborative is an effective means for improving implementation of TTT, this strategy could serve as a way of implementing disseminating TTT more widely.

Personalised medicine, new discoveries and studies on rare exposures or outcomes require large samples that are increasingly difficult for any single investigator to obtain. Collaborative work is limited by heterogeneities, both what is being collected and how it is defined. To develop a core set for data collection in rheumatoid arthritis (RA) research which (1) allows harmonisation of data collection in future observational studies, (2) acts as a common data model against which existing databases can be mapped and (3) serves as a template for standardised data collection in routine clinical practice to support generation of research-quality data. A multistep, international multistakeholder consensus process was carried out involving voting via online surveys and two face-to-face meetings. A core set of 21 items (‘what to collect’) and their instruments (‘how to collect’) was agreed: age, gender, disease duration, diagnosis of RA, body mass index, smoking, swollen/tender joints, patient/evaluator global, pain, quality of life, function, composite scores, acute phase reactants, serology, structural damage, treatment and comorbidities. The core set should facilitate collaborative research, allow for comparisons across studies and harmonise future data from clinical practice via electronic medical record systems.

In patients with rheumatic conditions, high prevalence of comorbid conditions can be observed. The increasing burden of being afflicted by more than one disease, so called multimorbidity, has a negative impact on many different outcomes such as functional ability, health-related quality of life or mortality. Owing to possible interaction of different diseases and therapeutic agents, and increased vulnerability, it requires a complex strategy when treating multimorbid patients. Most common comorbidities in patients with rheumatic conditions are cardiovascular disease, depression, osteoporosis, and gastrointestinal disease. Screening and preventing comorbidities is essential when treating patients with rheumatic conditions. By understanding and implementing the concept of multimorbidity, quality of care and clinical outcomes can be improved.

To develop a multimorbidity index (MMI) based on health-related quality of life (HRQol).The index was developed in an observational RA cohort. In all, 40 morbidities recommended as core were identified using ICD-9 codes. MMIs of two types were calculated: one by enumerating morbidities (MMI.count) and the other by weighting morbidities based on their association with HRQol as assessed by EQ-5D in multiple linear regression analysis (using β-coefficients; MMI.weight). MMIs were compared to the Charlson comorbidity index (CCI) and externally validated in an international RA cohort (COMORA Study).In all, 544 out of 876 patients were multimorbid. MMI.count was in the range 1-16 (median = 2) and MMI.weight in the range 0-38 (median = 1). Both indices were more strongly associated with EQ-5D than CCI (Spearman: MMI.count = -0.20, MMI.weight = -0.26, and CCI = -0.10; p0.01). R(2) obtained by linear regression using EQ-5D as a dependent variable and various indices as independent variables, adjusted for age and gender, was the highest for MMI (R(2): MMI.count = 0.05, MMI.weight = 0.11, and CCI = 0.02). When accounting for clinical disease activity index (CDAI) R(2) increased: MMI.count = 0.18, MMI.weight = 0.22, and CCI = 0.17, still showing higher values of MMI compared with CCI. External validation in different RA cohorts (COMORA, n = 3864) showed good performance of both indices (linear regression including age, gender, and disease activity R(2) = 0.30 for both MMIs).In our cohort, MMI based on EQ-5D performed better than did CCI. Findings were reproducible in another large RA cohort. Not much improvement was gained by weighting; therefore a simple counted index could be useful to control for the effect of multimorbidity on patient's overall well-being.

Objective To identify overlaps, discrepancies, and perceived utility of the currently collected data in European clinical rheumatoid arthritis (RA) cohorts and registers. Heterogeneity of data collection and data representation may limit comparative and collaborative RA research. Defining data standards is important and should be informed by which data items are currently collected and their perceived utility in scientific analyses. Methods A web survey was sent to 27 European RA registers/clinical cohorts, requesting information on which specific data items were collected, how and with what frequency they were collected, how often data were missing, and if the items collected were regarded as useful for research. Results Twenty-five of 27 contacted RA cohorts/registers from 16 different European countries, totaling 189,633 patients (range 130–55,000), completed the survey. Items collected by the majority of data sources and used frequently for research were composite disease activity scores, acute-phase reactants, joint counts, information on RA-specific treatments, physical function, and patient global assessment of disease activity. Many of the collected items showed large variability in terms of measurement and time point of collection. Among all items collected, disease activity, RA treatment, and joint counts were regarded as the most important. When not collected, smoking, imaging, and comorbidities were the top-ranked variables felt to have been worth collecting. Conclusion Even though certain items are regularly collected, the mode of data collection and the data definition are heterogeneous. Harmonization of data collection across European clinical RA data sources is therefore pivotal for future collaborative studies.

Objective. When treating RA patients, remission (REM) or at least low disease activity (LDA) is the ultimate therapeutic goal. The aim of this study was to assess the impact of multimorbidity on achieving REM or LDA. Methods. In a prospective RA cohort, we identified patients initiating any DMARD with follow-up data 1 year after. Treatment effects were measured using the clinical disease activity index (CDAI) and the modified health assessment questionnaire (MHAQ); multimorbidity status was assessed using a counted multimorbidity index (cMMI). The proportion of patients reaching REM or LDA 1 year after DMARD commencement with respect to the cMMI was evaluated. In regression models, we calculated the odds ratio of achieving REM or LDA, and predicted CDAI and MHAQ 1 year after DMARD commencement for various levels of cMMI, adjusting for age, sex, disease duration, serostatus, disease activity at DMARD commencement, number of previous DMARDs, and type of DMARD, steroid and NSAID use. Results. A total of 815 patients started DMARDs; 414 were on the same DMARD after 1 year. The proportion of these patients achieving REM or LDA after 1 year was significantly lower in the patients with higher cMMI, following a linear trend (P

Objective.To describe the treatment profile of multimorbid patients with rheumatoid arthritis (RA) in contrast to patients with RA only.Methods.COMORA (Comorbidities in Rheumatoid Arthritis) is a cross-sectional, international study assessing morbidities, outcomes, and treatment of patients with RA. Patients were grouped according to their multimorbidity profile assessed by a counted multimorbidity index (cMMI). Treatment for RA was categorized as use of biologic disease-modifying antirheumatic drugs (bDMARD), in particular tumor necrosis factor inhibitors (TNFi), synthetic DMARD (sDMARD) use only, nonsteroidal antiinflammatory drug (NSAID) use, and corticosteroid use. Logistic regression models were performed to determine the OR of bDMARD, TNFi, sDMARD, NSAID, or corticosteroid use based on a patient’s cMMI and global region after adjusting for age, disease activity, disease duration, educational level, and previous DMARD therapy.Results.Out of 3920 patients, 32.7% received bDMARD; 59.9% sDMARD only, 51.1% used concomitant NSAID, and 54.8% used corticosteroid. Regional differences were observed with the most frequent use of bDMARD in the United States (46.5%) and lowest in North Africa (9%). After adjusting for confounders in logistic regression, the OR for bDMARD use was reduced for each additional morbidity (OR 0.89, 95% CI 0.83–0.96). Similar results were found for TNFi (OR 0.91, 95% CI 0.84–0.99), whereas the OR for use of sDMARD was increased (1.13, 95% CI 1.05–1.22). No significant change of OR was found for NSAID or corticosteroid use.Conclusion.In this study, the odds of bDMARD use decreases 11% for each additional chronic morbid condition after adjustment for regional differences, disease activity, and other covariates.

Current recommendations advocate treatment with disease-modifying anti-rheumatic drugs (DMARDs) in all patients with active rheumatoid arthritis (RA). We analyzed short-term disease outcome in patients according to the consistency of DMARD use in a clinical rheumatology cohort.Patients in an RA registry (n = 617) were studied for DMARD use at semi-annual study time points during the first 18 months of follow-up and were divided into 4 groups according to the number of study time points with any DMARD use [0-1 study time points (n = 31), 2 study time points (n = 24), 3 study time points (n = 77), and 4 study time points (n = 485)]. The primary outcome analyses were performed at 24 months and included Disease Activity Score 28 (DAS28-CRP), modified Health Assessment Questionnaire (MHAQ) change, Short Form Health Survey-12 physical and mental summary scores (SF-12 PCS, SF-12 MCS), EuroQol 5-Dimensional health index (EQ-5D), and radiographic progression. Unadjusted, adjusted, and analyses stratified for seropositivity and disease activity were performed. A secondary analysis investigated 36-month outcomes.No significant 24-month outcome differences could be found between the DMARD use categories. For seropositive patients, there was evidence of a linear trend for SF-12 PCS (p = 0.02) and EQ-5D (p = 0.01) with worse outcomes for inconsistent DMARD users. At 36 months, there was a linear trend for higher DAS28-CRP scores for inconsistent users (p0.01).Overall, we found poor correlation between inconsistent DMARD use and short-term disease outcome. However, outcome in the longer term could be negatively influenced by inconsistent DMARD use, as well as short-term outcome in seropositive patients.

Background A characteristic feature of RA is the presence of autoantibodies (AAB), such as rheumatoid factor (RF) and antibodies against citrullinated peptides (ACPA). RF and ACPA are not only diagnostically helpful but are also prognostic indicators for progression of joint destruction. Objectives This is an on-going prospective study to investigate the prevalence of AAB in healthy individuals presenting to community health centres and to subsequently determine the incidence of RA in AAB-positive individuals compared to AAB-negative persons over five years considering the presence of certain risk factors. Methods Blood drawn at the time of the screening examination was anonymously analyzed for the presence of AAB. AAB positive and age and sex matched AAB negative individuals (2 for each AAB positive subject) were enrolled for further assessment at the central outpatient clinic and examined every 6 months over 5 years. Assessment included laboratory testing (AAB, acute phase parameters), questionnaires on nutrition, lifestyle and general health, 28 joint counts (SJC28, TJC28), the health assessment questionnaire (HAQ), and visual analogue scales for pain and global health. Risk factors were analysed by clusters according to EULAR recommendations for terminology of individuals at risk of RA: hereditary, environmental, systemic autoimmunity and unclassified arthritis and the number of clusters per individual was reported at baseline (1). The primary outcome was the development of RA; individuals lost to follow up were telephone-interviewed for signs and symptoms of RA. Results 4858 sera were obtained from which 148 (3%) were seropositive (14 ACPA, 124 RF, 10 both). 113 individuals (2,3%) were followed over 5 years. 37 (32,7%) were seropositive of whom 32 (28,3%) were RF-positive, 2 (5,4%) were ACPA-positive and 3 (8,1%) positive for both. We found no significant differences in demographics and risk factors between seropositive and seronegative individuals at baseline (Table 1). The number of risk clusters per individuals is reported in figure 1. Until now, 43 people were followed for 5 years; additional 52 telephone interviews were conducted. No evidence of RA (clinically or by history) was found. Conclusions By now none of the followed individuals had any evidence of inflammatory joint disease based on patient-telephone interviews conducted and completed 5-year follow-up examinations. We were unable to find evidence for practical value of routine AAB screening in healthy individuals without clinical signs of inflammatory joint diseases. References Gerlag et al. (2012) Ann Rheum Dis 2012;71:638–641. Disclosure of Interest None declared

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

The concept of multimorbidity is still poorly understood and not well integrated into medical care and research. For clinicians involved in rheumatology care for an ageing patient population who have multiple diseases, multimorbidity is the rule not the exception. The interaction of different diseases and the impact they have on important clinical outcomes, such as physical function, quality of life and mortality, should all be considered by the rheumatologist. Treatment decisions must be adapted for the patient with multimorbidity to best serve the individual and society. This Perspectives article describes the concept of multimorbidity, how it differs from comorbidity, and outlines why an increased understanding of multimorbiditiy will enhance our overall clinical practice and research focus.

Objective Sonography, as compared with clinical assessment, is a sensitive tool for evaluating synovitis in rheumatoid arthritis (RA). However, differences between these assessment tools may depend on how joint activity (i.e., an active joint) is defined. The present study was undertaken to compare clinically active joints with sonographically active joints in patients with RA, applying different sonographic definitions of an active joint. Methods Sonographic assessment of the finger and wrist joints (total of 11 joints) of each hand was performed in RA patients whose disease was in remission (Clinical Disease Activity Index ≤2.8; n = 60). Gray-scale (GS) and power Doppler (PD) ultrasound signals for synovitis were evaluated on a 4-point scale (grade 0 = none, grade 3 = severe). The sensitivity and specificity of swollen joint counts were investigated using, as reference, increasingly stringent sonographic definitions of an active joint. Sonographic findings were also assessed for correlations with other clinical variables, including the Health Assessment Questionnaire (HAQ) disability index (DI). Followup analyses were performed after 6–12 months. Results GS ultrasound signals yielded positive findings for synovitis in 67.2% of the 1,320 joints assessed, and PD ultrasound signals indicated signs of synovitis in 20.4% of the joints assessed. Clinical identification of joint swelling was 100% specific for sonographic joint activity, independent of the stringency of the sonographic definition used; maximum sensitivity of the swollen joint counts was 25% for the most stringent definition (i.e., GS grade 3 and PD grade 3). Furthermore, patients with a higher-grade PD signal (grade 3) showed a higher HAQ DI score compared to patients with lower-grade PD signals (mean ± SD HAQ DI 0.45 ± 0.62 versus 0.20 ± 0.35). A higher grade of PD signal at baseline was found in joints that were assessed as clinically swollen at the consecutive followup visit. Conclusion Low-grade PD and GS ultrasound signals may not necessarily reflect the presence of active synovitis in RA joints. High-grade PD signals correlate well with the presence of clinical joint swelling and clinical disease activity, and a higher grade of PD signal is associated with higher degrees of functional impairment.

To investigate changes of rheumatoid factor (RF) and antibodies against citrullinated peptides (ACPA) during therapy with disease modifying antirheumatic drugs.We obtained clinical and serological data of patients from the treatment start and after 6 months of therapy. With non-parametric tests, we analysed changes of ACPA and RF levels between the two visits and the influence of treatment response. Furthermore, we analysed potential influential factors as disease chronicity, different therapeutics and the trend over 18 months.143 ACPA and RF positive patients were included. The median (25th/75th percentile) relative changes after 6 months were -35.6% (-63.3; -8.3) for RF and -15.2% (-40.0; 10.0) for ACPA (p0.001 for both). Changes of RF levels were significantly greater than those seen for ACPA (p0.001). The decrease of ACPA and RF was significantly higher in treatment responders (p=0.034 and p=0.01, respectively). Aside from changes in disease activity, only a short disease duration showed an independent effect on changes of RF levels (p=0.087).ACPA and RF levels decreased significantly after 6 months of therapy. Reductions of both autoantibodies were closely linked to a reduction of disease activity. RF declined faster, to a larger extent and in greater numbers of patients than ACPA.

International audience; Patient-reported outcomes (PROs) reflect the patient’s perspective and are used in rheumatoid arthritis (RA) routine clinical practice. Patient global assessment (PGA) is one of the most widely used PROs in RA practice and research and is included in several composite scores such as the 28-joint Disease Activity Score (DAS28). PGA is often assessed by a single question with a 0–10 or 0–100 response. The content can vary and relates either to global health (e.g., how is your health overall) or to disease activity (e.g., how active is your arthritis). The wordings used as anchors, i.e., for the score of 0, 10, or 100 according to the scale used, and the timing (i.e., this day or this week) also vary. The different possible ways of measuring PGA translate into variations in its interpretation and reporting and may impact on measures of disease activity and consequently achievement of treat-to-target goals. Furthermore, although PGA is associated with objective measures of disease activity, it is also associated with other aspects of health, such as psychological distress or comorbidities, which leads to situations of discordance between objective RA assessments and PGA. Focusing on the role of PGA, its use and interpretation in RA, this review explores its validity and correlations with other disease measures and its overall value for research and routine clinical practice.

Treat-to-target (TTT) is an accepted paradigm for the management of rheumatoid arthritis (RA), but some evidence suggests poor adherence. The purpose of this study was to test the effects of a group-based multisite improvement learning collaborative on adherence to TTT.We conducted a cluster-randomized quality-improvement trial with waitlist control across 11 rheumatology sites in the US. The intervention entailed a 9-month group-based learning collaborative that incorporated rapid-cycle improvement methods. A composite TTT implementation score was calculated as the percentage of 4 required items documented in the visit notes for each patient at 2 time points, as evaluated by trained staff. The mean change in the implementation score for TTT across all patients for the intervention sites was compared with that for the control sites after accounting for intracluster correlation using linear mixed models.Five sites with a total of 23 participating rheumatology providers were randomized to intervention and 6 sites with 23 participating rheumatology providers were randomized to the waitlist control. The intervention included 320 patients, and the control included 321 patients. At baseline, the mean TTT implementation score was 11% in both arms; after the 9-month intervention, the mean TTT implementation score was 57% in the intervention group and 25% in the control group (change in score of 46% for intervention and 14% for control; P = 0.004). We did not observe excessive use of resources or excessive occurrence of adverse events in the intervention arm.A learning collaborative resulted in substantial improvements in adherence to TTT for the management of RA. This study supports the use of an educational collaborative to improve quality.