Objective To investigate the effect of Body Mass Index (BMI) on long-term radiographic damage in an inception rheumatoid arthritis (RA) cohort.Methods The study population, n=1813, originated from the observational Better AntiRheumatic FarmacoTherapy cohort. X-rays of hands and feet at inclusion, 1, 2, 5, 8 and 15 years were quantified for erosion score (ES), joint space narrowing (JSN) and the sum of modified Sharp-van der Heijde total score (mTSS). Patients were grouped by baseline BMI categories, including additional cut-off BMI ≥27 kg/m2. Curve estimation regression analysis and multivariate mixed models were performed.Results Inverse relationship between BMI and log-transformed mTSS was identified. In general, patients with higher BMI, compared with normal weight and/or underweight patients, had more favourable radiographic outcomes defined by annualised progression rates of mTSS, ES and JSN, less frequent rapid and clinically relevant radiographic progression, and maintained structural integrity. In contrast to consistently higher 28-joint Disease Activity Score (DAS28) levels, BMI ≥30 kg/m2 was associated with less severe mTSS progression, beta=0.946 (95% CI 0.902 to 0.995) per year, p=0.029, while BMI ≤20 kg/m2 with more joint damage, beta=1.091 (1.019–1.169) per year, p=0.014. The findings were confirmed in separate analyses regarding ES and JSN, and in anticitrullinated protein antibody-positive patients. The effect sizes of association between mTSS change and over time levels of C-reactive protein, erythrocyte sedimentation rate and DAS28 declined over time and varied across BMI strata. The latter finding indicates effect modification by BMI. The results in BMI ≥27 kg/m2 group largely mirrored those in BMI ≥30 kg/m2.Conclusions BMI is one of the determinants of radiographic progression in early RA. Lower and higher BMI have opposite effects on radiographic progression.

Objective To assess patient’s self-reported global assessment of health (PGA) in relation to inflammation, pain and disability in patients with rheumatoid arthritis (RA).Methods Data were obtained from the Better Anti-Rheumatic PharmacOTherapy early RA cohort, in which patients were scheduled for follow-up of 15 years. Longitudinal PGA trajectories were identified using hierarchical agglomerative clustering procedure with Wards methods, based on PGA assessments during the first 2 years. Multivariate linear regression and mixed models were used to evaluate associations between PGA, inflammation, pain and disability.Results Totally 2238 patients were included in 1991–2006. Three PGA trajectories were identified, low, medium and high, including 34%, 48% and 18% of the patients, respectively. The similar PGA patterns were shown for the inclusion periods before and after 1999. The patients in the low PGA group were less often women, had lower body mass index, lower levels of inflammatory variables, visual analogue scale (VAS) pain and Health Assessment Questionnaire (HAQ) scores at baseline than patients in the higher PGA groups. After adjustments, smoking and antibodies to cyclic citrullinated peptide status differentiated between being in low and high PGA groups. During the first year, all PGA groups showed improved outcomes, most pronounced in low PGA group. Fewer patients in high PGA group achieved remission, independent of remission criteria used. The outcomes were consistently different between the PGA groups from 6 months and onwards. The PGA levels from baseline over 15 years were best explained by VAS pain, followed by HAQ score, Disease Activity Score on 28 joints-3 and tender joint count, adjusted R2 up to 77%, 41%, 27% and 26%, respectively.Conclusion Persistently higher PGA levels in RA were mostly related to pain and disability.

BACKGROUND:The European Alliance of Associations for Rheumatology recommendations for cardiovascular risk management highlighted the importance of traditional cardiovascular risk factor control in antiphospholipid syndrome (APS). However, cardiovascular risk factor target attainment in APS and differences between primary APS and systemic lupus erythematosus (SLE)-related APS remain uncertain. METHODS:Cardiovascular risk factor data were collected from medical records of patients in 17 centres from 11 countries between Jan 1, 2015, and Jan 1, 2020 (extended to 2022 for some centres unable to complete the survey by the end of 2020 due to the COVID-19 pandemic), and analysed cross-sectionally. Included patients were 18 years or older and met the revised Sapporo APS classification criteria. Patients who also met the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE were classified as having SLE-related APS. Patients with APS in association with systemic autoimmune diseases other than SLE were excluded. Cardiovascular risk was estimated using the Systematic Coronary Risk Evaluation algorithm, and cardiovascular risk factor target attainment was assessed using European Society of Cardiology guidelines. Unadjusted and adjusted mixed effects logistic regression models were fitted. People with lived experience were not involved in the study design. FINDINGS:In total, 1003 patients with APS were included (779 [78%] women and 224 [22%] men; 662 [66%] of 1000 were White), with a median age of 47·0 years (IQR 38·0-57·0) and a median disease duration of 11·0 years (5·0-18·0). 539 (54%) patients had primary APS and 464 (46%) had SLE-related APS. We found a high prevalence of cardiovascular risk factors (hypertension, 411 [41%] of 1003; hyperlipidaemia, 344 [34%] of 1003; obesity, 295 [32%] of 919; current smoking, 186 [19%] of 963) and inadequate individual (blood pressure less than 130/80 mm Hg, BMI, and lipids) and composite cardiovascular risk factor control in all patients. A higher prevalence of hypertension (234 [50%] of 464 vs 177 [33%] of 539; p<0·0001) and hyperlipidaemia (184 [40%] of 464 vs 160 [30%] of 539; p=0·0009) was observed in SLE-related APS versus primary APS, but a lower prevalence of current smoking (72 [16%] of 452 vs 114 [22%] of 511; p=0·012). Patients with primary APS had worse target attainment for smoking cessation (397 [78%] of 511 vs 380 [84%] of 452; p=0·012), blood pressure less than 130/80 mm Hg (246 [48%] of 514 vs 258 [57%] of 456; p=0·0067), and two or more cardiovascular risk factor targets (of smoking, BMI, blood pressure, LDL) than patients with SLE-related APS in the entire group, as well as worse target attainment for smoking cessation, blood pressure less than 130/80 mmHg, BMI, LDL, triglycerides, two or more and three or more targets in the high and very high cardiovascular risk subgroup. Age and arterial thrombosis history were associated with lower odds of attaining three or more or all four cardiovascular risk factor targets. INTERPRETATION:In this large real-world study, high prevalence and suboptimal cardiovascular risk factor control were observed in patients with APS, highlighting the need for increased cardiovascular risk awareness, especially in those with primary APS, whose cardiovascular risk is often overlooked. FUNDING:None.

OBJECTIVES:Anticitrullinated protein antibodies (ACPAs) are associated with increased mortality in patients with rheumatoid arthritis (RA). Previous data suggest ACPAs might be associated with worse disease outcomes in patients without RA with coronary artery disease (CAD). Therefore, we investigated ACPA prevalence and its association with mortality in patients with CAD without RA. Furthermore, the role of systemic inflammation in the relation between ACPAs and mortality was investigated in RA. METHODS:The prevalence of ACPAs in patients with CAD without RA was investigated in 2 CAD cohorts (LUdwigshafen Risk and Cardiovascular Health n = 2189 patients and 656 controls; CLARIthromycin for patients with stable CORonary heart disease n = 959 patients) using a commercial enzyme-linked immunosorbent assay. Multivariable Cox proportional hazards models were performed to investigate the association between ACPAs and all-cause mortality. In 2 RA cohorts (Early Arthritis Clinic [EAC] n = 764; Better Anti-rheumatic Farmaco-therapy [BARFOT] n = 794), joint models were applied to investigate the role of C-reactive protein (CRP) on the association between ACPAs and (cardiovascular) mortality. RESULTS:Average follow-up time in the cohorts ranged between 8.2 and 11.8 years. In both CAD cohorts, ACPA prevalence was low (0.9% and 4.6%), and no association was found between seropositivity and all-cause mortality. In patients with RA, the association between ACPA positivity and all-cause mortality was no longer significant after adjustment for CRP. In contrast, CRP was significantly associated with all-cause and cardiovascular mortality in RA (indirect effect hazard ratio [95% CI]: EAC 1.24 [1.14-1.34], BARFOT 1.33 [1.24-1.42]). CONCLUSIONS:ACPA prevalence is not increased in patients with CAD without RA. In RA, the association between ACPA positivity and increased (cardiovascular) mortality was primarily explained by CRP. This highlights the impact of chronic inflammation on cardiovascular outcomes in RA.

Background and ObjectivesRheumatoid arthritis (RA) has been linked to an increased risk of dementia, yet little is known about how RA affects the progression of cognitive impairment and the risk of mortality in people with dementia. We aimed to investigate whether RA is linked to an accelerated cognitive decline and a higher risk of all-cause mortality in patients with dementia. MethodsWe conducted a propensity score-matched register-based cohort study based on the Swedish Registry for Cognitive/Dementia Disorders-SveDem. Patients diagnosed with dementia and registered in SveDem between May 1, 2007, and October 16, 2018, were included. The main outcome for the study was cognitive decline, measured by Mini-Mental State Examination (MMSE) score changes over years. The secondary outcome was all-cause death. We used mixed-effects models to examine the association between RA and cognitive decline, and Cox proportional hazards models to investigate the risk of all-cause mortality. We also conducted subgroup analyses to explore the potential effects of sociodemographic, baseline MMSE, comorbidities, and the use of dementia medications on the association between RA and outcomes. ResultsWe included 1,685 dementia patients with RA (mean [SD] age, 79.9 [6.7] years; 73.4% were women) and 5,055 dementia patients with non-RA (80.1 [7.5] years; 73.1% were women). The median follow-up was 2.9 years (interquartile range, 1.5-4.6 years) for non-RA and 2.6 years (interquartile range, 1.4-4.2 years) for RA. In total, 111,266 MMSE measurements were available for analysis. Compared with non-RA patients, patients with RA presented faster cognitive decline (beta = -0.24 points/y; 95% CI -0.38 to -0.10) and an increased risk of death (hazard ratio 1.15; 95% CI 1.06-1.24). In subgroup analysis, significant interactions were observed between RA and baseline MMSE scores as well as living conditions regarding cognitive decline (p for interaction <0.05). DiscussionWe identified a worse cognitive function and an increased mortality risk in dementia patients with RA compared with non-RA. However, we lacked information on the duration of RA before the onset of dementia and on disease activity, which could influence our findings. Further studies are needed to validate these results in comparable populations.

Objectives To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.Methods CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score – C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.Results Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=−0.204, (95% CI –0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%).Conclusion Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.Trial registration number NCT03649061.CTR pilot approval Belgium S59474, EudraCT number: 2017-004054-41.

Patients with systemic lupus erythematosus (SLE) are at increased risk of coronary heart disease (CHD). Even though the absolute risk of cardiovascular disease (CVD) among SLE patients increases with advancing age, younger female patients are at the greatest risk of developing acute myocardial infarction (AMI). These young patients are not considered to be at high risk for CVD using traditional risk assessment tools. Also, subclinical atherosclerosis is less common among young lupus patients. AMI could present with or without significant obstruction in coronary arteries in younger patients. There are no guidelines on appropriate cardiac screening of younger lupus patients, often without chest pain or who present with non-specific complaints. In recent years, the incidence of acute coronary syndrome (ACS) and ST-segment elevation AMI has decreased in the general population and in older lupus patients. Why has a similar decline in cardiovascular (CV) events not been seen in younger lupus patients? Since the issue of CVD in younger lupus patients is under-researched, a narrative review, rather than a systematic literature review was performed, based on the selected articles and points of view relevant to the topic. The aim of this review is to raise awareness of the relationship between SLE and CVD in younger ages, discuss possible non-atherosclerotic mechanisms of obstructive and non-obstructive CHD in lupus, elaborate on acute coronary syndromes unique for young patients, point out current challenges in identifiing at-risk patients for ACS, potential for new imaging techniques, the need for individualised treatment, with or without coronary stenting in ACS, and to underscore the relevance of CVD studies in young patients with SLE.

Background Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus. Methods In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process. Findings 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33–54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome. Interpretation High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted. Funding None.

Background Risk of fragility fractures in patients with rheumatoid arthritis (RA) is increased. Disease-related inflammation in RA is associated with low Bone Mineral Density (BMD). However, effects of specific disease factors on fracture occurrence and whether or not such disease effects are independent of BMD are unknown. Methods Analysis of fracture outcome in the prospective cohort of 2557 patients with early RA (67% women, mean age 58.1 ± 15.6 years) during an observation period of 10.6 ± 4.7 years. In 602 patients BMD was measured at baseline. The first major fragility fractures were considered. Kaplan-Meier and Cox regression analysis, adjusted for traditional factors, prior fracture, disease activity and period of inclusion, were used to estimate the risk of the outcome. Results During follow-up fracture occurred in 352 patients (13.8%), a rate of 13/1000 p-y. A proportional risk reduction for the outcome was associated with Body Mass Index (BMI) at baseline, BMI ≥ 30 kg/m 2 , and over the first two years sustained Disease Activity Score (DAS28)-remission, DAS28-low disease activity and Health Assessment Questionnaire (HAQ) ≤ 0.5. The proportional risk elevation for fractures was associated with BMI ≤ 20 kg/m 2 , DAS28 at baseline, 6-month and at 1-year, cumulative DAS28 over the two years, RF, erosion score progression at 2-year, HAQ score and HAQ ≥ 1 at 6-month and 1-year and showed a trend for ACPA positivity. The estimated fracture risk was increased in users of glucocorticoids (GC), associated with a higher GC-dosage at follow-ups and a higher cumulative dosage over two years, independently of disease activity. With adjustment for BMD, there was no difference in fracture outcome by exposure to GC. The effects of a higher BMI, DAS28-remission and low HAQ ≤ 0.5 attained at 6-month of treatment initiation and sustained up to 2 years, RF, ACPA, and erosion score progression at 2-year were independent of low BMD. Conclusions This analysis supports importance of RA-specific risk factors in early RA for future major fragility fractures. Treat-to-target strategy and restored functional capacity in early RA-disease are important to prevent fractures. Autoantibody positivity, progressively erosive disease, and low weight could have additional value for personalized fracture preventive strategies in early RA.

How to manage patients perceived as having a mild form of early arthritis?

Systemic inflammation is a shared pathogenesis in dementia and rheumatoid arthritis (RA). It has been postulated that patients with RA are at higher risk of dementia, however, prior studies showed conflicting results. In addition, recent research suggested that biological disease-modifying antirheumatic drugs (DMARDs) could potentially have a protective effect on dementia. Using data from the Stockholm CREAtinine Measurements (SCREAM) cohort, we identified all individuals with an incident diagnosis of RA (ICD-10 codes: M05, M06) during 2008-2019 in the region of Stockholm. For each individual with RA, 10 age- and sex-matched individuals without RA were randomly selected from the general population as reference individuals. The primary outcome was all-cause dementia, ascertained via linkage with the Swedish Dementia Registry, clinical diagnoses, or initiation of anti-dementia drugs. Incidence of dementia was compared between RA patients and reference individuals using Cox proportional hazards models. Subsequently, among patients with RA, we examined the association of initiation of any type of DAMRDs, and specifically initiation of biological DAMRDs, with the risk of dementia using inverse probability weighted Cox models. Socio-demographics, kidney function, comorbidities, and concurrent use of medications were included as potential confounders. A total of 8939 patients with RA (median [IQR] age, 63 [51, 73] years; 6237 [69.8%] women) were identified, with a median follow-up of 5.2 (IQR: 2.5, 8.9) years. Compared with the reference individuals, patients with RA associated with a higher risk of all-cause dementia (hazard ratio [HR]: 1.18; 95% CI: 1.01, 1.37). Among RA patients, initiation of biological DMARDs was associated with a reduced risk of dementia (HR: 0.34; 95% CI: 0.13, 0.92). However, initiation of any-type of DMARDs within 3 months was not associated with the risk of dementia (HR: 0.91; 95% CI: 0.71, 1.18). Patients with RA had a higher risk of developing dementia, and treatment with biological DMARDs might be associated with a decreased risk of dementia. These findings suggest more attention to cognitive function in the clinical management of RA and further investigation on biological DMARDs as a potential therapeutic candidate for dementia.

Background EULAR recommends methotrexate (MTX), combined with short-term glucocorticoids as first-line treatment for early Rheumatoid Arthritis (RA). In the CareRA trial, the COBRA-Slim regimen (MTX 15 mg/w + step-down prednisone 30, 20, 12.5, 10, 7.5, 5 mg/d), including a treat to target (T2T) approach starting with addition of leflunomide and only at a later stage bDMARDs, provided the best balance between efficacy, safety and cost-effectiveness. The potential advantage of temporary bDMARD use earlier in the T2T setting needs further investigation. Objectives To determine the long-term effectiveness of accelerated access to a temporary course of etanercept compared to addition of leflunomide in patients with early RA who insufficiently respond to initial COBRA-Slim induction therapy. Methods DMARD-naïve patients with a recent diagnosis of RA (≤1 year ago) were included in the 2-year, open-label, multicentre, pragmatic randomised controlled superiority trial Care in Early RA 2020 (CareRA2020). All patients started the COBRA-Slim induction regimen. Patients were classified as insufficient responders if, even despite MTX dose increase, they did not achieve DAS28-CRP ≤3.2 between week 8 and week 32 or if DAS28-CRP was ≥2.6 at week 32 regardless of MTX dose. Insufficient responders were randomised to either Standard COBRA-Slim (addition of leflunomide 10 mg/d) or COBRA-Slim Bio-induction (addition of etanercept 50 mg/w for 24 weeks). Additional treatment adaptations followed the T2T principle. Primary outcome was the difference in DAS28-CRP over time, determined via a linear mixed model including random intercepts and a random slope for time, adjusting for baseline DAS28-CRP and seropositivity. Missing data were imputed with the Expectation-Maximisation algorithm. Results In total, 276 patients were included, of which 155 (56%) were classified as sufficient and 121 (44%) as insufficient responders. Of the insufficient responders, 9 patients were not randomised by investigator decision, 2 were randomisation errors, 55 were randomised to Standard COBRA-Slim, and 55 to COBRA-Slim Bio-Induction. The mean ± SD area under the DAS28-CRP curve over 104 weeks was 232 ± 66 for the initial sufficient responders, 310 ± 82 for the Standard COBRA-Slim group, and 316 ± 73 for the COBRA-Slim Bio-induction group. Both randomisation groups had comparable DAS28-CRP scores over time (ß = -0.095, 95% CI (-0.299 to 0.108), p=0.351). At the end of the trial, 82% (127/155), 9% (5/55), and 36% (20/55) of patients were on csDMARD monotherapy in the initial sufficient responders, Standard COBRA-Slim, and COBRA-slim Bio-induction group, respectively. Moreover, 6% (9/155) sufficient responders, 58% (32/55) in the Standard COBRA-Slim, and 45% (25/55) in the COBRA-Slim Bio-induction group were treated with a b- or tsDMARD. Conclusion More than half of the CareRA2020 participants achieved remission with COBRA-Slim induction therapy. DAS28-CRP over 104 weeks was not superior with COBRA-Slim Bio-induction versus the Standard COBRA-Slim T2T regimen in initial insufficient responders. However, compared to the Standard COBRA-Slim group, more patients in the Bio-induction group were treated with csDMARD monotherapy and less with advanced therapies at the end of the study. Acknowledgements The CareRA2020 trial was funded by the Belgian Health Care Knowledge Centre (KCE) Trials Program, a national public funding program of non-commercial trials. Disclosure of Interests None Declared.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

BackgroundBone erosions may appear early or later during rheumatoid arthritis (RA), causing joint damage and functional impairment. However, in some patients erosions do not occur, even after several years of disease. This study evaluates the prevalence, clinical relevance and possible predictors of erosion-free RA. MethodsSix hundred and eight patients from an early RA cohort (BARFOT) having radiographs of hands and feet at inclusion and after 1, 2, 5 and 8 years were studied. Clinical and functional assessments were performed on all these time-points. ResultsIn all, 144 patients (24%) did not develop erosions up to 8 years follow-up (Never erosive group), while 464 patients (76%) had erosions on one or more assessments (Ever erosive group). At diagnosis, the patients in the Never erosive group were significantly younger, satisfied fewer ACR criteria, and were less frequently RF- and/or anti-CCP- positive compared with those in the Ever erosive group. The Never erosive patients had consistently more tender joints, lower erythrocyte sedimentation rate (ESR) and, from two years and onwards, fewer swollen joints. Absence of rheumatoid factor (RF) and/or anti-CCP were strong independent predictors for erosion-free disease. The erosion-free patients were less frequently treated with DMARDs and/or prednisolone. ConclusionsOne-quarter of the patients was erosion-free during eight years in this early RA cohort. Erosion-free patients had a less severe disease course as to disease activity and were more often seronegative compared with those with erosive disease. The results suggest that non-erosive RA represents a milder form of RA.

Objective: Correct diagnosis of early rheumatoid arthritis (RA) is essential for optimal treatment choices. No pathognomonic test is available, and diagnosis is based on classification criteria, which can result in misdiagnosis. Here, we examined the differences between actual and misdiagnosed RA cases in a long-term cohort of patients included based on the ACR-1987 classification criteria. Methods: Patients in the BARFOT (Better Anti-Rheumatic PharmacOTherapy) cohort (n=2543) with at least four follow-up visits during the initial 5 years from enrolment were assessed, and a change in diagnosis was reported by the treating rheumatologist. The groups were analysed with respect to the individual classification criteria, antibodies to citrullinated proteins (ACPA), disease activity (DAS28) and radiographic changes from inclusion up to 2 years. Results: Forty-five patients (1.8%) were misdiagnosed ( RA-change group). When compared to those in the RA-change group, the patients who kept their diagnosis ( RA-keep ) were more often RF positive (64% vs 21%, p<0.001) or ACPA positive (59% vs 8%, p<0.001). They were also more likely to fulfil more than four ACR-1987 criteria (64% vs 33%, p<0.001) and to have radiographic changes at inclusion ( RA-keep 27% vs RA-change 12%, p=0.04). The groups had a similar evolution of DAS28 and its components as well as of radiological joint destruction. Conclusion: Diagnosis of RA according to the ACR-1987 criteria had a high precision in this long-term cohort. A diagnosis of RA should be re-evaluated in patients who do not fulfil more than four ACR-1987 criteria especially in patients negative for RF.

OBJECTIVE:We study activation of T helper 17 (Th17) and regulatory T (Treg) cells and induction of apoptosis in cells from patients with systemic lupus erythematosus (SLE) compared with controls and effects of atorvastatin and its simulated interactions with other compounds.METHODS:Mononuclear cells from 10 patients with SLE and 10 controls were cultured in conditions that induce Th17 and/or Treg cell polarization and/or apoptosis and were studied by FACScan. Gene expression was determined by quantitative real-time reverse transcription-polymerase chain reaction. Cytokines in plasma were determined by enzyme-linked immunosorbent assay. The Search Tool for Interactions of Chemicals (STITCH) was used to retrieve information regarding the binding properties of atorvastatin.RESULTS:Among patients with SLE, the proportion of Th17 (CD4+ IL17+ ) cells was higher compared with controls after activation, with Th17 or Treg polarizing cytokines, phorbol myristate acetate, and ionomycin. In contrast, Treg cells (CD4+ CD25+ CD127dim/- ) frequencies were lower. CD95 stimulation induced relatively more apoptosis in Treg cells and less in Th17 cells, as compared with controls. Addition of atorvastatin normalized Th17/Treg cell balance and apoptosis induction. Accordingly, the ratio of RORC/FoxP3 decreased in patients with SLE. Interleukin 17 and interleukin 6 (IL-6) levels were increased in patients with SLE. Atorvastatin interacted strongly with C-reactive protein (CRP) and also significantly with IL-6.CONCLUSION:There is a higher proportion of Th17 cells and a lower proportion of Treg cells in patients with SLE after activation. Th17 cells were more resistant than Treg cells to CD95-induced apoptosis in SLE. Atorvastatin normalized these effects. Our findings reveal a novel mechanism behind the imbalance of Th17/Treg cells with implications for treatment in SLE. We determine for the first time simulated interaction between atorvastatin, CRP, and IL-6, implying a novel role of atorvastatin.