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Patients with immune-mediated inflammatory diseases (IMIDs) may have impaired initial humoral responses after SARS-CoV-2 vaccination depending on the type of immunosuppression (ISP) used.1 It is largely unknown how antibody titres develop over time and whether it is needed to adjust timing of booster campaigns for patients with IMID.

The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI.We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group.Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment.We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

Background: Studies on long-term consequences of COVID-19, commonly referred to as post-COVID condition, in patients with inflammatory rheumatic diseases are scarce and inconclusive. Furthermore, classifying patients with inflammatory rheumatic diseases as having post-COVID condition is complicated because of overlapping symptoms. Therefore, we investigated the risk of post-COVID condition and time until recovery, and compared the prevalence of symptoms seen in post-COVID condition, between patients with inflammatory rheumatic diseases and healthy controls, with and without a history of COVID-19. Methods: In this substudy we used data from an ongoing prospective cohort study in the Netherlands. All adult patients with inflammatory rheumatic diseases from the Amsterdam Rheumatology and Immunology Center in Amsterdam, the Netherlands, were invited to participate in the study between April 26, 2020, and March 1, 2021. All patients were asked, but not obliged, to recruit their own control participant of the same sex, of comparable age (< 5 years), and without an inflammatory rheumatic disease. Demographic and clinical data, including data on the occurrence of SARS-CoV-2 infections, were collected via online questionnaires. On March 10, 2022, all study participants received a questionnaire on the occurrence, onset, severity, and duration of persistent symptoms during the first 2 years of the COVID-19 pandemic, independent of their history of SARS-CoV-2 infection. Additionally, we prospectively monitored a subset of participants who had a PCR or antigen confirmed SARS-CoV-2 infection in the 2-month period surrounding the questionnaire in order to assess COVID-19 sequelae. In line with WHO guidelines, post-COVID condition was defined as persistent symptoms that lasted at least 8 weeks, started after the onset and within 3 months of a PCR or antigen-confirmed SARS-CoV-2 infection, and could not be explained by an alternative diagnosis. Statistical analyses included descriptive statistics, logistic regression analyses, logistic-based causal mediation analyses, and Kaplan-Meier survival analyses for time until recovery from post-COVID condition. In exploratory analyses, E-values were calculated to investigate unmeasured confounding. Findings: A total of 1974 patients with inflammatory rheumatic disease (1268 [64%] women and 706 [36%] men; mean age 59 years [SD 13]) and 733 healthy controls (495 [68%] women and 238 [32%] men; mean age 59 years [12]) participated. 468 (24%) of 1974 patients with inflammatory rheumatic disease and 218 (30%) of 733 healthy controls had a recent SARS-CoV-2 omicron infection. Of those, 365 (78%) of 468 patients with inflammatory rheumatic disease and 172 (79%) of 218 healthy controls completed the prospective follow-up COVID-19 sequelae questionnaires. More patients than controls fulfilled post-COVID condition criteria: 77 (21%) of 365 versus 23 (13%) of 172 (odds ratio [OR] 1·73 [95% CI 1·04–2·87]; p=0·033). The OR was attenuated after adjusting for potential confounders (adjusted OR 1·53 [95% CI 0·90–2·59]; p=0·12). Among those without a history of COVID-19, patients with inflammatory diseases were more likely to report persistent symptoms consistent with post-COVID condition than were healthy controls (OR 2·52 [95% CI 1·92–3·32]; p

Objective The aim of this study was to investigate the effect of treat-to-target combination therapy with intensification at 13 weeks in early RA. Methods Early RA patients were classified as being at high or low risk of worsening RA based on disease activity and prognostic factors. High-risk patients received COBRA-light (prednisolone 30 mg/day tapered to 7.5 mg/day, MTX increasing to 25 mg/week), and low-risk patients received MTX monotherapy increasing to 25 mg/week. The primary outcome (target) was DAS44 Results In the high-risk group (n = 150), 110 patients (73%) reached the target at 13 weeks, and 9 dropped out. Non-responders were randomized to intensification (n = 15) or continuation (n = 16), and after 26 weeks, 12 (80%) vs 7 (44%) of these, respectively, reached the target [difference: 36%, (95% CI 2%, 71%); P = 0.04]. In the low-risk group (n = 40), 17 (43%) reached the target. Non-responders were randomized to intensification (n = 8) or continuation (n = 7); 4 vs 3, respectively, reached the target. Adverse event rates were higher in the high-risk group, and higher in the intensification subgroup of that group. Serious adverse events were rare. Protocol violations were frequent and mostly led to mitigation of actual treatment intensification. Conclusion Initial combination therapy was very successful in high-risk RA, and early intensification was beneficial in patients not reaching the strict target. The low-risk group was too small for drawing conclusions. In routine practice, adherence to early intensification based on strict targets is difficult. Trial registration Netherlands Trial Register (NTR), NL4393, https://www.trialregister.nl/.

ObjectiveTo investigate the potential of whole-body positron emission tomography/computed tomography (PET/CT) with a macrophage tracer to image arthritis in patients with early rheumatoid arthritis (RA).MethodsThirty-five previously untreated, clinically active patients with early RA underwent whole-body PET/CT scanning with the macrophage tracer (R)-[11C]PK11195 in addition to clinical assessment (Disease Activity Score in 44 joints [DAS44]). Tracer uptake was assessed quantitatively as standardized uptake values (SUVs). In addition, 2 readers blinded to clinical assessment visually scored tracer uptake in joints. Clinical and PET variables were compared using Cohen , linear regression/correlation, and t tests, where appropriate.ResultsAll but 1 patient showed enhanced tracer uptake in at least 1 joint. Twelve percent of all joints (171/1470) were visually positive on the PET scan, most frequently the small joints in feet (40%) and hands (37%), followed by wrists (15%). Correlations of visual scores with clinical findings both at patient and joint levels were absent or weak. In contrast, average SUVs in the hands, feet, and whole body showed significant correlations with DAS44 scores, with the best correlation seen in the feet (R2 = 0.29, P < 0.01).ConclusionClinically active patients with early RA had increased joint uptake of a macrophage PET tracer, especially in the feet. Quantitative, but not visual PET measures of whole body and joint groups, particularly the feet, showed moderate and statistically significant correlations with clinical outcome.

Contains fulltext : 251784.pdf (Publisher’s version ) (Closed access) BACKGROUND: Concerns have been raised regarding the risks of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory diseases treated with immunosuppressants, but clinical data on breakthrough infections are still scarce. The primary objective of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections between patients with immune-mediated inflammatory diseases using immunosuppressants, and controls (patients with immune-mediated inflammatory diseases not taking immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary objective was to explore determinants of breakthrough infections of the delta (B.1.617.2) variant of SARS-CoV-2, including humoral immune responses after vaccination. METHODS: In this substudy, we pooled data collected in two large ongoing prospective multicentre cohort studies conducted in the Netherlands (Target to-B! [T2B!] study and Amsterdam Rheumatology Center COVID [ARC-COVID] study). Both studies recruited adult patients (age ≥18 years) with immune-mediated inflammatory diseases and healthy controls. We sourced clinical data from standardised electronic case record forms, digital questionnaires, and medical files. We only included individuals who were vaccinated against SARS-CoV-2. For T2B!, participants were recruited between Feb 2 and Aug 1, 2021, and for ARC-COVID, participants were recruited between April 26, 2020, and March 1, 2021. In this study we assessed data on breakthrough infections collected between July 1 and Dec 15, 2021, a period in which the delta SARS-CoV-2 variant was the dominant variant in the Netherlands. We defined a SARS-CoV-2 breakthrough infection as a PCR-confirmed or antigen test-confirmed SARS-CoV-2 infection that occurred at least 14 days after vaccination. All breakthrough infections during this period were assumed to be due to the delta variant due to its dominance during the study period. We analysed post-vaccination serum samples for anti-receptor binding domain (RBD) antibodies to assess the humoral vaccination response (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC-COVID study only). We used multivariable logistic regression analyses to explore potential clinical and humoral determinants associated with the odds of breakthrough infections. The T2B! study is registered with the Dutch Trial Register, Trial ID NL8900, and the ARC-COVID study is registered with Dutch Trial Register, trial ID NL8513. FINDINGS: We included 3207 patients with immune-mediated inflammatory diseases who receive immunosuppressants, and 1807 controls (985 patients with immune-mediated inflammatory disease not on immunosuppressants and 822 healthy controls). Among patients receiving immunosuppressants, mean age was 53 years (SD 14), 2042 (64%) of 3207 were female and 1165 (36%) were male; among patients not receiving immunosuppressants, mean age was 54 years (SD 14), 598 (61%) of 985 were female and 387 (39%) were male; and among healthy controls, mean age was 57 years (SD 13), 549 (67%) of 822 were female and 273 (33%) were male. The cumulative incidence of PCR-test or antigen-test confirmed SARS-CoV-2 breakthrough infections was similar in patients on immunosuppressants (148 of 3207; 4·6% [95% CI 3·9-5·4]), patients not on immunosuppressants (52 of 985; 5·3% [95% CI 4·0-6·9]), and healthy controls (33 of 822; 4·0% [95% CI 2·8-5·6]). There was no difference in the odds of breakthrough infection for patients with immune-mediate inflammatory disease on immunosuppressants versus combined controls (ie, patients not on immunosuppressants and healthy controls; adjusted odds ratio 0·88 [95% CI 0·66-1·18]). Seroconversion after vaccination (odds ratio 0·58 [95% CI 0·34-0·98]; T2B! cohort only) and SARS-CoV-2 infection before vaccination (0·34 [0·18-0·56]) were associated with a lower odds of breakthrough infections. INTERPRETATION: The incidence and severity of SARS-CoV-2 breakthrough infections in patients with immune-mediated inflammatory diseases on immunosuppressants was similar to that in controls. However, caution might still be warranted for those on anti-CD20 therapy and those with traditional risk factors. FUNDING: ZonMw (the Netherlands Organization for Health Research and Development) and Reade foundation.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with cardiovascular (CV) morbidity and mortality. Interferon regulatory factor 5 (IRF5) gene polymorphisms rs2004640 and rs4728142 have been associated with autoimmune diseases, but also with atherosclerosis. Differences in IRF5 gene expression can lead to the production of different interferons and might play a role in the atherogenic process in RA.METHODS: We investigated the effects of IRF5 gene variants rs2004640 and rs4728142 on clinical parameters related to atherosclerosis, such as cIMT (in subgroup n=101), and new CV events (in whole cohort n=353).RESULTS: For rs2004640, cIMT values at baseline were highest within the group of patients carrying the GG-genotype, followed by GT- and TT- genotypes, which was statistically significant. Over time patients with the TT-genotype had the highest increase in cIMT. For rs4728142 cIMT values were also the highest for patients with the GG-genotype at baseline, but the difference between the groups was not statistically significant. Over time the highest increase in cIMT was in the patients with the AA-genotype. Both rs2004640 and rs4728142 were not associated with new CV events during follow-up.CONCLUSIONS: IRF5 alleles are associated with changes in cIMT, but not with new CV events in RA. Although these findings implicate a role of the IRF5 transcription pathway in atherosclerosis, IRF5 single nucleotide polymorphisms do not appear to increase the risk of future CV events.

OBJECTIVES: To extend our investigation of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients to a follow up of more than 20 years, with a special focus on patients without prevalent CVD.METHODS: The CARRÉ study is an ongoing prospective cohort study on CV endpoints in RA patients. Results were compared to those of a reference cohort (n = 2484) enriched for type 2 diabetes mellitus (DM). Hazard ratios (HR) for RA and DM patients compared to non-RA/-DM controls were calculated with cox proportional hazard models, and adjusted for baseline SCORE1 (estimated 10-year CVD mortality risk based on CV risk factors).RESULTS: 238 RA patients, 117 DM patients and 1282 controls, without prevalent CVD at baseline were included. Analysis of events in these patients shows that after adjustment, no relevant 'RA-specific' risk remains (HR 1.16; 95%CI 0.88 - 1.53), whereas a 'DM-specific' risk is retained (1.73; 1.24 - 2.42). In contrast, adjusted analyses of all cases confirm the presence of an 'RA-specific' risk (1.50; 1.19 - 1.89).CONCLUSIONS: In RA patients without prevalent CVD the increased CVD risk is mainly attributable to increased presence of traditional risk factors. After adjustment for these factors, an increased risk attributable to RA only was thus preferentially seen in the patients with prevalent CVD at baseline. As RA treatment has improved, this data suggests that the 'RA-specific' effect of inflammation is preferentially seen in patients with prevalent CVD. We suggest that with modern (early) treatment of RA, most of the current increased CVD risk is mediated through traditional risk factors.

Background: Data are scarce on immunogenicity of COVID-19 vaccines in patients with autoimmune diseases, who are often treated with immunosuppressive drugs. We aimed to investigate the effect of different immunosuppressive drugs on antibody development after COVID-19 vaccination in patients with autoimmune diseases. Methods: In this study, we used serum samples collected from patients with autoimmune diseases and healthy controls who were included in two ongoing prospective cohort studies in the Netherlands. Participants were eligible for inclusion in this substudy if they had been vaccinated with any COVID-19 vaccine via the Dutch national vaccine programme, which at the time was prioritising vaccination of older individuals. Samples were collected after the first or second COVID-19 vaccination. No serial samples were collected. Seroconversion rates and IgG antibody titres against the receptor-binding domain of the SARS-CoV-2 spike protein were measured. Logistic and linear regression analyses were used to investigate the association between medication use at the time of vaccination and at least until sampling, seroconversion rates, and IgG antibody titres. The studies from which data were collected are registered on the Netherlands Trial Register, Trial ID NL8513, and ClinicalTrials.org, NCT04498286.Findings: Between April 26, 2020, and March 1, 2021, 3682 patients with rheumatic diseases, 546 patients with multiple sclerosis, and 1147 healthy controls were recruited to participate in the two prospective cohort studies. Samples were collected from patients with autoimmune diseases (n=632) and healthy controls (n=289) after their first (507 patients and 239 controls) or second (125 patients and 50 controls) COVID-19 vaccination. The mean age of both patients and controls was 63 years (SD 11), and 423 (67%) of 632 patients with autoimmune diseases and 195 (67%) of 289 controls were female. Among participants without previous SARS-CoV-2 infection, seroconversion after first vaccination were significantly lower in patients than in controls (210 [49%] of 432 patients vs 154 [73%] of 210 controls; adjusted odds ratio 0·33 [95% CI 0·23-0·48]; pInterpretation: Our data suggest that seroconversion after a first COVID-19 vaccination is delayed in older patients on specific immunosuppressive drugs, but that second or repeated exposure to SARS-CoV-2, either via infection or vaccination, improves humoral immunity in patients treated with immunosuppressive drugs. Therefore, delayed second dosing of COVID-19 vaccines should be avoided in patients receiving immunosuppressive drugs. Future studies that include younger patients need to be done to confirm the generalisability of our results.FUNDING: ZonMw, Reade Foundation, and MS Center Amsterdam.

ObjectivesTo compare the cumulative incidence and disease severity of reported SARS-CoV-2 omicron breakthrough infections between patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants and controls, and to investigate determinants for breakthrough infections.MethodsData were used from an ongoing national prospective multicentre cohort study on SARS-CoV-2 vaccination responses in patients with IMID in the Netherlands (Target-to-B! (T2B!) study). Patients wih IMID on immunosuppressants and controls (patients with IMID not on immunosuppressants and healthy controls) who completed primary immunisation were included. The observation period was between 1 January 2022 and 1 April 2022, during which the SARS-CoV-2 omicron (BA.1 and BA.2 subvariant) was dominant. A SARS-CoV-2 breakthrough infection was defined as a reported positive PCR and/or antigen test at least 14 days after primary immunisation. A multivariate logistic regression model was used to investigate determinants.Results1593 patients with IMID on immunosuppressants and 579 controls were included. The cumulative incidence of breakthrough infections was 472/1593 (29.6%; 95% CI 27% to 32%) in patients with IMID on immunosuppressants and 181/579 (31.3%; 95% CI 28% to 35%) in controls (p=0.42). Three (0.5%) participants had severe disease. Seroconversion after primary immunisation (relative risk, RR 0.71; 95% CI 0.52 to 0.96), additional vaccinations (RR 0.61; 95% CI 0.49 to 0.76) and a prior SARS-CoV-2 infection (RR 0.60; 95% CI 0.48 to 0.75) were associated with decreased risk of breakthrough infection.ConclusionsThe cumulative incidence of reported SARS-CoV-2 omicron breakthrough infections was high, but similar between patients with IMID on immunosuppressants and controls, and disease severity was mostly mild. Additional vaccinations and prior SARS-CoV-2 infections may reduce the incidence of breakthrough infections.

Objective RA is associated with higher risk of cardiovascular (CV) disease. Ongoing systemic inflammation is presumed to accelerate atherosclerosis by increasing inflammation in the arterial wall. However, evidence supporting this hypothesis is limited. We aimed to investigate arterial wall inflammation in RA vs OA, and its association with markers of inflammation and CV risk factors. Methods 18-fluorodeoxyglucose PET combined with CT (18F-FDG-PET/CT) was performed in RA (n = 61) and OA (n = 28) to investigate inflammatory activity in the wall of large arteries. Secondary analyses were performed in patients with early untreated RA (n = 30), and established RA, active under DMARD treatment (n = 31) vs OA. Results Patients with RA had significantly higher 18F-FDG uptake in the wall of the carotid arteries (beta 0.27, 95%CI 0.11—0.44, P Conclusion Patients with RA have increased 18F-FDG uptake in the arterial wall compared with patients with OA, as a possible marker of early atherosclerosis. Furthermore, a higher level of clinical disease activity and circulating inflammatory markers was associated with higher arterial 18F-FDG uptake, which may support a role of arterial wall inflammation in the pathogenesis of vascular complications in patients with RA.

Resume Objectifs Les personnes atteintes de vascularite a ANCA presentent un risque accru d’evenements cardiovasculaires. L’objectif de cette etude etait d’evaluer les facteurs predictifs d’evenements cardiovasculaires chez des patients atteints de granulomatose avec polyangeite ou de granulomatose eosinophilique avec polyangeite. Methodes Il s’agit d’une etude longitudinale retrospective menee sur des patients de la cohorte du reseau de recherche Canadian Vasculitis de Toronto. Les caracteristiques au moment du diagnostic ont ete collectees. Pendant la periode de suivi, les evenements cardiovasculaires non mortels ont ete determines a partir de l’indice VDI (sequelles liees a la vascularite) et la mortalite a ete enregistree avec les causes de deces. Des modeles de regression de Cox ont ete elabores pour identifier les facteurs predictifs d’evenements cardiovasculaires, definis comme un AVC ou un infarctus du myocarde. Resultats Au total, 336 patients ont ete inclus : 231 (69 %) atteints de granulomatose avec polyangeite et 105 (31 %) de granulomatose eosinophilique avec polyangeite. L’âge moyen au moment du diagnostic etait de 44 ans (± 18) et 44 % des patients etaient des hommes. Le taux d’incidence du critere combine de l’ensemble des evenements mortels et non mortels etait de 7,2 evenements pour 1000 annees–patient. Dans un modele multivarie, les antecedents familiaux d’evenements cardiovasculaires et un score BVAS (Birmingham Vasculitis Activity Score) plus eleve au moment du diagnostic etaient predictifs d’evenements cardiovasculaires (odds ratio et intervalle de confiance a 95 % : 3,46 [1,06–11,28] et 1,09 [1,02–1,16], respectivement). Une analyse de sous-groupe n’a pas montre d’association entre les caracteristiques cardiovasculaires ou specifiques a la maladie et la survenue d’evenements cardiovasculaires dans la granulomatose eosinophilique avec polyangeite. Conclusions Dans cette cohorte de patients atteints de granulomatose avec polyangeite et de granulomatose eosinophilique avec polyangeite, des facteurs de risque traditionnels et specifiques a la maladie etaient predictifs d’evenements cardiovasculaires. Des etudes prospectives complementaires devraient permettre de preciser leurs effets, ainsi que ceux d’autres facteurs de risque modifiables, sur le risque cardiovasculaire dans la vascularite a ANCA.

ObjectiveTo develop recommendations for cardiovascular risk (CVR) management in gout, vasculitis, systemic sclerosis (SSc), myositis, mixed connective tissue disease (MCTD), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).MethodsFollowing European League against Rheumatism (EULAR) standardised procedures, a multidisciplinary task force formulated recommendations for CVR prediction and management based on systematic literature reviews and expert opinion.ResultsFour overarching principles emphasising the need of regular screening and management of modifiable CVR factors and patient education were endorsed. Nineteen recommendations (eleven for gout, vasculitis, SSc, MCTD, myositis, SS; eight for SLE, APS) were developed covering three topics: (1) CVR prediction tools; (2) interventions on traditional CVR factors and (3) interventions on disease-related CVR factors. Several statements relied on expert opinion because high-quality evidence was lacking. Use of generic CVR prediction tools is recommended due to lack of validated rheumatic diseases-specific tools. Diuretics should be avoided in gout and beta-blockers in SSc, and a blood pressure target ConclusionThese recommendations can guide clinical practice and future research for improving CVR management in rheumatic and musculoskeletal diseases.

The Physician Global Assessment International Standardisation COnsensus in Systemic Lupus Erythematosus (PISCOS) study aimed to obtain an evidence-based and expert-based consensus standardisation of the Physician Global Assessment (PGA) scoring of disease activity in systemic lupus erythematosus (SLE). An international panel of 79 SLE experts participated in a three-round Delphi consensus process, in which 41 statements related to the PGA in SLE were rated, using a 0 (strongly disagree) to 10 (strongly agree) numerical rating scale. Statements with agreement of 75% or greater were selected and further validated by the expert panel. Consensus was reached on 27 statements, grouped in 14 recommendations, for the use of the PGA in SLE, design of the PGA scale, practical considerations for PGA scoring, and the relationship between PGA values and levels of disease activity. Among these recommendations, the expert panel agreed that the PGA should consist of a 0–3 visual analogue scale for measuring disease activity in patients with SLE in the preceding month. The PGA is intended to rate the overall disease activity, taking into account the severity of active manifestations and clinical laboratory results, but excluding organ damage, serology, and subjective findings unrelated to disease activity. The PGA scale ranges from “no disease activity” (0) to the “most severe disease activity” (3) and incorporates the values 1 and 2 as inner markers to categorise disease activity as mild (≥0·5 to 1), moderate (>1 and ≤2) and severe (>2 to 3). Only experienced physicians can rate the PGA, and it should be preferably scored by the same rater at each visit. The PISCOS results will allow for increased homogeneity and reliability of PGA ratings in routine clinical practice, definitions of remission and low disease activity, and future SLE trials.

Objectives To identify predictors of complete renal response (CRR) and renal flares in SLE patients with active proliferative LN. Methods This was a retrospective cohort study over 36 months including patients with biopsy-proven proliferative LN (class III/IV), from two European tertiary centres. CRR and renal flare were defined as proteinuria 1 g/day after CRR attainment, respectively. Demographic, clinical and analytic parameters were evaluated as early predictors of renal outcome, using survival analysis. Candidate variables were tested as predictors for CRR at time 0, 3 and 6 months after starting induction treatment. Potential predictors for renal flare were evaluated at time of reaching CRR. Variables with P Results We included 104 patients [81.7% female, mean (s.d.) age at baseline 32.0 (13.3) years]. Over follow-up, 91.7% reached CRR, within a median time of 6.0 months. Proteinuria Conclusion In patients with SLE and proliferative LN, factors assessed at baseline and 3 months from starting induction treatment can predict CRR and renal flares once CRR is achieved.

Objective.Cardiovascular (CV) disease (CVD) risk is increased in rheumatoid arthritis (RA). However, longterm followup studies investigating this risk are scarce.Methods.The CARRÉ (CARdiovascular research and RhEumatoid arthritis) study is a prospective cohort study investigating CVD and its risk factors in 353 patients with longstanding RA. CV endpoints were assessed at baseline and 3, 10, and 15 years after the start of the study and are compared to a reference cohort (n = 2540), including a large number of patients with type 2 diabetes (DM).Results.Ninety-five patients with RA developed a CV event over 2973 person-years, resulting in an incidence rate of 3.20 per 100 person-years. Two hundred fifty-seven CV events were reported in the reference cohort during 18,874 person-years, resulting in an incidence rate of 1.36 per 100 person-years. Age- and sex-adjusted HR for CV events were increased for RA (HR 2.07, 95% CI 1.57–2.72, p < 0.01) and DM (HR 1.51, 95% CI 1.02–2.22, p = 0.04) compared to the nondiabetic participants. HR was still increased in RA (HR 1.82, 95% CI 1.32–2.50, p < 0.01) after additional adjustment for CV risk factors. Patients with both RA and DM or insulin resistance had the highest HR for developing CVD (2.21, 95% CI 1.01–4.80, p = 0.046 and 2.67, 95% CI 1.30–5.46, p < 0.01, respectively).Conclusion.The incidence rate of CV events in established RA was more than double that of the general population. Patients with RA have an even higher risk of CVD than patients with DM. This risk remained after adjustment for traditional CV risk factors, suggesting that systemic inflammation is an independent contributor to CV risk.

Contains fulltext : 251785.pdf (Publisher’s version ) (Closed access)

Background: Disease-specific studies have reported impaired humoral responses after SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders treated with specific immunosuppressants. Disease-overarching studies, and data on recall responses and third vaccinations are scarce. Our primary objective was to investigate the effects of immunosuppressive monotherapies on the humoral immune response after SARS-CoV-2 vaccination in patients with prevalent immune-mediated inflammatory disorders.Methods: We did a cohort study in participants treated in outpatient clinics in seven university hospitals and one rheumatology treatment centre in the Netherlands as well as participants included in two national cohort studies on COVID-19-related disease severity. We included patients aged older than 18 years, diagnosed with any of the prespecified immune-mediated inflammatory disorders, who were able to understand and complete questionnaires in Dutch. Participants with immune-mediated inflammatory disorders who were not on systemic immunosuppressants and healthy participants were included as controls. Anti-receptor binding domain IgG responses and neutralisation capacity were monitored following standard vaccination regimens and a three-vaccination regimen in subgroups. Hybrid immune responses-ie, vaccination after previous SARS-CoV-2 infection-were studied as a proxy for recall responses.Findings: Between Feb 2 and Aug 1, 2021, we included 3222 participants in our cohort. Sera from 2339 participants, 1869 without and 470 participants with previous SARS-CoV-2 infection were analysed (mean age 49·9 years [SD 13·7]; 1470 [62·8%] females and 869 [37·2%] males). Humoral responses did not differ between disorders. Anti-CD20 therapy, sphingosine 1-phosphate receptor (S1P) modulators, and mycophenolate mofetil combined with corticosteroids were associated with lower relative risks for reaching seroconversion following standard vaccination (0·32 [95% CI 0·19-0·49] for anti-CD20 therapy, 0·35 [0·21-0·55] for S1P modulators, and 0·61 [0·40-0·90] for mycophenolate mofetil combined with corticosteroids). A third vaccination increased seroconversion for mycophenolate mofetil combination treatments (from 52·6% after the second vaccination to 89·5% after the third) but not significantly for anti-CD20 therapies (from 36·8% to 45·6%) and S1P modulators (from 35·5% to 48·4%). Most other immunosuppressant groups showed moderately reduced antibody titres after standard vaccination that did not increase after a third vaccination, although seroconversion rates and neutralisation capacity were unaffected. In participants with previous SARS-CoV-2 infection, SARS-CoV-2 antibodies were boosted after vaccination, regardless of immunosuppressive treatment.Interpretation: Humoral responses following vaccination are impaired by specific immunosuppressants. After standard vaccination regimens, patients with immune-mediated inflammatory disorders taking most immunosuppressants show similar seroconversion to controls, although antibody titres might be moderately reduced. As neutralisation capacity and recall responses are also preserved in these patients, this is not likely to translate to loss of (short-term) protection. In patients on immunosuppressants showing poor humoral responses after standard vaccination regimens, a third vaccination resulted in additional seroconversion in patients taking mycophenolate mofetil combination treatments, whereas the effect of a third vaccination in patients on anti-CD20 therapy and S1P modulators was limited.Funding: ZonMw (The Netherlands Organization for Health Research and Development).

BackgroundResearch on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking.MethodsAdult patients with rheumatic IMIDs from the Amsterdam Rheumatology and Immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex-matched and age-matched control subject. Clinical data were collected via online questionnaires (at baseline, and after 1–4 and 5–9 months of follow-up). Serum samples were collected twice and analysed for the presence of SARS-CoV-2-specific antibodies. Subsequently, IgG titres were quantified in samples with a positive test result.FindingsIn total, 3080 consecutive patients and 1102 controls with comparable age and sex distribution were included for analyses. Patients were more frequently hospitalised compared with controls when infected with SARS-CoV-2; 7% vs 0.7% (adjusted OR: 7.33, 95% CI: 0.96 to 55.77). Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19-related hospitalisation (adjusted OR: 14.62, 95% CI: 2.31 to 92.39). IgG antibody titres were higher in hospitalised compared with non-hospitalised patients, and slowly declined with time in similar patterns for patients in all treatment subgroups and controls.InterpretationWe observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalised when infected with SARS-CoV-2. Treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.

The treat-to-target (T2T) concept has improved outcomes for patients with diabetes, hypertension and rheumatoid arthritis. This therapeutic strategy involves choosing a well-defined, relevant target, taking therapeutic steps, evaluating whether the target has been achieved, and taking action if it has not. The T2T principle has been embraced by systemic lupus erythematosus (SLE) experts, but measurable and achievable outcomes, and therapeutic options, are needed to make this approach possible in practice. Considerable evidence has been generated regarding meaningful ‘state’ outcomes for SLE. Low disease activity has been defined and studied, and the most aspirational goal, remission, has been defined by the Definition of Remission in SLE task force. By contrast, current therapeutic options in SLE are limited, and more effective and safer therapies are urgently needed. Fortunately, clinical trial activity in SLE has been unprecedented, and encouraging results have been seen for novel therapies, including biologic and small-molecule agents. Thus, with the expected advent of such treatments, it is likely that sufficiently diverse therapies for SLE will be available in the foreseeable future, allowing the routine implementation of T2T approaches in the care of patients with SLE.

BackgroundPsoriatic arthritis (PsA) can present with peripheral (i.e. arthritis, enthesitis, dactylitis) and/or axial (spondyloarthritis) manifestations. Positron Emission Tomography (PET) may be a promising imaging technique for detection of whole body disease activity since it combines quantification and picomolar sensitivity for accurate depiction of pathologic processes with anatomical low dose CT imaging as a reference (3, 4). It was recently demonstrated that [18F]Fluoride PET-CT scans can successfully visualize and monitor ankylosing spondylitis disease activity by imaging of bone formation in the axial skeleton (5). Since bone formation is associated with enthesitis and synovitis in PsA, [18F]Fluoride may enable sensitive, whole body detection of disease activity in PsA.ObjectivesTo investigate the feasibility of [18F]Fluoride PET-CT to visualize disease activity of PsA by imaging of bone formation at axial and peripheral sites in PsA patients.MethodsSixteen patients (female 10/16, age 50.6 ±8.9 years) with PsA fulfilling CASPAR criteria and clinically active disease including ≥1 clinically active enthesitis site were included. Clinical disease activity was assessed by swollen joint count/tender joint count 44, MASES and SPARCC. Of each patient, a whole body [18F]Fluoride PET-CT scan at 45 minutes post injection was performed. All scans were dichotomously scored by two board certified readers (blinded for clinical data) for PET-positive lesions in the joints, peripheral enthesis sites and spine. Low dose CT was used for anatomical reference.ResultsOut of 1088 evaluated joints, 109 joints showed PET enhancement, most frequently in the interphalangeal- and metatarsal joints of the feet (14/109, 12,9%) (Figure 1A) and the distal interphalangeal joints of the hands (14/109, 12,9%). Out of 416 evaluated entheseal sites, PET positivity was found at 44 sites, mainly located at the patella tendon insertion (11/44, 25%) (Figure 1B) and the quadriceps tendon insertion (10/44, 22.7%). Of the PET positive joints and entheses sites, respectively 81.1% and 70.5% were not associated with tender or swollen joints and clinical enthesitis, respectively. In 11 out of the 16 patients ≥1 axial PET positive lesion was observed (Figure 1C), most frequently located in the cervical spine (19/49 observed axial lesions, 38.8%). Two patients showed PET enhancement in one sacro-iliac joint (SIJ) without any inflammatory back pain (IBP). Only four out of 15 patients reported IBP and missing data for 1 patient. In two patients clinical dactylitis was observed which was also depicted on PET-CT.Figure 1.[18F]Fluoride uptake in the metatarsal and IP-joints of the feet (A), in the patella tendon (B) and in the spine (C)Conclusion[18F]Fluoride PET-CT scans can visualize disease activity at whole body musculoskeletal manifestations of PsA by demonstrating local bone formation in joints, entheses and the axial skeleton. By sensitive imaging of bone formation at active sites, [18F]Fluoride PET-CT adds information to clinical disease activity, reflected by a high number of clinically negative, PET positive sites on top of concordant findings.References[1]Kaeley GS, Eder L, Aydin SZ, Gutierrez M, Bakewell C. Enthesitis: A hallmark of psoriatic arthritis. Semin Arthritis Rheum. 2018;48(1):35-43.[2]Ogdie A, Coates LC, Gladman DD. Treatment guidelines in psoriatic arthritis. Rheumatology (Oxford). 2020;59(Suppl 1):i37-i46.[3]von Schulthess GK, Steinert HC, Hany TF. Integrated PET/CT: current applications and future directions. Radiology. 2006;238(2):405-22.[4]Jones T. The role of positron emission tomography within the spectrum of medical imaging. Eur J Nucl Med. 1996;23(2):207-11.[5]Bruijnen STG, Verweij NJF, van Duivenvoorde LM, Bravenboer N, Baeten DLP, van Denderen CJ, et al. Bone formation in ankylosing spondylitis during anti-tumour necrosis factor therapy imaged by 18F-fluoride positron emission tomography. Rheumatology (Oxford). 2018;57(4):770.AcknowledgementsWe thank Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of InterestsJerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer, MSD, Consultant of: AbbVie, UCB, MSD, Novartis, Eli Lilly, Grant/research support from: Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie, UCB, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Advisory board AbbVie, Eli Lilly, Novartis, UCB, Grant/research support from: Novartis, Janssen, UCB, Eli Lilly, Arno Van Kuijk Speakers bureau: Novartis, Consultant of: Novartis, AbbVie, Janssen, Irene Bultink Speakers bureau: Eli Lilly, MSD, Amgen, UCB, GSK, Roche, Sanofi Genzyme (outsite the submitted work), Consultant of: Sanofi Genzyme, Astrazeneca (outside the submitted work), Lot Burgemeister Consultant of: Advisory board Novartis, Galapagos, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared

BackgroundIntercurrent infections are presumed potential triggers of systemic lupus erythematosus (SLE) disease flares.(1) However, most of the evidence is obtained from a limited number of observational studies, and the results of these studies are conflicting.(2,3)ObjectivesTo determine whether intercurrent infections are a risk factor for disease flares in SLE.MethodsDemographic and clinical characteristics of 203 SLE patients from the Amsterdam SLE cohort were collected at baseline, and at the start of an intercurrent infection that either was or was not followed by a flare within three months. Relevant data regarding infections and flares were collected systematically by chart review. Major and minor infections were defined as, respectively: infections for which hospital admission or intravenous antibiotic therapy was required, and infections (proven or not proven, but highly likely based on clinical symptoms and/or response to therapy) for which hospital admission was not warranted. SLE flares were defined as an increase in disease activity requiring intensification of immunosuppressive therapy. Flares were categorized as major or minor depending on fulfillment of a predefined set of criteria.(4) Incidence rates for infections, flares, and infections followed by a flare within three months were calculated using Poisson regression. Descriptive analyses were performed where appropriate. Proportional hazard models with recurrent events and time-varying covariates were used to estimate the hazard ratio of SLE flares.ResultsTable 1 shows the demographic and clinical characteristics of all 203 SLE patients. Fifty-six major infections occurred in 1060 patient years, and 670 minor infections occurred in 1048 patient years. The incidence rates of major and minor infections were 5.3 per 100 patient years (95% CI: 4.1 – 6.9) and 63.9 per 100 patient years (95% CI: 59.3 – 69.0), respectively. In total, 198 flares occurred within 1060 patient years. The incidence rate of flares is 18.7 per 100 patient years (95% CI: 16.3 – 21.5), 3.6 per 100 patient years (95% CI: 2.6 – 4.9) for major flares and 15.1 per 100 patient years (95% CI: 12.9 – 17.6) for minor flares.The incidence rates of, respectively, major and minor infections followed by a flare within three months were 0.7 per 100 patient years (95% CI: 0.3 – 1.4) and 2.3 per 100 patient years (95% CI: 1.5 – 3.4). Intercurrent infections (major and minor) were associated with the occurrence of SLE flares (major and minor; HR 1.9, 95% CI:1.3 – 2.9) (Figure 1). The hazard ratio for a major SLE flare following a major infection was 7.4 (95% CI 2.2 – 24.6). Major infections were not associated with the occurrence of minor flares.Table 1.Baseline demographic and clinical characteristicsVariablesSLE patients (n = 203)Sex, Female, n (%)184 (91)Age, years (median (IQR))40.0 (32.0 – 47.0)Caucasian ethnicity, n (%)137 (68)SLICC/ACR damage index (median (IQR))1 (0 – 2)SELENA-SLEDAI2k (median (IQR))4 (2 – 6)Disease duration, years (median (IQR))6 (1 – 11)History of: Biopsy proven lupus nephritis, n (%)38 (19) Renal insufficiency (eGFR < 45), n (%)6 (3) Diabetes mellitus, n (%)7 (3) Malignancy, n (%)5 (3) Stroke, n (%)12 (6) Asplenia, n (%)5 (3)Treatment variables: Glucocorticoids, n (%)106 (52) Antimalarials, n (%)151 (74) Immunosuppressants, n (%)75 (37) NSAIDs, n (%)67 (33)Figure 1.Estimated cumulative incidence of SLE flares (major and minor) following an intercurrent infection within three monthsConclusionThe results of the present study confirm a high frequency of infections in SLE patients and suggest that intercurrent infection is a risk factor for SLE flares. These findings underline the importance of prevention and treatment of infections in SLE patients and create awareness of infections as potential triggers of SLE flares.References[1]Fernandez D, et al. Curr. Rheumatol. Rep. 2016;18(3):14.[2]Bosch X, et al. Lupus. 2006;15(9):584-9.[3]Tsai PH, et al. Lupus. 2020;29(2):191-8.[4]Bootsma H, et al. Lancet. 1995;345(8965):1595-9.Disclosure of InterestsNone declared

Objectives The reversibility of interstitial lung disease (ILD) in SSc is difficult to assess by current diagnostic modalities and there is clinical need for imaging techniques that allow for treatment stratification and monitoring. 18F-Fluorodeoxyglucose (FDG) PET/CT scanning may be of interest for this purpose by detection of metabolic activity in lung tissue. This study aimed to investigate the potential role of 18F-FDG PET/CT scanning for the quantitative assessment of SSc-related active ILD. Methods 18F-FDG PET/CT scans and high resolution CT scans of eight SSc patients, including five with ILD, were analysed. For comparison, reference groups were included: eight SLE patients and four primary Sjögren’s syndrome (pSS) patients, all without ILD. A total of 22 regions of interest were drawn in each patient at apical, medial and dorsobasal lung levels. 18F-FDG uptake was measured as mean standardized uptake value (SUVmean) in each region of interest. Subsequently, basal/apical (B/A) and medial/apical (M/A) ratios were calculated at patient level (B/A-p and M/A-p) and at tissue level (B/A-t and M/A-t). Results SUVmean values in dorsobasal ROIs and B/A-p ratios were increased in SSc with ILD compared with SSc without ILD (P = 0.04 and P = 0.07, respectively), SLE (P = 0.003 and P = 0.002, respectively) and pSS (P = 0.03 and P = 0.02, respectively). Increased uptake in the dorsobasal lungs and increased B/A-t ratios corresponded to both ground glass and reticulation on high resolution CT. Conclusion Semi-quantitative assessment of 18F-FDG PET/CT is able to distinguish ILD from non-affected lung tissue in SSc, suggesting that it may be used as a new biomarker for SSc-ILD disease activity.

Summary In this study, no difference in bone loss was observed between patients with early RA initially treated with COmbinatietherapie Bij Reumatoide Artritis (COBRA) (including initially 60 mg/day prednisolone) and patients treated with COBRA-light (including initially 30 mg/day prednisolone) during 4-year observation. Purpose To assess changes in bone mineral density (BMD) after 4 years in early rheumatoid arthritis (RA) patients initially treated with COBRA-light or COBRA therapy. Methods In a 1 year, open-label, randomised, non-inferiority trial, patients were assigned to COBRA-light (methotrexate 25 mg/week plus initially prednisolone 30 mg/day) or COBRA (methotrexate 7.5 mg/week, sulfasalazine 2 g/day plus initially prednisolone 60 mg/day) therapy. After 1 year, antirheumatic treatment was at the discretion of treating rheumatologists. BMD was measured at baseline and after 1, 2 and 4 years at hips and lumbar spine with dual-energy X-ray absorptiometry. BMD changes between treatment strategies on average over time were compared with GEE analysis. Results Data from 155 out of 162 patients could be analysed: 68% were female with a mean age of 52 (SD 13) years. Both COBRA-light and COBRA therapy showed declines in BMD at the total hip of −3.3% and −1.7%, respectively (p = 0.12), and the femoral neck, −3.7% and −3.0%, respectively (p = 0.95). At the lumbar spine, both treatment groups showed minor decline in BMD over 4 years: −0.5% and −1.0%, respectively (p = 0.10). Conclusion In a treat-to-target design in early RA, over 4 years, no differences between groups were found in change in BMD at total hip, femoral neck and the lumbar spine. At the hip, bone loss was around 3% in both groups, while mild bone loss was observed at lumbar spine, both in patients starting prednisolone 60 and 30 mg/day. These data suggest that the well-known negative effects of prednisolone can be modulated by modern treatment of RA. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-020-05781-7.

Objectives This systematic review assessed which variables are associated with or are predictors for work participation outcomes in patients with systematic lupus erythematosus (SLE). Methods A literature search using MEDLINE, The Cochrane Library, Embase and CINAHL was conducted to identify all studies published from inception (1947) to June 2021 on factors related to and/or predicting employment status, absenteeism and/or presenteeism in SLE patients aged ≥18 years. The quality of included articles was assessed using the QUIPS tool. Narrative summaries were used to present the data. Results Fifteen studies (nine on associations, four on predictions, and two assessing both) were included, encompassing data of 3800 employed patients. Younger age, Caucasian ethnicity, higher educational level, lower disease activity score, shorter disease duration, absence of specific disease manifestations, higher levels of physical functioning and less physical job demands and higher levels of psychological/cognitive functioning were associated with or predicted favorable work outcomes. Older age, non-Caucasian ethnicity, female gender, never being married, poverty, lower educational level, higher disease activity score, longer disease duration, specific disease manifestations, lower levels of physical functioning, more physical job demands and low job control, less job tenure and lower levels of cognitive functioning were associated with or predicted an unfavorable work outcome. Limitations of the evidence were the quality of the studies and the use of heterogeneous outcome measures, applied statistical methods and instruments used to assess work participation. Conclusion We recommend applying the EULAR points to consider for designing, analysing and reporting on work participation in inflammatory arthritis also to SLE studies on work participation, to enhance the quality and comparability between studies and to better understand the impact of SLE on work participation. Trial registration registration in PROSPERO (CRD42020161275; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=161275).

Objectives The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

Objective: Autoimmune thyroid disease often coexists with rheumatoid arthritis (RA) and is associated with elevated cardiovascular (CV) risk. However, studies in RA patients are scarce. Our aim was to investigate whether autoimmune thyroid disease increases the risk of new cardiovascular disease (CVD) in RA. Method: Thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) were assessed in 323 RA patients participating in an ongoing prospective cohort study designed to assess CV risk factors, morbidity, and mortality. Cox proportional hazard models were used to calculate hazard ratios (HRs) for new CVD and adjusted for age, gender, smoking, prevalent CVD, thyroxine replacement therapy, and RA duration. Results: Of the 323 participants, 65.3% were female, and mean ± sd age was 63 ± 7 years. At baseline, 8.1% were hypothyroid (n = 26, 16 clinical, 10 subclinical), 6.8% hyperthyroid (n = 22, 13 clinical, 9 subclinical), and 85.1% (n = 275) euthyroid. A new CV event developed in 94 patients (29.1%) during follow-up. Compared to euthyroid patients, the HR adjusted for age, gender, and prevalent CVD was 2.83 [95% confidence interval (CI) 1.13–7.09; p = 0.026] for subclinical hypothyroidism. Further adjustment for smoking, thyroxine replacement therapy, and RA duration resulted in an HR of 3.0 (95% CI 1.19–7.54; p = 0.02) for CV events in patients with subclinical hypothyroidism. Conclusion: There was no difference in CVD between RA patients with hypothyroidism and hyperthyroidism versus euthyroid patients. Coexistence of subclinical hypothyroidism with RA is associated with a higher occurrence of new CV events. Treatment trials are needed to determine whether thyroxine supplementation can further improve CV outcome in these patients.

IntroductionSystemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure.Methods and analysisThe UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years.Ethics and disseminationThe study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels.Trial registration numbersNCT04464434; NL 8720.

Background Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD), partly due to an increased prevalence of cardiovascular risk factors, but also due to chronic systemic inflammation inducing atherosclerotic changes of the arterial wall. The aim of this study was to determine whether anti-inflammatory therapy for the treatment of RA has favorable effects on arterial wall inflammation in RA patients. Methods Arterial wall inflammation before and after 6 months of anti-inflammatory treatment was assessed in 49 early and established RA patients using 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (18F-FDG-PET/CT). Arterial 18F-FDG uptake was quantified as maximum standardized uptake value (SUVmax) in the thoracic aorta, abdominal aorta, carotid, iliac and femoral arteries. Early RA patients (n = 26) were treated with conventional synthetic disease modifying anti-rheumatic drugs with or without corticosteroids, whereas established RA patients (n = 23) were treated with adalimumab. Results In RA patients, overall SUVmax was over time reduced by 4% (difference −0.06, 95%CI −0.12 to −0.01, p = 0.02), with largest reductions in carotid (-8%, p = 0.001) and femoral arteries (−7%, p = 0.005). There was no difference in arterial wall inflammation change between early and established RA patients (SUVmax difference 0.003, 95%CI −0.11 to 0.12, p = 0.95). Change in arterial wall inflammation significantly correlated with change in serological inflammatory markers (erythrocyte sedimentation rate and C-reactive protein). Conclusion Arterial wall inflammation in RA patients is reduced by anti-inflammatory treatment and this reduction correlates with reductions of serological inflammatory markers. These results suggest that anti-inflammatory treatment of RA has favorable effects on the risk of cardiovascular events in RA patients.

Systemic lupus erythematosus (SLE) is a heterogeneous disease, characterised by a wide spectrum of clinical manifestations (ranging from arthritis and skin manifestations to renal insufficiency or central nervous system involvement) with an unpredictable relapsing-remitting course. SLE primarily affects young women in their childbearing lifetime, and perinatal complications due to SLE and/or the coexistence of the presence of antiphospholipid antibodies, can occur. Also, low complement levels and many antibodies can be found in SLE, among which anti-ds DNA and anti-Sm. During the disease course, irreversible organ damage can accrue due to SLE and/or its treatment. In addition, comorbidities can develop, including infections, osteoporosis and atherosclerosis. Compared to the general population, quality of life is reduced, frequently due to severe fatigue or psychological issues, amongst other reasons. As such reduced work capacity and/or work loss may occur. So, how should we assess and monitor patients with SLE?1 2 The (frequency of) assessments depends on the stage of disease (diagnosis and follow-up). Disease activity (active disease [i.e. every 1–3 months] versus stable disease [i.e. every 6–12 months]), and specific conditions (i.e. pregnancy, thrombosis and bone fractures). Measuring disease activity with validated instruments (i.e. SLEDAI-2k, BILAG 2004) at each visit is recommended, in addition to a history and clinical examination, laboratory assessments (including blood, urine and immunology test) and eventually other investigations (i.e. imaging or biopsy); using these instruments results in better outcome, although the evidence is of low-moderate quality. However, high disease activity is associated with poor outcome (higher mortality rate, higher level of organ damage and comorbidities). Conversely, lower levels of disease activity and remission are associated with better outcome. It is important that clinical symptoms can be due to one or any combination of the following: disease activity, thrombosis or active inflammation, drug toxicity, chronic damage due to the disease or to its treatment, or to comorbidity (i.e. infection). Yearly assessment of disease damage (with SLICC Damage Index, SDI) is recommended, although the evidence of better outcome is of low-moderate quality. However, early and late damage is associated with small to moderate increase in mortality, further damage in the future and reduced quality of life and therefore is justified to assess. Regular assessment of cardiovascular (CV) risk factors in particular as well as corticosteroid-associated adverse events is recommended, with moderate-high quality evidence for CV assessment. The rationale and principles of treat-to-target (T2T) in SLE and how to incorporate T2T in daily clinical practice will be discussed.3–5 Learning Objectives Describe the relevance of systematic assessment of disease activity, disease damage, comorbidities and quality of life Explain the current clinical practice guidelines in SLE, and define unmet needs in order to improve our daily practice Discuss the current state of T2T in SLE References Gordon C, Amissah-Arthur MB, Gayed M, et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults: Executive Summary. Rheumatology (Oxford) 2018;57(1):14–18. Keeling SO, Alabdurubalnabi Z, Avina-Zubieta A, et al. Canadian Rheumatology Association Recommendations for the Assessment and Monitoring of Systemic Lupus Erythematosus. J Rheumatol 2018;45(10):1426–39. Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 2020;79(6):713–23. Golder V, Kandane-Rathnayake R, Hoi AY, et al. Association of the lupus low disease activity state (LLDAS) with health-related quality of life in a multinational prospective study. Arthritis Res Ther 2017;19(1):62. van Vollenhoven R, Voskuyl A, Bertsias G, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis 2017;76(3):554–61.

Funder: European League Against Rheumatism; FundRef: http://dx.doi.org/10.13039/501100008741, Objective: To update the 2012 EULAR/ERA–EDTA recommendations for the management of lupus nephritis (LN). Methods: Following the EULAR standardised operating procedures, a systematic literature review was performed. Members of a multidisciplinary Task Force voted independently on their level of agreeement with the formed statements. Results: The changes include recommendations for treatment targets, use of glucocorticoids and calcineurin inhibitors (CNIs) and management of end-stage kidney disease (ESKD). The target of therapy is complete response (proteinuria 1 g/24 hours despite renin–angiotensin–aldosterone blockade, MMF in combination with glucocorticoids is preferred. Assessment for kidney and extra-renal disease activity, and management of comorbidities is lifelong with repeat kidney biopsy in cases of incomplete response or nephritic flares. In ESKD, transplantation is the preferred kidney replacement option with immunosuppression guided by transplant protocols and/or extra-renal manifestations. Treatment of LN in children follows the same principles as adult disease. Conclusions: We have updated the EULAR recommendations for the management of LN to facilitate homogenization of patient care.

Objectives To gain insight into SSc patients’ perspective on quality of care and to survey their preferred quality indicators. Methods An online questionnaire about healthcare setting, perceived quality of care (CQ index) and quality indicators, was sent to 2093 patients from 13 Dutch hospitals. Results Six hundred and fifty patients (mean age 59 years, 75% women, 32% limited cutaneous SSc, 20% diffuse cutaneous SSc) completed the questionnaire. Mean time to diagnosis was 4.3 years (s.d. 6.9) and was longer in women compared with men (4.8 (s.d. 7.3) vs 2.5 (s.d. 5.0) years). Treatment took place in a SSc expert centre for 58%, regional centre for 29% or in both for 39% of patients. Thirteen percent of patients was not aware of whether their hospital was specialized in SSc. The perceived quality of care was rated with a mean score of 3.2 (s.d. 0.5) (range 1.0–4.0). There were no relevant differences between expert and regional centres. The three prioritized process indicators were: good patient-physician interaction (80%), structural multidisciplinary collaboration (46%) and receiving treatment according to SSc guidelines (44%). Absence of disease progression (66%), organ involvement (33%) and digital ulcers (27%) were the three highest rated outcome indicators. Conclusion The perceived quality of care evaluated in our study was fair to good. No differences between expert and regional centres were observed. Our prioritized process and outcome indicators can be added to indicators suggested by SSc experts in earlier studies and can be used to evaluate the quality of care in SSc.

Objectives: To gain insight into the experiences of patients with diffuse cutaneous systemic sclerosis during and after autologous hematopoietic stem cell transplantation. Methods: Semi-structured interviews were conducted with patients who underwent hematopoietic stem cell transplantation in four university hospitals in the Netherlands. Interviews were transcribed verbatim and thematically analyzed. Results: Nine male and seven female patients were interviewed, median age 47 years (range: 27–68). Patients mentioned their life was severely disrupted before hematopoietic stem cell transplantation and remained unsettled a long time after treatment. Uncertainty because of disease progression, loss of control over health and the sense of time and fear of treatment-related adverse events were common during hospitalization. After hematopoietic stem cell transplantation, patients experienced more physical limitations than they had expected, and recovery took longer and was mentally taxing. Going back to work and finding a new balance in personal relations and social life was complicated. Patients described various strategies to deal with challenges. Family and friends provided essential support, although many experienced a dwindling social circle. Most patients also appreciated peer support. All patients were satisfied with the low threshold for contact with physicians and nurses during hospitalization. However, aftercare focused on medical aspects rather than on psychological well-being and social issues. Moreover, patients would have preferred to be better prepared on what to expect after discharge, and lacked information about self-management, prognosis, optimal recovery, work, sexuality, and family planning. Conclusion: Hematopoietic stem cell transplantation has a major physical and psychological impact on patients with diffuse cutaneous systemic sclerosis. The course of recovery after this intensive therapy was unexpectedly long for some patients and offer of support was far less pro-active post-HSCT compared to pre-HSCT and during HSCT.

BackgroundBone formation is a histopathologic feature of ankylosing spondylitis (AS), causing structural changes through the formation of syndesmophytes and spinal ankyloses (1, 2) Recent studies with [18F]Fluoride Positron emission tomography (PET) demonstrated that disease activity of AS is best reflected by bone formation rather than inflammation and is sensitive to change during therapy (2, 3). [18F]Fluoride PET(/CT) identifies more lesions in active AS than bone marrow edema on MRI, so may provide complementary information about the disease activity (3). A direct comparison between [18F]Fluoride PET(/CT) and MRI and X-rays will allow better understanding of PET-CT positive lesions and will support further positioning of the technique for diagnostics and monitoring of AS.ObjectivesTo relate uptake of [18F]Fluoride on PET-CT to abnormalities on MRI and conventional radiography in patients with clinically active AS.MethodsTen patients (female 6/10, age 38±11 years) with AS based on modified New York criteria, a BASDAI of ≥ 4 and naïve to biologicals were included. All patients received a [18F]Fluoride PET(/CT) scan, MRI scan and x-rays of the spine and SI-joints. Experienced readers blinded to clinical data and findings on other modalities scored the respective scans. PET scans were dichotomously scored for PET-positivity. MRI scans were scored in the spine for fatty lesions, erosions, ankylosis and bone marrow edema (BME) and erosions, ankylosis and BME in the SI-joints. X-rays were scored for erosions, syndesmophytes and ankylosis. Lesions on all modalities were compared with Cohen’s kappa, linear regression, and univariate and multivariate analysis with a generalized mixed model.ResultsIn total, 69 lesions with enhanced [18F]Fluoride uptake compared to local background, 257 MRI lesions and 88 x-ray lesions were observed in the spine (Table 1). Most lesions were found in the thoracic spine. PET lesions were frequently located outside the field of view (FOV) of the MRI and X-ray in respectively costovertebral and facet joints (31/69; 45%). Univariate analysis PET positivity had the strongest association with the presence of MRI BME and x-ray bridges (OR 6.6, 95% C.I. 2.0 – 21.1, p = 0.002 and OR 34, 95% C.I. 6.0 – 183, p p < 0.01 and OR 6.4, 95% 1.7 – 23.5, p < 0.01 respectively) (Figure 1). However, of all PET-positive lesions only 7/24; 29% within the FOV of the MRI showed BME and 13/23; 56% of the PET lesions within the FOV of the X-ray showed bridges on X-ray. In the SI-joints, a total of 15 lesions (15/20; 75%) with PET enhancement were found. Erosions, ankylosis and BME lesions on MRI were observed in respectively 13/15; 87%, 4/15; 27% and 13/15; 87% of the lesions with PET enhancement.Table 1.Distribution of lesions throughout the spine on different modalities.Number of lesionsCervical spineThoracic spineLumbar spineTotalPET4422369PET, within FOV MRI1111224PET, within FOV x-ray1101223MRI – fatty lesions15301560MRI – erosions0011MRI – ankylosis212127150MRI – BME1351046X-ray erosions1425039x-ray syndesmophytes1012X-ray bridges4311247FOV: field of viewFigure 1.Example of Fluoride uptake on PET (A), corresponding BME on MRI (B) and bridges on X-ray (C).ConclusionLesions with [18F]Fluoride on PET showed significant correlation to MRI BME and x-ray bridge lesions. It showed partial agreement with BME of MRI and bridges on X-ray. This suggests that [18F]Fluoride PET visualizes different mechanisms central to AS disease activity compared to MRI and X-ray, thereby providing novel and additional information.References[1]Lee SG et al. Clin Exp Rheumatol. 2015;33(1):90-7.[2]Bruijnen STG et al. Rheumatology (Oxford). 2018;57(4):770.[3]Bruijnen ST et al. Arthritis Res Ther. 2012;14(2):R71.Disclosure of InterestsJerney de Jongh: None declared, Nicki Pouw-Verweij: None declared, Gerben C.J. Zwezerijnen: None declared, J.C. van Denderen: None declared, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer, MSD, Consultant of: AbbVie, UCB, MSD, Novartis, Eli Lilly, Grant/research support from: Unrestricted Grants received for investigator initiated studies from MSD, Pfizer, AbbVie, UCB, Joost Bot: None declared, B.J.H. Boden: None declared, Robert Hemke: None declared, Frank F Smithuis: None declared, Alexandre Voskuyl: None declared, Maarten Boers Consultant of: Novartis, Maqsood Yaqub: None declared, Conny J. van der Laken: None declared

Objectives To validate the IFN response gene (IRG) set for the prediction of non-response to rituximab in rheumatoid arthritis (RA) and assess the predictive performance upon combination of this gene set with clinical parameters. Methods In two independent cohorts of 93 (cohort I) and 133 (cohort II) rituximab-starting RA patients, baseline peripheral blood expression of eight IRGs was determined, and averaged into an IFN score. Predictive performance of IFN score and clinical parameters was assessed by logistic regression. A multivariate prediction model was developed using a forward stepwise selection procedure. Patients with a decrease in disease activity score (ΔDAS28) ≥ 1.8 after 6 months of therapy were considered responders. Results The mean IFN score was higher in non-responders compared to responders in both cohorts, but this difference was most pronounced in patients who did not use prednisone, as described before. Univariate analysis in cohort I showed that baseline DAS28, IFN score, DMARD use and negativity for IgM-RF and/or ACPA were associated with rituximab non-response. The multivariate model consisted of DAS28, IFN score and DMARD use, which showed an area under the curve (AUC) of 0.82. In cohort II, this model revealed a comparable AUC in PREDN-negative patients (0.78), but AUC in PREDN-positive patients was significantly lower (0.63), which seemed due to effect modification of the IFN score by prednisone. Conclusions Combination of predictive parameters provided a promising model for the prediction of non-response to rituximab, with possibilities for optimization via definition of the exact interfering effect of prednisone on IFN score. Trial registration (Cohort II, SMART trial) NCT01126541 , registered 18 May 2010.

ObjectiveTo determine whether macrophage positron emission tomography (PET)/computed tomography (CT) imaging using (R)-[11C]PK11195 at 0 and 2 weeks is associated with clinical response at 13 weeks in patients with early rheumatoid arthritis (RA).MethodsWhole-body (R)-[11C]PK11195 PET/CT scans were performed at baseline and after 2 weeks of COBRA-light (combination therapy of methotrexate and prednisone) treatment in 35 patients with clinically active early RA. Clinical assessment (Disease Activity Score of 44 joints (DAS44)) was performed at 0, 2 and 13 weeks of treatment. PET/CT scans were assessed visually by two blinded, experienced readers, and by calculating standardised uptake values (SUVs) for shoulders, elbows, hips, knees, and hand and feet joints. Clinical and PET variables were compared using (multivariate) linear regression.Results18 males and 17 females were included (baseline DAS44=3.2 ± 1.0). 171 out of 1470 joints were visually PET positive at baseline, decreasing to 100 joints after 2 weeks. In general, small feet joints showed the highest uptake at baseline, and the largest decrease after 2 weeks (Δ0-2). Neither baseline nor Δ0-2 PET measures correlated with DAS44 at 13 weeks. However, at 2 weeks, average SUV of the feet significantly correlated with DAS44 at 13 weeks (R2=0.14, p=0.04). In a multivariable model, DAS44 and average SUV of the feet at 2 weeks showed substantial combined predictive value (combined R2=0.297, pConclusionQuantitative macrophage PET assessment of feet joints, together with DAS44, after 2 weeks of COBRA light treatment in patients with early RA correlates with clinical response after 3 months of treatment.

Systemic sclerosis (SSc) is an orphan disease characterised by autoimmunity, fibrosis of the skin and internal organs, and vasculopathy. SSc may be associated with high morbidity and mortality. In this narrative review we summarise the results of a systematic literature research, which was performed as part of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases project, aimed at evaluating existing clinical practice guidelines or recommendations. Only in the domains ‘Vascular & Ulcers’ (ie, non-pharmacological approach to digital ulcer), ‘PAH’ (ie, screening and treatment), ‘Treatment’ and ‘Juveniles’ (ie, evaluation of juveniles with Raynaud’s phenomenon) evidence-based and consensus-based guidelines could be included. Hence there is a preponderance of unmet needs in SSc referring to the diagnosis and (non-)pharmacological treatment of several SSc-specific complications. Patients with SSc experience significant uncertainty concerning SSc-related taxonomy, management (both pharmacological and non-pharmacological) and education. Day-to-day impact of the disease (loss of self-esteem, fatigue, sexual dysfunction, and occupational, nutritional and relational problems) is underestimated and needs evaluation.

Objectives: Several chronic inflammatory diseases are associated with cardiovascular disease, but the risk in ANCA-associated vasculitis is poorly quantified. The aim of the present study was to review the evidence for an increased cardiovascular risk, including ischaemic heart disease, cerebrovascular accidents and peripheral arterial disease, in patients with ANCA-associated vasculitis.Methods: A comprehensive systematic review was conducted in accordance with guidelines of preferred reporting items for systematic reviews and meta-analyses. The databases PubMed, Embase.com and the Cochrane Library (Wiley) were searched for original observational studies comparing vasculitis patients with at least one control group. Summary estimates were derived with a random-effects model and reported as relative risks.Results: One thousand three hundred and seventy-five studies were identified. Seven studies were included, comprising almost 14 000 ANCA-associated vasculitis patients vs general population controls in six studies and chronic kidney disease patients in one study. ANCA-associated vasculitis carried a relative risk of 1.65 (95% CI: 1.23, 2.22) for all cardiovascular events, 1.60 (95% CI: 1.39, 1.84) for ischaemic heart disease and 1.20 (95% CI: 0.98, 1.48) for cerebrovascular accidents. We did not find studies that addressed the risk for peripheral arterial disease separately. No heterogeneity was seen in the estimates.Conclusion: This meta-analysis of observational studies supports an increase in cardiovascular risk in patients with ANCA-associated vasculitis of ∼65%, similar to that found in other chronic inflammatory diseases. Hence, there is a clear need for active cardiovascular risk management in patients with ANCA-associated vasculitis.

To investigate whether remission at single and consecutive visits predicts good outcome in early rheumatoid arthritis (RA). The presence of remission according to American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) and other criteria (Boolean clinical, Clinical Disease Activity Index, Disease Activity Score [DAS], DAS in 28 joints, and Routine Assessment of Patient Index Data 3) was assessed in early RA patients during the first year of the Combination Therapy for Rheumatoid Arthritis light trial. Likelihood ratios were used to assess whether meeting the remission criteria at single visits (13, 26, 39, or 52 weeks) and consecutive visits (13 and 26, 26 and 39, or 39 and 52 weeks) predicted good outcome in the second year (52-104 weeks). Good outcome was defined for function (Health Assessment Questionnaire score consistently ≤0.5 and no deterioration), radiographic damage progression (no deterioration in Sharp/van der Heijde scores), and both ("overall good outcome"). Of the original 164 trial patients, 144 had evaluable data. In the second year, good functional outcome was observed in 35%, good radiographic outcome in 79%, and both in 28% of the patients. Almost all criteria predicted good functional and good overall outcome, at both single and consecutive visits; only single DAS remission did not significantly predict good overall outcome (P = 0.07). Sustained remission periods resulted in higher likelihood ratios than remission at single visits. None of the criteria predicted good radiographic outcome. Early RA patients who reached remission according to ACR/EULAR and other criteria during short or sustained periods were likely to retain good physical function in the subsequent months. Sustained remission periods were a stronger predictor than remission at single visits. However, in the setting of low overall damage progression, (sustained) remission was not predictive of good radiographic outcome

ObjectivesTreat-to-target recommendations have identified ‘remission’ as a target in systemic lupus erythematosus (SLE), but recognise that there is no universally accepted definition for this. Therefore, we initiated a process to achieve consensus on potential definitions for remission in SLE.MethodsAn international task force of 60 specialists and patient representatives participated in preparatory exercises, a face-to-face meeting and follow-up electronic voting. The level for agreement was set at 90%.ResultsThe task force agreed on eight key statements regarding remission in SLE and three principles to guide the further development of remission definitions:1. Definitions of remission will be worded as follows: remission in SLE is a durable state characterised by …………………. (reference to symptoms, signs, routine labs).2. For defining remission, a validated index must be used, for example, clinical systemic lupus erythematosus disease activity index (SLEDAI)=0, British Isles lupus assessment group (BILAG) 2004 D/E only, clinical European consensus lupus outcome measure (ECLAM)=0; with routine laboratory assessments included, and supplemented with physician's global assessment.3. Distinction is made between remission off and on therapy: remission off therapy requires the patient to be on no other treatment for SLE than maintenance antimalarials; and remission on therapy allows patients to be on stable maintenance antimalarials, low-dose corticosteroids (prednisone ≤5 mg/day), maintenance immunosuppressives and/or maintenance biologics.The task force also agreed that the most appropriate outcomes (dependent variables) for testing the prognostic value (construct validity) of potential remission definitions are: death, damage, flares and measures of health-related quality of life.ConclusionsThe work of this international task force provides a framework for testing different definitions of remission against long-term outcomes.

Objectives Patients with ANCA-associated vasculitis are at increased risk of cardiovascular events. The aim of the present study was to assess predictors of cardiovascular events in patients with granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis. Methods This retrospective cohort study included patients from the Canadian Vasculitis Research Network cohort in Toronto. Characteristics at diagnosis were collected. During follow-up, non-fatal cardiovascular events were determined from the Vasculitis Damage Index; mortality and causes of death were recorded. Cox regression models were developed to determine predictors of cardiovascular events, defined as stroke or myocardial infarction. Results A total of 336 patients were included (231 [69%] granulomatosis with polyangiitis; 105 [31%] eosinophilic granulomatosis with polyangiitis). The mean age at diagnosis was 44 (±18) years and 44% were male. The incidence rate for the combined outcome of all fatal and non-fatal events was 7.2 events per 1000 patient-years. In a multivariate model, family history of cardiovascular events and a higher Birmingham Vasculitis Activity Score at diagnosis were predictive of cardiovascular events (hazard ratio and 95% confidence interval 3.46 [1.06–11.28] and 1.09 [1.02–1.16] respectively). In a subgroup analysis there was no association between cardiovascular or disease-specific characteristics and cardiovascular events in eosinophilic granulomatosis with polyangiitis. Conclusions In this cohort of patients with granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, both traditional and disease-related risk factors were predictive of cardiovascular events. Further prospective studies should elucidate the impact of these and other modifiable risk factors on cardiovascular risk in ANCA-associated vasculitis.

Objectives To examine the treatment decision-making process of patients with dcSSc in the context of haematopoietic stem cell transplantation (HSCT). Methods A qualitative semi-structured interview study was done in patients before or after HSCT, or patients who chose another treatment than HSCT. Thematic analysis was used. Shared decision-making (SDM) was assessed with the 9-item Shared Decision Making Questionnaire (SDM-Q-9). Results Twenty-five patients [16 male/nine female, median age 47 (range 27–68) years] were interviewed: five pre-HSCT, 16 post-HSCT and four following other treatment. Whereas the SDM-Q-9 showed the decision-making process was perceived as shared [median score 81/100 (range 49–100)], we learned from the interviews that the decision was predominantly made by the rheumatologist, and patients were often steered towards a treatment option. Strong guidance of the rheumatologist was appreciated because of a lack of accessible, reliable and SSc-specific information, due to the approach of the decision-making process of the rheumatologist, the large consequence of the decision and the trust in their doctor. Expectations of outcomes and risks also differed between patients. Furthermore, more than half of patients felt they had no choice but to go for HSCT, due to rapid deterioration of health and the perception of HSCT as ‘the holy grail’. Conclusion This is the first study that provides insight into the decision-making process in dcSSc. This process is negatively impacted by a lack of disease-specific education about treatment options. Additionally, we recommend exploring patients’ preferences and understanding of the illness to optimally guide decision-making and to provide tailor-made information.

Objective: To identify predictors of sick leave and improved worker productivity in patients with early rheumatoid arthritis (RA) treated for 52 weeks with intensive combination strategies. Methods: Patients with early RA were included in the COmbinatietherapie Bij Reumatoïde Artritis (COBRA)-light trial and followed for 52 weeks. As the COBRA-light strategy proved to be non-inferior to the COBRA strategy, all patients were pooled. Predictors for sick leave and improved worker productivity were assessed through a 3 month time-lag multivariable logistic generalized estimating equations model. Results: At baseline, 97 patients had a paid job, 59 had no job, and for six patients the work status was unknown. During the trial, 13 patients stopped working (8%) and six started working (4%). Only sick leave in the past 3 months predicted sick leave. By excluding this variable, patient global assessment and actual hours of sick leave became predictors. Increased worker productivity was predicted by higher patient global assessment levels, Sharp van der Heijde score ≥ 1, actual hours on sick leave, and higher worker productivity in the past 3 months. Conclusion: Sick leave and improved worker productivity were mainly predicted by non-disease-specific variables. Both outcomes can be predicted on a 3 month basis, using the outcome over the past 3 months for the next 3 months. By applying this model in daily practice, decisions for therapy change could be based not solely on disease activity but also taking into account a possible high risk for sick leave in the upcoming 3 months.

Background: Patients with ANCA-associated vasculitis (AAV) are at increased risk of cardiovascular (CV) disease.(1) Objectives: The aim of the present study was to determine the prevalence of CV risk factors in patients with AAV and to evaluate the management of CV risk factors according to current guidelines. Methods: A cross-sectional study was performed in patients with AAV in the Netherlands and Canada. Information on traditional CV risk factors, as well as markers of inflammation and kidney function, were collected. Their prevalence and treatment were studied and compared with recommendations in current guidelines. Results: A total of 144 consecutive patients with AAV were included (71 from the Netherlands; 73 from Canada). Mean age was 62 ± 15 years, and 56% were male. The mean disease duration was 7.0 ± 6.6 years; 69% had granulomatosis with polyangiitis, 17% microscopic polyangiitis and 14% eosinophilic granulomatosis with polyangiitis. Mean body mass index was 28 ± 6 kg/m2 and 65 patients (45%) had an estimated glomerular filtration rate Conclusion: Patients with AAV have a high prevalence of traditional CV risk factors. Whether past or persistent inflammation and chronic kidney disease further increases the CV risk remains to be studied. Strict adherence to CV risk management guidelines should be encouraged. Reference: [1] Houben E, Penne EL, Voskuyl AE, van der Heijden JW, Otten RHJ, Boers M, et al. Cardiovascular events in anti-neutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of observational studies. Rheumatology (Oxford) 2018; 57: 555-62. Disclosure of Interests: None declared

Background:Remission is the stated goal for both patient and care-giver (1), but consensus on a definition of remission has been lacking. Previously, an international task force consisting of patient representatives and medical specialists published a frame-work for such a definition (2), but without making a final recommendation.Objectives:To achieve consensus around a definition of remission in SLE (DORIS).Methods:The DORIS task force met annually from 2015 to 2020 and consisted of patient representatives and specialists in rheumatology, nephrology, dermatology, and clinical immunology. Systemic literature reviews of several key topics were done and specific research questions were examined in suitably chosen datasets. The findings were discussed, reformulated as recommendations, and voted upon. Level of evidence (LoE), strength of recommendation (SoR), and agreement were determined in standard fashion. The final recommendation for the DORIS definition of remission was established by electronic vote after finalization of the minutes of the most recent task force meeting.Results:Based on data from the literature and from several SLE-specific data sets, five key recommendations were endorsed (Table 1) that should be seen as additions to those published previously (2). Literature reviews identified strong support for the face-, content-, construct- and criterion validity of the definition based on the clinical SLEDAI (not including anti-DNA and complement) equal to zero plus low physician global assessment and allowing stable medical treatment. Thus, the DORIS Task Force recommended a single definition of remission in SLE, based on clinical SLEDAI = 0, evaluator’s global assessment Table 1.Vote in favorLoESoRAgreement1.Inclusion of serology [anti-DNA, complement] in the DORIS definition of remission-on-treatment does not meaningfully alter the construct validity and therefore it is not recommended to include it90%2aB8.382.While the goal of treatment is sustained remission, a definition of remission should be able to be met at any point in time; therefore, duration should not be included in the definition100%5C9.023.To date, the SLEDAI-based definitions of remission have formally been investigated more extensively than BILAG-or ECLAM-based definitions. The SLEDAI-based definitions can therefore more confidently be recommended91%2aB9.254.Remission off treatment, while the ultimate goal for many patients and providers, is achieved very rarely. In clinical research and as an outcome in clinical trials, the definition for remission-on-treatment is recommended92%2aB9.525.In clinical trials, the LLDAS definition for low disease activity and the DORIS definition of remission are both recommended as outcomes100%5C9.25The 2021 DORIS definition of remission in SLE:Conclusion:The 2021 DORIS definition of remission in SLE was established. It is recommended for use as an aspirational treatment target in clinical care, a clear concept in education, and a key outcome in research including clinical trials and observational studies.References:[1]van Vollenhoven RF, Mosca M, Bertsias G, et al. Treat-to-target in systemic lupus erythematosus: recommendations from an international task force. Ann Rheum Dis 2014;73:958-67.[2]van Vollenhoven R, Voskuyl A, Bertsias G, et al. A framework for remission in SLE: consensus findings from a large international task force on definitions of remission in SLE (DORIS). Ann Rheum Dis 2016.Disclosure of Interests:Ronald van Vollenhoven Speakers bureau: AbbVie, Galapagos, GSK, Janssen, Pfizer, UCB, Consultant of: AbbVie, AstraZeneca, Biogen, Biotest, Celgene, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB, Vielabo, Grant/research support from: BMS, GSK, Lilly, UCB, George Bertsias: None declared, Andrea Doria: None declared, David Isenberg: None declared, Eric F. Morand: None declared, Michelle A Petri: None declared, Bernardo Pons-Estel Consultant of: GSK, Janssen, Anisur Rahman: None declared, Manuel Ugarte-Gil Grant/research support from: Janssen, Pfizer, Alexandre Voskuyl: None declared, Laurent Arnaud Consultant of: Alexion, Amgen, Astra-Zeneca, BMS, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Medac, Novartis, Pfizer, Roche-Chugaï, UCB., Ian N. Bruce: None declared, Ricard Cervera Consultant of: GSK, Alexion, Eli Lilly, Astra Zeneca, Termo-Fisher, Rubió, Nathalie Costedoat-Chalumeau: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MGP, Sanofi, UCB, Frederic Houssiau: None declared, Marta Mosca: None declared, Matthias Schneider: None declared, Michael Ward: None declared, Cynthia Aranow: None declared.

Background:Patients with rheumatoid arthritis have an increased risk for developing cardiovascular diseases (CVD) compared to the general population, similar to the CVD risk in patients with diabetes mellitus. However, there are no controlled studies investigating the incidence of cardiovascular (CV) events in RA patients with follow up of more than 20 years.Objectives:The objectives of the current study were to investigate the incidence rates of CV events in a long-term follow up cohort of RA patients, and to compare these to a similar cohort representing the general population, ie. The Hoorn study.Methods:The CARRÉ study is an ongoing prospective cohort study, which started in 2001, investigating CV mortality and morbidity in 353 randomly selected patients with RA. Primary endpoints, i.e. verified medical history of coronary, cerebral or peripheral arterial disease, were determined at baseline, and after three, ten, fifteen and twenty years of follow up. Patients were censored at the date of an experienced CV event or their death. Incidence density rates per 100 patient years were calculated. Data were compared to results from the Hoorn study, a Dutch cohort study of glucose metabolism and other CV risk factors that began in 1989. All 2,484 participants were subject to an extensive and repeated CV screening program similar to that used in the CARRÉ study.Results:After 20 years of follow up 118 patients (33%) developed at least one CV event in the Carré group. Mean (SD) follow up time was 11 (6) years with a total of 3,500 years at risk and an incidence rate of 3.4 per 100 patient-years; this is slightly up from the figure reported at 15 years, i.e. 3.2 per 100 patient-years. A CV event-free survival curve is shown in figure 1. After 30 years of follow up, 295 participants of the Hoorn study had developed a CV event, during a mean follow up time 20 (8) years. Total time at risk was 50,000 years, with an incidence rate of 0.6 CV events per 100 patient years.Conclusion:In our cohort the incidence rate of CV events in RA patients has remained consistently high when compared with the general population, despite better control of RA inflammation in recent years. This again confirms the need for timely CVD-risk screening and management.References:[1]Agca R, Hopman L, Laan KJC, van Halm VP, Peters MJL, Smulders YM, et al. Cardiovascular Event Risk in Rheumatoid Arthritis Compared with Type 2 Diabetes: A 15-year Longitudinal Study. J Rheumatol. 2020;47(3):316-24.Figure 1.Survival curve of participants with rheumatoid arthritis. RA = rheumatoid arthritisDisclosure of Interests:None declared