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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

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.

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 evaluate whether a third vaccination shows an added effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell responses in patients with multiple sclerosis treated with ocrelizumab or fingolimod.MethodsThis is a substudy of a prospective multicenter study on SARS-CoV-2 vaccination in patients with immune-mediated diseases. Patients with MS treated with ocrelizumab, fingolimod, and no disease-modifying therapies and healthy controls were included. The number of interferon (IFN)-γ secreting SARS-CoV-2–specific T cells at multiple time points before and after 3 SARS-CoV-2 vaccinations were evaluated.ResultsIn ocrelizumab-treated patients (N = 24), IFN-γ–producing SARS-CoV-2–specific T-cell responses were induced after 2 vaccinations with median levels comparable to healthy controls (N = 12) and patients with MS without disease-modifying therapies (N = 10). A third vaccination in ocrelizumab-treated patients (N = 8) boosted T-cell responses that had declined after the second vaccination, but did not lead to higher overall T-cell responses as compared to immediately after a second vaccination. In fingolimod-treated patients, no SARS-CoV-2–specific T cells were detected after second (N = 12) and third (N = 9) vaccinations.DiscussionIn ocrelizumab-treated patients with MS, a third SARS-CoV-2 vaccination had no additive effect on the maximal T-cell response but did induce a boost response. In fingolimod-treated patients, no T-cell responses could be detected following both a second and third SARS-CoV-2 vaccination.

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.

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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).

OBJECTIVE: The objective of this study was to measure humoral responses after SARS-CoV-2 vaccination in MS patients treated with ocrelizumab (OCR) compared to MS patients without disease modifying therapies (DMTs) in relation to timing of vaccination and B-cell count.METHODS: OCR treated patients were divided into an early and a late group (cut-off time 12 weeks between infusion and first vaccination). Patients were vaccinated with mRNA-1273 (Moderna). B-cells were measured at baseline (time of first vaccination) and SARS-CoV-2 antibodies were measured at baseline, day 28, 42, 52 and 70.RESULTS: 87 patients were included (62 OCR patients, 29 patients without DMTs). At day 70, seroconversion occurred in 39.3% of OCR patients compared to 100% of MS patients without DMTs. In OCR patients, seroconversion varied between 26% (early group) to 50% (late group) and between 27% (low B-cells) to 56% (at least 1 detectable B-cell/µL).CONCLUSIONS: Low B-cell counts prior to vaccination and shorter time between OCR infusion and vaccination may negatively influence humoral response but does not preclude seroconversion. We advise OCR treated patients to get their first vaccination as soon as possible. In case of an additional booster vaccination, timing of vaccination based on B-cell count and time after last infusion may be considered.

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.

Objectives: The aim of the present study was to determine the prevalence of specific cardiac manifestations, i.e., conduction disorders, valvular disease and diastolic left ventricular (LV) dysfunction, in a large cross-sectional controlled cohort of elderly ankylosing spondylitis (AS) patients. Methods: This cross-sectional study assessed the prevalence of valvular disease, conduction disorders and LV dysfunction in 193 randomly selected AS patients compared with 74 osteoarthritis (OA) controls aged 50–75 years. Patients underwent conventional and tissue Doppler echocardiography in combination with clinical and laboratory assessments. Multivariate regression analyses were performed to compare the odds of mitral valve regurgitation (MVR) and aortic valve regurgitation (AVR) between AS patients and OA controls. Results: The prevalence of diastolic dysfunction was trivial and comparable in AS patients compared to controls (respectively, 4% and 3%) and had no further clinical relevance. In addition, the prevalence of conduction disturbances was similar in both groups, with little clinical relevance, respectively 23% vs. 24%. The prevalence of AVR was significantly higher in AS patients compared to the controls, respectively 23% (9% trace, 12% mild, 1% moderate, 1% severe, 1% prosthesis) vs. 11%, p = 0.04. After correcting for age, sex and CV risk factors, AS patients had an odds ratio of 4.5 (95% CI 1.1–13.6) for AVR compared to the controls. In contrast, the prevalence values of MVR were similar and mostly not clinically relevant in AS patients and controls, respectively 36% and 32% and p = 0.46. Conclusion: The prevalence of diastolic LV dysfunction and conduction disorders was mostly not clinically relevant, and similar in AS patients and controls. However, AS patients had an up to five times increased odds to develop AVR compared to controls. Therefore, echocardiographic screening of elderly (50–75 years) AS patients should be considered.

Clinical research projects often use traditional methods in which data collection and signing informed consent forms rely on patients’ visits to the research institutes. However, during challenging times when the medical community is in dire need of information, such as the current COVID-19 pandemic, it becomes more urgent to use digital platforms that can rapidly collect data on large numbers of patients. In the current manuscript, we describe a novel digital rheumatology research platform, consisting of almost 5000 patients with autoimmune diseases and healthy controls, that was set up rapidly during the COVID-19 pandemic, but which is sustainable for the future. Using this platform, uniform patient data can be collected via questionnaires and stored in a single database readily available for analysis. In addition, the platform facilitates two-way communication between patients and researchers, so patients become true research partners. Furthermore, blood collection via a finger prick for routine and specific laboratory measurements has been implemented in this large cohort of patients, which may not only be applicable for research settings but also for clinical care. Finally, we discuss the challenges and potential future applications of our platform, including supplying tailored information to selected patient groups and facilitation of patient recruitment for clinical trials. Supplementary Information The online version contains supplementary material available at 10.1186/s13075-021-02574-z.

Introduction: Data on immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases are still scarce, because these patients were largely excluded from SARS-CoV-2 vaccine trials. Methods: Serum samples of patients with autoimmune diseases (n = 480) and healthy controls (n = 204) included in two ongoing prospective cohort studies were collected after first or second SARS-CoV-2 vaccinations. Seroconversion rates and IgG antibody titers against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were measured. Multivariable logistic and linear regression analyses were used to investigate associations between medication, seroconversion rates and IgG antibody titers respectively. Findings: Seroconversion rates after a first SARS-CoV-2 vaccination in 111 patients on methotrexate (25%, adjusted OR: 0.1, 95% CI: 0.1 – 0.2, P < 0.001) and 15 patients on anti-CD20 therapies (0%, P < 0.001) were lower compared to 103 healthy controls (71%). For patients on tumor necrosis factor (TNF) inhibitors (adjusted OR: 0.7, 95% CI: 0.4 – 1.4, P = 0.20) and patients on prednisone monotherapy (adjusted OR: 0.6, 95% CI: 0.2 – 1.5, P = 0.25) seroconversion rates were similar compared to controls. After the second SARS-CoV-2 vaccination seroconversion rates exceeded 88% in all patient subgroups, except in patients treated with anti-CD20 therapies (2 (33%) of 6). Seroconversion rates and IgG antibody titers were similar for patients with a prior SARS-CoV-2 infection who had received a single vaccine dose and patients without a prior SARS-CoV-2 who had received two vaccine doses. Interpretation: Treatment regimens other than anti-CD20 therapies of patients with autoimmune diseases do not need to be postponed when these patients receive a SARS-CoV-2 vaccination. Patients receiving anti-CD20 therapies may benefit from a second booster vaccination, as our data suggest that repeated exposure to SARS-CoV-2 vaccines or the virus itself enhances the development of humoral immunity in these patients. Funding: ZonMw, Reade Foundation and MS Center Amsterdam. Declaration of Interest: None to declare. Ethical Approval: The research protocols were approved by the medical ethical committee of the VU University medical center (registration number 2020.169 and 2020.370). All participants gave informed consent.

Vitamin D (VitD) insufficiency is common in multiple sclerosis (MS). VitD has possible anti-inflammatory effects on the immune system. The ratio between VitD metabolites in MS patients and the severity of the disease are suggested to be related. However, the exact effect of the bone-derived hormone fibroblast-growth-factor-23 (FGF23) and VitD binding protein (VDBP) on this ratio is not fully elucidated yet. Therefore, the aim is to study differences in total, free, and bioavailable VD metabolites and FGF23 between MS patients and healthy controls (HCs). FGF23, vitD (25(OH)D), active vitD (1,25(OH)2D), inactive 24,25(OH)D, and VDBP were measured in 91 MS patients and 92 HCs. Bioavailable and free concentrations were calculated. No difference in FGF23 (p = 0.65) and 25(OH)D/24.25(OH)2D ratio (p = 0.21) between MS patients and HCs was observed. Bioavailable 25(OH)D and bioavailable 1.25(OH)2D were lower (p < 0.01), while VDBP concentrations were higher in MS patients (p = 0.02) compared with HCs, specifically in male MS patients (p = 0.01). In conclusion, FGF23 and 25(OH)D/24.25(OH)2D did not differ between MS patients and HCs, yet bioavailable VitD concentrations are of potential clinical relevance in MS patients. The possible immunomodulating role of VDBP and gender-related differences in the VD-FGF23 axis in MS need further study.

Background:Patients with inflammatory rheumatic diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are at a higher risk for developing cardiovascular diseases (CVD) than the general population. This increased risk is partly due to a higher incidence of traditional cardiovascular (CV) risk factors, such as hypertension and dyslipidemia, and partly due to the underlying systemic inflammation. During the past two decades, the burden of the systemic inflammation has been reduced by more efficacious anti-inflammatory treatment, which somewhat attenuated the increased CV risk of rheumatic patients. However, it remains important to monitor the effects of these new treatment strategies on the prevalence of CVD in patients with a rheumatic disease in systematically controlled cohorts.Objectives:The aim of the current report was to evaluate whether the CV risk of patients with inflammatory rheumatic diseases still differs from the general population, despite advances In anti-rheumatic treatment strategies.Methods:In March 2020, all adult patients with an inflammatory rheumatic disease from the Amsterdam Rheumatology and Immunology Center, location “Reade” were systematically asked to participate in a prospective cohort study. The primary aim of this study was to monitor the impact of the COVID-19 pandemic on patients with inflammatory rheumatic diseases compared to age and sex matched healthy controls. Between April 26, 2020 and May 27, 2020, participants completed the first online questionnaire of the study. Amongst others, information on demographic data, including CV comorbidities and risk factors, and medication use was collected. The baseline characteristics and prevalence of CVD were compared between RA, PsA or AS and healthy controls.Results:In total, 1455 consecutive patients with an inflammatory rheumatic disease (979 RA patients, 261 PsA patients and 215 AS patients), and 414 healthy controls completed the first questionnaire, as shown in table 1. CV comorbidities were more frequently reported in RA, PsA and AS patients compared to healthy controls; 107 (11%), 28 (11%) and 22 (10%) compared to 30 (7%), respectively.Table 1.Biological DMARD usage in RA, PsA and AS patientsPatient characteristicsAll patients (n=1455)RA (n=979)PsA (N=261)AS (n=215)Controls (n=414)Mean age - yr55 ± 1358 ± 1255 ± 1348 ± 1353 ± 13Female sex - no (%)934 (64)728 (74)119 (46)87 (41)298 (72)BMI (IQR)25 (23-28)25 (22-28)26 (24-30)25 (22-28)24 (22-27)Smoking - no (%)178 (12)126 (13)17 (7)35 (16)34 (8)Cardiovascular disease – no (%)157 (11)107 (11)28 (11)22 (10)30 (7)Rheumatic medication - no (%)csDMARDs877 (60)712 (73)148 (57)17 (8)N.A.Oral glucocorticoids161 (11)139 (14)17 (7)5 (2)2 (0.4)TNF inhibitor563 (39)336 (34)121 (46)106 (49)N.A.IL-6 inhibitor19 (1)19 (2)00N.A.IL-17 inhibitor17 (1)2 (0.2)7 (3)8 (4)N.A.Table 1. Baseline characteristics. Values are displayed as mean ± standard deviation (SD), median with interquartile range (IQR) or frequencies with percentages (%). RA = rheumatoid arthritis, PsA = psoriatic arthritis, AS = ankylosing spondylitis, BMI = body mass index, TNF = anti-tumor necrosis factor, IL = interleukin.Conclusion:We demonstrated that the prevalence of CVD is approximately 1.5 times higher in patients with rheumatic diseases compared to healthy controls (11% vs. 7%, respectively). This corresponds with previous research, although the reported prevalence of CVD in PsA and AS patients is even higher compared to prior studies. This suggests that the CVD risk of patients with rheumatic diseases is still elevated in 2020 compared to the general population, despite the improved management of rheumatic disease activity. Therefore, adequate and timely treatment of CV risk factors remains relevant, not only in patients with RA, but in patients other rheumatic diseases as well.References:[1]Hooijberg F et al. (2020) Patients with rheumatic diseases adhere to COVID-19 isolation measures more strictly than the general population. The Lancet rheumatology 2(10), 583-585.Disclosure of Interests:None declared

Background:The overall mortality rate in ankylosing spondylitis (AS) patients is increased by 60–90% compared with the general population. This higher mortality rate is predominately caused by cardiovascular disease (CVD) comprising an increased prevalence of cardiac diseases such as valvular heart disease, conduction disturbances and cardiomyopathies as well as atherosclerotic diseases such as myocardial infarctions. However, there is a lack of contemporary studies. Therefore, we investigated current prevalences of cardiac disorders in a well characterized cohort of Dutch patients with AS compared to osteoarthritis (OA) controls.Objectives:To assess the prevalence of CVD in AS patients in comparison to OA controls in a Dutch population.Methods:We performed a cross-sectional study in AS and OA patients between 50-75 years. Subjects were recruited from a large rheumatology outpatient clinic (Reade) in Amsterdam, the Netherlands. Patients underwent echocardiography with 2D, spectral and Color Doppler imaging. The echocardiogram was evaluated by an experienced and certified cardiologist. Diastolic dysfunction was assessed according to the ASE/EACVI 2016 guideline. Furthermore, blood sample, surveys and physical examination were done. Disease activity and function were measured with the BASFI, BASDAI and the ASDAS-CRP.Results:A total of 193 consecutive AS patients were included with a median age of 60 (±7) years of which 72% men (138). The control group consisted of 70 OA patients (table 1). In the AS cohort the disease activity measures, BASDAI, ASDAS-CRP and BASFI, indicated moderate disease activity and were, respectively 3.1 (1.6-5.0), 2.1 (±1.0) and 3.5 (1.7-5.7). Anti-TNF was used by 43% of the AS patients. History of cardiovascular disease (CVD), i.e. angina pectoris, myocardial infarction, stroke and/or peripheral ischemia was comparable between the AS and OA cohort, respectively 9% (17) and 10% (7), p=0.81. Antihypertensives were significantly more often used in AS patients, 85 (44%) vs 19 (27%), p=0.02. Prevalences of systolic dysfunction and diastolic dysfunction did not differ significantly in AS and OA patients, respectively 6 (5%) vs 2 (5%), p=0.96 in systolic dysfunction and 7 (3%) vs 2 (3%), p=0.86 in diastolic dysfunction. Prevalence of aortic valve (AV) regurgitation was significantly higher in AS patients compared to OA patients, respectively 41 (22%) and 7 (10%), mostly with mild severity. The prevalence of mitral valve (MV) regurgitation did not differ between the AS and OA patients, respectively 68 (36%) vs 21 (33%), p=0.59. When corrected for age, gender and cardiovascular risk factors in a regression analysis, AS patients still had a substantially increased risk for AV regurgitation, odds ratio (OR) 2.8 95%CI 1.1-7.2, p=0.038.Table 1.Patient characteristicsASOApN19370Men (n, %)138 (72)40 (57)0.028*Age (years)60 ±763 ±70.004*Disease activityBASDAI3.1 (1.6-5.0)-ASDAS-CRP2.1 ±1.0-BASFI3.5 (1.7-5.7)-CVDHistory of CVD* (n, %)17 (9)7 (10)0.81Antihypertensives (n, %)85 (44)19 (27)0.02Aortic valve regurgitation (n, %)41 (22)7 (10)0.04* Trace (n, %)16 (9)6 (9) Mild (n, %)23 (12)6 (9) Moderate (n, %)1 (1)0 Severe (n, %)1 (1)0 Prosthesis (n, %)1(1)0Mitral valve regurgitation (n, %)68 (36)21 (33)0.59Diastolic dysfunction (n, %)7 (3)2 (3)0.86*Angina pectoris, myocardial infarction, stroke and/or peripheral ischemiaConclusion:This study demonstrates an almost tripled risk for developing AV regurgitation in Dutch AS patients. Although mostly mild in this age, due to the progressive nature of AV regurgitation in AS, echocardiographic screening should be considered in elderly AS patients.Disclosure of Interests:Milad Baniaamam: None declared, Sjoerd C. Heslinga: None declared, M.L. Handoko: None declared, Laura Boekel: None declared, Thelma C. Konings: None declared, Otto Kamp: None declared, Vokko P. van Halm: None declared, J.C. van Denderen: None declared, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research

Vitamin D (VitD) insufficiency is common in multiple sclerosis (MS). VitD has possible anti-inflammatory effects on the immune system. The ratio between VitD metabolites in MS patients and the severity of the disease are suggested to be related. However, the exact effect of the bone-derived hormone fibroblast-growth-factor-23 (FGF23) and VitD binding protein (VDBP) on this ratio is not fully elucidated yet. Therefore, the aim is to study differences in total, free, and bioavailable VD metabolites and FGF23 between MS patients and healthy controls (HCs). FGF23, vitD (25(OH)D), active vitD (1,25(OH)2D), inactive 24,25(OH)D, and VDBP were measured in 91 MS patients and 92 HCs. Bioavailable and free concentrations were calculated. No difference in FGF23 (p = 0.65) and 25(OH)D/24.25(OH)2D ratio (p = 0.21) between MS patients and HCs was observed. Bioavailable 25(OH)D and bioavailable 1.25(OH)2D were lower (p &lt, 0.01), while VDBP concentrations were higher in MS patients (p = 0.02) compared with HCs, specifically in male MS patients (p = 0.01). In conclusion, FGF23 and 25(OH)D/24.25(OH)2D did not differ between MS patients and HCs, yet bioavailable VitD concentrations are of potential clinical relevance in MS patients. The possible immunomodulating role of VDBP and gender-related differences in the VD-FGF23 axis in MS need further study.