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BackgroundPrevious studies have shown that using a finger prick as the primary method for blood withdrawal is an efficient way to collect blood samples remotely, and data on blood levels from a finger prick are directly comparable to that obtained by a venepuncture. During the COVID-19 pandemic, we therefore complemented our large digital research platform with serum collection via a home finger prick testing in order to collect samples without the need of visits to a hospital. This repeatedly enabled us to rapidly answer new and relevant clinical research questions about COVID-19, thereby showing the potential of the finger prick for research purposes. However, the use of finger pricks in a research or clinical practice setting is still uncommon, and not yet tested on a large scale. In addition, there is limited data on peoples' willingness and ability to successfully use the finger prick at home, especially in patients with inflammatory rheumatic diseases (iRD) who may have impaired hand function.ObjectivesTo investigate the feasibility of finger prick testing in combination with a digital research platform by evaluating the success rate and patients' perspective towards the use of the finger prick.MethodsData were collected from an ongoing prospective cohort study including patients with iRD from the Amsterdam Rheumatology & immunology Center and healthy controls. Serum samples were collected up to eight times during follow-up via blood withdrawal by venepuncture at the local research institute or via a finger prick that could be performed at home. For the latter option, participants were instructed to collect three drops of blood, which would yield approximately 40-80 µL of serum after clotting. All study participants were questioned about their preference for a particular sampling method for individual healthcare and for scientific research. Participants who received a finger prick test before June 26, 2021, were asked to complete a digital evaluation questionnaire of the finger prick after their attempt. The finger prick was defined as failed when less than 10 µL of serum could be recovered from the collection device, or if no sample was returned to the laboratory and participants indicated in the questionnaires that they did not succeed in collecting the required amount of serum.ResultsA total of 3080 patients with iRD and 1102 healthy controls were included in the study. Of these, 2135 (69%) patients and 899 (82%) controls attempted to execute at least one finger prick, and 1439 (67%) patients and 712 (21%) controls executed multiple finger pricks. The first finger prick was successfully done by 92% (CI 90 – 93) of iRD patients, 94% (CI 92 – 95) of healthy controls, 93% (CI: 92 – 94) of all participants aged 70 years or younger, and 89% (CI 86 – 92) of all participants aged above 70 years (Table 1). Sex did not impact these success rates. Repeated failure occurred in 11 of 1439 (0.8%) patients and 4 of 712 (0.6%) controls. The two most common reasons for perceived failure of the finger prick were related to insufficient blood yield when applying the finger prick. Finally, both patients and controls were less willing to perform a finger prick for individual healthcare compared to scientific research;31% of patients and 61% of controls were willing to perform a finger prick for scientific research compared to 19% of patients and 39% of controls for healthcare. The most important reason for this was lower confidence in the execution and laboratory measurements when blood was drawn via a venepuncture compared to a finger prick.ConclusionIn this study, we demonstrated that the vast majority of participants, among which elderly and patients of whom hand function may be impaired by an underlying rheumatic disease, were able to successfully draw the required amount of blood for serological analyses. This shows that the finger prick testing is suitable for a high-throughput implementation to monitor patients remotely, which will likely contribute to improving the efficiency and cost-effectiveness of b th healthcare and scientific research.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Background: Concerns have been raised regarding risks of COVID-19 breakthrough infections in vaccinated patients with immune-mediated infammatory diseases (IMIDs) treated with immunosuppressants, but data on COVID-19 breakthrough infections in these patients are still scarce. Objectives: The primary objective was to compare the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 delta variant between fully vaccinated IMID patients with immunosuppressants, and controls (IMID patients without immunosuppressants and healthy controls). The secondary objective was to explore determinants of breakthrough infections. Methods: In this study we pooled data collected from two large ongoing prospective multi-center cohort studies (Target to-B! [T2B!] study and ARC study). Clinical data were collected between February and December 2021, using digital questionnaires, standardized electronic case record forms and medical files. Post-vaccination serum samples were analyzed for anti-RBD antibodies (T2B! study only) and anti-nucleocapsid antibodies to identify asymptomatic breakthrough infections (ARC study only). Logistic regression analyses were used to assess associations with the incidence of breakthrough infections. Multivariable models were adjusted for age, sex, cardiovascular disease, chronic pulmonary disease, obesity and vaccine type. Results: We included 3207 IMID patients with immunosuppressants and 1810 controls (985 IMID patients without immunosuppressants and 825 healthy controls). The incidence of COVID-19 breakthrough infections was comparable between patients with immunosuppressants (5%) and controls (5%). The absence of SARS-CoV-2 IgG antibodies after COVID-19 vaccination was independently associated with an increased incidence of breakthrough infections (P 0.044). The proportion of asymptomatic COVID-19 breakthrough cases that were additionally identifed serologically in the ARC cohort was comparable between IMID patients with immunosuppressants and controls;66 (10%) of 695 patients vs. 64 (10%) of 647 controls. Hospitalization was required in 8 (5%) of 149 IMID patients with immunosuppressants and 5 (6%) of 86 controls with a COVID-19 breakthrough infection. Hospitalized cases were generally older, and had more comorbidities compared with non-hospitalized cases (Table 1). Hospitalization rates were signifcantly higher among IMID patients treated with anti-CD20 therapy compared to IMID patients using any other immunosuppres-sant (3 [23%] of 13 patients vs. 5 [4%] of 128 patients, P 0.041;Table 1). Conclusion: The incidence of COVID-19 breakthrough infections in IMID patients with immunosuppressants was comparable to controls, and infections were mostly mild. Anti-CD20 therapy might increase patients' susceptibility to severe COVID-19 breakthrough infections, but traditional risk factors also continue to have a critical contribution to the disease course of COVID-19. Therefore, we argue that most patients with IMIDs should not necessarily be seen as a risk group for severe COVID-19, and that integrating other risk factors should become standard practice when discussing treatment options, COVID-19 vaccination, and adherence to infection prevention measures with patients.
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Background: Many countries are promoting booster SARS-CoV-2 vaccination campaigns as the COVID-19 pandemic continues. Incremental short-term adverse events after two SARS-CoV-2 vaccinations have been reported in healthy individuals.1,2 However, data on incremental short-term adverse events in patients with various immune-mediated infammatory diseases (IMIDs) after repeated SARS-CoV-2 vaccination is scarce. Objectives: We report risk factors for short-term adverse events in IMID patients after SARS-CoV-2 vaccination. Methods: Self-reported daily questionnaires on adverse events in the frst seven days after SARS-CoV-2 vaccination were obtained from individuals participating in an ongoing prospective multi-arm multicenter cohort study on SARS-CoV-2 vaccination in patients with various IMIDs in the Netherlands (T2B! immunity after SARS-CoV-2). Clinically relevant adverse events were defned as systemic adverse advents lasting longer than two days or hindering daily activities. Adjusted relative risks for developing clinically relevant adverse events were calculated using a logistic mixed-effects model. Results: Data of 2081 patients and 178 healthy controls were obtained. Infammatory bowel disease (N:480), Multiple sclerosis (N:343) and Rheumatoid arthritis (N:266) were the largest disease groups. Adjusted relative risks for relevant adverse events are presented in Figure 1. Third vaccination was not associated with increased risk on adverse events when compared to a second vaccination (aRR: 0.93 95% CI: 0.84-1.02). Patients with IMIDs were at increased risk for developing adverse events after vaccination when compared to controls (aRR: 1.16 95% CI: 1.01-1.34). Female sex (aRR 1.43 95% CI: 1.32-1.56), age below 50 (aRR 1.14 95% CI: 1.06-1.23) and a preceding SARS-CoV-2 infection (aRR: 1.14 95% CI: 1.01-1.29) were also associated with increased risk of adverse events following vaccination. Allergic reactions and hospital admission were uncommon (0.67% and 0.19% respectively);7.4% and 6.8% of patients reported adverse events impacting daily life on day seven after second and third vaccination, respectively. Data on increase in disease activity of the IMID following vaccination are currently being investigated. Conclusion: A third SARS-CoV-2 vaccination was not associated with an increased risk on short-term clinically relevant adverse events when compared to a second vaccination. Although patients with IMIDs may be slightly more at risk to develop adverse events after SARS-CoV-2 vaccination, most adverse events were transient and disappeared within seven days. This message should reassure IMID patients who are hesitant on booster vaccination. Data on potential IMID fare-ups after vaccination will follow.
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Background: Patients with infammatory rheumatic diseases as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA) are at higher risk for developing cardiovascular diseases (CVD) than the general population. This is due to a higher prevalence of 'traditional' CV risk factors as hypertension and dyslipidemia, and the underlying systemic infammation. During the past two decades, the burden of infammation has been reduced by more efficacious anti-rheumatic treatment, leading to a reduced CVD risk, albeit still elevated in comparison to the general population. Therefore, it remains important to monitor the presence of CVD in rheumatic patients in systematically controlled cohorts. Objectives: To evaluate whether, nowadays, the CVD risk of patients with infammatory rheumatic diseases still differs from the general population. Methods: In March 2020, all adult patients with an infammatory rheumatic disease from the Amsterdam Rheumatology and Immunology Center, location 'Reade' were systematically asked to participate in a prospective cohort study, which focused on the impact of the COVID-19 pandemic. The patients were compared with age and sex matched controls. In the third questionnaire, sent out in January 2021, questions regarding CV risk factors and comorbidities were added. Baseline characteristics and prevalence of CV risk factors and CVD were compared between RA, PsA or SpA patients, and healthy controls. Results: 2050 consecutive patients with an infammatory rheumatic disease (1312 RA patients, 353 PsA patients, 385 SpA patients), and 939 healthy controls completed the questionnaires (Table 1). The prevalence of at least one CV comorbidity was more frequently reported in RA, PsA and SpA patients compared to healthy controls: 69 (5%), 24 (7%), 17 (4%) compared to 31 (3%), respectively. Events were primarily cardiac (I.e. myocardial infarction and coronary angioplasty). Infammatory arthritis patients more often had hypertension or hypercholesterolemia than healthy controls, which were untreated in nearly half the cases. RA patients most often used anticoagulant medication. Conclusion: The prevalence of CVD was approximately 1.5 times higher in patients with inflammatory rheumatic diseases compared to healthy controls (5% vs 3%), similar to older investigations. The prevalence of CV risk factors also remained elevated, and often undertreated. This indicates that the CVD risk in arthritis patients is still elevated in 2021 compared to the general population, despite improved anti-rheumatic treatment. Therefore, adequate and timely treatment of CV risk factors and optimization of anti-rheumatic drug treatment remains important in all inflammatory arthritis patients.
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Background: Therapeutic Drug Monitoring (TDM) is a tool to determine the optimal dose of a drug for individual patients using measurement of blood concentrations and, optionally, anti-drug antibodies (ADA). In the feld of rheumatology interest in applying TDM is increasing. A recent study by Syversen et al., the NOR-DRUM B trail, supports TDM as a treatment strategy. This study showed that treatment with proactive TDM was more effective then treatment without TDM. Applying TDM creates a more personalized treatment for individual patients, therefore it is relevant to understand the patients perspective towards TDM. Objectives: To study the perspective of rheumatology patients treated with a bDMARD in a personalized fashion using TDM. Methods: Adult rheumatology patients from the Amsterdam Rheumatology and immunology Center who participate in the COVID-19 prospective cohort study (Nederlands Trial Register, trial ID NL8513) received a digital questionnaire which comprised, in addition to demographic items, of three TDM topics: familiarity, attitude and risk assessment. Results: Participants were selected based on the following criteria: treatment with a bDMARD and a fully completed questionnaire (n=888). Table 1 shows characteristics of study population. Sixty-six percent (n=582) of the participants had never heard of the concept 'personalized dosing, using TDM'. After explaining the concept 60% (n=535) of the participants answered they have a positive attitude towards the concept (Figure 1). Participants with a positive attitude received a follow-up question. They were asked which of the following related aspects: individual dosing, costs, safety and other, they thought was most relevant regarding the concept. Multiple answers were possible. Ninety-four percent (n=502) reported as the main reason for having a positive attitude, that the treatment can be personally adjusted. The second and third reasons, respectively, were safety 43% (n=230) and costs 27% (n=142) of the treatment. Five percent (n=43) of the participants had a negative attitude towards the concept. Main reasons were;previous experience with unsuccessful dose reduction and unwillingness to change current treatment due to the fact that several previous treatments were ineffective. Participants were also asked what amount of risk they are willing to take when presented with five different situations;worsening rheumatologically symptoms: e.g. pain and swelling, increased fatigability, necessary treatment with prednisone, switching to another bDMARD or more frequent visits to rheumatologist. Majority of the patients reported for each of the five situations, respectively: 37% (n=330), 40% (n=359), 51% (n=453), 48% (n= 426) and 29% (n=262) that they would only be willing to take a negligible risk, < 0.1%. Conclusion: Majority of participants was not familiar with the concept of personalized dosing using TDM. However, the majority had a positive attitude towards the concept. The main reason for a positive attitude is that the treatment can be personally adjusted. On the other hand, patients who are currently being treated with a bDMARD were only willing to take a negligible risk when it comes to their own treatment.
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Background The aim of this study was to investigate the effect of various immunosuppressants on the humoral immune responses after vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). Methods The Target to B! SARS-CoV-2 study is a multicentre study, taking place in 7 Dutch academic hospitals. Patients with the following IMIDs were recruited: Crohn’s disease (CD), ulcerative colitis (UC), auto-immune hepatitis, rheumatic (e.g. rheumatoid arthritis), neurological (e.g. multiple sclerosis) and dermatological IMIDs (e.g. atopic dermatitis). Patients were recruited based on immunosuppressants (table 1) and previous SARS-CoV-2 infection. The control group consisted of healthy subjects and IMID patients without immunosuppressants. SARS-CoV-2 receptor binding domain (RBD) antibodies were measured 28 days after completed SARS-CoV-2 vaccination. Seroconversion was defined as anti-RBD IgG >4 AU/mL. In this , we focus on therapies relevant for inflammatory bowel diseases (IBD) and present results for these treatments from patients with IBD, but also other IMIDs. Results Numbers of recruited patients with each immunosuppressant are shown in table 1. Amongst these patients, 312 patients had CD and 176 UC, the rest was diagnosed with another IMID. Seroconversion was reduced in patients receiving sphingosine 1-phosphate (S1P) modulators (all multiple sclerosis patients) while seroconversion was similar to controls in the other treatment groups. However, use of Anti-tumour necrosis factor (TNF), methotrexate, janus kinase (JAK) inhibitor monotherapy and all combination therapies (except for corticosteroids combined with other immunosuppressants) were associated with reduced Sars-CoV-2 antibody titres. Patients with a previous SARS-CoV-2 infection had higher median antibody titres after second vaccination than those without a previous SARS-CoV-2 infection. The type of IMID did not affect seroconversion rates. Conclusion No immunosuppressant, registered for IBD, reduced the rates of seroconversion after vaccination against SARS-CoV-2. Some immunosuppressants were associated with lower antibody titres. However, the clinical relevance of lower antibody titres remains unknown. S1P modulators, had a clear negative impact on the humoral response against SARS-CoV-2 after vaccination. This might be relevant in the future as this therapy is currently being approved for UC. Disease aetiology did not impair immunity against SARS-CoV-2 immunity after vaccination. Disclaimer: Absolute numbers of antibody titres and rates of seroconversion will be reported at the conference and are not reported in this as this might negatively impact the current submission process.
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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.
Subject(s)
COVID-19 , Multiple Sclerosis , Antibodies, Monoclonal, Humanized , COVID-19 Vaccines , Humans , SARS-CoV-2 , VaccinationABSTRACT
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.Di closure of Interests:None declared
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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.