DETECTION OF SARS COV-2 ANTIBODIES FOLLOWING VACCINATION IN PATIENTS WITH RHEUMATIC MUSCULOSKELETAL DISEASE (DECODIR) – A REPORT FROM A DANISH PROSPECTIVE COHORT STUDY

BackgroundThe COVID-19 pandemic caused concerns whether patients with rheumatic musculoskeletal disease (RMD) treated with conventional (cs) or biologic (b) disease modifying drugs (DMARDs) and/or prednisolone exhibit an adequate immune response to the applied SARS-CoV2 vaccines.ObjectivesWe established the DECODIR study to assess and compare the efficacy of the SARS-CoV2 vaccines administered as part of the national vaccine roll-out: BNT162b2 vaccine (Pfizer/BioNTech) and mRNA-1273 vaccine (Moderna). The vaccines were offered as two doses four weeks apart;followed by a booster vaccination six months later. This national regimen included inflammatory rheumatic patients regardless of their respective anti-inflammatory treatment. We used patients' SARS-CoV2 IgG serum level as proxy for vaccination response (1).MethodsThe study was conducted as a longitudinal prospective cohort study. Patients with rheumatoid arthritis (RA), spondyloarthropathies (SpA) or psoriatic arthritis (PsA) receiving their outpatient treatment at the Danish Hospital for Rheumatic Diseases, Sonderborg, and monitored in the Danish DANBIO registry, were included.Blood samples, Disease activity and treatment information (cs/bDMARD, prednisolone) were collected at baseline (i.e. prior to vaccination), after six weeks, six and twelve months. SARS-CoV-2 IgG levels in serum were assessed by ELISA (Thermo-Fischer), and manufacturer's cut-off (>=10 EliA U/mL) selected as definition of sufficient IgG response. Antibody response was measured and compared at all four time points.Associations between antibody response, age, gender, disease (RA/PsA/SpA), treatment (none, cs/bDMARD or prednisolone) and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR) and bootstrapped 95% confidence interval (CI) of the median.ResultsA total of 243 patients were included at baseline and all were followed-up after six weeks;data from 233 patients were available at six months and for 229 patients at twelve months' follow-up. Those 229 patients had completed the national vaccination programme.The measurements performed 6 months after baseline demonstrated a per se decrease of IgG levels for the whole study population (median of 2.08 EliA U/mL at 6 months vs. 16 EliA U/mL at 6 weeks). The final measurements performed after twelve months demonstrated a significant increase of IgG levels. Thus, the completed vaccination programme, was followed by a significant increase in IgG levels (median of 100 EliA U/mL at twelve months vs. 16.5 EliA U/mL at six months, p < 0.001).Sufficient response rates were now recorded in all treatment scenarios, also in patients treated with prednisolone or combination of csDMARD and bDMARD. These two groups were at 6 months characterized by significant lower response rates, when compared with patients without any DMARD treatment.ConclusionCompleted vaccination programme defined as two doses plus booster vaccination resulted in a sufficient vaccination response as measured by IgG levels regardless of RA treatment.It is noteworthy that IgG levels increased markedly in patients treated with a combination of cs/bDMARD or oral prednisolone, who had low IgG levels (below manufacturer's cut-off >=10 EliA U/mL) after 6 months. Our results strongly support the efficacy of the complete vaccination programme including the 3rd booster vaccine in patients with inflammatory rheumatic diseases.Figure 1.Serum IgG-levels at baseline, 6 weeks, 6 months and 12 months;stratified by antirheumatic treatment. (Box plot showing median and interquartile range).[Figure omitted. See PDF]Reference[1]Schreiber K. et al. Reduced Humoral Response of SARS-CoV-2 Antibodies following Vaccination in Patients with Inflammatory Rheumatic Diseases— an Interim Report from a Danish Prospective Cohort Study. Vaccines 2022, 10(1), 35;https://doi.org/10.3390/vaccines10010035AcknowledgementsWe acknowledge all patients contributing to the DANBIO registry.The Danish Rheumatologic Biobank is a knowledged for handling and storage of biological material.Lab chieftechnician Charlotte Drachmann is acknowledged for her assistance.Disclosure of InterestsChristine Graversgaard: None declared, Karen Schreiber Speakers bureau: Lilly, UCB, Henning Jakobsen: None declared, Randi Petersen: None declared, Anders Bo Bojesen: None declared, Niels Steen Krogh: None declared, Bente Glintborg Grant/research support from: Pfizer, AbbVie, BMS, Sandoz, Merete Lund Hetland: None declared, Oliver Hendricks Speakers bureau: Pfizer, Lilly, Novartis.

DETECTION of SARS COV-2 ANTIBODIES FOLLOWING VACCINATION in PATIENTS with RHEUMATIC MUSCULOSKELETAL DISEASE (DECODIR)-AN INTERIM REPORT from A DANISH PROSPECTIVE COHORT STUDY

Background: During the COVID-19 pandemic, it remains a major concern whether patients with rheumatic musculoskeletal disease treated with conventional (cs) or biologic (b) disease modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV2 vaccines. There remains an urgent need for more data on SARS-CoV-2 vaccine efficacy to inform healthcare providers on the efficiency of the applied vaccination, potential need of and period for booster and/or re-vaccination. Objectives: To assess and compare the efficacy of the SARS-CoV2 vaccines BNT162b2 vaccine (Pfzer/BioNTech) and mRNA-1273 vaccine (Moderna). (The vaccines were administered as part of the Danish vaccine roll out and offered each with two doses and approximately four weeks apart). Patients' SARS-CoV2 IgG serum level was used as proxy to determine vaccination response. Methods: We established the 'Detection of SARS-CoV2 antibodies in Danish Infammatory Rheumatic Outpatients' study (DECODIR) as a longitudinal prospective cohort study. Patients with rheumatoid arthritis (RA), spondyloarthrop-athies (SpA) or psoriatic arthritis (PsA) receiving their outpatient treatment and monitored in the Danish DANBIO registry at the Danish Hospital for Rheumatic Diseases (DG), Sonderborg were included (April-June 2021). Bloods, patient reported outcome measurements (PROMS), clinical data and treatment information (cs/bDMARD) were collected at baseline (prior to vaccination) and after six weeks and six months. SARS-CoV2 IgG levels in serum were assessed by ELISA (ThermoFischer), and manufacturer's cut-off (>=10 EliA U/mL) selected as defnition of sufficient IgG response. Associations between antibody response, age, gender, disease (RA/PsA/SpA), treatment with no or cs/bDMARDs and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR) and bootstrapped 95% confdence interval (CI) of the median. Results: A total of 243 patients were included at baseline and after six weeks;at six months' follow-up data were available for 233 patients. After six weeks, vaccination was followed by a signifcant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 36.5 EliA U/mL). Patients treated with a combination of both cDMARD and bDMARD had signifcantly lower IgG levels compared to patients without any DMARD treatment (8,2 EliA U/mL vs 19.5 EliA U/mL (p<0.001)). Patients treated with oral prednisolone (any dose) also showed signifcantly lower median IgG levels compared to patients without DMARD treatment (3,8 EliA U/mL vs 19.5 EliA U/mL (p<0.01)). The actual measurements six months after baseline demonstrated a signifcant decrease of IgG levels for the whole study population (median of 16 EliA U/mL at six month vs 36.5 EliA U/mL at six weeks, p < 0.001) (Figure 1). Similar to week 6, lowest response rates were found in patients treated with prednisolone or combination of csDMARD and bDMARD. After 6 months, the proportional odds model revealed signifcantly lower median IgG antibody level in patients who received Pfzer compared to Moderna (median 15 EliA U/mL (95%CI: 13-18) vs 44.5 EliA U/mL (95%CI: 36-83) (p<0.001). Conclusion: IgG levels decreased markedly six months after the initial double dose regimen. Patients treated with a combination of cs/bDMARD or oral pred-nisolone are at higher risk of inadequate vaccine response as measured by IgG level. Our results support the decision for the need of a third booster vaccine in patients with infammatory rheumatic diseases, especially in the case of cs/bDMARD combination treatment and prednisolone. The data may indicate a need for further revaccination in these patients.

EXPERIENCES during the COVID-19 PANDEMIC among PEOPLE with INFLAMMATORY ARTHRITIS. 'rEOPENING of SOCIETY IS HARDER THAN LOCK-DOWN'-A QUALITATIVE INTERVIEW STUDY

Background: People with infammatory arthritis (IA) treated with conventional or biological immunosuppressive disease-modifying anti rheumatic drugs (DMARDs), were initially considered to have an increased risk of severe illness from SARS-CoV-19 (COVID-19) infection compared to the general population. Although resent studies have not confrmed this, people with IA have reported high level of anxiety and self-isolation during the pandemic (1). Only few studies have qualitatively explored how people with IA experience the impact the COVID-19 pandemic and the SARS-CoV-19 vaccinations. Objectives: To explore how people with IA experienced restrictions during the COVID-19 pandemic and the possible impact of vaccination on their protection against COVID-19 and their everyday lives. Methods: Semi-structured in-depth interviews were conducted via telephone or video with 19 people with IA in May-August 2021, shortly after they were enrolled in the national COVID-19 vaccination programme (all Danish citizens >18 years of age invited for SARS-CoV-19 vaccination, free of charge, with timing depending on age and comorbidities). At the same time, society gradually reopened after a complete lock-down. Qualitative content analysis, inspired by Graneheim and Lundman (2), was applied to analyse the data. Two patient research partners were involved in development of the study protocol, an interview guide and in the interpretation of fndings. Results: The participants' age ranged from 21 to 64 years, median 50 years. 7 male and 12 female, all diagnosed with IA (Psoriatic arthritis n=4, Axial Spondyloarthropathy n=4, Rheumatoid arthritis n=9, and Juvenile arthritis n=2) and 14 were treated with DMARDs. Two had not accepted vaccination. The analysis derived five themes: 1: 'Changing and divergent information'. The participants experienced there was an overload of general information to the public, while targeted information on the specific risk for people with IA was lacking;2: 'Individual interpretation of own risk', refilecting that participants had to find their own level of daily-life restrictions, a task they found to be very difficult;3: 'Impact on everyday life'. They took self-imposed precautions to protect themselves and their families from attracting COVID-19;4: 'Position in society and the vaccination programme', emphasizing that participants were affected by the inconsistent announcements from authorities whether they were considered to be in particular risk or not, and some expressed concerns regarding the DMARDs influence on the effect of the vaccine and 5: 'Reopening is somehow harder than lock down'. A societal spirit of being 'in this together' emerged through the lock-down and some were concerned that fewer restrictions during reopening of the society would put them in higher risk of a COVID-19 infection and force them to continue self-isolation. Conclusion: The COVID-19 pandemic affected the everyday lives of people with IA due to the authorities' restrictions and further self-imposed precautions throughout lock down and reopening of society. People with IA experienced a lack of consistent information and felt alone to assess their own SARS-Cov-19 infection risk.

CLINICAL FACTORS ASSOCIATED with A POSITIVE SARS-COV-19 TEST and with FREQUENT TESTING during the COVID-19 PANDEMIC in >10.000 PATIENTS with INFLAMMATORY RHEUMATIC DISEASES. RESULTS from A NATIONWIDE SURVEY from the DANISH DANBIO REGISTRY

Background: Patients with infammatory rheumatic diseases (IRD) have used self-isolation and social distancing during the pandemic to avoid SARS-CoV-19 infection (reference). In countries with unlimited and free access to SARS-CoV-19 testing, anxiety or other patient related factors might potentially increase test-frequency. Objectives: In patients with IRD followed in the nationwide DANBIO registry we aimed to explore clinical factors including self-isolation associated with a) a positive SARS-CoV-19 test result ('infection'), b) higher frequency of SARS-CoV-19 testing during the frst 1/ year of the pandemic. Methods: In May-June 2020, IRD patients followed in the quality registry, DANBIO (n=36,152), were invited to participate in the voluntary online questionnaire survey 'You and your rheumatic disease during times with corona-virus'. Patient characteristics, treatment and patient reported outcomes were captured in DANBIO and from the questionnaire. Patients were considered as self-isolating if they agreed to the question: I stay at home and avoid others as much as possible. After written consent, information on dates and SARS-CoV-19 test results (by PCR, polymerase chain reaction) during follow-up (until Nov 2021 and thus before entry of the Omicron variant) was obtained through linkage to the nationwide laboratory system. Time to frst positive PCR and associated characteristics were explored by multivariable Cox regression analyses with hazard ratios, HR, adjusted for: gender/age-group/diagnosis/biologic therapy/working/self-isolation/HAQ/EQ-5D. Day 0 was defned as the date of frst positive test in cohort (May-07-2020). Number of SARS-CoV-19 tests (median (IQR)), and characteristics associated with higher test frequency (upper quartile) was explored with multivariable logistic regression analyses (odds ratios, OR, adjustment like above). Results: In 10,098 included patients, 2.8% were infected during follow-up (Table 1). Age and HAQ seemed lower in infected (Table 1, Figure 1). In multivariable Cox regression analyses, male gender was associated with higher infection risk (HR 1.38 (1.05;1.80) whereas risk was lower in the age-group 61-80 years (0.60 (0.39;0.92) vs. below 40 years). Other factors were statistically insignifcant. Median number of PCR tests was 4 (IQR 1-9). In patients with <9 tests, 2.6% were infected whereas for patients with ≥9 tests, 3.2% were infected. Patients with ≥9 tests were younger, more frequently female and working in univariate (Table 1) and adjusted analyses, whereas other characteristics were statistically insignifcant (details not shown). Conclusion: Few patients with IRD were infected during the frst 1/ years of the pandemic. Gender and age were associated with infection risk and frequency of testing. Self-isolation and a range of other clinical characteristics had no impact, which to some extent may be due to behavioral differences across age-groups.

WHO ARE in and WHO ARE NOT? CHARACTERISTICS of PATIENTS with INFLAMMATORY RHEUMATIC DISEASES ACCEPTING AN ONLINE SYSTEM for REMOTELY ENTERING PATIENT REPORTED OUTCOMES. EXPERIENCE from the DANISH DANBIO REGISTRY

Background: Digital solutions for online monitoring of chronic diseases are increasingly implemented in health care, but not all patients might have access, skills, or interest in using them. Fueled by the COVID-19 pandemic and the urgent need for remote consultations, an online website to enter patient-reported outcomes (PROs) from home (DANBIO-from-home, https://danbio.dk) was implemented on May 15th 2020 for patients with infammatory rheumatic diseases (IRD) followed in the Danish nationwide DANBIO registry. Objectives: To explore the use of DANBIO-from-home during the frst 1/year after launching, with focus on a) characteristics of patients who did versus who did not access the webpage, and b) impact of patient age on time to frst entry. Methods: DANBIO-from-home allows PROs to be entered remotely by computer, tablet, or smartphone after secure log-on. All patients followed in DANBIO were informed about this option by invitations sent through eBoks, a national infrastructure for electronic communication, available to 80-90% of Danish citizens. Patients were encouraged to access DANBIO-from-home before planned rheumatology consultations, or when participating in the voluntary questionnaire survey 'You and your rheumatic disease during times with corona-virus' (on three occasions: May 2020, Nov 2020, June 2021) (ref). Follow-up ended Dec 1st 2021. Characteristics of patients who did/did not access DANBIO-from-home during follow-up are explored by multivariable logistic regression analyses adjusted by clinical factors (gender/age-group/diagnosis/disease duration/use of biologics/HAQ/PASS). Time to frst entry of PRO using DANBIO-from-home is presented as cumulative incidence curves by age group. Results: Among 33,776 patients with infammatory rheumatic diseases followed in DANBIO, 68% used DANBIO-from-home at least once during follow-up (Table 1). Patients who used the system were less frequently below 40 years or above 80 years old, more frequently biologically treated and had lower HAQ-score than patients who did not use it. In logistic regression analyses, factors associated with DANBIO-from-home access were: female gender (odds ratio, OR 1. 2 (1.1;1.3)), age group 40-60 (1.8 (1.6;2.0)) or 61-80 yrs (1.9 (1.7;2.19) and not age >80 yrs (0.6 (0.5;0.7) with age <40 as the reference), biologic treatment (1.4 (1.3;1.5)), higher HAQ (1.3 (0.3;1.4)), scoring PASS 'no' (1.1 (1.02;1.2)) (all p <0.001), whereas disease duration and diagnosis had no impact. Time to frst entry was longest in in patients >80 yrs followed by the <40 yrs group. For all age-groups, and most pronounced for age <40 yrs, the use increased when invitations to questionnaire surveys were sent out. (Figure 1) Conclusion: A web-based system for secure remote entry of PROs was well-received after a nationwide launch. Patient-related factors had a substantial impact on the use. Lower use in the elderly might indicate lack of technical skills or facilities, whereas low use in younger age groups, which improved over time, is likely driven by other factors. Further analyses are planned to explore if lack of use impacts treatment outcomes.

REMOTE and PHYSICAL CONSULTATIONS during the FIRST 15 MONTHS of the COVID-19 PANDEMIC: USE and PATIENT-SATISFACTION in PATIENTS with INFLAMMATORY RHEUMATIC DISEASES FOLLOWED in the DANBIO REGISTRY

Background: During COVID-19 related lockdowns, physical attendance may be replaced by remote (by telephone, email, video consultations in patients with infammatory rheumatic diseases (IRD). During re-opening of society, reallocation of health-care resources could potentially cause persistent changes in access to physical consultations. Objectives: To explore use of remote consultations in patients with IRD followed in the nationwide DANBIO registry at three time points (lockdown from spring 2020 followed by gradual reopening of society) during the COVID-19 pandemic. Furthermore, to explore satisfaction with treatment access, and preferred mode of consultation including potentially associated clinical factors. Methods: We performed a nationwide survey where three times, an online questionnaire (Q) 'Yo u and your arthritis in times of COVID-19' with questions regarding use of and access to remote and physical consultations was sent to all patients in DANBIO (Q1: March-April 2020, Q2: November 2020, Q3: May 2021). (ref) Patient characteristics were captured in DANBIO (gender/age/diagnosis/biological therapy) and from the questionnaire (work status/comorbidities/EQ-5D). Use of physical and/or remote consultations 0-3 months before surveys and satisfaction with access was identifed. Clinical factors associated with a preference for physical consultations at time of Q3 (versus remote contact (telephone/e-mail/video)) were explored with multivariable logistic regression analysis. Results: Totally, 12,789/14,755/13,921 patients responded to Q1/Q2/Q3, respectively, with 23,311 unique patients participating in at least one survey. Characteristics of patients responding to Q3 are shown in Table 1. During the preceding 3 months, proportions of patients with physical/remote consultations were 22%/45%, 41%/38%, 40%/39% for Q1, Q2, Q3, respectively. Remote consultations were mainly by telephone, whereas email (<5%) and video (<1%) were rarely used. In all three surveys, only 7% of respondents found that access to counseling with their rheumatologist had deteriorated during the pandemic (Figure 1A) whereas the majority found it to be unchanged or did not know. The preferred contact form was physical consultations (68-74%, Figure 1B, not available for Q1). Factors associated with preference for physical consultation were female gender, higher age (>60 years), biological treatment, low EQ-5D and not having axial spondyloarthritis, whereas work status and comorbidities were without signifcance (logistic regression analyses, details not shown). Conclusion: Despite a widespread use of remote consultations during the pandemic, nationwide questionnaire surveys performed at three time-points during the COVID-19 pandemic showed that most patients were satisfed with access to rheumatic counseling. Nevertheless, in-person contacts were preferred by most patients, mainly women and elderly.

Self-protection strategies, health behavior and disease activity during the first wave, re-opening and second wave of the COVID-19 pandemic in ≥7000 danish patients with inflammatory arthritis

Background: The COVID-19 pandemic has caused lockdown, reduced access to face-to-face consultations, anxiety about taking immunosuppressive agents and self-isolation1 which potentially impact rheumatic disease control negatively. However, changes in behavior including self-protection strategies during the ongoing pandemic and impact on rheumatic disease activity have only been scarcely described. The first COVID-19 wave hit Denmark in March 2020 followed by a gradual re-opening from mid-April and the second surge began in the late autumn of 2020. Objectives: To describe changes over time in self-protection strategies and health behavior during the first 8 months of the COVID-19 pandemic and to explore impact on self-reported disease activity and quality of life (=patient reported outcomes, PROs) in patients with inflammatory rheumatic disease (IRD) in DANBIO. Methods: Patients were invited to answer two on-line questionnaires regarding current behavior and disease specific PROs: One in June 2020 (including also questions regarding behavior in March 2020), and one in November 2020. Responses were linked to PROs collected as part of routine care before March 2020 (=Before) in DANBIO. For each PRO, changes (=delta values) between the two timepoints were calculated in individual patients. Results: Overall, 7,836 patients (22% of eligible patients) answered both questionnaires and were included (rheumatoid arthritis(RA): 5270(67%), psoriatic arthritis(PsA): 1217(15%), axial spondyloarthritis(AxSpA): 932(12%), other IRD: 417(5%). Patients reported highest levels of anxiety and self-protection in March with an improvement in June that was largely unchanged in November (Figure 1), e.g. proportions staying at home avoiding others as much as possible (completely or mostly agree) were 87%/49%/51% in March/June/November, respectively (Figure 1, Panel C). Disease activity and proportions of patients reporting acceptable symptom state remained stable at the three time points (Table 1), with all median delta values being close to zero (not shown). Conclusion: In this large cohort of patients with inflammatory rheumatic diseases followed in the nationwide DANBIO registry, COVID-19 related self-protection strategies were highest in March 2020, but more than half of the patients also reported self-isolation in June and November. We found no negative impact of the pandemic on patient-reported outcomes, which remained largely unchanged and were similar to before the pandemic. The latter finding probably reflects that few patients reduced or withdrew from treatment due to fear of COVID-191.

Anxiety and concerns related to the work situation during the COVID-19 pandemic in >5,000 patients with inflammatory rheumatic disease followed in the danish danbio registry, results from a nationwide questionnaire

Background: During the COVID-19 pandemic, widespread changes in how we work have been observed. Working from home is not an option for everyone. At work it may be difficult to keep social distance, which may lead to fear and anxiety of being infected with SARS-CoV-19 or of spreading the virus. Objectives: To explore frequency of anxiety and concerns related to work in patients with inflammatory rheumatic diseases(IRD) during the COVID-19 pandemic and to identify patient and disease characteristics associated with increased anxiety. Methods: Patients in routine care followed in the nationwide Danish DANBIO registry were invited to answer an on-line questionnaire regarding current rheumatic disease activity, behavior and anxiety including current work-status and -concerns. Responses were linked to patient data previously recorded in DANBIO. Clinical factors associated with work-related concerns (completely/mostly agree versus neither/nor, completely/mostly disagree) were explored with multivariable logistic regression. Results: Among 14,758 respondents (38% of eligible patients), 5,950 patients (40%) were currently working (60% full time/31% part time/9% self-employed) (61% female, 53% rheumatoid arthritis/19% psoriatic arthritis/ 20% axial spondyloarthritis/9% other). Although 68% reported that the workplace helped to make necessary interventions, work-related concerns and anxiety were frequent. Thus, 22% found it difficult (completely/mostly agree) to keep physical distance at work and 20% were worried about going to work (Figure 1). Factors associated with concerns about going to work were female gender, longer education, other chronic conditions, biological therapy, and higher (=poorer) EQ-5D, whereas diagnosis was without significance. Similar patterns were found for other work-related concerns (not shown). Conclusion: In this cohort of >5,000 patients with inflammatory rheumatic diseases followed in a nationwide registry, during the COVID-19 pandemic anxiety and concerns related to the work situation were frequent, especially in women and patients treated with biologicals, with other chronic diseases and with poor quality of life.