Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry

ObjectivesTo describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD).MethodsPhysician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively.ResultsThe study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD).ConclusionThe safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.

Incidence and factors related to SARS-CoV-2 infection in a cohort of patients with rheumatoid arthritis in Colombia during the COVID-19 pandemic v1

Introduction:Patients with rheumatoid arthritis (RA) have an increased risk of SARS-CoV-2 infection due to intrinsic characteristics of the pathology and the medications used to treat it. Objective: To evaluate the incidence of and factors related to SARS-CoV-2 infection in patients with RA in Colombia. Materials and methods: This was an observational study of patients diagnosed with RA who were treated at a health care institution in Colombia. The study evaluated whether the patients presented SARS-CoV-2 infection and other clinical variables. Variables associated with the risk of SARS-CoV-2 infection were identified. Results: A total of 2,566 patients with RA were identified. They had a median age of 61.9 years, and 81.1% were women. They were mainly treated with synthetic disease-modifying antirheumatic drugs (DMARDs) (85.3%), glucocorticoids (52.2%) and biological DMARDs (26.8%). The incidence of SARS-CoV-2 infection was 5.1%, and the factors that increased the risk included treatment with synthetic DMARDs with or without biological DMARDs but with concomitant systemic glucocorticoids (OR: 2.18, 95% CI: 1.21-3.93 and OR: 1.69, 95% CI: 1.05-2.74, respectively) and receiving antidiabetic drugs (OR: 2.24, 95% CI: 1.27-3.94). A total of 20.8% of patients with COVID-19 required hospitalization, and 3.8% died. Conclusions: The incidence of COVID-19 is higher among patients with RA who receive DMARDs and glucocorticoids simultaneously or who have diabetes mellitus than among RA patients not receiving these drug combinations, which should guide treatment strategies.

OP0097 LISTERIA MONOCYTOGENES. DESCRIPTION AND ANALYSIS OF CASES IN AN IMMUNODEPRESSED POPULATION BY RHEUMATIC DISEASES

Background:Listeria monocytogenes is a gram-positive bacteria that cause the invasive disease listeriosis. Human clinical syndromes are infrequent, mostly appearing in immunosuppressed individuals, newborns, the elderly, pregnant women, and occasionally healthy patients.Objectives:We describe and analyze Listeria-related demographics and clinical features to determine the predisposing conditions for severe infections in an immunodepressed population by rheumatic diseases.Methods:Descriptive Observational Study. A retrospective analysis of 143 patients were performed affected by listeriosis, with positive isolation of Listeria monocytogenes from blood, treated in the H.U. Virgen del Rocío (Seville- Spain) between 2003-2019. Of them 9 were rheumatic patients. The type of clinical manifestation was analyzed, paying special attention to the characteristics associated with patients with neurological complications or unfavorable outcome (death and / or abortion in pregnant women), immunosuppression (associated with cancer or rheumatic disease) was assessed as independent variables, chronic diseases (Hypertension, Diabetes Mellitus, dyslipidemia, COPD, Renal Insufficiency and Ischemic Heart Disease) as well as other baseline characteristics of the patient. (age, sex, pregnancy) and their toxic habits (tobacco and alcohol).Results:The sample includes a similar proportion of men (70 cases) and women (73 cases), of all ages. Of the total patients, most (85%) required hospital admission, with a duration median (non-parametric data) of 11 days. 78% of the cases admitted showed a favorable evolution. However, 15.4% resulted in death and 5.6% in abortion. This percentage of abortions represented 29% of the total pregnant women admitted Of all the patients admitted, a third (33%) were immunocompromised, including patiets with cancer (79%) and rheumatic diseases (21%). Include lupus (33%), RA (22%), APs (11%), polymyalgia rheumatica (11%), panuveitis (11%) and ANCA vasculitis MPO specificity (11%). All of them required admission although the majority showed a favorable evolution, except one of the patient. which resulted in death, in which case in addition to lupus he presented with prostate cancer. Regarding the baseline treatment of these patients, 7 underwent treatment with synthetic DMARDs and three with biological DMARDs (1 Adalimumab, 1 Infliximab and 1 Rituximab) As a result of the listeria infection, most of them had fever or digestive symptoms and two of they experienced neurological manifestations (meningoencephalitis) None of these last two (with lupus and RA) had biological DMARDs.Conclusion:Listeriosis is an uncommon but potentially serious infection usually in older people, pregnant women and immunocompromised patients. In our sample, 33% of the patients were immunocompromised. Of the 9 patients. affected by listeria with rheumatic disease we find a death for meningoencephalitis. Given the impact of this infection in immunosuppressed patients should pay attention in our patients with fever and neurological manifestations.Reference:[1]Eleftherios Mylonakis et al. A Case Series and Review of 222 Cases. Medicine 2002; 81: 260-269.[2]Alcoba Lez M et al.Meningitis por Listeria monocytogenes en el adulto en España. Presentación de 10 casos y revisión de la literatura. Rev Clin Esp 2002; 202 (12): 638-643.[3]Eleftherios Mylonakis et al. Central Nervous Sistem Infection with Listeria monocytogenes. 33 Years’ Experience at a General Hospital and Review of 776 Episodes from tha Literature. Medicine 1998; 77: 313-336.Disclosure of Interests:None declared

POS0273-HPR PHARMACIST’S IMPACT ON SELF-MANAGEMENT FOR PATIENTS WITH CHRONIC INFLAMMATORY ARTHRITIS TREATED WITH BIOLOGICAL DMARDS

Background:Knowledge about chronic inflammatory rheumatisc diseases and skills to administer and manage subcutaneous (subcut) biological DMARDs (bDMARDs) are key aspects to optimize patient’s self-management. Intervention of several successive health professionals (e.g comprehensive multidisciplinary team) has proven to be an effective method to improve patient’s self-management of their disease and treatment.Objectives:To assess the pharmacist’s impact on patient’s knowledge and skills during a multidisciplinary annual review. The secondary objectives were to assess this impact on therapeutic adherence and patient’s satisfaction as well as to determine the factors associated with the level of knowledge at baseline.Methods:Study type: prospective, monocentric, 6 months-follow-up, non-controlled study approved by Local Ethical Committee. Inclusion criteria: patient with either rheumatoid arthritis (RA) or spondyloarthritis (SpA), and treated with subcut bDMARDs. Intervention: The visit with a pharmacist evaluating and discussing patient’s knowledge and treatment adherence. At baseline (M0): date of the visit and, 3 (M3) and 6 months (M6) later, knowledge and adherence were assessed using self-administered questionnaires: Biosecure and CQR-5 respectively. A questionnaire was sent at M3 in order to evaluate the patient satisfaction. Endpoints: Primary: Changes in Biosecure score Secondary: Percentage of patients with high level of knowledge (score > 84) and percentage of patients with high adherence at M3 and M6; patient’s satisfaction; identification of patient’s factors (socio-demographics, rheumatisc disease treatments) associated with different levels of knowledge at baseline.Statistical analysis: repeated measures ANOVA, Bonferroni and Generalized Estimating Equation, univariate and multivariate linear regression.Results:The study was conducted from October 2019 to July 2020; 79 patients were included (age (years) = 50±15; sex ratio = 1.1; RA=25, SpA=54). The Biosecure scores changed from 71±18 to 82±15 (M3) and to 84±14 (M6) (p<0.001). At M0, M3 and M6, the rate of patients with a high level of knowledge was 24.1%, 59.5% and 63.3% respectively (p<0.001). No difference was observed for the change in the 92% of patients considered as high adherent (92% versus 95% at M0 and M6 respectively; p=0.077). Patient’s satisfaction regarding the pharmaceutical intervention was 25±3 (max = 28).Factors associated with a better Biosecure score in the multivariate analysis were the following, lifestyle as a couple (p<0.001), information given by a nurse (p=0.033), information searched for on patient associations (p=0.013) and a low Charlson score (p=0.001)Conclusion:Pharmacist’s intervention in the comprehensive multidisciplinary annual review resulted in a beneficial impact on patients’ knowledge and skills to manage their bDMARDs with a high level of satisfaction from a patient perspective.Disclosure of Interests:None declared

POS0641 INCIDENCE OF GASTRO-INTESTINAL COMPLICATIONS IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING BIOLOGICAL DMARDS IN OBSERVATIONAL COHORT STUDIES: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS

Background:Rheumatoid arthritis (RA) patients are at increased risk of gastro-intestinal (GI) perforations compared with non-RA patients, resulting in increased mortality. Clinical trials, post-marketing studies and registries have reported an increased risk of GI perforations in RA patients treated with tocilizumab.Objectives:The aim of our study was to assess the incidence of GI complications among RA patients receiving bDMARDs in observational cohort studiesMethods:A systematic literature review was carried out through September 2020 on the Pubmed, Embase and international congress databases, selecting observational cohort studies assessing the incidence of GI complications, including perforations and diverticulitis, in RA patients receiving bDMARDS. Keywords were “gastrointestinal perforation”, “gastrointestinal disease”, “diverticulitis”, “biological DMARDs” and “rheumatoid arthritis” with no publication date limit. Studies were selected independently by two readers. Data were extracted by one investigator and independently checked by another. A meta-analysis was performed with Review Manager Software, with random-effects models, whenever methodologically possible and relevant.Results:The literature search revealed 232 articles and abstracts of potential interest, and further examination resulted in 7 studies fulfilling required criteria. Among bDMARDs, Tocilizumab was associated with an increased incidence of GI perforations, with an overall incidence of 2.40 per 1000 person-years (95% confidence interval [95% CI] 1.45-3.35). The overall incidences of GI perforations were 1.01 per 1000 PY [0.75-1.27] for TNF inhibitors, 1.07 per 1000 PY [0.53-1.62] for abatacept and 1.12 per 1000 PY [0.16-2.08] for rituximab (Figure 1). In RA patients treated with tocilizumab, most of the perforations were located in the lower GI tract, with an incidence of 2.24 per 1000 PY [1.24-3.52]. The incidences of upper GI perforations were similar across the different bDMARDs. The incidences of diverticulitis were 4.99 per 1000 PY [4.08-5.99] in RA patients receiving tocilizumab and 1.81 per 1000 PY [1.47-2.19] in those receiving TNF inhibitors.Figure 1.Meta-analysis of the incidences of gastro-intestinal perforations in RA patients receiving bDMARDs in observational cohort studiesConclusion:In our meta-analysis, focused in RA patients receiving bDMARDs in observational cohort studies, tocilizumab was associated with an increased incidence of GI perforations, mainly located in the lower GI tract. An history of diverticulitis and long-term corticosteroid therapy were associated with an increased risk of GI perforations.Acknowledgements:We cannot express enough thanks to PhD Constantin and PhD Morel for their support and encouragement.We would like to address a special word of thanks to PhD Lukas for his accuracy.Special Thanks to Claire Rempenault for her precious advices. You have been a role model for us.Disclosure of Interests:None declared

POS0364 EFFECT OF BIOLOGIC DMARDS TREATMENT ON GENE EXPRESSION AND ACTIVITY OF NATURAL KILLER CELLS IN RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) is the most common inflammatory type of arthritis, with various immune players implicated in its pathogenesis. Natural killer (NK) cells are innate lymphocytes that showed controversial roles in RA, whether pathogenic or protective (Shegarfi, H. et al. 2012, Yap, H.-Y. et al. 2018). Previously, we were able to identify a gene signature in NK cells of RA patients that can aid in understanding the state of NK cells in RA disease and identify RA patients from healthy controls (Elemam, N.M. et al. 2019, Elemam, N.M. et al. 2020). Furthermore, this signature might facilitate the selection of biomarkers that can be used for early detection of RA and prediction of effectiveness of RA treatment.Objectives:In this study we aimed at exploring the effect of several RA therapeutic agents such as tocilizumab, rituximab and anti-TNFα (adalimumab, etanercept and golimumab) on the previously identified gene signature in NK cells of RA patients.Methods:Whole blood transcriptomic data from publicly available dataset (GSE93272) was used to predict the percentage of activated NK cells in the blood of RA patients using the software CIBERSORT. Then, a correlation analysis was done between the percentage of NK cells and number of days of receiving tocilizumab treatment. Whole blood samples were collected from the recruited 17 RA patients (satisfying the 2010 ACR/EULAR classification criteria for RA). NK cells were isolated using RosetteSep negative selection method and RNA was extracted and gene expression was assessed using qRT-PCR. RA patients taking tocilizumab, rituximab, or anti-TNFα (adalimumab, etanercept or golimumab but none of the patients received infliximab) were compared to those not receiving any biological DMARDs. Statistical analysis was done using Student’s t-test.Results:In silico analysis has shown that the percentage of activated NK cells is positively correlated with the number of days of tocilizumab therapy in RA patients, suggesting a direct enhancing effect of tocilizumab on NK cell activity. Then, it was crucial to investigate the effect of different biological DMARDs on NK gene expression in RA patients. All the investigated chemokines (CCL2, CXCL10, CXCL16, CXCR1, CXCR2, CXCR6 and CCR4) in the identified gene signature showed a significant change in RA patients receiving tocilizumab, rituximab, or anti-TNFα therapies. Furthermore, the other genes including RELA, ICAM, IL1RN, TLR3 and TLR10 were significantly changed in NK cells of RA patients receiving biological DMARDs in comparison to patients not receiving the treatments. However, some of the genes including CD56, BTK, IBTK, ITGB7, IL1B, PECAM-1, IL12RB2, IFNG and CKLF did not show a significant change upon receipt of biological DMARDs.Conclusion:In conclusion, NK cell activity and gene expression could be affected by the type of biological DMARDs received by RA patients. Therefore, this identified gene signature of NK cells could be used as a diagnostic tool to identify RA patients and a target for biological DMARDs in RA.References:[1]Elemam, N. M., M. Y. Hachim, S. Hannawi and A. A. Maghazachi (2019). “Natural Killer Cells Gene Expression Can Differentiate Rheumatoid Arthritis Patients from Healthy Controls [abstract].” ACR/ARP Annual Meeting, supplement of Arthritis & Rheumatology71(suppl 10).[2]Elemam, N. M., M. Y. Hachim, S. Hannawi and A. A. Maghazachi (2020). “Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls.” Genes (Basel)11(5).[3]Shegarfi, H., F. Naddafi and A. Mirshafiey (2012). “Natural killer cells and their role in rheumatoid arthritis: friend or foe?” TheScientificWorldJournal2012: 491974-491974.[4]Yap, H.-Y., S. Z.-Y. Tee, M. M.-T. Wong, S.-K. Chow, S.-C. Peh and S.-Y. Teow (2018). “Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development.” Cells7(10): 161.Figure 1.In silico analysis and correlation of NK cell activity with the number of days of Tocilizumab therapy in RA patients.Disclosure of Interests:None declared