Long-Term Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis Refractory to Biologic Therapies: 2-Year Results from the Phase 3 Select-Psa 2 Study

Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.

Comparing Ankylosing Spondylitis Disease Activity during the Covid-19 Pandemic Using Patient-Reported Outcome Measures with Face-Toface Clinical Evaluation of Disease Scores Prepandemic

Background/Aims During the COVID-19 pandemic, asynchronous consultations were introduced for patients with ankylosing spondylitis (AS). To assess disease activity in the absence of face-to-face clinical review and blood testing, patients submitted patient-reported outcome measures (PROMs) via electronic survey forms which were subsequently triaged by clinicians. We compared pre-pandemic clinician-reported scores with intra-pandemic self-reported scores and assessed clinical outcomes including allocation of follow-up and further management/ treatment escalation. Methods Clinician-reported scores were obtained in-person pre-pandemic (defined as 01/01/2019-01/03/2020). Self-reported BASDAI scores were submitted by patients via electronic forms sent out duringpandemic (defined as 01/12/2020-31/03/22). The responses were stored and analysed in a secure database. These scores are analogous to disease activity scores completed by clinicians during outpatient appointments. Score comparison was performed using Wilcoxon Sign Rank testing. We used the need for a follow-up within 3 months as target for those with severe disease. Data analysis was performed in Microsoft Excel and R (version 4.2.1). Results We noted a significantly higher overall level of patient-reported disease activity during the pandemic. In the total cohort of AS patients, the median BASDAI Score collected during-pandemic increased from 5.30 (n=124, range 0-10) compared to 2.80 pre-pandemic (n=590, range 0-12) (p<0.001). The proportion of patients with severe/active disease (defined as BASDAI >4) increased from 36% pre- to 65% during pandemic. In a smaller cohort of 34 patients for whom we had both pre- and during-pandemic scores, all patient parameters worsened during the pandemic. Notably, median BASDAI increased from 2.65 to 5.62 (p<0.0001). Patients with severe AS increased from 10 (29.4%) to 21 (61.8%) intra-pandemic. Follow-up data was available for 12/21 patients with severe AS during-pandemic. 7/12 patients (58%) received a follow-up appointment within one month;11/12 (91%) were seen within three months. On subsequent clinician assessment, only 7 (58%) of patients with self-reported severe AS were felt to have active disease;treatment was escalated for 3 patients. Conclusion There was a significantly higher reported level of AS disease activity during the COVID-19 pandemic, with 62 % of patients qualifying for biologic therapy (BASDAI >4). In a focussed sample, 91% of patients with new severe disease during-pandemic were followed up within the target of 3 months. The BASDAI score is independent from clinical examination and inflammatory markers, and therefore self-reported score should reliably reflect a patient's perception of disease activity. Further work is required to determine the reason for the increased disease activity observed during pandemic, and for the disparity between clinician impression and score results.

Changes in Juvenile Dermatomyositis after the Covid-19 Pandemic

Background. Prior research has shown that viruses may trigger JDM, although the degree to which COVID-19 may serve as a trigger for JDM remains unknown. We present two case reports of JDM occurring after COVID-19 infection. We also provide case numbers of new JDM diagnoses pre-and post-COVID-19 as well as an analysis of JDM population characteristics pre-and post-COVID-19. A 5year-old female developed upper respiratory infection (URI) symptoms and was diagnosed with COVID-19 in December of 2020. She developed Gottron's sign, heliotrope rash, and weakness resulting in admission in February of 2021. She had elevated CK, AST, ALT, LDH, and aldolase. Her CMAS (childhood myositis assessment scale) was 24. An MRI showed diffuse myositis. Myositis specific antibody (MSA) testing revealed a positive MJ antibody. She was diagnosed with JDM and started on steroids, methotrexate, hydroxychloroquine, and IVIG with improvement. The second patient was a 4year-old female who was diagnosed with COVID-19 in October 2020. In January 2021, she developed heliotrope rash and Gottron's papules. She developed decreased exercise tolerance in May 2021 found to have elevated Aldolase and LDH. Her CMAS was 34. An MRI showed diffuse myositis. MSA testing was significant for a positive P155/140 antibody. She was started on hydroxychloroquine, steroids, IVIG and methotrexate with improvement. Due to the aforementioned cases a retrospective analysis was performed assessing the characteristics of JDM pre-and post-COVID-19 at Lurie Children's Hospital. Methods. The Cure JM biorepository houses clinical data, laboratory data, and patient samples obtained at the onset of JDM. The following information was obtained from newly diagnosed JDM patients: MSA, DAS (disease activity score), flow cytometry results, vWF antigen, neopterin, CMAS, capillary end row loop(ERL), LDH, Aldolase, ESR, CRP, IgG, complements, ANA, and age at diagnosis. We identified 10 patients with a diagnosis of JDM from January 1st 2020 -July 1st 2021 who were designated as the post-COVID-19 group. This population was compared to a total of 51 patients diagnosed with JDM between Jan 1st 2010 and December 31st 2019 who were designated as the pre-COVID-19 group. Data analysis was performed using Welch T-testing. Research enrollment was impacted due to the COVID-19 pandemic. To better assess JDM rates, chart review and EMR reports were obtained to determine the total number of JDM diagnoses. Results. T-testing showed no significant change in DAS, ERL count, T or B cell flow cytometry, vWF antigen, CK, CMAS, CRP, Aldolase, LDH, IgG, complements or ANA titer between the pre-and post-COVID-19 JDM groups. The analysis showed a significant change in NK cell population with a decrease in the absolute NK cell number (pre 163, post 90.75. P value 0.03), and NK cell percentage (pre 6.6%, post 3.625%, P value 0.008). Both of the patients presented in this case report showed a low NK cell number (1% and 3% respectively). The total number of new JDM cases rose from an average of 6.3 cases per year to an average 9 cases per year from January 1st 2020 to December 31st 2021. Conclusion. This study provides two case reports of COVID-19 likely triggering JDM. This study also shows a modest increase in the number of new JDM cases since the onset of the pandemic. Interestingly, the NK cell population in the post-COVID-19 JDM patients were significantly decreased. NK cells have multiple roles in not only immune regulation, but also the immune response to viruses. This study suggests that NK cells play a role in the development of in virally mediated JDM, specifically in cases triggered by COVID-19. Future studies will be important to further delineate the function of NK cells in these patients. Markers of JDM disease severity, including DAS, Neopterin, CK, and CMAS, did not significantly change in our institution's JDM population after the onset of the COVID-19 pandemic.

Switching from intravenous to subcutaneous infliximab: Clinical and patient experience outcomes

Background: Intravenous (IV) infliximab (IFX) monotherapy is associated with significant loss of response. Therapeutic drug monitoring shows an association with low serum trough drug levels and development of anti-IFX antibodies. Combination therapy with immunomodulators is not always possible, and IFX dose escalation leads to higher drug costs and time pressure on infusion units. Both approaches have raised heightened patient safety concerns due to the Covid-19 pandemic. Subcutaneous (SC) IFX pharmacokinetics lead to improved drug trough levels, which could lead to better clinical outcomes. Method(s): The NHS Greater Glasgow and Clyde biologics database was used to identify selected patients currently treated with IV IFX for IBD for suitability for SC switch. Patients were contacted to allow informed choice to opt in or out of switch. Baseline clinical data was collected, and patients were reviewed at week 8 and week 24 for assessment of clinical disease activity scores, IFX trough levels/anti-drug antibody levels, and faecal calprotectin. Patient experience outcomes were assessed using a quality of life questionnaire (CUCQ-8). Result(s): 31 patients consented to switch;F:M = 17:14. The majority of patients (16) had Crohn's disease, with 13 with UC and 2 IBDU. Mean duration of disease was 9.1 years and duration of prior IV therapy was 3.3 years. 28 patients were reviewed at week 8 and 24 at week 24. At week 24, 71% of patients were in clinical remission (Harvey-Bradshaw index score <5 or partial Mayo score <2), 96% had CRP <5 mg/Land 87% had FCP <250mug/g. 21% of patients had subtherapeutic IFX trough levels at baseline, all had increased by week 8 and there were no subtherapeutic levels measured by week 24. One patient had detectable antibodies at week 24, compared with 9 patients at baseline. Three patients required oral steroid therapy during the 24-week follow up period. There were no hospital admissions, significant infections or adverse reactions within the cohort. 15 patients submitted CUCQ-8 scores, of these 7 patients' scores had worsened at week 8 but by week 24 13/15 were stable or improved compared to baseline. Conclusion(s): Switching from IV to SC infliximab is welcomed by most patients. The efficacy, tolerability, increased drug level and safety which has previously been demonstrated is reproduced in our cohort. This study is the first to explore patient experience outcomes. The finding of initial worsening of the CUCQ-8 score, but overall improvement by week 24 opens further opportunity for engaging patient involvement in switch programmes.

COVID-19 in pregnant patients with ankylosing spondylitis

Objective: To describe the course of COVID-19 in women with AS during pregnancy and the effect of COVID-19 on AS activity. Material and Methods: 75 pregnant women with confirmed AS (modified New York criteria, 1984) were included for prospective observation. 26 of them were followed during the Covid-19 pandemic (03.2020 -04.2022). The average age of the patients was 33.0 ± 3.9 years, the duration of the disease was 117.0 ± 72 months. The activity according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in the 1st, 2nd and 3rd trimesters of pregnancy was 2.0 ± 1.4;2.0 ± 1.4 and 1.9 ± 1.5, respectively. The Ankylosing Spondylitis Disease Activity Score CRP (ASDAS-CRP) was 1.5 [1.3;2.1];1.8 [1.3;2.5] and 1.7 [1.1;2.0], respectively. The delivery period was 38.7 ± 1.6 weeks. Results: COVID-19 was transferred to 4 pregnant women, 3 of them -at the end of the 1st -beginning of the 2nd trimester, one -at 38 weeks of pregnancy. No women have been vaccinated against COVID-19. In 3 cases, the activity of AS was low, in one -high due to axial manifestations and arthritis. In 3 women, the course of COVID-19 was mild, in one -moderate (febrile temperature for more than 3 days);only 1 woman had a dry cough. One pregnant woman canceled AS therapy (certolizumab pegol, CZP), against which the back pain of the inflammatory rhythm increased. In other cases, AS therapy was not canceled, there was no effect of COVID-19 on AS activity. (Table Presented) Conclusion: According to preliminary data, COVID-19 in pregnant women with AS can be characterized by a mild and moderate course. There was no increase in AS activity during ongoing AS therapy.

Nail ridging in rheumatoid arthritis patients and relation to disease activity: An integrated rheumatology-dermatology multi-centre study

Aim of the work: To evaluate the frequency of nail ridging (NR) in patients with rheumatoid arthritis (RA) and to study its relation to disease activity. Patients and methods: 230 RA patients and 97 matched controls from Helwan, Ain Shams and Mansoura university hospitals were studied. Disease activity score (DAS28) was assessed. NR has been searched for in all patients. The number of affected fingers was recorded. NR was determined by a magnifying lens, seen by naked eye or seen and felt. Dermoscopic photography of the NR using Dermalite DL4 3Gen dermatoscope has been recorded. Results: The median age of patients was 49 years (42–58 years);they were 221 females and 19 males (F:M 11.1:1) with a disease duration 9 years (5–11 years). Their DAS28 was 3.6 (2.9–4.6). NR was significantly increased in RA cases vs. control;73% vs 20%;p < 0.001. In patients, NR was detected by a magnifying lens in 32.6%, seen in 27% and seen and felt in 13.5%. Joint deformities were significantly higher in those with NR. DAS28 was a significant independent predictor of NR;for every one-point increase in DAS28, there was a 153 times higher odds to exhibit NR at a sensitivity of 93.5%, specificity 80.3% and at a diagnostic accuracy of 90%. Conclusion: NR is a frequent finding in RA. An integrated rheumatological- dermatological clinical evaluation may be helpful and further studies are required to prove the importance of this sign for follow up of RA patients.

Systemic lupus erythematosus cutaneous flare following COVID-19 vaccination: A case report

Objective: To present a case of a SLE cutaneous flare following COVID-19 vaccination in a patient with low disease activity Background: Disease flare in a patient with underlying autoimmune rheumatic disease (AIRD) after vaccination had already been experienced with other vaccines, such as influenza, hepatitis B, and HPV vaccines. Given the relatively unknown safety profile of the COVID-19 vaccine among patients with AIRD, the probability of a disease flare is not a remote possibility. Several case reports available had already reported few cases of AIRD disease flare following vaccination, some of which requiring escalation of the treatment regimen. Molecular mimicry, as had been described with other vaccines, is still implicated as the possible explanation for such a phenomenon. Case: A 57 year old female with systemic lupus erythematosus with nephritis since 1994 with low disease activity, maintained on hydroxychloroquine and low dose methylprednisolone daily who developed multiple well-defined elevated erythematous and pruritic plaques on both thighs, spreading to the face, scalp, trunk, and extremities 3 weeks after receiving her first dose of viral vector vaccine. Work-ups included eosinophilia on CBC, elevated ESR, anti-dsDNA, ferritin, and LDH, with low C3, with proteinuria and hematuria on urinalysis. She was admitted and her glucocorticoid was increased and tapered accordingly. Skin punch biopsy with alcian blue staining was also done which revealed interface dermatitis consistent with lupus erythematosus. Few days after increasing her glucocorticoid, cutaneous lesions gradually resolved and she was discharged improved. She received her second dose of vaccine 2 months after her first dose with no reported incidents of adverse events. Conclusion(s): This is one of the few cases of a reported SLE flare confirmed by disease activity index and biopsy-confirmed skin rashes. The development of such an adverse reaction to a vaccine may be relatively low but still possible due to intricate interaction of the immune system and vaccine.

Comparison of disease activity outcome virtually (tele-rheumatology) and face-to- face disease activity scores for patients with rheumatoid arthritis: A prospective study

Background and Aim: Since the emergence of COVID-19, tele-rheumatology care has presented as an appealing alternative way for accessing health care. The efficacy of tele-care needs to be evaluated in our setting. This study aimed at assessing the agreement between the tele-visit and the face-to- face clinic-based visit. Methodology: We prospectively recruited patients with rheumatoid arthritis;who were following up in the out-patient department clinics between December 2021 and May 2022. Each patient underwent disease activity assessment by means of disease activity score 28-c- reactive protein (DAS28-CRP) and disease activity score28-erythrocyte sedimentation rate (DAS28-ESR). Within two weeks from the face-to- face visit, we virtually assessed their disease activity, through a telephone-based interview, by applying Routine Assessment of Patient Index Data 3 (RAPID3) score, collecting data on demographics and inquiring about satisfaction with the tele-visit. Disease activity scores were categorized into remission or low disease activity, and moderate to high disease activity. Result(s): In our study, 78 patients were recruited and completed the two-points interview. A total of 62(79.49%) of the participants were female;mean age of 54.73 +/- 13.71 years. Seropositivity for rheumatoid factor and/or anti-citrullinated peptide was found in 51(83.61%) participants. 27% of patients with RAPID3 had remission or low disease activity. While this was 71% and 33% for DAS28-CRP and DAS28-ESR, respectively. Moderate to high disease activity percentage of 73%, 29% and 67% were found in RAPID3, DAS28-CRP and DAS28-ESR, respectively. Furthermore, the correlations of RAPID 3 were relatively moderate but significant with DAS28-CRP (r = 0.6, P-value < 0.001) and DAS28-ESR (r = 0.4, P-value = 0.001), respectively. Satisfaction rates with the tele-visit were at odds with other reported publications. Conclusion(s): Tele-rheumatology assessment of disease activity for patients with rheumatoid arthritis appears to be feasible in our setting. Further studies should aim at assessing patients' satisfaction and the recently implemented video-based tele-clinics.

COVID-19 within a year after childbirth in women with ankylosing spondylitis (AS)

Objective: Describe the course of COVID-19 and its effect on AS activity in women infected within 1 year after childbirth. Material(s) and Method(s): 75 pregnant women with confirmed AS (modified New York criteria, 1984) were included for prospective observation. 22 of them were followed during the COVID-19 pandemic (03.2020 -04.2022) for a maximum of 12 months after childbirth. The average age of the patients was 31.5 +/- 4.3 years, the duration of the disease was 124.8 +/- 75.7 months. The activity according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at 1, 6 and 12 months after delivery was 2.0 +/- 1.3;2.2 +/- 1.3 and 2.5 +/- 2.0, respectively. The Ankylosing Spondylitis Disease Activity Score CRP (ASDAS-CRP) was 2.2 [1.2;2.9];2.0 [1.5;2.8] and 1.7 [1.3;2.3], respectively. Result(s): 4 women suffered COVID-19 within a year after giving birth. None of them have been vaccinated against COVID-19. At the time of infection, the activity of AS in all patients was low, 3 women received certolizumab pegol (CZP). In all cases, COVID-19 proceeded with febrile fever for at least 1 day, while the general symptoms were stopped for a maximum of 7 days. Only 1 woman had a dry cough. The effect of COVID-19 on the activity of AS was not revealed, including 2 patients who canceled CZP. All the women continued lactation. 2 children had mild catarrhal phenomena for 3 days, one child underwent a PCR test, SARS-CoV- 2 RNA was detected. Conclusion(s): According to preliminary data, there is no effect of COVID-19 on initially low AS activity in women during lactation. One of the main symptoms of COVID-19 in all patients was febrile fever, regardless of the time of infection that has passed after childbirth.

COVID-19 in rheumatoid arthritis patients receiving baricitinib: Observations from patient registry

Background/Purpose: Rheumatoid arthritis (RA) patients have higher COVID-19 risks [1,2]. Data suggest that some RA biologics, including baricitinib, may be beneficial for COVID-19 outcomes [3,4]. We used data from RA registry to evaluate impact of COVID-19 on RA activity in patients receiving baricitinib. Method(s): Current study is a single center registry of RA patients receiving baricitinib as a part of routine treatment. Study center accumulates most of RA patients who started baricitinib in Moscow (Russia) from July 2020 to data cutoff (January 2022). We analyzed medical records data for demographics, disease history, and change of disease activity indexes. Medical record data were allocated to visit 1 (baseline), closest to 4 and 8 months after baricitinib initiation (visits 2 and 3). Patients, who had no baricitinib interruptions, were divided in strata according to COVID status between visits 1 and 2. Result(s): At the time of data cutoff registry included data from 142 RA patients receiving baricitinib. Median duration of treatment was 14.5 (interquartile range [IQR] 10-29) weeks. Clinical RA indexes measures are compiled in Table 1. Of 142 patients, 52 had COVID-19 between visits 1 and 2 without baricitinib interruption. Swollen joint counts (SJCs) and tender joint counts (TJCs) were comparable across 3 visits except TJC at visit 3 (P < 0.05). Disease Activity Score-28 for Rheumatoid Arthritis with C-Reactive Protein (DAS28-CRP), Disease Activity Score-28 for Rheumatoid Arthritis with Erythrocyte Sedimentation Rate (DAS28-ESR) had comparable change regardless of COVID-19 status (P > 0.05). Simplified Disease Activity Index for Rheumatoid Arthritis (SDAI) and Clinical Disease Activity Index (CDAI) were higher in COVID-19 survivors at visit 3 (P < 0.05). (Table Presented) Conclusion(s): We conclude that, overall, COVID-19 had no significant impact on RA activity during baricitinib treatment. Further follow-up needed to find out reasons for TJC/SDAI/CDAI increase in COVID-19 survivors >=4 months after infection.

Effect of SARS-CoV- 2 mRNA vaccination on thrombin generation in children with inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), is associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. IBD patients were underrepresented in SARS-CoV- 2 mRNA vaccine trials. Case reports indicated that adverse events post-vaccination, including IBD flare, were more common among children, and those with prior COVID-19. Aim(s): To find out whether TG is increased in children with IBD as compared to healthy controls and whether TG parameters show significant changes following SARS-CoV- 2 mRNA vaccination. Method(s): In this observational case-control study, 37 children with IBD (CD:16, UC: 21) aged 12-18 years and 55 healthy age-matched children were enrolled. Blood was collected before and 2-4 weeks after the second dose of BNT162b2 (Pfizer-BioNTech) vaccine dose. Whole blood count, fibrinogen, inflammatory markers (CRP, ferritin), anti-SARS- CoV- 2 antibody levels were investigated, TG assay was carried-out using platelet-poor plasma. Lag time, endogen thrombin potential (ETP), peak thrombin, time-to- peak were calculated. Detailed clinical parameters including post-vaccination symptoms, COVID-19 history, disease activity scores (PUCAI, Mayo score, PCDAI) were registered. Result(s): CRP was significantly elevated in children with IBD and showed a positive correlation with ETP (CD: R = 0.700;p = 0.003 and CU: R = 0.501;p = 0.020). TG parameters did not differ between patients and controls pre-or post-vaccination. TG parameters remained unaltered post-vaccination in both groups. IBD disease flare was not observed post-vaccination, but reduced anti-SARS- CoV- 2 antibody titers were found in 4 patients receiving immunosuppressive therapies. Previous COVID-19 infection had no effect on TG levels. Conclusion(s): Although TG parameters correlated with the level of inflammation in children with IBD, the extent of TG was not significantly different from healthy controls. TG parameters and IBD disease activity scores did not increase significantly following mRNA vaccination. Our results support the safety of SARS-CoV- 2 mRNA vaccination in children with IBD, highlighting observations of lower antibody titers in immunosuppressed children.

The Association of uPA, uPAR, and suPAR System with Inflammation and Joint Damage in Rheumatoid Arthritis: suPAR as a Biomarker in the Light of a Personalized Medicine Perspective.

BACKGROUND: In recent years, the involvement of the soluble urokinase Plasminogen Activator Receptor (suPAR) in the pathophysiological modulation of Rheumatoid Arthritis (RA) has been documented, resulting in the activation of several intracellular inflammatory pathways. METHODS: We investigated the correlation of urokinase Plasminogen Activator (uPA)/urokinase Plasminogen Activator Receptor (uPAR) expression and suPAR with inflammation and joint damage in RA, evaluating their potential role in a precision medicine context. RESULTS: Currently, suPAR has been shown to be a potential biomarker for the monitoring of Systemic Chronic Inflammation (SCI) and COVID-19. However, the effects due to suPAR interaction in immune cells are also involved in both RA onset and progression. To date, the literature data on suPAR in RA endorse its potential application as a biomarker of inflammation and subsequent joint damage. CONCLUSION: Available evidence about suPAR utility in the RA field is promising, and future research should further investigate its use in clinical practice, resulting in a big step forward for precision medicine. As it is elevated in different types of inflammation, suPAR could potentially work as an adjunctive tool for the screening of RA patients. In addition, a suPAR system has been shown to be involved in RA pathogenesis, so new data about the therapeutic response to Jak inhibitors can represent a possible way to develop further studies.

A Single-Center Covid Vaccination Experience in Patients with Sjogren's Syndrome

Introduction. Vaccination against SARS-CoV2 is beneficial for patients with autoimmune disease. Therefore, we recommended basic immunization as soon as it has become available for our patients. We preferred mRNAbased vaccination based on the international recommendations. However, several patients received other types of vaccines at their own or their general practitioner's discretion. Based on the antibody levels against the SARSCoV2 spike protein measured at the Institute of Laboratory Medicine of our university, we were able to draw initial conclusions about the effectiveness of vaccination regarding our primary Sjogren's syndrome patients. Patients and methods. Antibodies to SARS-CoV2 spike protein were analyzed in the sera of 77 patients with primary Sjogren's syndrome after being vaccinated with two doses between 1st January and 30th April, 2021, at least 30 days after the second vaccination. Antibody responses were classified as high (above 250 U/ml), moderate (between 50 and 250 U/ml) and low (below 50 U/ml). Relying on the SPSS statistical program, we were seeking correlations between the serum levels and the EULAR Sjogren's syndrome disease activity index (ESSDAI) and the potential influence of the different immunosuppressive treatment modalities, respectively. For the statistical analysis, chi2 tests were performed. Result(s): Pfizer vaccine was given to 58 patients, and the rest of our cohort received Moderna (2 patients), Sinopharm (10 patients), Astra Zeneca (6 patients) and Sputnik vaccine (1 patient). High antibody levels were found in 54 subjects (70.1%), moderate levels in 11 subjects (14.3%), and low levels in 12 subjects (15.6%). After having received the Pfizer vaccine, 86.2% had high, and only 5.2% had low antibody levels. One patient vaccinated with Moderna had high, while the other had low antibody level. The majority (55%) of those vaccinated with Astra Zeneca achieved high titers, and 17% were classified as low responders. After immunization with Sinopharm vaccine, 20% of the patients were classified into moderate response category, while the rest (80%) presented low antibody levels. We also measured low value in the serum of the patient that received the Sputnik vaccine. Serum levels of specific antibodies in patients not receiving any specific therapy (14 subjects) did not differ significantly from those treated with antimalarials (18 subjects), methotrexate (19 subjects), azathioprine (6 subjects), or low-dose steroids (20 subjects). Based on our results, the type of immunosuppressive treatment had less effect on the protection developed than the type of vaccination. There was no significant correlation between Sjogren's syndrome disease activity and the degree of specific antibody response to the vaccine. Conclusions. Our initial results suggest that the use of COVID vaccines is safe and effective for Sjogren's syndrome patients, regardless of the treatment used or of the ESSDAI.

WITHDRAWING METHOTREXATE after BOTH VERSUS only SECOND DOSE of the CHADOX1 NCOV-19 VACCINE in PATIENTS with AUTOIMMUNE INFLAMMATORY ARTHRITIS: TWO INDEPENDENT RANDOMIZED CONTROLLED TRIALS (MIVAC i and II)

Background: Pausing methotrexate (MTX) for two to four weeks, improved immunogenicity of infuenza vaccination in patients with rheumatoid arthritis (RA), albeit a risk of disease fare (1). This guided the framing of guidelines on MTX withdrawal for COVID-19 vaccination (2). However, evidence for MTX withdrawal for COVID-19 vaccination is limited to observational studies only. Objectives: To compare the efficacy and safety of holding MTX after each (MIVAC 1) and only after the second dose (MIVAC II) of the ChAdOx1 vaccine versus continuation of MTX in two randomized controlled trials (RCTs). Methods: Two single centre, investigator-blinded, RCTs were conducted in patients with RA or Psoriatic arthritis (PsA) on stable doses of MTX without prior COVID-19 (CTRI reg. no. MIVAC I: CTRI/2021/07/03463 & MIVAC II: CTRI/2021/07/035307). In MIVAC I, unvaccinated patients were randomised (1:1) to hold or continue MTX for two weeks after each dose of the vaccine. MIVAC II included patients who had continued MTX during the frst dose of ChA-dOx1 and were randomised (1:1) to hold or continue MTX for 2 weeks after the second vaccine dose. The primary outcome for both the trials was the anti-Receptor Binding Domain (RBD) antibody titres measured four weeks after the second vaccine dose (per protocol analysis). Secondary outcome was the fare rate, defned as an increase in disease activity scores (DAS28/cDAPSA) or physician intent to hike DMARDs. Results: 250 patients were randomized for MIVAC 1 and 178 for MIVAC II and after due exclusions, 158 and 157 were eligible for analysis respectively (Figure 1). In MIVAC I, median anti-RBD titres were signifcantly high in the MTX hold group [2484 (1050-4388) versus 1147(433-2360), p=0.001] but the fare rate was higher in the hold group [20 (25%) versus 6(8%) p=0.005] compared to continue group. In MIVAC II median anti-RBD titres were signifcantly high for the MTX hold group [2553 (1792-4823) versus 990 (356-2252), p=0.001] when compared to continue group but there was no difference in the fare rate between the groups [9(11.8%) and 4(7.9%), p=0.15] (Table 1). Since both were parallel studies in similar population, MTX hold arms across both the trials were compared for anti-RBD titres and fare. There was no difference in the anti-RBD titres [p=0.2] between the groups. In MIVAC I, 29(36.25%) patients had reported fare (19 in either frst or second dose, 10 for both doses) when compared to MIVAC II where only 9(11.84%) patients had reported fare after the second dose (P <0.001). Conclusion: Holding MTX after both the doses or only after the second dose of ChAdOx1 yields higher anti-RBD antibody titres as compared to continuing MTX. Comparing across the trials, holding MTX only after the second dose appears to be non-inferior to holding MTX after both doses of the vaccine with a lesser risk of fare.

COVID-19 VACCINE: HESITANCY, ACCEPTANCE and TOLERANCE among PATIENTS with RHEUMATOID ARTHRITIS

Background: Patients with rheumatoid arthritis (RA) are considered a high-risk population to develop severe COVID-19 [1] and therefore vaccination is strongly recommended. Previous reports have shown a high hesitancy rate to receive a COVID-19 vaccine among RA. Objectives: This study aimed to evaluate the attitude of patients with RA to vaccination against SARS-CoV-2, explore the factors which may influence it, and assess adverse events of SARS-CoV-2 vaccines. Methods: This is a cross-sectional study including 106 patients with RA diagnosed according to the ACR/EULAR 2010 classification criteria and followed in the Rheumatology Department, over a period of 10 months from March to December 2021.Demographic and disease parameters were collected: age, gender, educational status, disease duration, erythrocyte sedimentation rate (ESR), disease activity score (DAS28), and treatments being used. All patients responded to a questionnaire on their perceptions and concerns about the covid-19 vaccine, and the adverse effects for those who got vaccinated. Results: Among the 106 patients, 90 (84,9%) were females and 16 (15,1%) were males. The mean age was 54 ±13 years old [23-77]. Sixty-four percent were from urban areas and 36 % were from rural areas. Thirty-three percent of patients were illiterate. The mean disease duration was 9.54 ±5.76 years [2-22]. The mean DAS28 ESR was 3,88 ±1.34 [1.2-7.58]. All of our patients were taking conventional synthetic DMARDs. Seventeen percent of patients were on biological DMARDs. The majority of the patients (90%) reported that they respected the preventive measures. Twenty-two percent of patients had stopped their treatment because they were afraid of the covid-19. Twenty-eight patients had contracted the SARS-CoV-2. Seventeen percent of the patients reported that they didn't get vaccinated against covid-19. The reasons given by these patients were: presumed adverse events (53,3%), presumed inef-fciency (25%), no recommendation from their doctor (46,7%), fear that the vaccine would make RA worse (64,7%). For the vaccinated patients, the vaccines administered were: 63,6 % Pfzer BioNTech, 6,8% Oxford/AstraZeneca, 5,7% Moderna, 4,5% Janssen/Johnson & Johnson, 2,3% Sinovac-Coro-naVac and 17% unspecifed. The majority of the patients (72,7 %) received two doses,14,8 % one dose and 12,5% 3 doses. After vaccination, 73,9% of patients reported adverse events, such as pain at the site of injection (88,1%), fatigue (35,8%), headache (14,9%), fever (13,4%) and muscle/joint pains (4,5%). Only 1 patient had experienced rheumatic disease fare. Hesitancy about the COVID-19 vaccination was associated with low intellectual level (p=0.004) and rural origin (p=0.001).RA disease duration, DAS28-ESR, and treatments have no influence on the attitude of patients towards COVID-19 Vaccination (p > 0,05). Conclusion: The acceptance of COVID-19 vaccination by RA patients in our study is quite promising. The majority of patients tolerated their vaccination well, with rare RA fares up. These results should reassure rheumatologists and patients. Education and outreach efforts need to be continued, especially for illiterate people and those who live in rural areas.

ATTITUDES and HESITANCY in PATIENTS with INFLAMMATORY RHEUMATIC DISEASES TOWARDS SARS-COV-2 VACCINATION: A SINGLE-CENTER STUDY from BULGARIA

Background: Bulgaria is among the countries with the lowest vaccination rate of adult population in Europe. The presence of autoimmune rheumatic disease could further contribute to vaccine hesitancy and skepticism and influence patients' attitudes towards vaccination [1, 2]. However, little is still known about the willingness and particular causes of hesitancy in patients with infammatory joint diseases in the skeptical part of adult population across Europe. Objectives: Our goal was to assess the rate of SARS-CoV-2 vaccination among patients with immune-mediated rheumatic joint diseases receiving biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) and to determine the modifable predictors of vaccination hesitancy. Methods: Patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis undergoing biological or targeted synthetic DMARDs therapy were consecutively selected and included in this single-center cross-sectional study. Excluding criteria in patients were psychiatric or neurological disease preventing understanding or responding to the questions, being illiterate, or not willing to participate in the study. Various demographic, anthropometric, and clinical data were collected. Disease activity was determined using DAS28-CRP for rheumatoid arthritis and peripheral psoriatic arthritis and ASDAS for ankylosing spondy-litis and psoriatic spondylitis. All patients were given a questionnaire assessing their vaccination status, hesitancy, and attitude towards vaccination. Binary logistic regression analysis was used to analyze the relationship between self-reported modifable parameters and vaccination status for SARS-CoV-2. Results: Two hundred and one participants were eligible for participating in the study with mean age and BMI of 54.6 years and 28.2, respectively. Of these, 40.3% were women;30.3% had rheumatoid arthritis, 17.9%-psoriatic arthritis, and 51.7%-ankylosing spondylitis. 29.4 % of all participants had already survived a COVID-19 infection with a mean time of 8.4 months since the COVID-19 onset. Only slightly above 1/3 (35.8%) of the study group was fully vaccinated and the majority of them were vaccinated with BNT162b2 (68.1%). Among the modifable factors, we identifed preceding discussion with a rheumatologist, hesitancy due to autoimmune disease presence and (un)awareness of vaccine safety and efficacy as signifcant predictors of vaccination status Conclusion: Our data suggest that there are still possibilities to influence rheumatic patients on their decision to vaccinate against SARS-CoV-2 in Bulgaria. Raising the awareness of the safety and efficacy of the SARS-CoV-2 vaccines and spending more time on the education of patients with rheumatic diseases may positively affect their attitude towards vaccination.

CLINICAL CHARACTERISTICS of PATIENTS with SPONDYLOARTHRITIS with COVID-19 in ANAMNESIS in the REPUBLIC of TATARSTAN

Background: The management of patients with spondyloarthritis (SpA) during the period of the novel coronavirus infection (NCI) pandemic is a signifcant problem due to insufficient evidence base. Objectives: To study the features of the course NCI and its influence on the course of SpA. Methods: From March 2020 to January 2022, 55 patients with SpA who underwent NCI (with a confrmed result of SarsCoV2 PCR and/or using X-ray computed tomography (CT) of the lungs): ankylosing spondylitis (AS) 37 people, with psoriatic arthritis (PsA) 18 people. Of these 32 (58.2%) were men, 23 (41.8%)-women, the average age of patients was 49 [37.5;57.5] years. The duration of SpA at the time of NCI was 11 [7;16] years. SpA activity before NCI was low in 15 (34.8%) patients, moderate in 25 (58.1%), and high in 3 (6.9%) patients. The results of clinical and laboratory examinations were evaluated during the NCI and after 1, 3, 6 months. Results: Symptoms of NCI in patients with SpA were comparable in frequency and severity to the course of infection in the population. 47.3% had a mild course of NCI, and 52.7% of those observed had a moderate course, which is comparable with the general population data. Lung involvement was detected in 29 (52.7%) patients. The outcome of COVID-19 in all patients is recovery. Analysis of the course of SpA showed an increase in activity 1 and 3 months after NCI: BASDAI from baseline to COVID-19 4.3±1.57 to 4.9±1.7 points after 3 months, similar to ASDAS-CRP from 2.6±1, 2 to 3.7±0.2, BASFI from 3.0±1.9 to 3.8±1.8. A positive correlation was found between the severity of NCI and the BASFI index after 3 months (0.870). Analysis of the course of PsA showed an increase in activity 1 and 3 months after NCI: DAS28 from the baseline 2.78±0.98 to 4.15±1.16 points after 3 months. Of the total number of recoveries, 72.2% of patients showed an increase in activity due to clinical and laboratory parameters. 78.1% of patients noted the presence of post-COVID symptoms after NCI, 56.3% had a combination of more than 3 different symptoms. Most often there was an increase/appearance of pain in the joints-in 78.1%: signifcant-in 61.8%, insignifcant-in 16.3% of respondents. Strengthening/appearance of muscle pain and/or headache and/or dysautonomia occurred in 72.7%. This can be assessed as an exacerbation of the underlying disease, or, conversely, the appearance of arthralgia and myalgia could have an impact on the increase in AS and PsA activity indices. The second most frequent were a decrease in the quality of life (QOL) and working capacity in 69.0% of patients: signifcant in 36.3% of patients, insignifcant in 32.7%. The appearance/intensifcation of shortness of breath and a decrease in exercise tolerance were noted by 60% of the respondents. Among them, 34.5% of patients with moderate severity, 25.4%-with mild NCI. Appearance/intensifcation of chest pain and/or palpitations was noted by 16.3% of patients Conclusion: The prevalence and course of the NCI in patients with SpA did not differ from that in the population. However, coronavirus infection has led to increased pain and an increase in AS activity, long-term persistence of post-COVID manifestations in the form of musculoskeletal pain and asthenic symptoms in the form of a decrease in the quality of life. At the same time, specifc respiratory symptoms occurred in a third of patients and were not associated with the severity of the NCI.

HOW CAN WE ASSESS CARDIOVASCULAR RISK in PATIENTS with JUVENILE IDIOPATHIC ARTHRITIS? PRELIMINARY RESULTS REGARDING MEASUREMENTS of CAROTID INTIMA-MEDIA THICKNESS during the COVID-19 PANDEMIC

Background: There is growing body of evidence that adults who were diagnosed as children with juvenile idiopathic arthritis (JIA) have signifcantly increased risk of developing cardiovascular disease. Risk factors including prolonged sedentary screen time, insufficient physical activity and unhealthy diet are even more essential in the era of the COVID-19 pandemic. However, there is lack of simple and reliable prognostic marker identifying children at higher risk of early development of cardiovascular disease. Non-invasive tests utilized in adults to screen for early phase of atherosclerosis involve examination of the carotid intima-media thickness (cIMT). Only a few research projects have evaluated performance of cIMT measurement in JIA patients and the results remain inconclusive. Objectives: The aim of this study was to evaluate the usefulness of cIMT testing as a screening method to determine cardiovascular risk in JIA patients. The secondary objective was to assess the frequency of risk factors related to the patients' lifestyle during the COVID-19 pandemic. Methods: The study involved forty-five patients at mean age 13.4±3.2 years who were already diagnosed with JIA and thirty-seven age-and sex-matched healthy controls. Children were enrolled in the study between March 2020 and September 2021. Study database included demographic data, conventional risk factors for developing cardiovascular disease (e.g. abnormal body mass index and exposure to secondhand smoking), infammatory markers and disease activity score. Measurements of cIMT were performed by a qualifed physician according to the standardized protocol using high resolution ultrasonography. Results: Measurement of cIMT revealed values above 94th percentile in four children (three males and one female) who were all diagnosed with JIA. The quantity of abnormal results was not enough to verify the hypothesis of increased cardiovascular risk in JIA patients, though (p=0.06296). However, children diagnosed with JIA are more likely to have abnormal body mass index than their healthy peers (51.1% vs. 21.6%, p=0.00614). Children who doubled their sedentary screen time during the COVID-19 pandemic skipped the sufficient physical activity (p=0.03352). Correlation between elevated ESR and higher cIMT values in right carotid artery was marginally signifcant (r=0.292, p=0.051443). Regardless of JIA, exposure to secondhand smoking was proved as a signifcant risk factor of atherosclerosis (18.2% vs. 2.8%, p=0.02771). Conclusion: Screening measurements of cIMT should be considered in the follow-up of JIA patients with higher disease activity with concurrent elevated ESR. Defning other indications for performing such examination requires further investigation involving larger study group. Healthy lifestyle, including reducing secondhand smoke exposure, needs to be promoted with utmost importance during the COVID-19 pandemic, especially in children with chronic diseases like JIA.

THE COURSE of COVID-19 in A COHORT of SPONDYLOARTHRITIS PATIENTS: A CASE-CONTROL PROSPECTIVE STUDY

Background: With the outbreak of the SARS-CoV-2 pandemic, the rheumatol-ogists' attention was directed at understanding whether infected patients could have a less favorable outcome. Available data seem to indicate that the course in rheumatic patients is not dissimilar from that in the general population. However, data on the outcome of COVID-19 in patients with spondyloarthritis (SpA) are scant. Objectives: To describe the outcome of COVID-19 in patients with SpA in terms of hospitalization, need of oxygen therapy, and symptoms compared to a control group. The variation in disease activity before and after COVID-19 was also assessed. Methods: We enrolled adult patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) classifed according to standard criteria, that received a diagnosis of COVID-19 through molecular or rapid antigen swab tests between September 2020 and January 2022. Demographic and clinical data, including age, body mass index (BMI), smoking habit, comorbidities, rheumatic treatment at diagnosis of COVID-19, date of COVID-19 diagnosis, symptoms and additional therapy during the infection and vaccination status were collected through a questionnaire and recorded on an electronic database. Disease activity, assessed by DAPSA in PsA patients and by BASDAI and ASDAS in AS patients, was evaluated before and at the frst visit after the infection. As controls, individuals with COVID-19 but with no known diagnosis of rheumatic/autoimmune disease were recruited using the 'best friend' system. Results: Sixty-two patients were enrolled [43 with PsA and 19 with AS;F:M=40:22;median age 51 years, 25th-75th percentile 39.5-61;median BMI 25.5, 25th-75th percentile 21.75-28;median disease duration 90 months, 25th-75th per-centile 36-192;6 (9.7%) smokers, 37 (59.7%) non-smokers, 19 (30.6%) past smokers;15 (24.2%) only treated with one conventional DMARD, 27 (43.5%) with bDMARDs and 20 (32.3%) with both;44 (71%) had received no vaccine, 18 (29%) one or more doses of vaccine]. Forty-eight controls were also recruited [F:M=29:19;median age 48 years, 25th-75th percentile 41.5-57;median BMI 23.86, 25th-75th percentile 20.69-28.03;10 (20.83%) smokers, 28 (58.33%) non-smokers, 10 (20.83%) past smokers;43 (89.6%) had received no vaccine, 5 (10.4%) one or more doses of vaccine]. Among patients, 10 (16.1%) were hospitalized, of whom 8 (80%) required noninvasive oxygen therapy. Among controls, 7 (14.5%) were hospitalized, of whom 5 (71.4%) required noninvasive oxygen therapy. No differences were observed compared to the control group in terms of hospitalization and need for oxygen support. Likewise, the two groups did not bear any statistically signifcant difference in terms of symptoms (fever, dys-geusia, dyspnoea) and cardiovascular and respiratory comorbidities. BMI and smoking habit did not influence the outcome of COVID-19 in SpA patients, while a BMI of 25 or above was associated with hospitalization in the control group (p=0.0004, RR 3.417). Baseline treatment with immunosuppressants did not influence the disease outcome. DAPSA, ASDAS, and BASDAI did not signif-cantly change after the infection (Table 1). We did not record any COVID-19-re-lated death in either group. Conclusion: Our data show that patients with SpA do not face a worse prognosis of COVID-19 than subjects without rheumatic/autoimmune diseases and that demographic and clinical features did not influence the course of the disease.