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.

C-Reactive Protein Rise in Rheumatology Patients Following Covid-19 Vaccination

Background/Aims With widespread implementation of COVID-19 vaccine, there has been concern that it would trigger an immune activation due to its immunogenic properties. There is low-level evidence that patients with rheumatological diagnosis often have a disease flare following COVID-19 vaccination which not only has personal health implications but also wider socioeconomic implications. Inflammatory arthritis patients are classified as vulnerable patients requiring booster vaccinations. Therefore, there is a need to ascertain whether there is a risk of disease flare in this group of patients so as to counsel them appropriately in order to ensure flares are managed in timely manner. This study aims to determine the proportion of patients with inflammatory arthritis who have a flare of their rheumatological disease within 30 days of receiving a COVID-19 vaccine using CRP as a surrogate marker. Methods A retrospective notes review was conducted of patients with inflammatory arthritis within 30 days of their COVID-19 vaccine. An electronic database (DAWN) was used to identify all patients that were currently on a disease-modifying anti-rheumatic drug (DMARD) or biologic therapy. This was then correlated with vaccine data from the National Immunisation and Vaccination system (NIVS) and C-reactive protein (CRP) within 30 days of their vaccination. Results 1620 adults were identified from DAWN databases (mean age 61 years, 64% female). Three types of vaccination were used: AstraZeneca (AZ), BioNTech-Pfizer or Moderna. Vaccine uptake was 1542/1620 (95.2% 1st dose), 1550/1620 (95.7% 2nd dose) and 1437/ 1620 (88.7% 3rd dose). 192/1542 patients (12.5%) had a CRP rise of greater than 10mg/L within 30 days of their vaccine, which was higher than baseline flare rate of 8.6% (p=0.0004). Conclusion Patients with inflammatory arthritis and on DMARDS have high uptake of COVID-19 vaccine (95%) which is greater than the national average. A CRP rise greater than 10mg/L within 30 days of vaccination was observed in roughly 1 in 10 patients in our study population on all three doses which is consistent with other studies in the literature. Our results show statistically significant increase in the rate of disease flare (12.5% compared with baseline rate of 8.6%). However, SARS-CoV-2 infection has been shown many times to be an independent risk factor for rheumatic disease flare ranging from 20-40%. Therefore, patients with inflammatory arthritis should still be encouraged to receive COVID-19 vaccination. To maintain high levels of vaccine uptake, it is important to ensure that patients are aware of the risks of vaccinations and sufficiently safety netted so flares are managed early. As on-going booster vaccinations are planned for rheumatology patients, we recommend further research to better inform and counsel our patients. Furthermore, this study calls for diligence in monitoring patients with inflammatory arthritis for disease flare and for swift intervention to prevent losing disease control.

Immunosuppression Doubles the Risk of Covid-19 Infection in a Large Vaccinated Cohort of 898 Patients with Rheumatic Diseases: Implications for Future Practice

Background/Aims It is recognised that immunosuppressive medications, often relied upon in the management of autoimmune rheumatic disease, inhibit vaccine-induced immunity against the SARS-CoV-2 virus. A key challenge for rheumatologists is maximising immunity provided by the vaccine in their patients. Recent data has implicated methotrexate (MXT), a commonly used disease modifying anti-rheumatic drug (DMARD), in reducing patients' vaccine-induced immunity against the virus and studies have demonstrated the effectiveness of pausing MXT medication for 2-weeks after receiving the vaccine in boosting patients' immunity. There is a lack of data exploring the impact of concurrent biologic-DMARD (b-DMARD) use with MXT on COVID-19 infection rates in vaccinated individuals. This analysis forms part of a larger programme of research (clinicaltrials.gov NCT04542031) exploring COVID-19 in patients with rheumatic disease. Here we provide a comparative analysis of COVID-19 infection rates between patients taking MXT either with or without b-DMARD therapy and those on no immunosuppression. Methods We distributed two web-based questionnaires via SMS-messaging in April 2020 and December 2021 and two interim monitoring questionnaires in December 2020 and June 2021. All rheumatology patients with a valid mobile telephone number under follow up at the Royal Wolverhampton Trust were invited to participate in the study;those that consented received follow up questionnaires. We collected information on demographics, rheumatology diagnosis and treatment, vaccination status, and COVID-19 infection rates. Data were collected 7-days following questionnaire distribution. Results Initial questionnaires were sent to 7911 active follow up patients, 1636/ 7911 (21%) responded and consented to further follow up;906/1636 (55.4%) provided a complete response to the final survey which was subsequently linked to survey one enabling analysis. Responders were female (622/906, 68.7%), white (865, 95.5%), 60 years or above (519, 57.3%), and vaccinated (898/906;99.1%). Of those vaccinated significantly more patients that were on any immunosuppressive therapy compared to those on no immunosuppression (92/530 (17.4%) vs. 26/368 (7.1%);p<0.001), and more in the MXT monotherapy group compared to no immunosuppression (33/222 (14.9%) vs. 26/368 (7.1%);p=0.001) contracted COVID-19. Similar numbers in the MTX and b-DMARD and b-DMARD without MXT groups (23/140 (16.4%) vs. 36/168 (21.4%);p=0.23) contracted COVID-19. Conclusion Recent trial data from the VROOM study has demonstrated that omitting a patients MXT therapy for a 2-week period following administration of the COVID-19 vaccine doubles their antibody response. This data highlights that the risk of COVID-19 infection in vaccinated rheumatology patients is doubled in patients on any immunosuppressive medication compared to those on no immunosuppression, while there is no significant difference in infection rates between patients on MXT and a b-DMARD and b-DMARD therapy without MXT. Further work exploring the impact of different types of immunosuppression on COVID-19 vaccine-induced immunity and simple interventions to maximise this immunity in immunosuppressed individuals is required.

Experience of Baricitinib in a Real-World Population with Efficacy and Side Effects: A South London Regional Analysis

Background/Aims Baricitinib is the most common Janus Kinase inhibitor (JAKi) used in the treatment of rheumatological conditions. Whilst randomised controlled trials have demonstrated the efficacy and safety profile of baricitinib, real-world data on the experience of JAKi use in clinical practice is lacking. The aim of this analysis was to evaluate baricitinib use in a real-world patient population in South London. Methods We looked at two rheumatology departments in South London (St George's Hospital;a tertiary teaching centre and Kingston Hospital;a district general hospital). All patients prescribed baricitinib between January 2017 to June 2022 were included. A retrospective assessment of electronic patient notes was performed to evaluate disease activity (determined by DAS-28 scores at baseline, 3-6 months and presently);adverse effects including side effects, rates of and reasons for discontinuation;and prescribing practice, including previous use of other biological disease modifying anti-rheumatic drugs (bDMARDs). Baseline data including age, gender, co-morbidities and rheumatological diagnoses were also included. Results 233 patients were included in this evaluation, with seropositive rheumatoid arthritis being the most common diagnosis (58%) and with a significant female population (87%). Baricitinib improved average DAS-28 scores from 5.75 (range 3.57-8.3) at baseline to 3.23 (range 0.28-7.49) at 3-6 months post-baricitinib, with the most recent DAS-28 score of 2.90 (range 0.56-6.77). Rates of adverse effects were low as shown in Table 1. Baricitinib was discontinued in 60/233 patients, with average duration to discontinuation of 9.5 months. The most common reasons for discontinuation were: ineffective disease control (28/60), recurrent bacterial infection (5/60), deranged liver function (3/60) and venous thromboembolism (2/60). Eight patients died whilst taking baricitinib. Where documented, the causes of death were Covid-19 (4/8) and malignancy (1/8). 110 out of 233 patients had received other bDMARDs before starting baricitinib. Documented reasons for baricitinib choice over tumour necrosis factor inhibitors (TNFi) included: previous lack of response to TNFi (89/233), contra-indication to TNFi (11/233) and preference of oral route (10/ 233). Conclusion Our real-world study of JAKi use shows that baricitinib is efficacious in the treatment of rheumatological conditions. Moreover, baricitinib is well tolerated, with low rates of adverse effects and subsequent discontinuation. (Table Presented).

Patients with Axial Spondyloarthritis Have Better Sars-Cov-2 Outcomes Compared with Patients with Rheumatoid Arthritis: Data from the National Sar-Covid Registry

Objectives: To assess the severity of SARS-CoV-2 infection in patients with axSpA from the SAR-COVID registry, comparing them with patients with rheumatoid arthritis (RA), and to determine the factors associated with poor outcomes and death. Method(s): Patients >=18 years of age from the SAR-COVID national registry with diagnosis of axSpA (2009 ASAS criteria) and RA (2010 ACR/EULAR criteria) who had confirmed SARS-CoV-2 infection (RT-PCR or positive serology), recruited from August 2020 to June 2022 were included. Sociodemographic and clinical data, comorbidities, treatment and outcomes of the infection were collected. Infection severity was assessed using the WHO-ordinal scale (WHO-OS): ambulatory (1), mild hospitalizations (2.3 y 4), severe hospitalizations (5.6 y 7) and death (8). Result(s): A total of 1226 patients were included, 59 (4.8%) with axSpA and 1167 (95.2%) with RA. RA patients were significantly older, more frequently female, and had a longer disease duration. 43.9 % presented comorbidities. t the time of SARS-Cov-2 diagnosis, patients with RA used glucocorticoids and conventional DMARDs more frequently than those with axSpA, while 74.6% of the latter were under treatment with biological DMARDs being anti-TNF the most used (61%). 94.9 % of the patients in both groups reported symptoms related to SARS-CoV-2 infection. During the SARS-CoV-2 infection, 6.8% and 23.5% of the patients with axSpA and RA were hospitalized, respectively. All the patients with axSpA were admitted to the general ward, while 26.6%of those with RA were admitted to the intensive care units. No patient with axSpA had complications or severe COVID-19 (WHO-OS> = 5) or died as a result of the infection while mortality in the RA group was 3.3% (Figure 1). In the multivariate analysis adjusted for poor prognosis factors, no association was found between the diagnosis of axSpA and severity of SARS-CoV-2 infection assessed with the WHO-OS (OR-0.18, IC 95%(-0.38, 0.01, p = 0.074). Conclusion(s): Patients with axSpA did not present complications from SARSCoV-2 infections and none of them died due COVID-19.

Vaccination in Patients with Inflammatory Rheumatic Diseases: Preliminary Results of an International, Real-World Life Panlar's Register

Objectives: To evaluate vaccination among patients with inflammatory rheumatic diseases initiating disease-modifying antirheumatic drugs (DMARD) Methods: Data from the real-world life PANLAR's register of consecutive patients diagnosed with RA, PsA, and axSpa (2010 ACR-EULAR /2006 CASPAR-2009 ASAS) from Dec 2021 to Dec 2022 were analyzed. Prevalence of recommended vaccinations were compared between different inflammatory rheumatic diseases. Categorical variables were expressed as %. Tables were analyzed with chi2 or Fisher tests, continuous variables (median, IQR)with the Kruskal-Wallis test, according with the variables type. A p value <=0.05 was considered significant. Result(s): 608 patients were included. Among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial Spondyloarthritis (axSpA) are presented in the table. RA and axSpA seemed to have lower vaccination rate of pneumococcal vaccines than PsA. (p = 0.045 for conjugate anti pneumococcal vaccine in RA vs PsA). A large percentage of the population was vaccinated against COVID-19. There was a high rate of influenza vaccination in all three diseases. Conclusion(s): In Latin America, anti-pneumococcal vaccination is low, especially in patients with RA and axSpA. For other vaccines there was an acceptable level of vaccination without differences between diseases.

Safety and Efficacy of Covid-19 Immunization in Systemic Vasculitides - a Multicentric Cohort

Objectives: Patients with immune-mediated rheumatic diseases (IMRDs) develop more severe outcomes of Coronavirus disease 2019 (COVID-19). Recent studies have contributed to understand the safety and efficacy of COVID-19 vaccines in IMRDs, suggesting that different diseases and therapies may interfere on immunization efficacy. In this study we analyze the immunogenicity of COVID-19 vaccines in patients with Systemic Vasculitides (VASC), the rate of COVID-19 and the frequency of disease relapse following immunization. Method(s): We included patients with VASC (n = 73), a subgroup of the SAFER study (Safety and Efficacy on COVID-19 Vaccine in Rheumatic Disease), a longitudinal, multicenter, Brazilian cohort.We analyzed the geometric means of IgG antibody against receptor-biding domain of protein spike of SARS-CoV-2 (anti-RBD) after two shots of CoronaVac (Inactivated vaccine), ChadOx-1 (AstraZeneca) or BNT162b2 (Pfizer-BioNTech). IgG anti-RBD was measured by chemiluminescence test. We assessed new-onset COVID-19 episodes, adverse events (AE) and disease activity for each VASC. Result(s): The sample included Behcet's disease (BD) (n = 41), Takayasu arteritis (TAK) (n = 15), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) (n = 14), polyarteritis nodosa (n = 7) and other small vessel VASC(n = 6). The majority of patients were female (69%) without comorbidities (49%) and a median age of 37 years. The most common medication was conventional synthetic disease-modifying anti-rheumatic drugs, followed by biologic drugs. No patient received rituximab at baseline. Most patients received CoronaVac (n = 25) or ChadOx-1 (n = 36), while four received BNT162b2. Baseline IgG-RBD means were 1.34 BAU/mL. They increased to 3.89 and 5.29 BAU/mL after the 1st and 2nd vaccine dose, respectively. ChadOx-1 had higher antibody titers than CoronaVac (p = 0.002). There were no differences between different VASC. There were 3 cases of COVID-19 after immunization with CoronaVac. BD patients had a tendency for more cutaneous-articular activity following ChadOx-1. There were no severe relapses and no serious adverse events. Conclusion(s): Our results show the safety of different SARS-CoV-2 vaccines in VASC population. A progressive increase of IgG-RBD antibodies was observed after each dose. ChadOx-1 led to higher IgG-RBDgeometricmeans compared toCoronaVac. Finally, even though ChadOx-1 presented a tendency of triggering mild disease activity, there were no significant disease activity following vaccination in VASC patients. .

British Society for Rheumatology Annual Conference 2023 Abstracts

The proceedings contain 343 papers. The topics discussed include: implementation of a disease modifying anti-rheumatic drug blood monitoring software: 8 years of experience in a single center;effectiveness of colchicine among patients with COVID-19 infection: a randomized, open labelled, clinical trial;rheumatic autoimmune diseases following COVID-19 infection: an observational study in Iraqi Kurdistan region;COVID-19 in male elite Irish-based athletes at a national sports institute;the effects of a pain management program for patients with an inflammatory arthritis;a retrospective analysis of the effectiveness safety of platelet rich plasma injections in primary osteoarthritis in knee joint, in patients attending a tertiary care hospital, Sri Lanka;a cohort study;do proformas used in fracture liaison service appointments reflect national osteoporosis clinical standards? a content analysis;calcium pyrophosphate dihydrate crystal in operated rheumatoid arthritis of the knee;cardiac amyloidosis: a case series of 31 patients with a comprehensive literature review;scoping review for the application of center of pressure for patient or intervention assessment in rheumatoid conditions;and four SNPs associated with monocyte/macrophage cell lineage uniquely associated with CRPS-1 in discovery and replication cohorts and suggest predisposition to regional osteopenia and digit misperception.

Patient Experience of Remote Healthcare during the Pandemic in Rheumatoid Arthritis and Adult Juvenile Idiopathic Arthritis

Background/Aims COVID-19 challenged traditional care models and necessitated introduction of remote consultations. We wanted to understand the experiences of people with rheumatoid arthritis (RA)/adult juvenile idiopathic arthritis (AJIA) on accessing healthcare remotely, and how well people understood their condition and treatment. Methods This collaborative work between the National Rheumatoid Arthritis Society (NRAS) and clinicians in Oxford led to the development of an electronic questionnaire that was disseminated in July 2021 for four weeks through e-newsletters and all NRAS social media platforms. Those living in the UK with RA and AJIA aged 18 and over were eligible. Analyses of data were performed in Microsoft Excel and IBM SPSSv28. Results We analysed 316 responses. There was a middle-aged (ages 46 to 54, 54.1%, n=171), Caucasian (97.5%, n=306), female (92.4%, n=292) preponderance. Most had RA (93%, n=294) followed by another inflammatory arthritis (4.1%, n=13) and AJIA (2.8%, n=9). The majority had their condition for >10 years (43.4%, n=137) but some were diagnosed <12 months ago (3.2%, n=10). Two thirds of participants (66.5%, n=210) did not know their DAS28 score. Of the remaining third, the most commonly reported measure was moderate disease activity (12%, n=38). Those with higher self-reported DAS28 scores were using analgesia more regularly (p<0.01) but we found no difference in NSAID, DMARD or steroid use. Age did not influence steroid usage (p=0.35), but those who had their condition for longer used more steroids and regular analgesia. Only 33.9% (n=107) of responders felt their condition had been managed adequately in the pandemic, with more reporting poor status (40.8%, n=129) rather than good (16.8%, n=53). Those living in the South of England reported statistically better disease control than those from the North, despite having more virtual assessments (p=0.02). Travelling and fear of Covid appeared more important than consultation skills. Just over a fifth (20.3%, n=64) felt greater focus should be given to patient concerns. Of the 9.1% of patients (n=29) with a new diagnosis made during the pandemic, 24.1% (n=7) unable to book a GP appointment easily. Patients experienced a median symptom time of 4-10 weeks before consulting GPs. Once assessed, 31% (n=9) were referred immediately while the median time was 4-8 weeks. We found 58.6% (n=17) of patients received their diagnosis within their initial rheumatology consultation and 76.5% (n=13) of these started a DMARD immediately. Conclusion Despite a greater emphasis on patient education and PROMs influencing clinical decision-making, it is staggering that two-thirds did not know their DAS28 score. Analgesia and steroid use were common in patients with well-established disease which remains a concern. Accessing appointments was a significant barrier to patients and delays in care were experienced at every step in the NHS management pathways. Remote consultations need greater emphasis on patient concerns.

Rituximab and Covid-19 Vaccines, Are They Fit for Purpose?

Background/Aims Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response. Methods Taking 39 patients currently on rituximab therapy, we measured Anti- SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died. Results Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels. Conclusion These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure.

Incidence and Management of Inflammatory Arthritis in England before and during the Covid- 19 Pandemic: A Population-Level Cohort Study Using Opensafely

Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care;2) time to first rheumatology assessment;3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days;IQR 8-35 days) than before (21 days;9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic;however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic;however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinelycaptured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

Telephone Clinic Consultations in the Covid- 19 Era: The Rates of Conversion to Face-to-Face Appointments and Discharges in the Post-Pandemic Years

Background/Aims It is vital to evaluate the implementation of telephone clinic (TEL) consultations since the COVID-19 pandemic began. We investigated the rates of conversion to face-to-face reviews (F2F) and discharges following a TEL consultation in our department, including the factors influencing these outcomes in 2 different years. Methods Patients who attended TEL consultations in April 2021 and March 2022 were retrospectively reviewed. Factors associated with conversion to F2F and discharges were identified using multivariate logistic regression analyses, adjusting for age and sex. Results 578 patients included [314 (2022) vs 264 (2021)];69% female (both years) with similar median ages [63 (2022) vs 65 years (2021)]. The most common diagnosis was rheumatoid arthritis [39% (2022) vs 54% (2021)]. The rate of conversion to F2F was lower in 2022 (15.3% vs 29.9%). In 2021, multivariate analyses found that a consultant's review was associated with a conversion to F2F [adjusted odds ratio (aOR) 2.22 95% CI (1.26, 3.90) P-value=0.005] whereas an SPN's (specialist nurse) review was associated with a reduced likelihood [aOR 0.48 (0.28, 0.82) P-value=0.008]. In contrast, an SPN's review in 2022 was associated with a conversion to F2F [aOR 2.02 (1.07, 3.90) Pvalue =0.032]. Other factors associated with F2F appointments in 2022 were current steroids [aOR 3.44 (1.63, 7.14) P-value<0.001] and conventional DMARD therapy [aOR 3.14 (1.60, 6.55) P-value=0.001]. The rate of TEL discharges was higher in 2022 (8.9% vs 5.7%). In 2022, a consultant's review was associated with discharges [aOR 4.07 (1.83, 9.53) P-value<0.001] whereas an SPN's review has a lower likelihood of discharges [aOR 0.04 (0.00, 0.17) P-value=0.001]. These associations were not identified in 2021. In both years, patients with inflammatory arthritis and on conventional DMARDs have a reduced likelihood of being discharged. Conclusion The lower rate of conversion to F2F and increased rate of discharges in 2022 suggest a higher level of confidence among clinicians in undertaking telephone consultations as they become more experienced. Patient factors such as diagnoses and current treatment influenced the decision regarding F2F appointments and/or discharges, as expected. In 2021, SPNs might have a higher threshold to request a F2F appointment as clinical services have been recovering since the pandemic began. As TEL reviews became more commonplace in 2022, their threshold may have been subsequently lowered. The increased likelihood of conversion to F2F following a consultant's review in 2021 suggests a higher incidence of flare-ups as remote consultations were increasing. In terms of discharges in 2022, the differences between consultants and SPNs may reflect the clinicians' level of experience in making these decisions. As telephone reviews become more regular, it is important to appreciate the evolving challenges that rheumatology clinicians may face in the postpandemic years and any issues are identified and addressed accordingly.

Clinicians' Levels of Experience and Roles Influence the Decisions Made in Telephone Clinic Consultations in Rheumatology

Background/Aims Since the outbreak of COVID-19, clinicians adapted by switching from face-to-face to remote consultations in order to limit transmission and continue delivering high-quality outpatient services. We aimed to investigate patient- and clinician-related factors which may affect outcomes in follow-up telephone consultations. Methods Patients who attended follow-up clinic appointments via telephone consultations in the month of March 2022 were retrospectively evaluated. Data collected were demographics, main active diagnosis, current treatment and the clinicians' grade. Factors associated with categorical outcomes i.e. decision to request a subsequent face-toface appointment, investigations, referrals to other specialties, and to discharge a patient, were assessed using univariate logistic regression analysis. Univariate linear regression analysis was performed to identify factors associated with the length of follow-up intervals. Results 314 patients were included;218 (69%) female, median (IQR) age 63 (53- 72) years. The most common diagnosis was rheumatoid arthritis (39%). 66% of patients were on DMARDs and 16% were on steroids. There were 48 (15.3%) requests for a subsequent face-to-face appointment and 28 (8.9%) discharges. There were more investigations (20.4%) requested compared to referrals (4.5%). Specialist nurses (SpNs) were the single largest group who conducted the telephone consultations (46%). SpNs were more likely to request face-to-face appointments [odds ratio (OR) 2.16 95%CI (1.16, 4.12) P=0.017] and investigations [OR 1.77 (1.02, 3.11) P=0.043] compared to other clinicians. In contrast, consultants were less likely to request investigations [OR 0.34 (0.16, 0.66) P=0.002]. Other factors associated with a subsequent face-to-face appointment were steroid [OR 3.00 (1.45, 6.02) P=0.002] and conventional DMARD therapy [OR 2.90 (1.50, 5.92) P=0.002]. In terms of discharges, consultants were more likely to discharge a patient [OR 4.05 (1.83, 9.46) P<0.001]. Patients with a diagnosis of inflammatory arthritis [OR 0.01 (0.00, 0.06) P<0.001] and on conventional DMARDs [OR 0.03 (0.00, 0.14) P<0.001] have a lower probability of being discharged. In terms of specialty referrals, there were no significant factors identified. An analysis of 197 clinic letters which specified follow-up intervals found that consultants were more likely to request longer follow-up intervals [beta coefficient 0.32 (0.13, 0.50) P<0.001] whereas SpNs were more likely to request shorter follow-up intervals [beta coefficient -0.52 (-0.65, -0.39), P<0.001]. Conclusion These findings suggest that clinicians' experiences and roles may influence the decisions made following a telephone clinic consultation. For example, SpNs are usually involved in drugmonitoring and therefore, have a higher likelihood to request face-to-face reviews, shorter followup intervals and investigations. The consultant's level of experience may explain the higher probability of discharging patients and the lower probability of requesting investigations. Further studies over a longer duration are needed to determine other factors which may affect the clinical decisions made from telephone clinic consultations.

Covid Vaccine Made My Joints Hurt: Effect of Covid Vaccine on Systemic Rheumatic Disease

Background/Aims Vaccination against SARS-CoV-2 is crucial for patients with systemic rheumatic diseases (SRDs) who may be at increased risk of severe outcomes post-COVID-19. Sparse data suggests vaccines used for COVID -19 may be associated with SRD flares, possibly from molecular mimicry triggering immune activation or non-specific adjuvant effects. As SRD flares are associated with disease deterioration, increased flares could have serious clinical implications. We report the interim results of a survey evaluating SRD flare incidence post-SARS-CoV-2 vaccine. Methods We surveyed 200 patients of different age group with different SRDs via telephone or paper copy during their appointment in Rheumatology department at North Cumbria Integrated Care NHS Foundation Trust, from September 2022 to March 2022 who received at least one dose of Pfizer or Astra Zeneca vaccine. The results of the survey were recorded. Results The mean age of the patients was 62.5 years. 63% of the patients (N- 126) were females. 53 (26.5 %) of these patients had Rheumatoid Arthritis (RA), 43 (21.5 %) had Psoriatic Arthritis, 37 (18.5%) had Serove Spondyloarthropathy, 22 (11%) had Ankylosing Spondylitis, 16 (8 %) had CTD, 12 (6%) had PMR, 10 (5%) Vasculitis and 7 (3.5%) had Palindromic arthritis. 96 (48%) of these patients were on synthetic DMARDs, 56 (28%) on Biologic DMARDs and 41 (20.5%) were on combination. 7(3.5%) patients were on NSAIDS. The most common adverse effects from the vaccine were pain at the site of injection and generalized body aches in 90%of patients followed by fatigue in 80%. 22% had fever. 21 (10.5 %) patients had flare up of their existing rheumatic disease after the first dose and 22 (11%) had a flare after 2nd dose and another 24 (12%) after the 3rd dose. 30 (15%) patients had some flare up after two doses. Out of these 26 had mild flare up and improved with Paracetamol/codeine. 30 had mild to moderate flare required different NSAIDs and 21 had severe requiring a course of prednisolone. 3 of these patients required step up of DMARDS. These flares were described as typical, suggesting these symptoms were not vaccine's adverse effects being misreported as disease flares. Conclusion Interim data from our cohort demonstrates about 12% of patients had severe flare up, with some lasting for weeks requiring switching of DMARDs. Although SARS-CoV-2 vaccine might be associated with some flare up in SRD, but the morbidity and mortality of non-vaccinated patients with SRD can be very devastating signifying the importance of the vaccine. Further data is required for a wider cohort.

Factors influencing the SARS-CoV-2 infection and vaccination induced immune response in rheumatoid arthritis.

Background: To investigate the factors that have significant impact on the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and vaccination induced immune response in rheumatoid arthritis (RA). Methods: Serological response was measured by quantifying anti-SARS-CoV-2 specific antibodies, while the cell-mediated response was measured by a whole-blood test quantifying the interferon (IFN)-γ response to different SARS-CoV-2-specific domains. Results: We prospectively enrolled 109 RA patients and 43 healthy controls. The median time (IQR) between the confirmed infection or the last vaccination dose and the day when samples were taken ("sampling interval") was 3.67 (2.03, 5.50) months in the RA group. Anti-Spike (anti-S) specific antibodies were detected in 94% of RA patients. Among the investigated patient related variables, age (p<0.004), sampling interval (p<0.001), the brand of the vaccine (p<0.001) and targeted RA therapy (TNF-inhibitor, IL-6 inhibitor, anti-CD20 therapy) had significant effect on the anti-S levels. After covariate adjustment TNF-inhibitor therapy decreased the anti-S antibody concentrations by 80% (p<0.001). The same figures for IL-6 inhibitor and anti-CD20 therapy were 74% (p=0.049) and 97% (p=0.002), respectively. Compared to subjects who were infected but were not vaccinated, the RNA COVID-19 vaccines increased the anti-S antibody levels to 71.1 (mRNA-1273) and 36.0 (BNT162b2) fold (p<0.001). The corresponding figure for the ChAdOx1s vaccine is 18.1(p=0.037). Anti-CCP (anti-cyclic citrullinated peptides) positive patients had 6.28 times (p= 0.00165) higher anti-S levels, than the anti-CCP negative patients. Positive T-cell response was observed in 87% of the healthy volunteer group and in 52% of the RA patient group. Following vaccination or infection it declined significantly (p= 0.044) but more slowly than that of anti-S titer (6%/month versus 25%). Specific T-cell responses were decreased by 65% in patients treated with anti-CD20 therapy (p=0.055). Conclusion: Our study showed that the SARS-CoV-2-specific antibody levels were substantially reduced in RA patients treated with TNF-α-inhibitors (N=51) and IL-6-inhibitor (N=15). In addition, anti-CD20 therapy (N=4) inhibited both SARS-CoV-2-induced humoral and cellular immune responses. Furthermore, the magnitude of humoral and cellular immune response was dependent on the age and decreased over time. The RNA vaccines and ChAdOx1s vaccine effectively increased the level of anti-S antibodies.

RESULTS OF A 12-WEEK OPEN-LABEL, NON-INTERVENTIONAL STUDY OF THE EFFICACY AND SAFETY OF OLOKIZUMAB THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS AFTER SWITCHING FROM ANTI-B-CELL THERAPY DURING THE SARS-COV-2 PANDEMIC.

The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic anti-inflammatory drugs (DMARDs) and biological DMARDs on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biological DMARDs and to search for alternative therapy programs to maintain control over disease activity. Purpose of the study - to evaluate the efficacy and safety of the drug Artlegia (olokizumab), solution for subcutaneous injection, 160 mg/ml - 0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. Materials and methods. The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. At 4, 8, 12 weeks after the switch, the severity of pain was assessed on the VAS scale, the number of painful and swollen joints (TJC28 and TSC28), the level of acute phase markers of inflammation, the DAS28 disease activity index calculated using ESR and CRP, and the CDAI (clinical activity index), functional state index HAQ, as well as assessment of the safety profile of therapy. Results. Data analysis was performed using median values (Me) were used for data analysis. A significant decrease of TJC28 was after the injection of olokizumab (Artlegia) in 8 and 12 weeks (Me baseline = 10;Me 8 weeks = 4;Me 12 weeks = 4;p<0.05) and a decrease of TSC28 in 4, 8 and 12 weeks (Me baseline = 9;Me 4 weeks = 3.5;Me 8 weeks = 2.5;Me 12 weeks = 2.0;p<0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me baseline = 21, Me 4 weeks = 1 (p<0.05);ESR: Me baseline = 31, Me 4 weeks = 7 (p<0.05)). Positive dynamics persisted at 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0;ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by the fourth week 4 became within the normal range, regardless of the initial values. All activity indices improved from the fourth week in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22 (p<0.05);DAS28-CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45 (p<0.05);CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0 (p<0.05). All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by the 12th week of the study: Me baseline = 1.62, Me 12 weeks = 1.31 (p<0.05). Conclusion. The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.Copyright © 2023 Ima-Press Publishing House. All rights reserved.

Covid-19 Outcomes in Patients with Dermatomyositis: A Registry-Based Cohort Analysis

Background. Rheumatic diseases (RDs) like Dermatomyositis (DM) are previously known to be vulnerable to various infections due to its aggressive activity mandating high dose immunosuppressive therapy. The severity of COVID-19 in RDs is limited in literature due to the heterogeneous nature of the condition. Therefore, specific details on mortality are essential to navigate any precautions required in the treatment. This study aimed to determine outcomes of COVID-19 in DM as compared to controls, and identify the risk association of gender, race, interstitial lung disease, neoplasms, and use of immunosuppressants. Methods. Retrospective data of individuals with DM and healthy controls (HCs), with COVID-19, between January and August 2020 was retrieved from the Tri-NetX database. A one-to-one matched COVID-19 positive control was selected using propensity score (PS) matching. We assessed COVID-19 outcomes such as mortality, hospitalisation, ICU admission, severe COVID-19, mechanical ventilation (MV), acute kidney injury (AKI), venous thromboembolism (VTE), ischemic stroke, acute respiratory distress syndrome (ARDS), renal replacement therapy (RRT) and sepsis. Subgroup analyses included gender, race, interstitial lung disease (ILD), cancer patients, disease-modifying rheumatic drugs (DMARDs) use, and glucocorticoids (GC) use. Results. We identified 5,574 DM patients with COVID-19, and 5,574 HCs with COVID-19. DM patients with COVID-19 had a lower risk of mortality [RR 0.76], hospitalisation [RR 0.8], severe COVID-19 [RR 0.76], AKI [RR 0.83], and sepsis [RR 0.73] in comparison to HCs. Males and African Americans were more likely to develop AKI [RR 1.35, 1.65], while African Americans were at a higher risk of severe COVID-19 [RR 1.62] and VTE [RR 1.54]. DM patients with ILD were also at a higher risk of severe COVID-19 infection [RR 1.64], and VTE [RR 2.06]. DM patients receiving DMARDs and glucocorticoids had a higher risk of hospitalisation [RR 1.46, 2.12], and sepsis [RR 3.25] (Table I). Subgroup analysis of neoplasms amongst DM patients with COVID-19 had inadequate numbers for meaningful comparison. Conclusions. DM patients are protected from certain poor clinical outcomes of COVID-19, including severe COVID-19, hospitalisation, and mortality, in comparison to healthy individuals. However, certain subgroups with DM have worse outcomes. Men, African Americans, and patients with interstitial lung disease, exhibited higher risk of severe COVID-19. DMARDs and glucocorticoid use were associated with frequent hospitalisations and severe sepsis.

Could biological disease modifying anti rheumatic drugs (bDMARDs) and small molecules have a key role in preventing COVID-19 infection?

Background: The clinical manifestations of COVID-19 infection are very heterogeneous. Rheumatic patients should be more susceptible to develop severe forms of COVID-19 pneumonia due to an unbalanced immune response and treatment immunodepressants (disease modifying anti rheumatic drugs-DMARDs). Aims and objectives: To investigate if the chronic use of biological DMARDs and small molecules may increase the susceptibility to COVID-19 and to developing severe disease. Method(s): We studied 43 consecutive patients on bDMARDs or small molecules from March 2020 to January 2022. Data collection included: rheumatic diagnosis, comorbidities, smoking history and COVID-19 clinical course according to MEWS (modifying early warning score) in 4 stages: 0=no symptoms at all;no hospitalization;1=not complicated disease with mild or non-specific symptoms;no hospitalization;2=mild pneumonia with clinical and/or radiological diagnosis, without any signs of severity;no hospitalization;3=severe pneumonia with respiratory failure with need of hospitalization;4=hospitalization in ICU or sub-ICU. Result(s): 30 patients (69.8%) got COVID infection: 26 were not hospitalized (MEWS 0=3.3%;1=70%;2=13.3%);of the four patients that required hospitalization, none was intubated. Hospitalized patients were obese and had hypertension, and 3 had a positive smoking history. Patients taking TNF-inhibitors compared to other treatment were not at major risk of COVID-19 infection (p=0.041). Conclusion(s): Rheumatic patients taking bDMARDs or small molecules appear more susceptible to contract SARSCoV-2 infection, but the development of severe forms appears to be rare.

Autoimmune reactions associated with various types of sars-cov- 2 vaccines among rheumatic disease patients: a case series

Background: Vaccinations are of paramount importance in eradicating various diseases. Currently, there have been numerous reports on the development of new-onset autoimmune phenomena and disease flares following COVID-19 vaccination. The etiology and vaccine trigger mechanism of autoimmune disease still remains unclear. Molecular mimicry, by-stander activation and role of vaccine adjuvants are the main pathogenic mechanisms linked to an autoimmune phenomenon. However, vaccines as inducers of an autoimmunity is still an arguable subject. Case: We report a case series of six patients who developed new onset autoimmune reaction and disease flares following SARS-COV 2 vaccine. The patients received viral vector vaccine, inactivated vaccine and mRNA vaccine who developed symptoms in an average of 7-28 days following inoculation. A 27 year old male, previously healthy developed new onset of clinical amyopathic dermatomyositis after a week of 1st and 2nd dose of a viral vector vaccine. Two patients with systemic lupus erythematous developed severe cutaneous, hematologic and renal flare 14 and 28 days following vaccination. Two rheumatoid arthritis patients in long remission, developed atypical arthritis and disease flares after 10 and 14 days of inactivated and mRNA vaccine inoculation. One patient with spondylarthritis in remission experienced disease flare 7 days following inactivated SARS-COV- 2 vaccination. The patient age ranges from 19-72 years old of whom two are males and four are females. The management was individualized which includes oral corticosteroid and disease modifying anti-rheumatic drugs which showed improvement of symptoms. Conclusion: Development of an autoimmune reaction following SARS-COV 2 vaccination is of scientific and public importance. Vaccination might potentially trigger an autoimmune disease, however further investigations need to be established. The causative link between vaccination and autoimmunity needs to be studied. Susceptibility to a vaccine-induced autoimmunity might be triggered by the individual's genetic predisposition and several pathomechanisms.