PSYCHOLOGICAL DISTRESS OVER 12 MONTHS POST-DIAGNOSIS IN A NATIONAL EARLY INFLAMMATORY ARTHRITIS COHORT

BackgroundIn inflammatory arthritis patients, the concomitant decline of their mental wellbeing is an increasing concern[1,2]. It is important to not only describe the trajectory of psychological distress in early disease stages, but also understand which clinical outcome measures are most associated with these changes.ObjectivesUsing data from the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological wellbeing over 12 months after initial diagnosis and mapped these against clinical outcomes to identify significant associations.MethodsNEIAA collects data from patients referred with suspected early inflammatory arthritis in rheumatology services in England and Wales. We used data provided by 20,472 patients eligible for follow-up (diagnosis of inflammatory arthritis) between May 1st, 2018, and April 1st, 2022. Data items included baseline demographics e.g., age and gender, and clinical variables e.g., rheumatic disease comorbidity index (RDCI), DAS28, and patient reported outcomes.Psychological distress was measured by the sum score of Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS). Using mixed effects regression models, we analysed the co-variability of PHQ4ADS with demographic factors and clinical outcomes over 12 months. Time was included as a dummy-coded covariant.ResultsThe analysis included 36% of patients (7,378 out of 20,472) who completed the baseline patient outcome survey. In this cohort, PHQ4ADS scores decreased from a baseline average of 4.7 (CI: [4.6, 4.8]) to 2.62 (CI: [2.5, 2.8]) at 12 months post-diagnosis. The proportion of patients screening positive decreased from 50.0% (CI: [48.9, 51.1]) at baseline to 23.8% (CI: [21.8, 25.9]) at 12 months.At baseline, psychological distress correlated significantly with age, gender, ethnicity, RDCI, prior depression diagnosis, and baseline DAS28 (Figure 1). No significant correlations were found between psychological distress and working diagnosis, seropositivity, or the assessment being recorded after the start of the COVID-19 pandemic. Younger ages were nonlinearly associated with higher distress levels (coefficient per decade: -0.006;p<0.001;CI: [-0.009, -0.003]) (Figure 1a). Distress levels in females were higher than that of males (coefficient: 0.5;p<0.001;CI: [0.4, 0.7]) (Figure 1b). White patients reported lower PHQ4ADS scores compared to non-white patients (coefficient: -0.7;p<0.001;CI: [-1.0, -0.4]) (Figure 1c). Higher distress levels were also associated with higher RDCI (coefficient: 0.2;p<0.001;CI: [0.1, 0.3]) and prior diagnosis of depression (coefficient: 1.8;p<0.001;CI: [1.5, 2.2]) (Figure 1d, 1e). Furthermore, higher baseline DAS28 scores correlated with more severe psychological distress (coefficient: 0.8;p<0.001;CI: [0.7, 0.8]) (Figure 1f).By 12-months, psychological distress decreased significantly overall, which correlated significantly with ethnicity (coefficient: 0.8;p=0.005;CI: [0.3, 1.4]) and baseline DAS28 (coefficient: -0.5;p<0.001;CI: [-0.6, -0.4]). Compared to white patients, the reduction was significantly greater for non-white patients, but the level of distress was no longer different at 12 months (Figure 1c). While those with higher baseline DAS28 showed a greater reduction in psychological distress, the distress levels remained higher at 12 months (Figure 1f).Figure 1.Changes in psychological distress correlated with age, gender, ethnicity, RDCI, prior depression diagnosis, and baseline DAS28.[Figure omitted. See PDF]ConclusionIn this early inflammatory arthritis cohort, mental health burden was high. Age, gender, ethnicity, RDCI, prior depression diagnosis and baseline DAS28 significantly correlated with psychological distress at baseline. Supporting mental health should be a focus of clinical care for this population and it may be beneficial to use an approach that is culturally valid for non-white patients and accounts for multimorbidity.References[1]Euesden, J, et al. Psychosomatic medicine 79.6 (2017): 638.[2]Lwin, MN, et al. Rheumatology and therapy 7.3 (2020): 457-471.AcknowledgementsThe authors would like to thank the Healthcare Quality Improvement Partnership (HQIP) as the commisioner of NEIAA, British Society for Rheumatology as the audit providers, Net Solving as the audit platform developers, and the Wellcome Trust (ST12406) for funding to support L.Z..Disclosure of InterestsLucy Zhao: None declared, James Galloway Speakers bureau: Has received honoraria from AbbVie Celgene, Chugai, Gillead, Janssen, Eli Lilly, Pfizer, Roche, and UCB, Jo Ledingham: None declared, Sarah Gallagher: None declared, Neena Garnavos: None declared, Paul Amlani-Hatcher: None declared, Nicky Wilson: None declared, Lewis Carpenter Consultant of: Statistical consultancy for Pfizer, Kirsty Bannister: None declared, Sam Norton Speakers bureau: Has received honoraria from Janssen and Pfizer.

IMPACT OF THE COVID-19 PANDEMIC ON SEPTIC ARTHRITIS MANAGEMENT

BackgroundSince 2020, the SARS-Cov-2 pandemic has disrupted the organization of healthcare systems worldwide.ObjectivesThis study aimed to assess the impact of this pandemic on septic arthritis management in a tertiary rheumatology department.MethodsIt was a single-center descriptive case-control study, which included patients hospitalized for septic arthritis between January 2018 and December 2021, whose diagnosis was retained after positive bacterial growthor on culture on according to presumptive criteria. Our patients were divided into two groups: G1: patients hospitalized during the COVID-19 pandemic (2020-2021), and G2: patients hospitalized during a similar period before the COVID-19 pandemic (2018-2019). In both groups, septic arthritis prevalence was calculated, socio-demographic characteristics, risk factors, clinical, paraclinical, and therapeutic data were collected. COVID-19 status was reported in the G1.ResultsTwenty-two patients were enrolled: G1 (n = 15), G2 (n = 7). The prevalence of septic arthritis was 0.77% and 0.36% respectively. The median age was 54.6±12.25 and 54.29±21.81 years old respectively. Diabetes was found in 26, 7% in G1 and 28.6% in G2. During the pandemic, arthropathy and oral corticosteroids use were noted in 53.3% and 28.6% of patients versus 26.7% and 14.3% in G2. The diagnosis delay and the prior use of antibiotic therapy were more significant in G1: 14.08[7-30] d versus 6.5[3.25-19.25] d, and 46.7% versus 14.3%. The knee was the most common localization in both groups. Other joints were affected in G1: shoulder (n = 2), hip (n = 1), and sacroiliac (n = 1). The most common germ was staphylococcus aureus. The duration of hospitalization and duration of antibiotic therapy in G1 and G2 were 26.07±9.12d versus 27.43±10.87d and 50±10d versus 48±25.79d, respectively. Concerning COVID-19 status, 33.3% of patients in G1 have received their vaccination and no recent SARS-Cov2 infection was noted before hospitalization. During the pandemic, synovectomy was required in three patients, one of whom was also transferred to intensive care for septic shock (two of these three patients are being followed for rheumatoid arthritis, and only one has never been vaccinated against COVID-19).ConclusionDuring the COVID-19 pandemic, the prevalence of septic arthritis in our department was higher and the diagnosis was delayed. Duration of hospitalization was not impacted, however, atypical localisations, prior use of antibiotics, recourse to synovectomy, and transfer to intensive care were reported. These results suggest an inadequate and difficult access to healthcare services during the lockdown, as well as an impact of social distancing on the immune system [1, 2]. More studies are needed to confirm these findings.References[1]Robinson E. Pires et al, What Do We Need to Know about Musculoskeletal Manifestations of COVID-19? A Systematic Review, JBJS Rev. 2022 Jun 3;10(6)[2]Pantea Kiani et al, Immune Fitness and the Psychosocial and Health Consequences of the COVID-19 Pandemic Lockdown in The Netherlands: Methodology and Design of the CLOFIT Study, Eur J Investig Health Psychol Educ. 2021 Feb 20;11(1):199-218Acknowledgements:NIL.Disclosure of InterestsNone Declared.

RHEUMATOID ARTHRITIS FLARE FOLLOWING COVID-19 VACCINATION IN MALAYSIAN POPULATION AND ITS ASSOCIATED RISK FACTORS

BackgroundFlare of Rheumatoid Arthritis (RA) following COVID-19 vaccination has been reported with a low occurrence observed in those patients with disease remission. However, no local data is available in our multi-ethnic Malaysian population.ObjectivesTo evaluate the prevalence of RA flare in Malaysian patients following COVID-19 vaccination and its associated risk factors.MethodsThis was a cross-sectional study assessing RA flare based on patient-reported disease flare through self-administered questionnaires and physician-reported flare. Patient self-reported disease flare was defined as ‘a sudden worsening of rheumatology condition or arthritis within 1 month post-vaccination' while physician-reported flare was defined as ‘an increment of disease activity score 28-joint documented within 3 months post-vaccination‘ from either a scheduled or unscheduled clinic visit. A total of 186 RA patients attended the rheumatology clinic in Hospital Putrajaya from May to July 2022 who completed the primary COVID-19 vaccination under the Malaysian National Vaccination Programme were recruited. Demographic data, disease parameters including serology for rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), cessation of disease modifying anti-rheumatic drugs (DMARDs) around vaccination, type of vaccines and adverse events were examined using descriptive and univariate analyses.ResultsMajority (93%) of RA patients enrolled were female with a mean age of 58 years old (standard deviation, SD 12.2) and mean disease duration was 12 years (SD 7.7). More than half were seropositive (66% RF, 63% ACPA) with 47.4% had double seropositivity (RF and ACPA positive). All patients received DMARDs with the majority (71%) were on methotrexate (MTX), 21.5% were on leflunomide, 17.7% on other DMARDs, with a small proportion (14%) of patients were receiving prednisolone. Only 4.8% of patients were on biologics or targeted synthetic disease modifying anti-rheumatic drugs. Half of the patients were in remission prior to vaccination. 62% of patients received Pfizer-BioNTech vaccine as the primary vaccine, followed by Sinovac-CoronaVac (24.6%) and Oxford-AstraZeneca (13.4%) vaccines. A booster dose had been administered to 80% of patients, of which 88.7% was Pfizer-BioNTech vaccine. MTX therapy were discontinued in 39.4% of patients (n=52) post-vaccination for a week duration. The prevalence of RA flare was only 12.9% (n=24) in which 14 were self-reported and 10 were physician-reported flares (4 severe flare, 6 mild-moderate flare). Flare rates were higher during the first and second dose of vaccination with 29.2% respectively, and only 12.5% were reported after booster vaccination. Common vaccine adverse effects were fever (16.8%), myalgia (8.6%) and arthralgia (6.4%). There were no significant differences in the occurrence of flare post-vaccination between age, gender, disease activity prior to vaccination, types of vaccine, usage of MTX and prednisolone, and discontinuation of MTX post-vaccination. Although seropositivity did not exhibit statistically significant flare rate post vaccination, sub-analysis revealed four times higher rate of flare in those who has double positivity compared to seronegative RA patients (12% vs 4%).ConclusionPrevelance of RA flare post-COVID-19 vaccination in Malaysian RA population is low. No significant associated risk factors were identified although double seropositivity appeared to have higher number of flares.References[1]Bixio, R., Bertelle, D., Masia, M., Pistillo, F., Carletto, A. and Rossini, M. (2021), Incidence of Disease Flare After BNT162b2 Coronavirus Disease 2019 Vaccination in Patients With Rheumatoid Arthritis in Remission. ACR Open Rheumatology, 3: 832-833.[2]Li X, Tong X, Yeung WWY, Kuan P, Yum SHH, Chui CSL, Lai FTT, Wan EYF, Wong CKH, Chan EWY, Lau CS, Wong ICK. Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong. Ann Rheum Dis. 2022 Apr;81(4):564-568.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Certolizumab

Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.

THE KINETICS OF HUMORAL AND CELLULAR RESPONSES AFTER THE BOOSTER DOSE OF COVID-19 VACCINE IN INFLAMMATORY ARTHRITIS PATIENTS

BackgroundImpaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown, due to unstudied kinetics of the immune response after booster vaccinations.ObjectivesThis study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster.MethodsIn 29 IA patients and 16 healthy controls (HC) humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2.ResultsIA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p=0.026 and p=0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. However, none of the immunomodulatory drugs affected the kinetics of both humoral and cellular responses (measured as the difference between response rates at T1 and T2).ConclusionOur study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

EVALUATION OF RESPONSE TO ADJUVANTED RECOMBINANT ZOSTER VACCINATION IN PATIENTS WITH RHEUMATOID ARTHRITIS RECEIVING UPADACITINIB: RESULTS FROM A RANDOMIZED TRIAL SUB-STUDY

BackgroundUpadacitinib (UPA) is an oral JAK inhibitor (JAKi) approved for the treatment of RA. JAKi have been associated with an elevated risk of herpes zoster (HZ) in patients (pts) with RA. The adjuvanted recombinant zoster vaccine (RZV, Shingrix) was shown to be well-tolerated and effective in preventing HZ in adults aged ≥ 50 years.[1] The efficacy and safety of RZV have not been studied in pts with RA while on UPA in combination with MTX.ObjectivesTo assess the immunogenicity of RZV in pts with RA receiving UPA 15 mg once daily (QD) with background MTX.MethodsEligible adults aged ≥ 50 years with RA enrolled in the ongoing SELECT-COMPARE phase 3 trial (NCT02629159) received two RZV doses, administered at the baseline and week (wk) 12 visits. Pts should have been on stable doses of UPA 15 mg QD and background MTX for ≥ 8 wks before the first vaccination and ≥ 4 wks after the second vaccination. Antibody titers were collected pre-vaccination (baseline), 4 wks post-dose 1 vaccination (wk 4), and 4 wks post-dose 2 vaccination (wk 16). The primary endpoint was the proportion of pts with a humoral response to RZV defined as ≥ 4-fold increase in pre-vaccination concentration of anti-glycoprotein E [gE] titer levels at wk 16. Secondary endpoints included humoral response to RZV at wk 4 and the geometric mean fold rise (GMFR) in anti-gE antibody levels at wks 4 and 16. Cell-mediated immunogenicity to RZV was an exploratory endpoint evaluated by the frequencies of gE-specific CD4+ [2+] T cells (CD4+ T cells expressing ≥ 2 of 4 activation markers: IFN-γ, IL-2, TNF-α, and CD40 ligand) measured by flow cytometry at wks 4 and 16 in a sub-cohort of pts.ResultsOf the 95 pts who received ≥ 1 RZV dose, 93 (98%) received both RZV doses. Pts had a mean (standard deviation) age of 62.4 (7.5) years. The median (range) disease duration was 11.7 (4.9–41.6) years and duration of UPA exposure was 3.9 (2.9–5.8) years. At baseline, all but 2 pts were receiving concomitant MTX and half (50%) were taking an oral corticosteroid (CS) at a median daily dose of 5.0 mg. One pt discontinued UPA by wk 16. Blood samples were available from 90/93 pts. Satisfactory humoral responses to RZV occurred in 64% (95% confidence interval [CI]: 55–74) of pts at wk 4 and 88% (81–95) at wk 16 (Figure 1). Age (50–< 65 years: 85% [95% CI: 75–94];≥ 65 years: 94% [85–100]) and concomitant CS (yes: 87% [77–97];no: 89% [80–98]) use at baseline did not affect humoral responses at wk 16. GMFR in anti-gE antibody levels compared with baseline values were observed at wks 4 (10.2 [95% CI: 7.3–14.3]) and 16 (22.6 [15.9–32.2]). Among the sub-cohort of pts, nearly two-thirds achieved a cell-mediated immune response to RZV (wk 4: n = 21/34, 62% [95% CI: 45–78];wk 16: n = 25/38;66% [51–81]). Within 30 days post-vaccination of either RZV dose, no serious adverse events (AEs) (Table 1) or HZ were reported. AEs that were possibly related to RZV were reported in 17% of pts. One death occurred more than 30 days after wk 16 due to COVID-19 pneumonia.ConclusionMore than three-quarters (88%) of pts with RA receiving UPA 15 mg QD on background MTX achieved a satisfactory humoral response to RZV at wk 16. In a subgroup of pts, two-thirds (66%) achieved a cell-mediated immune response to RZV at wk 16. Age and concomitant CS use did not negatively affect RZV response.Reference[1]Syed YY. Drugs Aging. 2018;35:1031–40.Table 1. Safety Results Through 30-Days Post-RZV Vaccination in UPA-Treated PatientsEvent, n (%)UPA 15 mg QD (N = 95)Any AE38 (40%)AE with reasonable possibility of being related to UPAa13 (14%)AE with reasonable possibility of being related to RZVa16 (17%)Severe AEb1 (1%)Serious AE0AE leading to discontinuation of UPA0Death0AE, adverse event;QD, once daily;RZV, adjuvanted recombinant zoster vaccine;UPA, upadacitinib.aAs assessed by the investigator.bHypersensitivity.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsKevin Winthrop Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, GSK, Novartis, Pfizer, Regeneron, Roche, Sanofi, and UCB, Justin Klaff Shareholder of: AbbVie, Employee of: AbbVie, Yanxi Liu Shareholder of: AbbVie, Employee of: AbbVie, CONRADO GARCIA GARCIA: None declared, Eduardo Mysler Speakers bureau: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Consultant of: AbbVie, Amgen, AstraZeneca, BMS, Eli Lilly, GlaxoSmithKline, Pfizer, Roche, and Sandoz, Alvin F. Wells Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Novartis, Pfizer, and Sanofi, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Michael Chen Shareholder of: AbbVie, Employee of: AbbVie, Heidi Camp Shareholder of: AbbVie, Employee of: AbbVie, Anthony Cunningham Consultant of: GSK, Merck Sharp & Dohme, and BioCSL/Sequirus.

THE SWEDISH OSTEOARTHRITIS REGISTRY. TRENDS IN SWEDISH OSTEOARTHRITIS HEALTH CARE BETWEEN 2008- 2021

BackgroundIn 2012 the Swedish national guidelines for osteoarthritis (OA) were published. The guidelines implicit that all patients with OA should obtain information and supervised exercise as first-line intervention and that OA is a clinical, not radiological diagnosis. The Swedish OA registry contains data which measure compliance to the guidelines since 2008 [2].ObjectivesTo describe the trends over time from 2008 to 2021 for patients who have received first-line interventions for hip and knee OA in Sweden and adherence of the healthcare staff to the national guidelines.MethodsDescriptive registry-based study including patients with hip or knee OA who participated in first-line interventions including education and exercise. Data were extracted from the Swedish OA registry between January 1st, 2008, and December 31, 2021. The registry contains patient-reported outcomes and physiotherapist-reported outcomes. In this study the following physiotherapist-reported outcomes were described over time: radiological examination before first-line intervention, if the first-line intervention was given the first time the patient seek health care caused of OA, which explanation patients had been given about their disease, intake of painkillers before the start of first-line intervention and the percent who got supervised exercise >10 times according to the guidelines of OA in Sweden. The following patient-reported outcomes were described over time: mean BMI at the first visit, and mean age at the first visit. To be included in the study, participants had to meet the following criteria: i) clinical diagnosis of OA, with hip or knee OA as the most symptomatic joint, ii) provided 3-month follow-up.ResultsA total of 175 764 participants with hip or knee OA were included in the study.The trends from 2008-2021 showed that the proportion of patients who had a radiological examination before entering the first-line intervention decreased from 97 % to 65 % in men and from 95% to 62 % in women. The proportion of patients who get assess to first-line intervention the first time they seek for their symptoms increased from 4 % to 10 % both in men and women. People that get the correct information about OA increased from 15% to 40 %, and patients that get the explanation that OA was a tear and wear disease decreased from 30 % to 5%. The mean BMI (28) is unchanged over time. The mean age increased from 64 years to 67 years between 2008-2020 but decreased during the covid-19 pandemic to 64 years. The percentage that was given supervised exercise more than 10 times was constant between 2012-2020 at 30 % but decreased during the covid-19 pandemic to 20%.ConclusionThe results implicit that the implementation of a supported OA self-management program in Sweden has been successful and changed the care given to patients with OA in Sweden. However, the national guidelines for OA, have still not been fully implemented. We need to keep implementing the guidelines so all patients with OA get the first-line intervention at the right time.References[1]Anon. (2012). Nationella riktlinjer för rörelseorganens sjukdomar 2012 - stöd för styrning och ledning. Socialstyrelsen.[2]Thorstensson CA, Garellick G, Rystedt H, Dahlberg LE. Better Management of Patients with Osteoarthritis: Development and Nationwide Implementation of an Evidence-Based Supported Osteoarthritis Self-Management Programme. Musculoskeletal Care. 2015 Jun;13(2):67-75. doi: 10.1002/msc.1085. Epub 2014 Oct 24. PMID: 25345913.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

THE PREVALENCE AND INCIDENCE OF PSORIASIS AND PSORIATIC ARTHRITIS IN ENGLAND FROM 2009-2019: AN OBSERVATIONAL STUDY USING PRIMARY CARE DATA

BackgroundPsoriasis (PsO) and psoriatic arthritis (PsA) can greatly impact quality of life and result in substantial personal and societal costs. Complete and up to date data on the prevalence and incidence of these conditions and whether these change over time and vary by age is important for healthcare service planning so that specialist care and funding can be appropriately allocated.ObjectivesTo determine the prevalence and incidence of PsO and PsA in males and females from 2009-2019 across all age groups in England.MethodsWe used Clinical Practice Research Datalink AURUM, a primary care electronic health record database, including 20% of the English population. The codes used to identify patients with PsO and PsA were selected by rheumatologists and dermatologists and cross-checked with published code lists from other studies to ensure inclusion of all relevant codes. All included patients must have data for at least 1 year before their diagnosis. The annual incidence and point prevalence were calculated from 2009-2019 and stratified by age/sex. The study period ended in 2019 to avoid COVID-19 pandemic affecting results.ResultsThe prevalence of PsO and PsA in males and females increased annually, peaking in 2019 (PsO males 2.41% [95% confidence interval (CI) 2.40, 2.42];PsO females 2.60% [95% CI 2.59-2.61];PsA males 0.20% [95% CI 0.20-0.20];PsA females 0.21% [95% CI 0.21- 0.22]), as illustrated in Table 1. In 2019, the prevalence of PsO and PsA was highest in the over 65 years age group;PsO 4.25% [95% CI 4.22-4.28] and PsA 0.38% [95% CI 0.37-0.38]. The annual incidence (per 100,000 person years) of PsO has gradually decreased in males (from 168 (164-171) in 2009 to 148 (145-151) in 2019) but in females it has been stable with a slight annual decrease (from 180 (177-184) in 2009 to 173 (170-176) in 2019). The annual incidence for PsA has increased in both males and females (13 (12-14) in 2009 and 15 (14-16) in 2019 for males and 12 (11-13) in 2009 and 18 (17-19) in 2019 for females).ConclusionThe increasing prevalence of PsO and PsA highlights the importance of organising healthcare services to meet this need, particularly in the elderly population.ReferencesNIL.Table 1.Prevalence of PsO and PsA from 2009-2019 in EnglandYear20092010201120122013201420152016201720182019Population (n)1073383110910802110318501118036711343299112249341137842211657996119336261223432512420998PsO (n)216841229106239819250667259988268032276804286499295712304568311104PsO prevalence (%, 95%CI)-Male1.98 (1.96-1.99)2.06 (2.05- 2.07)2.13 (2.12-2.14)2.19 (2.18-2.20)2.24 (2.23- 2.25)2.33 (2.32- 2.34)2.37 (2.36- 2.38)2.39 (2.38- 2.40)2.40 (2.39- 2.41)2.40 (2.39- 2.42)2.41 (2.40- 2.42)-Female2.07 (2.05- 2.08)2.14 (2.13- 2.16)2.22 (2.21- 2.23)2.29 (2.28- 2.31)2.35 (2.33- 2.36)2.45 (2.43- 2.46)2.50 (2.49- 2.51)2.53 (2.52- 2.54)2.56 (2.54- 2.57)2.58 (2.56- 2.59)2.60 (2.59- 2.61)PsO incidence (100,000 person years)-Male168 (164-171)158 (155- 162)161 (158-165)153 (150-157)161 (157- 164)156 (153- 159)155 (152- 159)154 (151- 157)153 (150-156)150 (147-153)148 (145-151)-Female180 (177-184)176 (172-179)181 (177-184)171 (167-174)175 (171-178)176 (172-180)179 (176-183)178 (174-181)177 (174-181)174 (170-177)173 (170-176)PsA (n)1444515443164681752218545196182072021994232572451425683PsA prevalence (%, 95%CI)-Male0.14 (0.14- 0.14)0.15 (0.14- 0.15)0.15 (0.15- 0.16)0.16 (0.16- 0.16)0.17 (0.16- 0.17)0.18 (0.17- 0.18)0.18 (0.18- 0.19)0.19 (0.18- 0.19)0.19 (0.19- 0.20)0.20 (0.19- 0.20)0.20 (0.20- 0.20)-Female0.13 (0.13- 0.13)0.14 (0.13- 0.14)0.15 (0.14- 0.15)0.15 (0.15- 0.16)0.16 (0.16- 0.16)0.17 (0.17- 0.18)0.18 (0.18- 0.18)0.19 (0.19- 0.19)0.20 (0.19- 0.20)0.20 (0.20- 0.21)0.21 (0.21- 0.22)PsA incidence (100,000 person years)-Male13 (12- 14)12 (11- 13)13 (12- 14)12 (11- 13)13 (12-14)14 (13- 15)14 (13- 15)14 (13-15)1514-16)14(13- 15)15 (14-16)-Female12 (11- 13)13 (12- 14)13 (12- 14)14 (13-15)14 (13-15)15 (14-16)17 (16- 18)16 (15- 17)17 (16- 18)18 (17-19)18 (17-19)Acknowledgements:NIL.Disclosure of InterestsArani Vivekanantham: None declared, Edward Burn: None dec ared, Marta Pineda-Moncusí: None declared, Sara Khalid Grant/research support from: SK has received research grant funding from the UKRI and Alan Turing Institute outside this work. SK's research group has received grant support from Amgen and UCB Biopharma., Daniel Prieto-Alhambra Grant/research support from: DPA's department has received grant/s from Amgen, Chiesi-Taylor, Lilly, Janssen, Novartis, and UCB Biopharma. His research group has received consultancy fees from Astra Zeneca and UCB Biopharma. Amgen, Astellas, Janssen, Synapse Management Partners and UCB Biopharma have funded or supported training programmes organised by DPA's department., Laura Coates Speakers bureau: LC has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB., Consultant of: LC has worked as a paid consultant for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB., Grant/research support from: LC has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Novartis and Pfizer.

SAFETY OUTCOMES IN PATIENTS (PTS) WITH RHEUMATOID ARTHRITIS (RA) TREATED WITH FILGOTINIB (FIL) IN FILOSOPHY: INTERIM RESULTS FROM A PROSPECTIVE OBSERVATIONAL STUDY

BackgroundConsideration is needed when using Janus kinase (JAK) inhibitors to treat RA in pts aged ≥65 years or those with cardiovascular (CV) risk factors. The JAK1 preferential inhibitor FIL was generally well tolerated in clinical trials[1];safety has not been determined in a real-world setting.ObjectivesTo report baseline characteristics and up to 6-month safety data from the first 480 pts treated with FIL in the FILOSOPHY study (NCT04871919), and in two mutually exclusive subgroups based on age and CV risk.MethodsFILOSOPHY is an ongoing, phase 4, non-interventional, European study of pts with RA who have been prescribed FIL for the first time and in accordance with the product label in daily practice. Baseline characteristics and the incidence of select adverse events (AEs) are assessed in pts aged ≥65 years and/or with ≥1 CV risk factor (Table 1), and in those aged <65 years with no CV risk factors.ResultsAs of the end of June 2022, 480 pts had been treated: 441 received FIL 200 mg and 39 received FIL 100 mg. Of the 480 pts, 148 (30.8%) were aged ≥65 years;332 (69.2%) were aged <65 years. In total, 86 (17.9%) were former smokers, 81 (16.9%) were current smokers and 203 (42.3%) were non-smokers (data were missing for 110 pts [22.9%]). In addition to smoking, the most frequent CV risk factors included a history of hypertension (32.3%), a history of dyslipidemia (10.2%) and a family history of myocardial infarction (8.5%;Table 1).23 pts (4.8%) discontinued treatment due to AEs. Of the 354 pts aged ≥65 years or with ≥1 CV risk factor, infections affected 64 pts (18.1%), 34 (9.6%) had COVID-19, 2 (0.6%) had herpes zoster, and cardiac disorders (angina pectoris, atrial fibrillation, palpitations and tachycardia) affected 5 pts (1.4%);no cases of malignancies were observed. In the subgroup aged <65 years and with no CV risk factors (n=126), infections occurred in 18 pts (14.3%) (9 [7.1%] had COVID-19;3 [2.4%] had herpes zoster) and malignancies (myeloproliferative neoplasm) affected 1 pt (0.8%);no pts had cardiac disorders. There were no cases of deep vein thrombosis or pulmonary embolism in either subgroup.ConclusionIn this interim analysis of FILOSOPHY, no unexpected safety signals emerged at up to 6 months. Although infections and cardiac disorders affected a numerically greater proportion of pts aged ≥65 years or with ≥1 CV risk vs those aged <65 years with no CV risk, longer follow-up on a broader cohort is necessary to further characterize the safety of FIL in different groups of pts with RA.Reference[1]Winthrop K, et al. Ann Rheum Dis 2022;81:184–92Table 1.Baseline characteristics and CV risk factorsBaseline demographics/CV risk factorsAll FIL-treated pts (N=480)≥65 years or with ≥1 CV risk factor (n=354)<65 years and no CV risk factor (n=126)*Female sex, n (%)351 (73.1)252 (71.2)99 (78.6)Age, years, mean (SD)57.6 (11.5)60.4 (10.8)49.6 (9.6)Rheumatoid factor positive, n (%)†228 (47.5)167 (47.2)61 (48.4)Anti-citrullinated protein antibody positive, n (%)‡243 (50.6)176 (49.7)67 (53. 2)Body mass index, kg/m2, mean (SD)27.6 (5.7) n=43728.0 (5.4) n=33126.3 (6.4) n=106RA disease duration, years, mean (SD)10.4 (9.4) n=47810.5 (9.5) n=35310.0 (8.8) n=125Tender joint count 28, mean (SD)8.6 (6.9) n=4578.7 (7.1) n=3408.3 (6.3) n=117Swollen joint count 28, mean (SD)5.6 (5.2) n=4525.7 (5.4) n=3365.4 (4.4) n=116Former smoker, n (%)§86 (17.9)86 (24.3)0Current smoker, n (%)§81 (16.9)81 (22.9)0Non-smoker, n (%)§203 (42.3)130 (36.7)73 (57.9)Family history of myocardial infarction, n (%)41 (8.5)41 (11.6)0Medical history of: n (%) CV disease33 (6.9)33 (9.3)0 Diabetes35 (7.3)35 (9.9)0 Dyslipidemia49 (10.2)49 (13.8)0 Hypertension155 (32.3)155 (43.8)0 Ischemic CNS  vascular disorders11 (2.3)11 (3.1)0 Peripheral vascular disease17 (3.5)17 (4.8)0*Includes 53 pts with missing smoking status data who were aged <65 years with no other CV risk factors.†Missing/unknown in 154 pts;‡Missing in 153 pts;§Smoking status data missing in 110 pts (22.9%).AcknowledgementsWe thank the physicia s and patients who participated in this study. The study was funded by Galapagos NV, Mechelen, Belgium. Publication coordination was provided by Fabien Debailleul, PhD, of Galapagos NV. Medical writing support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), and funded by Galapagos NV.Disclosure of InterestsPatrick Verschueren Speakers bureau: AbbVie, Eli Lilly, Galapagos, Roularta, Consultant of: Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Sidekick Health, Grant/research support from: Galapagos, Pfizer, Jérôme Avouac Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sandoz, Sanofi, Consultant of: AbbVie, Fresenius Kabi, Galapagos, Sanofi, Grant/research support from: BMS, Fresenius Kabi, Novartis, Pfizer, Karen Bevers Grant/research support from: Galapagos, Susana Romero-Yuste Speakers bureau: AbbVie, Biogen, BMS, Lilly, Pfizer, Consultant of: Sanofi, Lilly, Grant/research support from: Lilly, MSD, Roberto Caporali Speakers bureau: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celltrion, Eli Lilly, Fresenius Kabi, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, UCB, Thomas Debray Consultant of: Biogen, Galapagos, Gilead, Francesco De Leonardis Employee of: Galapagos, James Galloway Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Grant/research support from: AstraZeneca, Celgene, Gilead, Janssen, Medicago, Novavax, Pfizer, Monia Zignani Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, BMS, Chugai, Galapagos, Lilly, Pfizer, Sanofi, Consultant of: AbbVie, Amgen, BMS, Galapagos, Lilly, Pfizer, Sanofi.

COMPARATIVE DISEASE BURDEN IN PATIENTS WITH RHEUMATOID ARTHRITIS, PSORIATIC ARTHRITIS OR ANKYLOSING SPONDYLITIS: DATA FROM COVAD PATIENT-REPORTED E-SURVEY

BackgroundRheumatoid arthritis (RA) and spondyloarthritis, including either Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS), are some of the most diagnosed autoimmune rheumatic diseases (AIRDs) in rheumatologists' routine clinical practice [1]. Understanding patients' health and functional status is crucial to provide personalized management strategies to optimize disease control and enhance the quality of life.ObjectivesWe aimed to compare disease burden in patients with RA, PsA or AS by assessing Patient-Reported Outcome Measurement Information System (PROMIS) Physical Health, Global Mental Health, Physical Function and Fatigue 4a together with VAS Pain.MethodsData were obtained in the international COVID vaccination in autoimmune rheumatic diseases study second e-survey (COVAD study). Demographics, AIRD diagnosis, disease activity, PROMIS Global Physical health, PROMIS Global Mental Health, PROMIS Physical Function SF10 and PROMIS Fatigue 4a score were extracted from the COVAD study database. For this study, we only included patients with self-reported RA or spondyloarthritis (either PsA or AS) undergoing active treatment with conventional synthetic disease-modifying drugs (DMARDs) and/or biologic DMARDs, who answered all the survey questions. Active disease was defined as the patient's perception of their disease as active in the four weeks before their first COVID-19 vaccine shot. Analysis of Variance with Bartlett's and Tukey's test was used to compare continuous variables between groups.ResultsFrom January to June 2022, n.1907 patients with RA, female 87.62% (1671/1907), with mean age (±SD) 50.95 ±13.67, n.311 patients with PsA, female 67.20% (209/311), with a mean age of 50.42 ±12.70, and n.336 patients with AS, male 51.31% (209/311), with a mean age of 43.13 ±12.75 years, responded to the COVAD e-survey.In those with active disease, neither physical health, global mental health, physical function, fatigue, nor pain were different among groups (Table 1, Figure 1). Patients with inactive AS had higher mean global physical health scores than RA patients (13.13 ±2.93 VS RA 12.48 ±2.90, p=0.01, Table 1). Those with inactive RA or PsA showed more severe fatigue (PsA 10.58 ±2.22, RA 10.45 ±4.08 VS 9.4 ±4.13, p =0.01 for both). Patients with inactive RA also reported poorer physical function and more residual pain than those with AS (37.79 ±8.86 VS 41.13 ±7.79, p<0.001;3.87 ±2.45 VS 3.34 ±2.39, p=0.01, respectively). Similarly, residual pain was perceived as higher in patients with inactive PsA than those with AS (4.04 ±2.50 VS 3.34 ±2.39, p=0.01)ConclusionDisease burden is roughly comparable in patients with active RA, PsA or AS. Patients with inactive RA and PsA suffer higher disease burden than those with inactive AS.Reference[1]Mease PJ, Liu M, Rebello S, Kang H, Yi E, Park Y, Greenberg JD. Comparative Disease Burden in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or Axial Spondyloarthritis: Data from Two Corrona Registries. Rheumatol Ther. 2019 Dec;6(4):529-542.Table 1.Patient-Reported Outcome Measures between groups.Inactive diseaseAS (n.185)PsA (n.179)RA (n.1167)MeanSDMeanSDMeanSDPROMIS Global Physical Health13.13*2.9512.433.2712.482.90p=0.01, VS RAPROMIS Global Mental Health13.313.3612.973.3312.843.17PROMIS Fatigue 4a9.44.1310.58*4.2210.45*4.08p=0.01, bothPROMIS Physical Function SF10 Score41.137.3939.279.0137.79*8.86p<0.001, VS ASVAS Pain3.342.394.04*2.503.87*2.45p=0.01, bothActive DiseaseAS (n.35)PsA (n.38)RA (n.189)MeanSDMeanSDMeanSDPROMIS Global Physical Health11.053.1910.102.7611.243.41PROMIS Global Mental Health11.313.2610.843.6311.893.30PROMIS Fatigue 4a12.944.8712.844.4211.754.68PROMIS Physical Function SF10 Score35.829.6233.528.7634.909.80VAS Pain4.682.775.02.544.682.61Figure 1.Violin plots showing kernel densities, quartiles and median for Patient-Reported Outcome Measures for patients with RA, PsA and AS, stratified by disease activity status.[Figure omitted. See PDF]Acknowledgements:NIL.Disclosure of InterestsVincenzo Venerito: None declared, Marc Fornaro: None declared, Florenzo Iannone: None declared, Lorenzo Cavagna: None declared, Masataka Kuwana: None declared, Vishwesh Agarwal: None declared, Naveen Ravichandran: None declared, Jessica Day Grant/research support from: JD has received research funding from CSL Limited., Mrudula Joshi: None declared, Sreoshy Saha: None declared, Syahrul Sazliyana Shaharir: None declared, Wanruchada Katchamart: None declared, Phonpen Akarawatcharangura Goo: None declared, Lisa Traboco: None declared, Yi-Ming Chen: None declared, Parikshit Sen: None declared, James B. Lilleker Speakers bureau: JBL has received speaker honoraria/participated in advisory boards for Sanofi Genzyme, Roche, and Biogen. None is related to this manuscript., Consultant of: JBL has received speaker honoraria/participated in advisory boards for Sanofi Genzyme, Roche, and Biogen. None is related to this manuscript., Arvind Nune: None declared, John Pauling: None declared, Chris Wincup: None declared, Ai Lyn Tan Speakers bureau: ALT has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Nelly Ziade Speakers bureau: NZ has received speaker fees, advisory board fees, and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre;none are related to this manuscript, Grant/research support from: NZ has received speaker fees, advisory board fees, and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre;none are related to this manuscript, Marcin Milchert: None declared, Abraham Edgar Gracia-Ramos: None declared, Carlo Vinicio Caballero: None declared, COVAD Study: None declared, Vikas Agarwal: None declared, Rohit Aggarwal Speakers bureau: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Grant/research support from: RA has a consultancy relationship with and/or has received research funding from the following companies: Bristol Myers-Squibb, Pfizer, Genentech, Octapharma, CSL Behring, Mallinckrodt, AstraZeneca, Corbus, Kezar, Abbvie, Janssen, Alexion, Argenx, Q32, EMD-Serono, Boehringer Ingelheim, and Roivant., Latika Gupta: None declared.

PLACEBO-CONTROLLED EFFICACY AND SAFETY OF UPADACITINIB THROUGH ONE YEAR IN PATIENTS WITH NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS

BackgroundUpadacitinib (UPA), a Janus kinase inhibitor, was effective and well tolerated in patients (pts) with non-radiographic axial spondyloarthritis (nr-axSpA) through 14 weeks (wks) of treatment.[1]ObjectivesThis analysis assessed the efficacy and safety of UPA vs placebo (PBO) through 1 year.MethodsThe SELECT-AXIS 2 nr-axSpA study included a 52-wk randomized, double-blind, PBO-controlled period. Enrolled adults had a clinical diagnosis of active nr-axSpA fulfilling the 2009 ASAS classification criteria, objective signs of inflammation based on MRI sacroiliitis and/or elevated C-reactive protein, and an inadequate response to NSAIDs. One-third of pts had an inadequate response to biologic DMARDs. Pts were randomized 1:1 to UPA 15 mg once daily or PBO. Concomitant medications, including NSAIDs, had to be kept stable through wk 52. The study protocol outlined that pts who did not achieve ASAS20 at any two consecutive study visits between wks 24 to 52 should receive rescue therapy with NSAIDs, corticosteroids, conventional synthetic/biologic DMARDs, or analgesics. Cochran-Mantel-Haenszel (CMH) test with non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle missing data and intercurrent events for binary efficacy endpoints. Mixed-effect model repeated measures (MMRM) was used to assess continuous efficacy endpoints. NRI was used for binary endpoints after rescue and as observed analysis excluding data after rescue for continuous endpoints. Treatment-emergent adverse events (TEAEs) are reported through wk 52.ResultsOf the 314 pts randomized, 259 (82%;UPA, n=130;PBO, n=129) completed wk 52 on study drug. More pts achieved an ASAS40 response with UPA vs PBO from wks 14 to 52 with a 20% treatment difference at wk 52 (63% vs 43%;nominal P <.001;Figure 1). The proportion of pts achieving ASDAS inactive disease with UPA remained higher than PBO at wk 52 (33% vs 11%;nominal P <.0001;Figure 1). Consistent improvements and maintenance of efficacy were also seen across other disease activity measures. Between wks 24 and 52, fewer pts on UPA (9%) than PBO (17%) received rescue therapy. A similar proportion of pts in each treatment group had a TEAE (Table 1). Infections were the most common TEAE;the rates of serious infections and herpes zoster were higher with UPA vs PBO, although no new serious infections were reported from wks 14 to 52. COVID-19 events were balanced between treatment groups. No opportunistic infections, malignancy excluding non-melanoma skin cancer, adjudicated major adverse cardiovascular events, inflammatory bowel disease, or deaths were reported. Two pts (1.3%) on PBO had adjudicated venous thromboembolic events.ConclusionUPA showed consistent improvement and maintenance of efficacy vs PBO through 1 year across multiple disease activity measures. No new safety risks were identified with longer-term UPA exposure. These results continue to support the benefit of UPA in pts with active nr-axSpA.Reference[1]Deodhar A, et al. Lancet. 2022;400(10349):369–379.Table 1.Safety through week 52Event, n (%)PBO (n = 157)UPA 15 mg QD (n = 156)Any AE103 (66%)107 (69%)Serious AE6 (3.8%)6 (3.8%)AE leading to D/C4 (2.5%)6 (3.8%)COVID-19-related AE22 (14%)24 (15%)Deaths00Infection60 (38%)68 (44%) Serious infection1 (0.6%)2 (1.3%) Herpes zoster1 (0.6%)5 (3.2%)Malignancy other than NMSC00NMSC1 (0.6%)0Hepatic disorder7 (4.5%)6 (3.8%)Neutropenia1 (0.6%)8 (5.1%)MACE (adjudicated)00VTE (adjudicated)2 (1.3%)a0Uveitisb3 (1.9%)2 (1.3%)Inflammatory bowel disease00aBoth patients had non-serious events of deep vein thrombosis in the lower limb with risk factors including obesity and prior deep vein thrombosis in one patient and concomitant COVID-19 infection in the other patient.bThree events of uveitis occurred in each treatment group (among n = 3 patients in the PBO group and n = 2 patients in the UPA group);two events in the PBO group and one in the UPA group occurred in patients with a history of uveitis.AcknowledgementsAbbVie funded this study and participated in the study design, res arch, analysis, data collection, interpretation of data, review, and approval of the . All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie.Disclosure of InterestsFilip van den Bosch Speakers bureau: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, MoonLake, Novartis, Pfizer, and UCB., Atul Deodhar Consultant of: AbbVie, Amgen, Aurinia, BMS, Celgene, GSK, Janssen, Lilly, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, GSK, Lilly, Novartis, Pfizer, and UCB, Denis Poddubnyy Speakers bureau: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Consultant of: AbbVie, Biocad, BMS, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB, Grant/research support from: AbbVie, Lilly, MSD, Novartis, and Pfizer., Walter P Maksymowych Consultant of: AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Employee of: Chief Medical Officer of CARE Arthritis Limited, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, and UCB, Employee of: Director of Imaging Rheumatology BV, Tae-Hwan Kim Speakers bureau: AbbVie, Celltrion, Kirin, Lilly, and Novartis., Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB., Xenofon Baraliakos Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie and Novartis, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Peter Wung Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie.

BIOLOGIC TREATMENT SUSPENSION AND ASSOCIATED FACTORS IN PATIENTS WITH RHEUMATIC DISEASES DURING THE COVID-19 PANDEMIC: DATA FROM MEXICAN ADVERSE REGISTRY (BIOBADAMEX)

BackgroundThe COVID-19 pandemic triggered serious challenges in the treatment of chronic diseases due to the lack of access to medical attention. Patients with rheumatic diseases (RD) must have adequate treatment compliance in order to reach and maintain remission or low activity of their diseases. Treatment suspension because of non-medical reasons might lead to disease activation and organ damage.ObjectivesIdentify the frequency of biologic treatment (bDMARD) suspension in patients with RD during the COVID-19 pandemic and determine the associated factors for suspension.MethodsIn this study we included all patients registered in the Mexican Biologics Adverse Events Registry (BIOBADAMEX), that started bDMARD before March 2019 and suspended treatment during the COVID-19 pandemic. We used descriptive statistic to analyze baseline characteristics and main treatment suspension causes. We used Chi[2] and Kruskal Wallis tests to analyze differences between groups.ResultsA total of 832 patients patients registered in BIOBADAMEX were included in this study, 143 (17%) suspended bDMARD during the COVID-19 pandemic. The main causes of suspension were inefficacy in 54 (38%) patients, followed by other motives in 49 (34%) patients from which 7 (5%) was loss of medical coverage. Adverse events and loss of patients to follow up were the motive in 16 (11%) and 15 (11%) patients respectively.When we compared the group that suspended bDMARD with the non-suspenders (Table 1), we found statistical differences in patient gender, with 125 (87%) female patients that suspended bDMARD, with a median age of 52 (42-60) years, and a treatment duration of 3.8 years.ConclusionIn our study we found that 17% of patients with RD suspended bDMARD treatment during the COVID-19 pandemic and that non-medical motives such as lack of patients follow up and loss of medical coverage due to unemployment were important motives. These results are related to the effect of the pandemic on other chronic diseases.Table 1.Patients baseline characteristicsPatients that did not suspended bDMARD during pandemic (n = 689)Patients that suspended bDMARD during pandemic (n = 143)pFemale gender, n(%)549 (79.7)125 (87.4)0.02Age, median (IQR)55 (45 – 63)52 (42 – 60)0.04Body mass index, median (IQR)26.4 (23 – 30.4)27.23 (24.2 – 30.46)0.13Social security, n(%)589 (85.5)128 (89.5)0.2Diagnosis0.7- Rheumatoid arthritis444 (64.4)97 (67.8)- Juvenil idiopathic athritis29 (4.2)2 (1.4)- Ankyosing sponylitis93 (13.5)19 (13.3)- Psoriasic arthritis43 (6.2)6 (4.2)- Systemic lupus erithematosus32 (4.6)9 (6.3)- Others48 (6.9)10 (6.9)Disease duration, median (IQR)11 (7 – 19.5)12 (6 - 18)0.95Comorbidities, n(%)305 (44.3)73 (51)0.08Previos biologic, n(%)249 (36.1)60 (42)0.1Treatment at pandemic iniciation, n(%)0.8 - Etanercept a34 (4.9)5 (3.5)- Infliximab a24 (3.5)5 (3.5)- Adalimumab130 (18.9)22 (15.4)- Rituximab a61 (8.9)25 (17.5)- Abatacept76 (11)20 (14)- Tocilizumab82 (11.9)18 (12.6)- Certolizumab92 (13.4)28 (19.6)- Rituximab b7 (1)0- Golimumab36 (5.2)5 (3.5)- Tofacitinib14 (2)1 (0.7)- Infliximab b4 (0.5)2 (1.4)- Etanercept b31 (4.5)6 (4.2)- Baricitinib12 (1.7)1 (0.7)- Belimumab5 (0.7)1 (0.7)- Secukinumb8 (1.2)3 (2.1)Steroids use, n(%):254 (36.9)57 (39.9)0.2Steroids dose (mg), median (IQR)6 (5 – 10)6 (5 – 10)0.47DMARD use, n(%):538 (78.1)118 (82.5)0.1Treatment duration, median (IQR)5.06 (4.04 – 5.78)3.82 (3.35 – 4.95)0.001Suspension motive, n(%)NA- Inefficacy-54 (37.8)- Adverse event-16 (11.2)- Pregnancy-2 (1.4)- Loss of patient-15 (10.5)- Remission-7 (4.9)- Others-49 (34.2)Adverse events, n(%):102 (14.8)24 (16.8)0.3- Severe, n(%)13 (1.9)5 (3.5)0.4a original, b biosimilarREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsVijaya Rivera Teran: None declared, Daniel Xavier Xibille Friedmann: None declared, David Vega-Morales: None declared, Sandra Sicsik: None declared, Angel Castillo Ortiz: None declared, Fedra Irazoque-Palazuelos: None declared, Dafhne Miranda: None declared, Iris Jazmin Colunga-Pedraza: None declared, Julio Cesar Casasola: None declared, Omar Elo Muñoz-Monroy: None declared, Sandra Carrilo: None declared, Angélica Peña: None declared, Sergio Duran Barragan: None declared, Luis Francisco Valdés Corona: None declared, Estefanía Torres Valdéz: None declared, Azucena Ramos: None declared, Aleni Paz: None declared, ERICK ADRIAN ZAMORA-TEHOZOL: None declared, Deshire Alpizar-Rodriguez Employee of: Scientific Advisor in GSK México.

ANTI-TNF TREATMENT MODIFIES PAIN MODULATION DESCENDING PATHWAYS. A PROSPECTIVE, 6 MONTHS STUDY IN ACTIVE CHRONIC INFLAMMATORY RHEUMATISM PATIENTS' NAÏVE OF BDMARD

BackgroundIn rheumatoid arthritis (RA) and spondyloarthritis (Spa), persistent pain remains challenging. In active disease, diffuse noxious inhibitory controls (assessed through conditioned pain modulation (CPM)) are impaired [1]. Little is known regarding impairment of pain pathways in patients under bMDARD.ObjectivesThe main objective of the RAPID (Rheumatism Pain Inhibitory Descending pathways) study, was to assess descending pain modulation (through CPM paradigm) in patients with active RA or Spa, after introduction of first bDMARD with anti-TNF.MethodsWe included 50 RA and 50 Spa patients with active disease, naïve of bDMARD. We assessed clinical disease variables for patients, together with responses to various psychological questionnaires. All participants underwent QST with the determination of heat and cold pain thresholds (HPT-CPT) on dominant forearm and CPM. CPM paradigm require a conditioning stimulus, here applied to the non-dominant foot (cold circulating bath at 8°C during 1min). Descending pain control was assessed as the change in HPT (in °C) following the conditioning stimulus: the higher the CPM effect, the more efficient the inhibitory control. Patients were followed at 3 and 6 months after TNF inhibitor initiation. At both follow-up visits, clinical monitoring of the rheumatism and repeated thermal QST and CPM.ResultsOne hundred patients were included, 59 women, mean age 45.8 (± 14.6) and mean disease duration 7.93 (± 7.96) years. Due to COVID surge 87 patients initiated an anti-TNF, 74 patients completed the follow-up. At 6 months, 40 patients achieved a good therapeutic response (good EULAR response or ASDAS major improvement), 19 patients had a moderate therapeutic response (moderate EULAR response or clinically important improvement) and 15 patients had no therapeutic response. At the end of follow-up, 51 patients were in remission or low disease activity and 47 patients had a pain intensity <4/10. Thermal pain thresholds did not significantly change during follow-up. Mean HPT was at beaseline 42.35°C (+/- 3.68) and at 6 months 42.17°C (+/- 3.67). Mean CPT was at baseline 13.11°C (+/- 10.04) and at 6 months 12.86°C (+/- 9.45). Conditioned pain modulation was significantly changed during follow-up. Mean CPM effect was at baseline 0.25°C (±2.57), 2.64°C (±2.12) at 3 months and 2.96°C (±2.50) at 6 months. At the end of the 6 months follow-up, mean CPM effect was significantly higher in patients with residual mean pain intensity <4/10 compared to patients with persisting pain ≥ 4/10: 3,25°C (± 2,68) vs 2,47 (± 2,11) (p=0.04).ConclusionAfter TNF inhibitor initiation in active RA or SpA, impaired diffuse noxious inhibitory controls are significantly improved. Apart from their articular efficacy, TNF inhibitor have an action on the central nervous system and pain modulation pathways. In patients with persisting pain under bDMARD, diffuse noxious inhibitory controls are not as efficient as patient without residual pain.Reference[1]Trouvin AP, Simunek A, Coste J, Medkour T, Carvès S, Bouhassira D, Perrot S. Mechanisms of chronic pain in inflammatory rheumatism: the role of descending modulation. Pain. 2022 Aug 3. doi: 10.1097/j.pain.0000000000002745.Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Whats' happening on the follicular unit of adolescents after the COVID-19 pandemic: Severe acne is a growing problem of nowadays

Objectives: Acne is a leading skin problem in adolescents. After the end of COVID-19 pandemic, with the gradual transition to the routine life, we started to encounter more severe forms of acne in the last 6-month than we had seen before in the 10 year period of our Paediatric Dermatology outpatient clinic. Method(s): We evaluated the demographic and clinical characteristics, COVID infection and vaccination status, and treatment of patients who were treated at our Paediatric Dermatology outpatient clinic in the last 6 months due to severe acne. Result(s): One of our patients had acne fulminans, and four patients had acne conglobata. The common features of these patients presenting with severe acne were that they were young boys aged 15- 16 years, medium height, normal weight, and skin type 3-4. All patients had a family history of acne in their parents. They had no known comorbidities, additional treatment, history of nutritional supplement use, or accompanying arthralgia or arthritis. Four patients were initially treated with isotretinoin for severe acne, developed acne conglobata, and one developed acne fulminans during the follow-up period. Dapsone therapy was initiated in all patients according to the severity of the lesions, and adalimumab was administered to acne fulminans. Discussion(s): The frequent occurrence of severe forms of acne after the pandemic raises the question of whether COVID-19 infection or vaccination may play a role in its aetiology. Cases of mask-related acne exacerbation during COVID-19 have been well-described in the literature. However, there are no data on the effects of COVID-19 vaccination or infection on the development of severe acne. In this report, we present cases of adolescent patients with severe acne to investigate the possible reasons for the increasing number of severe acne cases presenting to our outpatient clinic during the postpandemic period.

COVID-19–RELATED ADVERSE EVENTS IN THE PHASE 3 POETYK TRIALS OF THE ALLOSTERIC TYROSINE KINASE 2 INHIBITOR, DEUCRAVACITINIB, IN PATIENTS WITH MODERATE TO SEVERE PLAQUE PSORIASIS

BackgroundDeucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor approved in multiple countries for the treatment of adults with plaque psoriasis. Deucravacitinib suppresses signaling of cytokines involved in the pathogenesis of immune-mediated diseases including psoriasis, psoriatic arthritis, and systemic lupus erythematosus. Deucravacitinib was efficacious compared with placebo in phase 2 trials in psoriatic arthritis and systemic lupus erythematosus.[1,2] In two phase 3 trials in patients with moderate to severe plaque psoriasis (POETYK PSO-1 [NCT03624127], PSO-2 [NCT03611751]), deucravacitinib showed superior efficacy versus placebo and apremilast.[3,4] Upon completion of either psoriasis trial, patients could enroll in the POETYK long-term extension (LTE) trial (NCT04036435).ObjectivesTo evaluate the incidence rate and severity of adverse events (AEs) due to COVID-19 with deucravacitinib treatment in the POETYK PSO-1 and POETYK PSO-2 trials and open-label POETYK LTE trial.MethodsIn PSO-1 (N=666) and PSO-2 (N=1020), adult patients with moderate to severe plaque psoriasis were randomized 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. At Week 16, placebo patients in both trials switched to deucravacitinib. Based on their Week 24 PASI response, apremilast patients continued with apremilast or switched to placebo or deucravacitinib. In PSO-1, patients randomized to deucravacitinib continued treatment for 52 weeks;in PSO-2, some patients randomized to deucravacitinib had a randomized treatment withdrawal period. At Week 52, patients could enroll in the open-label LTE and receive deucravacitinib. Incidence rates and severity of COVID-19–related AEs in the POETYK trials (n=1364;2076.7 person-years [PY] of follow-up) were compared with the Janssen/Johnson & Johnson COVID-19 vaccine trial placebo group (n=19,544;3096.1 PY of follow-up). This reference population was selected due to the study design and timing of the trial, which occurred when variants were in circulation.ResultsAs of October 1, 2021, 1519 patients received ≥1 dose of deucravacitinib over a 2-year follow-up period;1364 patients met criteria for this analysis, with deucravacitinib exposure since the pandemic onset (estimated to be January 1, 2020). In total, 153 deucravacitinib patients reported a COVID-19–related AE, for an overall exposure-adjusted incidence rate (EAIR) of 7.4/100 PY (95% CI, 6.2–8.6). Serious COVID-19–related AEs occurred in 43 patients (EAIR, 2.1/100 PY;95% CI, 1.5–2.8), including 30 with COVID-19 and 13 with COVID-19 pneumonia;this rate was within the margins of those for moderate to severe COVID-19 reported in the reference population (EAIR, 16.5/100 PY;95% CI, 15.0–17.9). Deaths due to COVID-19 occurred in 6 patients (EAIR, 0.3/100 PY;95% CI, 0.1–0.6), with the COVID-19–related mortality rate being consistent with the reference population (EAIR, 0.23/100 PY;95% CI, 0.1–0.5). Treatment was discontinued due to COVID-19 or COVID-19 pneumonia in 7 patients, including the 6 patients who died due to COVID-19.ConclusionCOVID-19 was among the most frequently reported AEs during the 2-year period of the pooled PSO-1, PSO-2, and LTE trials due to the temporal overlap of the pandemic with the trials. However, COVID-19 infection and death rates did not differ from the reference population;most infections were not serious and did not lead to treatment discontinuation. Based on this analysis, deucravacitinib did not appear to increase the risk of COVID-19 nor its progression to severe outcomes.References[1]Mease PJ, et al. Ann Rheum Dis. 2022;81:815-822.[2]Morand E, et al. Arthritis Rheumatol. 2022;Nov 11 (Epub ahead of print).[3]Armstrong A, et al. J Am Acad Dermatol. 2022;S0190-9622(22)02256-3.[4]Strober B, et al. J Am Acad Dermatol. 2022;S0190-9622(22)02643-3.AcknowledgementsThese clinical trials were sponsored by Bristol Myers Squibb.Disclosure of InterestsDiamant Thaçi Speakers bureau: AbbVie, Almirall, Amgen, Biogen Idec, Boeh inger Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target Solution, and UCB, Consultant of: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target Solution, and UCB, Grant/research support from: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche, Sandoz-Hexal, Sanofi, Target Solution, and UCB, Kenneth B Gordon Consultant of: Amgen, Almirall, Dermira, Leo Pharma, Pfizer, and Sun Pharma, Grant/research support from: Amgen, Almirall, Dermira, Leo Pharma, Pfizer, and Sun Pharma, AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB, Melinda Gooderham Speakers bureau: Glenmark, Actelion, AbbVie, Galderma, Leo Pharma, Pfizer, and Regeneron, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Sanofi Genzyme, and Valeant, Consultant of: Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Novartis, Sanofi Genzyme, and Valeant, Andrew Alexis Speakers bureau: Pfizer, Regeneron, and Sanofi Genzyme, Consultant of: AbbVie, Allergan, Almirall, Amgen, Arcutis, AstraZeneca, Bausch Health, Beiersdorf, Bristol Myers Squibb, Dermavant, Galderma, Janssen, Leo Pharma, L'Oreal, Pfizer, Sanofi-Regeneron, Sol-Gel, UCB, Valeant, VisualDx, and Vyne, Grant/research support from: Almirall, Amgen, Arcutis, Bristol Myers Squibb, Cara, Galderma, Leo Pharma, Menlo, Novartis, and Valeant (Bausch Health), Varsha Lalchandani Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Julie Scotto Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Lauren Hippeli Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Matthew J Colombo Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Tamara Lezhava Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Mark Lebwohl Consultant of: Aditum Bio, Almirall, AltruBio, AnaptysBio, Arcutis, Arena, Aristea, Arrive Technologies, Avotres, BiomX, Boehringer Ingelheim, Brickell Biotech, Bristol Myers Squibb, Cara, Castle Biosciences, CorEvitas' (Corrona) Psoriasis Registry, Dermavant, Dr. Reddy's Laboratories, Evelo Biosciences, Evommune, Forte Biosciences, Helsinn Therapeutics, Hexima, Leo Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica, Grant/research support from: AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen, Ortho Dermatologics, Regeneron, and UCB.

POSSIBLE ROLE OF PEPTIDE EPITOPES OF COVID-19 BNT-162B2 MRNA VACCINE IN FOMENTING AUTOIMMUNITY: AN IN SILICO ANALYSIS

BackgroundFollowing the launch of the global COVID-19 vaccination campaign, there have been increased reports of autoimmune diseases developing de novo following vaccination. These cases include rheumatoid arthritis, autoimmune hepatitis, immune thrombotic thrombocytopenia, and connective tissue diseases. Nevertheless, COVID-19 vaccines are considered safe for patients with autoimmune diseases and are strongly recommended.ObjectivesThe aim of this in silico analysis is to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most commonly administered COVID-19 vaccines, that could elicit an aberrant adaptive immune response in predisposed individuals.MethodsThe FASTA sequence of the protein encoded by the BNT-162b2 vaccine was retrieved from http://genome.ucsc.edu and used as a key input to the Immune Epitope Database and Analysis Resource (www.iedb.org). Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC ligand assays without MHC restriction were searched and evaluated. HLA-disease associations were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in) by selecting only positive markers.ResultsA total of 183 epitopes were found, corresponding to 178 SARS-CoV-2 and 5 SARS-CoV spike epitopes, respectively. Results were obtained from 22 T-cell assays, 398 B-cell assays, and 2 MHC ligand assays. Complementary receptors included 1080 T-cell receptors and 0 B-cell receptors.Specifically, the IEDB_epitope:1329790 (NATNVVIKVCEFQFCNDPFLGVYY) was shown to bind to HLA-DRB1*15:02 and HLA-DRB1*15:03 alleles, whereas the IEDB_epitope:1392457 (TKCTLKSFTVEKGIYQTSNFRVQPT) was reported to bind to HLA-DRB1*07:01, HLA-DRB1*03:01, HLA-DRB3*01:01, and HLA-DRB4*01:01 alleles. The HLA alleles detected were found to be positively associated with various immunological disorders (Table 1).Table 1.MHC-restricted epitopes of the BNT-162b2 vaccine and potentially associated immunological conditionsEpitopeAssayMHC moleculeAssociated disease (population)NATNVVIKVCEFQFCNDPFLGVYY + OX(C10)cellular MHC/mass spectrometry ligand presentationHLA-DRB1*15:02Takayasu arteritis (Japanese) Arthritis (Taiwanese) Scleroderma (Japanese) Colitis (Japanese)HLA-DRB1*15:03Systemic lupus erythematosus (Mexican American)TKCTLKSFTVEKGIYQTSNFRVQPT + SCM(K2)as aboveHLA-DRB1*07:01Allergy, hypersensitivity (Caucasian)HLA-DRB1*03:01Type 1 diabetes (African) Sarcoidosis, good prognosis (Finnish)HLA-DRB3*01:01Graves' disease (Caucasian) Thymoma (Caucasian) Sarcoidosis (Scandinavian) Autoimmune hepatitis (Caucasian)HLA-DRB4*01:01Vitiligo (Saudi Arabian)ConclusionSimilar to the SARS-CoV-2 spike protein, the protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals. Genotyping for HLA alleles may help identify at-risk individuals. However, further research is needed to elucidate the underlying mechanisms and potential clinical implications.References[1]Vita R, Mahajan S, Overton JA et al. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2019 Jan 8;47(D1):D339-D343. doi: 10.1093/nar/gky1006.[2]Dholakia D, Kalra A, Misir BR et al. HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed s. BMC Genomics 23, 10 (2022). https://doi.org/10.1186/s12864-021-08239-0[3]Parker R, Partridge T, Wormald C et al. Mapping the SARS-CoV-2 spike glycoprotein-derived peptidome presented by HLA class II on dendritic cells. Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179.[4]Knierman MD, Lannan MB, Spindler LJ et al. The Human Leukocyte Antigen Class II Immunopeptidome of the SARS-CoV-2 Spike Glycoprotein. Cell Rep. 2020 Dec 1;33(9):108454. doi: 10.1016/j.celrep.2020.108454.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

CHARACTERISTICS OF PATIENTS WHO RECEIVED BIOLOGICAL TREATMENT AFTER KIDNEY TRANSPLANTATION AND THE INCIDENCE OF SERIOUS INFECTIONS: A MULTICENTER STUDY

BackgroundKidney transplant patients due to both primary kidney involvement of chronic/autoimmune inflammatory diseases and end-stage kidney disease related to amyloidosis are followed up in rheumatology clinics. Biological agents one of the treatment options in kidney transplant recipients with chronic/autoimmune inflammatory disease.ObjectivesHowever, there is insufficient data on the development of infection in kidney transplant recipients who received biological treatment. Herein, we aimed to determine the incidence of serious infections in patients with kidney transplant recipients who are received biological therapy.MethodsKidney transplant recipients who are received biological agents due to rheumatologic disease were included in the study. Patients' demographic features, transplantation data, biological treatment, development of infection and severity of infection were screened retrospectively. Infections that requiring hospitalization were defined as severe infections.ResultsA total of 31 patients were included in the study, 14 (45%) of whom were female and mean age was 41 ±9 years. Twenty-five patients (80%) of them were non-preemptive kidney transplant and mean duration of hemodialysis before the transplantation was 40 ±40 months. Twenty-three patients (74%) had end stage kidney failure due to FMF-amyloidosis(Figure-1-). Seventeen patients (54%) received anakinra, 11 patients (35%) received canakinumab and 3 patients (10%) received etanercept with other immunosuppressive treatment. Mean treatment duration of biological agents was 4.2±2.6 years. Two patients developed solid organ malignancy and one patient developed hematological malignancy after transplantation. Sixteen of the patients (52%) were hospitalized at least once due to infection and 4 patients (13%) died due to infection. The cause of decease in two patients was COVID-19.ConclusionRheumatic diseases are an important cause of end-stage renal disease and definitive treatment is kidney transplantation. Kidney transplant recipients due to rheumatological disease also use biological agents in the post-transplantation period. Kidney transplant recipients have higher risk for the development of infection since they receive immunosuppressive therapy and use of biologic agents may further increase the risk for development infection. Meyer et al reported that infection developed in 54 of 187 solid organ transplant recipients using biological agents.[1] Mean treatment duration of biological agents was 12 months in this study. The incidence of infection was 54% in our study. Mean treatment duration of biological agent was 4.2 year was considered main reason for higher incidence of infection in our study.Reference[1]Meyer F, Weil-Verhoeven D, Prati C, Wendling D, Verhoeven F. Safety of biologic treatments in solid organ transplant recipients: A systematic review. Semin Arthritis Rheum. 2021 Dec;51(6):1263-1273. doi: 10.1016/j.semarthrit.2021.08.013. Epub 2021 Aug 26. Erratum in: Semin Arthritis Rheum. 2022 Aug;55:152015. PMID: 34507811.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

A prolonged pandemic impacts the mental health of orthopaedic patients

Background and aimsMajority of elective orthopaedic operations are postponed to accommodate the reallocation of healthcare resources to combat the pandemic. The aim of this paper is to evaluate the mental state of orthopaedic patients amidst limited orthopaedic management options. The secondary aim of this paper is to identify areas of significant stressors and to provide avenues for improvements.MethodsA survey was administered on patients in outpatient clinics within a tertiary institution from 31 May to 13 June 2021 where government interventions prevented elective orthopaedic surgeries from being performed. Individuals' fatigue level were assessed with Chalder fatigue scale (CFS) and they were surveyed on their areas of stressors.ResultsA total of 160 orthopaedic patients (67 males and 93 females) were surveyed with an average age of 48.3 years old (range 17-88). 65 out of 160 (40.6%) were deemed to be severely fatigued (CFS > 4) with a higher prevalence amongst females than males (47.3% vs 31.3% respectively.) The top three areas identified as stressors included transmitting to family/friends, travel restrictions/quarantine orders and limitation on recreational/social activities (67.5%, 45.6% and 57.5% respectively). 25.6% of the patients indicated that the increased difficulty in accessing healthcare was a stress factor.Discussion and conclusionThere is a high proportion of severe fatigue amongst orthopaedic patients. Combined with postponement of orthopaedic care and treatment, the detrimental effects of a prolong pandemic can be more pronounced on orthopaedic patients. Identified areas of stressors provide avenues for improvements to safeguard the mental health of orthopaedic patients.

INTAKE OF ACETAMINOPHEN SUPPRESSES ANTIVIRAL HUMORAL IMMUNE RESPONSES IN PATIENTS WITH RA FOLLOWING VACCINATION WITH ANTI SARS-CoV-2 mRNA BASED VACCINES

BackgroundAcetaminophen (APAP = paracetamol) may potentially impact vaccine-associated immune responses as the intake of APAP has been associated with a worse outcome in tumor patients receiving checkpoint inhibitors.[1]Different DMARD regimen have been shown to impair the humoral immune response to mRNA SARS-CoV-2 vaccines in patients with rheumatoid arthritis but the effect of paracetamol has not been explored thus far.ObjectivesTo analyse whether the intake of APAP may interfere with antiviral humoral immune responses following two doses of an anti-SARS-CoV-2 mRNA based vaccine in patients with rheumatoid arthritis (RA) on DMARD therapy.MethodsThe RECOVER trial (Rheumatoid Covid-19 Vaccine Immune Response) was a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 healthy controls (HC). We performed a posthoc analysis of blood samples taken before the first vaccine dose (T0), two (T1) and three (T2) weeks after the first and second vaccine dose, and at 12 (T3) weeks. APAP intake was measured using ELISA. The antibody response (anti-S) to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The neutralizing activity NT50 at week 12 was assessed using an HIV-based pseudovirus neutralization assay against Wuhan-Hu-1.ResultsBaseline characteristics of participants are detailed in Table 1. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein at baseline). APAP was detected in serum samples from 34/73 (25%) RA patients and in 7/21 (33%) HC (least at one timepoint T0, T1 and/or T2). APAP intake in HC did not affect levels of anti-S at any timepoint and all HC developed potent neutralizing activity (NT50 ≥ 250) at week 12. RA patients, who tested positive for APAP at T1, showed comparable anti-S levels at T1, T2 and T3 compared to RA patients not exposed to APAP. The detection of APAP at T2 corresponded to lower anti-S levels at T2 (Figure 1 A, B). The detection of APAP at T2 was associated with a significantly lower SARS-CoV-2 neutralizing activity at week 12 compared to patients without perivaccination APAP exposure (p =0.04) (Figure 1 C).ConclusionA decrease of antiviral humoral immune responses was observed in RA patients (but not in HC) who were exposed to APAP at the time of the second mRNA vaccine dose compared to patients in whom APAP was not detected. Our data suggest that the use of paracetamol within the time period around vaccination may impair vaccine-induced immune responses in patients with an already higher risk for blunted immune responses.Reference[1]Bessede A et al. Ann Oncol 2022;33: 909-915Table 1.Baseline characteristics: RA patients and HC with/without APAP exposureRA APAP – n = 37RA APAP + n = 36p-valueHC APAP – n = 8HC APAP + n = 13p-valueAge (yrs), mean (± SD)62 (13)67 (10)0.07 (NS)45 (12)44 (14)0.90 (NS)Female sex, n (%)24 (65)19 (53)0.29 (NS)2 (25)5 (38)0.53 (NS)Vaccination type/schedulemRNA-1273, n (%)4 (11)8 (22.2)0.19 (NS)0 (0)0 (0)BNT162b2, n (%)33 (89)28 (77.8)0.19 (NS)8 (100)13 (100)RA disease characteristicsACPA ± RF, n (%)17/37 (46)19/36 (53)0.56 (NS)NANANARA disease duration (yrs ± SD)9.2 (9.8)10.2 (8.1)0.67 (NS)NANANADMARD therapycsDMARD-mono, n (%)13/37 (35)9/36 (25)0.35 (NS)NANANAbDMARD-mono/combo, n (%)16/37 (43)16/36 (44)0.92 (NS)NANANAtsDMARDs-mono/combo, n (%)8/37 (22)11/36 (31)0.38 (NS)NANANAPrednisone, n (%)15/37 (41)12/36 (33.3)0.52 (NS)NANANAMean daily dose prednisone (mg ± SD)4.6 ± 1.13.9 ± 2.30.39 (NS)NANANA* APAP = acetaminophenFigure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

FACTORS ASSOCIATED WITH ADHERENCE TO ANTI TNF-Α THERAPY DURING THE COVID-19 PANDEMIC IN PATIENTS WITH RHEUMATOID ARTHRITIS

BackgroundRheumatoid Arthritis (RA) patients are effectively treated with anti-TNF-α therapy. However, pharmacological non-adherence limits the achievement of the therapeutic objective. This is a multifactorial behavior where factors such as the route of administration, frequency, tolerance, perception of improvement, polypharmacy and social factors are involved [1,2].ObjectivesTo explore the factors associated with non-adherence to anti TNF-α in RA patients during the COVID-19 pandemic.MethodsThis is a cohort of RA patients treated with anti TNF-α in Medicarte SAS, a Colombian center for Immune-Mediated Diseases, between January to December 2021. The program implements strategies such as pharmacotherapeutic support, informed dispensing, phone calls, text messages and home care services to increase adherence. Adherence was defined as dispensing at least 10/12 (>0.80) prescribed monthly doses for 1 year. Sociodemographic characteristics, time in the program, DAS28-CRP, HAQ and treatment were included as exposure variables. For continuous variables, median and interquartile range (IQR) were calculated. Adjusted Odds Ratio (AOR) with logistic regression were calculated, and a p-value <0.05 was considered as statistically significant.Results565 patients were included, 85.8% (n=485) were women, median age 56 years (IQR: 49-65), disease evolution time 13.7 years (IQR: 7.7-20.8), 51% (n=288) had been in the program for more than 3 years, the median time in treatment with anti TNF-α was 3 years (IQR: 1-3) and DAS-28-CRP 2.4 (IQR: 1.6-3.4). The most frequently anti TNF-α prescribed was etanercept 46.0% (n=260), followed by adalimumab 23% (n=130), subcutaneous golimumab 13.3% (n=75), certolizumab 11.0% (n=62) and intravenous golimumab 6.7% (n=38). At the admission, 18.2% (n=103) of the patients had high activity, 38.6% (n=218) mild activity, 9.2% (n=52) low activity and 34% (n=192) were in remission. At the end of follow-up, 6.4% (n=36) of patients had high activity, 18.2% (n=103) mild activity, 14.3% (n= 81) low activity and 61.1% (n= 345) were in remission. The 51.5% (n=291) did not have pharmacological adherence. The use of etanercept (AOR 0.36 CI95% 0.23- 0.58, p < 0.001) and adequate functionality measured through HAQ (AOR 0.64 CI95% 0.42- 0.97, p < 0.04) were associated with a lower risk of non-adherence. Higher DAS28-CRP at the end of follow up was associated with non-adherence (AOR 1.29 CI95% 1.12 - 1.48, p < 0.001).ConclusionDuring COVID-19 pandemic, the implementation of strategies in the home care patient program guaranteed adherence close to 50% in our cohort. Higher values of DAS28-CRP were associated with non-adherence, whilst etanercept use and a normal HAQ value were associated with a higher probability of adherence.References[1]Marengo MF, Suarez-Almazor ME. Improving treatment adherence in patients with rheumatoid arthritis: what are the options? Int J Clin Rheumtol. 2015 Oct 1;10(5):345-356.[2]Smolen JS, Gladman D, McNeil HP, Mease PJ, Sieper J, Hojnik M, et al. Predicting adherence to therapy in rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis: a large cross-sectional study. RMD Open. 2019 Jan 11;5(1):e000585.Acknowledgements:NIL.Disclosure of InterestsWilmer Gerardo Rojas Zuleta Speakers bureau: Pfizer, Jannsen Cilag, Bristol Myers Squibb, Amgen, Eli lilly, Mario Barbosa: None declared, Oscar Jair Felipe Díaz Speakers bureau: Pfizer, Jannsen Cilag, Bristol Myers Squibb, Amgen, Eli lilly, Adelis Enrique Pantoja Marquez: None declared, Jeixa Canizales: None declared, Carolina Becerra-Arias: None declared, Jorge Hernando Donado Gómez: None declared, Natalia Duque Zapata: None declared.