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The consequences of the COVID-19 outbreak are unprecedented and have been felt by everyone around the world, including people with rheumatic and musculoskeletal diseases (RMDs). With the development of vaccines, the future is becoming brighter. Vaccines are a key pillar of public health and have been proven to prevent many serious diseases. However, vaccination also raises questions, especially for patients with inflammatory RMDs and/or treated with drugs that influence their immune system. Our aim was to collect safety data among RMD patients receiving COVID-19 vaccines. The EULAR COVID-19 Vaccination (COVAX) Registry is an observational registry launched on 5 February 2021. Data are entered voluntarily by clinicians or associated healthcare staff; patients are eligible for inclusion if they have an RMD and have been vaccinated against SARS-CoV-2. Descriptive statistics are presented. As of 27 April 2021, 1519 patients were reported to the registry. The majority were female (68%) and above the age of 60 (57%). Mean age was 63 years (SD 16), ranging from 15 to 97 years. A total of 28 countries contributed to the registry, with France (60%) and Italy (13%) as the highest contributors. The majority (91%) had inflammatory RMDs. Inflammatory joint diseases accounted for 51% of cases, connective tissue diseases 19%, vasculitis 16%, other immune mediated inflammatory diseases 4%, and non-inflammatory/mechanical RMDs 9%. The most frequent individual diagnoses were rheumatoid arthritis (30%), axial spondyloarthritis (8%), psoriatic arthritis (8%), systemic lupus erythematosus (SLE, 7%) and polymyalgia rheumatica (6%). At the time of vaccination, 45% were taking conventional synthetic DMARDs, 36% biological DMARDs, 31% systemic glucocorticoids, 6% other immunosuppressants (azathioprine; mycophenolate; cyclosporine; cyclophosphamide; tacrolimus), and 3% targeted synthetic DMARDs. The most frequent individual DMARDs were methotrexate (29%), TNF-inhibitors (18%), antimalarials (10%) and rituximab (6%). The vaccines administered were: 78% Pfizer, 16% AstraZeneca, 5% Moderna and 1% other/unknown; 66% of cases received two doses and 34% one dose. Mean time from 1st and 2nd dose to case report was 41 days (SD 26) and 26 days (SD 23), respectively. COVID-19 diagnosis after vaccination was reported in 1% (18/1519) of cases. Mean time from first vaccination until COVID-19 diagnosis was 24 days (SD 17). Disease flares were reported by 5% (73/1375) of patients with inflammatory RMDs, with 1.2% (17/1375) classified as severe flares. Mean time from closest vaccination date to inflammatory RMD flare was 5 days (SD 5). The most common flare types were arthritis (35/1375=2.5%), arthralgia (29/1375=2.1%), cutaneous flare (11/1375=0.8%) and increase in fatigue (11/1375=0.8%). Potential vaccine side effects were reported by 31% of patients (467/1519). The majority were typical early adverse events within 7 days of vaccination, namely pain at the site of injection (281/1519=19%), fatigue (171/1519=11%) and headache (103/1519=7%). Organ/system adverse events were reported by 2% (33/1519) but only 0.1% (2/1519) reported severe adverse events, namely a case of hemiparesis in a patient with systemic sclerosis/SLE overlap syndrome (ongoing at the time of reporting), and a case of giant cell arteritis in a patient with osteoarthritis (recovered/resolved without sequelae). The safety profiles for COVID-19 vaccines in RMD patients was reassuring. Most adverse events were the same as in the general population, they were non-serious and involved short term local and systemic symptoms. The overwhelming majority of patients tolerated their vaccination well with rare reports of inflammatory RMD flare (5%; 1.2% severe) and very rare reports of severe adverse events (0.1%). These initial findings should provide reassurance to rheumatologists and vaccine recipients, and promote confidence in COVID-19 vaccine safety in RMD patients, namely those with inflammatory RMDs and/or taking treatments that influence their immune system. EULAR COVID-19 Task Force; European Reference Network on rare and Complex Connective Tissue and Musculoskeletal Diseases; European Reference Network on Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network; all rheumatologists contributing to the EULAR COVAX Registry. Pedro M Machado Consultant of: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Grant/research support from: Orphazyme, unrelated to this manuscript., Speakers bureau: Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript., Saskia Lawson-Tovey: None declared, Kimme Hyrich Grant/research support from: BMS, UCB, and Pfizer, all unrelated to this manuscript., Speakers bureau: Abbvie, Loreto Carmona Consultant of: her institute works by contract for laboratories among other institutions, such as Abbvie Spain, Eisai, Gebro Pharma, Merck Sharp & Dohme España, S.A., Novartis Farmaceutica, Pfizer, Roche Farma, Sanofi Aventis, Astellas Pharma, Actelion Pharmaceuticals España, Grünenthal GmbH, and UCB Pharma, all unrelated to this manuscript., Laure Gossec Grant/research support from: AbbVie, Amgen, BMS, Biogen, Celgene, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, all unrelated to this manuscript., Speakers bureau: Amgen, Lilly, Janssen, Pfizer, Sandoz, Sanofi, Galapagos, all unrelated to this manuscript., Elsa Mateus Grant/research support from: LPCDR received support for specific activities: grants from Abbvie, Novartis, Janssen-Cilag, Lilly Portugal, Sanofi, Grünenthal S.A., MSD, Celgene, Medac, Pharmakern, GAfPA; grants and non-financial support from Pfizer; non-financial support from Grünenthal GmbH, outside the submitted work., Anja Strangfeld Speakers bureau: AbbVie, MSD, Roche, BMS, and Pfizer, all unrelated with this manuscript., BERND RAFFEINER: None declared, Tiphaine Goulenok: None declared, Olilvier Brocq: None declared, Martina Cornalba: None declared, José A Gómez-Puerta Speakers bureau: AbbVie, BMS, GSK, Janssen, Lilly, MSD, Roche and Sanofi., Eric Veillard: None declared, Ludovic Trefond: None declared, Jacques-Eric Gottenberg: None declared, Julien Henry: None declared, Patrick Durez: None declared, Gerd Rüdiger Burmester: None declared, Marta Mosca: None declared, Eric Hachulla: None declared, Hans Bijlsma: None declared, Iain McInnes: None declared, Xavier Mariette Consultant of: BMS, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sanofi-Aventis, UCB, and grant from Ose, all unrelated to this manuscript.

BackgroundSystemic autoimmunity is a complex and multifactorial process for which underlying mechanism are unclear. Several theories have been formulated to explain the development of autoimmunity, including excessive self-immunosurveillance, danger, and antigen discontinuity. The antigen discontinuity and the self-criticality theories presume that repetitive antigen exposure leads to a dysregulated immune response. Supporting these theories, Tsumiyama and Shiozawa have shown that repetitive immunization of BALB/c mice with ovalbumin induces auto-antibodies production and a glomerulonephritis with immune deposit resembling lupus nephritis [1].These data prompted us to consider the potential impact of repetitive SARS-CoV-2 infection in the onset of autoimmune diseases in human. Indeed, since 2020, a large majority of the population has encountered SARS-CoV-2 antigens multiples times, either through vaccination or through infection/reinfection. Hence, we hypothesized that repetitive exposure to the SARS-CoV-2 spike antigen may induce autoimmunity in healthy individuals.ObjectivesEvaluate whether repetitive exposure to SARS-CoV-2 spike protein induces autoimmunity in mice.MethodsWe immunized intraperitoneally C57Bl/6 mice (n = 5/group) with recombinant SARS-CoV-2 spike protein (1µg per injection) or vehicle (phosphate buffered saline [PBS]); Figure 1A). The first injection was mixed with Alum as an adjuvant, and the other injections were diluted in PBS, administered intraperitoneally every 5 days, 16 times in total. Five days after the final injection, the mice were sacrificed to retrieve serum. We measured anti-spike and anti-dsDNA IgG using ELISA. The serum from 5 34-week-old C57Bl/6.lpr autoimmune mice were used as positive control. Briefly, 96-well plate were coated overnight with either spike protein (0.2µg/mL) or calf thymus DNA (0.1mg/mL; after precoating with poly-L-lysin 0.05mg/mL). After blocking with PBS-BSA, the diluted serum samples were incubated on the plate for 2 hours at room temperature. Plate-bound IgG were revealed using an alkaline phosphatase-conjugated anti-mouse IgG (1:5000). For anti-dsDNA IgG measurement, the serum of an autoimmune mice was used as a reference standard and the result expressed in unit per mL.ResultsAfter immunization, the phenotype of control and spike-immunized mice was clinically similar. All the immunized mice were exempt of proteinuria (Figure 1B). Only the mice which were injected with spike protein developed measurable amounts of anti-spike IgG as determined by ELISA, while those injected with PBS and the C57Bl/6.lpr mice did not (Figure 1C). None of the mice in the immunization group developed measurable anti-dsDNA IgG (Figure 1D).ConclusionIn our study, the repetitive exposure of C57Bl/6 mice to the SARS-CoV-2 spike antigen did not lead to autoimmunity. Although these results are reassuring, large scale epidemiological studies are needed to evaluate the incidence of autoimmune diseases in individuals with multiple exposure to SARS-CoV-2 antigens.Reference[1]K. Tsumiyama, Y. Miyazaki, S. Shiozawa, Self-Organized Criticality Theory of Autoimmunity, PLOS ONE. 4 (2009) e8382.Figure 1.Acknowledgements:NIL.Disclosure of InterestsMarc SCHERLINGER Speakers bureau: Amgen, Sandoz, Nordic Pharma, Jean Sibilia Speakers bureau: Roche, Chugai, Bristol-Myers Squibb, UCB, GSK, LFB, Actelion, Pfizer, MSD, Novartis, Amgen, Abbvie, Sandoz, Gilead, Lilly, Sanofi Genzyme, Janssen, Mylan, Galapagos, Sobi., Grant/research support from: Pfizer, BMS, Roche, MSD, George Tsokos: None declared, Jacques-Eric Gottenberg Speakers bureau: AbbVie, BMS, CSL Behring, Galapagos, Gilead, Lilly, Roche-Chugai, Pfizer, Sanofi, and UCB., Grant/research support from: BMS.

Background:In about 10% of patients, the immune response to immune check-point inhibitors (ICI) exceeds the anti-tumor response and leads to autoimmune complications (immune-related Adverse Events, irAEs), which can sometimes be severe and require the use of targeted therapies. Pre-existing autoimmune disease (AD) seems to increase the risk of irAE in patients treated with ICI.Objectives:To compare the prevalence and mortality of irAEs in patients with or without a pre-existing autoimmune or inflammatory disease.Methods:This retrospective study analyzed adults from the French nationwide healthcare information system (“système national des données de santé” [SNDS]) who initiated any immune checkpoint inhibitor (ICI) therapy for any cancer between 2016 and 2022. The aim was to investigate the occurrence of immune-related adverse events (irAEs) during ICI treatment and in the 12 months post-administration, comparing patients with and without a history of autoimmune disease. IrAEs were defined by the combination of (1) hospitalization for a cause evoking an irAE of any nature, and (2) either the initiation of corticosteroids, or of a conventional DMARD or a b/tsDMARD, or death. Propensity score matching was performed for patients with and without a pre-existing autoimmune or inflammatory disease. The propensity score included gender, age, type of cancer, type of ICI, time from cancer to initiation of ICI and from initiation of ICI to irAE, use of corticosteroids, hospitalization in intensive care unit, type of irAE, number of LTDs, Charlson’s index and FDep social deprivation index. Overall survival was compared between the two groups using a Cox model.Results:69,745 patients (men: 69.0%, mean age: 65.8 years) initiating an ICI were analysed. 5,252 (7.4%) patients had a pre-existing autoimmune or inflammatory disease, before initiation of ICI, notably including 594 patients with rheumatoid arthritis and 847 patients with inflammatory bowel disease. IrAE occurred in 568 patients (11%) in patients with a pre-existing autoimmune or inflammatory disease and 4374 patients (6.8%) without a pre-existing autoimmune or inflammatory disease, with a statistically significant increased risk (HR 3.07 (2.78-3.39)). Mortality was significantly increased in patients with a pre-existing autoimmune or inflammatory disease (HR 1.16 (1.1-1.22)).Conclusion:This extensive epidemiological nationwide study identified an increased risk of irAEs and a higher mortality in patients with a pre-existing autoimmune or inflammatory disease. Further investigations are needed to confirm and elucidate the determinants of these findings.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundPatients with IMID, and notably patients with rheumatoid arthritis RA, are at increased risk of cancer compared with the general population [1,2]. It is hence paramount to assess the impact of biological or targeted DMARD (e.g.., tofacitinib and TNFi) on the risk of cancer outcome in patients already at-risk, particularly in the context of ORAL Surveillance which showed a higher risk for malignancies (excluding nonmelanoma skin cancer, NMSC) with tofacitinib, in comparison with TNFI, in RA patients [3].ObjectivesTo assess the impact of tofacitinib and TNFi on the risk of malignancies in patients with RA treated in real-world clinical practice.MethodsThe RELATION study is a retrospective observational cohort study using the French nationwide healthcare database (SNDS). Patients aged 18 years or older, affiliated to the national health insurance with a diagnosis of RA and initiating tofacitinib after November 1, 2017 or TNFi after January 1, 2010 (including adalimumab, etanercept, or other TNFi, without previous exposure to tofacitinib) were followed from treatment initiation to December 31, 2020. Patients with a previous history of a malignancy (excluding NMSC) in the 4 years preceding cohort entry were excluded. All malignancies events were defined by the first hospitalization for malignancy during follow-up. Comorbidities and traditional cardiovascular (CV) risk factors were identified using hospitalizations, procedures, or medication dispensing in the 4 years prior cohort entry. The unadjusted incidence rate (IR) of malignancies (excluding NMSC) was assessed in patients initiating either tofacitinib or a TNFi (with associated 95% confidence intervals (95% CI)). A 1:3 PS matching was conducted to balance the baseline characteristics of patients initiating tofacitinib and TNFi. Cox proportional hazards regression models were used to compare the risk of malignancy with tofacitinib vs TNFi during the follow-up period.ResultsBetween 2010 and 2020, a total of 39,578 patients with RA were included in the study. Among these, 2,811 initiated tofacitinib and 36,767 initiated a TNFi (adalimumab: 10,621, etanercept: 16,512, other TNFi: 9,634). Patients had a mean age of 53 years at cohort entry, and 72% to 81% were women. Around 61% of the cohort had at least one CV risk factor (66.3%for tofacitinib compared to 60.9% for TNFi). The two major co-medications at treatment initiation in the two groups were methotrexate (60.9%) and corticosteroids (50.8%).After PS matching, the tofacitinib cohort included 2,628 patients, and the TNFi cohort included 7,884 patients. Over a median follow-up period of 11.31 months (tofacitinib: 8.56 months, TNFi: 12.52 months), 15 incident malignancy events occurred in the tofacitinib group (IR: 5.89 (3.55–9.77) per 1,000 patient-year (PY)) and 135 occurred in the TNFi group (8.03 (6.78–9.50)). The risk of malignancies was similar with tofacitinib vs TNFi (adjusted HR 0.76 [95%CI 0.44, 1.32]; p=0.3347). Similar results were found for other (other than breast, melanoma, colorectal, lung cancer or lymphoma) active cancers (HR 0.97 [95% CI 0.50, 1.89]; p=0.9382). For other specific cancer types (cited above), the number of events was too low to perform these analyses.ConclusionIn this large population-based study, tofacitinib was not associated with an increased risk of malignancies (excluding NMSC) in comparison with TNFI in patients with RA treated in real-world settings. Studies with longer follow-up durations may be necessary to understand the long-term implications of tofacitinib vs TNFi on the risk of malignancies.References[1]Smitten AL et al. Arthritis Res Ther 2008; 10: 1-8.[2]Simon TA et al. Arthritis Res Ther 2015; 17: 1-0.[3]Ytterberg SR et al. N Engl J Med 2022; 386: 316-26.AcknowledgementsThis study was sponsored by Pfize.r.Disclosure of InterestsJacques-Eric Gottenberg Consultant of: AbbVie, Bristol Myers Squibb, Galapagos, Gilead, Lilly, MSD, Novartis, Pfizer, Grant/research support from: Pfizer, Bristol Myers Squibb, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Jeremie Rudant Shareholder of: Pfizer, Employee of: Pfizer, Nada Assi Employee of: Heva, Fanny Raguideau Employee of: Heva, Julien Kirchgesner Speakers bureau: Pfizer, Consultant of: Gilead, Pfizer, Roche.

Background Hydroxychloroquine (HQ, Plaquenil) is often prescribed in patients with primary Sjögren’s syndrome (pSS). However, except a crossover trial, no controlled trial has ever evaluated HQ versus placebo. Objectives Methods 120 patients with pSS were randomly assigned to receive HQ (400 mg/j) or placebo for 24 weeks (controlled phase) and were all prescribed HQ between week 24 and week 48 (open extension). All patients fulfilled the AECG criteria. A favorable overall response (primary outcome criteria) was defined as the patient having >or= 30% improvement between weeks 0 and 24 in the values on 2 of the 3 patient’s VAS evaluating dryness, pain and fatigue. Secondary end points were the evolution of the ESSDAI, the ESSPRI, Schirmer’s test and unstimulated salivary flow, serum gammaglobulin levels, and of SF-36, HAD, PROFAD, and SSI. Serum interferon-regulated chemokines (CXCL10, CCL2 and CCL19) were assessed at baseline and W24 in the 45 patients with available serum. Results Baseline characteristics of the 120 patients were as following: mean age 55.9 years, 91.7% of women, median disease duration: 5 years, anti-SSA positivity : 55.1%, patients with systemic involvement at enrollment: 30%. At 6 months, 19.2% of patients receiving placebo and 19.6% of patients treated with HQ had a favorable overall response (p = 0.9). At 12 months, 18.8% of patients treated for 6 months with placebo, then 6 months with HQ and 32.1% patients treated with 12 months with HQ were responders (p= 0.1). No significant difference was observed in any of the secondary outcome criteria. No significant difference was observed in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. In patients treated with HQ, a trend towards a decrease of serum IgG was observed, as well as a significant decrease of IgM. In patients with HQ, a decrease in serum CXCL10 (from 50.5 to 35.8 pg/ml vs from 27.7 to 38.7 pg/ml under placebo, p=0.001) and CCL19 (from 241.6 to 160.9 pg/ml vs from 142.3 to 131.1 pg/ml, p=0.3), but not CCL2, was observed. In the HQ arm, all except 1 had detectable blood levels of HQ at 6 months. Baseline levels of HQ or of IFN-regulated chemokines were not associated with a favorable overall response. Tolerance of HQ was comparable to placebo. Conclusions The results of this controlled trial did not show any evidence of short term efficacy of HQ in pSS. HQ induced a decrease in serum level of CXCL10 and CCL19, 2 IFN-induced chemokines but no association with response to HQ could be identified in any subgroup of patients. Disclosure of Interest None Declared

Background:The Newcastle Sjogren’s Stratification Tool (NSST) stratifies Sjogren’s disease (SjD) patients into four subtypes.[1] These subtypes have distinct molecular profiles and may respond differently to immunomodulatory therapies.[1] NSST captures the patient experience using validated patient-reported outcomes (PROs), namely EULAR SS Patient Reported Index (ESSPRI) and Hospital Anxiety and Depression Scale (HADS) with the allocation of subtype membership then based on the probability of the patient belonging to a particular subtype.Objectives:To understand how symptom-based subtypes vary over time and factors influencing subtype change. Such data are important for understanding the patient experience and are vital if PROs, and PRO-guided stratification, are adopted in trial design and clinical management.Methods:274 patients from the United Kingdom Primary Sjogren’s Syndrome Registry (UKPSSR) with data permitting NSST subtype assignment from two study visits were included. The follow up interval was not standardised with a median of 4 years. The French Assessment of Systemic Signs and Evolution of Sjögren’s Syndrome (ASSESS) cohort acted as an independent comparator. ASSESS follow up data were available at 12-month intervals for 5 years. 237 patients had data to assign NSST subtype at baseline and year 5; 134 patients had NSST data at all timepoints. Group analyses of significant differences were performed using Wilcoxon analysis, pairwise comparisons were performed using Tukey-Kramer HSD analysis. Fisher’s Exact Test was used for categorical data. Logistic regression models were performed with the following covariates at baseline: age, sex, BMI, disease duration, Ro status, NSST probability score, ESSDAI score, C3, C4, IgG, WCC, current medication prescriptions, Chronic Conditions Indicator score (CCI) and polypharmacy score. Separate logistic regression models were used for the covariates: delta anxiety, delta depression, delta fatigue, delta pain, delta dryness, delta EQ-5D UK utility, delta CCI, delta polypharmacy score. Statistical tests and graphical rendering were performed using the R and SAS JMP Statistical Data Visualization software 23.Results:UKPSSR and ASSESS cohorts showed broadly similar proportion of subjects in each subtype and, similar baseline clinical characteristics except BMI. Several baseline characteristics differ significantly between the subtypes, most notably Ro+ status (higher in dryness-fatigue and low-symptom burden types) and BMI (higher in high-symptom burden type). Subtype membership was reasonably stable in both cohorts with 60% and 56% retaining subtype between the initial and final clinic visits. The high-symptom burden subtype was the most stable over time with 70% and 67% retaining subtype. Higher baseline probability score was the greatest predictor of subtype stability with higher C4 levels, antidepressant use and a higher CCI also predicting increased subtype stability.Conclusion:NSST subtype membership remains stable over time in a large proportion of patients. When subtype transition is associated with factors at baseline, it is most strongly associated with an uncertain subtype allocation. Our findings support the hypothesis that symptom-based subtypes reflect genuine pathobiological endotypes and therefore maybe important to consider in trial design and clinical management.REFERENCES:[1] Tarn JR et al. Symptom-based stratification of patients with primary Sjogren’s syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol. 2019 Oct 1;1(2):e85–94.Figure 1.Tracking the ASSESS cohort. Baseline (BL) probability score alongside subtype at 12-monthly intervals for ASSESS patients.Acknowledgements:This work was supported in part by the Medical Research Council (Grant REFERENCES: G0800629 & MR/J002720/1), FOREUM, NECESSITY, NIHR Biomedical Research Centre at Newcastle University and the Newcastle upon Tyne Hospitals NHS Trust.Disclosure of Interests:Joe Berry: None declared, Jessica Tarn: None declared, John Casement: None declared, Kyle Thompson: None declared, Dennis Lendrem: None declared, Jacques-Eric Gottenberg: None declared, Wan-Fai Ng WFN has undertaken clinical trials and provided consultancy or expert advice in the area of Sjögren’s syndrome to the following companies: GlaxoSmithKline, MedImmune, UCB, Abbvie, Takeda, Resolves Therapeutics, Sanofi, Novartis, Bain Capitals and Argenx., WFN has undertaken clinical trials and provided consultancy or expert advice in the area of Sjögren’s syndrome to the following companies: GlaxoSmithKline, MedImmune, UCB, Abbvie, Takeda, Resolves Therapeutics, Sanofi, Novartis, Bain Capitals and Argenx.

Background:Patients (pts) with Psoriasis (PsO) or Psoriatic Arthritis (PsA) are at increased risk for developing gout; and hyperuricemia (HU) prevalence is higher in PsO/PsA pts than the general population1. The pathogenic role of chronic hyperuricemia in the development and maintenance of PsA is based on basic science, epidemiological, and clinical arguments and hence does not appear fortuitous. These two pathological processes can influence each other. Pts with PsA with HU appeared to be more severe and difficult-to-treat than normo-uricemic ones2. Previous post-hoc analysis showed that the profile of pts with vs without HU was distinct but the efficacy of secukinumab (SEC) or guselkumab (GUS) was comparable in hyper- and normo-uricemic pts.3Objectives:This post-hoc analysis sought to compare PsA patients with vs without HU and evaluate the safety and efficacy of upadacitinib (UPA), a JAK inhibitor, and adalimumab, a TNF-α inhibitor, through 1 year in pts with or without hyperuricemia.Methods:Adults in SELECT-PsA 1&2 with active PsA despite standard therapies were included. HU was defined as baseline (BL) serum urate levels ≥360 μmol/L. Pts without HU (no HU) but with history of gout or urate-lowering therapies were excluded. Patients’ clinical and demographic characteristics were collected at baseline. Adverse events between baseline and week 56 (W56) were recorded. Treatment-Emergent Adverse Events (TEAE) and efficacy were compared between 1049 patients with or without HU and treatment arms up to W56 in pooled UPA 15 mg QD patients from SELECT-PsA 1 & 2 and adalimumab patients from SELECT-PsA 1. The UPA 30 mg QD arms of the studies were excluded from the efficacy and safety analysis as this dosage is not approved in rheumatology. The evaluation of efficacy included the assessment of American College of Rheumatology responses (ACR20/50/70), the Enthesitis Index of the Spondyloarthritis Research Consortium of Canada (SPARCC), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriasis Area and Severity Index (PASI90), the Psoriatic Arthritis Response Criteria (PsARC), radiographic progression (vdH-mTSS), and quality of life (QoL) over W56. The results of the statistical analysis are presented in descriptive form.Results:2347 pts were included in SELECT-PsA studies (SELECT-PsA 1: 1705 pts & SELECT-PsA 2: 642 pts). Relative to no HU pts (n=1540), those with HU (n=770) were more likely to be male (66.4% vs 36.1%) with higher BMI (32.3 vs 29.7 kg/m2) and more severe PsO. The two cohorts had generally comparable severity of articular symptoms and patient-reported outcomes (Table 1). Incidence of Treatment-Emergent Adverse Events (AE) were comparable between patients with or without HU (any AE 77.8 vs 77.9%). HU pts developed more often metabolic disorders (such as hypertension or diabetes mellitus) but MACE incidence were similar across HU and non-HU pts (0.3% in HU pts vs 0.9% in non-HU) (Table 2). Clinically meaningful and comparable improvements in all studied outcomes were observed at W56 across HU and non-HU cohorts and ADA and UPA groups.Conclusion:In this pooled analysis of pts with active PsA, HU pts were more likely to be male and have a higher BMI and more severe PsO. The observed differential clinical profile and comorbidities, which confirm previous studies3, underscore the value of assessing serum urate levels in PsA pts. Pts with HU were more prone to develop hypertension or diabetes mellitus. UPA was not associated with an increased risk of TEAE event in the HU cohort. UPA and ADA provided clinically meaningful improvements across key PsA domains through W56, irrespective of HU presence.REFERENCES:[1] Felten et al. Clin Rheumatol. 2020 May;39(5):1405-1413[2] Widawski et al. Clin Rheumatol. 2022 May;41(5):1421-1429[3] Felten R. et al. RMD Open. 2023 Nov;9(4):e003428Acknowledgements:AbbVie funded the studies and participated in the data collection, analysis, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the review, and approval of this publication. No honoraria or payments were made for authorship.Disclosure of Interests:Renaud Felten AbbVie, Amgen, BMS, GSK, Lilly, Nordic, Novartis, Medac, MSD, Pfizer, Sanofi, UCB, Laura WIDAWSKI: None declared, Lionel SPIELMANN: None declared, Jacques-Eric Gottenberg AbbVie, MSD, Novartis, Lilly, Galapagos, Gilead, Pfizer, UCB, AbbVie, MSD, Novartis, Lilly, Galapagos, Gilead, Pfizer, UCB, Pierre-Marie DURET AbbVie, Novartis, Medac, BMS, Sanofi, Pfizer, Sandra VEGAT AbbVie, Laurent MESSER: None declared.