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Objectives The prevalence of psoriatic arthritis (PsA) is the same in men and women; however, the latter experience a higher burden of disease and are affected more frequently by polyarthritis. Here, we performed an early PsA cohort analysis to assess sex-related differences in demographics, disease characteristics, and evolution over 1 year including applied treatment strategies. Methods Our study is embedded in the Dutch south-west Early Psoriatic Arthritis cohoRt. We described patient characteristics and treatment decisions. For the comparison across sexes and baseline and 1 year follow-up, appropriate tests depending on the distribution were used. Results Two hundred seventy-three men and 294 women with no significant differences in age and ethnicity were included. Women reported significantly longer duration of symptoms before diagnosis and significantly higher tender joint count, a higher disease activity, higher levels of pain, and lower functional capacity. Although minimal disease activity (MDA) rates increased over time for both sexes, MDA remained significantly more prevalent among men at 1 year (58.1% vs 35.7%, p < 0.00 ). Initially, treatment strategies were similar in both sexes with methotrexate being the most frequently used drug during the first year. Women received methotrexate for a shorter period [196 (93–364) vs 306 (157–365), p < 0.00 ] and therefore received a lower cumulative dose compared to men. Retention time was shorter for all DMARDs, and women had a delayed start on b-DMARDs. Conclusion After 1 year of standard-of-care treatment, women did not surpass their baseline disadvantages. Despite the overall improvement, they still presented higher disease activity, higher levels of pain, and lower functional capacity score than men. The nature of these findings may advocate a need for sex specific adjustment of treatment strategies and evaluation in early PsA patients.

Background Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory musculoskeletal disease, manifesting as peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis. A core set of domains for measuring the impact of PsA has been developed, including pain, patient global assessment, physical function, health-related quality of life (HRQoL), and fatigue. To understand the impact of PsA on health domains from a patient’s perspective, a global survey was developed and results reported in the context of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire. Methods An online patient-based global survey was conducted by The Harris Poll in Australia, Brazil, Canada, France, Spain, Taiwan, the UK, and the US between November 2, 2017 and March 12, 2018. Eligible patients were ≥ 18 years old with a diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months and reported using ≥ 1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported on PsA severity and symptoms, and the impact of PsA on HRQoL. After survey completion, responses were aligned with PsAID health domains. Descriptive statistics and chi-square tests were conducted. Results This analysis included 1286 patients from eight countries. Most patients (97%) reported musculoskeletal symptoms relating to PsA in the past year. Common moderate/major impacts of PsA were on physical activity (78%), ability to perform certain activities (76%), work productivity (62%), and career path (57%). Skin/nail symptoms occurred in 80% of patients. Overall, 69% of patients reported that PsA had a moderate/major impact on emotional/mental wellbeing, 56% on romantic relationships/intimacy, and 44% on relationships with family and friends. Social impacts included emotional distress (58%), social shame or disapproval (32%), and ceased participation in social activities (45%). Over half of all patients experienced unusual fatigue over the past 12 months (52%). The health domains that patients reported as being impacted by PsA aligned with life impact domains of the patient-derived PsAID health domains. Conclusion These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during shared decision-making processes between healthcare providers and patients.

Background Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study. Methods PASDAS (cut-off scores: remission ≤ 1.9; LDA > 1.9 and < 3.2; Moderate Disease Activity ≥ 3.2 and < 5.4; and high disease activity [HDA] ≥ 5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150 mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures. Results In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300 mg and in 15.2% and 19.2%, respectively, in the secukinumab 150 mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission + LDA at week 16 with secukinumab 300 and 150 mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2 years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2 years. Conclusions Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2 years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA. Trial registration ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.

Objective:To create minimal disease activity (MDA) criteria for psoriatic arthritis (PsA). With recent therapeutic advances, this is now a goal for treatment and may represent a measure to compare therapies. It defines a satisfactory state of disease activity rather than a change, and encompasses all aspects of the disease.Methods:40 patient profiles were sampled from an observational PsA database. Sixty experts in PsA classified these as in MDA or not. A consensus of ⩾70% was accepted, identifying 13 profiles in MDA. Summary statistics created possible cut-off points for the definition. Considering the number of measures that must be met, 35 candidate definitions were created and tested using receiver operating characteristic curves (ROC) for sensitivity and specificity.Results:Four candidate definitions showed high area under the curve values on ROC testing. Definitions with high outlying values were excluded as they were not considered to represent MDA. Aiming for high specificity to reduce false positives resulted in a preference for the following definition: “A patient is classified as achieving MDA when meeting 5 of the 7 following criteria: tender joint count ⩽1; swollen joint count ⩽1; Psoriasis Activity and Severity Index ⩽1 or body surface area ⩽3; patient pain visual analogue score (VAS) ⩽15; patient global disease activity VAS ⩽20; health assessment questionnaire ⩽0.5; tender entheseal points ⩽1”.Conclusion:This study provides the first definition of a “state” of MDA in PsA and defines a target for treatment. It must now be validated in other populations and tested in clinical trials.

IntroductionC-reactive protein (CRP) is an important non-specific marker of both acute and chronic inflammation and can be elevated in patients with psoriatic arthritis (PsA). However, the use of CRP testing in the management of PsA can vary. This study investigated how CRP testing is implemented in real-world clinical practice for disease management of PsA.MethodsA point-in-time survey of rheumatologists and dermatologists and their next six consulting patients with PsA was conducted in France, Germany, Italy, Spain, UK (EU5), and the USA between June and August 2018. Use of CRP testing was obtained by asking the physician to state (yes/no) whether CRP was used to aid PsA diagnosis and/or to monitor the patient’s disease activity. The number of CRP tests conducted in the last 12 months for each patient enrolled was provided.ResultsData were collected for 2270 patients (USA, n = 595; EU5, n = 1675). In the EU5, CRP testing was conducted to aid diagnosis in 78.7% of patients (vs. 43.4% in USA) and CRP was used to monitor disease activity in 72.0% (vs. 34.6% in USA). The majority (80.9%) of patients in the EU5 had at least one CRP test in the last 12 months compared to 42.9% in the USA. Patients treated by rheumatologists (vs. dermatologists) were at least 50% more likely to have CRP tested for monitoring purposes, this difference being most pronounced in the USA. In the EU5, CRP testing was conducted a mean ± standard deviation of 2.7 ± 1.7 times during the last 12 months, versus 2.0 ± 1.4 in the USA.ConclusionsCRP was more commonly used for the diagnosis and monitoring of PsA in Europe compared to the USA and was more commonly ordered by rheumatologists than dermatologists. In the absence of a better serum biomarker of inflammation, more data are needed to understand how CRP testing should be used in the diagnosis and management PsA.

Background:It is unclear whether synovial tissue adipocytes play a role in the pathogenesis and resolution of inflammatory arthritis. Intra-articular methylprednisolone is routinely used in clinical practice for treatment of knee arthritis in rheumatoid and psoriatic arthritis. Understanding how synovial cell types, including adipocytes, respond to treatment may provide insight into the cellular and molecular basis of inflammatory arthritis. Single cell RNA sequencing (scRNA-seq) is increasingly used to analyse how cells in synovium contribute to arthritis at single cell resolution in an unbiased approach but scRNA-seq requires tissue disaggregation that may lead to loss of cells such as adipocytes which are large, fragile, and buoyant. Single nuclei RNA sequencing (snRNA-seq) does not require tissue disaggregation and has the advantage of sequencing cells that would otherwise be lost with scRNA-seq.Objectives:This study aims to characterize the effects of intra-articular methylprednisolone on single nuclei transcriptomic profiles on ultrasound guided synovial tissue biopsies from patients with rheumatoid arthritis and psoriatic arthritis.Methods:Patients with rheumatoid arthritis and psoriatic arthritis who were referred for intra-articular methylprednisolone injection for clinical care at Nuffield Orthopaedic Centre (Oxford, UK) were invited to participate. Pairs of ultrasound guided synovial tissue biopsies of knee from rheumatoid arthritis (n = 4) and psoriatic arthritis (n = 4) patients taken at the time of intra-articular 80 mg methylprednisolone injection and after 28 days, were snapfrozen and processed for snRNA-seq analysis (Figure 1a).Results:Paired synovium from 4 RA patients and 4 PsA patients were used for this study with clinical data shown in Table 1. snRNA-seq identified known synovial cell types from previous scRNA-seq studies as well as adipocytes and skeletal myocytes (Figure 1b and 1c). The presence of skeletal myocytes may be due to accidental biopsy. Myocytes were excluded from downstream analysis. There were fewer adipocytes in the post-treatment synovium (odds ratio 0.53; 95% CI 0.45 – 0.63) (Figure 1d). Tissue Inhibitor of Metalloproteinases 1 (TIMP1) was previously shown to be reduced in synovium with intra-articular glucocorticoid injection[1]. In our study, differential gene expression analysis revealed downregulation of TIMP1 in lining fibroblasts (P < 0.05) consistent with previous studies, as well as novel findings of lipid metabolic genes upregulation such as Glycerol-3-Phosphate Acyltransferase Mitochondrial (GPAM) in adipocytes (P < 0.005) (Figure 1e). In all cell types, the only statistically significant gene pathway change was upregulation of monocarboxylic acid metabolic process (GO:0032787) in adipocytes (P < 0.05) in synovial tissue after treatment.Figure 1.(a) Study overview. (b) Cluster marker dotplot. (c) UMAP of cell types. (d) Differential abundance comparison. (e) Differential expression of TIMP1 in lining fibroblasts and GPAM in adipocytes (* denotes P < 0.05, ** denotes P < 0.005).Table 1. Clinical dataConclusion:This is the first ever longitudinal study of intra-articular methylprednisolone effects on single nuclei transcriptomics of inflammatory arthritis synovium. This study has the advantage of characterising paired synovium tissues before and after treatment, at single cell resolution in an unbiased approach, allowing characterisation of gene pathway analysis in cells such as adipocytes. These novel insights will advance our understanding of the cells including adipocytes involved in the pathogenesis and resolution of inflammatory arthritis.REFERENCES:[1] Firestein GS et al. GENE-EXPRESSION (COLLAGENASE, TISSUE INHIBITOR OF METALLOPROTEINASES, COMPLEMENT, AND HLA DR) IN RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS SYNOVIUM - QUANTITATIVE-ANALYSIS AND EFFECT OF INTRAARTICULAR CORTICOSTEROIDS. Arthritis and Rheumatism 1991;34(9):1094-1105. DOI: 10.1002/art.1780340905.Acknowledgements:This research was supported by the Climax Donation and National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre. Shing Law is funded by the NIHR Oxford Biomedical Research Centre.Disclosure of Interests:None declared.

Background:Existing evidence on the association between physical activity and rheumatoid arthritis (RA) remains conflicted due to a reliance on self-reported physical activity questionnaires, which are crude and prone to recall bias. Wearable devices, such as accelerometers can continuously and more objectively measure physical activity level.Objectives:We aimed to examine the dose-response association between accelerometer-measured daily step count and incident rheumatoid arthritis.Methods:This prospective cohort study was based on wrist-worn accelerometer data from the UK Biobank, where participants wore a device for seven days. Participants with prevalent inflammatory arthritis (RA, psoriatic arthritis or ankylosing spondylitis) were excluded. Daily steps were computed using a validated hybrid self-supervised machine learning step detection algorithm. Physical activity was characterised as median daily step count over a seven-day period, as a continuous measurement, in quarters of steps (<6818, 6818-9055, 9056-11659, >11659 daily steps) and per 1000 step increase. Incident RA cases were identified via record linkage with hospital inpatient data. Cox proportional hazards models were utilised to investigate the association between daily step count and incident RA adjusting for sociodemographic and lifestyle factors. Subgroup analyses were conducted to explore the association per 1000 step increase and incident RA, stratified by sex, age group (40-49, 50-59, 60-69 and 70-79) and body mass index (BMI by categories: <25, 25-29.9, >30 kg/m2). Sensitivity analyses removing RA diagnoses within 2 and 4 years of accelerometer wear and further adjusting for BMI were conducted.Results:Amongst 91,069 participants aged 62.3 (SD 7.8) years and with a median follow-up of 7.9 years, there were 629 incident RA cases (87.4 cases per 100,000 person years). Higher median daily step count was associated with lower risk of incident RA, and this association was approximately inverse log-linear. Compared to individuals in the lowest quarter (<6818 daily steps), higher median daily step count was associated with a lower risk of incident RA, with individuals in the highest quarter (>11659 daily steps) having a 45% lower risk of RA (HR 0.55, [95% confidence interval [CI] 0.44-0.68]) (Figure 1A). There was lower risk of RA across both the second (6818-9055 steps) (HR 0.77 [0.65-0.95]) and third (9056-11659 steps) (HR 0.72 [0.60 – 0.86]) quarters of daily steps when compared to the lowest quarter. Per 1000 increase in steps, we observed a 5% lower risk of RA (HR 0.95 [CI 0.93-0.97]). Additional analyses where all diagnoses of RA within 2 and 4 years of accelerometer wear were removed and addition of BMI into the primary model had little impact on the associations. In subgroup analyses, a 1000 step increase per day was associated with a lower risk for individuals in the overweight and obese BMI categories, age bands 50-59, 60-69 and 70-79 and in females (Figure 1C).Conclusion:In this cohort study of UK Biobank participants, a higher daily step count was associated with a lower risk of developing RA. The findings highlight that even incremental increases in daily steps are associated with a lower risk of RA, notably in specific subgroups such as those with higher BMI, older age groups, and females. Further studies are needed to explore the association between physical activity and incident RA in at-risk individuals.Figures 1A and 1B.Association of accelerometer-measured median daily step count as (A) quarters of steps and (B) continuous steps with risk of incident RA.Figure 1C. Association per 1000 increase in accelerometer-measured median daily steps with risk of incident RA, stratified by different subgroups.All models were adjusted for sex, ethnicity, smoking status, alcohol consumption, deprivation, education, red and processed meat consumption and fruit and vegetable consumption.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Dylan McGagh: None declared, Aidan. Acquah GlaxoSmithKline, Laura Portas: None declared, Charilaos Zisou: None declared, Alaina Shreves: None declared, Charlie Harper: None declared, Sally Fenton: None declared, Aiden Doherty: None declared, Laura C. Coates AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB, AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB.

Background:Psoriatic arthritis (PsA) and psoriasis (PsO) are chronic joint and skin inflammatory conditions. With obesity as a recognised comorbidity, people with PsA and PsO are at risk of developing steatotic liver disease (SLD) and steatohepatitis, characterised by the accumulation of fat in the liver progressing to parenchymal inflammation and fibrosis. Furthermore, methotrexate (MTX), a standard treatment for PsA and PsO, can have a direct hepatotoxic effect[1]. The impact of psoriatic treatments on liver health has never been reported using quantitative multiparametric MRI (mpMRI) measures of liver tissue characteristics.Objectives:To evaluate liver health in participants with PsA and PsO in comparison to matched non-psoriatic controls (NPCs) using mpMRI and serum biomarkers.Methods:COLIPSO (REC: 20/LO/0616) is an ongoing prospective study recruiting patients with PsA and PsO who are starting a new disease-modifying anti-rheumatic drugs (DMARDs), such as MTX or biologic DMARDs, such as secukinumab. Clinical and imaging data from 29 participants were compared with 87 NPCs (from UK Biobank application 9914 and COVERSCAN [NCT04369807]). The NPCs were matched for age, sex, and body mass index (BMI). Liver mpMRI scans were analysed using mpMRI for fat (MRI-PDFF) and disease activity quantification (iron corrected T1 mapping, cT1). cT1 is recognised in clinical guidelines as a sensitive biomarker for measuring liver disease activity and predicting clinical outcomes. Quantitative mpMRI criteria were used to define SLD (fat ≥5%) and steatohepatitis (fat ≥5% and cT1 (≥800ms)[2]. Liver health was also evaluated using the non-invasive enhanced liver fibrosis (ELF) score, based on three measures of fibrosis from a blood test. For groupwise statistical comparisons, Wilcoxon rank sum tests were applied for continuous variables and Fishers exact tests for categorical variables. Linear and logistic regression models were used to control for the effects for age, sex and BMI.Results:In the psoriatic cohort (29 patients), the mean age was 49 years, and the majority were overweight or obese (79%) with a mean BMI of 29 kg/m2. The psoriatic group had significantly higher prevalence of abnormally elevated liver cT1 (≥800ms) compared to NPCs (34% vs 14%, p = 0.027). After controlling for differences in age, sex and BMI, individuals with psoriatic disease had on average cT1 and PDFF approximately 87ms and 3.4% (absolute) higher than NPCs (Figure 1). Moreover, MASH was more prevalent in psoriatic cohort (31% vs. 13%; p-value 0.044) (Table 1). At baseline, individuals with prior use of MTX showed no difference in prevalence of liver disease as compared to those with no historical usage, measured by both MRI and serum biomarkers.Data was available on 15 people at follow-up, 6 months after switching to a new DMARDs. Of these, patients who switched to MTX (n=5) showed possible signs of deterioration in both cT1 and PDFF as compared to all other treatments, although this was not statistically significant (p=0.075). No changes were observed in any serum biomarkers. In contrast, patients switching to secukinumab (n=3) showed improvements in PDFF (-1.2% vs 2.2%, p = 0.031) and cT1 (-62ms vs 30ms, p = 0.1), but no difference in serum biomarkers.Conclusion:There is a significantly high rate of liver disease activity in patients with psoriatic disease as compared to NPCs, even at higher BMI groups. Elevated liver disease activity in patients with PsA/PsO may result from chronic underlying inflammation. There were no significant differences in the progression of liver disease seen between different DMARD treatments, but this comparison is based on a small number of patients. Further research is required to provide insight into MASLD/MASH in psoriatic disease, the effects of MTX and biologic DMARDs on liver health. MpMRI is well positioned as a surveillance tool for monitoring liver health in psoriatic disease.REFERENCES:[1] Di Martino, V., et al. (2023). Nat Rev Rheumatol, 19(2), 96–110.[2] Rinella, M. E., et al. (2023). Hepatology, 77(5), 1797– 1835.Figure 1.BMI- matched patients with PsA/PsO have higher cT1 than NPCs.Table 1: Baseline demographics and liver metrics for psoriatic and control groups. Liver disease spectrum defined liver disease: cT1 ≥ 800ms; severe liver disease: cT1 ≥ 875ms; Steatohepatitis: cT1 ≥ 800ms and liver fat (PDFF) ≥ 5%Acknowledgements:NIL.Disclosure of Interests:Lija James: None declared, Charlie Diamond: None declared, Elizabeth Shumbayawonda: None declared, Hussein Al-Mossawi Novartis, Pfizer, UCB, Speaker at educational events previously for Novartis, Pfizer, UCB, Shares in UCB, GSK, BMS, Previous Employee at UCB, AstraZeneca and current employee of Immunocore, Advisory boards for Abbvie, Roche, Novartis, Unrestricted funding (Personal fellowship) from UCB, Helena Thomaides Brears: None declared, Rajarshi Banerjee: None declared, Laura C. Coates AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB, AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB.

Background:The optimal treatment strategy in Psoriatic Arthritis (PsA) is unknown despite the growing number of therapies available. Current European guidance on first line treatment recommends a step-up approach with methotrexate (MTX) or other conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs). The hypothesis underpinning the GOLMePsA clinical trial (EudraCT: 2013-004122-28) is that a treatment strategy aimed at ablating inflammation in early disease and incorporating a bDMARD in first line treatment would lead to improved outcomes.Objectives:To assess whether the combination of MTX and golimumab (GOL) plus steroids (CS) is superior to MTX plus CS in reducing clinical disease activity, measured by the PASDAS composite index in early, treatment naïve PsA.Methods:GOLMePsA is an Investigator initiated, double-blind, randomized, placebo-controlled, two-armed, parallel-group, single centre, 52-weeks clinical trial. Adult patients with PsA (CASPAR criteria) of ≤ 24-month duration, active disease by either ≥ 3 swollen and 3 tender joints or 2 swollen and 2 tender joints plus one tender enthesis (Achilles’ tendon or plantar fascia) and naïve to DMARDs (for both PsA and psoriasis) were invited to participate. At baseline (BL, week 0), all participants were started on MTX 15 mg/week and randomized (1:1) to GOL 50 mg (or 100 mg if body weight ≥100 kg) SC Q4wks (GOLMTX arm) or placebo (PBOMTX arm). Randomisation was stratified by the number of active joints (oligoarticular: ≤4/polyarticular: >4). Both treatment arms had a “bolus” dose of methylprednisolone (MTP, 120mg IM) at BL. In all participants MTX was titrated up to 25 mg/week by week 4. Further IM/IA CS were allowed only at weeks 8 or 12 to a maximum of 120 mg MTP before primary endpoint (week 24). At week 24, PBO/GOL were stopped, MTX 25 mg/week was continued if tolerated and other treatment options were allowed if clinically needed. The primary endpoint was the mean difference in PASDAS score at week 24 (intention-to-treat analysis). A 84 persons sample size was needed to achieve power at 80% with level of significance 0.05. Analysis of covariance by multiple linear regression was used to compare PASDAS between the two arms, controlling for PASDAS score and stratification factor at BL. For those who withdrew early, withdrawal visit data were carried forward for continuous data and non-response was assumed for response variables. Multiple imputation by chained equations addressed any remaining missing data.Results:Recruitment occurred between November 2015 and February 2022. Table 1 shows BL variables. At week 24, no clinically or statistically significant difference in PASDAS score was observed between treatment arms [adjusted mean difference (95% CI) -0.55 (-1.12 to 0.03); p=0.064]. ACR20 was achieved by 65.9% (27/41) of PBOMTX and 65.1% (28/43) of GOLMTX arm [odds ratio (95% CI) 0.97 (0.39 to 2.38); p=0.939] and Minimal Disease Activity (MDA) was observed in >50% of the study population [58.5% (24/41) of PBOMTX arm and 55.8% (24/43) of GOLMTX arm; OR 0.90 (95% CI 0.68 to 2.13); p=0.802]. More participants in the PBOMTX arm received additional IM/IA CS prior to week 24 [48.8% (20/41) vs 20.9% (9/43); p=0.009). 91.7% (77/84) of patients attended week 52 visit. ACR20 was seen in 75.7% (28/37) and 54.8% (23/42) and MDA in 54.1% (20/37) and 40.5% (17/42) in the PBOMTX and GOLMTX arm, respectively. MTX 25 mg/week retention was good [PBOMTX 63.2% (24/38), GOLMTX 53.8% (21/39)], with comparable low use of bDMARDs in both groups (3/38 vs 5/39). PBOMTX arm participants received more IM/IA CS through week 52 (total median dose 240 mg vs 120 mg). No Serious Adverse Events (SAEs) occurred, with most non-SAEs being mild (mostly gastrointestinal disorders or infections) and observed slightly more frequently in the GOLMTX arm (217 vs 186 events).Conclusion:These data show that the combination of GOLMTX was not significantly superior in ameliorating PASDAS-measured disease activity at 24 weeks. First line treatment of early, DMARD naïve PsA with MTX 25 mg/week and CS produced effective disease control at week 24 and was well tolerated. Of note was the low utilisation of bDMARDs at 52 weeks in both groups.Table 1.Figure 1.REFERENCES:NIL.Acknowledgements:The GOLMePsA trial is an Investigator-Initiated Study funded by Janssen (CNTO148ART2002) and supported by the National Institute for Health and Care Research (NIHR) Leeds Biomedical Research Centre (BRC) and the Oxford BRC. The views expressed are those of the author(s) and not necessarily those of the NIHR or the University of Leeds or the University of Oxford or the Department of Health and Social Care. LCC is funded by a National Institute for Health Research Clinician Scientist award. The Sponsor Organisation of the GOLMePsA trial is the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom. Sponsor Number: RR13/10782. Ethical approval was granted by Health Research Authority (HRA) Research Ethics Committee (REC) -NRES Committee East Midlands – Northampton- reference: 14/EM/0124.Disclosure of Interests:Gabriele De Marco speaker/consultancy fees from Janssen, Novartis, speaker/consultancy fees from Janssen, Novartis, Elizabeth Hensor: None declared, Philip S Helliwell speaker fees from Novartis and Janssen, consultancy fees from Amgen, Shabina Sultan: None declared, Sayam R Dubash: None declared, Xabier Michelena Abbvie, Janssen, Lilly, Novartis and UCB, Abbvie, Janssen, Lilly, Novartis and UCB, Laura C. Coates speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB, worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Ai Lyn Tan Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB, Paul Emery: None declared, Dennis McGonagle speaker/consultancy fees from AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB., speaker/consultancy fees from AbbVie, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB., received grants/research support from: AbbVie, BMS, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, UCB, Helena Marzo-Ortega received honoraria/speaker fees from AbbVie, Celgene, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB, received honoraria/speaker fees from AbbVie, Celgene, Eli-Lilly, Janssen, Moonlake, Novartis, Pfizer, Takeda and UCB, research grants from Janssen, Novartis and UCB.

Background:Bimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated clinically meaningful, sustained joint and skin efficacy responses at Week (Wk) 52, in patients (pts) with psoriatic arthritis (PsA).[1,2] PsA is a clinically heterogenous inflammatory disease characterised by multiple domains, including skin and joint disease.[3] Treatment efficacy can therefore be comprehensively evaluated using composite outcome measures that assess disease activity across the multiple affected domains.[3] Minimal disease activity (MDA) and remission have been recommended as key treatment targets.[4]Objectives:To assess the efficacy of BKZ using composite outcomes, including MDA and remission, in pts with active PsA using data from two phase 3 studies up to 2 years.Methods:The phase 3 BE OPTIMAL (NCT03895203) and BE COMPLETE (NCT03896581) trials, both placebo (PBO)-controlled to Wk 16, assessed BKZ 160 mg every 4 wks (Q4W) in pts with PsA who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had inadequate response/intolerance to tumour necrosis factor inhibitors (TNFi-IR), respectively. BE OPTIMAL included a reference arm (adalimumab [ADA] 40 mg every 2 weeks [Q2W]). PBO pts switched to BKZ (PBO/BKZ) at Wk 16. BE OPTIMAL Wk 52 and BE COMPLETE Wk 16 completers were eligible to enter BE VITAL (open-label extension; NCT04009499), in which all pts received BKZ. Pt populations are hereafter referred to by the name of their starting study.Endpoints include minimal and very low disease activity (MDA, VLDA) responses and components, Disease Activity Index for Psoriatic Arthritis (DAPSA) remission or low disease activity (REM ≤4; REM+LDA ≤14) responses and DAPSA change from baseline (CfB). Interim data cut reported. Data reported to Wk 104 for BE OPTIMAL and Wk 88 for BE COMPLETE as some BE COMPLETE pts had not completed Wk 100 at time of data cut. Missing data were imputed using non-responder imputation (binary) or worst-category imputation (categorical; missing data are set to the most severe category).Results:At the time of data cut, 710/852 (83.3%) and 330/400 (82.5%) pts had completed Wk 104/88 of BE OPTIMAL and BE COMPLETE. Outcomes are reported to Wk 88 for BE COMPLETE because 18 (4.5%) had not yet attended their Wk 100 visit. Baseline MDA components were generally comparable between treatment groups within trials (Table 1).In BKZ-randomised pts, achievement of MDA by Wk 52 (bDMARD-naïve 54.8%; TNFi-IR 46.4%) was sustained to Wk 104/88 in both trial populations (bDMARD-naïve 52.4%; TNFi-IR 46.1%; Figure 1A). In PBO/BKZ pts, MDA achievement was sustained from 53.7% at Wk 52 to 49.8% at Wk 104 in bDMARD-naïve pts, and from 33.1% at Wk 52 to 36.8% at Wk 88 in TNFi-IR pts. In bDMARD-naïve ADA/BKZ pts, MDA achievement was sustained from 52.9% at Wk 52 to 50.7% at Wk 104. Trends were similar at Wk 104/88 for achievement of VLDA and DAPSA REM+LDA (Table 1), and improvements in DAPSA scores to Wk 104/88 (Figure 1B).BKZ treatment led to improvements to Wk 104/88 in most MDA components across all treatment arms in both trial populations (Table 1). Substantial improvements were achieved to Wk 104/88, including in objective clinical measures (swollen and tender joint count; skin improvements) and patient-reported components (pain; physical function).Conclusion:BKZ-treated pts with PsA achieved sustained MDA and DAPSA REM+LDA responses up to 2 years, regardless of prior bDMARD use. Improvements were observed across all patient-reported and most clinical components of MDA, with robust improvements observed in joint and skin outcomes.REFERENCES:[1] Ritchlin CT. Ann Rheum Dis 2023;82:1404–14.[2] Coates LC. Ann Rheum Dis 2023;82:346–347.[3] Coates LC. Rheum Dis Clin North Am 2015;41:699–710.[4] Coates LC. Nat Rev Rheumatol 2022;18:465–79.Acknowledgements:Funded by UCB Pharma. Medical writing support provided by Costello Medical and funded by UCB Pharma.Disclosure of Interests:Laura C. Coates Speaking fees from AbbVie, Amgen, Biogen and Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer, and UCB Pharma, Consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Immunotherapeutics, Novartis, Pfizer and UCB Pharma, Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer and UCB Pharma, Lars Erik Kristensen Speaking and consultancy from AbbVie, Amgen, Biogen, BMS, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB Pharma, IIT research grants from AbbVie, Eli Lilly, Novartis, and UCB Pharma, Alexis Ogdie Consultant of AbbVie, Amgen, BMS, Celgene, CorEvitas, Eli Lilly, GSK, Gilead, Janssen, Novartis, Pfizer, Takeda and UCB Pharma, Grant/research support from AbbVie, Amgen, Janssen, Novartis and Pfizer, William Tillett Research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono Pharma, Pfizer and UCB Pharma., Research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono Pharma, Pfizer and UCB Pharma., Research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono Pharma, Pfizer and UCB Pharma., Barbara Ink Shareholder of AbbVie, GSK and UCB Pharma, Employee of UCB Pharma, Nadine Goldammer Shareholder of UCB Pharma, Employee of UCB Pharma, Rajan Bajracharya Shareholder of UCB Pharma, Employee of UCB Pharma, Jason Coarse Shareholder of UCB Pharma, Employee of UCB Pharma, Ana-Maria Orbai Consulting fees from BMS, Janssen, Sanofi and UCB Pharma, Research grants to Johns Hopkins University from AbbVie, Amgen and Janssen