Abstract Background/Aims Adults with rheumatic and musculoskeletal diseases (RMDs), particularly those receiving immunosuppressive therapy, are at increased risk of pneumococcal infection. Despite national recommendations, limited evidence suggests that vaccine uptake in this population is suboptimal. This study aimed to quantify pneumococcal vaccine use for RMDs specifically and to assess pneumonia-related hospitalisation and mortality outcomes in adults with RMDs in the NHS Greater Glasgow and Clyde Health Board area in Scotland, UK. Methods A retrospective cohort study was conducted using linked health data from the West of Scotland Safe Haven. Adults aged 18-64 years who had attended ≥3 rheumatology outpatient appointments between 2010-2025 and were unvaccinated at diagnosis were included. For uptake analysis, patients ≥65 years at time of rheumatology diagnosis were excluded as these patients are eligible for pneumococcal vaccination due to their age. A high-risk subgroup was defined of those with RMDs in receipt of homecare targeted therapies. Vaccine uptake, infection rates and 30-day mortality following all-cause pneumonia hospitalisation were analysed using logistic regression, incidence rate calculations, and Cox proportional hazard models. Results Among 20,707 eligible RMD patients, 33.0% received a pneumococcal vaccine before age 65, rising to 58.4% in the high-risk homecare cohort (N = 3,215). An additional 10.5% in the main cohort and 6.5% in the high-risk cohort were vaccinated after age 65. In the main cohort, compared to those aged 50-64 years, individuals aged 18-34 years had significantly lower odds of receiving a pneumococcal vaccination (OR = 0.78, 95% CI: 0.71-0.85), while those aged 35-49 years were more likely to be vaccinated early (OR = 1.40, 95% CI: 1.31-1.50). Patients from the most deprived quintile were less likely to be vaccinated before age 65. Among the high-risk group, male sex was associated with reduced uptake (OR = 0.79, 95% CI: 0.68-0.92). Hospitalisation rates for all-cause pneumonia increased with age and were consistently higher in the high-risk homecare group. Among those aged ≥65, infection rates were 20.6 per 1,000 person-years in the main cohort and 29.8 in the high-risk cohort. 30-day mortality following all-cause pneumonia hospitalisation rose steeply with age. In the main cohort, mortality was 20.4% in those aged ≥65, compared to 11.6% (50-64 years) and 7.7% (35-49 years). Male sex was associated with increased mortality risk (HR = 1.56, p < 0.001). In the high-risk group, age remained a significant predictor of mortality (HR = 1.09/year, p < 0.001), but sex was not. Conclusion Pneumococcal vaccination uptake among adults with RMDs remains suboptimal, particularly in younger and socioeconomically deprived populations. Age is associated with increased all-cause pneumonia hospitalisation and mortality, particularly in those receiving targeted therapies, highlighting the need for targeted and strengthened pneumococcal vaccination strategies. These efforts are essential to prevent avoidable all-cause pneumonia-related morbidity and mortality in this vulnerable group. This study was sponsored by Pfizer. Disclosure F. Morton: None. A. Barkaway: Shareholder/stock ownership; Pfizer. Other; Pfizer employee. J. Campling: Shareholder/stock ownership; Pfizer. Other; Pfizer employee. A. Vyse: Shareholder/stock ownership; Pfizer. Other; Pfizer employee. M. McLean: Other; Former Pfizer employee. D. Lowe: Corporate appointments; Director Codebase / ScribePro and board of HI paediatric charity. Consultancies; AstraZeneca, Boehringer Ingelheim, BT Health, MHRA, Novo Nordisk. Shareholder/stock ownership; ScribePro, DK Holdings. Honoraria; (Covered by consultancies) and Qure.ai, AiDoc. Grants/research support; AiDoc, Qure.ai, Annalise.ai, Newton tree, Health Navigator. M. Murphy: Consultancies; Tillotts, Shionogi. Honoraria; (covered by consultancies). Grants/research support; Pfizer, Biomerieux. S. Siebert: Consultancies; Astrazeneca. Honoraria; (covered by consultancies). Member of speakers’ bureau; Pfizer. Grants/research support; Pfizer.

Key advances from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) pilot research grant program were presented at the GRAPPA 2025 annual meeting. Areas of study included hypoxia-inducible factor 1α (HIF1A) as a potential factor in psoriatic arthritis (PsA), plasma extracellular vesicle cytokines as potential biomarkers for predicting response to tumor necrosis factor inhibitors in PsA, bone properties and biomechanics in psoriatic disease (PsD), better understanding of differences in body composition in PsD, and the effect of sleep on PsD severity.

Objectives The HIPPOCRATES project is a 5-year, international research partnership dedicated to studying and treating psoriatic disease. Integrating Patient Research Partners (PRPs) into large scientific groups, particularly those heavily focused on preclinical or laboratory-based science, is challenging. This paper details a midterm evaluation of how effectively PRPs have been engaged in the HIPPOCRATES project. Methods Our evaluation used a mixed-method approach comprising 7 dedicated reflective PRP meetings, 2 midterm surveys among PRPs and researchers, a modified World Café discussion, and 5 structured dialogue meetings. We used descriptive statistics and pragmatic constant comparative analysis. Results Substantial PRP input occurred early during the project’s presubmission phase, which resulted in a formal strategy for patient involvement. However, 3 years after approval, significant differences emerged between researcher and PRP perspectives. Compared with researchers, PRPs reported more challenges, had differing expectations, and perceived a lower overall impact. Although PRPs were highly motivated at the start and contributed significantly to clinical components, motivation decreased for some regarding the laboratory components. This was attributed to highly technical language, long contract negotiations, and a lack of clear opportunities for input or tangible results. Consortium members collaboratively agreed upon a set of specific changes during the 5 dialogue sessions. Conclusions Despite the early and substantial involvement of PRPs in the initial study design, the PRPs themselves rated their influence on HIPPOCRATES lower than the researchers did. Further evaluation over the next 2 years will show whether the jointly developed solutions successfully enhance their impact on future research outcomes.

Abstract Background/Aims While randomised controlled trials (RCTs) in psoriatic arthritis (PsA) show early and durable efficacy of IL-23 inhibitors (i) and IL-17i, real-world data are limited. Previous interim analysis of the PsABIOnd study showed similar 6-month guselkumab (GUS) and IL-17i persistence and effectiveness across PsA domains. This analysis aimed to assess 12-month treatment persistence and effectiveness. Methods PsABIOnd (NCT05049798) is an ongoing global observational study in participants with PsA starting GUS or IL17i as 1st-to-4th line of biologic therapy per standard of care. The primary outcome is treatment persistence at 36 months. In this interim analysis, PsABIOnd participants who had a baseline and ≥1 follow-up assessment up until the 12-month visit (±3 months) were analysed according to their initial treatment, regardless of later switches. Treatment persistence (i.e., no stop/switch) for the overall population and by subgroups of interest (prior biologic experience, biological sex) was assessed over 12 months via Kaplan-Meier estimator function. Propensity score (PS) analysis was used to evaluate hazard ratio (HR) of stopping/switching GUS vs IL-17i prior to the 12-month visit, adjusting for baseline variable imbalances across cohorts. Rates of achievement of clinical Disease Activity Index for PsA (cDAPSA) based minimal clinically important improvement (MCII; improvement by ≥ 5.7), low disease activity (LDA)/remission (REM; ≤13), and REM (≤4), minimal disease activity (MDA), psoriasis body surface area (BSA)<3%, and Dermatology Life Quality Index (DLQI; ≥4) at the 12-month visit were assessed. Results A total of 511 and 504 participants received GUS or IL-17i, respectively, as their initial treatment. Mean age (53.0/53.7 years) and prior targeted therapy use (not GUS/IL-17i; 62.6%/62.9%) were comparable across GUS/IL17i cohorts at baseline. Treatment persistence up to the 12-month visit was high in both cohorts, with 407/511 (79.6%) GUS and 417/504 (82.7%) IL-17i cohort participants remaining on their initial treatment line (PS-adjusted HR GUS vs IL-17i stop/switch [95% confidence interval]: 1.11 [0.85-1.44]). Reasons for initial treatment line discontinuation were generally consistent across groups. Persistence on GUS and IL-17i remained comparable across prior biologic experience and biological sex subgroups. Improvements in joint, skin, and overall disease activity at 12 months were also similar with GUS and IL-17i. Conclusion Participants with PsA had similar 12-month treatment persistence and rates of effectiveness across key PsA domains with GUS or IL-17i, overall and across subgroups of interest. These results add to real-world evidence of the long-term effectiveness of GUS and IL-17i, supporting efficacy data from RTCs. Disclosure S. Siebert: Consultancies; Abbvie, Amgen, Astrazeneca, Johnson & Johnson, Syncona, Teijin Pharma, UCB. Honoraria; AbbVie, Amgen, AstraZeneca, Johnson & Johnson, Syncona, Teijin Pharma, UCB. Member of speakers’ bureau; AbbVie, Amgen, Johnson & Johnson, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, GSK, Johnson & Johnson, Pfizer, UCB. M. Sharaf: Corporate appointments; Johnson & Johnson. Shareholder/stock ownership; Johnson & Johnson. F. Behrens: Consultancies; Abbvie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. Honoraria; Abbvie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. Grants/research support; Celgene, Chugai, Johnson & Johnson, Pfizer, Roche. P. Rahman: Consultancies; Abbvie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Johnson & Johnson, Merck, Novartis, Pfizer, UCB. Grants/research support; Johnson & Johnson, Novartis. Other; Meeting attendance/travel support: Johnson & Johnson. M. Kishimoto: Consultancies; AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Johnson & Johnson, Novartis, Pfizer, Tanabe-Mitsubishi, UCB. Honoraria; AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Johnson & Johnson, Novartis, Pfizer, Tanabe-Mitsubishi, UCB. E. Soriano: Consultancies; AbbVie, Johnson & Johnson, Novartis, Roche. Member of speakers’ bureau; AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Johnson & Johnson, Novartis, Pfizer, Roche, UCB. E. Rampakakis: Corporate appointments; JSS Medical Research. Consultancies; Johnson & Johnson. L. Köleséri: Corporate appointments; IQVIA. Consultancies; Johnson & Johnson. K. Lozenski: Corporate appointments; Johnson & Johnson. Shareholder/stock ownership; Johnson & Johnson, Bristol Myers Squibb. M. Koivunen: Corporate appointments; Former employee of Johnson & Johnson. Shareholder/stock ownership; Johnson & Johnson. R. Queiro: Consultancies; AbbVie, Amgen, Celgene, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer. Honoraria; AbbVie, Amgen, Celgene, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer. Grants/research support; AbbVie, Johnson & Johnson, Novartis. E. Lubrano: Honoraria; AbbVie, Amgen, Eli Lilly, GSK, Johnson & Johnson, Novartis, UCB. D. Aletaha: Consultancies; Abbvie, Gilead, Galapagos, Eli Lilly, Johnson & Johnson, Merck, Novartis. Honoraria; Abbvie, Gilead, Galapagos, Eli Lilly, Johnson & Johnson, Merck, Novartis. Grants/research support; Abbvie, Gilead, Galapagos, Eli Lilly, Johnson & Johnson, Merck, Novartis. L. Gossec: Consultancies; AbbVie, AlfaSigma, Amgen, Bristol Myers Squibb, Celltrion, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer, Stada, UCB. Honoraria; AbbVie, AlfaSigma, Amgen, Bristol Myers Squibb, Celltrion, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer, Stada, UCB. Grants/research support; AbbVie, Biogen, Eli Lilly, Novartis, UCB.

Abstract Background/Aims Increased patient treatment satisfaction may improve therapeutic adherence and long-term outcomes. The efficacy of targeted drugs in psoriatic arthritis (PsA), including clinical and patient-reported outcomes (PROs), has been demonstrated in randomised controlled trials; however, real-world data are scarcer, particularly for IL-23 and IL-17 inhibitors (i). This analysis aimed to assess PsA PROs and patient satisfaction with guselkumab (GUS) and IL-17i treatment at 12 months. Methods PsABIOnd (NCT05049798) is an ongoing, global, observational, study in PsA patients starting GUS or IL17i as 1st to-4th line of biologic therapy per standard of care.1 In this interim analysis, PsABIOnd participants with a baseline and ≥1 follow-up assessment through the 12-month visit (+/ 3 months) were analysed according to their initial treatment, regardless of later switches. Patient-reported impact was assessed with the PsA Impact of Disease-12 (PsAID12; 0-10) questionnaire and patient global assessment of PsA activity (PtGA; 0-100 VAS). Mean changes from baseline to 12 months in PsAID-12 total score and PtGA, and proportions of participants achieving PsAID-12 minimal clinically important improvement (MCII; improvement ≥1.4) were determined. Patient satisfaction with treatment was descriptively assessed with mean scores (0-100; higher being better) in effectiveness, convenience, and global satisfaction domains of the Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)2 and with proportions of participants rating their well-being as improved and symptoms as acceptable using the Patient Acceptable Symptom State (PASS) scale.3 No statistical comparisons were performed. Results A total of 511 and 504 participants received GUS or IL-17i, respectively, as initial treatment. Sex (60.7%/59.7% female), prior targeted drug use (62.6%/62.9%), and mean age (53.0/53.7 years), PsAID-12 total score (5.1/5.1), and PtGA (59.4/60.7) were comparable for GUS/IL-17i at baseline. At the 12-month visit, mean changes from baseline in PsAID-12 total score (-1.6/-1.7) and in PtGA (-17.0/- 19.1), and rates of participants achieving PsAID-12 MCII (56.8%/53.7%) were similar with GUS and IL-17i. Patient satisfaction with GUS vs IL-17i at the 12-month visit was high, with similar proportions of participants rating their overall well-being as better (57.7%/64.9%) and in an acceptable state (61.0%/64.2%), and comparable mean TSQM-9 scores across domains (61.8/63.8). Conclusion By 12 months of treatment, clinically meaningful improvements in multidomain PROs and high levels of satisfaction were seen in participants treated in real-world with GUS or IL-17i, with the majority reporting achievement of acceptable state. These results may aid shared treatment decision-making by facilitating discussions on patient expectations.References:1. Siebert S, et al. Rheumatol Ther. 2023;10(2):489-5052. Atkinson MJ, et al. Health Qual Life Outcomes. 2004;2:123. Tubach F, et al. Arthritis Rheum. 2006;55(6):960-3 Disclosure L. Gossec: Consultancies; AbbVie, AlfaSigma, Amgen, Bristol Myers Squibb, Celltrion, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer, Stada, UCB. Honoraria; AbbVie, AlfaSigma, Amgen, Bristol Myers Squibb, Celltrion, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer, Stada, UCB. Grants/research support; AbbVie, Biogen, Eli Lilly, Novartis, UCB. M. Sharaf: Corporate appointments; Johnson & Johnson. Shareholder/stock ownership; Johnson & Johnson. X. Baraliakos: Consultancies; Abbvie, Chugai, Eli Lilly, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB. Honoraria; Abbvie, Chugai, Eli Lilly, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB. Member of speakers’ bureau; AbbVie, Chugai, Eli Lilly, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Eli Lilly, Johnson & Johnson, MSD, Novartis. M. Kishimoto: Consultancies; Abbvie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Daichii-Sankyo, Eisai, Eli Lilly, Gilead, Johnson & Johnson, Novartis, Tanabe-Mitsubishi, UCB. Honoraria; Abbvie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Daichii-Sankyo, Eisai, Eli Lilly, Gilead, Johnson & Johnson, Novartis, Tanabe-Mitsubishi, UCB. R. Queiro: Consultancies; Abbvie, Amgen, Celgene, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer. Honoraria; Abbvie, Amgen, Celgene, Johnson & Johnson, Eli Lilly, MSD, Novartis, Pfizer. Grants/research support; Abbvie, Johnson & Johnson, Novartis. E. Lubrano: Honoraria; Abbvie, Amgen, Eli Lilly, GSK, Johnson & Johnson, Novartis, UCB. E. Rampakakis: Corporate appointments; JSS Medical Research. Consultancies; Johnson & Johnson. L. Köleséri: Corporate appointments; IQVIA. Consultancies; Johnson & Johnson. K. Lozenski: Corporate appointments; Johnson & Johnson. Shareholder/stock ownership; Johnson & Johnson, Bristol Myers Squibb. C. Roux: Consultancies; Galapagos. E. Soriano: Consultancies; Abbvie, Johnson & Johnson, Novartis, Roche. Honoraria; Abbvie, Johnson & Johnson, Novartis, Roche. Member of speakers’ bureau; Abbvie, Amgen, Bristol Myers Squibb, Eli Lilly, Johnson & Johnson, Novartis, Pfizer, Roche, UCB. Grants/research support; AbbVie, Johnson & Johnson, Novartis, Pfizer, Roche, UCB. P. Rahman: Consultancies; Abbvie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Johnson & Johnson, Merck, Novartis, Pfizer, UCB. Honoraria; Abbvie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Johnson & Johnson, Merck, Novartis, Pfizer, UCB. Grants/research support; Johnson & Johnson, Novartis. Other; Meeting attendance/travel support: Johnson & Johnson. F. Behrens: Consultancies; AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. Honoraria; AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Chugai, Eli Lilly, Galapagos, Genzyme, Gilead, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. Grants/research support; Celgene, Chugai, Johnson & Johnson, Pfizer, Roche. S. Siebert: Consultancies; AbbVie, Amgen, AstraZeneca, Johnson & Johnson, Syncona, Teijin Pharma, UCB. Honoraria; AbbVie, Amgen, AstraZeneca, Johnson & Johnson, Syncona, Teijin Pharma, UCB. Member of speakers’ bureau; AbbVie, Amgen, Johnson & Johnson, Novartis, Pfizer, UCB. Grants/research support; Eli Lilly, GSK, Johnson & Johnson, Pfizer, UCB.

Predicting treatment response is a key unmet need for people with psoriatic disease. In this article, the importance of personalized medicine is emphasized and molecular biomarker concepts are discussed. The literature related to biomarkers of treatment response in psoriatic disease is reviewed in detail. Finally, the limitations of current candidate biomarkers, emerging biomarkers, and future directions and challenges in biomarker research are highlighted.

Objectives This article aimed to articulate the most important unmet scientific needs in rheumatology. Methods At the 25th Advances in Targeted Therapies (ATT) meeting, over 100 investigators joined 6 disease-focused breakout groups (rheumatoid arthritis [RA], psoriatic arthritis [PsA], axial spondyloarthritis [axSpA], systemic lupus erythematous [SLE], systemic sclerosis [SSc], and osteoarthritis [OA]). Each group, led by a facilitator and rapporteur, mapped (i) key unmet needs, (ii) promising mechanistic or therapeutic approaches, and (iii) near-term priorities for research and trials. This report synthesises the consensus highlights. Results Six disease-focused groups (RA, PsA, axSpA, SLE, SSc, and OA) identified convergent priorities: earlier detection and interception; validated molecular and clinical endotypes to guide therapy; strategies for immune reset and short-course induction combinations with strict safety oversight; metabolic modifiers; precision targets in axSpA and fibroblast-directed approaches in RA; phenotype-driven therapeutic development and intra-articular options in OA; and pragmatic trial designs that include pregnant persons and very early disease. Conclusions Across immune-mediated diseases, progress will hinge on validated endotypes, practical interception strategies, and trials that reflect real-world populations. The immediate agenda is to de-risk immune reset and induction approaches, standardise tissue and digital biomarkers, and close evidence gaps for refractory disease. Prevention—and ultimately cure—remains the horizon.

It is 50 years since the original spondyloarthritis concept was proposed by Moll and Wright, and in November 2025, rheumatologists (and other health and research professionals in rheumatology and dermatology) gathered in Leeds, the birthplace of spondyloarthritis, to celebrate the milestone. Here, we report on the proceedings of the meeting, which looked back over the last 50 years, noted the current state of the art, and had a look at what might develop in the next 50 years.

Rheumatic and musculoskeletal diseases are chronic, heterogeneous conditions shaped by complex interactions between immune, metabolic, behavioural, and environmental factors. Despite substantial advances in pharmacological therapies, many patients continue to have pain, fatigue, functional impairment, and accumulating comorbidity burden, highlighting the need for complementary strategies beyond inflammation control. Prehabilitation is a proactive and multimodal approach aimed at optimising physical, metabolic, and psychological health before periods of increased vulnerability. Although originally developed in surgical and oncological settings, its principles might be relevant across the continuum of chronic inflammatory diseases. Psoriatic disease represents a particularly attractive model given its identifiable preclinical phases, heterogeneous course, and strong influence of modifiable lifestyle factors. In this Personal View, we discuss the rationale for translating prehabilitation to psoriatic disease, explore potential windows of opportunity and intervention domains across the disease continuum, and consider the conceptual challenges, current evidence gaps, and uncertainties surrounding its application in this clinical setting.

Background: Differences in body fat distribution and muscle composition, beyond body mass index (BMI), may be functionally important in immune-mediated-inflammatory-diseases (IMIDs). We compared body composition in psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and gout, propensity to type 2 diabetes (T2DM) and coronary heart disease (CHD), and body composition predicted risk of incident psoriasis, RA, and gout. Methods: MRI body composition parameters were compared amongst 236 individuals with psoriasis, 61 with PsA, 281 with gout, and 308 with RA, each matched 1:5 on age, sex, and BMI to 1180, 305, 1405, and 1540 metabolic-disease-free controls from UK Biobank. Fat distribution-derived propensities to T2DM and CHD were calculated using adaptive k-nearest neighbours algorithm. Body composition predicted risks of incident psoriasis, RA, and gout were calculated using Cox regression, adjusted for age, sex, and BMI. Findings: Psoriasis, PsA, and gout displayed metabolically adverse body fat distribution with greater liver and muscle fat and 1.23, 1.39-, and 1.20-times greater propensity to T2DM compared to matched controls, respectively (p<0.05). RA displayed greater muscle fat and 1.18-times greater propensity to CHD compared to matched controls (p=0.002). 1 in 7 to 1 in 5 individuals with IMIDs displayed adverse muscle composition, significantly associated with greater T2DM and CHD propensity. During a mean follow-up of 3.9years (SD 2.2), adverse muscle composition (low muscle volume and high muscle fat) was associated with increased incidence of psoriasis (adj.HR 2.12, 95% CI (1.29, 3.50)), gout (adj.HR 1.66 (1.10, 2.50)), and RA (adj.HR 1.79 (1.14, 2.81)) compared to normal muscle composition. Greater visceral and liver and lower subcutaneous fat were associated with greater risk of incident gout (p<0.05). Interpretation: Psoriasis, PsA, gout, and RA display adverse body fat distributions and muscle compositions, which may help assess cardiometabolic risk and potential mechanistic insights into greater cardiometabolic disease susceptibility in IMIDs. Adverse muscle composition is also linked to greater susceptibility to these IMIDs. Effective weight management, targeting ectopic fat while maintaining muscle quality, should be integral to IMID management. Funding: GRAPPA Pilot Research Grant and Mason Medical Research Trust (grant number G4)

Abstract Background/Aims Obesity impacts psoriatic disease (PsD) particularly regarding disease onset, disease severity and treatment non-response. The new weight-loss agents, such as Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) have potential benefits for PsD disease activity and related co-morbidities but come with significant cost. We were therefore keen to explore rheumatologists and dermatologists’ opinions on the potential role of these drugs in the management of PsD. Methods We conducted an online survey of rheumatology and dermatology colleagues between the 7th April and 22nd of September 2025. Questions were developed through expert consensus and covered speciality, job role, region of practice, clinical setting, the impact of excess weight on disease and treatment response, and the monitoring and management of adiposity in PsD. Target health professionals included consultants, speciality doctors, registrars, research fellows, physiotherapists, and nurse specialists. The survey was disseminated ad hoc via professional and institutional mailing lists. Although originally meant for UK-based clinicians, the survey was later opened to international colleagues. Results were analysed with descriptive statistics. Results We received 190 responses, 150 from the UK (79%), with rheumatology contributing 131 (69%) and dermatology 59 (31%). Most respondents were consultants (68%) working in academic units/teaching hospitals (64%). Only 25% of respondents measured weight and BMI at every clinic visit, despite the majority believing that excess adiposity decreases treatment response to csDMARDs (73%) and ts/bDMARDs (75%), increases inflammatory drive and/or disease activity (87%), and is associated with cardiovascular/diabetic comorbidities (93%). Overall, 62% of respondents said that they consistently address excess adiposity in their patients, mainly through weight loss advice (92%) or weight management referral (47%). Barriers to addressing excess adiposity included time pressures, a lack of expertise and a lack of local services. Respondents were more favourable towards a hypocaloric diet over a GLP-1RA for the management of PsD in those living with overweight or obesity, including before PsA-onset in high-risk patients (35% vs 27%), before initiating systemic DMARD (52% vs 27%) or alongside the prescription of a systemic DMARD (46% vs 36%). Opinions around GLP-1-RA therapy were generally positive, with the caveat that further evidence of their efficacy and safety in PsA is required (28%). Only 1 respondent (<1%) felt GLP-1RA had no role in the management of PsD. Conclusion Clinicians treating PsD agree that excess adiposity promotes higher disease activity and cardiometabolic comorbidity, and lower treatment response, in alignment with the current literature. Interestingly, despite the current interest around GLP-1-RA agents, colleagues were relatively cautious, citing the need for further high-quality evidence for the safety and efficacy of these drugs in PsD. As such, high-quality randomised controlled trials are needed to assess the utility of these medications as an adjunctive treatment in the management of PsD. Disclosure J.C. Williams: None. P. Helliwell: None. D. McGonagle: None. J. Freeston: None. L. Ferguson: None. N. Gullick: None. S.R. Harrison: None. P. Laws: None. G. De Marco: None. J. Packham: None. J. Weddell: None. K. Shams: None. A. Tan: None. W. Tillett: None. S. Zhao: None. N. Sattar: None. S. Siebert: None. H. Marzo-Ortega: None.

BACKGROUND:Clinical trials aimed at preventing rheumatoid arthritis in individuals at risk have had variable results. The long-term outcomes of disease interception, however, are not known. We aimed to examine the long-term effect of therapeutic intervention, with emphasis on efficacy and safety. METHODS:The Arthritis Prevention In the Preclinical Phase of Rheumatoid arthritis with Abatacept (APIPPRA) phase 2b, randomised controlled trial recruited 213 anti-citrullinated protein antibody (ACPA) positive individuals with arthralgia in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands, randomly assigning participants to 52 weekly subcutaneous injections of 125 mg abatacept (n=110) or placebo (n=103), with another 52 weeks of follow-up. The APIPPRA Long-Term Outcome (ALTO) study extended follow-up for between 4 and 8 years and study participants and clinical assessors remained masked to treatment group. The primary outcome was the time from randomisation to development of clinical synovitis in at least three joints, rheumatoid arthritis according to American College of Rheumatology-European Alliance of Associations for Rheumatology 2010 criteria, or first treatment with disease modifying anti-rheumatic drugs, whichever was met first. The primary outcome was also stratified by autoantibody profiles defined at the time of randomisation. People with lived experience of rheumatoid arthritis had input into the APIPPRA study design. The study was registered at ISRCTN (ISRCTN-12680338), and is completed. FINDINGS:Between April 26, 2021, and Jan 31, 2023, 143 APIPPRA study participants enrolled in ALTO: 71 in the abatacept group and 72 in the placebo group (mean age 48·2 years [SD 11·2], 112 [78%] females, 31 [22%] males, 116 [81%] White). Median follow-up time from randomisation was 55 months (IQR 23-74). Primary events increased by 54 to 119. The initial between-group difference in restricted mean arthritis-free survival time observed at 2 years in APIPPRA remained significant at 4 years (4·9 months 95% CI 0·1-9·6; p=0·044), although the magnitude of this difference diminished over time. Assessments of disease activity and patient reported outcomes revealed no significant differences between groups beyond the treatment period. However, although participants with a broad autoantibody profile at baseline were at highest risk of progressing, this subgroup responded better to abatacept. There were 18 serious adverse events in the abatacept group and 13 in the placebo group; none deemed related to study drug. INTERPRETATION:In this at-risk population, 1-year treatment with abatacept delayed progression to rheumatoid arthritis for up to 4 years. Those at highest risk of progression have a broad autoantibody profile but are more responsive to abatacept treatment. FUNDING:Bristol Myers Squibb.

OBJECTIVE:Here we investigate the status of the adiponectin-PEPITEM pathway in early, treatment naive rheumatoid arthritis (RA) and psoriatic arthritis (PsA) and the therapeutic efficacy of PEPITEM administration in preclinical models. METHODS:Peripheral blood was isolated from patients with clinical suspect arthralgia and suspected inflammatory arthritis and analyzed by flow cytometry or Western blot. Effect of PEPITEM treatment on inflammatory arthritis was assessed in mice by histology, single-cell RNA sequencing, flow cytometry, or multiplex analysis. RESULTS:Patients newly diagnosed with RA and PsA had significantly reduced expression of adiponectin receptor 2 and its downstream signaling adapter protein APPL-1 on their peripheral-blood mononuclear cells, resulting in diminished response to adiponectin and local synovial concentrations of PEPITEM. Building on these observations, treatment with PEPITEM in three distinct inflammatory arthritis animal models significantly reduced arthritis severity, joint swelling, leukocyte infiltration, and expression of several pro-inflammatory mediators (eg, JE [CCL2], RANTES, interleukin-16) in the synovium. Mechanistically, PEPITEM treatment suppressed the cyclooxygenase 2 and NF-κB signaling pathways. Moreover, PEPITEM altered the composition of leukocyte subsets recruited into the joint. CONCLUSION:Collectively, these findings underscore the importance of understanding the dysregulation of the adiponectin-PEPITEM pathway in different immune-mediated inflammatory diseases (IMIDs), such as RA and PsA. The observed differences in expression and downstream signaling through adiponectin receptors suggest potential targets for therapeutic intervention to restore the balance of this regulatory pathway to mitigate chronic inflammation and disease progression in these patients, paving the way for its clinical use as an alternative and/or combination therapy for early IMIDs.

BackgroundPatients with immune-mediated inflammatory disease (IMID), including autoimmunity, fared substantially worse than the general population during the COVID-19 pandemic, both in terms of infection outcomes and disruption to daily life. Despite this, COVID-19 vaccine uptake has not been universal in this population. The absence of patients with IMID from clinical trials and the subsequent lack of precision in vaccine safety profiling have resulted in vaccine hesitancy in this high-risk group. ObjectiveThis protocol sets out an investigation that aims to address this by enhancing COVID-19 vaccine pharmacovigilance for patients with IMID. Combining the international data and knowledge assets of the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 1 study and the electronic Delphi Study to Define and Risk-Stratify Immunosuppression (DESTINIES), the objective is to differentiate patient-reported COVID-19 infection and vaccine outcomes between participants with systemic, single organ, and overlap IMID and general population controls. MethodsThe COVAD-1 study successfully collected anonymized data on the demographic, health, COVID-19 infection, and COVID-19 vaccination outcomes of a broad range of participants with IMID between March and December 2021. This protocol expands on this initial analysis by using IMID specialists within the DESTINIES Consortium to allocate survey respondents into single organ and systemic categories and thereby produce comparative vaccine benefit-risk profiles between these and general population controls. Because of the respondents’ ability to self-report multiple diagnoses, an overlap group was introduced for those affected by both single organ and systemic disease. Descriptive statistics and both single and multivariable logistic regressions will be used to test for significant differences in COVID-19 infection rates, severity, duration, and vaccine side effects between these study groups and general population controls. ResultsA panel of 7 IMID experts successfully allocated COVAD-1 diagnoses into single organ and systemic categories; this also directed overlap category membership. Although this work is preliminary and highly exploratory, we anticipate that subsequent analysis will reveal disproportionate levels of severe COVID-19 infection outcomes (hospitalization with and without oxygen support) and vaccine side effects (mild and major) among participants with systemic manifestations of IMID, especially those that qualify for the overlap IMID category. ConclusionsAdvocating for direct-to-patient vaccine reporting pathways, this study intends to produce more precise vaccine safety profiles of patients with IMID. It seeks to resolve current gaps in pharmacovigilance and potentially remedy vaccine hesitancy in high-risk groups by doing so. The international nature of COVAD-1 data collection and the nuance of information made available through participant self-report are to the advantage of this protocol. However, the dependence of this study on participant recall, the small sample sizes handled, and the questionable relevance of these data in the contemporary Omicron era are to the detriment of this work. International Registered Report Identifier (IRRID)DERR1-10.2196/68785

Background Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease associated with psoriasis, affecting an estimated 0.13% of adults worldwide. People living with PsA often experience multiple long-term conditions (MLTCs) or multimorbidity (the presence of two or more long-term health conditions), such as hypertension, diabetes, obesity, and metabolic syndrome. Multimorbidity and treatment burden which is the workload of healthcare experienced by individuals and its impact on wellbeing may exacerbate poor health outcomes and complicate disease management in PsA. However, the influence of MLTCs and/or treatment burden on adverse health-related outcomes in this population remains poorly understood. Objective This systematic review protocol will outline the methods to evaluate the current evidence regarding the impact, if any, of MLTCs and/or treatment burden on mortality and other adverse health-related outcomes in individuals with PsA. Design Systematic review of the literature. The following databases will be searched: MEDLINE, EMBASE, CINAHL, PsycINFO, and Scopus. Longitudinal quantitative studies will be eligible for inclusion. Study selection will follow predefined eligibility criteria, and methodological quality and risk of bias will be assessed using the Cochrane Quality in Prognostic Studies tool. A narrative synthesis will be undertaken, and meta-analysis will be considered where appropriate. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 guidelines. Conclusions Understanding the impact of MLTCs and/or treatment burden on health-related outcomes in PsA is essential for improving future clinical management. This review will help identify existing knowledge gaps and advance precision medicine strategies to improve health-related outcomes for individuals living with PsA.